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  1. Genetic variation in ABCA1 predicts ischemic heart disease in the general population

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    Frikke-Schmidt, Ruth; Nordestgaard, BG; Jensen, Gorm B

    2008-01-01

    We tested the hypothesis that 6 nonsynonymous single nucleotide polymorphisms (SNPs) in ATP-Binding-Cassette transporter A1 (ABCA1) affect risk of ischemic heart disease (IHD) in the general population.......We tested the hypothesis that 6 nonsynonymous single nucleotide polymorphisms (SNPs) in ATP-Binding-Cassette transporter A1 (ABCA1) affect risk of ischemic heart disease (IHD) in the general population....

  2. Genetic variation in the ABCA1 gene, HDL cholesterol, and risk of ischemic heart disease in the general population

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    Frikke-Schmidt, Ruth

    2010-01-01

    Epidemiological studies consistently demonstrate a strong inverse association between low levels of high-density lipoprotein (HDL) cholesterol and increased risk of ischemic heart disease (IHD). This review focuses on whether both rare and common genetic variation in ABCA1 contributes to plasma...... levels of HDL cholesterol and to risk of IHD in the general population, and further seeks to understand whether low levels of HDL cholesterol per se are causally related to IHD. Studies of the ABCA1 gene demonstrate a general strategy for detecting functional genetic variants, and show that both common...... and rare ABCA1 variants contribute to levels of HDL cholesterol and risk of IHD in the general population. The association between ABCA1 variants and risk of IHD appears, however, to be independent of plasma levels of HDL cholesterol. With the recent identification of the largest number of individuals...

  3. Accurate prediction of the functional significance of single nucleotide polymorphisms and mutations in the ABCA1 gene.

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    Liam R Brunham

    2005-12-01

    Full Text Available The human genome contains an estimated 100,000 to 300,000 DNA variants that alter an amino acid in an encoded protein. However, our ability to predict which of these variants are functionally significant is limited. We used a bioinformatics approach to define the functional significance of genetic variation in the ABCA1 gene, a cholesterol transporter crucial for the metabolism of high density lipoprotein cholesterol. To predict the functional consequence of each coding single nucleotide polymorphism and mutation in this gene, we calculated a substitution position-specific evolutionary conservation score for each variant, which considers site-specific variation among evolutionarily related proteins. To test the bioinformatics predictions experimentally, we evaluated the biochemical consequence of these sequence variants by examining the ability of cell lines stably transfected with the ABCA1 alleles to elicit cholesterol efflux. Our bioinformatics approach correctly predicted the functional impact of greater than 94% of the naturally occurring variants we assessed. The bioinformatics predictions were significantly correlated with the degree of functional impairment of ABCA1 mutations (r2 = 0.62, p = 0.0008. These results have allowed us to define the impact of genetic variation on ABCA1 function and to suggest that the in silico evolutionary approach we used may be a useful tool in general for predicting the effects of DNA variation on gene function. In addition, our data suggest that considering patterns of positive selection, along with patterns of negative selection such as evolutionary conservation, may improve our ability to predict the functional effects of amino acid variation.

  4. PPARγ activates ABCA1 gene transcription but reduces the level of ABCA1 protein in HepG2 cells

    International Nuclear Information System (INIS)

    Mogilenko, Denis A.; Shavva, Vladimir S.; Dizhe, Ella B.; Orlov, Sergey V.; Perevozchikov, Andrej P.

    2010-01-01

    Research highlights: → PPARγ activates ABCA1 gene expression but decreases ABCA1 protein content in human hepatoma cell line HepG2. → Treatment of HepG2 cells with PPARγ agonist GW1929 leads to dissociation of LXRβ from ABCA1-LXRβ complex. → Inhibition of protein kinases MEK1/2 abolishes PPARγ-mediated dissociation of LXRβ from ABCA1/LXRβ complex. → Activation of PPARγ leads to increasing of the level of LXRβ associated with LXRE within ABCA1 gene promoter. -- Abstract: Synthesis of ABCA1 protein in liver is necessary for high-density lipoproteins (HDL) formation in mammals. Nuclear receptor PPARγ is known as activator of ABCA1 expression, but details of PPARγ-mediated regulation of ABCA1 at both transcriptional and post-transcriptional levels in hepatocytes have not still been well elucidated. In this study we have shown, that PPARγ activates ABCA1 gene transcription in human hepatoma cells HepG2 through increasing of LXRβ binding with promoter region of ABCA1 gene. Treatment of HepG2 cells with PPARγ agonist GW1929 leads to dissociation of LXRβ from ABCA1/LXRβ complex and to nuclear translocation of this nuclear receptor resulting in reduction of ABCA1 protein level 24 h after treatment. Inhibition of protein kinases MEK1/2 abolishes PPARγ-mediated dissociation of LXRβ from ABCA1/LXRβ complex, but does not block PPARγ-dependent down-regulation of ABCA1 protein in HepG2 cells. These data suggest that PPARγ may be important for regulation of the level of hepatic ABCA1 protein and indicate the new interplays between PPARγ, LXRβ and MEK1/2 in regulation of ABCA1 mRNA and protein expression.

  5. ABCA7 and risk of dementia and vascular disease in the Danish population

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    Kjeldsen, Emilie W.; Tybjærg-Hansen, Anne; Nordestgaard, Børge G.

    2018-01-01

    Objective: ATP-binding-cassette transporter A7(ABCA7) is suggested to be involved in lipid transport as well as in phagocytosis of amyloid-β in the brain. We tested the hypothesis that a common genetic variant in ABCA7 is associated with dementia, ischemic heart disease, ischemic cerebrovascular ...

  6. An ABCA1 truncation shows no dominant negative effect in a familial hypoalphalipoproteinemia pedigree with three ABCA1 mutations

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    Sorrenson, Brie; Suetani, Rachel J. [Department of Biochemistry, University of Otago, Dunedin (New Zealand); Bickley, Vivienne M.; George, Peter M. [Clinical Biochemistry, Canterbury Health Laboratories, Christchurch (New Zealand); Williams, Michael J.A. [Department of Medicine, University of Otago, Dunedin (New Zealand); Scott, Russell S. [Lipid and Diabetes Research Group, Christchurch Hospital (New Zealand); McCormick, Sally P.A., E-mail: sally.mccormick@otago.ac.nz [Department of Biochemistry, University of Otago, Dunedin (New Zealand)

    2011-06-10

    Highlights: {yields} Characterisation of an ABCA1 truncation mutant, C978fsX988, in a pedigree with three ABCA1 mutations. {yields} Functional analysis of C978fsX988 in patient fibroblasts and HEK 293 cells shows no cholesterol efflux function. {yields} Allele-specific quantification shows C978fsX988 not expressed at mRNA level in fibroblasts. {yields} Unlike other ABCA1 truncations, C978fsX988 mutant shows no dominant negative effect at mRNA or protein level. -- Abstract: The ATP binding cassette transporter (ABCA1) A1 is a key determinant of circulating high density lipoprotein cholesterol (HDL-C) levels. Mutations in ABCA1 are a major genetic contributor to low HDL-C levels within the general population. Following the finding of three different ABCA1 mutations, p.C978fsX988, p.T1512M and p.N1800H in a subject with hypoalphalipoproteinemia, we aimed to establish whether the p.C978fsX988 truncation exerted a dominant negative effect on the full-length ABCA1 alleles within family members as has been reported for other ABCA1 truncations. Characterisation of the p.C978fsX988 mutant in transfected HEK 293 cells showed it to be expressed as a GFP fusion protein but lacking in cholesterol efflux function. This was in keeping with results from cholesterol efflux assays in the fibroblasts of p.C978fsX988 carriers which also showed impaired efflux. Allele- specific quantification of p.C978fsX988 mRNA and analysis of ABCA1 protein levels in the fibroblasts of p.C978fsX988 heterozygotes showed negligible levels of mRNA and protein expression. There was no evidence of a dominant negative effect on wildtype or p.N1800H protein levels. We conclude that in the case of the p.C978fsX988 truncated mutant a lack of expression precludes it from having a dominant negative effect.

  7. The translational expression of ABCA2 and ABCA3 is a strong prognostic biomarker for multidrug resistance in pediatric acute lymphoblastic leukemia

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    Aberuyi N

    2017-07-01

    Full Text Available Narges Aberuyi,1 Soheila Rahgozar,1 Zohreh Khosravi Dehaghi,1 Alireza Moafi,2 Andrea Masotti,3,* Alessandro Paolini3,* 1Department of Biology, Faculty of Science, University of Isfahan, 2Department of Pediatric-Hematology-Oncology, Sayed-ol-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran; 3Gene Expression – Microarrays Laboratory, Bambino Gesù Children’s Hospital-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS, Rome, Italy *These authors contributed equally to the manuscript Purpose: The aim of this work was to study the correlation between the expressions of the ABCA2 and ABCA3 genes at the mRNA and protein levels in children with acute lymphoblastic leukemia (ALL and the effects of this association on multidrug resistance (MDR.Materials and methods: Sixty-nine children with de novo ALL and 25 controls were enrolled in the study. Mononuclear cells were isolated from the bone marrow. The mRNA levels of ABCA2 and ABCA3 were measured by real-time polymerase chain reaction (PCR. Samples with high mRNA levels were assessed for respective protein levels by Western blotting. Following the first year of treatment, persistent monoclonality of T-cell gamma receptors or immunoglobulin H (IgH gene rearrangement was assessed and considered as the MDR. The tertiary structure of ABCA2 was predicted using Phyre2 and I-TASSER web systems and compared to that of ABCA3, which has been previously reported. Molecular docking was performed using DOCK 6.7.Results: Real-time quantitative PCR (qRT-PCR showed high levels of ABCA2 and ABCA3 mRNAs in 13 and 17 samples, respectively. Among them, five and eight individuals demonstrated high levels of ABCA2 and ABCA3, respectively. Response to chemotherapy was significantly decreased (P=0.001 when the mRNA and protein of both genes were overexpressed compared to individuals with high transcriptional levels of either ABCA2 or ABCA3 alone. Close similarity between ABCA2 and ABCA3

  8. Functional rescue of mutant ABCA1 proteins by sodium 4-phenylbutyrate.

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    Sorrenson, Brie; Suetani, Rachel J; Williams, Michael J A; Bickley, Vivienne M; George, Peter M; Jones, Gregory T; McCormick, Sally P A

    2013-01-01

    Mutations in the ATP-binding cassette transporter A1 (ABCA1) are a major cause of decreased HDL cholesterol (HDL-C), which infers an increased risk of cardiovascular disease (CVD). Many ABCA1 mutants show impaired localization to the plasma membrane. The aim of this study was to investigate whether the chemical chaperone, sodium 4-phenylbutyrate (4-PBA) could improve cellular localization and function of ABCA1 mutants. Nine different ABCA1 mutants (p.A594T, p.I659V, p.R1068H, p.T1512M, p.Y1767D, p.N1800H, p.R2004K, p.A2028V, p.Q2239N) expressed in HEK293 cells, displaying different degrees of mislocalization to the plasma membrane and discrete impacts on cholesterol efflux, were subject to treatment with 4-PBA. Treatment restored localization to the plasma membrane and increased cholesterol efflux function for the majority of mutants. Treatment with 4-PBA also increased ABCA1 protein expression in all transfected cell lines. In fibroblast cells obtained from low HDL-C subjects expressing two of the ABCA1 mutants (p.R1068H and p.N1800H), 4-PBA increased cholesterol efflux without any increase in ABCA1 expression. Our study is the first to investigate the effect of the chemical chaperone, 4-PBA on ABCA1 and shows that it is capable of restoring plasma membrane localization and enhancing the cholesterol efflux function of mutant ABCA1s both in vitro and ex vivo. These results suggest 4-PBA may warrant further investigation as a potential therapy for increasing cholesterol efflux and HDL-C levels.

  9. Screening for functional sequence variations and mutations in ABCA1

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    Probst, Mario C. O.; Thumann, Harald; Aslanidis, Charalampos; Langmann, Thomas; Buechler, Christa; Patsch, Wolfgang; Baralle, Francisco E.; Dallinga-Thie, Geesje M.; Geisel, Jürgen; Keller, Christiane; Menys, Valentine C.; Schmitz, Gerd

    2004-01-01

    Mutations in the ATP-binding cassette 1 transporter gene (ABCA1) are responsible for the genetic HDL-deficiency syndromes, which are characterized by severely diminished plasma HDL-C levels and a predisposition to cardiovascular disease and splenomegaly. The ABCA1 gene contains 50 exons and codes

  10. ABCA7 rare variants and Alzheimer disease risk.

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    Le Guennec, Kilan; Nicolas, Gaël; Quenez, Olivier; Charbonnier, Camille; Wallon, David; Bellenguez, Céline; Grenier-Boley, Benjamin; Rousseau, Stéphane; Richard, Anne-Claire; Rovelet-Lecrux, Anne; Bacq, Delphine; Garnier, Jean-Guillaume; Olaso, Robert; Boland, Anne; Meyer, Vincent; Deleuze, Jean-François; Amouyel, Philippe; Munter, Hans Markus; Bourque, Guillaume; Lathrop, Mark; Frebourg, Thierry; Redon, Richard; Letenneur, Luc; Dartigues, Jean-François; Pasquier, Florence; Rollin-Sillaire, Adeline; Génin, Emmanuelle; Lambert, Jean-Charles; Hannequin, Didier; Campion, Dominique

    2016-06-07

    To study the association between ABCA7 rare coding variants and Alzheimer disease (AD) in a case-control setting. We conducted a whole exome analysis among 484 French patients with early-onset AD and 590 ethnically matched controls. After collapsing rare variants (minor allele frequency ≤1%), we detected an enrichment of ABCA7 loss of function (LOF) and predicted damaging missense variants in cases (odds ratio [OR] 3.40, 95% confidence interval [CI] 1.68-7.35, p = 0.0002). Performing a meta-analysis with previously published data, we found that in a combined sample of 1,256 patients and 1,347 controls from France and Belgium, the OR was 2.81 (95% CI 1.89-4.20, p = 3.60 × 10(-7)). These results confirm that ABCA7 LOF variants are enriched in patients with AD and extend this finding to predicted damaging missense variants. © 2016 American Academy of Neurology.

  11. Post-transcriptional regulation of macrophage ABCA1, an early response gene to IFN-γ

    International Nuclear Information System (INIS)

    Alfaro Leon, Martha Leticia; Evans, Glenn F.; Farmen, Mark W.; Zuckerman, Steven H.

    2005-01-01

    Interferon-γ (IFN-γ) down-regulates receptors associated with reverse cholesterol transport including ABCA1. In the present study, the kinetics and mechanism of ABCA1 down-regulation were determined in mouse peritoneal macrophages. IFN-γ decreased ABCA1 mRNA 1 h following IFN-γ addition and was maximally reduced by 3 h. Down-regulation was protein synthesis dependent and involved post-transcriptional processes. ABCA1 message had a T 1/2 of 115 min in actinomycin treated cells that was reduced to a T 1/2 of 37 min by IFN-γ. The decrease in message stability was also associated with a rapid loss of ABCA1 protein, significant 3 h following IFN-γ addition. The kinetics of ABCA1 message and protein decrease was consistent with the early IFN-γ-induced changes in Stat1 phosphorylation and nuclear translocation observed in these cells. Therefore, ABCA1 can be considered as an early response gene to macrophage activation by IFN-γ with down-regulation occurring by message destabilization

  12. Cellular Cholesterol Regulates Ubiquitination and Degradation of the Cholesterol Export Proteins ABCA1 and ABCG1*

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    Hsieh, Victar; Kim, Mi-Jurng; Gelissen, Ingrid C.; Brown, Andrew J.; Sandoval, Cecilia; Hallab, Jeannette C.; Kockx, Maaike; Traini, Mathew; Jessup, Wendy; Kritharides, Leonard

    2014-01-01

    The objective of this study was to examine the influence of cholesterol in post-translational control of ABCA1 and ABCG1 protein expression. Using CHO cell lines stably expressing human ABCA1 or ABCG1, we observed that the abundance of these proteins is increased by cell cholesterol loading. The response to increased cholesterol is rapid, is independent of transcription, and appears to be specific for these membrane proteins. The effect is mediated through cholesterol-dependent inhibition of transporter protein degradation. Cell cholesterol loading similarly regulates degradation of endogenously expressed ABCA1 and ABCG1 in human THP-1 macrophages. Turnover of ABCA1 and ABCG1 is strongly inhibited by proteasomal inhibitors and is unresponsive to inhibitors of lysosomal proteolysis. Furthermore, cell cholesterol loading inhibits ubiquitination of ABCA1 and ABCG1. Our findings provide evidence for a rapid, cholesterol-dependent, post-translational control of ABCA1 and ABCG1 protein levels, mediated through a specific and sterol-sensitive mechanism for suppression of transporter protein ubiquitination, which in turn decreases proteasomal degradation. This provides a mechanism for acute fine-tuning of cholesterol transporter activity in response to fluctuations in cell cholesterol levels, in addition to the longer term cholesterol-dependent transcriptional regulation of these genes. PMID:24500716

  13. Alterations of plasma lipids in mice via adenoviral-mediated hepatic overexpression of human ABCA1

    NARCIS (Netherlands)

    Wellington, Cheryl L.; Brunham, Liam R.; Zhou, Steven; Singaraja, Roshni R.; Visscher, Henk; Gelfer, Allison; Ross, Colin; James, Erick; Liu, Guoqing; Huber, Mary T.; Yang, Yu-Zhou; Parks, Robin J.; Groen, Albert; Fruchart-Najib, Jamila; Hayden, Michael R.

    2003-01-01

    ATP binding cassette transporter A1 (ABCA1) is a widely expressed lipid transporter essential for the generation of HDL. ABCA1 is particularly abundant in the liver, suggesting that the liver may play a major role in HDL homeostasis. To determine how hepatic ABCA1 affects plasma HDL cholesterol

  14. Recurrent amplification of RTEL1 and ABCA13 and its synergistic effect associated with clinicopathological data of gastric adenocarcinoma.

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    Araújo, T M; Seabra, A D; Lima, E M; Assumpção, P P; Montenegro, R C; Demachki, S; Burbano, R M; Khayat, A S

    2016-01-01

    Despite progression in treatment of gastric cancer, prognosis of patients remains poor, in part due to the low rate of diagnosis during its early stages. This paradigm implies the necessity to identify molecular biomarkers for early gastric cancer diagnosis, as well as for disease monitoring, thus contributing to the development of new therapeutic approaches. In a previous study, performed by array-Comparative Genomic Hybridization, we described for the first time in literature recurrent amplification of RTEL1 and ABCA13 genes in gastric cancer. Thus, the aim of the present study was to validate recurrent amplification of RTEL1 and ABCA13 genes and associate CNV status with clinicopathological data. Results showed RTEL1 and ABCA13 amplification in 38 % of samples. Statistical analysis demonstrated that RTEL amplification is more common in older patients and more associated with intestinal type and ABCA13 amplification increases the risk of lymph node metastasis and is more common in men. Co-amplification of these genes showed a significant association with advanced staging. aCGH is a very useful tool for investigating novel genes associated with carcinogenesis and RTEL1 amplification may be important for the development of gastric cancer in older patients, besides being a probable event contributing for chromosomal instability in intestinal gastric carcinogenesis. ABCA13 amplification may have age-specific function and could be considered a useful marker for predicting lymph node metastasis in resected gastric cancer patients in early stage. Lastly, RTEL1 and ABCA13 synergistic effect may be considered as a putative marker for advanced staging in gastric cancer patients.

  15. Apolipoprotein E levels in cerebrospinal fluid and the effects of ABCA1 polymorphisms

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    Mayo Kevin

    2007-04-01

    Full Text Available Abstract Background Animal studies suggest that brain apolipoprotein E (apoE levels influence amyloid-β (Aβ deposition and thus risk for Alzheimer's disease (AD. We have previously demonstrated that deletion of the ATP-binding cassette A1 transporter (ABCA1 in mice causes dramatic reductions in brain and cerebrospinal fluid (CSF apoE levels and lipidation. To examine whether polymorphisms in ABCA1 affect CSF apoE levels in humans, we measured apoE in CSF taken from 168 subjects who were 43 to 91 years old and were either cognitively normal or who had mild AD. We then genotyped the subjects for ten previously identified ABCA1 single nucleotide polymorphisms (SNPs. Results In all subjects, the mean CSF apoE level was 9.09 μg/ml with a standard deviation of 2.70 μg/ml. Levels of apoE in CSF samples taken from the same individual two weeks apart were strongly correlated (r2 = 0.93, p APOE genotype, gender or race. Average apoE levels increased with age by ~0.5 μg/ml per 10 years (r2 = 0.05, p = 0.003. We found no significant associations between CSF apoE levels and the ten ABCA1 SNPs we genotyped. Moreover, in a separate sample of 1225 AD cases and 1431 controls, we found no association between the ABCA1 SNP rs2230806 and AD as has been previously reported. Conclusion We found that CSF apoE levels vary widely between individuals, but are stable within individuals over a two-week interval. AD status, APOE genotype, gender and race do not affect CSF apoE levels, but average CSF apoE levels increase with age. Given the lack of association between CSF apoE levels and genotypes for the ABCA1 SNPs we examined, either these SNPs do not affect ABCA1 function or if they do, they do not have strong effects in the CNS. Finally, we find no evidence for an association between the ABCA1 SNP rs2230806 and AD in a large sample set.

  16. Large-scale deletions of the ABCA1 gene in patients with hypoalphalipoproteinemia.

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    Dron, Jacqueline S; Wang, Jian; Berberich, Amanda J; Iacocca, Michael A; Cao, Henian; Yang, Ping; Knoll, Joan; Tremblay, Karine; Brisson, Diane; Netzer, Christian; Gouni-Berthold, Ioanna; Gaudet, Daniel; Hegele, Robert A

    2018-06-04

    Copy-number variations (CNVs) have been studied in the context of familial hypercholesterolemia but have not yet been evaluated in patients with extremes of high-density lipoprotein (HDL) cholesterol levels. We evaluated targeted next-generation sequencing data from patients with very low HDL cholesterol (i.e. hypoalphalipoproteinemia) using the VarSeq-CNV caller algorithm to screen for CNVs disrupting the ABCA1, LCAT or APOA1 genes. In four individuals, we found three unique deletions in ABCA1: a heterozygous deletion of exon 4, a heterozygous deletion spanning exons 8 to 31, and a heterozygous deletion of the entire ABCA1 gene. Breakpoints were identified using Sanger sequencing, and the full-gene deletion was also confirmed using exome sequencing and the Affymetrix CytoScanTM HD Array. Before now, large-scale deletions in candidate HDL genes have not been associated with hypoalphalipoproteinemia; our findings indicate that CNVs in ABCA1 may be a previously unappreciated genetic determinant of low HDL cholesterol levels. By coupling bioinformatic analyses with next-generation sequencing data, we can successfully assess the spectrum of genetic determinants of many dyslipidemias, now including hypoalphalipoproteinemia. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Cholesterol Transporters ABCA1 and ABCG1 Gene Expression in Peripheral Blood Mononuclear Cells in Patients with Metabolic Syndrome

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    Zahra Tavoosi

    2015-01-01

    Full Text Available ABCA1 and ABCG1 genes encode the cholesterol transporter proteins that play a key role in cholesterol and phospholipids homeostasis. This study was aimed at evaluating and comparing ABCA1 and ABCG1 genes expression in metabolic syndrome patients and healthy individuals. This case-control study was performed on 36 patients with metabolic syndrome and the same number of healthy individuals in Hamadan (west of Iran during 2013-2014. Total RNA was extracted from mononuclear cells and purified using RNeasy Mini Kit column. The expression of ABCA1 and ABCG1 genes was performed by qRT-PCR. Lipid profile and fasting blood glucose were measured using colorimetric procedures. ABCG1 expression in metabolic syndrome patients was significantly lower (about 75% compared to that of control group, while for ABCA1 expression, there was no significant difference between the two studied groups. Comparison of other parameters such as HDL-C, FBS, BMI, waist circumference, and systolic and diastolic blood pressure between metabolic syndrome patients and healthy individuals showed significant differences (P<0.05. Decrease in ABCG1 expression in metabolic syndrome patients compared to healthy individuals suggests that hyperglycemia, related metabolites, and hyperlipidemia over the transporter capacity resulted in decreased expression of ABCG1. Absence of a significant change in ABCA1 gene expression between two groups can indicate a different regulation mechanism for ABCA1 expression.

  18. Urotensin II increases foam cell formation by repressing ABCA1 expression through the ERK/NF-κB pathway in THP-1 macrophages

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    Wang, Yan [Department of Anesthesiology, The Second Affiliated Hospital of University of South China, Hengyang 421001, Hunan (China); Wu, Jian-Feng [Department of Cardiovascular Medicine, The Second Affiliated Hospital of University of South China, Hengyang 421001, Hunan (China); Tang, Yan-Yan; Zhang, Min; Li, Yuan [Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang 421001, Hunan (China); Chen, Kong; Zeng, Meng-Ya [Department of Cardiovascular Medicine, The Second Affiliated Hospital of University of South China, Hengyang 421001, Hunan (China); Yao, Feng; Xie, Wei [Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang 421001, Hunan (China); Zheng, Xi-Long [Department of Biochemistry and Molecular Biology, Libin Cardiovascular Institute of Alberta, University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1 (Canada); Zeng, Gao-Feng, E-mail: qichingnudou@tom.com [Department of Cardiovascular Medicine, The Second Affiliated Hospital of University of South China, Hengyang 421001, Hunan (China); Tang, Chao-Ke, E-mail: tangchaoke@qq.com [Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang 421001, Hunan (China)

    2014-10-03

    Highlights: • U II reduces cholesterol efflux in THP-1 macrophages. • U II decreases the expression of ABCA1. • Inhibition of the ERK/NF-κB pathway reduces U II effects on ABCA1 expression and cholesterol efflux. - Abstract: Objective: Foam cell formation in the arterial wall plays a key role in the development of atherosclerosis. Recent studies showed that Urotensin II (U II) is involved in the pathogenesis of atherosclerosis. Here we examined the effects of human U II on ATP-binding cassette transporter A1 (ABCA1) expression and the underlying mechanism in THP-1 macrophages. Methods and results: Cultured THP-1 macrophages were treated with U II, followed by measuring the intracellular lipid contents, cholesterol efflux and ABCA1 levels. The results showed that U II dramatically decreased ABCA1 levels and impaired cholesterol efflux. However, the effects of U II on ABCA1 protein expression and cellular cholesterol efflux were partially reversed by inhibition of extracellular signal regulated kinase 1/2 (ERK1/2) and nuclear factor kappa B (NF-κB) activity, suggesting the potential roles of ERK1/2 and NF-κB in ABCA1 expression, respectively. Conclusion: Our current data indicate that U II may have promoting effects on the progression of atherosclerosis, likely through suppressing ABCA1 expression via activation of the ERK/NF-κB pathway and reducing cholesterol efflux to promote macrophage foam cell formation.

  19. Activation of Liver X Receptor Decreases Atherosclerosis in Ldlr−/− mice in the Absence of ABCA1 and ABCG1 in Myeloid Cells

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    Kappus, Mojdeh S.; Murphy, Andrew J.; Abramowicz, Sandra; Ntonga, Vusisizwe; Welch, Carrie L.; Tall, Alan R.; Westerterp, Marit

    2014-01-01

    Objective Liver X Receptor (LXR) activators decrease atherosclerosis in mice. LXR activators (1) directly up-regulate genes involved in reverse cholesterol transport (RCT) and (2) exert anti-inflammatory effects mediated by transrepression of NFκB target genes. We investigated whether myeloid cell deficiency of ATP-binding cassette transporters A1 and G1 (ABCA1/G1), principal targets of LXR that promote macrophage cholesterol efflux and initiate RCT, would abolish the beneficial effects of LXR activation on atherosclerosis. Approach and Results LXR activator T0901317 (T0) substantially reduced inflammatory gene expression in macrophages lacking ABCA1/G1. Ldlr−/− mice were transplanted with Abca1−/−Abcg1−/− or wild-type bone marrow (BM) and fed a Western-type diet (WTD) for 6 weeks with or without T0 supplementation. Abca1/g1 BM deficiency increased atherosclerotic lesion complexity and inflammatory cell infiltration into the adventitia and myocardium. T0 markedly decreased lesion area, complexity and inflammatory cell infiltration in the Abca1−/−Abcg1−/− BM transplanted mice. To investigate whether this was due to macrophage Abca1/g1 deficiency, Ldlr−/− mice were transplanted with LysmCreAbca1fl/flAbcg1fl/fl or Abca1fl/flAbcg1fl/fl BM and fed WTD with or without the more specific LXR agonist GW3965 for 12 weeks. GW3965 decreased lesion size in both groups and the decrease was more prominent in the LysmCreAbca1fl/flAbcg1fl/fl group. Conclusions The results suggest that anti-inflammatory effects of LXR activators are of key importance to their anti-atherosclerotic effects in vivo independent of cholesterol efflux pathways mediated by macrophage ABCA1/G1. This has implications for the development of LXR activators that lack adverse effects on lipogenic genes while maintaining the ability to trans-repress inflammatory genes. PMID:24311381

  20. Akt inhibition promotes ABCA1-mediated cholesterol efflux to ApoA-I through suppressing mTORC1.

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    Fumin Dong

    Full Text Available ATP-binding cassette transporter A1 (ABCA1 plays an essential role in mediating cholesterol efflux to apolipoprotein A-I (apoA-I, a major housekeeping mechanism for cellular cholesterol homeostasis. After initial engagement with ABCA1, apoA-I directly interacts with the plasma membrane to acquire cholesterol. This apoA-I lipidation process is also known to require cellular signaling processes, presumably to support cholesterol trafficking to the plasma membrane. We report here that one of major signaling pathways in mammalian cells, Akt, is also involved. In several cell models that express ABCA1 including macrophages, pancreatic beta cells and hepatocytes, inhibition of Akt increases cholesterol efflux to apoA-I. Importantly, Akt inhibition has little effect on cells expressing non-functional mutant of ABCA1, implicating a specific role of Akt in ABCA1 function. Furthermore, we provide evidence that mTORC1, a major downstream target of Akt, is also a negative regulator of cholesterol efflux. In cells where mTORC1 is constitutively activated due to tuberous sclerosis complex 2 deletion, cholesterol efflux to apoA-I is no longer sensitive to Akt activity. This suggests that Akt suppresses cholesterol efflux through mTORC1 activation. Indeed, inhibition of mTORC1 by rapamycin or Torin-1 promotes cholesterol efflux. On the other hand, autophagy, one of the major pathways of cholesterol trafficking, is increased upon Akt inhibition. Furthermore, Akt inhibition disrupts lipid rafts, which is known to promote cholesterol efflux to apoA-I. We therefore conclude that Akt, through its downstream targets, mTORC1 and hence autophagy, negatively regulates cholesterol efflux to apoA-I.

  1. The effect of Alcoholic garlic (Allium sativum extract on ABCA1 expression in human THP-1 macrophages

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    Malekpour-Dehkordi Z

    2011-06-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: ATP-binding cassette transporter A1 (ABCA1 is a key mediator of cholesterol efflux to apoA-I in lipid-laden macrophages, the first step of reverse cholesterol transport (RCT in vivo and a critical step in preventing atherosclerosis. Enhanced ABCA1 expression may inhibit foam cell formation and consequently reduce atherogenic risk. On the other hand, garlic, Allium sativum, and garlic extracts have been demonstrated to have potential cardiovascular benefits. Moreover, garlic has direct antiatherogenic and antiathersclerotic effects on artery walls. The aim of this study was to evaluate the effects of alcoholic garlic extract on the expression of ABCA1 in macrophages."n"nMethods: Cell viability assay was used in order to detect the cytotoxic dose of alcoholic garlic extract on macrophages. Real-time PCR and Western blotting were performed to study the effects of alcoholic garlic extract on the expression of ABCA1. Macrophage cells were treated by different concentrations of alcoholic garlic extract for 48 h. The total RNA of the treated macrophages were extracted and analyzed by real-time PCR. ABCA1 protein expression was also analyzed using the Western blotting technique."n"nResults: Alcoholic garlic extract

  2. Quercetin-3-O-glucuronide induces ABCA1 expression by LXRα activation in murine macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Ohara, Kazuaki, E-mail: Kazuaki_Ohara@kirin.co.jp [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan); Wakabayashi, Hideyuki [Laboratory for New Product Development, Kirin Beverage Company Limited, 1-17-1 Namamugi, Tsurumi-ku, Yokohama 230-8628 (Japan); Taniguchi, Yoshimasa [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan); Shindo, Kazutoshi [Department of Food and Nutrition, Japan Women’s University, 2-8-1 Mejirodai, Bunkyo-ku, Tokyo 112-8681 (Japan); Yajima, Hiroaki [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan); Yoshida, Aruto [Central Laboratories for Key Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan)

    2013-11-29

    Highlights: •The major circulating quercetin metabolite (Q3GA) activated LXRα. •Q3GA induced ABCA1 via LXRα activation in macrophages. •Nelumbo nucifera leaf extracts contained quercetin glycosides. •N. nucifera leaf extract feeding elevated HDLC in mice. -- Abstract: Reverse cholesterol transport (RCT) removes excess cholesterol from macrophages to prevent atherosclerosis. ATP-binding cassette, subfamily A, member 1 (ABCA1) is a crucial cholesterol transporter involved in RCT to produce high density lipoprotein-cholesterol (HDLC), and is transcriptionally regulated by liver X receptor alpha (LXRα), a nuclear receptor. Quercetin is a widely distributed flavonoid in edible plants which prevented atherosclerosis in an animal model. We found that quercetin-3-O-glucuronide (Q3GA), a major quercetin metabolite after absorption from the digestive tract, enhanced ABCA1 expression, in vitro, via LXRα in macrophages. In addition, leaf extracts of a traditional Asian edible plant, Nelumbo nucifera (NNE), which contained abundant amounts of quercetin glycosides, significantly elevated plasma HDLC in mice. We are the first to present experimental evidence that Q3GA induced ABCA1 in macrophages, and to provide an alternative explanation to previous studies on arteriosclerosis prevention by quercetin.

  3. Inhibition of macrophage oxidative stress prevents the reduction of ABCA-1 transporter induced by advanced glycated albumin.

    Science.gov (United States)

    de Souza Pinto, Raphael; Castilho, Gabriela; Paim, Bruno Alves; Machado-Lima, Adriana; Inada, Natalia M; Nakandakare, Edna Regina; Vercesi, Aníbal Eugênio; Passarelli, Marisa

    2012-05-01

    We investigated the role of aminoguanidine and benfotiamine on the inhibition of reactive oxygen species (ROS) generation in macrophages induced by advanced glycated albumin (AGE-albumin) and its relationship with cell cholesterol homeostasis, emphasizing the expression of the ATP binding cassette transporter A-1 (ABCA-1). AGE-albumin was made by incubating fatty acid-free albumin with 10 mM glycolaldehyde. ROS production and ABCA-1 protein level were determined by flow cytometry in J774 macrophages treated along time with control (C) or AGE-albumin alone or in the presence of aminoguanidine or benfotiamine. Mitochondrial function was evaluated by oxygraphy. Compared to C-albumin, AGE-albumin increased ROS production in macrophages, which was ascribed to the activities of NADPH oxidase and of the mitochondrial system. Mitochondrial respiratory chain activity was reduced in cells incubated with AGE-albumin. ROS generation along time was associated with the reduction in macrophage ABCA-1 protein level. Aminoguanidine prevented ROS elevation and restored the ABCA-1 content in macrophages; on the other hand, benfotiamine that promoted a lesser reduction in ROS generation was not able to restore ABCA-1 levels. Inhibition of oxidative stress induced by AGE-albumin prevents disturbances in reverse cholesterol transport by curbing the reduction of ABCA-1 elicited by advanced glycation in macrophages and therefore may contribute to the prevention of atherosclerosis in diabetes mellitus.

  4. Contribution to Alzheimer's disease risk of rare variants in TREM2, SORL1, and ABCA7 in 1779 cases and 1273 controls.

    Science.gov (United States)

    Bellenguez, Céline; Charbonnier, Camille; Grenier-Boley, Benjamin; Quenez, Olivier; Le Guennec, Kilan; Nicolas, Gaël; Chauhan, Ganesh; Wallon, David; Rousseau, Stéphane; Richard, Anne Claire; Boland, Anne; Bourque, Guillaume; Munter, Hans Markus; Olaso, Robert; Meyer, Vincent; Rollin-Sillaire, Adeline; Pasquier, Florence; Letenneur, Luc; Redon, Richard; Dartigues, Jean-François; Tzourio, Christophe; Frebourg, Thierry; Lathrop, Mark; Deleuze, Jean-François; Hannequin, Didier; Genin, Emmanuelle; Amouyel, Philippe; Debette, Stéphanie; Lambert, Jean-Charles; Campion, Dominique

    2017-11-01

    We performed whole-exome and whole-genome sequencing in 927 late-onset Alzheimer disease (LOAD) cases, 852 early-onset AD (EOAD) cases, and 1273 controls from France. We assessed the evidence for gene-based association of rare variants with AD in 6 genes for which an association with such variants was previously claimed. When aggregating protein-truncating and missense-predicted damaging variants, we found exome-wide significant association between EOAD risk and rare variants in SORL1, TREM2, and ABCA7. No exome-wide significant signal was obtained in the LOAD sample, and significance of the order of 10 -6 was observed in the whole AD group for TREM2. Our study confirms previous gene-level results for TREM2, SORL1, and ABCA7 and provides a clearer insight into the classes of rare variants involved. Despite different effect sizes and varying cumulative minor allele frequencies, the rare protein-truncating and missense-predicted damaging variants in TREM2, SORL1, and ABCA7 contribute similarly to the heritability of EOAD and explain between 1.1% and 1.5% of EOAD heritability each, compared with 9.12% for APOE ε4. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Hsp27 promotes ABCA1 expression and cholesterol efflux through the PI3K/PKCζ/Sp1 pathway in THP-1 macrophages.

    Science.gov (United States)

    Kuang, Hai-Jun; Zhao, Guo-Jun; Chen, Wu-Jun; Zhang, Min; Zeng, Gao-Feng; Zheng, Xi-Long; Tang, Chao-Ke

    2017-09-05

    Heat shock protein 27 (Hsp27) is a putative biomarker and therapeutic target in atherosclerosis. This study was to explore the potential mechanisms underlying Hsp27 effects on ATP-binding cassette transporter A1 (ABCA1) expression and cellular cholesterol efflux. THP-1 macrophage-derived foam cells were infected with adenovirus to express wild-type Hsp27, hyper-phosphorylated Hsp27 mimic (3D Hsp27), antisense Hsp27 or hypo-phosphorylated Hsp27 mimic (3A Hsp27). Wild-type and 3D Hsp27 were found to up-regulate ABCA1 mRNA and protein expression and increase cholesterol efflux from cells. Expression of antisense or 3A Hsp27 suppressed the expression of ABCA1 and cholesterol efflux. Furthermore, over-expression of wild-type and 3D Hsp27 significantly increased the levels of phosphorylated specificity protein 1 (Sp1), protein kinase C ζ (PKCζ) and phosphatidylinositol 3-kinase (PI3K). In addition, the up-regulation of ABCA1 expression and cholesterol efflux induced by 3D Hsp27 was suppressed by inhibition of Sp1, PKCζ and PI3K with specific kinase inhibitors. Taken together, our results revealed that Hsp27 may up-regulate the expression of ABCA1 and promotes cholesterol efflux through activation of the PI3K/PKCζ/Sp1 signal pathway in THP-1 macrophage-derived foam cells. Our findings may partly explain the mechanisms underlying the anti-atherogenic effect of Hsp27. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. ABCA Transporter Gene Expression and Poor Outcome in Epithelial Ovarian Cancer

    DEFF Research Database (Denmark)

    Hedditch, Ellen L; Gao, Bo; Russell, Amanda J

    2014-01-01

    -wide association study. Impact of short interfering RNA-mediated gene suppression was determined by colony forming and migration assays. Association with survival was assessed with Kaplan-Meier analysis and log-rank tests. All statistical tests were two-sided. RESULTS: Associations with outcome were observed...... with ABC transporters of the "A" subfamily, but not with multidrug transporters. High-level expression of ABCA1, ABCA6, ABCA8, and ABCA9 in primary tumors was statistically significantly associated with reduced survival in serous ovarian cancer patients. Low levels of ABCA5 and the C-allele of rs536009...... ABCA1, ABCA5 and ABCA9 gene expression = 33.2 months, 95% CI = 26.4 to 40.1; vs 55.3 months in the group with favorable ABCA gene expression, 95% CI = 49.8 to 60.8; P = .001), independently of tumor stage or surgical debulking status. Suppression of cholesterol transporter ABCA1 inhibited ovarian...

  7. Multiple splice defects in ABCA1 cause low HDL-C in a family with Hypoalphalipoproteinemia and premature coronary disease

    Directory of Open Access Journals (Sweden)

    Miller Michael

    2009-01-01

    Full Text Available Abstract Background Mutations at splice junctions causing exon skipping are uncommon compared to exonic mutations, and two intronic mutations causing an aberrant phenotype have rarely been reported. Despite the high number of functional ABCA1 mutations reported to date, splice variants have been reported infrequently. We screened DNA from a 41 year-old male with low HDL-C (12 mg/dL [0.31 mmol/L] and a family history of premature coronary heart disease (CHD using polymerase chain reaction single-strand conformation polymorphism (SSCP analysis. Methods Family members with low levels of HDL-C (n = 6 were screened by SSCP for mutations in ABCA1. Samples with altered SSCP patterns were sequenced directly using either an ABI 3700 or ABI3730Xl DNA Analyzer. To screen for splicing defects, cDNA was isolated from the proband's RNA and was sequenced as above. A series of minigenes were constructed to determine the contribution of normal and defective alleles. Results Two novel splice variants in ABCA1 were identified. The first mutation was a single base pair change (T->C in IVS 7, 6 bps downstream from the exon7/intron7 junction. Amplification of cDNA and allelic subcloning identified skipping of Exon 7 that results in the elimination of 59 amino acids from the first extracellular loop of the ABCA1 protein. The second mutation was a single base pair change (G->C at IVS 31 -1, at the intron/exon junction of exon 32. This mutation causes skipping of exon 32, resulting in 8 novel amino acids followed by a stop codon and a predicted protein size of 1496 AA, compared to normal (2261 AA. Bioinformatic studies predicted an impact on splicing as confirmed by in vitro assays of constitutive splicing. Conclusion In addition to carnitine-acylcarnitine translocase (CACT deficiency and Hermansky-Pudlak syndrome type 3, this represents only the third reported case in which 2 different splice mutations has resulted in an aberrant clinical phenotype.

  8. Hepatic ACAT2 knock down increases ABCA1 and modifies HDL metabolism in mice.

    Directory of Open Access Journals (Sweden)

    Matteo Pedrelli

    Full Text Available OBJECTIVES: ACAT2 is the exclusive cholesterol-esterifying enzyme in hepatocytes and enterocytes. Hepatic ABCA1 transfers unesterified cholesterol (UC to apoAI, thus generating HDL. By changing the hepatic UC pool available for ABCA1, ACAT2 may affect HDL metabolism. The aim of this study was to reveal whether hepatic ACAT2 influences HDL metabolism. DESIGN: WT and LXRα/β double knockout (DOKO mice were fed a western-type diet for 8 weeks. Animals were i.p. injected with an antisense oligonucleotide targeted to hepatic ACAT2 (ASO6, or with an ASO control. Injections started 4 weeks after, or concomitantly with, the beginning of the diet. RESULTS: ASO6 reduced liver cholesteryl esters, while not inducing UC accumulation. ASO6 increased hepatic ABCA1 protein independently of the diet conditions. ASO6 affected HDL lipids (increased UC only in DOKO, while it increased apoE-containing HDL in both genotypes. In WT mice ASO6 led to the appearance of large HDL enriched in apoAI and apoE. CONCLUSIONS: The use of ASO6 revealed a new pathway by which the liver may contribute to HDL metabolism in mice. ACAT2 seems to be a hepatic player affecting the cholesterol fluxes fated to VLDL or to HDL, the latter via up-regulation of ABCA1.

  9. Tangshen Formula Attenuates Diabetic Nephropathy by Promoting ABCA1-Mediated Renal Cholesterol Efflux in db/db Mice.

    Science.gov (United States)

    Liu, Peng; Peng, Liang; Zhang, Haojun; Tang, Patrick Ming-Kuen; Zhao, Tingting; Yan, Meihua; Zhao, Hailing; Huang, Xiaoru; Lan, Huiyao; Li, Ping

    2018-01-01

    The commonly prescribed Tangshen Formula (TSF) is a traditional Chinese formulation that has been shown to reduce plasma lipid metabolism and proteinuria and improve the estimated glomerular filtration rate (eGFR) in patients with diabetic kidney disease. This study investigated the underlying mechanism whereby TSF regulates renal lipid accumulation and ameliorates diabetic renal injuries in spontaneous diabetic db/db mice and in vitro in sodium palmitate (PA)-stimulated and Abca1-SiRNA-transfected mouse tubular epithelial cells (mTECs). The results revealed that TSF treatment significantly ameliorated the renal injuries by lowering urinary albumin excretion and improving renal tissue injuries in diabetic (db/db) mice. Interestingly, the treatment with TSF also resulted in decreased cholesterol levels in the renal tissues of db/db mice, which was associated with increased expression of the peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), the Liver X receptors (LXR), and ATP-binding cassette subfamily A member 1 (ABCA1), suggesting that TSF might attenuate diabetic kidney injury via a mechanism associated with improving cholesterol efflux in the diabetic kidney. This was investigated in vitro in mTECs, and the results showed that TSF reduced the PA-stimulated cholesterol accumulation in mTECs. Mechanistically, the addition of TSF was capable of reversing PA-induced downregulation of PGC-1α, LXR, and ABCA1 expression and cholesterol accumulation in mTECs, suggesting that TSF might act the protection via the PGC-1α-LXR-ABCA1 pathway to improve the cholesterol efflux in the renal tissues of db/db mice. This was further confirmed by silencing ABCA1 to block the promotive effect of TSF on cholesterol efflux in vitro . In conclusion, TSF might ameliorate diabetic kidney injuries by promoting ABCA1-mediated renal cholesterol efflux.

  10. A Computational Approach From Gene to Structure Analysis of the Human ABCA4 Transporter Involved in Genetic Retinal Diseases.

    Science.gov (United States)

    Trezza, Alfonso; Bernini, Andrea; Langella, Andrea; Ascher, David B; Pires, Douglas E V; Sodi, Andrea; Passerini, Ilaria; Pelo, Elisabetta; Rizzo, Stanislao; Niccolai, Neri; Spiga, Ottavia

    2017-10-01

    The aim of this article is to report the investigation of the structural features of ABCA4, a protein associated with a genetic retinal disease. A new database collecting knowledge of ABCA4 structure may facilitate predictions about the possible functional consequences of gene mutations observed in clinical practice. In order to correlate structural and functional effects of the observed mutations, the structure of mouse P-glycoprotein was used as a template for homology modeling. The obtained structural information and genetic data are the basis of our relational database (ABCA4Database). Sequence variability among all ABCA4-deposited entries was calculated and reported as Shannon entropy score at the residue level. The three-dimensional model of ABCA4 structure was used to locate the spatial distribution of the observed variable regions. Our predictions from structural in silico tools were able to accurately link the functional effects of mutations to phenotype. The development of the ABCA4Database gathers all the available genetic and structural information, yielding a global view of the molecular basis of some retinal diseases. ABCA4 modeled structure provides a molecular basis on which to analyze protein sequence mutations related to genetic retinal disease in order to predict the risk of retinal disease across all possible ABCA4 mutations. Additionally, our ABCA4 predicted structure is a good starting point for the creation of a new data analysis model, appropriate for precision medicine, in order to develop a deeper knowledge network of the disease and to improve the management of patients.

  11. Neopterin negatively regulates expression of ABCA1 and ABCG1 by the LXRα signaling pathway in THP-1 macrophage-derived foam cells.

    Science.gov (United States)

    Yan, Jin-quan; Tan, Chun-zhi; Wu, Jin-hua; Zhang, Dong-cui; Chen, Ji-ling; Zeng, Bin-yuan; Jiang, Yu-ping; Nie, Jin; Liu, Wei; Liu, Qin; Dai, Hao

    2013-07-01

    To investigate the effects of neopterin on ABCA1 expression and cholesterol efflux in human THP-1 macrophage-derived foam cells, and to explore the role of the liver X receptor alpha (LXRα) involved. In the present study, THP-1 cells were pre-incubated with ox-LDL to become foam cells. The protein and mRNA expression were examined by Western blot assays and real-time quantitative PCR, respectively. Liquid scintillation counting and high performance liquid chromatography assays were used to test cellular cholesterol efflux and cholesterol content. Neopterin decreased ABCA1 expression and cholesterol efflux in a time- and concentration-dependent manner in THP-1 macrophage-derived foam cells, and the LXRα siRNA can reverse the inhibitory effects induced by neopterin. Neoterin has a negative regulation on ABCA1 expression via the LXRα signaling pathway, which suggests the aggravated effects of neopterin on atherosclerosis.

  12. Proteomic Analysis of ABCA1-Null Macrophages Reveals a Role for Stomatin-Like Protein-2 in Raft Composition and Toll-Like Receptor Signaling.

    Science.gov (United States)

    Chowdhury, Saiful M; Zhu, Xuewei; Aloor, Jim J; Azzam, Kathleen M; Gabor, Kristin A; Ge, William; Addo, Kezia A; Tomer, Kenneth B; Parks, John S; Fessler, Michael B

    2015-07-01

    Lipid raft membrane microdomains organize signaling by many prototypical receptors, including the Toll-like receptors (TLRs) of the innate immune system. Raft-localization of proteins is widely thought to be regulated by raft cholesterol levels, but this is largely on the basis of studies that have manipulated cell cholesterol using crude and poorly specific chemical tools, such as β-cyclodextrins. To date, there has been no proteome-scale investigation of whether endogenous regulators of intracellular cholesterol trafficking, such as the ATP binding cassette (ABC)A1 lipid efflux transporter, regulate targeting of proteins to rafts. Abca1(-/-) macrophages have cholesterol-laden rafts that have been reported to contain increased levels of select proteins, including TLR4, the lipopolysaccharide receptor. Here, using quantitative proteomic profiling, we identified 383 proteins in raft isolates from Abca1(+/+) and Abca1(-/-) macrophages. ABCA1 deletion induced wide-ranging changes to the raft proteome. Remarkably, many of these changes were similar to those seen in Abca1(+/+) macrophages after lipopolysaccharide exposure. Stomatin-like protein (SLP)-2, a member of the stomatin-prohibitin-flotillin-HflK/C family of membrane scaffolding proteins, was robustly and specifically increased in Abca1(-/-) rafts. Pursuing SLP-2 function, we found that rafts of SLP-2-silenced macrophages had markedly abnormal composition. SLP-2 silencing did not compromise ABCA1-dependent cholesterol efflux but reduced macrophage responsiveness to multiple TLR ligands. This was associated with reduced raft levels of the TLR co-receptor, CD14, and defective lipopolysaccharide-induced recruitment of the common TLR adaptor, MyD88, to rafts. Taken together, we show that the lipid transporter ABCA1 regulates the protein repertoire of rafts and identify SLP-2 as an ABCA1-dependent regulator of raft composition and of the innate immune response. © 2015 by The American Society for Biochemistry and

  13. Proteomic Analysis of ABCA1-Null Macrophages Reveals a Role for Stomatin-Like Protein-2 in Raft Composition and Toll-Like Receptor Signaling*

    Science.gov (United States)

    Chowdhury, Saiful M.; Zhu, Xuewei; Aloor, Jim J.; Azzam, Kathleen M.; Gabor, Kristin A.; Ge, William; Addo, Kezia A.; Tomer, Kenneth B.; Parks, John S.; Fessler, Michael B.

    2015-01-01

    Lipid raft membrane microdomains organize signaling by many prototypical receptors, including the Toll-like receptors (TLRs) of the innate immune system. Raft-localization of proteins is widely thought to be regulated by raft cholesterol levels, but this is largely on the basis of studies that have manipulated cell cholesterol using crude and poorly specific chemical tools, such as β-cyclodextrins. To date, there has been no proteome-scale investigation of whether endogenous regulators of intracellular cholesterol trafficking, such as the ATP binding cassette (ABC)A1 lipid efflux transporter, regulate targeting of proteins to rafts. Abca1−/− macrophages have cholesterol-laden rafts that have been reported to contain increased levels of select proteins, including TLR4, the lipopolysaccharide receptor. Here, using quantitative proteomic profiling, we identified 383 proteins in raft isolates from Abca1+/+ and Abca1−/− macrophages. ABCA1 deletion induced wide-ranging changes to the raft proteome. Remarkably, many of these changes were similar to those seen in Abca1+/+ macrophages after lipopolysaccharide exposure. Stomatin-like protein (SLP)-2, a member of the stomatin-prohibitin-flotillin-HflK/C family of membrane scaffolding proteins, was robustly and specifically increased in Abca1−/− rafts. Pursuing SLP-2 function, we found that rafts of SLP-2-silenced macrophages had markedly abnormal composition. SLP-2 silencing did not compromise ABCA1-dependent cholesterol efflux but reduced macrophage responsiveness to multiple TLR ligands. This was associated with reduced raft levels of the TLR co-receptor, CD14, and defective lipopolysaccharide-induced recruitment of the common TLR adaptor, MyD88, to rafts. Taken together, we show that the lipid transporter ABCA1 regulates the protein repertoire of rafts and identify SLP-2 as an ABCA1-dependent regulator of raft composition and of the innate immune response. PMID:25910759

  14. ApoA-I induces S1P release from endothelial cells through ABCA1 and SR-BI in a positive feedback manner.

    Science.gov (United States)

    Liu, Xing; Ren, Kun; Suo, Rong; Xiong, Sheng-Lin; Zhang, Qing-Hai; Mo, Zhong-Cheng; Tang, Zhen-Li; Jiang, Yue; Peng, Xiao-Shan; Yi, Guang-Hui

    2016-12-01

    Sphingosine-1-phosphate (S1P), which has emerged as a pivotal signaling mediator that participates in the regulation of multiple cellular processes, is derived from various cells, including vascular endothelial cells. S1P accumulates in lipoproteins, especially HDL, and the majority of free plasma S1P is bound to HDL. We hypothesized that HDL-associated S1P is released through mechanisms associated with the HDL maturation process. ApoA-I, a major HDL apolipoprotein, is a critical factor for nascent HDL formation and lipid trafficking via ABCA1. Moreover, apoA-I is capable of promoting bidirectional lipid movement through SR-BI. In the present study, we confirmed that apoA-I can facilitate the production and release of S1P by HUVECs. Furthermore, we demonstrated that ERK1/2 and SphK activation induced by apoA-I is involved in the release of S1P from HUVECs. Inhibitor and siRNA experiments showed that ABCA1 and SR-BI are required for S1P release and ERK1/2 phosphorylation induced by apoA-I. However, the effects triggered by apoA-I were not suppressed by inhibiting ABCA1/JAK2 or the SR-BI/Src pathway. S1P released due to apoA-I activation can stimulate the (ERK1/2)/SphK1 pathway through S1PR (S1P receptor) 1/3. These results indicated that apoA-I not only promotes S1P release through ABCA1 and SR-BI but also indirectly activates the (ERK1/2)/SphK1 pathway by releasing S1P to trigger their receptors. In conclusion, we suggest that release of S1P induced by apoA-I from endothelial cells through ABCA1 and SR-BI is a self-positive-feedback process: apoA-I-(ABCA1 and SR-BI)-(S1P release)-S1PR-ERK1/2-SphK1-(S1P production)-(more S1P release induced by apoA-I).

  15. Salvianolic acid B accelerated ABCA1-dependent cholesterol efflux by targeting PPAR-γ and LXRα

    Energy Technology Data Exchange (ETDEWEB)

    Yue, Jianmei [Department of Endocrinology, Shandong Province Hospital Affiliated to Shandong University, 324# Jing 5 Road, Jinan 255021 (China); Department of Endocrinology, The First Hospital of Zibo, 4# E Mei Shan Dong Road, Zibo 255200 (China); Li, Bo, E-mail: libosubmit@163.com [Department of Cardiology, Central Hospital of Zibo, 54# Gong Qing Tuan Xi Road, Zibo, Shandong Province (China); Jing, Qingping [Department of Endocrinology, The First Hospital of Zibo, 4# E Mei Shan Dong Road, Zibo 255200 (China); Guan, Qingbo, E-mail: guanqingbosubmit@163.com [Department of Endocrinology, Shandong Province Hospital Affiliated to Shandong University, 324# Jing 5 Road, Jinan 255021 (China)

    2015-07-03

    Objectives: Cholesterol efflux has been thought to be the main and basic mechanism by which free cholesterol is transferred from extra hepatic cells to the liver or intestine for excretion. Salvianolic acid B (Sal B) has been widely used for the prevention and treatment of atherosclerotic diseases. Here, we sought to investigate the effects of Sal B on the cholesterol efflux in THP-1 macrophages. Methods: After PMA-stimulated THP-1 cells were exposed to 50 mg/L of oxLDL and [{sup 3}H] cholesterol (1.0 μCi/mL) for another 24 h, the effect of Sal B on cholesterol efflux was evaluated in the presence of apoA-1, HDL{sub 2} or HDL{sub 3}. The expression of ATP binding cassette transporter A1 (ABCA1), peroxisome proliferator-activated receptor-gamma (PPAR-γ), and liver X receptor-alpha (LXRα) was detected both at protein and mRNA levels in THP-1 cells after the stimulation of Sal B. Meanwhile, specific inhibition of PPAR-γ and LXRα were performed to investigate the mechanism. Results: The results showed that Sal B significantly accelerated apoA-I- and HDL-mediated cholesterol efflux in both dose- and time-dependent manners. Meanwhile, Sal B treatment also enhanced the expression of ABCA1 at both mRNA and protein levels. Then the data demonstrated that Sal B increased the expression of PPAR-γ and LXRα. And the application of specific agonists and inhibitors of further confirmed that Sal exert the function through PPAR-γ and LXRα. Conclusion: These results demonstrate that Sal B promotes cholesterol efflux in THP-1 macrophages through ABCA1/PPAR-γ/LXRα pathway. - Highlights: • Sal B promotes the expression of ABCA1. • Sal B promotes cholesterol efflux in macrophages. • Sal B promotes the expression of ABCA1 and cholesterol efflux through PPAR-γ/LXRα signaling pathway.

  16. ABCA7 frameshift deletion associated with Alzheimer disease in African Americans

    Science.gov (United States)

    Cukier, Holly N.; Kunkle, Brian W.; Vardarajan, Badri N.; Rolati, Sophie; Hamilton-Nelson, Kara L.; Kohli, Martin A.; Whitehead, Patrice L.; Dombroski, Beth A.; Van Booven, Derek; Lang, Rosalyn; Dykxhoorn, Derek M.; Farrer, Lindsay A.; Cuccaro, Michael L.; Vance, Jeffery M.; Gilbert, John R.; Beecham, Gary W.; Martin, Eden R.; Carney, Regina M.; Mayeux, Richard; Schellenberg, Gerard D.; Byrd, Goldie S.; Haines, Jonathan L.

    2016-01-01

    Objective: To identify a causative variant(s) that may contribute to Alzheimer disease (AD) in African Americans (AA) in the ATP-binding cassette, subfamily A (ABC1), member 7 (ABCA7) gene, a known risk factor for late-onset AD. Methods: Custom capture sequencing was performed on ∼150 kb encompassing ABCA7 in 40 AA cases and 37 AA controls carrying the AA risk allele (rs115550680). Association testing was performed for an ABCA7 deletion identified in large AA data sets (discovery n = 1,068; replication n = 1,749) and whole exome sequencing of Caribbean Hispanic (CH) AD families. Results: A 44-base pair deletion (rs142076058) was identified in all 77 risk genotype carriers, which shows that the deletion is in high linkage disequilibrium with the risk allele. The deletion was assessed in a large data set (531 cases and 527 controls) and, after adjustments for age, sex, and APOE status, was significantly associated with disease (p = 0.0002, odds ratio [OR] = 2.13 [95% confidence interval (CI): 1.42–3.20]). An independent data set replicated the association (447 cases and 880 controls, p = 0.0117, OR = 1.65 [95% CI: 1.12–2.44]), and joint analysis increased the significance (p = 1.414 × 10−5, OR = 1.81 [95% CI: 1.38–2.37]). The deletion is common in AA cases (15.2%) and AA controls (9.74%), but in only 0.12% of our non-Hispanic white cohort. Whole exome sequencing of multiplex, CH families identified the deletion cosegregating with disease in a large sibship. The deleted allele produces a stable, detectable RNA strand and is predicted to result in a frameshift mutation (p.Arg578Alafs) that could interfere with protein function. Conclusions: This common ABCA7 deletion could represent an ethnic-specific pathogenic alteration in AD. PMID:27231719

  17. Deficiency of ABCA1 and ABCG1 in Macrophages Increases Inflammation and Accelerates Atherosclerosis in Mice

    Science.gov (United States)

    Westerterp, Marit; Murphy, Andrew J.; Wang, Mi; Pagler, Tamara A.; Vengrenyuk, Yuliya; Kappus, Mojdeh S.; Gorman, Darren J.; Nagareddy, Prabhakara R.; Zhu, Xuewei; Abramowicz, Sandra; Parks, John S.; Welch, Carrie; Fisher, Edward A.; Wang, Nan; Yvan-Charvet, Laurent; Tall, Alan R.

    2013-01-01

    Rationale Plasma HDL levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is due to the ability of HDL to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking. Objective To assess the role of macrophage cholesterol efflux pathways in atherogenesis. Methods and Results We developed MAC-ABCDKO mice with efficient deletion of the ATP Binding Cassette Transporters A1 and G1 (ABCA1 and ABCG1) in macrophages but not in hematopoietic stem or progenitor populations. MAC-ABCDKO bone marrow (BM) was transplanted into Ldlr-/- recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared to controls. On the Western type diet (WTD), MAC-ABCDKO BM transplanted Ldlr-/- mice had disproportionate atherosclerosis, considering they also had lower VLDL/LDL cholesterol levels than controls. ABCA1/G1 deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, WTD-fed MAC-ABCDKO BM transplanted Ldlr-/- mice displayed monocytosis and neutrophilia in the absence of HSPC proliferation. Mechanistic studies revealed increased expression of M-CSF and G-CSF in splenic macrophage foam cells, driving BM monocyte and neutrophil production. Conclusion These studies 1) show that macrophage deficiency of ABCA1/G1 is pro-atherogenic likely by promoting plaque inflammation and 2) uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways. PMID:23572498

  18. Gene therapy for Stargardt disease associated with ABCA4 gene.

    Science.gov (United States)

    Han, Zongchao; Conley, Shannon M; Naash, Muna I

    2014-01-01

    Mutations in the photoreceptor-specific flippase ABCA4 lead to accumulation of the toxic bisretinoid A2E, resulting in atrophy of the retinal pigment epithelium (RPE) and death of the photoreceptor cells. Many blinding diseases are associated with these mutations including Stargardt's disease (STGD1), cone-rod dystrophy, retinitis pigmentosa (RP), and increased susceptibility to age-related macular degeneration. There are no curative treatments for any of these dsystrophies. While the monogenic nature of many of these conditions makes them amenable to treatment with gene therapy, the ABCA4 cDNA is 6.8 kb and is thus too large for the AAV vectors which have been most successful for other ocular genes. Here we review approaches to ABCA4 gene therapy including treatment with novel AAV vectors, lentiviral vectors, and non-viral compacted DNA nanoparticles. Lentiviral and compacted DNA nanoparticles in particular have a large capacity and have been successful in improving disease phenotypes in the Abca4 (-/-) murine model. Excitingly, two Phase I/IIa clinical trials are underway to treat patients with ABCA4-associated Startgardt's disease (STGD1). As a result of the development of these novel technologies, effective therapies for ABCA4-associated diseases may finally be within reach.

  19. Novel Apo E-Derived ABCA1 Agonist Peptide (CS-6253 Promotes Reverse Cholesterol Transport and Induces Formation of preβ-1 HDL In Vitro.

    Directory of Open Access Journals (Sweden)

    Anouar Hafiane

    Full Text Available Apolipoprotein (apo mimetic peptides replicate some aspects of HDL function. We have previously reported the effects of compound ATI-5261 on its ability to replicate many functions of native apo A-I in the process of HDL biogenesis. ATI-5261 induced muscle toxicity in wild type C57Bl/6 mice, increased CPK, ALT and AST and increase in triglyceride (Tg levels. Aromatic phenylalanine residues on the non-polar face of ATI-5261, together with positively charged arginine residues at the lipid-water interface were responsible for these effects. This information was used to create a novel analog (CS-6253 that was non-toxic. We evaluated this peptide designed from the carboxyl terminus of apo E, in its ability to mimic apo A-I functionality. Our data shows that the lipidated particles generated by incubating cells overexpressing ABCA1 with lipid free CS-6253 enhances the rate of ABCA1 lipid efflux with high affinity interactions with native ABCA1 oligomeric forms and plasma membrane micro-domains. Interaction between ABCA1 and lipid free CS-6253 resulted in formation of nascent HDL-CS-6253 particles that are actively remodeled in plasma. Mature HDL-CS-6253 particles deliver cholesterol to liver cells via SR-BI in-vitro. CS-6253 significantly increases cholesterol efflux in murine macrophages and in human THP-1 macrophage-derived foam cells expressing ABCA1. Addition of CS-6253 to plasma dose-dependently displaced apo A-I from α-HDL particles and led to de novo formation of preβ-1 HDL that stimulates ABCA1 dependent cholesterol efflux efficiently. When incubated with human plasma CS-6253 was also found to bind with HDL and LDL and promoted the transfer of cholesterol from HDL to LDL predominantly. Our data shows that CS-6253 mimics apo A-I in its ability to promote ABCA1-mediated formation of nascent HDL particles, and enhances formation of preβ-1 HDL with increase in the cycling of apo A-I between the preβ and α-HDL particles in-vitro. These

  20. Effects of miR-33a-5P on ABCA1/G1-mediated cholesterol efflux under inflammatory stress in THP-1 macrophages.

    Directory of Open Access Journals (Sweden)

    Min Mao

    Full Text Available The present study is to investigate whether inflammatory cytokines inhibit ABCA1/ABCG1-mediated cholesterol efflux by regulating miR-33a-5P in THP-1 macrophages. We used interleukin-6 and tumor necrosis factor-alpha in the presence or absence of native low density lipoprotein (LDL to stimulate THP-1 macrophages. THP-1 macrophages were infected by either control lentivirus vectors or lentivirus encoding miR-33a-5P or antisense miR-33a-5P. The effects of inflammatory cytokines, miR-33a-5P and antisense miR-33a-5P on intracellular lipids accumulation and intracellular cholesterol contents were assessed by oil red O staining and quantitative intracellular cholesterol assay. ApoA-I-mediated cholesterol efflux was examined using the fluorescent sterol (BODIPY-cholesterol. The gene and protein expressions of the molecules involved in cholesterol trafficking were examined using quantitative real-time polymerase chain reaction and Western blotting. Inflammatory cytokines or miR-33a-5P increased intracellular lipid accumulation and decreased apoA-I-mediated cholesterol efflux via decreasing the expression of ABCA1 and ABCG1 in the absence or presence of LDL in THP-1 macrophages. However, antisense miR-33a-5P reversed the effects of inflammatory cytokines on intracellular lipid accumulation, cholesterol efflux, and the expression of miR-33a-5P, ABCA1 and ABCG1 in the absence or presence of LDL in THP-1 macrophages. This study indicated that inflammatory cytokines inhibited ABCA1/ABCG1-mediated cholesterol efflux by up-regulating miR-33a-5P in THP-1 macrophages.

  1. Complete functional rescue of the ABCA1(-/-) mouse by human BAC transgenesis

    NARCIS (Netherlands)

    Coutinho, Jonathan M.; Singaraja, Roshni R.; Kang, Martin; Arenillas, David J.; Bertram, Lisa N.; Bissada, Nagat; Staels, Bart; Fruchart, Jean-Charles; Fievet, Catherine; Joseph-George, Ann M.; Wasserman, Wyeth W.; Hayden, Michael R.

    2005-01-01

    Humanized mouse models are useful tools to explore the functional and regulatory differences between human and murine orthologous genes. We have combined a bioinformatics approach and an in vivo approach to assess the functional and regulatory differences between the human and mouse ABCA1 genes.

  2. 22(R)-hydroxycholesterol and pioglitazone synergistically decrease cholesterol ester via the PPARγ–LXRα–ABCA1 pathway in cholesterosis of the gallbladder

    International Nuclear Information System (INIS)

    Wang, Jing-Min; Wang, Dong; Tan, Yu-Yan; Zhao, Gang; Ji, Zhen-Ling

    2014-01-01

    Highlights: • Cholesterosis is a metabolic disease characterized by excessive lipid droplets. • Lipid droplet efflux is mediated by the ABCA1 transporter. • 22(R)-hydroxycholesterol can activate LXRα and up-regulate ABCA1. • Pioglitazone up-regulates ABCA1 in a PPARγ–LXRα–ABCA1-dependent manner. • 22(R)-hydroxycholesterol and pioglitazone synergistically decrease lipid droplets. - Abstract: Cholesterosis is a disease of cholesterol metabolism characterized by the presence of excessive lipid droplets in the cytoplasm. These lipid droplets are mainly composed of cholesterol esters derived from free cholesterol. The removal of excess cholesterol from gallbladder epithelial cells (GBECs) is very important for the maintenance of intracellular cholesterol homeostasis and the preservation of gallbladder function. Several lines of evidence have indicated that the activation of either peroxisome proliferator-activated receptor gamma (PPARγ) or liver X receptor α (LXRα) relates to cholesterol efflux. While pioglitazone can regulate the activation of PPARγ, 22(R)-hydroxycholesterol can activate LXRα and is a metabolic intermediate in the biosynthesis of steroid hormones. However, the effect of 22(R)-hydroxycholesterol in combination with pioglitazone on cholesterosis of the gallbladder is unclear. GBECs were treated with pioglitazone, 22(R)-hydroxycholesterol or PPARγ siRNA followed by Western blot analysis for ATP-binding cassette transporter A1 (ABCA1), PPARγ and LXRα. Cholesterol efflux to apoA-I was determined, and Oil Red O staining was performed to monitor variations in lipid levels in treated GBECs. Our data showed that 22(R)-hydroxycholesterol can modestly up-regulate LXRα while simultaneously increasing ABCA1 by 56%. The combination of 22(R)-hydroxycholesterol and pioglitazone resulted in a 3.64-fold increase in ABCA1 expression and a high rate of cholesterol efflux. Oil Red O staining showed an obvious reduction in the lipid droplets

  3. ABCA7 frameshift deletion associated with Alzheimer disease in African Americans

    OpenAIRE

    Cukier, Holly N.; Kunkle, Brian W.; Vardarajan, Badri N.; Rolati, Sophie; Hamilton-Nelson, Kara L.; Kohli, Martin A.; Whitehead, Patrice L.; Dombroski, Beth A.; Van Booven, Derek; Lang, Rosalyn; Dykxhoorn, Derek M.; Farrer, Lindsay A.; Cuccaro, Michael L.; Vance, Jeffery M.; Gilbert, John R.

    2016-01-01

    Objective: To identify a causative variant(s) that may contribute to Alzheimer disease (AD) in African Americans (AA) in the ATP-binding cassette, subfamily A (ABC1), member 7 (ABCA7) gene, a known risk factor for late-onset AD. Methods: Custom capture sequencing was performed on ?150 kb encompassing ABCA7 in 40 AA cases and 37 AA controls carrying the AA risk allele (rs115550680). Association testing was performed for an ABCA7 deletion identified in large AA data sets (discovery n = 1,068; r...

  4. ABCA1 C69T gene polymorphism and risk of type 2 diabetes ...

    Indian Academy of Sciences (India)

    2013-11-06

    Nov 6, 2013 ... especially in high-density lipoprotein cholesterol (HDL-C). (Daimona et al. 2005 ... glucose, triglyceride (TG), total cholesterol (TC) and HDL-C levels were ... relationship between ABCA1 C69T genotypes and lipid profiles was ...

  5. Cloning, characterization and tissue distribution of the rat ATP-binding cassette (ABC) transporter ABC2/ABCA2.

    OpenAIRE

    Zhao, L X; Zhou, C J; Tanaka, A; Nakata, M; Hirabayashi, T; Amachi, T; Shioda, S; Ueda, K; Inagaki, N

    2000-01-01

    The ABC1 (ABCA) subfamily of the ATP-binding cassette (ABC) transporter superfamily has a structural feature that distinguishes it from other ABC transporters. Here we report the cloning, molecular characterization and tissue distribution of ABC2/ABCA2, which belongs to the ABC1 subfamily. Rat ABC2 is a protein of 2434 amino acids that has 44.5%, 40.0% and 40.8% identity with mouse ABC1/ABCA1, human ABC3/ABCA3 and human ABCR/ABCA4 respectively. Immunoblot analysis showed that proteins of 260 ...

  6. Corticotropin-Releasing Hormone (CRH Promotes Macrophage Foam Cell Formation via Reduced Expression of ATP Binding Cassette Transporter-1 (ABCA1.

    Directory of Open Access Journals (Sweden)

    Wonkyoung Cho

    Full Text Available Atherosclerosis, the major pathology of cardiovascular disease, is caused by multiple factors involving psychological stress. Corticotropin-releasing hormone (CRH, which is released by neurosecretory cells in the hypothalamus, peripheral nerve terminals and epithelial cells, regulates various stress-related responses. Our current study aimed to verify the role of CRH in macrophage foam cell formation, the initial critical stage of atherosclerosis. Our quantitative real-time reverse transcriptase PCR (qRT-PCR, semi-quantitative reverse transcriptase PCR, and Western blot results indicate that CRH down-regulates ATP-binding cassette transporter-1 (ABCA1 and liver X receptor (LXR-α, a transcription factor for ABCA1, in murine peritoneal macrophages and human monocyte-derived macrophages. Oil-red O (ORO staining and intracellular cholesterol measurement of macrophages treated with or without oxidized LDL (oxLDL and with or without CRH (10 nM in the presence of apolipoprotein A1 (apoA1 revealed that CRH treatment promotes macrophage foam cell formation. The boron-dipyrromethene (BODIPY-conjugated cholesterol efflux assay showed that CRH treatment reduces macrophage cholesterol efflux. Western blot analysis showed that CRH-induced down-regulation of ABCA1 is dependent on phosphorylation of Akt (Ser473 induced by interaction between CRH and CRH receptor 1(CRHR1. We conclude that activation of this pathway by CRH accelerates macrophage foam cell formation and may promote stress-related atherosclerosis.

  7. ABCA1 C69T gene polymorphism and risk of type 2 diabetes ...

    Indian Academy of Sciences (India)

    ABCA1 C69T gene polymorphism and risk of type 2 diabetes mellitus in a Saudi population. KHALID K ALHARBI, IMRAN ALI KHAN, NASSER M AL-DAGHRI, ANJANA MUNSHI, VANDANA SHARMA,. ABDUL KHADER MOHAMMED, KAISER A WANI, YAZEED A AL-SHEIK. MAY SALEM AL-NBAHEEN,. MOHAMMED ...

  8. Improving prediction of ischemic cardiovascular disease in the general population using apolipoprotein B

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Jensen, Gorm Boje

    2007-01-01

    Apolipoprotein B (apoB) levels predict fatal myocardial infarction. Whether apoB also predicts nonfatal ischemic cardiovascular events is unclear. We tested the following hypotheses: apoB predicts ischemic cardiovascular events, and apoB is a better predictor of ischemic cardiovascular events tha...

  9. A novel mutation in ABCA1 gene causing Tangier Disease in an Italian family with uncommon neurological presentation

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    Marco Ceccanti

    2016-11-01

    Full Text Available Tangier disease is an autosomal recessive disorder characterized by severe reduction in HDL-cholesterol and peripheral lipid storage. We describe a family with c.5094C>A p.Tyr16980* mutation in the ABCA1 gene, clinically characterized by syringomyelic-like anesthesia, demyelinating multineuropathy and reduction in intraepidermal small fibers innervation. In the proband patient, cardiac involvement determined a myocardial infarction; lipid storage was demonstrated in gut, cornea and aortic wall. The reported ABCA1 mutation has never been described before in a Tangier family.

  10. The AbcA Transporter of Staphylococcus aureus Affects Cell Autolysis

    Science.gov (United States)

    Schrader-Fischer, Gesine; Berger-Bächi, Brigitte

    2001-01-01

    Increased production of penicillin-binding protein PBP 4 is known to increase peptidoglycan cross-linking and contributes to methicillin resistance in Staphylococcus aureus. The pbp4 gene shares a 400-nucleotide intercistronic region with the divergently transcribed abcA gene, encoding an ATP-binding cassette transporter of unknown function. Our study revealed that methicillin stimulated abcA transcription but had no effects on pbp4 transcription. Analysis of abcA expression in mutants defective for global regulators showed that abcA is under the control of agr. Insertional inactivation of abcA by an erythromycin resistance determinant did not influence pbp4 transcription, nor did it alter resistance to methicillin and other cell wall-directed antibiotics. However, abcA mutants showed spontaneous partial lysis on plates containing subinhibitory concentrations of methicillin due to increased spontaneous autolysis. Since the autolytic zymograms of cell extracts were identical in mutants and parental strains, we postulate an indirect role of AbcA in control of autolytic activities and in protection of the cells against methicillin. PMID:11158733

  11. Loss-of-function mutation in ABCA1 and risk of Alzheimer's disease and cerebrovascular disease

    DEFF Research Database (Denmark)

    Nordestgaard, Liv Tybjærg; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2015-01-01

    .2%) versus AA (99.8%) was associated with a 13% lower plasma level of apoE (P = 1 × 10(-11)). Multifactorially adjusted hazard ratios for N1800H AC versus AA were 4.13 (95% confidence interval, 1.32-12.9) for AD, 2.46 (1.10-5.50) for cerebrovascular disease, and 8.28 (2.03-33.7) for the hemorrhagic stroke......-brain barrier via apoE-mediated pathways. METHODS: We tested whether a loss-of-function mutation in ABCA1, N1800H, is associated with plasma levels of apoE and with risk of Alzheimer's disease (AD) in 92,726 individuals and with risk of cerebrovascular disease in 64,181 individuals. RESULTS: N1800H AC (0...... subtype. DISCUSSION: A loss-of-function mutation in ABCA1, present in 1:500 individuals, was associated with low plasma levels of apoE and with high risk of AD and cerebrovascular disease in the general population....

  12. Gene-gene combination effect and interactions among ABCA1, APOA1, SR-B1, and CETP polymorphisms for serum high-density lipoprotein-cholesterol in the Japanese population.

    Directory of Open Access Journals (Sweden)

    Akihiko Nakamura

    Full Text Available BACKGROUND/OBJECTIVE: Gene-gene interactions in the reverse cholesterol transport system for high-density lipoprotein-cholesterol (HDL-C are poorly understood. The present study observed gene-gene combination effect and interactions between single nucleotide polymorphisms (SNPs in ABCA1, APOA1, SR-B1, and CETP in serum HDL-C from a cross-sectional study in the Japanese population. METHODS: The study population comprised 1,535 men and 1,515 women aged 35-69 years who were enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC Study. We selected 13 SNPs in the ABCA1, APOA1, CETP, and SR-B1 genes in the reverse cholesterol transport system. The effects of genetic and environmental factors were assessed using general linear and logistic regression models after adjusting for age, sex, and region. PRINCIPAL FINDINGS: Alcohol consumption and daily activity were positively associated with HDL-C levels, whereas smoking had a negative relationship. The T allele of CETP, rs3764261, was correlated with higher HDL-C levels and had the highest coefficient (2.93 mg/dL/allele among the 13 SNPs, which was statistically significant after applying the Bonferroni correction (p<0.001. Gene-gene combination analysis revealed that CETP rs3764261 was associated with high HDL-C levels with any combination of SNPs from ABCA1, APOA1, and SR-B1, although no gene-gene interaction was apparent. An increasing trend for serum HDL-C was also observed with an increasing number of alleles (p<0.001. CONCLUSIONS: The present study identified a multiplier effect from a polymorphism in CETP with ABCA1, APOA1, and SR-B1, as well as a dose-dependence according to the number of alleles present.

  13. Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy.

    Science.gov (United States)

    Maugeri, A; Klevering, B J; Rohrschneider, K; Blankenagel, A; Brunner, H G; Deutman, A F; Hoyng, C B; Cremers, F P

    2000-10-01

    The photoreceptor cell-specific ATP-binding cassette transporter gene (ABCA4; previously denoted "ABCR") is mutated, in most patients, with autosomal recessive (AR) Stargardt disease (STGD1) or fundus flavimaculatus (FFM). In addition, a few cases with AR retinitis pigmentosa (RP) and AR cone-rod dystrophy (CRD) have been found to have ABCA4 mutations. To evaluate the importance of the ABCA4 gene as a cause of AR CRD, we selected 5 patients with AR CRD and 15 patients from Germany and The Netherlands with isolated CRD. Single-strand conformation-polymorphism analysis and sequencing revealed 19 ABCA4 mutations in 13 (65%) of 20 patients. In six patients, mutations were identified in both ABCA4 alleles; in seven patients, mutations were detected in one allele. One complex ABCA4 allele (L541P;A1038V) was found exclusively in German patients with CRD; one patient carried this complex allele homozygously, and five others were compound heterozygous. These findings suggest that mutations in the ABCA4 gene are the major cause of AR CRD. A primary role of the ABCA4 gene in STGD1/FFM and AR CRD, together with the gene's involvement in an as-yet-unknown proportion of cases with AR RP, strengthens the idea that mutations in the ABCA4 gene could be the most frequent cause of inherited retinal dystrophy in humans.

  14. HDL and CER-001 Inverse-Dose Dependent Inhibition of Atherosclerotic Plaque Formation in apoE-/- Mice: Evidence of ABCA1 Down-Regulation.

    Science.gov (United States)

    Tardy, Claudine; Goffinet, Marine; Boubekeur, Nadia; Cholez, Guy; Ackermann, Rose; Sy, Gavin; Keyserling, Constance; Lalwani, Narendra; Paolini, John F; Dasseux, Jean-Louis; Barbaras, Ronald; Baron, Rudi

    2015-01-01

    CER-001 is a novel engineered HDL-mimetic comprised of recombinant human apoA-I and charged phospholipids that was designed to mimic the beneficial properties of nascent pre-ß HDL. In this study, we have evaluated the dose-dependent regulation of ABCA1 expression in vitro and in vivo in the presence of CER-001 and native HDL (HDL3). CER-001 induced cholesterol efflux from J774 macrophages in a dose-dependent manner similar to natural HDL. A strong down-regulation of the ATP-binding cassette A1 (ABCA1) transporter mRNA (- 50%) as well as the ABCA1 membrane protein expression (- 50%) was observed at higher doses of CER-001 and HDL3 compared to non-lipidated apoA-I. In vivo, in an apoE-/- mouse "flow cessation model," in which the left carotid artery was ligatured to induce local inflammation, the inhibition of atherosclerotic plaque burden progression in response to a dose-range of every-other-day CER-001 or HDL in the presence of a high-fat diet for two weeks was assessed. We observed a U-shaped dose-response curve: inhibition of the plaque total cholesterol content increased with increasing doses of CER-001 or HDL3 up to a maximum inhibition (- 51%) at 5 mg/kg; however, as the dose was increased above this threshold, a progressively less pronounced inhibition of progression was observed, reaching a complete absence of inhibition of progression at doses of 20 mg/kg and over. ABCA1 protein expression in the same atherosclerotic plaque was decreased by-45% and-68% at 50 mg/kg for CER-001 and HDL respectively. Conversely, a-12% and 0% decrease in ABCA1 protein expression was observed at the 5 mg/kg dose for CER-001 and HDL respectively. These data demonstrate that high doses of HDL and CER-001 are less effective at slowing progression of atherosclerotic plaque in apoE-/- mice compared to lower doses, following a U-shaped dose-response curve. A potential mechanism for this phenomenon is supported by the observation that high doses of HDL and CER-001 induce a rapid and

  15. Analysis of the Proteolytic Processing of ABCA3: Identification of Cleavage Site and Involved Proteases.

    Directory of Open Access Journals (Sweden)

    Nicole Hofmann

    Full Text Available ABCA3 is a lipid transporter in the limiting membrane of lamellar bodies in alveolar type II cells. Mutations in the ABCA3 gene cause respiratory distress syndrome in new-borns and childhood interstitial lung disease. ABCA3 is N-terminally cleaved by an as yet unknown protease, a process believed to regulate ABCA3 activity.The exact site where ABCA3 is cleaved was localized using mass spectrometry (MS. Proteases involved in ABCA3 processing were identified using small molecule inhibitors and siRNA mediated gene knockdown. Results were verified by in vitro digestion of a synthetic peptide substrate mimicking ABCA3's cleavage region, followed by MS analysis.We found that cleavage of ABCA3 occurs after Lys174 which is located in the proteins' first luminal loop. Inhibition of cathepsin L and, to a lesser extent, cathepsin B resulted in attenuation of ABCA3 cleavage. Both enzymes showed activity against the ABCA3 peptide in vitro with cathepsin L being more active.We show here that, like some other proteins of the lysosomal membrane, ABCA3 is a substrate of cathepsin L. Therefore, cathepsin L may represent a potential target to therapeutically influence ABCA3 activity in ABCA3-associated lung disease.

  16. Role of Abca7 in mouse behaviours relevant to neurodegenerative diseases.

    Directory of Open Access Journals (Sweden)

    Warren Logge

    Full Text Available ATP-binding cassette transporters of the subfamily A (ABCA are responsible for the translocation of lipids including cholesterol, which is crucial for neurological function. Recent studies suggest that the ABC transporter ABCA7 may play a role in the development of brain disorders such as schizophrenia and Alzheimer's disease. However, Abca7's role in cognition and other behaviours has not been investigated. Therefore, we characterised homozygous Abca7 knockout mice in a battery of tests for baseline behaviours (i.e. physical exam, baseline locomotion and anxiety and behaviours relevant to schizophrenia (i.e. prepulse inhibition and locomotor response to psychotropic drugs and Alzheimer's disease (i.e. cognitive domains. Knockout mice had normal motor functions and sensory abilities and performed the same as wild type-like animals in anxiety tasks. Short-term spatial memory and fear-associated learning was also intact in Abca7 knockout mice. However, male knockout mice exhibited significantly impaired novel object recognition memory. Task acquisition was unaffected in the cheeseboard task. Female mice exhibited impaired spatial reference memory. This phenomenon was more pronounced in female Abca7 null mice. Acoustic startle response, sensorimotor gating and baseline locomotion was unaltered in Abca7 knockout mice. Female knockouts showed a moderately increased motor response to MK-801 than control mice. In conclusion, Abca7 appears to play only a minor role in behavioural domains with a subtle sex-specific impact on particular cognitive domains.

  17. Seminal Plasma Characteristics and Expression of ATP-binding Cassette Transporter A1 (ABCA1) in Canine Spermatozoa from Ejaculates with Good and Bad Freezability.

    Science.gov (United States)

    Schäfer-Somi, S; Palme, N

    2016-04-01

    The composition of seminal plasma and the localization of the ATP-binding cassette transporter A1 (ABCA1) in spermatozoa from good and bad freezers were compared to frozen-thawed spermatozoa from the same dog. Ejaculates were obtained from 31 stud dogs, and the sperm-rich fraction (SRF) was kept for analysis. One aliquot was used for the analysis of concentration, progressive motility (P; CASA), viability (V; CASA) and leucocyte count, and the analysis was performed by flow cytometry (FITC-PNA/PI), SCSA and HOST. In seminal plasma, concentration of albumin, cholesterol, calcium, inorganic phosphate, sodium, potassium, zinc and copper was measured. Semen smears were prepared and evaluated for the expression of ABCA1. The remainder of each ejaculate was frozen. After thawing, the quality assessment was repeated and further smears were prepared. According to post-thaw semen quality, dogs were assigned to good freezers (n = 20) or bad freezers (n = 11), the latter were defined as 40% morphologically abnormal sperm and/or < 50% viability. Bad freezers were older than good freezers (5.3 vs 3.4 years, p < 0.05). In bad freezers, the percentage of sperm with ABCA1 signal in the acrosome was lower (26.3% vs 35.7%, p < 0.01) and the percentage of sperm with complete loss of ABCA1 signal higher (46.7% vs 30%, p < 0.01); the percentage of dead spermatozoa was higher (36.1% vs 25.5%, p < 0.05), and the concentration of cholesterol and sodium in seminal plasma was lower than in good freezers (p < 0.05). We conclude that in thawed bad freezer sperm, an increase in acrosome damages coincided with an increased loss of cholesterol transporters and cell death, and a lower cholesterol concentration in seminal plasma. Follow-up studies revealed whether a relation exists between these findings. © 2016 Blackwell Verlag GmbH.

  18. Genetic and Epigenetic Factors at COL2A1 and ABCA4 Influence Clinical Outcome in Congenital Toxoplasmosis

    Science.gov (United States)

    Jamieson, Sarra E.; de Roubaix, Lee-Anne; Cortina-Borja, Mario; Tan, Hooi Kuan; Mui, Ernest J.; Cordell, Heather J.; Kirisits, Michael J.; Miller, E. Nancy; Peacock, Christopher S.; Hargrave, Aubrey C.; Coyne, Jessica J.; Boyer, Kenneth; Bessieres, Marie-Hélène; Buffolano, Wilma; Ferret, Nicole; Franck, Jacqueline; Kieffer, François; Meier, Paul; Nowakowska, Dorota E.; Paul, Malgorzata; Peyron, François; Stray-Pedersen, Babill; Prusa, Andrea-Romana; Thulliez, Philippe; Wallon, Martine; Petersen, Eskild; McLeod, Rima; Gilbert, Ruth E.; Blackwell, Jenefer M.

    2008-01-01

    Background Primary Toxoplasma gondii infection during pregnancy can be transmitted to the fetus. At birth, infected infants may have intracranial calcification, hydrocephalus, and retinochoroiditis, and new ocular lesions can occur at any age after birth. Not all children who acquire infection in utero develop these clinical signs of disease. Whilst severity of disease is influenced by trimester in which infection is acquired by the mother, other factors including genetic predisposition may contribute. Methods and Findings In 457 mother-child pairs from Europe, and 149 child/parent trios from North America, we show that ocular and brain disease in congenital toxoplasmosis associate with polymorphisms in ABCA4 encoding ATP-binding cassette transporter, subfamily A, member 4. Polymorphisms at COL2A1 encoding type II collagen associate only with ocular disease. Both loci showed unusual inheritance patterns for the disease allele when comparing outcomes in heterozygous affected children with outcomes in affected children of heterozygous mothers. Modeling suggested either an effect of mother's genotype, or parent-of-origin effects. Experimental studies showed that both ABCA4 and COL2A1 show isoform-specific epigenetic modifications consistent with imprinting. Conclusions These associations between clinical outcomes of congenital toxoplasmosis and polymorphisms at ABCA4 and COL2A1 provide novel insight into the molecular pathways that can be affected by congenital infection with this parasite. PMID:18523590

  19. Genetic and epigenetic factors at COL2A1 and ABCA4 influence clinical outcome in congenital toxoplasmosis.

    Directory of Open Access Journals (Sweden)

    Sarra E Jamieson

    2008-06-01

    Full Text Available Primary Toxoplasma gondii infection during pregnancy can be transmitted to the fetus. At birth, infected infants may have intracranial calcification, hydrocephalus, and retinochoroiditis, and new ocular lesions can occur at any age after birth. Not all children who acquire infection in utero develop these clinical signs of disease. Whilst severity of disease is influenced by trimester in which infection is acquired by the mother, other factors including genetic predisposition may contribute.In 457 mother-child pairs from Europe, and 149 child/parent trios from North America, we show that ocular and brain disease in congenital toxoplasmosis associate with polymorphisms in ABCA4 encoding ATP-binding cassette transporter, subfamily A, member 4. Polymorphisms at COL2A1 encoding type II collagen associate only with ocular disease. Both loci showed unusual inheritance patterns for the disease allele when comparing outcomes in heterozygous affected children with outcomes in affected children of heterozygous mothers. Modeling suggested either an effect of mother's genotype, or parent-of-origin effects. Experimental studies showed that both ABCA4 and COL2A1 show isoform-specific epigenetic modifications consistent with imprinting.These associations between clinical outcomes of congenital toxoplasmosis and polymorphisms at ABCA4 and COL2A1 provide novel insight into the molecular pathways that can be affected by congenital infection with this parasite.

  20. Common genetic markers and prediction of recurrent events after ischemic stroke in young adults.

    Science.gov (United States)

    Pezzini, A; Grassi, M; Del Zotto, E; Lodigiani, C; Ferrazzi, P; Spalloni, A; Patella, R; Giossi, A; Volonghi, I; Iacoviello, L; Magoni, M; Rota, L L; Rasura, M; Padovani, A

    2009-09-01

    Scarce information is available on the usefulness of new prediction markers for identifying young ischemic stroke patients at highest risk of recurrence. The predictive effect of traditional risk factors as well as of the 20210A variant of prothrombin gene, the 1691A variant of factor V gene, and the TT677 genotype of the methylenetetrahydrofolate reductase (MTHFR) gene on the risk of recurrence was investigated in a hospital-based cohort study of 511 ischemic stroke patients younger than 45 years followed up for a mean of 43.4 months. Outcome measures were fatal/nonfatal myocardial infarction, ischemic stroke, or TIA. Risk prediction was assessed with the use of the concordance c (c index), and the Net Reclassification Improvement (NRI). The risk of recurrence increased with increasing number of traditional factors (hazard ratio [HR] 2.29, 95% confidence interval [CI] 1.57-3.35 for subjects with 1 factor: HR 5.25, 95% CI 2.45-11.2 for subjects with 2), as well as with that of predisposing genotypes (HR 1.96, 95% CI 1.33-2.89 for subjects carrying 1 at-risk genotype; HR 3.83, 95% CI 1.76-8.34 for those carrying 2). The c statistics increased significantly when the genotypes were included into a model with traditional risk factors (0.696 vs 0.635, test z = 2.41). The NRI was also significant (NRI = 0.172, test z = 2.17). Addition of common genetic variants to traditional risk factors may be an effective method for discriminating young stroke patients at different risk of future ischemic events.

  1. Phenotype/genotype correlation in a case series of Stargardt's patients identifies novel mutations in the ABCA4 gene.

    Science.gov (United States)

    Gemenetzi, M; Lotery, A J

    2013-11-01

    To investigate phenotypic variability in terms of best-corrected visual acuity (BCVA) in patients with Stargardt disease (STGD) and confirmed ABCA4 mutations. Entire coding region analysis of the ABCA4 gene by direct sequencing of seven patients with clinical findings of STGD seen in the Retina Clinics of Southampton Eye Unit between 2002 and 2011.Phenotypic variables recorded were BCVA, fluorescein angiographic appearance, electrophysiology, and visual fields. All patients had heterozygous amino acid-changing variants (missense mutations) in the ABCA4 gene. A splice sequence change was found in a 30-year-old patient with severly affected vision. Two novel sequence changes were identified: a missense mutation in a mildly affected 44-year-old patient and a frameshift mutation in a severly affected 34-year-old patient. The identified ABCA4 mutations were compatible with the resulting phenotypes in terms of BCVA. Higher BCVAs were recorded in patients with missense mutations. Sequence changes, predicted to have more deleterious effect on protein function, resulted in a more severe phenotype. This case series of STGD patients demonstrates novel genotype/phenotype correlations, which may be useful to counselling of patients. This information may prove useful in selection of candidates for clinical trials in ABCA4 disease.

  2. Phenotypic and genetic spectrum of Danish patients with ABCA4-related retinopathy

    DEFF Research Database (Denmark)

    Duno, Morten; Schwartz, Marianne; Larsen, Pernille L.

    2012-01-01

    Pathogenic variations in the ABCA4 gene were originally recognized as genetic background for the autosomal recessive disorders Stargardt disease and fundus flavimaculatus, but have expanded to embrace a diversity of retinal diseases, giving rise to the new diagnostic term, ABCA4-related retinopathy...... diagnosis must rely on a comprehensive genetic screening as the mutation spectrum of ABCA4-related retinopathies continues to expand....

  3. Macrophage ABCA2 deletion modulates intracellular cholesterol deposition, affects macrophage apoptosis, and decreases early atherosclerosis in LDL receptor knockout mice.

    Science.gov (United States)

    Calpe-Berdiel, Laura; Zhao, Ying; de Graauw, Marjo; Ye, Dan; van Santbrink, Peter J; Mommaas, A Mieke; Foks, Amanda; Bot, Martine; Meurs, Illiana; Kuiper, Johan; Mack, Jody T; Van Eck, Miranda; Tew, Kenneth D; van Berkel, Theo J C

    2012-08-01

    The ABCA2 transporter shares high structural homology to ABCA1, which is crucial for the removal of excess cholesterol from macrophages and, by extension, in atherosclerosis. It has been suggested that ABCA2 sequesters cholesterol inside the lysosomes, however, little is known of the macrophage-specific role of ABCA2 in regulating lipid homeostasis in vivo and in modulating susceptibility to atherosclerosis. Chimeras with dysfunctional macrophage ABCA2 were generated by transplantation of bone marrow from ABCA2 knockout (KO) mice into irradiated LDL receptor (LDLr) KO mice. Interestingly, lack of ABCA2 in macrophages resulted in a diminished lesion size in the aortic root (-24.5%) and descending thoracic aorta (-36.6%) associated with a 3-fold increase in apoptotic cells, as measured by both caspase 3 and TUNEL. Upon oxidized LDL exposure, macrophages from wildtype (WT) transplanted animals developed filipin-positive droplets in lysosomal-like compartments, corresponding to free cholesterol (FC) accumulation. In contrast, ABCA2-deficient macrophages displayed an abnormal diffuse distribution of FC over peripheral regions. The accumulation of neutral sterols in lipid droplets was increased in ABCA2-deficient macrophages, but primarily in cytoplasmic clusters and not in lysosomes. Importantly, apoptosis of oxLDL loaded macrophages lacking ABCA2 was increased 2.7-fold, probably as a consequence of the broad cellular distribution of FC. Lack of functional ABCA2 generates abnormalities in intracellular lipid distribution/trafficking in macrophages consistent with its lysosomal sequestering role, leading to an increased susceptibility to apoptosis in response to oxidized lipids and reduced atherosclerotic lesion development. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. Mutations in the ABCA4 (ABCR) Gene Are the Major Cause of Autosomal Recessive Cone-Rod Dystrophy

    OpenAIRE

    Maugeri, Alessandra; Klevering, B. Jeroen; Rohrschneider, Klaus; Blankenagel, Anita; Brunner, Han G.; Deutman, August F.; Hoyng, Carel B.; Cremers, Frans P. M.

    2000-01-01

    The photoreceptor cell–specific ATP-binding cassette transporter gene (ABCA4; previously denoted “ABCR”) is mutated in most patients with autosomal recessive (AR) Stargardt disease (STGD1) or fundus flavimaculatus (FFM). In addition, a few cases with AR retinitis pigmentosa (RP) and AR cone-rod dystrophy (CRD) have been found to have ABCA4 mutations. To evaluate the importance of the ABCA4 gene as a cause of AR CRD, we selected 5 patients with AR CRD and 15 patients with isolated CRD, all fro...

  5. A mouse model of harlequin ichthyosis delineates a key role for Abca12 in lipid homeostasis.

    Directory of Open Access Journals (Sweden)

    Ian Smyth

    2008-09-01

    Full Text Available Harlequin Ichthyosis (HI is a severe and often lethal hyperkeratotic skin disease caused by mutations in the ABCA12 transport protein. In keratinocytes, ABCA12 is thought to regulate the transfer of lipids into small intracellular trafficking vesicles known as lamellar bodies. However, the nature and scope of this regulation remains unclear. As part of an original recessive mouse ENU mutagenesis screen, we have identified and characterised an animal model of HI and showed that it displays many of the hallmarks of the disease including hyperkeratosis, loss of barrier function, and defects in lipid homeostasis. We have used this model to follow disease progression in utero and present evidence that loss of Abca12 function leads to premature differentiation of basal keratinocytes. A comprehensive analysis of lipid levels in mutant epidermis demonstrated profound defects in lipid homeostasis, illustrating for the first time the extent to which Abca12 plays a pivotal role in maintaining lipid balance in the skin. To further investigate the scope of Abca12's activity, we have utilised cells from the mutant mouse to ascribe direct transport functions to the protein and, in doing so, we demonstrate activities independent of its role in lamellar body function. These cells have severely impaired lipid efflux leading to intracellular accumulation of neutral lipids. Furthermore, we identify Abca12 as a mediator of Abca1-regulated cellular cholesterol efflux, a finding that may have significant implications for other diseases of lipid metabolism and homeostasis, including atherosclerosis.

  6. Mitochondrial targeting overcomes ABCA1-dependent resistance of lung carcinoma to alpha-tocopheryl succinate

    Czech Academy of Sciences Publication Activity Database

    Procházka, L.; Koudelka, Š.; Dong, L. F.; Štursa, Jan; Goodwin, J.; Neca, J.; Slavík, J.; Cigánek, M.; Mašek, J.; Klučková, Katarína; Nguyen, M.; Turánek, J.; Neužil, Jiří

    2013-01-01

    Roč. 18, č. 3 (2013), s. 286-299 ISSN 1360-8185 R&D Projects: GA ČR GAP301/10/1937; GA ČR(CZ) GAP304/10/1951 Grant - others:GA ČR(CZ) GP204/09/P632 Institutional research plan: CEZ:AV0Z50520701; CEZ:AV0Z40550506 Keywords : vitamin E analogues * apoptosis * mitochondrial targeting * ABCA1 * acquired resistance Subject RIV: CE - Biochemistry; EA - Cell Biology (BTO-N) Impact factor: 3.614, year: 2013

  7. Generalized Choriocapillaris Dystrophy, a Distinct Phenotype in the Spectrum of ABCA4-Associated Retinopathies

    DEFF Research Database (Denmark)

    Bertelsen, Mette; Zernant, Jana; Larsen, Michael

    2014-01-01

    PURPOSE: We describe a particular form of autosomal recessive generalized choriocapillaris dystrophy phenotype associated with ABCA4 mutations. METHODS: A cohort of 30 patients with identified ABCA4 mutations and a distinct phenotype was studied. A retrospective review of history, fundus photogra......PURPOSE: We describe a particular form of autosomal recessive generalized choriocapillaris dystrophy phenotype associated with ABCA4 mutations. METHODS: A cohort of 30 patients with identified ABCA4 mutations and a distinct phenotype was studied. A retrospective review of history, fundus...... photographs, electroretinography, visual field testing, dark adaptometry, and optical coherence tomography was performed. Genetic analyses were performed by ABCA4 microarray analysis, high resolution melting, and/or next generation sequencing of all protein-coding sequences of the ABCA4 gene. RESULTS...

  8. C-reactive protein predicts further ischemic events in first-ever transient ischemic attack or stroke patients with intracranial large-artery occlusive disease.

    Science.gov (United States)

    Arenillas, Juan F; Alvarez-Sabín, José; Molina, Carlos A; Chacón, Pilar; Montaner, Joan; Rovira, Alex; Ibarra, Bernardo; Quintana, Manuel

    2003-10-01

    The role of inflammation in intracranial large-artery occlusive disease is unclear. We sought to investigate the relationship between high-sensitivity C-reactive protein (CRP) levels and the risk of further ischemic events in first-ever transient ischemic attack (TIA) or stroke patients with intracranial large-artery occlusive disease. Of a total of 127 consecutive first-ever TIA or ischemic stroke patients with intracranial stenoses detected by transcranial Doppler ultrasonography, 71 fulfilled all inclusion criteria, which included angiographic confirmation. Serum high-sensitivity CRP level was determined a minimum of 3 months after the qualifying event. Patients were followed up during 1 year after blood sampling. Thirteen patients (18.3%) with intracranial large-artery occlusive disease experienced an end point event: 9 cerebral ischemic events, 7 of which were attributable to intracranial large-artery occlusive disease, and 4 myocardial infarctions. Patients in the highest quintile of high-sensitivity CRP level had a significantly higher adjusted odds ratio for new events compared with those in the first quintile (odds ratio, 8.66; 95% CI, 1.39 to 53.84; P=0.01). A high-sensitivity CRP level above the receiver operating characteristic curve cutoff value of 1.41 mg/dL emerged as an independent predictor of new end point events (hazard ratio, 7.14; 95% CI, 1.77 to 28.73; P=0.005) and of further intracranial large-artery occlusive disease-related ischemic events (hazard ratio, 30.67; 95% CI, 3.6 to 255.5; P=0.0015), after adjustment for age, sex, and risk factors. Kaplan-Meier curves showed that a significantly lower proportion of patients with a high-sensitivity CRP >1.41 mg/dL remained free of a new ischemic event (P<0.0001). High-sensitivity CRP serum level predicts further intracranial large-artery occlusive disease-related and any major ischemic events in patients with first-ever TIA or stroke with intracranial large-artery occlusive disease. These findings

  9. N-retinylidene-phosphatidylethanolamine is the preferred retinoid substrate for the photoreceptor-specific ABC transporter ABCA4 (ABCR).

    Science.gov (United States)

    Beharry, Seelochan; Zhong, Ming; Molday, Robert S

    2004-12-24

    ABCA4, a member of the family of ATP binding cassette (ABC) proteins found in rod and cone photoreceptors, has been implicated in the transport of retinoid compounds across the outer segment disk membrane following the photoactivation of rhodopsin. Mutations in the ABCA4 gene are responsible for Stargardt macular dystrophy and related retinal degenerative diseases that cause a loss in vision. To identify the retinoid substrate that interacts with ABCA4, we have isolated ABCA4 from rod outer segment disk membranes on an immunoaffinity matrix and analyzed retinoid compounds that bind to ABCA4 using high performance liquid chromatography and radiolabeling methods. When all-trans-retinal was added to ABCA4 in the presence of phosphatidylethanolamine, approximately 0.9 mol of N-retinylidene-phosphatidylethanolamine and 0.3 mol of all-trans-retinal were bound per mol of ABCA4 with an apparent K(d) of 2-5 microm. ATP and GTP released these retinoids from ABCA4, whereas ADP, GDP, and nonhydrolyzable derivatives, adenosine 5'-(beta,gamma-imido)triphosphate and guanosine 5'-(beta,gamma-imido)triphosphate, were ineffective. One mole of N-retinyl-phosphatidylethanolamine, the reduced form of N-retinylidene-phosphatidylethanolamine, bound per mol of ABCA4, whereas 0.3 mol of all-trans-retinal were bound in the absence of phosphatidylethanolamine. No binding of all-trans-retinol to ABCA4 was observed. Our results indicate that ABCA4 preferentially binds N-retinylidene-phosphatidylethanolamine with high affinity in the absence of ATP. Our studies further suggest that ATP binding and hydrolysis induces a protein conformational change that causes N-retinylidene-phosphatidylethanolamine to dissociate from ABCA4.

  10. Predicting functional outcomes of posterior circulation acute ischemic stroke in first 36 h of stroke onset.

    Science.gov (United States)

    Lin, Sheng-Feng; Chen, Chin-I; Hu, Han-Hwa; Bai, Chyi-Huey

    2018-04-01

    Posterior circulation acute ischemic stroke constitutes one-fourth of all ischemic strokes and can be efficiently quantified using the posterior circulation Alberta stroke program early computed tomography score (PC-ASPECTS) through diffusion-weighted imaging. We investigated whether the PC-ASPECTS and National Institutes of Health Stroke Scale (NIHSS) facilitate functional outcome prediction among Chinese patients with posterior circulation acute ischemic stroke. Participants were selected from our prospective stroke registry from January 1, 2015, to December 31, 2016. The baseline NIHSS score was assessed on the first day of admission, and brain magnetic resonance imaging was performed within 36 h after stroke onset. Simple and multiple logistic regressions were conducted to determine stroke risk factors and the PC-ASPECTS. Receiver operating characteristics (ROC) curve analysis was performed to compare the NIHSS and PC-ASPECTS. Of 549 patients from our prospective stroke admission registry database, 125 (22.8%) had a diagnosis of posterior circulation acute ischemic stroke. The optimal cutoff for the PC-ASPECTS in predicting outcomes was 7. The odds ratios of the PC-ASPECTS (≤ 7 vs > 7) in predicting outcomes were 6.33 (p = 0.0002) and 8.49 (p = 0.0060) in the univariate and multivariate models, respectively, and 7.52 (p = 0.0041) in the aging group. On ROC curve analysis, the PC-ASPECTS demonstrated more reliability than the baseline NIHSS for predicting functional outcomes of minor posterior circulation stroke. In conclusion, both the PC-ASPECTS and NIHSS help clinicians predict functional outcomes. PC-ASPECTS > 7 is a helpful discriminator for achieving favorable functional outcome prediction in posterior circulation acute ischemic stroke.

  11. 维生素A缺乏对大鼠肾脏ABCA1介导的脂质外流途径的影响%Effect of vitamin A deficiency on ABCA1-mediated lipid efflux pathway in rat kidneys

    Institute of Scientific and Technical Information of China (English)

    阳海平; 陈科; 张萱; 王莉; 李翠萃; 王莉佳; 李秋

    2010-01-01

    目的 探讨维生素A缺乏(vitaminA deficiency,VAD)大鼠模型肾脏脂质代谢状况及相关分子机制.方法 从孕期开始,给予Wistar大鼠正常饮食(正常对照组,维生素A含量为4000 IU/kg的饲料), VAD饮食(VAD组,维生素A含量为400 IU/kg的饲料),持续至8周后VAD组继续补充维生素A (VAS组,维生素A含量为6500 IU/kg的饲料) 15 d,每组6只.免疫组化分析肾脏载脂蛋白B100 (Apo-B100)、三磷酸腺苷结合盒转运体A1(adenosine triphosphate binding cassette A1,ABCA1)表达,Real-time PCR技术检测肾脏ABCA1、过氧化物酶体增殖物激活受体α(PPARα)、肝X受体α(LXRα)、视黄醇X受体α/β (RXRα/β) mRNA水平. 结果免疫组化分析,第8周VAD组肾脏Apo-B100水平(14.27±0.05)明显高于正常对照组(8.25±0.49)(P0.05);以上改变随维生素A补充即恢复至正常水平.结论 VAD可致PPARα/RXRs-LXRα/RXRs-ABCA1介导的脂质外流途径受损而导致大鼠肾脏脂质沉积增多,但及时补充维生素A能有效使肾脏脂质代谢恢复正常.

  12. Comparison of statistical and clinical predictions of functional outcome after ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Douglas D Thompson

    Full Text Available To determine whether the predictions of functional outcome after ischemic stroke made at the bedside using a doctor's clinical experience were more or less accurate than the predictions made by clinical prediction models (CPMs.A prospective cohort study of nine hundred and thirty one ischemic stroke patients recruited consecutively at the outpatient, inpatient and emergency departments of the Western General Hospital, Edinburgh between 2002 and 2005. Doctors made informal predictions of six month functional outcome on the Oxford Handicap Scale (OHS. Patients were followed up at six months with a validated postal questionnaire. For each patient we calculated the absolute predicted risk of death or dependence (OHS≥3 using five previously described CPMs. The specificity of a doctor's informal predictions of OHS≥3 at six months was good 0.96 (95% CI: 0.94 to 0.97 and similar to CPMs (range 0.94 to 0.96; however the sensitivity of both informal clinical predictions 0.44 (95% CI: 0.39 to 0.49 and clinical prediction models (range 0.38 to 0.45 was poor. The prediction of the level of disability after stroke was similar for informal clinical predictions (ordinal c-statistic 0.74 with 95% CI 0.72 to 0.76 and CPMs (range 0.69 to 0.75. No patient or clinician characteristic affected the accuracy of informal predictions, though predictions were more accurate in outpatients.CPMs are at least as good as informal clinical predictions in discriminating between good and bad functional outcome after ischemic stroke. The place of these models in clinical practice has yet to be determined.

  13. Deleterious ABCA7 mutations and transcript rescue mechanisms in early onset Alzheimer's disease.

    Science.gov (United States)

    De Roeck, Arne; Van den Bossche, Tobi; van der Zee, Julie; Verheijen, Jan; De Coster, Wouter; Van Dongen, Jasper; Dillen, Lubina; Baradaran-Heravi, Yalda; Heeman, Bavo; Sanchez-Valle, Raquel; Lladó, Albert; Nacmias, Benedetta; Sorbi, Sandro; Gelpi, Ellen; Grau-Rivera, Oriol; Gómez-Tortosa, Estrella; Pastor, Pau; Ortega-Cubero, Sara; Pastor, Maria A; Graff, Caroline; Thonberg, Håkan; Benussi, Luisa; Ghidoni, Roberta; Binetti, Giuliano; de Mendonça, Alexandre; Martins, Madalena; Borroni, Barbara; Padovani, Alessandro; Almeida, Maria Rosário; Santana, Isabel; Diehl-Schmid, Janine; Alexopoulos, Panagiotis; Clarimon, Jordi; Lleó, Alberto; Fortea, Juan; Tsolaki, Magda; Koutroumani, Maria; Matěj, Radoslav; Rohan, Zdenek; De Deyn, Peter; Engelborghs, Sebastiaan; Cras, Patrick; Van Broeckhoven, Christine; Sleegers, Kristel

    2017-09-01

    Premature termination codon (PTC) mutations in the ATP-Binding Cassette, Sub-Family A, Member 7 gene (ABCA7) have recently been identified as intermediate-to-high penetrant risk factor for late-onset Alzheimer's disease (LOAD). High variability, however, is observed in downstream ABCA7 mRNA and protein expression, disease penetrance, and onset age, indicative of unknown modifying factors. Here, we investigated the prevalence and disease penetrance of ABCA7 PTC mutations in a large early onset AD (EOAD)-control cohort, and examined the effect on transcript level with comprehensive third-generation long-read sequencing. We characterized the ABCA7 coding sequence with next-generation sequencing in 928 EOAD patients and 980 matched control individuals. With MetaSKAT rare variant association analysis, we observed a fivefold enrichment (p = 0.0004) of PTC mutations in EOAD patients (3%) versus controls (0.6%). Ten novel PTC mutations were only observed in patients, and PTC mutation carriers in general had an increased familial AD load. In addition, we observed nominal risk reducing trends for three common coding variants. Seven PTC mutations were further analyzed using targeted long-read cDNA sequencing on an Oxford Nanopore MinION platform. PTC-containing transcripts for each investigated PTC mutation were observed at varying proportion (5-41% of the total read count), implying incomplete nonsense-mediated mRNA decay (NMD). Furthermore, we distinguished and phased several previously unknown alternative splicing events (up to 30% of transcripts). In conjunction with PTC mutations, several of these novel ABCA7 isoforms have the potential to rescue deleterious PTC effects. In conclusion, ABCA7 PTC mutations play a substantial role in EOAD, warranting genetic screening of ABCA7 in genetically unexplained patients. Long-read cDNA sequencing revealed both varying degrees of NMD and transcript-modifying events, which may influence ABCA7 dosage, disease severity, and may

  14. Effect Of G2706A and G1051A polymorphisms of the ABCA1 gene on the lipid, oxidative stress and homocystein levels in Turkish patients with polycystıc ovary syndrome.

    Science.gov (United States)

    Karadeniz, Muammer; Erdoğan, Mehmet; Ayhan, Zengi; Yalcin, Murat; Olukman, Murat; Cetinkalp, Sevki; Alper, Gulinnaz E; Eroglu, Zuhal; Tetik, Asli; Cetintas, Vildan; Ozgen, Ahmet G; Saygili, Fusun; Yilmaz, Candeger

    2011-10-28

    Obesity, insulin resistance and hyperandrogenism, crucial parameters of Polycystic ovary syndrome (PCOS) play significant pathophysiological roles in lipidemic aberrations associated within the syndrome. Parts of the metabolic syndrome (low HDL and insulin resistance) appeared to facilitate the association between PCOS and coronary artery disease, independently of obesity. ABCA1 gene polymorphism may be altered this components in PCOS patients.In this study, we studied 98 PCOS patients and 93 healthy controls. All subjects underwent venous blood drawing for complete hormonal assays, lipid profile, glucose, insulin, malondialdehyde, nitric oxide, disulfide levels and ABCA genetic study. In PCOS group fasting glucose, DHEAS, 17-OHP, free testosterone, total-cholesterol, triglyceride, LDL-cholesterol and fibrinogen were significantly different compare to controls. The genotype ABCA G2706A distribution differed between the control group (GG 60.7%, GA 32.1%, AA 7.1%) and the PCOS patients (GG 8.7%, GA 8.7%, AA 76.8%). The frequency of the A allele (ABCAG2706A) was higher in PCOS patients than control group with 13,0% and 23,2%, respectively. In this study, the homocystein and insulin levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes. We found higher percentage of AA genotype and A allele of ABCA G2706A in PCOS patients compare to controls. The fasting insulin and homocystein levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.

  15. Effect Of G2706A and G1051A polymorphisms of the ABCA1 gene on the lipid, oxidative stress and homocystein levels in Turkish patients with polycystıc ovary syndrome

    Directory of Open Access Journals (Sweden)

    Tetik Asli

    2011-10-01

    Full Text Available Abstract Background Obesity, insulin resistance and hyperandrogenism, crucial parameters of Polycystic ovary syndrome (PCOS play significant pathophysiological roles in lipidemic aberrations associated within the syndrome. Parts of the metabolic syndrome (low HDL and insulin resistance appeared to facilitate the association between PCOS and coronary artery disease, independently of obesity. ABCA1 gene polymorphism may be altered this components in PCOS patients. In this study, we studied 98 PCOS patients and 93 healthy controls. All subjects underwent venous blood drawing for complete hormonal assays, lipid profile, glucose, insulin, malondialdehyde, nitric oxide, disulfide levels and ABCA genetic study. Results In PCOS group fasting glucose, DHEAS, 17-OHP, free testosterone, total-cholesterol, triglyceride, LDL-cholesterol and fibrinogen were significantly different compare to controls. The genotype ABCA G2706A distribution differed between the control group (GG 60.7%, GA 32.1%, AA 7.1% and the PCOS patients (GG 8.7%, GA 8.7%, AA 76.8%. The frequency of the A allele (ABCAG2706A was higher in PCOS patients than control group with 13,0% and 23,2%, respectively. In this study, the homocystein and insulin levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes. Conclusions We found higher percentage of AA genotype and A allele of ABCA G2706A in PCOS patients compare to controls. The fasting insulin and homocystein levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.

  16. Analysis of the ABCA4 genomic locus in Stargardt disease

    DEFF Research Database (Denmark)

    Zernant, Jana; Xie, Yajing Angela; Ayuso, Carmen

    2014-01-01

    excluded since they were not conserved in non-human primates, were frequent in African populations and, therefore, represented ancestral, and not disease-associated, variants. The sequence variability in the ABCA4 locus is extensive and the non-coding sequences do not harbor frequent mutations in STGD...... patients of European-American descent. Defining disease-associated alleles in the ABCA4 locus requires exceptionally well characterized large cohorts and extensive analyses by a combination of various approaches....

  17. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

    DEFF Research Database (Denmark)

    Van Leeuwen, Elisabeth M.; Karssen, Lennart C.; Deelen, Joris

    2015-01-01

    created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value -4), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted...

  18. Microarray-based mutation analysis of the ABCA4 (ABCR) gene in autosomal recessive cone-rod dystrophy and retinitis pigmentosa.

    NARCIS (Netherlands)

    Klevering, B.J.; Ijzer, S.; Rohrschneider, K.; Zonneveld-Vrieling, M.N.; Allikmets, R.; Born, L.I. van den; Maugeri, A.; Hoyng, C.B.; Cremers, F.P.M.

    2004-01-01

    Mutations in the ABCA4 gene have been associated with autosomal recessive Stargardt disease (STGD1), cone-rod dystrophy (CRD), and retinitis pigmentosa (RP). We employed a recently developed genotyping microarray, the ABCR400-chip, to search for known ABCA4 mutations in patients with isolated or

  19. Targeted inactivation of the murine Abca3 gene leads to respiratory failure in newborns with defective lamellar bodies

    International Nuclear Information System (INIS)

    Hammel, Markus; Michel, Geert; Hoefer, Christina; Klaften, Matthias; Mueller-Hoecker, Josef; Angelis, Martin Hrabe de; Holzinger, Andreas

    2007-01-01

    Mutations in the human ABCA3 gene, encoding an ABC-transporter, are associated with respiratory failure in newborns and pediatric interstitial lung disease. In order to study disease mechanisms, a transgenic mouse model with a disrupted Abca3 gene was generated by targeting embryonic stem cells. While heterozygous animals developed normally and were fertile, individuals homozygous for the altered allele (Abca3-/-) died within one hour after birth from respiratory failure, ABCA3 protein being undetectable. Abca3-/- newborns showed atelectasis of the lung in comparison to a normal gas content in unaffected or heterozygous littermates. Electron microscopy demonstrated the absence of normal lamellar bodies in type II pneumocytes. Instead, condensed structures with apparent absence of lipid content were found. We conclude that ABCA3 is required for the formation of lamellar bodies and lung surfactant function. The phenotype of respiratory failure immediately after birth corresponds to the clinical course of severe ABCA3 mutations in human newborns

  20. A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans

    NARCIS (Netherlands)

    Acuña-Alonzo, Víctor; Flores-Dorantes, Teresa; Kruit, Janine K; Villarreal-Molina, Teresa; Arellano-Campos, Olimpia; Hünemeier, Tábita; Moreno-Estrada, Andrés; Ortiz-López, Ma Guadalupe; Villamil-Ramírez, Hugo; León-Mimila, Paola; Villalobos-Comparan, Marisela; Jacobo-Albavera, Leonor; Ramírez-Jiménez, Salvador; Sikora, Martin; Zhang, Lin-Hua; Pape, Terry D; Granados-Silvestre, Ma de Angeles; Montufar-Robles, Isela; Tito-Alvarez, Ana M; Zurita-Salinas, Camilo; Bustos-Arriaga, José; Cedillo-Barrón, Leticia; Gómez-Trejo, Celta; Barquera-Lozano, Rodrigo; Vieira-Filho, Joao P; Granados, Julio; Romero-Hidalgo, Sandra; Huertas-Vázquez, Adriana; González-Martín, Antonio; Gorostiza, Amaya; Bonatto, Sandro L; Rodríguez-Cruz, Maricela; Wang, Li; Tusié-Luna, Teresa; Aguilar-Salinas, Carlos A; Lisker, Ruben; Moises, Regina S; Menjivar, Marta; Salzano, Francisco M; Knowler, William C; Bortolini, M Cátira; Hayden, Michael R; Baier, Leslie J; Canizales-Quinteros, Samuel

    2010-01-01

    It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was

  1. Retinal-specific ATP-binding cassette transporter (ABCR/ABCA4) is expressed at the choroid plexus in rat brain.

    Science.gov (United States)

    Bhongsatiern, Jiraganya; Ohtsuki, Sumio; Tachikawa, Masanori; Hori, Satoko; Terasaki, Tetsuya

    2005-03-01

    ATP-binding cassette (ABC) transporter A4 is a member of the ABC transporter subfamily A which has been reported to be exclusively expressed in the retina. In contrast, a previous report has suggested a possible relationship between ABCA4 and CNS function. The purpose of the present study was to investigate the localization of ABCA4 mRNA and protein in rat brain. In situ hybridization analysis revealed that ABCA4 mRNA was localized in the lateral ventricles. RT-PCR analysis detected ABCA4 mRNA in isolated rat choroid plexus and conditionally immortalized rat choroid plexus epithelial cells (TR-CSFB). Furthermore, ABCA4 protein was also detected in the isolated rat choroid plexus at about 250 kDa by western blot analysis, and its apparent molecular size was reduced by N-glycosidase F treatment. These results suggest that glycosylated ABCA4 protein is expressed in rat choroid plexus epithelial cells. ABCA4 may play a role in the function of the blood-cerebrospinal fluid barrier and affect CSF conditions.

  2. Blood pressure, risk of ischemic cerebrovascular and ischemic heart disease, and longevity in alpha(1)-antitrypsin deficiency

    DEFF Research Database (Denmark)

    Dahl, Morten; Tybjaerg-Hansen, Anne; Sillesen, Henrik

    2003-01-01

    Because elastase in alpha(1)-antitrypsin deficiency may attack elastin in the arterial wall, we tested whether alpha(1)-antitrypsin deficiency is associated with reduced blood pressure, risk of ischemic cerebrovascular (ICVD) and ischemic heart disease (IHD), and longevity.......Because elastase in alpha(1)-antitrypsin deficiency may attack elastin in the arterial wall, we tested whether alpha(1)-antitrypsin deficiency is associated with reduced blood pressure, risk of ischemic cerebrovascular (ICVD) and ischemic heart disease (IHD), and longevity....

  3. Predicting Long-term Ischemic Events Using Routine Clinical Parameters in Patients with Coronary Artery Disease: The OPT-CAD Risk Score.

    Science.gov (United States)

    Han, Yaling; Chen, Jiyan; Qiu, Miaohan; Li, Yi; Li, Jing; Feng, Yingqing; Qiu, Jian; Meng, Liang; Sun, Yihong; Tao, Guizhou; Wu, Zhaohui; Yang, Chunyu; Guo, Jincheng; Pu, Kui; Chen, Shaoliang; Wang, Xiaozeng

    2018-06-05

    The prognosis of patients with coronary artery disease (CAD) at hospital discharge was constantly varying, and post-discharge risk of ischemic events remain a concern. However, risk prediction tools to identify risk of ischemia for these patients has not yet been reported. We sought to develop a scoring system for predicting long-term ischemic events in CAD patients receiving antiplatelet therapy that would be beneficial in appropriate personalized decision-making for these patients. In this prospective Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD, NCT01735305) registry, a total of 14,032 patients with CAD receiving at least one kind of antiplatelet agent were enrolled from 107 centers across China, from January 2012 to March 2014. The risk scoring system was developed in a derivation cohort (enrolled initially 10,000 patients in the database) using a logistic regression model and was subsequently tested in a validation cohort (the last 4,032 patients). Points in risk score was assigned based on the multivariable odds ratio of each factor. Ischemic events were defined as the composite of cardiac death, myocardial infarction or stroke. Ischemic events occurred in 342 (3.4%) patients in the derivation cohort and 160 (4.0%) patients in the validation cohort during 1-year follow-up. The OPT-CAD score, ranging from 0-257 points, consist of 10 independent risk factors, including age (0-71 points), heart rates (0-36 points), hypertension (0-20 points), prior myocardial infarction (16 points), prior stroke (16 points), renal insufficient (21 points), anemia (19 points), low ejection fraction (22 points), positive cardiac troponin (23 points) and ST-segment deviation (13 points). In predicting 1-year ischemic events, the area under receiver operating characteristics curve were 0.73 and 0.72 in derivation and validation cohort, respectively. The incidences of ischemic events in low- (0-90 points), medium- (91-150 points) and

  4. Novel Mutation in the ATP-Binding Cassette Transporter A3 (ABCA3) Encoding Gene Causes Respiratory Distress Syndrome in A Term Newborn in Southwest Iran

    Science.gov (United States)

    Rezaei, Farideh; Shafiei, Mohammad; Shariati, Gholamreza; Dehdashtian, Ali; Mohebbi, Maryam; Galehdari, Hamid

    2016-01-01

    Introduction ABCA3 glycoprotein belongs to the ATP-binding cassette (ABC) superfamily of transporters, which utilize the energy derived from hydrolysis of ATP for the translocation of a wide variety of substrates across the plasma membrane. Mutations in the ABCA3 gene are knowingly causative for fatal surfactant deficiency, particularly respiratory distress syndrome (RDS) in term babies. Case Presentation In this study, Sanger sequencing of the whole ABCA3 gene (NCBI NM_001089) was performed in a neonatal boy with severe RDS. A homozygous mutation has been identified in the patient. Parents were heterozygous for the same missense mutation GGA > AGA at position 202 in exon 6 of the ABCA3 gene (c.604G > A; p.G202R). Furthermore, 70 normal individuals have been analyzed for the mentioned change with negative results. Conclusions Regarding Human Genome Mutation Database (HGMD) and other literature recherche, the detected change is a novel mutation and has not been reported before. Bioinformatics mutation predicting tools prefer it as pathogenic. PMID:27437095

  5. Macular Pigment and Lutein Supplementation in ABCA4-associated Retinal Degenerations

    Science.gov (United States)

    Aleman, Tomas S.; Cideciyan, Artur V.; Windsor, Elizabeth A. M.; Schwartz, Sharon B.; Swider, Malgorzata; Chico, John D.; Sumaroka, Alexander; Pantelyat, Alexander Y.; Duncan, Keith G.; Gardner, Leigh M.; Emmons, Jessica M.; Steinberg, Janet D.; Stone, Edwin M.; Jacobson, Samuel G.

    2008-01-01

    PURPOSE To determine macular pigment (MP) optical density (OD) in patients with ABCA4-associated retinal degenerations (ABCA4-RD) and the response of MP and vision to supplementation with lutein. METHODS Stargardt disease or cone-rod dystrophy patients with foveal fixation and with known or suspected disease-causing mutations in the ABCA4 gene were included. MPOD profiles were measured with heterochromatic flicker photometry. Serum carotenoids, visual acuity, foveal sensitivity and retinal thickness were quantified. Changes in MPOD and central vision were determined in a subset of patients receiving oral supplementation with lutein for 6 months. RESULTS MPOD in patients ranged from normal to markedly abnormal. As a group, ABCA4-RD patients had reduced foveal MPOD and there was strong correlation with retinal thickness. Average foveal tissue concentration of MP, estimated by dividing MPOD by retinal thickness, was normal in patients whereas serum concentration of lutein and zeaxanthin was significantly lower than normal. After oral lutein supplementation for 6 months, 91% of the patients showed significant increases in serum lutein and 63% of the patient eyes showed a significant augmentation in MPOD. The retinal responders tended to be female, and have lower serum lutein and zeaxanthin, lower MPOD and greater retinal thickness at baseline. Responding eyes had significantly lower baseline MP concentration compared to non-responding eyes. Central vision was unchanged after the period of supplementation. CONCLUSIONS MP is strongly affected by the stage of ABCA4 disease leading to abnormal foveal architecture. MP could be augmented by supplemental lutein in some patients. There was no change in central vision after 6 months of lutein supplementation. Long-term influences on the natural history of this supplement on macular degenerations require further study. PMID:17325179

  6. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

    Science.gov (United States)

    van Leeuwen, Elisabeth M.; Karssen, Lennart C.; Deelen, Joris; Isaacs, Aaron; Medina-Gomez, Carolina; Mbarek, Hamdi; Kanterakis, Alexandros; Trompet, Stella; Postmus, Iris; Verweij, Niek; van Enckevort, David J.; Huffman, Jennifer E.; White, Charles C.; Feitosa, Mary F.; Bartz, Traci M.; Manichaikul, Ani; Joshi, Peter K.; Peloso, Gina M.; Deelen, Patrick; van Dijk, Freerk; Willemsen, Gonneke; de Geus, Eco J.; Milaneschi, Yuri; Penninx, Brenda W.J.H.; Francioli, Laurent C.; Menelaou, Androniki; Pulit, Sara L.; Rivadeneira, Fernando; Hofman, Albert; Oostra, Ben A.; Franco, Oscar H.; Leach, Irene Mateo; Beekman, Marian; de Craen, Anton J.M.; Uh, Hae-Won; Trochet, Holly; Hocking, Lynne J.; Porteous, David J.; Sattar, Naveed; Packard, Chris J.; Buckley, Brendan M.; Brody, Jennifer A.; Bis, Joshua C.; Rotter, Jerome I.; Mychaleckyj, Josyf C.; Campbell, Harry; Duan, Qing; Lange, Leslie A.; Wilson, James F.; Hayward, Caroline; Polasek, Ozren; Vitart, Veronique; Rudan, Igor; Wright, Alan F.; Rich, Stephen S.; Psaty, Bruce M.; Borecki, Ingrid B.; Kearney, Patricia M.; Stott, David J.; Adrienne Cupples, L.; Neerincx, Pieter B.T.; Elbers, Clara C.; Francesco Palamara, Pier; Pe'er, Itsik; Abdellaoui, Abdel; Kloosterman, Wigard P.; van Oven, Mannis; Vermaat, Martijn; Li, Mingkun; Laros, Jeroen F.J.; Stoneking, Mark; de Knijff, Peter; Kayser, Manfred; Veldink, Jan H.; van den Berg, Leonard H.; Byelas, Heorhiy; den Dunnen, Johan T.; Dijkstra, Martijn; Amin, Najaf; Joeri van der Velde, K.; van Setten, Jessica; Kattenberg, Mathijs; van Schaik, Barbera D.C.; Bot, Jan; Nijman, Isaäc J.; Mei, Hailiang; Koval, Vyacheslav; Ye, Kai; Lameijer, Eric-Wubbo; Moed, Matthijs H.; Hehir-Kwa, Jayne Y.; Handsaker, Robert E.; Sunyaev, Shamil R.; Sohail, Mashaal; Hormozdiari, Fereydoun; Marschall, Tobias; Schönhuth, Alexander; Guryev, Victor; Suchiman, H. Eka D.; Wolffenbuttel, Bruce H.; Platteel, Mathieu; Pitts, Steven J.; Potluri, Shobha; Cox, David R.; Li, Qibin; Li, Yingrui; Du, Yuanping; Chen, Ruoyan; Cao, Hongzhi; Li, Ning; Cao, Sujie; Wang, Jun; Bovenberg, Jasper A.; Jukema, J. Wouter; van der Harst, Pim; Sijbrands, Eric J.; Hottenga, Jouke-Jan; Uitterlinden, Andre G.; Swertz, Morris A.; van Ommen, Gert-Jan B.; de Bakker, Paul I.W.; Eline Slagboom, P.; Boomsma, Dorret I.; Wijmenga, Cisca; van Duijn, Cornelia M.

    2015-01-01

    Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value <6.61 × 10−4), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this ABCA6 variant is 3.65-fold increased in the Dutch and its effect (βLDL-C=0.135, βTC=0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR. PMID:25751400

  7. Use of APACHE II and SAPS II to predict mortality for hemorrhagic and ischemic stroke patients.

    Science.gov (United States)

    Moon, Byeong Hoo; Park, Sang Kyu; Jang, Dong Kyu; Jang, Kyoung Sool; Kim, Jong Tae; Han, Yong Min

    2015-01-01

    We studied the applicability of the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) in patients admitted to the intensive care unit (ICU) with acute stroke and compared the results with the Glasgow Coma Scale (GCS) and National Institutes of Health Stroke Scale (NIHSS). We also conducted a comparative study of accuracy for predicting hemorrhagic and ischemic stroke mortality. Between January 2011 and December 2012, ischemic or hemorrhagic stroke patients admitted to the ICU were included in the study. APACHE II and SAPS II-predicted mortalities were compared using a calibration curve, the Hosmer-Lemeshow goodness-of-fit test, and the receiver operating characteristic (ROC) curve, and the results were compared with the GCS and NIHSS. Overall 498 patients were included in this study. The observed mortality was 26.3%, whereas APACHE II and SAPS II-predicted mortalities were 35.12% and 35.34%, respectively. The mean GCS and NIHSS scores were 9.43 and 21.63, respectively. The calibration curve was close to the line of perfect prediction. The ROC curve showed a slightly better prediction of mortality for APACHE II in hemorrhagic stroke patients and SAPS II in ischemic stroke patients. The GCS and NIHSS were inferior in predicting mortality in both patient groups. Although both the APACHE II and SAPS II systems can be used to measure performance in the neurosurgical ICU setting, the accuracy of APACHE II in hemorrhagic stroke patients and SAPS II in ischemic stroke patients was superior. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Subretinal Fibrosis in Stargardt’s Disease with Fundus Flavimaculatus and ABCA4 Gene Mutation

    Directory of Open Access Journals (Sweden)

    Settimio Rossi

    2012-12-01

    Full Text Available Purpose: To report on 4 patients affected by Stargardt’s disease (STGD with fundus flavimaculatus (FFM and ABCA4 gene mutation associated with subretinal fibrosis. Methods: Four patients with a diagnosis of STGD were clinically examined. All 4 cases underwent a full ophthalmologic evaluation, including best-corrected visual acuity measured by the Snellen visual chart, biomicroscopic examination, fundus examination, fundus photography, electroretinogram, microperimetry, optical coherence tomography and fundus autofluorescence. All patients were subsequently screened for ABCA4 gene mutations, identified by microarray genotyping and confirmed by conventional DNA sequencing of the relevant exons. Results: In all 4 patients, ophthalmologic exam showed areas of subretinal fibrosis in different retinal sectors. In only 1 case, these lesions were correlated to an ocular trauma as confirmed by biomicroscopic examination of the anterior segment that showed a nuclear cataract dislocated to the superior site and vitreous opacities along the lens capsule. The other patients reported a lifestyle characterized by competitive sport activities. The performed instrumental diagnostic investigations confirmed the diagnosis of STGD with FFM in all patients. Moreover, in all 4 affected individuals, mutations in the ABCA4 gene were found. Conclusions: Patients with the diagnosis of STGD associated with FFM can show atypical fundus findings. We report on 4 patients affected by STGD with ABCA4 gene mutation associated with subretinal fibrosis. Our findings suggest that this phenomenon can be accelerated by ocular trauma and also by ocular microtrauma caused by sport activities, highlighting that lifestyle can play a role in the onset of these lesions.

  9. Microarray-based mutation analysis of the ABCA4 (ABCR) gene in autosomal recessive cone-rod dystrophy and retinitis pigmentosa.

    Science.gov (United States)

    Klevering, B Jeroen; Yzer, Suzanne; Rohrschneider, Klaus; Zonneveld, Marijke; Allikmets, Rando; van den Born, L Ingeborgh; Maugeri, Alessandra; Hoyng, Carel B; Cremers, Frans P M

    2004-12-01

    Mutations in the ABCA4 gene have been associated with autosomal recessive Stargardt disease (STGD1), cone-rod dystrophy (CRD), and retinitis pigmentosa (RP). We employed a recently developed genotyping microarray, the ABCR400-chip, to search for known ABCA4 mutations in patients with isolated or autosomal recessive CRD (54 cases) or RP (90 cases). We performed detailed ophthalmologic examinations and identified at least one ABCA4 mutation in 18 patients (33%) with CRD and in five patients (5.6%) with RP. Single-strand conformation polymorphism (SSCP) analysis and subsequent DNA sequencing revealed four novel missense mutations (R24C, E161K, P597S, G618E) and a novel 1-bp deletion (5888delG). Ophthalmoscopic abnormalities in CRD patients ranged from minor granular pigmentary changes in the posterior pole to widespread atrophy. In 12 patients with recordable electroretinogram (ERG) tracings, a cone-rod pattern was detected. Three patients demonstrated progression from a retinal dystrophy resembling STGD1 to a more widespread degeneration, and were subsequently diagnosed as CRD. In addition to a variable degree of atrophy, all RP patients displayed ophthalmologic characteristics of classic RP. When detectable, ERG recordings in these patients demonstrated rod-cone patterns of photoreceptor degeneration. In conclusion, in this study, we show that the ABCA4 mutation chip is an efficient first screening tool for arCRD.

  10. Multivariate prediction of spontaneous repetitive responses in ventricular myocardium exposed in vitro to simulated ischemic conditions.

    Science.gov (United States)

    Schiariti, M; Puddu, P E; Rouet, R

    1994-06-01

    Guinea-pig ventricular myocardium was partly exposed to normal Tyrode's superfusion and partly to altered conditions (using modified Tyrode's solution) set to simulate acute myocardial ischemia (PO2 80 +/- 10 mmHg; no glucose; pH 7.00 +/- 0.05; K+ 12 mM). Using a double-chamber tissue bath and standard microelectrode technique, the occurrence of spontaneous repetitive responses was investigated during simulated ischemia (occlusion) and after reperfusing the previously ischemic superfused tissue with normal Tyrode's solution (reperfusion). In 62 experiments (42 animals) the effects of: (1) duration of simulated ischemia (1321 +/- 435 s), (2) stimulation rate (1002 +/- 549 ms) and (3) number of successive simulated ischemic periods (occlusions) (1.58 +/- 0.92) on: (1) resting membrane potential, (2) action potential amplitude, (3) duration of 50 and 90% action potentials and (4) maximal upstroke velocity of action potential were studied. All variables were considered as gradients (delta) between normal and ischemic tissue. Both during occlusion and upon reperfusion, spontaneous repetitive responses were coded as single, couplets, salvos (three to nine and > 10) or total spontaneous repetitive responses (coded present when at least one of the above-mentioned types was seen). The incidence of total spontaneous repetitive responses was 31% (19/62) on occlusion and 85% (53/62) upon reperfusion. Cox's models (forced and stepwise) were used to predict multivariately the occurrence of arrhythmic events considered as both total spontaneous repetitive responses and as separate entities. These models were applicable since continuous monitoring of the experiments enabled exact timing of spontaneous repetitive response onset during both occlusion and reperfusion. In predicting reperfusion spontaneous repetitive responses, total spontaneous repetitive responses and blocks observed during the occlusion period were also considered. Total occlusion spontaneous repetitive responses

  11. Multi-site laser Doppler flowmetry for assessing collateral flow in experimental ischemic stroke: Validation of outcome prediction with acute MRI.

    Science.gov (United States)

    Cuccione, Elisa; Versace, Alessandro; Cho, Tae-Hee; Carone, Davide; Berner, Lise-Prune; Ong, Elodie; Rousseau, David; Cai, Ruiyao; Monza, Laura; Ferrarese, Carlo; Sganzerla, Erik P; Berthezène, Yves; Nighoghossian, Norbert; Wiart, Marlène; Beretta, Simone; Chauveau, Fabien

    2017-06-01

    High variability in infarct size is common in experimental stroke models and affects statistical power and validity of neuroprotection trials. The aim of this study was to explore cerebral collateral flow as a stratification factor for the prediction of ischemic outcome. Transient intraluminal occlusion of the middle cerebral artery was induced for 90 min in 18 Wistar rats. Cerebral collateral flow was assessed intra-procedurally using multi-site laser Doppler flowmetry monitoring in both the lateral middle cerebral artery territory and the borderzone territory between middle cerebral artery and anterior cerebral artery. Multi-modal magnetic resonance imaging was used to assess acute ischemic lesion (diffusion-weighted imaging, DWI), acute perfusion deficit (time-to-peak, TTP), and final ischemic lesion at 24 h. Infarct volumes and typology at 24 h (large hemispheric versus basal ganglia infarcts) were predicted by both intra-ischemic collateral perfusion and acute DWI lesion volume. Collateral flow assessed by multi-site laser Doppler flowmetry correlated with the corresponding acute perfusion deficit using TTP maps. Multi-site laser Doppler flowmetry monitoring was able to predict ischemic outcome and perfusion deficit in good agreement with acute MRI. Our results support the additional value of cerebral collateral flow monitoring for outcome prediction in experimental ischemic stroke, especially when acute MRI facilities are not available.

  12. Heat shock protein 27-derived atheroprotection involves reverse cholesterol transport that is dependent on GM-CSF to maintain ABCA1 and ABCG1 expression in ApoE-/- mice.

    Science.gov (United States)

    Pulakazhi Venu, Vivek Krishna; Adijiang, Ayinuer; Seibert, Tara; Chen, Yong-Xiang; Shi, Chunhua; Batulan, Zarah; O'Brien, Edward R

    2017-06-01

    Recently, we demonstrated that heat shock protein (HSP)-27 is protective against the development of experimental atherosclerosis, reducing plaque cholesterol content by more than 30%. Moreover, elevated HSP-27 levels are predictive of relative freedom from clinical cardiovascular events. HSP-27 signaling occurs via the activation of NF-κB, which induces a marked up-regulation in expression of granulocyte-monocyte colony-stimulating factor (GM-CSF), a cytokine that is known to alter ABC transporters involved in reverse cholesterol transport (RCT). Therefore, we hypothesized that HSP-27-derived GM-CSF has a potent role in impeding plaque formation by promoting macrophage RCT and sought to better characterize this pathway. Treatment of THP-1 cells, RAW-Blue cells, and primary macrophages with recombinant HSP-27 resulted in NF-κB activation via TLR-4 and was inhibited by various pharmacologic blockers of this pathway. Moreover, HSP-27-induced upregulation of GM-CSF expression was dependent on TLR-4 signaling. Recombinant (r)HSP-27 treatment of ApoE -/- female (but not male) mice for 4 wk yielded reductions in plaque area and cholesterol clefts of 33 and 47%, respectively, with no effect on GM-CSF -/- ApoE -/- mice. With 12 wk of rHSP-27 treatment, both female and male mice showed reductions in plaque burden (55 and 42%, respectively) and a 60% reduction in necrotic core area but no treatment effect in GM-CSF -/- ApoE -/- mice. In vitro functional studies revealed that HSP-27 enhanced the expression of ABCA1 and ABCG1, as well as facilitated cholesterol efflux in vitro by ∼10%. These novel findings establish a paradigm for HSP-27-mediated RCT and set the stage for the development of HSP-27 atheroprotective therapeutics.-Pulakazhi Venu, V. K., Adijiang, A., Seibert, T., Chen, Y.-X., Shi, C., Batulan, Z., O'Brien, E. R. Heat shock protein 27-derived atheroprotection involves reverse cholesterol transport that is dependent on GM-CSF to maintain ABCA1 and ABCG1

  13. Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Frikke-Schmidt, R.; Nordestgaard, B.G.; Stene, M.C.A.

    2008-01-01

    increased risk of ischemic heart disease ( IHD). Design, Setting, and Participants Three studies of white individuals from Copenhagen, Denmark, were used: the Copenhagen City Heart Study ( CCHS), a 31-year prospective general population study ( n= 9022; 28 heterozygotes); the Copenhagen General Population...

  14. Pre-Ischemic Treadmill Training for Prevention of Ischemic Brain Injury via Regulation of Glutamate and Its Transporter GLT-1

    Directory of Open Access Journals (Sweden)

    Jingchun Guo

    2012-07-01

    Full Text Available Pre-ischemic treadmill training exerts cerebral protection in the prevention of cerebral ischemia by alleviating neurotoxicity induced by excessive glutamate release following ischemic stroke. However, the underlying mechanism of this process remains unclear. Cerebral ischemia-reperfusion injury was observed in a rat model after 2 weeks of pre-ischemic treadmill training. Cerebrospinal fluid was collected using the microdialysis sampling method, and the concentration of glutamate was determined every 40 min from the beginning of ischemia to 4 h after reperfusion with high-performance liquid chromatography (HPLC-fluorescence detection. At 3, 12, 24, and 48 h after ischemia, the expression of the glutamate transporter-1 (GLT-1 protein in brain tissues was determined by Western blot respectively. The effect of pre-ischemic treadmill training on glutamate concentration and GLT-1 expression after cerebral ischemia in rats along with changes in neurobehavioral score and cerebral infarct volume after 24 h ischemia yields critical information necessary to understand the protection mechanism exhibited by pre-ischemic treadmill training. The results demonstrated that pre-ischemic treadmill training up-regulates GLT-1 expression, decreases extracellular glutamate concentration, reduces cerebral infarct volume, and improves neurobehavioral score. Pre-ischemic treadmill training is likely to induce neuroprotection after cerebral ischemia by regulating GLT-1 expression, which results in re-uptake of excessive glutamate.

  15. Outcome of ABCA4 disease-associated alleles in autosomal recessive retinal dystrophies: retrospective analysis in 420 Spanish families.

    Science.gov (United States)

    Riveiro-Alvarez, Rosa; Lopez-Martinez, Miguel-Angel; Zernant, Jana; Aguirre-Lamban, Jana; Cantalapiedra, Diego; Avila-Fernandez, Almudena; Gimenez, Ascension; Lopez-Molina, Maria-Isabel; Garcia-Sandoval, Blanca; Blanco-Kelly, Fiona; Corton, Marta; Tatu, Sorina; Fernandez-San Jose, Patricia; Trujillo-Tiebas, Maria-Jose; Ramos, Carmen; Allikmets, Rando; Ayuso, Carmen

    2013-11-01

    To provide a comprehensive overview of all detected mutations in the ABCA4 gene in Spanish families with autosomal recessive retinal disorders, including Stargardt's disease (arSTGD), cone-rod dystrophy (arCRD), and retinitis pigmentosa (arRP), and to assess genotype-phenotype correlation and disease progression in 10 years by considering the type of variants and age at onset. Case series. A total of 420 unrelated Spanish families: 259 arSTGD, 86 arCRD, and 75 arRP. Spanish families were analyzed through a combination of ABCR400 genotyping microarray, denaturing high-performance liquid chromatography, and high-resolution melting scanning. Direct sequencing was used as a confirmation technique for the identified variants. Screening by multiple ligation probe analysis was used to detect possible large deletions or insertions in the ABCA4 gene. Selected families were analyzed further by next generation sequencing. DNA sequence variants, mutation detection rates, haplotypes, age at onset, central or peripheral vision loss, and night blindness. Overall, we detected 70.5% and 36.6% of all expected ABCA4 mutations in arSTGD and arCRD patient cohorts, respectively. In the fraction of the cohort where the ABCA4 gene was sequenced completely, the detection rates reached 73.6% for arSTGD and 66.7% for arCRD. However, the frequency of possibly pathogenic ABCA4 alleles in arRP families was only slightly higher than that in the general population. Moreover, in some families, mutations in other known arRP genes segregated with the disease phenotype. An increasing understanding of causal ABCA4 alleles in arSTGD and arCRD facilitates disease diagnosis and prognosis and also is paramount in selecting patients for emerging clinical trials of therapeutic interventions. Because ABCA4-associated diseases are evolving retinal dystrophies, assessment of age at onset, accurate clinical diagnosis, and genetic testing are crucial. We suggest that ABCA4 mutations may be associated with a

  16. A lower baseline glomerular filtration rate predicts high mortality and newly cerebrovascular accidents in acute ischemic stroke patients.

    Science.gov (United States)

    Dong, Kai; Huang, Xiaoqin; Zhang, Qian; Yu, Zhipeng; Ding, Jianping; Song, Haiqing

    2017-02-01

    Chronic kidney disease (CKD) is gradually recognized as an independent risk factor for cardiovascular and cardio-/cerebrovascular disease. This study aimed to examine the association of the estimated glomerular filtration rate (eGFR) and clinical outcomes at 3 months after the onset of ischemic stroke in a hospitalized Chinese population.Totally, 972 patients with acute ischemic stroke were enrolled into this study. Modified of Diet in Renal Disease (MDRD) equations were used to calculate eGFR and define CKD. The site and degree of the stenosis were examined. Patients were followed-up for 3 months. Endpoint events included all-cause death and newly ischemic events. The multivariate logistic model was used to determine the association between renal dysfunction and patients' outcomes.Of all patients, 130 patients (13.4%) had reduced eGFR (<60 mL/min/1.73 m), and 556 patients had a normal eGFR (≥90 mL/min/1.73 m). A total of 694 patients suffered from cerebral artery stenosis, in which 293 patients only had intracranial artery stenosis (ICAS), 110 only with extracranial carotid atherosclerotic stenosis (ECAS), and 301 with both ICAS and ECAS. The patients with eGFR <60 mL/min/1.73m had a higher proportion of death and newly ischemic events compared with those with a relatively normal eGFR. Multivariate analysis revealed that a baseline eGFR <60 mL/min/1.73 m increased the risk of mortality by 3.089-fold and newly ischemic events by 4.067-fold. In further analysis, a reduced eGFR was associated with increased rates of mortality and newly events both in ICAS patients and ECAS patients. However, only an increased risk of newly events was found as the degree of renal function deteriorated in ICAS patients (odds ratio = 8.169, 95% confidence interval = 2.445-14.127).A low baseline eGFR predicted a high mortality and newly ischemic events at 3 months in ischemic stroke patients. A low baseline eGFR was also a strong independent predictor for newly

  17. Low free triiodothyronine predicts poor functional outcome after acute ischemic stroke.

    Science.gov (United States)

    Suda, Satoshi; Muraga, Kanako; Kanamaru, Takuya; Okubo, Seiji; Abe, Arata; Aoki, Junya; Suzuki, Kentaro; Sakamoto, Yuki; Shimoyama, Takashi; Nito, Chikako; Kimura, Kazumi

    2016-09-15

    The aim of this study was to investigate the association of admission serum thyroid hormone concentration with clinical characteristics and functional outcomes in patients after acute ischemic stroke. We retrospectively enrolled 398 consecutive patients admitted to our stroke center between July 2010 and April 2012. Serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were evaluated upon admission. Neurological severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) upon admission and the modified Rankin Scale (mRS) upon discharge. Poor outcome was defined as a mRS score of 3-5 or death (mRS score 6). Separate analyses were conducted according to outcome and quartile serum FT3 concentration. In total, 164 patients (41.2%) demonstrated a poor outcome. Age, male gender, blood glucose level, arterial fibrillation, dyslipidemia, smoking, NIHSS score, cardioembolic stroke type, and periventricular hyperintensities, but not FT4 or TSH, were significantly associated with poor functional outcome. Furthermore, poor functional outcome was independently associated with low FT3 (<2.29pg/mL). In comparisons between FT3 quartiles (Q1 [≤2.11pg/mL], Q2 [2.12-2.45pg/mL], Q3 [2.46-2.77pg/mL], Q4 [≥2.78pg/mL]), patients with poor outcomes were more frequent in Q1 than in Q4 after multivariate adjustment. Death was more frequent in Q1 than in Q4 after adjustment for risk factors and comorbidities, but this difference was non-significant after additional adjustment for age and NIHSS score. Our data suggest that a lower FT3 value upon admission may predict a poor functional outcome in patients with acute ischemic stroke. Further large-scale prospective studies are required to clarify the role of thyroid hormone in the acute phase of ischemic stroke. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Predicting final extent of ischemic infarction using artificial neural network analysis of multi-parametric MRI in patients with stroke.

    Directory of Open Access Journals (Sweden)

    Hassan Bagher-Ebadian

    Full Text Available In hemispheric ischemic stroke, the final size of the ischemic lesion is the most important correlate of clinical functional outcome. Using a set of acute-phase MR images (Diffusion-weighted--DWI, T(1-weighted--T1WI, T(2-weighted--T2WI, and proton density weighted--PDWI for inputs, and the chronic T2WI at 3 months as an outcome measure, an Artificial Neural Network (ANN was trained to predict the 3-month outcome in the form of a voxel-by-voxel forecast of the chronic T2WI. The ANN was trained and tested using 12 subjects (with 83 slices and 140218 voxels using a leave-one-out cross-validation method with calculation of the Area Under the Receiver Operator Characteristic Curve (AUROC for training, testing and optimization of the ANN. After training and optimization, the ANN produced maps of predicted outcome that were well correlated (r = 0.80, p<0.0001 with the T2WI at 3 months for all 12 patients. This result implies that the trained ANN can provide an estimate of 3-month ischemic lesion on T2WI in a stable and accurate manner (AUROC = 0.89.

  19. A Comprehensive Survey of Sequence Variation in the ABCA4 (ABCR) Gene in Stargardt Disease and Age-Related Macular Degeneration

    OpenAIRE

    Rivera, Andrea; White, Karen; Stöhr, Heidi; Steiner, Klaus; Hemmrich, Nadine; Grimm, Timo; Jurklies, Bernhard; Lorenz, Birgit; Scholl, Hendrik P. N.; Apfelstedt-Sylla, Eckhart; Weber, Bernhard H. F.

    2000-01-01

    Stargardt disease (STGD) is a common autosomal recessive maculopathy of early and young-adult onset and is caused by alterations in the gene encoding the photoreceptor-specific ATP-binding cassette (ABC) transporter (ABCA4). We have studied 144 patients with STGD and 220 unaffected individuals ascertained from the German population, to complete a comprehensive, population-specific survey of the sequence variation in the ABCA4 gene. In addition, we have assessed the proposed role for ABCA4 in ...

  20. [From gene to disease: from the ABCA4 gene to Stargardt disease, cone-rod dystrophy and retinitis pigmentosa

    NARCIS (Netherlands)

    Cremers, F.P.M.; Maugeri, A.; Klevering, B.J.; Hoefsloot, L.H.; Hoyng, C.B.

    2002-01-01

    Autosomal recessive Stargardt disease is caused by mutations in the ABCA4 gene. Mutations in ABCA4 are also found in two-thirds of cases with autosomal recessive cone-rod dystrophy, and a small fraction of patients with autosomal recessive retinitis pigmentosa. Patients with autosomal recessive

  1. Artificial neural network prediction of ischemic tissue fate in acute stroke imaging

    Science.gov (United States)

    Huang, Shiliang; Shen, Qiang; Duong, Timothy Q

    2010-01-01

    Multimodal magnetic resonance imaging of acute stroke provides predictive value that can be used to guide stroke therapy. A flexible artificial neural network (ANN) algorithm was developed and applied to predict ischemic tissue fate on three stroke groups: 30-, 60-minute, and permanent middle cerebral artery occlusion in rats. Cerebral blood flow (CBF), apparent diffusion coefficient (ADC), and spin–spin relaxation time constant (T2) were acquired during the acute phase up to 3 hours and again at 24 hours followed by histology. Infarct was predicted on a pixel-by-pixel basis using only acute (30-minute) stroke data. In addition, neighboring pixel information and infarction incidence were also incorporated into the ANN model to improve prediction accuracy. Receiver-operating characteristic analysis was used to quantify prediction accuracy. The major findings were the following: (1) CBF alone poorly predicted the final infarct across three experimental groups; (2) ADC alone adequately predicted the infarct; (3) CBF+ADC improved the prediction accuracy; (4) inclusion of neighboring pixel information and infarction incidence further improved the prediction accuracy; and (5) prediction was more accurate for permanent occlusion, followed by 60- and 30-minute occlusion. The ANN predictive model could thus provide a flexible and objective framework for clinicians to evaluate stroke treatment options on an individual patient basis. PMID:20424631

  2. Genotyping microarray (gene chip) for the ABCR (ABCA4) gene.

    NARCIS (Netherlands)

    Jaakson, K.; Zernant, J.; Kulm, M.; Hutchinson, A.; Tonisson, N.; Glavac, D.; Ravnik-Glavac, M.; Hawlina, M.; Meltzer, M.R.; Caruso, R.C.; Testa, F.; Maugeri, A.; Hoyng, C.B.; Gouras, P.; Simonelli, F.; Lewis, R.A.; Lupski, J.R.; Cremers, F.P.M.; Allikmets, R.

    2003-01-01

    Genetic variation in the ABCR (ABCA4) gene has been associated with five distinct retinal phenotypes, including Stargardt disease/fundus flavimaculatus (STGD/FFM), cone-rod dystrophy (CRD), and age-related macular degeneration (AMD). Comparative genetic analyses of ABCR variation and diagnostics

  3. Hemostatic system changes predictive value in patients with ischemic brain disorders

    Directory of Open Access Journals (Sweden)

    Raičević Ranko

    2002-01-01

    Full Text Available The aim of this research was to determine the importance of tracking the dynamics of changes of the hemostatic system factors (aggregation of thrombocytes, D-dimer, PAI-1, antithrombin III, protein C and protein S, factor VII and factor VIII, fibrin degradation products, euglobulin test and the activated partial thromboplastin time – aPTPV in relation to the level of the severity of ischemic brain disorders (IBD and the level of neurological and functional deficiency in the beginning of IBD manifestation from 7 to 10 days, 19 to 21 day, and after 3 to 6 months. The research results confirmed significant predictive value of changes of hemostatic system with the predomination of procoagulant factors, together with the insufficiency of fibrinolysis. Concerning the IBD severity and it's outcome, the significant predictive value was shown in the higher levels of PAI-1 and the lower level of antithrombin III, and borderline significant value was shown in the accelerated aggregation of thrombocytes and the increased concentration of D-dimer. It could be concluded that the tracking of the dynamics of changes in parameters of hemostatic system proved to be an easily accessible method with the significant predictive value regarding the development of more severe. IBD cases and the outcome of the disease itself.

  4. Predictors of ischemic versus hemorrhagic strokes in hypertensive patients

    International Nuclear Information System (INIS)

    Khealani, B.A.; Syed, N.A.; Maken, S.; Mapari, U.U.; Hameed, B.; Ali, S.; Qureshi, R.; Akhter, N.; Hassan, A.; Sonawalla, A.B.; Baig, S.M.; Wasay, M.

    2005-01-01

    Objective: To identify the factors that predispose to ischemic versus hemorrhagic stroke in hypertensive patients. Materials and Methods: All the hypertensive patients, who were registered in AKUH acute stroke outcome data base, over a period of 22 months, were identified and from this cohort the patients with first ever stroke were selected. The data regarding demographics, stroke type (ischemic vs. hemorrhagic), pre-existing medical problems, laboratory and radiological investigations was recorded and analyzed. Results: Five hundred and nineteen patients with either ischemic stroke or parenchymal hemorrhage were registered over a period of 22 months. Three hundred and forty-eight patients (67%) had hypertension and of these, 250 had first ever stroke at the time of admission. Presence of diabetes mellitus (OR: 3.76; Cl:1.67-8.46) and ischemic heart disease (OR: 6.97; Cl:1.57-30.98) were found to be independent predictors of ischemic strokes. Conclusion: Presence of diabetes mellitus and ischemic heart disease predict ischemic stroke in a patient with hypertension. (author)

  5. Phenotypic spectrum of autosomal recessive cone-rod dystrophies caused by mutations in the ABCA4 (ABCR) gene.

    Science.gov (United States)

    Klevering, B Jeroen; Blankenagel, Anita; Maugeri, Alessandra; Cremers, Frans P M; Hoyng, Carel B; Rohrschneider, Klaus

    2002-06-01

    To describe the phenotype of 12 patients with autosomal recessive or isolated cone-rod types of progressive retinal degeneration (CRD) caused by mutations in the ABCA4 gene. The charts of patients who had originally received a diagnosis of isolated or autosomal recessive CRD were reviewed after molecular analysis revealed mutations in the ABCA4 gene. In two of the patients both the photopic and scotopic electroretinogram were nonrecordable. In the remainder, the photopic cone b-wave amplitudes appeared to be more seriously affected than the scotopic rod b-wave amplitudes. Although the clinical presentation was heterogeneous, all patients experienced visual loss early in life, impaired color vision, and a central scotoma. Fundoscopy revealed evidence of early-onset maculopathy, sometimes accompanied by involvement of the retinal periphery in the later stages of the disease. Mutations in the ABCA4 gene are the pathologic cause of the CRD-like dystrophy in these patients, and the resultant clinical pictures are complex and heterogeneous. Given this wide clinical spectrum of CRD-like phenotypes associated with ABCA4 mutations, detailed clinical subclassifications are difficult and may not be very useful.

  6. Risk score to predict gastrointestinal bleeding after acute ischemic stroke.

    Science.gov (United States)

    Ji, Ruijun; Shen, Haipeng; Pan, Yuesong; Wang, Penglian; Liu, Gaifen; Wang, Yilong; Li, Hao; Singhal, Aneesh B; Wang, Yongjun

    2014-07-25

    Gastrointestinal bleeding (GIB) is a common and often serious complication after stroke. Although several risk factors for post-stroke GIB have been identified, no reliable or validated scoring system is currently available to predict GIB after acute stroke in routine clinical practice or clinical trials. In the present study, we aimed to develop and validate a risk model (acute ischemic stroke associated gastrointestinal bleeding score, the AIS-GIB score) to predict in-hospital GIB after acute ischemic stroke. The AIS-GIB score was developed from data in the China National Stroke Registry (CNSR). Eligible patients in the CNSR were randomly divided into derivation (60%) and internal validation (40%) cohorts. External validation was performed using data from the prospective Chinese Intracranial Atherosclerosis Study (CICAS). Independent predictors of in-hospital GIB were obtained using multivariable logistic regression in the derivation cohort, and β-coefficients were used to generate point scoring system for the AIS-GIB. The area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration, respectively. A total of 8,820, 5,882, and 2,938 patients were enrolled in the derivation, internal validation and external validation cohorts. The overall in-hospital GIB after AIS was 2.6%, 2.3%, and 1.5% in the derivation, internal, and external validation cohort, respectively. An 18-point AIS-GIB score was developed from the set of independent predictors of GIB including age, gender, history of hypertension, hepatic cirrhosis, peptic ulcer or previous GIB, pre-stroke dependence, admission National Institutes of Health stroke scale score, Glasgow Coma Scale score and stroke subtype (Oxfordshire). The AIS-GIB score showed good discrimination in the derivation (0.79; 95% CI, 0.764-0.825), internal (0.78; 95% CI, 0.74-0.82) and external (0.76; 95% CI, 0.71-0.82) validation cohorts

  7. Mutation Spectrum of the ABCA4 Gene in a Greek Cohort with Stargardt Disease: Identification of Novel Mutations and Evidence of Three Prevalent Mutated Alleles

    Directory of Open Access Journals (Sweden)

    Kamakari Smaragda

    2018-01-01

    Full Text Available Aim. To evaluate the frequency and pattern of disease-associated mutations of ABCA4 gene among Greek patients with presumed Stargardt disease (STGD1. Materials and Methods. A total of 59 patients were analyzed for ABCA4 mutations using the ABCR400 microarray and PCR-based sequencing of all coding exons and flanking intronic regions. MLPA analysis as well as sequencing of two regions in introns 30 and 36 reported earlier to harbor deep intronic disease-associated variants was used in 4 selected cases. Results. An overall detection rate of at least one mutant allele was achieved in 52 of the 59 patients (88.1%. Direct sequencing improved significantly the complete characterization rate, that is, identification of two mutations compared to the microarray analysis (93.1% versus 50%. In total, 40 distinct potentially disease-causing variants of the ABCA4 gene were detected, including six previously unreported potentially pathogenic variants. Among the disease-causing variants, in this cohort, the most frequent was c.5714+5G>A representing 16.1%, while p.Gly1961Glu and p.Leu541Pro represented 15.2% and 8.5%, respectively. Conclusions. By using a combination of methods, we completely molecularly diagnosed 48 of the 59 patients studied. In addition, we identified six previously unreported, potentially pathogenic ABCA4 mutations.

  8. Predicting Hemorrhagic Transformation of Acute Ischemic Stroke: Prospective Validation of the HeRS Score.

    Science.gov (United States)

    Marsh, Elisabeth B; Llinas, Rafael H; Schneider, Andrea L C; Hillis, Argye E; Lawrence, Erin; Dziedzic, Peter; Gottesman, Rebecca F

    2016-01-01

    Hemorrhagic transformation (HT) increases the morbidity and mortality of ischemic stroke. Anticoagulation is often indicated in patients with atrial fibrillation, low ejection fraction, or mechanical valves who are hospitalized with acute stroke, but increases the risk of HT. Risk quantification would be useful. Prior studies have investigated risk of systemic hemorrhage in anticoagulated patients, but none looked specifically at HT. In our previously published work, age, infarct volume, and estimated glomerular filtration rate (eGFR) significantly predicted HT. We created the hemorrhage risk stratification (HeRS) score based on regression coefficients in multivariable modeling and now determine its validity in a prospectively followed inpatient cohort.A total of 241 consecutive patients presenting to 2 academic stroke centers with acute ischemic stroke and an indication for anticoagulation over a 2.75-year period were included. Neuroimaging was evaluated for infarct volume and HT. Hemorrhages were classified as symptomatic versus asymptomatic, and by severity. HeRS scores were calculated for each patient and compared to actual hemorrhage status using receiver operating curve analysis.Area under the curve (AUC) comparing predicted odds of hemorrhage (HeRS score) to actual hemorrhage status was 0.701. Serum glucose (P hemorrhages were more likely to be symptomatic and more severe.The HeRS score is a valid predictor of HT in patients with ischemic stroke and indication for anticoagulation.

  9. Clinical study on HAT and SEDAN score scales and related risk factors for predicting hemorrhagic transformation following thrombolysis in acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Heng WEI

    2015-03-01

    Full Text Available Objective To investigate the value of HAT and SEDAN score scales in predicting hemorrhagic transformation (HT following the recombinant tissue-type plasminogen activator (rt-PA intravenous thrombolysis in acute ischemic stroke patients and risk factors affecting HT.  Methods A total of 143 patients with acute ischemic stroke underwent rt-PA intravenous thrombolysis within 4.50 h of onset and their clinical data were collected. According to head CT after thrombolysis, patients were divided into HT group (18 cases and non-HT group (125 cases. Single factor analysis was used to assess differences in HAT and SEDAN score scales and related risk factors of ischemic stroke in 2 groups, and further Logistic regression analysis was used to investigate independent predictors of HT. Receiver operating characteristic (ROC curve was used to evaluate the sensitivity and specificity of HAT and SEDAN score scales in predicting HT.  Results Univariate Logistic regression analysis showed that history of atrial fibrillation (AF, admission systolic blood pressure (SBP, admission blood glucose level, early low density of head CT, thrombolytic time window, National Institute of Health Stroke Scale (NIHSS, HAT and SEDAN scores were all risk factors for HT after thrombolysis (P < 0.05, for all. Multivariate Logistic regression analysis showed that history of AF (OR = 1.677, 95% CI: 1.332-2.111; P = 0.000, admission SBP (OR = 1.102, 95% CI: 1.009-1.204; P = 0.031, admission blood glucose level (OR = 1.870, 95% CI: 1.119-3.125; P = 0.017, thrombolysis time window (OR = 1.030, 95%CI: 1.009-1.052; P = 0.005, NIHSS score (OR = 1.574, 95%CI: 1.186-2.090; P = 0.002, HAT score (OR = 2.515, 95%CI: 1.273-4.970;P = 0.008 and SEDAN score (OR = 2.413, 95%CI: 1.123-5.185; P = 0.024 were risk factors for HT after thrombolysis. ROC curve analysis showed that HAT score could predict HT with 94.40% sensitivity and 41.60% specificity, and area under curve (AUC was 0.70. SEDAN

  10. Functional promoter variant in zinc finger protein 202 predicts severe atherosclerosis and ischemic heart disease

    DEFF Research Database (Denmark)

    Frikke-Schmidt, R.; Nordestgaard, Børge; Grande, Peer

    2008-01-01

    Objectives This study was designed to test the hypotheses that single nucleotide polymorphisms ( SNPs), in zinc finger protein 202 ( ZNF202), predict severe atherosclerosis and ischemic heart disease ( IHD). Background ZNF202 is a transcriptional repressor controlling promoter elements in genes...... involved in vascular maintenance and lipid metabolism. Methods We first determined genotype association for 9 ZNF202 SNPs with severe atherosclerosis ( ankle brachial index >0.7 vs. ...,998 controls. Finally, we determined whether g. -660A>G altered transcriptional activity of the ZNF202 promoter in vitro. Results Cross-sectionally, ZNF202 g. -660 GG versus AA homozygosity predicted an odds ratio for severe atherosclerosis of 2.01 ( 95% confidence interval [CI]: 1.34 to 3.01). Prospectively...

  11. Insulin-like Growth Factor 1 Regulates the Expression of ATP-Binding Cassette Transporter A1 in Pancreatic Beta Cells.

    Science.gov (United States)

    Lyu, J; Imachi, H; Iwama, H; Zhang, H; Murao, K

    2016-05-01

    ATP-binding cassette transporter A1 (ABCA1) in pancreatic beta cells influences insulin secretion and cholesterol homeostasis. The present study investigates whether insulin-like growth factor 1 (IGF-1), which mediates stimulation of ABCA1 gene expression, could also interfere with the phosphatidylinositol 3-kinase (PI3-K) cascade.ABCA1 expression was examined by real-time polymerase chain reaction (PCR), Western blot analysis, and a reporter gene assay in rat insulin-secreting INS-1 cells incubated with IGF-1. The binding of forkhead box O1 (FoxO1) protein to the ABCA1 promoter was assessed by a chromatin immunoprecipitation (ChIP) assay. ABCA1 protein levels increased in response to rising concentrations of IGF-1. Real-time PCR analysis showed a significant increase in ABCA1 mRNA expression. However, both effects were suppressed after silencing the IGF-1 receptor. In parallel with its effect on endogenous ABCA1 mRNA levels, IGF-1 induced the activity of a reporter construct containing the ABCA1 promoter, while it was abrogated by LY294002, a specific inhibitor of PI3-K. Constitutively active Akt stimulated activity of the ABCA1 promoter, and a dominant-negative mutant of Akt or mutagenesis of the FoxO1 response element in the ABCA1 promoter abolished the ability of IGF-1 to stimulate promoter activity. A ChIP assay showed that FoxO1 mediated its transcriptional activity by directly binding to the ABCA1 promoter region. The knockdown of FoxO1 disrupted the effect of IGF-1 on ABCA1 expression. Furthermore, IGF-1 promoted cholesterol efflux and reduced the pancreatic lipotoxicity. These results demonstrate that the PI3-K/Akt/FoxO1 pathway contributes to the regulation of ABCA1 expression in response to IGF-1 stimulation. © Georg Thieme Verlag KG Stuttgart · New York.

  12. [Collateral score based on CT perfusion can predict the prognosis of patients with anterior circulation ischemic stroke after thrombectomy].

    Science.gov (United States)

    Wang, Qingsong; Zhang, Sheng; Zhang, Meixia; Chen, Zhicai; Lou, Min

    2017-07-25

    To evaluate the value of collateral score based on CT perfusion (CTP-CS) in predicting the clinical outcome of patients with anterior circulation ischemic stroke after thrombectomy. Clinical data of acute ischemic stroke patients with anterior artery occlusion undergoing endovascular treatment in the Second Affiliated Hospital, Zhejiang University School of Medicine during October 2013 and October 2016 were retrospectively reviewed. Collateral scores were assessed based on CTP and digital subtraction angiography (DSA) images, respectively. And DSA-CS or CTP-CS 3-4 was defined as good collateral vessels. Good clinical outcome was defined as a modified Rankin Scale (mRS) ≤ 2 at 3 months after stroke. The binary logistic regression model was used to analyze the correlation between the collateral score and clinical outcome, and the receiver operating characteristic (ROC) curve was used to analyze the value of DSA-CS and CTP-CS in predicting the clinical outcome. Among 40 patients, 33 (82.5%) acquired recanalization and 16 (40.0%) got good outcome. Compared with poor outcome group, the collateral score (all P collateral vessels were higher in good outcome group (all P collateral vessels were independent factor of good outcome (CTP-CS: OR =48.404, 95% CI :1.373-1706.585, P Collateral scores based on CTP and DSA had good consistency ( κ =0.697, P <0.01), and ROC curve showed that the predictive value of CTP-CS and DSA-CS were comparable (both AUC=0.726, 95% CI :0.559-0.893, P <0.05). CTP-CS can predict the clinical outcome of patients with anterior circulation ischemic stroke after thrombectomy.

  13. The ischemic perinatal brain damage

    International Nuclear Information System (INIS)

    Crisi, G.; Mauri, C.; Canossi, G.; Della Giustina, E.

    1986-01-01

    The term ''hypoxic-ischemic encephalopathy'' covers a large part of neonatal neuropathology including the various forms of intracerebral haemorrhage. In the present work the term is confined to ischemic brain edema and actual infarction, be it diffuse or focal. Eighteen newborns with CT evidence of ischemic brain lesions and infarctual necrosis were selected. Emphasis is placed on current data on neuropathology of ischemic brain edema and its CT appearance. Particular entities such as periventricular leukomalacia and multicystic encephalopathy are discussed. Relationship between CT and temporal profile of cerebral damage is emphasized in order to predict the structural sequelae and the longterm prognosis

  14. Deducing the pathogenic contribution of recessive ABCA4 alleles in an outbred population.

    Science.gov (United States)

    Schindler, Emily I; Nylen, Erik L; Ko, Audrey C; Affatigato, Louisa M; Heggen, Andrew C; Wang, Kai; Sheffield, Val C; Stone, Edwin M

    2010-10-01

    Accurate prediction of the pathogenic effects of specific genotypes is important for the design and execution of clinical trials as well as for meaningful counseling of individual patients. However, for many autosomal recessive diseases, it can be difficult to deduce the relative pathogenic contribution of individual alleles because relatively few affected individuals share the same two disease-causing variations. In this study, we used multiple regression analysis to estimate the pathogenicity of specific alleles of ABCA4 in patients with retinal phenotypes ranging from Stargardt disease to retinitis pigmentosa. This analysis revealed quantitative allelic effects on two aspects of the visual phenotype, visual acuity (P disease and will also aid in the optimal selection of subjects for clinical trials of new therapies.

  15. IQGAP1 is involved in post-ischemic neovascularization by regulating angiogenesis and macrophage infiltration.

    Directory of Open Access Journals (Sweden)

    Norifumi Urao

    2010-10-01

    Full Text Available Neovascularization is an important repair mechanism in response to ischemic injury and is dependent on inflammation, angiogenesis and reactive oxygen species (ROS. IQGAP1, an actin-binding scaffold protein, is a key regulator for actin cytoskeleton and motility. We previously demonstrated that IQGAP1 mediates vascular endothelial growth factor (VEGF-induced ROS production and migration of cultured endothelial cells (ECs; however, its role in post-ischemic neovascularization is unknown.Ischemia was induced by left femoral artery ligation, which resulted in increased IQGAP1 expression in Mac3(+ macrophages and CD31(+ capillary-like ECs in ischemic legs. Mice lacking IQGAP1 exhibited a significant reduction in the post-ischemic neovascularization as evaluated by laser Doppler blood flow, capillary density and α-actin positive arterioles. Furthermore, IQGAP1(-/- mice showed a decrease in macrophage infiltration and ROS production in ischemic muscles, leading to impaired muscle regeneration and increased necrosis and fibrosis. The numbers of bone marrow (BM-derived cells in the peripheral blood were not affected in these knockout mice. BM transplantation revealed that IQGAP1 expressed in both BM-derived cells and tissue resident cells, such as ECs, is required for post-ischemic neovascularization. Moreover, thioglycollate-induced peritoneal macrophage recruitment and ROS production were inhibited in IQGAP1(-/- mice. In vitro, IQGAP1(-/- BM-derived macrophages showed inhibition of migration and adhesion capacity, which may explain the defective macrophage recruitment into the ischemic tissue in IQGAP1(-/- mice.IQGAP1 plays a key role in post-ischemic neovascularization by regulating, not only, ECs-mediated angiogenesis but also macrophage infiltration as well as ROS production. Thus, IQGAP1 is a potential therapeutic target for inflammation- and angiogenesis-dependent ischemic cardiovascular diseases.

  16. Early functional MRI activation predicts motor outcome after ischemic stroke: a longitudinal, multimodal study.

    Science.gov (United States)

    Du, Juan; Yang, Fang; Zhang, Zhiqiang; Hu, Jingze; Xu, Qiang; Hu, Jianping; Zeng, Fanyong; Lu, Guangming; Liu, Xinfeng

    2018-05-15

    An accurate prediction of long term outcome after stroke is urgently required to provide early individualized neurorehabilitation. This study aimed to examine the added value of early neuroimaging measures and identify the best approaches for predicting motor outcome after stroke. This prospective study involved 34 first-ever ischemic stroke patients (time since stroke: 1-14 days) with upper limb impairment. All patients underwent baseline multimodal assessments that included clinical (age, motor impairment), neurophysiological (motor-evoked potentials, MEP) and neuroimaging (diffusion tensor imaging and motor task-based fMRI) measures, and also underwent reassessment 3 months after stroke. Bivariate analysis and multivariate linear regression models were used to predict the motor scores (Fugl-Meyer assessment, FMA) at 3 months post-stroke. With bivariate analysis, better motor outcome significantly correlated with (1) less initial motor impairment and disability, (2) less corticospinal tract injury, (3) the initial presence of MEPs, (4) stronger baseline motor fMRI activations. In multivariate analysis, incorporating neuroimaging data improved the predictive accuracy relative to only clinical and neurophysiological assessments. Baseline fMRI activation in SMA was an independent predictor of motor outcome after stroke. A multimodal model incorporating fMRI and clinical measures best predicted the motor outcome following stroke. fMRI measures obtained early after stroke provided independent prediction of long-term motor outcome.

  17. Serum Insulin-Like Growth Factor 1 and the Risk of Ischemic Stroke: The Framingham Study.

    Science.gov (United States)

    Saber, Hamidreza; Himali, Jayandra J; Beiser, Alexa S; Shoamanesh, Ashkan; Pikula, Aleksandra; Roubenoff, Ronenn; Romero, Jose R; Kase, Carlos S; Vasan, Ramachandran S; Seshadri, Sudha

    2017-07-01

    Low insulin-like growth factor 1 (IGF-1) has been associated with increased risk of atherosclerosis and atrial fibrillation in cross-sectional studies. Yet, prospective data linking IGF-1 levels to the development of ischemic stroke remain inconclusive. We examined prospectively the association between serum IGF-1 levels and incident ischemic stroke. We measured serum IGF-1 levels in 757 elderly individuals (mean age 79±5, 62% women), free of prevalent stroke, from the Framingham original cohort participants at the 22nd examination cycle (1990-1994) and were followed up for the development of ischemic stroke. Cox models were used to relate IGF-1 levels to the risk for incident ischemic stroke, adjusted for potential confounders. During a mean follow-up of 10.2 years, 99 individuals developed ischemic stroke. After adjustment for age, sex, and potential confounders, higher IGF-1 levels were associated with a lower risk of incident ischemic stroke, with subjects in the lowest quintile of IGF-1 levels having a 2.3-fold higher risk of incident ischemic stroke (95% confidence interval, 1.09-5.06; P =0.03) as compared with those in the top quintile. We observed an effect modification by diabetes mellitus and waist-hip ratio for the association between IGF-1 and ischemic stroke ( P <0.1). In subgroup analyses, the effects were restricted to subjects with diabetics and those in top waist-hip ratio quartile, in whom each standard deviation increase in IGF-1 was associated with a 61% (hazard ratio, 0.39; 95% confidence interval, 0.20-0.78; P =0.007) and 41% (hazard ratio, 0.59; 95% confidence interval, 0.37-0.95; P =0.031) lower risk of incident ischemic stroke, respectively. IGF-1 levels were inversely associated with ischemic stroke, especially among persons with insulin resistance. © 2017 American Heart Association, Inc.

  18. Renal dysfunction and chronic kidney disease in ischemic stroke and transient ischemic attack: A population-based study.

    Science.gov (United States)

    Hayden, Derek; McCarthy, Christine; Akijian, Layan; Callaly, Elizabeth; Ní Chróinín, Danielle; Horgan, Gillian; Kyne, Lorraine; Duggan, Joseph; Dolan, Eamon; O' Rourke, Killian; Williams, David; Murphy, Sean; O'Meara, Yvonne; Kelly, Peter J

    2017-10-01

    Background and purpose The prevalence of chronic kidney disease (estimated glomerular filtration rate (eGFR) chronic kidney disease (CKD)) in ischemic stroke and transient ischemic attack (TIA) is unknown, as estimates have been based on single-point estimates of renal function. Studies investigating the effect of renal dysfunction (eGFR < 60 mL/min per 1.73 m 2 , renal dysfunction) on post-stroke outcomes are limited to hospitalized cohorts and have provided conflicting results. Methods We investigated rates, determinants and outcomes of renal dysfunction in ischemic stroke and TIA in the North Dublin Population Stroke Study. We also investigate the persistence of renal dysfunction in 90-day survivors to determine the prevalence of CKD. Ascertainment included hot and cold pursuit using multiple overlapping sources. Survival analysis was performed using Kaplan-Meier survival curves and Cox proportional hazards modeling. Results In 547 patients (ischemic stroke in 76.4%, TIA in 23.6%), the mean eGFR at presentation was 63.7 mL/min/1.73 m 2 (SD 22.1). Renal dysfunction was observed in 44.6% (244/547). Among 90-day survivors, 31.2% (139/446) met criteria for CKD. After adjusting for age and stroke severity, eGFR < 45 mL/min/1.73 m 2 (hazard ratio 2.53, p = 0.01) independently predicted 28-day fatality but not at two years. Poor post-stroke functional outcome (Modified Rankin Scale 3-5) at two years was more common in those with renal dysfunction (52.5% vs. 20.6%, p < 0.001). After adjusting for age, stroke severity and pre-stroke disability, renal dysfunction (OR 2.17, p = 0.04) predicted poor functional outcome. Conclusion Renal dysfunction and CKD are common in ischemic stroke and TIA. Renal dysfunction is associated with considerable post-stroke morbidity and mortality. Further studies are needed to investigate if modifiable mechanisms underlie these associations.

  19. Characteristics of Misclassified CT Perfusion Ischemic Core in Patients with Acute Ischemic Stroke.

    Directory of Open Access Journals (Sweden)

    Ralph R E G Geuskens

    Full Text Available CT perfusion (CTP is used to estimate the extent of ischemic core and penumbra in patients with acute ischemic stroke. CTP reliability, however, is limited. This study aims to identify regions misclassified as ischemic core on CTP, using infarct on follow-up noncontrast CT. We aim to assess differences in volumetric and perfusion characteristics in these regions compared to areas that ended up as infarct on follow-up.This study included 35 patients with >100 mm brain coverage CTP. CTP processing was performed using Philips software (IntelliSpace 7.0. Final infarct was automatically segmented on follow-up noncontrast CT and used as reference. CTP and follow-up noncontrast CT image data were registered. This allowed classification of ischemic lesion agreement (core on CTP: rMTT≥145%, aCBV<2.0 ml/100g and infarct on follow-up noncontrast CT and misclassified ischemic core (core on CTP, not identified on follow-up noncontrast CT regions. False discovery ratio (FDR, defined as misclassified ischemic core volume divided by total CTP ischemic core volume, was calculated. Absolute and relative CTP parameters (CBV, CBF, and MTT were calculated for both misclassified CTP ischemic core and ischemic lesion agreement regions and compared using paired rank-sum tests.Median total CTP ischemic core volume was 49.7ml (IQR:29.9ml-132ml; median misclassified ischemic core volume was 30.4ml (IQR:20.9ml-77.0ml. Median FDR between patients was 62% (IQR:49%-80%. Median relative mean transit time was 243% (IQR:198%-289% and 342% (IQR:249%-432% for misclassified and ischemic lesion agreement regions, respectively. Median absolute cerebral blood volume was 1.59 (IQR:1.43-1.79 ml/100g (P<0.01 and 1.38 (IQR:1.15-1.49 ml/100g (P<0.01 for misclassified ischemic core and ischemic lesion agreement, respectively. All CTP parameter values differed significantly.For all patients a considerable region of the CTP ischemic core is misclassified. CTP parameters significantly

  20. Association of a homozygous nonsense mutation in the ABCA4 (ABCR) gene with cone-rod dystrophy phenotype in an Italian family.

    Science.gov (United States)

    Simonelli, Francesca; Testa, Francesco; Zernant, Jana; Nesti, Anna; Rossi, Settimio; Rinaldi, Ernesto; Allikmets, Rando

    2004-01-01

    Genetic variation in the ABCA4 (ABCR) gene has been associated with several distinct retinal phenotypes, including Stargardt disease/fundus flavimaculatus (STGD/FFM), cone-rod dystrophy (CRD), retinitis pigmentosa (RP) and age-related macular degeneration. The current model of genotype/phenotype association suggests that patients harboring deleterious mutations in both ABCR alleles would develop RP-like retinal pathology. Here we describe ABCA4-associated phenotypes, including a proband with a homozygous nonsense mutation in a family from Southern Italy. The proband had been originally diagnosed with STGD. Ophthalmologic examination included kinetic perimetry, electrophysiological studies and fluorescein angiography. DNA of the affected individual and family members was analyzed for variants in all 50 exons of the ABCA4 gene by screening on the ABCR400 microarray. A homozygous nonsense mutation 2971G>T (G991X) was detected in a patient initially diagnosed with STGD based on funduscopic evidence, including bull's eye depigmentation of the fovea and flecks at the posterior pole extending to the mid-peripheral retina. Since this novel nucleotide substitution results in a truncated, nonfunctional, ABCA4 protein, the patient was examined in-depth for the severity of the disease phenotype. Indeed, subsequent electrophysiological studies determined severely reduced cone amplitude as compared to the rod amplitude, suggesting the diagnosis of CRD. ABCR400 microarray is an efficient tool for determining causal genetic variation, including new mutations. A homozygous protein-truncating mutation in ABCA4 can cause a phenotype ranging from STGD to CRD as diagnosed at an early stage of the disease. Only a combination of comprehensive genotype/phenotype correlation studies will determine the proper diagnosis and prognosis of ABCA4-associated pathology. Copyright 2004 S. Karger AG, Basel

  1. Reduced-illuminance autofluorescence imaging in ABCA4-associated retinal degenerations

    Science.gov (United States)

    Cideciyan, Artur V.; Swider, Malgorzata; Aleman, Tomas S.; Roman, Marisa I.; Sumaroka, Alexander; Schwartz, Sharon B.; Stone, Edwin M.; Jacobson, Samuel G.

    2007-05-01

    The health of the retinal pigment epithelium (RPE) can be estimated with autofluorescence (AF) imaging of lipofuscin, which accumulates as a byproduct of retinal exposure to light. Lipofuscin may be toxic to the RPE, and its toxicity may be enhanced by short-wavelength (SW) illumination. The high-intensity and SW excitation light used in conventional AF imaging could, at least in principle, increase the rate of lipofuscin accumulation and/or increase its toxicity. We considered two reduced-illuminance AF imaging (RAFI) methods as alternatives to conventional AF imaging. RAFI methods use either near-infrared (NIR) light or reduced-radiance SW illumination for excitation of fluorophores. We quantified the distribution of RAFI signals in relation to retinal structure and function in patients with the prototypical lipofuscin accumulation disease caused by mutations in ABCA4. There was evidence for two subclinical stages of macular ABCA4 disease involving hyperautofluorescence of both SW- and NIR-RAFI with and without associated loss of visual function. Use of RAFI methods and microperimetry in future clinical trials involving lipofuscinopathies should allow quantification of subclinical disease expression and progression without subjecting the diseased retina/RPE to undue light exposure.

  2. Prediction of the ischemic origin of functional mitral regurgitation in patients with systolic heart failure through posterior mitral leaflet angle

    Directory of Open Access Journals (Sweden)

    Fereshteh Ghaderi

    2018-01-01

    Full Text Available BACKGROUND: Differentiating ischemic from non-ischemic functional mitral regurgitation‎ (FMR in patients with cardiomyopathy is important in terms of the therapeutic decision-making and prognosis, but might be clinically challenging. In this study, the deformation of mitral valve (MV indices in the prediction of the etiology of FMR was assessed using 2D transthoracic and tissue Doppler echocardiography.METHODS: This case-control study was conducted from April 2015 to January 2016 in Imam Reza Hospital in Mashhad, Iran. The participants consisted of 40 patients with ischemic cardiomyopathy (ICM and 22 with non-ischemic dilated cardiomyopathy (DCM who referred to the heart failure clinic. Transthoracic echocardiography was performed using the conventional 2D and tissue Doppler imaging (TDI. MV tenting area (TA, coaptation distance (CD, anterior and posterior mitral leaflet angles (AMLA and PMLA, and regional systolic myocardial velocity (Sm were measured.RESULTS: There were no significant differences in echocardiographic indices between the two groups, besides Sm and PMLA which were significantly lower and higher, respectively, in ICM subjects in comparison with DCM patients (P = 0.002. PMLA ≥ 40 degrees and Sm ≤ 4 cm/second have a relatively high value for discriminating the ischemic from non-ischemic origin of functional MR in subjects with systolic heart failure (sensitivity: 80.0% and 70.0%, specificity: 73.0% and 77.3%; P = 0.001 and P < 0.001; respectively. Multivariable logistic regression identified PMLA and anterior Sm as major determinants for ischemic MR {Odds ratio (OR [95% confidence interval (CI] = 0.89 (0.82-0.96, P = 0.003, OR (95% CI = 0.29 (0.14-0.60, P = 0.001, respectively}.CONCLUSION: The present study showed that PMLA and Sm had an independent significant association with the mechanism of FMR. These findings are suggestive of the predictive role of mitral deformation echocardiographic indices in the determination of the

  3. A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans

    Science.gov (United States)

    Acuña-Alonzo, Víctor; Flores-Dorantes, Teresa; Kruit, Janine K.; Villarreal-Molina, Teresa; Arellano-Campos, Olimpia; Hünemeier, Tábita; Moreno-Estrada, Andrés; Ortiz-López, Ma Guadalupe; Villamil-Ramírez, Hugo; León-Mimila, Paola; Villalobos-Comparan, Marisela; Jacobo-Albavera, Leonor; Ramírez-Jiménez, Salvador; Sikora, Martin; Zhang, Lin-Hua; Pape, Terry D.; de Ángeles Granados-Silvestre, Ma; Montufar-Robles, Isela; Tito-Alvarez, Ana M.; Zurita-Salinas, Camilo; Bustos-Arriaga, José; Cedillo-Barrón, Leticia; Gómez-Trejo, Celta; Barquera-Lozano, Rodrigo; Vieira-Filho, Joao P.; Granados, Julio; Romero-Hidalgo, Sandra; Huertas-Vázquez, Adriana; González-Martín, Antonio; Gorostiza, Amaya; Bonatto, Sandro L.; Rodríguez-Cruz, Maricela; Wang, Li; Tusié-Luna, Teresa; Aguilar-Salinas, Carlos A.; Lisker, Ruben; Moises, Regina S.; Menjivar, Marta; Salzano, Francisco M.; Knowler, William C.; Bortolini, M. Cátira; Hayden, Michael R.; Baier, Leslie J.; Canizales-Quinteros, Samuel

    2010-01-01

    It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was associated with low high-density lipoprotein cholesterol (HDL-C) levels, obesity and type 2 diabetes in Mexican Mestizos. We performed a more extensive analysis of this variant in 4405 Native Americans and 863 individuals from other ethnic groups to investigate genetic evidence of positive selection, to assess its functional effect in vitro and to explore associations with HDL-C levels and other metabolic traits. The C230 allele was found in 29 of 36 Native American groups, but not in European, Asian or African individuals. C230 was observed on a single haplotype, and C230-bearing chromosomes showed longer relative haplotype extension compared with other haplotypes in the Americas. Additionally, single-nucleotide polymorphism data from the Human Genome Diversity Panel Native American populations were enriched in significant integrated haplotype score values in the region upstream of the ABCA1 gene. Cells expressing the C230 allele showed a 27% cholesterol efflux reduction (P< 0.001), confirming this variant has a functional effect in vitro. Moreover, the C230 allele was associated with lower HDL-C levels (P = 1.77 × 10−11) and with higher body mass index (P = 0.0001) in the combined analysis of Native American populations. This is the first report of a common functional variant exclusive to Native American and descent populations, which is a major determinant of HDL-C levels and may have contributed to the adaptive evolution of Native American populations. PMID:20418488

  4. Relationship between pattern of ischemic manifestation and hemodynamics in symptomatic M1 stenosis

    International Nuclear Information System (INIS)

    Tokumitsu, Naoki; Sako, Kazuhiro; Aizawa, Shizuka; Shirai, Wakako

    2002-01-01

    The mechanism through which ischemic manifestations develop in patients with middle cerebral artery (MCA) stenosis is still uncertain. It may cause ischemic symptoms through both embolic and hemodynamic mechanisms. In this study, we compared the findings from cerebral angiograms with single photon emission computed tomography (SPECT) in patients with M1 stenosis to determine the pathogenesis of ischema. At our hospital from 1994 to 2000, 14 patients (12 males and 2 females; mean age, 60.9; range, 31 to 85 years) with angiographically demonstrated symptomatic M1 stenosis were enrolled in this study. In 10, their stenotic lesion was located at the proximal site of the perforating arteries and for the other 4, stenosis was found at the distal site. Nine presented with transient ischemic attack (TIA) and 5 with completed stroke for an initial episode. The discrepancy in regional cerebral blood flow (rCBF) was evaluated in relation to the site and degree of stenosis, type of ischemic presentation, and frequency of ischemic events. There was no significant difference in CBF between the patients with stenosis involving the proximal site and those with distal stenosis; but the cortical CBF decreased significantly in those with severe stenosis compared with moderate stenosis. The cortical CBF of those who had a complete stroke is similar to that of the patients with TIA; but CBF of BGA decreased significantly in those with a complete stroke. The single ischemic event group showed a significant decrease in cortical CBF. On the other hand, the group with multiple ischemic events exhibited normal hemodynamics. We concluded that multiple ischemic events that occurred in M1 stenosis are caused by an embolic mechanism. (author)

  5. Predictive value of vertebral artery extracranial color-coded duplex sonography for ischemic stroke-related vertigo.

    Science.gov (United States)

    Liou, Li-Min; Lin, Hsiu-Fen; Huang, I-Fang; Chang, Yang-Pei; Lin, Ruey-Tay; Lai, Chiou-Lian

    2013-12-01

    Vertigo can be a major presentation of posterior circulation stroke and can be easily misdiagnosed because of its complicated presentation. We thus prospectively assessed the predictive value of vertebral artery extracranial color-coded duplex sonography (ECCS) for the prediction of ischemic stroke-related vertigo. The inclusion criteria were: (1) a sensation of whirling (vertigo); (2) intractable vertigo for more than 1 hour despite appropriate treatment; and (3) those who could complete cranial magnetic resonance imaging (MRI) and vertebral artery (V2 segment) ECCS studies. Eventually, 76 consecutive participants with vertigo were enrolled from Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan between August 2010 and August 2011. Demographic data, neurological symptoms, neurologic examinations, and V2 ECCS were assessed. We chose the parameters of peak systolic velocity (PSV), end diastolic velocity (EDV), PSV/EDV, mean velocity (MV), resistance index (RI), and pulsatility index (PI) to represent the hemodynamics. Values from both sides of V2 segments were averaged. We then calculated the average RI (aRI), average PI (aPI), average PSV (aPSV)/EDV, and average (aMV). Axial and coronal diffusion-weighted MRI findings determined the existence of acute ischemic stroke. We grouped and analyzed participants in two ways (way I and way II analyses) based on the diffusion-weighted MRI findings (to determine whether there was acute stroke) and neurological examinations. Using way I analysis, the "MRI (+)" group had significantly higher impedance (aRI, aPI, and aPSV/EDV ratio) and lower velocity (aPSV, aEDV, and aMV(PSV + EDV/2)), compared to the "MRI (-)" group. The cutoff value/sensitivity/specificity of aPSV, aEDV, aMV, aPI, aRI, and aPSV/EDV between the MRI (+) and MRI (-) groups were 41.15/61.5/66.0 (p = 0.0101), 14.55/69.2/72.0 (p = 0.0003), 29.10/92.1/38.0 (p = 0.0013), 1.07/76.9/64.0 (p = 0.0066), 0.62/76.9/64.0 (p = 0.0076), and 2.69/80.8/66.0 (p = 0

  6. The ABCA4 2588G>C Stargardt mutation: single origin and increasing frequency from South-West to North-East Europe.

    NARCIS (Netherlands)

    Maugeri, A.; Flothmann, K.; Hemmrich, N.; Ingvast, S.; Jorge, P.; Paloma, E.; Patel, R.; Rozet, J.M.; Tammur, J.; Testa, F.; Balcells, S.; Bird, A.C.; Brunner, H.G.; Hoyng, C.B.; Metspalu, A.; Simonelli, F.; Allikmets, R.; Bhattacharya, S.S.; Urso, M. D'; Gonzalez-Duarte, R.; Kaplan, J.; Meerman, G.J. te; Santos, R.L.; Schwartz, M.; Camp, G. van; Wadelius, C.; Weber, B.; Cremers, F.P.M.

    2002-01-01

    Inherited retinal dystrophies represent the most important cause of vision impairment in adolescence, affecting approximately 1 out of 3000 individuals. Mutations of the photoreceptor-specific gene ABCA4 (ABCR) are a common cause of retinal dystrophy. A number of mutations have been repeatedly

  7. The ABCA4 2588G > C Stargardt mutation : Single origin and increasing frequency from South-West to North-East Europe

    NARCIS (Netherlands)

    Maugeri, A; Flothmann, K; Hemmrich, N; Ingvast, S; Jorge, P; Paloma, E; Patel, R; Rozet, JM; Tammur, J; Testa, F; Balcells, S; Bird, AC; Brunner, HG; Hoyng, CB; Metspalu, A; Simonelli, F; Allikmets, R; Bhattacharya, SS; D'Urso, M; Gonzalez-Duarte, R; Kaplan, J; Meerman, GJT; Santoss, R; Schwartz, M; Van Camp, G; Wadelius, C; Weber, BHF; Cremers, FPM

    Inherited retinal dystrophies represent the most important cause of vision impairment in adolescence, affecting approximately 1 out of 3000 individuals. Mutations of the photoreceptor-specific gene ABCA4 (ABCR) are a common cause of retinal dystrophy. A number of mutations have been repeatedly

  8. FLAIR vascular hyperintensities predict early ischemic recurrence in TIA.

    Science.gov (United States)

    Nam, Ki-Woong; Kim, Chi Kyung; Kim, Tae Jung; Oh, Kyungmi; Han, Moon-Ku; Ko, Sang-Bae; Yoon, Byung-Woo

    2018-02-27

    To evaluate the relationship between fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) and early ischemic lesion recurrence (follow-up diffusion-weighted imaging [FU-DWI] [+]) in patients with lesion-negative TIA. We recruited consecutive patients with lesion-negative TIA within 24 hours of symptom onset, who underwent follow-up MRI during the acute period. FVH was defined as a focal or serpentine high signal intensity on FLAIR images. Other potential confounders were adjusted to evaluate the relationship between FVH and FU-DWI (+). Furthermore, to compare clinical outcomes between the FU-DWI (+) and FU-DWI (-) groups, we assessed 1-year recurrent ischemic stroke or TIA. Among 392 patients with lesion-negative TIA, 82 patients had FU-DWI (+) on the follow-up MRI. In the multivariate analysis, FVH remained an independent predictor of FU-DWI (+) (adjusted odds ratio [aOR] = 4.77, 95% confidence interval [CI] 2.45-9.29, p TIA. As FU-DWI (+) frequently occurs during the acute period and has a subsequent worse outcome after discharge, additional radiologic or clinical markers for it are necessary. © 2018 American Academy of Neurology.

  9. Comparison of classification methods for voxel-based prediction of acute ischemic stroke outcome following intra-arterial intervention

    Science.gov (United States)

    Winder, Anthony J.; Siemonsen, Susanne; Flottmann, Fabian; Fiehler, Jens; Forkert, Nils D.

    2017-03-01

    Voxel-based tissue outcome prediction in acute ischemic stroke patients is highly relevant for both clinical routine and research. Previous research has shown that features extracted from baseline multi-parametric MRI datasets have a high predictive value and can be used for the training of classifiers, which can generate tissue outcome predictions for both intravenous and conservative treatments. However, with the recent advent and popularization of intra-arterial thrombectomy treatment, novel research specifically addressing the utility of predictive classi- fiers for thrombectomy intervention is necessary for a holistic understanding of current stroke treatment options. The aim of this work was to develop three clinically viable tissue outcome prediction models using approximate nearest-neighbor, generalized linear model, and random decision forest approaches and to evaluate the accuracy of predicting tissue outcome after intra-arterial treatment. Therefore, the three machine learning models were trained, evaluated, and compared using datasets of 42 acute ischemic stroke patients treated with intra-arterial thrombectomy. Classifier training utilized eight voxel-based features extracted from baseline MRI datasets and five global features. Evaluation of classifier-based predictions was performed via comparison to the known tissue outcome, which was determined in follow-up imaging, using the Dice coefficient and leave-on-patient-out cross validation. The random decision forest prediction model led to the best tissue outcome predictions with a mean Dice coefficient of 0.37. The approximate nearest-neighbor and generalized linear model performed equally suboptimally with average Dice coefficients of 0.28 and 0.27 respectively, suggesting that both non-linearity and machine learning are desirable properties of a classifier well-suited to the intra-arterial tissue outcome prediction problem.

  10. [G894T (NOS3) and G1958A (MTHFD1) gene polymorphisms and risk of ischemic heart disease in Yucatan, Mexico].

    Science.gov (United States)

    García-González, Igrid; Solís-Cárdenas, Alberto de Jesús; Flores-Ocampo, Jorge A; Alejos-Mex, Ricardo; Herrera-Sánchez, Luis Fernando; González-Herrera, Lizbeth Josefina

    2015-01-01

    Cardiovascular medicine is focused on the search for genetic risk markers with predictive and/or prognostic value. Among the genetic variants of interest are G894T endothelial nitric oxide synthase and G1958A methylenetetrahydrofolate dehydrogenase1 gene polymorphisms. The aim of this study was to determine the possible association between these polymorphisms and ischemic heart disease in patients from Southern of Mexico (Yucatán). Case-control study matched by age, sex and origin was designed. We studied 98 patients with coronary disease and 101 controls. Participants were evaluated for the usual risk factors. The polymorphisms were identified using the polymerase chain reaction/restriction fragment length polymorphism analysis. Informed consent was obtained from all participants. The G894T and G1958A polymorphisms were not associated with ischemic heart disease, however, the TT genotype (G894T) was associated with the angina (OR=10.2; 95%CI, 1.51-68.8; p=0.025). The genotype GT (G894T) was the most frequent in patients with family history of coronary artery disease. Multiple logistic regression analysis identified smoking (OR=5.21; 95%CI, 2.1-12.9; p=0.000), hypertension (OR=3.54; 95%CI, 1.47-8.56; p=0.005) and obesity (OR=1.16; 95%CI, 1.1-1.27; p=0.001) as risk factors predicting the ischemic heart disease. The G894T and G1958A polymorphisms showed not association with ischemic heart disease. However, homozygosis for the 894T allele (NOS3) confers at risk to develop angina on Yucatán. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  11. Ginsenoside Rg1 improves ischemic brain injury by balancing ...

    African Journals Online (AJOL)

    Ginsenoside Rg1 improves ischemic brain injury by balancing mitochondrial ... and autophagy-related proteins were determined by reat time-polymerase chain ... Treatment with autophagy inhibitors decreased the mitochondrial protective ...

  12. Antiplatelet Treatment After Transient Ischemic Attack and Ischemic Stroke in Patients With Cerebral Microbleeds in 2 Large Cohorts and an Updated Systematic Review.

    Science.gov (United States)

    Lau, Kui Kai; Lovelock, Caroline E; Li, Linxin; Simoni, Michela; Gutnikov, Sergei; Küker, Wilhelm; Mak, Henry Ka Fung; Rothwell, Peter M

    2018-06-01

    In patients with transient ischemic attack/ischemic stroke, microbleed burden predicts intracerebral hemorrhage (ICH), and ischemic stroke, but implications for antiplatelet treatment are uncertain. Previous cohort studies have had insufficient follow-up to assess the time course of risks, have not stratified risks by antithrombotic use, and have not reported extracranial bleeds or functional outcome of ICH versus ischemic stroke. In 2 independent prospective cohorts with transient ischemic attack/ischemic stroke (Oxford Vascular Study/mainly white; University of Hong Kong/mainly Chinese), antiplatelet treatment was started routinely irrespective of microbleed burden. Risks, time course and outcome of ICH, extracranial bleeds, and recurrent ischemic events were determined and stratified by microbleed burden (0 versus 1, 2-4, and ≥5), adjusting for age, sex, and vascular risk factors. Microbleeds were more frequent in the Chinese cohort (450 of 1003 versus 165 of 1080; P <0.0001), but risk associations were similar during 7433 patient-years of follow-up. Among 1811 patients on antiplatelet drugs, risk of major extracranial bleeds was unrelated to microbleed burden ( P trend =0.87), but the 5-year risk of ICH was steeply related ( P trend <0.0001), with 11 of 15 (73%) of ICH in 140 of 1811 (7.7%) patients with ≥5 microbleeds. However, risk of ischemic stroke also increased with microbleed burden ( P trend =0.013), such that risk of ischemic stroke and coronary events exceeded ICH and major extracranial bleeds during the first year, even among patients with ≥5 microbleeds (11.6% versus 3.9%). However, this ratio changed over time, with risk of hemorrhage (11.2%) matching that of ischemic events (12.0%) after 1 year. Moreover, whereas the association between microbleed burden and risk of ischemic stroke was due mainly to nondisabling events ( P trend =0.007), the association with ICH was accounted for ( P trend <0.0001) by disabling/fatal events (≥5 microbleeds

  13. Occurrence and predictors of persistent impaired glucose tolerance after acute ischemic stroke or transient ischemic attack

    OpenAIRE

    Fonville, Susanne; Hertog, Heleen; Zandbergen, Adrienne; Koudstaal, Peter Jan; Lingsma, Hester

    2014-01-01

    textabstractBackground Impaired glucose tolerance is often present in patients with a transient ischemic attack (TIA) or ischemic stroke and doubles the risk of recurrent stroke. This impaired glucose tolerance can be transient, reflecting an acute stress response, or persistent, representing undiagnosed impaired glucose metabolism possibly requiring treatment. We aimed to assess the occurrence of persistent impaired glucose tolerance after a stroke or TIA and to develop a prediction model to...

  14. Single residue AAV capsid mutation improves transduction of photoreceptors in the Abca4-/- mouse and bipolar cells in the rd1 mouse and human retina ex vivo.

    Science.gov (United States)

    De Silva, Samantha R; Charbel Issa, Peter; Singh, Mandeep S; Lipinski, Daniel M; Barnea-Cramer, Alona O; Walker, Nathan J; Barnard, Alun R; Hankins, Mark W; MacLaren, Robert E

    2016-11-01

    Gene therapy using adeno-associated viral (AAV) vectors for the treatment of retinal degenerations has shown safety and efficacy in clinical trials. However, very high levels of vector expression may be necessary for the treatment of conditions such as Stargardt disease where a dual vector approach is potentially needed, or in optogenetic strategies for end-stage degeneration in order to achieve maximal light sensitivity. In this study, we assessed two vectors with single capsid mutations, rAAV2/2(Y444F) and rAAV2/8(Y733F) in their ability to transduce retina in the Abca4 -/- and rd1 mouse models of retinal degeneration. We noted significantly increased photoreceptor transduction using rAAV2/8(Y733F) in the Abca4 -/- mouse, in contrast to previous work where vectors tested in this model have shown low levels of photoreceptor transduction. Bipolar cell transduction was achieved following subretinal delivery of both vectors in the rd1 mouse, and via intravitreal delivery of rAAV2/2(Y444F). The successful use of rAAV2/8(Y733F) to target bipolar cells was further validated on human tissue using an ex vivo culture system of retinal explants. Capsid mutant AAV vectors transduce human retinal cells and may be particularly suited to treat retinal degenerations in which high levels of transgene expression are required.

  15. Prediction of Clinical Outcome After Acute Ischemic Stroke: The Value of Repeated Noncontrast Computed Tomography, Computed Tomographic Angiography, and Computed Tomographic Perfusion.

    Science.gov (United States)

    Dankbaar, Jan W; Horsch, Alexander D; van den Hoven, Andor F; Kappelle, L Jaap; van der Schaaf, Irene C; van Seeters, Tom; Velthuis, Birgitta K

    2017-09-01

    Early prediction of outcome in acute ischemic stroke is important for clinical management. This study aimed to compare the relationship between early follow-up multimodality computed tomographic (CT) imaging and clinical outcome at 90 days in a large multicenter stroke study. From the DUST study (Dutch Acute Stroke Study), patients were selected with (1) anterior circulation occlusion on CT angiography (CTA) and ischemic deficit on CT perfusion (CTP) on admission, and (2) day 3 follow-up noncontrast CT, CTP, and CTA. Follow-up infarct volume on noncontrast CT, poor recanalization on CTA, and poor reperfusion on CTP (mean transit time index ≤75%) were related to unfavorable outcome after 90 days defined as modified Rankin Scale 3 to 6. Four multivariable models were constructed: (1) only baseline variables (model 1), (2) model 1 with addition of infarct volume, (3) model 1 with addition of recanalization, and (4) model 1 with addition of reperfusion. Area under the curves of the receiver operating characteristic curves of the models were compared using the DeLong test. A total of 242 patients were included. Poor recanalization was found in 21%, poor reperfusion in 37%, and unfavorable outcome in 44%. The area under the curve of the receiver operating characteristic curve without follow-up imaging was 0.81, with follow-up noncontrast CT 0.85 ( P =0.02), CTA 0.86 ( P =0.01), and CTP 0.86 ( P =0.01). All 3 follow-up imaging modalities improved outcome prediction compared with no imaging. There was no difference between the imaging models. Follow-up imaging after 3 days improves outcome prediction compared with prediction based on baseline variables alone. CTA recanalization and CTP reperfusion do not outperform noncontrast CT at this time point. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00880113. © 2017 American Heart Association, Inc.

  16. Activation of liver X receptor decreases atherosclerosis in Ldlr⁻/⁻ mice in the absence of ATP-binding cassette transporters A1 and G1 in myeloid cells.

    Science.gov (United States)

    Kappus, Mojdeh S; Murphy, Andrew J; Abramowicz, Sandra; Ntonga, Vusisizwe; Welch, Carrie L; Tall, Alan R; Westerterp, Marit

    2014-02-01

    Liver X receptor (LXR) activators decrease atherosclerosis in mice. LXR activators (1) directly upregulate genes involved in reverse cholesterol transport and (2) exert anti-inflammatory effects mediated by transrepression of nuclear factor-κB target genes. We investigated whether myeloid cell deficiency of ATP-binding cassette transporters A1 and G1 (ABCA1/G1), principal targets of LXR that promote macrophage cholesterol efflux and initiate reverse cholesterol transport, would abolish the beneficial effects of LXR activation on atherosclerosis. LXR activator T0901317 substantially reduced inflammatory gene expression in macrophages lacking ABCA1/G1. Ldlr(-/-) mice were transplanted with Abca1(-/-)Abcg1(-/-) or wild-type bone marrow (BM) and fed a Western-type diet for 6 weeks with or without T0901317 supplementation. Abca1/g1 BM deficiency increased atherosclerotic lesion complexity and inflammatory cell infiltration into the adventitia and myocardium. T0901317 markedly decreased lesion area, complexity, and inflammatory cell infiltration in the Abca1(-/-)Abcg1(-/-) BM-transplanted mice. To investigate whether this was because of macrophage Abca1/g1 deficiency, Ldlr(-/-) mice were transplanted with LysmCreAbca1(fl/fl)Abcg1(fl/fl) or Abca1(fl/fl)Abcg1(fl/fl) BM and fed Western-type diet with or without the more specific LXR agonist GW3965 for 12 weeks. GW3965 decreased lesion size in both groups, and the decrease was more prominent in the LysmCreAbca1(fl/fl)Abcg1(fl/fl) group. The results suggest that anti-inflammatory effects of LXR activators are of key importance to their antiatherosclerotic effects in vivo independent of cholesterol efflux pathways mediated by macrophage ABCA1/G1. This has implications for the development of LXR activators that lack adverse effects on lipogenic genes while maintaining the ability to transrepress inflammatory genes.

  17. Ischemic preconditioning protects against ischemic brain injury

    Directory of Open Access Journals (Sweden)

    Xiao-meng Ma

    2016-01-01

    Full Text Available In this study, we hypothesized that an increase in integrin αv ß 3 and its co-activator vascular endothelial growth factor play important neuroprotective roles in ischemic injury. We performed ischemic preconditioning with bilateral common carotid artery occlusion for 5 minutes in C57BL/6J mice. This was followed by ischemic injury with bilateral common carotid artery occlusion for 30 minutes. The time interval between ischemic preconditioning and lethal ischemia was 48 hours. Histopathological analysis showed that ischemic preconditioning substantially diminished damage to neurons in the hippocampus 7 days after ischemia. Evans Blue dye assay showed that ischemic preconditioning reduced damage to the blood-brain barrier 24 hours after ischemia. This demonstrates the neuroprotective effect of ischemic preconditioning. Western blot assay revealed a significant reduction in protein levels of integrin αv ß 3, vascular endothelial growth factor and its receptor in mice given ischemic preconditioning compared with mice not given ischemic preconditioning 24 hours after ischemia. These findings suggest that the neuroprotective effect of ischemic preconditioning is associated with lower integrin αv ß 3 and vascular endothelial growth factor levels in the brain following ischemia.

  18. 7-ketocholesteryl-9-carboxynonanoate enhances ATP binding cassette transporter A1 expression mediated by PPARγ in THP-1 macrophages.

    Science.gov (United States)

    Chi, Yan; Wang, Le; Liu, Yuanyuan; Ma, Yanhua; Wang, Renjun; Han, Xiaofei; Qiao, Hui; Lin, Jiabin; Matsuura, Eiji; Liu, Shuqian; Liu, Qingping

    2014-06-01

    ATP binding cassette transporter A1 (ABCA1) is a member of the ATP-binding cassette transporter family. It plays an essential role in mediating the efflux of excess cholesterol. It is known that peroxisome proliferator-activated receptor gamma (PPARγ) promoted ABCA1 expression. We previously found 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) upregulated ABCA1 partially through CD36 mediated signals. In the present study, we intended to test if PPARγ signally is involved in the upregulation mediated by oxLig-1. First, we docked oxLig-1 and the ligand-binding domain (LBD) of PPARγ by using AutoDock 3.05 and subsequently confirmed the binding by ELISA assay. Western blotting analyses showed that oxLig-1 induces liver X receptor alpha (LXRα), PPARγ and consequently ABCA1 expression. Furthermore, oxLig-1 significantly enhanced ApoA-I-mediated cholesterol efflux. Pretreatment with an inhibitor for PPARγ (GW9662) or/and LXRα (GGPP) attenuated oxLig-1-induced ABCA1 expression. Under PPARγ knockdown by using PPARγ-shRNA, oxLig-1-induced ABCA1 expression and cholesterol efflux in THP-1 macrophages was blocked by 62% and 25% respectively. These observations suggest that oxLig-1 is a novel PPARγ agonist, promoting ApoA-I-mediated cholesterol efflux from THP-1 macrophages by increasing ABCA1 expression via induction of PPARγ. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Novel association of the R230C variant of the ABCA1 gene with high triglyceride levels and low high-density lipoprotein cholesterol levels in Mexican school-age children with high prevalence of obesity.

    Science.gov (United States)

    Gamboa-Meléndez, Marco Alberto; Galindo-Gómez, Carlos; Juárez-Martínez, Liliana; Gómez, F Enrique; Diaz-Diaz, Eulises; Ávila-Arcos, Marco Antonio; Ávila-Curiel, Abelardo

    2015-08-01

    Metabolic syndrome (MetS) is a disorder that includes a cluster of several risk factors for the development of type 2 diabetes and cardiovascular disease. The R230C variant of the ABCA1 gene has been associated with low HDL-cholesterol in several studies, but its association with MetS in children remains to be determined. The aim of this study was to analyze the association of the R230C variant with MetS and other metabolic traits in school-aged Mexican children. The study was performed in seven urban primary schools in the State of Mexico. Four hundred thirty-two Mexican school-age children 6-13 years old were recruited. MetS was identified using the International Diabetes Federation definition. The R230C variant of the ABCA1 gene was genotyped to seek associations with MetS and other metabolic traits. The prevalence of MetS was 29% in children aged 10-13 years. The R230C variant was not associated with MetS (OR = 1.65; p = 0.139). Furthermore, in the whole population, the R230C variant was associated with low HDL-cholesterol levels (β coefficient = -3.28, p <0.001). Interestingly, in the total population we found a novel association of this variant with high triglyceride levels (β coefficient = 14.34; p = 0.027). We found a new association of the R230C variant of the ABCA1 gene with high triglyceride levels. Our findings also replicate the association of this variant with low HDL-cholesterol levels in Mexican school-age children. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

  20. The value of preoperative 3-dimensional over 2-dimensional valve analysis in predicting recurrent ischemic mitral regurgitation after mitral annuloplasty

    NARCIS (Netherlands)

    Wijdh-den Hamer, Inez J.; Bouma, Wobbe; Lai, Eric K.; Levack, Melissa M.; Shang, Eric K.; Pouch, Alison M.; Eperjesi, Thomas J.; Plappert, Theodore J.; Yushkevich, Paul A.; Hung, Judy; Mariani, Massimo A.; Khabbaz, Kamal R.; Gleason, Thomas G.; Mahmood, Feroze; Acker, Michael A.; Woo, Y. Joseph; Cheung, Albert T.; Gillespie, Matthew J.; Jackson, Benjamin M.; Gorman, Joseph H.; Gorman, Robert C.

    Objectives: Repair for ischemic mitral regurgitation with undersized annuloplasty is characterized by high recurrence rates. We sought to determine the value of pre-repair 3-dimensional echocardiography over 2-dimensional echocardiography in predicting recurrence at 6 months. Methods: Intraoperative

  1. Ischemic perinatal brain damage. Neuropathologic and CT correlations

    Energy Technology Data Exchange (ETDEWEB)

    Crisi, G; Mauri, C; Canossi, G; Della Giustina, E

    1986-01-01

    The term ''hypoxic-ischemic encephalopathy'' covers a large part of neonatal neuropathology including the various forms of intracerebral haemorrhage. In the present work the term is confined to ischemic brain edema and actual infarction, be it diffuse or focal. Eighteen newborns with CT evidence of ischemic brain lesions and infarctual necrosis were selected. Emphasis is placed on current data on neuropathology of ischemic brain edema and its CT appearance. Particular entities such as periventricular leukomalacia and multicystic encephalopathy are discussed. Relationship between CT and temporal profile of cerebral damage is emphasized in order to predict the structural sequelae and the longterm prognosis. 31 refs.

  2. Early Dynamics of P-selectin and Interleukin 6 Predicts Outcomes in Ischemic Stroke

    DEFF Research Database (Denmark)

    Pusch, Gabriella; Debrabant, Birgit; Molnar, Tihamer

    2015-01-01

    with acute ischemic stroke (6, 24, and 72 hours after onset); (2) compared with 44 patients with asymptomatic severe (≥70%) carotid stenosis and 66 patients with Parkinson disease; and (3) we applied multiple regression methods, relating biological biomarkers combined with demographic data and comorbidities......BACKGROUND: Thromboinflammatory molecules connect the prothrombotic state, endothelial dysfunction, and systemic/local inflammation in the acute phase of ischemic stroke. METHODS: We prospectively investigated (1) serial changes in the levels of thromboinflammatory biomarkers in 76 patients...... hours were higher in patients with large-artery versus lacunar stroke. High concentration of IL-6, monocyte chemotactic protein 1, and S100B at 6 hours were associated with poststroke infections; high concentration of IL-6, S100B, and high-sensitivity C-reactive protein (hsCRP) correlated with death...

  3. Stargardt disease: towards developing a model to predict phenotype.

    Science.gov (United States)

    Heathfield, Laura; Lacerda, Miguel; Nossek, Christel; Roberts, Lisa; Ramesar, Rajkumar S

    2013-10-01

    Stargardt disease is an ABCA4-associated retinopathy, which generally follows an autosomal recessive inheritance pattern and is a frequent cause of macular degeneration in childhood. ABCA4 displays significant allelic heterogeneity whereby different mutations can cause retinal diseases with varying severity and age of onset. A genotype-phenotype model has been proposed linking ABCA4 mutations, purported ABCA4 functional protein activity and severity of disease, as measured by degree of visual loss and the age of onset. It has, however, been difficult to verify this model statistically in observational studies, as the number of individuals sharing any particular mutation combination is typically low. Seven founder mutations have been identified in a large number of Caucasian Afrikaner patients in South Africa, making it possible to test the genotype-phenotype model. A generalised linear model was developed to predict and assess the relative pathogenic contribution of the seven mutations to the age of onset of Stargardt disease. It is shown that the pathogenicity of an individual mutation can differ significantly depending on the genetic context in which it occurs. The results reported here may be used to identify suitable candidates for inclusion in clinical trials, as well as guide the genetic counselling of affected individuals and families.

  4. Unusual long survival despite severe lung disease of a child with biallelic loss of function mutations in ABCA-3

    Directory of Open Access Journals (Sweden)

    P. El Boustany

    Full Text Available Homozygous or compound heterozygous for frameshift or nonsense mutations in the ATP–binding cassette transporter A3 (ABCA3 is associated with neonatal respiratory failure and death within the first year of life without lung transplantation. We report the case of a newborn baby girl who developed severe respiratory distress soon after birth. She was diagnosed with compound heterozygous frameshift mutation of the ABCA3 gene. Despite extensive treatment (intravenous corticosteroids pulse therapy, oral corticosteroids, azithromycin, and hydroxychloroquine, she developed chronic respiratory failure. As the parents refused cardio-pulmonary transplantation and couldn't resolve to an accompaniment of end of life, a tracheostomy was performed resulting in continuous mechanical ventilation. A neurodevelopmental delay and an overall muscular dystrophy were noted. At the age of 5 years, after 2 episodes of pneumothorax, the patient died from severe respiratory failure. To our knowledge, this was the first case of a child with compound heterozygous frameshift mutation who posed such an ethical dilemma with a patient surviving till the age of five years. Keywords: ABCA3 deficiency, Compound heterozygous frameshift mutation, Neonatal respiratory failure, Tracheostomy, Mechanical ventilation, Ethical dilemma

  5. Will Lipidation of ApoA1 through Interaction with ABCA1 at the Intestinal Level Affect the Protective Functions of HDL?

    Directory of Open Access Journals (Sweden)

    Eric J. Niesor

    2015-01-01

    Full Text Available The relationship between levels of high-density lipoprotein cholesterol (HDL-C and cardiovascular (CV risk is well recognized; however, in recent years, large-scale phase III studies with HDL-C-raising or -mimicking agents have failed to demonstrate a clinical benefit on CV outcomes associated with raising HDL-C, casting doubt on the “HDL hypothesis.” This article reviews potential reasons for the observed negative findings with these pharmaceutical compounds, focusing on the paucity of translational models and relevant biomarkers related to HDL metabolism that may have confounded understanding of in vivo mechanisms. A unique function of HDL is its ability to interact with the ATP-binding cassette transporter (ABC A1 via apolipoprotein (Apo A1. Only recently, studies have shown that this process may be involved in the intestinal uptake of dietary sterols and antioxidants (vitamin E, lutein and zeaxanthin at the basolateral surface of enterocytes. This parameter should be assessed for HDL-raising drugs in addition to the more documented reverse cholesterol transport (RCT from peripheral tissues to the liver. Indeed, a single mechanism involving the same interaction between ApoA1 and ABCA1 may encompass two HDL functions previously considered as separate: antioxidant through the intestinal uptake of antioxidants and RCT through cholesterol efflux from loaded cells such as macrophages.

  6. Improved Outcome Prediction Using CT Angiography in Addition to Standard Ischemic Stroke Assessment: Results from the STOPStroke Study

    Science.gov (United States)

    González, R. Gilberto; Lev, Michael H.; Goldmacher, Gregory V.; Smith, Wade S.; Payabvash, Seyedmehdi; Harris, Gordon J.; Halpern, Elkan F.; Koroshetz, Walter J.; Camargo, Erica C. S.; Dillon, William P.; Furie, Karen L.

    2012-01-01

    Purpose To improve ischemic stroke outcome prediction using imaging information from a prospective cohort who received admission CT angiography (CTA). Methods In a prospectively designed study, 649 stroke patients diagnosed with acute ischemic stroke had admission NIH stroke scale scores, noncontrast CT (NCCT), CTA, and 6-month outcome assessed using the modified Rankin scale (mRS) scores. Poor outcome was defined as mRS>2. Strokes were classified as “major” by the (1) Alberta Stroke Program Early CT Score (ASPECTS+) if NCCT ASPECTS was≤7; (2) Boston Acute Stroke Imaging Scale (BASIS+) if they were ASPECTS+ or CTA showed occlusion of the distal internal carotid, proximal middle cerebral, or basilar arteries; and (3) NIHSS for scores>10. Results Of 649 patients, 253 (39.0%) had poor outcomes. NIHSS, BASIS, and age, but not ASPECTS, were independent predictors of outcome. BASIS and NIHSS had similar sensitivities, both superior to ASPECTS (p10/BASIS+ had poor outcomes, versus 21.5% (77/358) with NIHSS≤10/BASIS− (p10/BASIS+ compared to patients who are NIHSS≤10/BASIS−; the odds ratio is 5.4 (95% CI: 3.5 to 8.5) when compared to patients who are only NIHSS>10 or BASIS+. Conclusions BASIS and NIHSS are independent outcome predictors. Their combination is stronger than either instrument alone in predicting outcomes. The findings suggest that CTA is a significant clinical tool in routine acute stroke assessment. PMID:22276182

  7. Neuronal SIRT1 (Silent Information Regulator 2 Homologue 1) Regulates Glycolysis and Mediates Resveratrol-Induced Ischemic Tolerance.

    Science.gov (United States)

    Koronowski, Kevin B; Khoury, Nathalie; Saul, Isabel; Loris, Zachary B; Cohan, Charles H; Stradecki-Cohan, Holly M; Dave, Kunjan R; Young, Juan I; Perez-Pinzon, Miguel A

    2017-11-01

    Resveratrol, at least in part via SIRT1 (silent information regulator 2 homologue 1) activation, protects against cerebral ischemia when administered 2 days before injury. However, it remains unclear if SIRT1 activation must occur, and in which brain cell types, for the induction of neuroprotection. We hypothesized that neuronal SIRT1 is essential for resveratrol-induced ischemic tolerance and sought to characterize the metabolic pathways regulated by neuronal Sirt1 at the cellular level in the brain. We assessed infarct size and functional outcome after transient 60 minute middle cerebral artery occlusion in control and inducible, neuronal-specific SIRT1 knockout mice. Nontargeted primary metabolomics analysis identified putative SIRT1-regulated pathways in brain. Glycolytic function was evaluated in acute brain slices from adult mice and primary neuronal-enriched cultures under ischemic penumbra-like conditions. Resveratrol-induced neuroprotection from stroke was lost in neuronal Sirt1 knockout mice. Metabolomics analysis revealed alterations in glucose metabolism on deletion of neuronal Sirt1 , accompanied by transcriptional changes in glucose metabolism machinery. Furthermore, glycolytic ATP production was impaired in acute brain slices from neuronal Sirt1 knockout mice. Conversely, resveratrol increased glycolytic rate in a SIRT1-dependent manner and under ischemic penumbra-like conditions in vitro. Our data demonstrate that resveratrol requires neuronal SIRT1 to elicit ischemic tolerance and identify a novel role for SIRT1 in the regulation of glycolytic function in brain. Identification of robust neuroprotective mechanisms that underlie ischemia tolerance and the metabolic adaptations mediated by SIRT1 in brain are crucial for the translation of therapies in cerebral ischemia and other neurological disorders. © 2017 American Heart Association, Inc.

  8. [Relationship between Q192R polymorphisms in paraoxonase 1 gene and young ischemic stroke].

    Science.gov (United States)

    Liu, Jing-li; Li, Jin-pin; Wang, Xiao-ling; Yang, Yi

    2010-04-06

    To investigate the relationship between polymorphisms in paraoxonase1 (PON1) gene Gln192Arg (Q192R) and arterial ischemic stroke in young adults. The Q192R genotype was analyzed by polymerase chain reaction in 131 young adults with ischemic stroke and 135 age- and gender-matched controls. The plasma lipids were also determined in patients and controls respectively. Furthermore, carotid artery intima-media thickness (IMT) in patients were measured by carotid ultrasonography. The distributions of Q192R genotype frequency were significantly different between patients with ischemic stroke and control individuals. And the patients had more RR genotypes than control individuals (P stroke were 1.743 (95% confidence interval [CI], 1.032-2.943) in subjects with RR genotype. We also studied the relationship between the polymorphisms and the lipid concentration in patients and control individuals. However, no significant association was detected between Q/R192 genotype and any of lipid measurements. Further, the prevalence of cigarette smoking, hypertension and diabetes showed no significant difference between RR and non-RR genotypes in patients. Body mass index (BMI) in two groups did not differ significantly. But IMT of patients with RR genotype obviously increased in comparison to those without RR genotype (P ischemic stroke in young adults. RR genotype is a genetic risk for young adults with ischemic stroke through an increased carotid artery intima-media thickness and an accelerated atherosclerotic process.

  9. PR interval prolongation in coronary patients or risk equivalent: excess risk of ischemic stroke and vascular pathophysiological insights.

    Science.gov (United States)

    Chan, Yap-Hang; Hai, Jo Jo; Lau, Kui-Kai; Li, Sheung-Wai; Lau, Chu-Pak; Siu, Chung-Wah; Yiu, Kai-Hang; Tse, Hung-Fat

    2017-08-24

    Whether PR prolongation independently predicts new-onset ischemic events of myocardial infarction and stroke was unclear. Underlying pathophysiological mechanisms of PR prolongation leading to adverse cardiovascular events were poorly understood. We investigated the role of PR prolongation in pathophysiologically-related adverse cardiovascular events and underlying mechanisms. We prospectively investigated 597 high-risk cardiovascular outpatients (mean age 66 ± 11 yrs.; male 67%; coronary disease 55%, stroke 22%, diabetes 52%) for new-onset ischemic stroke, myocardial infarction (MI), congestive heart failure (CHF), and cardiovascular death. Vascular phenotype was determined by carotid intima-media thickness (IMT). PR prolongation >200 ms was present in 79 patients (13%) at baseline. PR prolongation >200 ms was associated with significantly higher mean carotid IMT (1.05 ± 0.37 mm vs 0.94 ± 0.28 mm, P = 0.010). After mean study period of 63 ± 11 months, increased PR interval significantly predicted new-onset ischemic stroke (P = 0.006), CHF (P = 0.040), cardiovascular death (P 200 ms. Using multivariable Cox regression, PR prolongation >200 ms independently predicted new-onset ischemic stroke (HR 8.6, 95% CI: 1.9-37.8, P = 0.005), cardiovascular death (HR 14.1, 95% CI: 3.8-51.4, P PR interval predicts new-onset MI at the exploratory cut-off >162 ms (C-statistic 0.70, P = 0.001; HR: 8.0, 95% CI: 1.65-38.85, P = 0.010). PR prolongation strongly predicts new-onset ischemic stroke, MI, cardiovascular death, and combined cardiovascular endpoint including CHF in coronary patients or risk equivalent. Adverse vascular function may implicate an intermediate pathophysiological phenotype or mediating mechanism.

  10. Changes in lactate dehydrogenase are associated with central gray matter lesions in newborns with hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Yum, Sook Kyung; Moon, Cheong-Jun; Youn, Young-Ah; Sung, In Kyung

    2017-05-01

    Biomarkers may predict neurological prognosis in infants with hypoxic-ischemic encephalopathy (HIE). We evaluated the relationship between serum lactate dehydrogenase (LDH) and brain magnetic resonance imaging (MRI), which predicts neurodevelopmental outcomes, in order to assess whether LDH levels are similarly predictive. Medical records were reviewed for infants with HIE and LDH levels were assessed on the first (LDH 1 ) and third (LDH 3 ) days following birth. Receiver operating characteristic curves were obtained in relation to central gray matter hypoxic-ischemic lesions. Of 92 patients, 52 (56.5%) had hypoxic-ischemic lesions on brain MRI, and 21 of these infants (40.4%) had central gray matter lesions. LDH 1 and LDH 3 did not differ; however, the percentage change (ΔLDH%) was significantly higher in infants with central gray matter lesions (36.9% versus 6.6%, p = 0.006). With cutoffs of 187 (IU/L, ΔLDH) and 19.4 (%, ΔLDH%), the sensitivity, specificity, positive predictive value and negative predictive value were 71.4, 69.0, 40.5 and 89.1%, respectively. The relative risk was 5.57 (p = 0.001). Changes in serum LDH may be a useful biomarker for predicting future neurodevelopmental prognosis in infants with HIE.

  11. Protection from ischemic heart injury by a vigilant heme oxygenase-1 plasmid system.

    Science.gov (United States)

    Tang, Yao Liang; Tang, Yi; Zhang, Y Clare; Qian, Keping; Shen, Leping; Phillips, M Ian

    2004-04-01

    Although human heme oxygenase-1 (hHO-1) could provide a useful approach for cellular protection in the ischemic heart, constitutive overexpression of hHO-1 may lead to unwanted side effects. To avoid this, we designed a hypoxia-regulated hHO-1 gene therapy system that can be switched on and off. This vigilant plasmid system is composed of myosin light chain-2v promoter and a gene switch that is based on an oxygen-dependent degradation domain from the hypoxia inducible factor-1-alpha. The vector can sense ischemia and switch on the hHO-1 gene system, specifically in the heart. In an in vivo experiment, the vigilant hHO-1 plasmid or saline was injected intramyocardially into myocardial infarction mice or sham operation mice. After gene transfer, expression of hHO-1 was only detected in the ischemic heart treated with vigilant hHO-1 plasmids. Masson trichrome staining showed significantly fewer fibrotic areas in vigilant hHO-1 plasmids-treated mice compared with saline control (43.0%+/-4.8% versus 62.5%+/-3.3%, PhHO-1 expression in peri-infarct border areas, concomitant with higher Bcl-2 levels and lower Bax, Bak, and caspase 3 levels in the ischemic myocardium compared with saline control. By use of a cardiac catheter, heart from vigilant hHO-1 plasmids-treated mice showed improved recovery of contractile and diastolic performance after myocardial infarction compared with saline control. This study documents the beneficial regulation and therapeutic potential of vigilant plasmid-mediated hHO-1 gene transfer. This novel gene transfer strategy can provide cardiac-specific protection from future repeated bouts of ischemic injury.

  12. C-reactive protein and homocysteine predict long-term mortality in young ischemic stroke patients.

    Science.gov (United States)

    Naess, Halvor; Nyland, Harald; Idicula, Titto; Waje-Andreassen, Ulrike

    2013-11-01

    We investigated the relationship between C-reactive protein (CRP) and homocysteine on follow-up and subsequent mortality in young ischemic stroke patients in a population-based study. Young ischemic stroke patients were followed-up on average 6 years after the index stroke. CRP and homocysteine levels were measured and risk factors were recorded, including myocardial infarction, diabetes mellitus, hypertension, smoking, alcoholism, and cancer. Stroke outcome was measured using the modified Rankin Scale score. Subsequent survival was obtained by examining the official population registry. Cox regression analyses were performed. In total, 198 patients were included in this study (82 [41%] women and 116 [59%] men). The mean age on follow-up was 47.8 years. In total, 36 (18.2%) patients died during the subsequent mean follow-up of 12.4 years. Cox regression analysis revealed that mortality was associated with CRP (hazard ratio [HR] 1.05; P=.001) and homocysteine levels (HR 1.04; P=.02) in patients without dissection. Kaplan-Meier curves grouped by dichotomized CRP (CRP≤1 v >1 mg/L) showed increasing separation between the survival curves, and likewise for dichotomized homocysteine (≤9 v >9 μg/L). There is an independent association between CRP and homocysteine levels obtained several years after ischemic stroke in young adults and subsequent mortality, even when adjusting for traditional risk factors. This association seems to continue for at least 12 years after the measurements. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  13. Arterial stiffness and functional outcome in acute ischemic stroke.

    Science.gov (United States)

    Lee, Yeong-Bae; Park, Joo-Hwan; Kim, Eunja; Kang, Chang-Ki; Park, Hyeon-Mi

    2014-03-01

    Arterial stiffness is a common change associated with aging and can be evaluated by measuring pulse wave velocity (PWV) between sites in the arterial tree, with the stiffer artery having the higher PWV. Arterial stiffness is associated with the risk of stroke in the general population and of fatal stroke in hypertensive patients. This study is to clarify whether PWV value predicts functional outcome of acute ischemic stroke. ONE HUNDRED PATIENTS WERE ENROLLED WITH A DIAGNOSIS OF ACUTE ISCHEMIC STROKE AND CATEGORIZED INTO TWO GROUPS: large-artery atherosclerosis (LAAS) or small vessel disease (SVD) subtype of Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Each group was divided into two sub-groups based on the functional outcome of acute ischemic stroke, indicated by modified Rankin Scale (mRS) at discharge. Poor functional outcome group was defined as a mRS ≥ 3 at discharge. Student's t-test or Mann-Whitney U-test were used to compare maximal brachial-ankle PWV (baPWV) values. Twenty-four patients whose state was inadequate to assess baPWV or mRS were excluded. There were 38 patients with good functional outcome (mRS vs. 1,789.80 ± 421.91, p = 0.022), while there was no significant difference of baPWV among patients with LAAS subtype (2,071.76 ± 618.42 vs. 1,878.00 ± 365.35, p = 0.579). Arterial stiffness indicated by baPWV is associated with the functional outcome of acute ischemic stroke. This finding suggests that measurement of baPWV predicts functional outcome in patients with stroke especially those whose TOAST classification was confirmed as SVD subtype.

  14. Dynamic changes in plasma tissue plasminogen activator, plasminogen activator inhibitor-1 and beta-thromboglobulin content in ischemic stroke.

    Science.gov (United States)

    Zhuang, Ping; Wo, Da; Xu, Zeng-Guang; Wei, Wei; Mao, Hui-ming

    2015-07-01

    The aim of this paper is to investigate the corresponding variations of plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) activities, and beta-thromboglobulin (β-TG) content in patients during different stages of ischemic stroke. Ischemic stroke is a common disease among aging people and its occurrence is associated with abnormalities in the fibrinolytic system and platelet function. However, few reports focus on the dynamic changes in the plasma fibrinolytic system and β-TG content in patients with ischemic stroke. Patients were divided into three groups: acute, convalescent and chronic. Plasma t-PA and PAI-1 activities were determined by chromogenic substrate analysis and plasma β-TG content was detected by radioimmunoassay. Patients in the acute stage of ischemic stroke had significantly increased levels of t-PA activity and β-TG content, but PAI-1 activity was significantly decreased. Negative correlations were found between plasma t-PA and PAI-1 activities and between plasma t-PA activity and β-TG content in patients with acute ischemic stroke. There were significant differences in plasma t-PA and PAI-1 activities in the aged control group, as well as in the acute, convalescent and chronic groups. It can be speculated that the increased activity of t-PA in patients during the acute stage was the result of compensatory function, and that the increase in plasma β-TG level not only implies the presence of ischemic stroke but is likely a cause of ischemic stroke. During the later stages of ischemic stroke, greater attention is required in monitoring levels of PAI-1. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Could infarct location predict the long-term functional outcome in childhood arterial ischemic stroke?

    Directory of Open Access Journals (Sweden)

    Mauricio López-Espejo

    Full Text Available ABSTRACT Objective: To explore the influence of infarct location on long-term functional outcome following a first-ever arterial ischemic stroke (AIS in non-neonate children. Method: The MRIs of 39 children with AIS (median age 5.38 years; 36% girls; mean follow-up time 5.87 years were prospectively evaluated. Infarct location was classified as the absence or presence of subcortical involvement. Functional outcome was measured using the modified Rankin scale (mRS for children after the follow-up assessment. We utilized multivariate logistic regression models to estimate the odds ratios (ORs for the outcome while adjusting for age, sex, infarct size and middle cerebral artery territory involvement (significance < 0.05. Results: Both infarcts ≥ 4% of total brain volume (OR 9.92; CI 1.76 – 55.9; p 0.009 and the presence of subcortical involvement (OR 8.36; CI 1.76 – 53.6; p 0.025 independently increased the risk of marked functional impairment (mRS 3 to 5. Conclusion: Infarct extension and location can help predict the extent of disability after childhood AIS.

  16. MicroRNA-20a/b regulates cholesterol efflux through post-transcriptional repression of ATP-binding cassette transporter A1.

    Science.gov (United States)

    Liang, Bin; Wang, Xin; Song, Xiaosu; Bai, Rui; Yang, Huiyu; Yang, Zhiming; Xiao, Chuanshi; Bian, Yunfei

    2017-09-01

    ATP-binding cassette transporter A1 (ABCA1) plays a crucial role in reverse cholesterol transport and exhibits anti-atherosclerosis effects. Some microRNAs (miRs) regulate ABCA1 expression, and recent studies have shown that miR-20a/b might play a critical role in atherosclerotic diseases. Here, we attempted to clarify the potential contribution of miR-20a/b in post-transcriptional regulation of ABCA1, cholesterol efflux, and atherosclerosis. We performed bioinformatics analysis and found that miR-20a/b was highly conserved and directly bound to ABCA1 mRNA with low binding free energy. Luciferase-reporter assay also confirmed that miR-20a/b significantly reduced luciferase activity associated with the ABCA1 3' untranslated region reporter construct. Additionally, miR-20a/b decreased ABCA1 expression, which, in turn, decreased cholesterol efflux and increased cholesterol content in THP-1 and RAW 264.7 macrophage-derived foam cells. In contrast, miR-20a/b inhibitors increased ABCA1 expression and cholesterol efflux, decreased cholesterol content, and inhibited foam-cell formation. Consistent with our in vitro results, miR-20a/b-treated ApoE -/- mice showed decreased ABCA1expression in the liver and reductions of reverse cholesterol transport in vivo. Furthermore, miR-20a/b regulated the formation of nascent high-density lipoprotein and promoted atherosclerotic development, whereas miR-20a/b knockdown attenuated atherosclerotic formation. miR-20 is a new miRNA capable of targeting ABCA1 and regulating ABCA1 expression. Therefore, miR-20 inhibition constitutes a new strategy for ABCA1-based treatment of atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Resting Heart Rate Predicts Depression and Cognition Early after Ischemic Stroke: A Pilot Study.

    Science.gov (United States)

    Tessier, Arnaud; Sibon, Igor; Poli, Mathilde; Audiffren, Michel; Allard, Michèle; Pfeuty, Micha

    2017-10-01

    Early detection of poststroke depression (PSD) and cognitive impairment (PSCI) remains challenging. It is well documented that the function of autonomic nervous system is associated with depression and cognition. However, their relationship has never been investigated in the early poststroke phase. This pilot study aimed at determining whether resting heart rate (HR) parameters measured in early poststroke phase (1) are associated with early-phase measures of depression and cognition and (2) could be used as new tools for early objective prediction of PSD or PSCI, which could be applicable to patients unable to answer usual questionnaires. Fifty-four patients with first-ever ischemic stroke, without cardiac arrhythmia, were assessed for resting HR and heart rate variability (HRV) within the first week after stroke and for depression and cognition during the first week and at 3 months after stroke. Multiple regression analyses controlled for age, gender, and stroke severity revealed that higher HR, lower HRV, and higher sympathovagal balance (low-frequency/high-frequency ratio of HRV) were associated with higher severity of depressive symptoms within the first week after stroke. Furthermore, higher sympathovagal balance in early phase predicted higher severity of depressive symptoms at the 3-month follow-up, whereas higher HR and lower HRV in early phase predicted lower global cognitive functioning at the 3-month follow-up. Resting HR measurements obtained in early poststroke phase could serve as an objective tool, applicable to patients unable to complete questionnaires, to help in the early prediction of PSD and PSCI. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  18. Defects in Stratum Corneum Desquamation Are the Predominant Effect of Impaired ABCA12 Function in a Novel Mouse Model of Harlequin Ichthyosis.

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    Full Text Available Harlequin Ichthyosis is a severe skin disease caused by mutations in the human gene encoding ABCA12. Here, we characterize a novel mutation in intron 29 of the mouse Abca12 gene that leads to the loss of a 5' splice donor site and truncation of the Abca12 RNA transcript. Homozygous mutants of this smooth skin or smsk allele die perinatally with shiny translucent skin, typical of animal models of Harlequin Ichthyosis. Characterization of smsk mutant skin showed that the delivery of glucosylceramides and CORNEODESMOSIN was defective, while ultrastructural analysis revealed abnormal lamellar bodies and the absence of lipid lamellae in smsk epidermis. Unexpectedly, mutant stratum corneum remained intact when subjected to harsh chemical dissociation procedures. Moreover, both KALLIKREIN 5 and -7 were drastically decreased, with retention of desmoplakin in mutant SC. In cultured wild type keratinocytes, both KALLIKREIN 5 and -7 colocalized with ceramide metabolites following calcium-induced differentiation. Reducing the intracellular levels of glucosylceramide with a glucosylceramide synthase inhibitor resulted in decreased secretion of KALLIKREIN proteases by wild type keratinocytes, but not by smsk mutant keratinocytes. Together, these findings suggest an essential role for ABCA12 in transferring not only lipids, which are required for the formation of multilamellar structures in the stratum corneum, but also proteolytic enzymes that are required for normal desquamation. Smsk mutant mice recapitulate many of the pathological features of HI and can be used to explore novel topical therapies against a potentially lethal and debilitating neonatal disease.

  19. National Institutes of Health Stroke Scale-Time Score Predicts Outcome after Endovascular Therapy in Acute Ischemic Stroke: A Retrospective Single-Center Study.

    Science.gov (United States)

    Todo, Kenichi; Sakai, Nobuyuki; Kono, Tomoyuki; Hoshi, Taku; Imamura, Hirotoshi; Adachi, Hidemitsu; Kohara, Nobuo

    2016-05-01

    Outcomes after successful endovascular therapy in acute ischemic stroke are associated with onset-to-reperfusion time (ORT) and the National Institutes of Health Stroke Scale (NIHSS) score. In intravenous recombinant tissue plasminogen activator therapy, the NIHSS-time score, calculated by multiplying onset-to-treatment time with the NIHSS score, has been shown to predict clinical outcomes. In this study, we assessed whether a similar combination of the ORT and the NIHSS score can be applied to predict the outcomes after endovascular therapy. We retrospectively reviewed the charts of 128 consecutive ischemic stroke patients with successful reperfusion after endovascular therapy. We analyzed the association of the ORT, the NIHSS score, and the NIHSS-time score with good outcome (modified Rankin Scale score ≤ 2 at 3 months). Good outcome rates for patients with NIHSS-time scores of 84.7 or lower, scores higher than 84.7 up to 127.5 or lower, and scores higher than 127.5 were 72.1%, 44.2%, and 14.3%, respectively (P < .01). Multivariate logistic regression analysis revealed that the NIHSS-time score was an independent predictor of good outcomes (odds ratio, .372; 95% confidence interval, .175-.789) after adjusting for age, sex, internal carotid artery occlusion, plasma glucose level, ORT, and NIHSS score. The NIHSS-time score can predict good clinical outcomes after endovascular treatment. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  20. Ischemic Tolerance of the Brain and Spinal Cord: A Review.

    Science.gov (United States)

    Yunoki, Masatoshi; Kanda, Takahiro; Suzuki, Kenta; Uneda, Atsuhito; Hirashita, Koji; Yoshino, Kimihiro

    2017-11-15

    Ischemic tolerance is an endogenous neuroprotective phenomenon induced by sublethal ischemia. Ischemic preconditioning (IPC), the first discovered form of ischemic tolerance, is widely seen in many species and in various organs including the brain and the spinal cord. Ischemic tolerance of the spinal cord is less familiar among neurosurgeons, although it has been reported from the viewpoint of preventing ischemic spinal cord injury during aortic surgery. It is important for neurosurgeons to have opportunities to see patients with spinal cord ischemia, and to understand ischemic tolerance of the spinal cord as well as the brain. IPC has a strong neuroprotective effect in animal models of ischemia; however, clinical application of IPC for ischemic brain and spinal diseases is difficult because they cannot be predicted. In addition, one drawback of preconditioning stimuli is that they are also capable of producing injury with only minor changes to their intensity or duration. Numerous methods to induce ischemic tolerance have been discovered that vary in their timing and the site at which short-term ischemia occurs. These methods include ischemic postconditioning (IPoC), remote ischemic preconditioning (RIPC), remote ischemic perconditioning (RIPerC) and remote ischemic postconditioning (RIPoC), which has had a great impact on clinical approaches to treatment of ischemic brain and spinal cord injury. Especially RIPerC and RIPoC to induce spinal cord tolerance are considered clinically useful, however the evidence supporting these methods is currently insufficient; further experimental or clinical research in this area is thus necessary.

  1. Prediction of hemorrhagic transformation in acute ischemic stroke using permeability surface of CT perfusion

    International Nuclear Information System (INIS)

    Xiong Bing; Chen Weijian; Fufengli

    2012-01-01

    Objective: To investigate the value of permeability surface (PS) in predicting hemorrhagic transformation (HT) in acute ischernic stroke (AIS) using CT perfusion (CTP). Methods: The study included 31 consecutive patients who presented symptoms suggestive of an AIS for 3-9 h. All patients underwent CT examination (noncontrast CT, CTP). HT was determined by follow-up CT images. According to presence of HT, the AIS was divided into HT group (PS HT , 11 patients) and non-HT group (PS No-HT , 20 patients). PS, cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) on both sides of brains were measured.The relative PS (rPS), relative CBF (rCBF), relative CBV (rCBV) and relative MTT(rMTT) were obtained by calculating the ratio of the values of bilateral regions. The rPS between PS HT and PS No-HT was compared with an exact Wilcoxon signed-rank test. The rCBF, rCBV, rMTT and the PS of the ischemic side between PS HT and PS No-HT were compared with independent-sample t test. Meanwhile, Spearman rank correlation analysis was conducted to analyze the relationship between the CTP parameters and HT. Results: The PS value of ischemic side was (1.61 ±0.77) ml · min -1 · 100 g -1 for the PS HT group,and the value was (0.91 ± 0.49) ml · min -1 · 100 g -1 for the PS No-HT group. For the PS HT group, rPS, rCBF, rCBV, rMTT were 2.76 ±0.78, 0.32 ±0.18, 0.66 ±0.31, 2.67 ±0.71, and for the PS No-HT group, rPS, rCBF, rCBV, rMTT were 1.35 ±0.19, 0.50±0.21, 0.91 ±0.28, 2.62 ± 1.31. Compared with PS No-HT ,PS HT had higher rPS and PS value,and there were significant statistical differences (U=0.000, t=3.070, P<0.01). But rCBF and rCBV values were lower in the PS HT group compared to the PS No-HT group, and there were significant statistical differences (t rCBF =2.343, t rCBV =2.210, P<0.05). There was no significant statistical difference in rMTT between the two groups (t=0.118, P>0.05). Significant positive correlations were detected between the r

  2. Stargardt disease: towards developing a model to predict phenotype

    OpenAIRE

    Heathfield, Laura; Lacerda, Miguel; Nossek, Christel; Roberts, Lisa; Ramesar, Rajkumar S

    2013-01-01

    Stargardt disease is an ABCA4-associated retinopathy, which generally follows an autosomal recessive inheritance pattern and is a frequent cause of macular degeneration in childhood. ABCA4 displays significant allelic heterogeneity whereby different mutations can cause retinal diseases with varying severity and age of onset. A genotype–phenotype model has been proposed linking ABCA4 mutations, purported ABCA4 functional protein activity and severity of disease, as measured by degree of visual...

  3. Exercise mediates the association between positive affect and 5-year mortality in patients with ischemic heart disease

    DEFF Research Database (Denmark)

    Hoogwegt, Madelein T; Versteeg, Henneke; Hansen, Tina B

    2013-01-01

    Background- Positive affect has been associated with better prognosis in patients with ischemic heart disease, but the underlying mechanisms remain unclear. We examined whether positive affect predicted time to first cardiac-related hospitalization and all-cause mortality, and whether exercise me...... between positive affect and mortality. Interventions aimed at increasing both positive affect and exercise may have better results with respect to patients' prognosis and psychological well-being than interventions focusing on 1 of these factors alone.......Background- Positive affect has been associated with better prognosis in patients with ischemic heart disease, but the underlying mechanisms remain unclear. We examined whether positive affect predicted time to first cardiac-related hospitalization and all-cause mortality, and whether exercise...... mediated this relationship in patients with established ischemic heart disease. Methods and Results- The sample comprised 607 patients with ischemic heart disease from Holbæk Hospital, Denmark. In 2005, patients completed the Global Mood Scale (GMS) to assess positive affect and a purpose-designed question...

  4. Population-based study of ABCD2 score, carotid stenosis, and atrial fibrillation for early stroke prediction after transient ischemic attack: the North Dublin TIA study.

    LENUS (Irish Health Repository)

    Sheehan, Orla C

    2010-05-01

    Transient ischemic attack (TIA) etiologic data and the ABCD(2) score may improve early stroke risk prediction, but studies are required in population-based cohorts. We investigated the external validity of the ABCD(2) score, carotid stenosis, and atrial fibrillation for prediction of early recurrent stroke after TIA.

  5. Prognostic Factors in Ischemic Arterial Stroke

    OpenAIRE

    J Gordon Millichap

    2001-01-01

    The predictive value of presenting symptoms, MRI and CT findings, and etiology in the outcome of ischemic arterial childhood stroke was determined in a consecutive series of 31 patients followed at the University Hospital, Rotterdam, The Netherlands.

  6. Late-onset Stargardt disease is associated with missense mutations that map outside known functional regions of ABCR (ABCA4).

    Science.gov (United States)

    Yatsenko, A N; Shroyer, N F; Lewis, R A; Lupski, J R

    2001-04-01

    Based on recent studies of the photoreceptor-specific ABC transporter gene ABCR (ABCA4) in Stargardt disease (STGD1) and other retinal dystrophies, we and others have developed a model in which the severity of retinal disease correlates inversely with residual ABCR activity. This model predicts that patients with late-onset STGDI may retain partial ABCR activity attributable to mild missense alleles. To test this hypothesis, we used late-onset STGDI patients (onset: > or =35 years) to provide an in vivo functional analysis of various combinations of mutant alleles. We sequenced directly the entire coding region of ABCR and detected mutations in 33/50 (66%) disease chromosomes, but surprisingly, 11/33 (33%) were truncating alleles. Importantly, all 22 missense mutations were located outside the known functional domains of ABCR (ATP-binding or transmembrane), whereas in our general cohort of STGDI subjects, alterations occurred with equal frequency across the entire protein. We suggest that these missense mutations in regions of unknown function are milder alleles and more susceptible to modifier effects. Thus, we have corroborated a prediction from the model of ABCR pathogenicity that (1) one mutant ABCR allele is always missense in late-onset STGD1 patients, and (2) the age-of-onset is correlated with the amount of ABCR activity of this allele. In addition, we report three new pseudodominant families that now comprise eight of 178 outbred STGD1 families and suggest a carrier frequency of STGD1-associated ABCR mutations of about 4.5% (approximately 1/22).

  7. Predicting ischemic mitral regurgitation in patients with acute ST-elevation myocardial infarction: Does time to reperfusion really matter and what is the role of collateral circulation?

    Science.gov (United States)

    Valuckiene, Zivile; Budrys, Povilas; Jurkevicius, Renaldas

    2016-01-15

    Ischemic mitral regurgitation (MR) is an adverse prognostic factor. We aimed to assess the role of time delay from symptom onset to reperfusion, and the impact of collateral circulation to incidence of MR in relation to established echocardiographic and clinical risk factors. Patients with STEMI presenting within 12 h from symptom onset and treated with primary percutaneous coronary intervention (PPCI) at Hospital of Lithuanian University of Health Sciences were enrolled. Echocardiography was performed after PPCI. Based on MR grade, patients were divided into no significant MR (NMR, grade 0-I MR, N = 102) and ischemic MR (IMR, grade ≥ 2 MR, N = 71) groups. Well-developed collaterals were defined as grade ≥ 2 by Rentrop classification. Continuous variables were compared by independent samples Student's T-test. Multivariate logistic regression analysis was used to identify independent predictors of ischemic MR. Time to reperfusion, MI localization, TIMI flow before/after PCI was similar between the groups. IMR group patients were elder, more often females and non-smokers, had lower body mass index, higher prevalence of multi-vessel coronary artery disease (CAD), better-developed collateral supply, greater left ventricular end-diastolic diameter index, left atrial index, pulmonary artery systolic pressure and lower ejection fraction. Multivariate logistic regression analysis revealed that ischemic MR is predicted by female gender, well-developed collateral supply, presence of multi-vessel CAD, and lower EF. In acute STEMI significant MR is unrelated to ischemic time and is predicted by female gender, lower EF, multi-vessel CAD and well-developed collateral supply to the infarct region.

  8. Phenotypic spectrum of autosomal recessive cone-rod dystrophies caused by mutations in the ABCA4 (ABCR) gene.

    NARCIS (Netherlands)

    Klevering, B.J.; Blankenagel, A.; Maugeri, A.; Cremers, F.P.M.; Hoyng, C.B.; Rohrschneider, K.

    2002-01-01

    PURPOSE: To describe the phenotype of 12 patients with autosomal recessive or isolated cone-rod types of progressive retinal degeneration (CRD) caused by mutations in the ABCA4 gene. METHODS: The charts of patients who had originally received a diagnosis of isolated or autosomal recessive CRD were

  9. Discovery of 3-n-butyl-2,3-dihydro-1H-isoindol-1-one as a potential anti-ischemic stroke agent

    Directory of Open Access Journals (Sweden)

    Lan Z

    2015-06-01

    Full Text Available Zujian Lan, Xiaoyu Xu, Wenkai Xu, Jin Li, Zengrong Liang, Xuefei Zhang, Ming Lei, Chunshun Zhao School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China Abstract: To develop novel anti-ischemic stroke agents with better therapeutic efficacy and bioavailability, we designed and synthesized a series of 3-alkyl-2,3-dihydro-1H-isoindol-1-ones compounds (3a–i derivatives, one of which (3d exhibited the strongest inhibitory activity for the adenosine diphosphate-induced and arachidonic acid-induced platelet aggregation. This activity is superior to that of 3-n-butylphthalide and comparable with aspirin and edaravone. Meanwhile, 3d not only exhibited a potent activity in scavenging free radicals and improving the survival of HT22 cells against the reactive oxygen species-mediated cytotoxicity in vitro but also significantly attenuated the ischemia/reperfusion-induced oxidative stress in ischemic rat brains. Results from transient middle cerebral artery occlusion and permanent middle cerebral artery occlusion model, indicated that 3d could significantly reduce infarct size, improve neurobehavioral deficits, and prominently decrease attenuation of cerebral damage. Most importantly, 3d possessed a very high absolute bioavailability and was rapidly distributed in brain tissue to keep high plasma drug concentration for the treatment of ischemic strokes. In conclusion, our findings suggest that 3-alkyl-2,3-dihydro-1H-isoindol-1-ones, a novel series of compounds, might be candidate drugs for the treatment of acute ischemic strokes, and 3d may be a promising therapeutic agent for the primary and secondary prevention of ischemic stroke. Keywords: stroke, platelet aggregation, ischemia/reperfusion, middle cerebral artery occlusion, 3-alkyl-2,3-dihydro-1H-isoindol-1-ones

  10. Apolipoprotein B levels, APOB alleles, and risk of ischemic cardiovascular disease in the general population, a review

    DEFF Research Database (Denmark)

    Benn, Marianne

    2009-01-01

    capturing the entire variation in APOB cannot be identified, and thus most polymorphisms must be evaluated separately in association studies; (3) APOB mutations and polymorphisms are associated with a range of apolipoprotein B and LDL cholesterol levels, although the magnitude of effect sizes of common...... for the E4154K polymorphism that possibly predicts a reduction in risk of ischemic cerebrovascular disease and ischemic stroke, common APOB polymorphisms with modest effect sizes on lipid levels do not predict risk of ischemic heart disease, myocardial infarction, ischemic cerebrovascular disease...

  11. Prediction of First Cardiovascular Disease Event in Type 1 Diabetes Mellitus: The Steno Type 1 Risk Engine.

    Science.gov (United States)

    Vistisen, Dorte; Andersen, Gregers Stig; Hansen, Christian Stevns; Hulman, Adam; Henriksen, Jan Erik; Bech-Nielsen, Henning; Jørgensen, Marit Eika

    2016-03-15

    Patients with type 1 diabetes mellitus are at increased risk of developing cardiovascular disease (CVD), but they are currently undertreated. There are no risk scores used on a regular basis in clinical practice for assessing the risk of CVD in type 1 diabetes mellitus. From 4306 clinically diagnosed adult patients with type 1 diabetes mellitus, we developed a prediction model for estimating the risk of first fatal or nonfatal CVD event (ischemic heart disease, ischemic stroke, heart failure, and peripheral artery disease). Detailed clinical data including lifestyle factors were linked to event data from validated national registers. The risk prediction model was developed by using a 2-stage approach. First, a nonparametric, data-driven approach was used to identify potentially informative risk factors and interactions (random forest and survival tree analysis). Second, based on results from the first step, Poisson regression analysis was used to derive the final model. The final CVD prediction model was externally validated in a different population of 2119 patients with type 1 diabetes mellitus. During a median follow-up of 6.8 years (interquartile range, 2.9-10.9) a total of 793 (18.4%) patients developed CVD. The final prediction model included age, sex, diabetes duration, systolic blood pressure, low-density lipoprotein cholesterol, hemoglobin A1c, albuminuria, glomerular filtration rate, smoking, and exercise. Discrimination was excellent for a 5-year CVD event with a C-statistic of 0.826 (95% confidence interval, 0.807-0.845) in the derivation data and a C-statistic of 0.803 (95% confidence interval, 0.767-0.839) in the validation data. The Hosmer-Lemeshow test showed good calibration (P>0.05) in both cohorts. This high-performing CVD risk model allows for the implementation of decision rules in a clinical setting. © 2016 American Heart Association, Inc.

  12. Contrast-enhanced T1 mapping-based extracellular volume fraction independently predicts clinical outcome in patients with non-ischemic dilated cardiomyopathy: a prospective cohort study

    Energy Technology Data Exchange (ETDEWEB)

    Youn, Jong-Chan [Hallym University College of Medicine, Division of Cardiology, Dongtan Sacred Heart Hospital, Hwaseong (Korea, Republic of); Yonsei University College of Medicine, Division of Cardiology, Severance Cardiovascular Hospital, Seoul (Korea, Republic of); Hong, Yoo Jin; Lee, Hye-Jeong; Han, Kyunghwa; Suh, Young Joo; Hur, Jin; Kim, Young Jin; Choi, Byoung Wook [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Seoul (Korea, Republic of); Shim, Chi Young; Hong, Geu-Ru; Kang, Seok-Min [Yonsei University College of Medicine, Division of Cardiology, Severance Cardiovascular Hospital, Seoul (Korea, Republic of)

    2017-09-15

    We aimed to evaluate the prognostic role of cardiac magnetic resonance imaging (CMR)-based extracellular volume fraction (ECV) in patients with non-ischemic dilated cardiomyopathy (NIDCM) and compare it with late gadolinium enhancement (LGE) parameters. This was a single-center, prospective, cohort study of 117 NIDCM patients (71 men, 51.9 ± 16.7 years) who underwent clinical 3.0-T CMR. Myocardial ECV and LGE were quantified on the left ventricular myocardium. The presence of midwall LGE was also detected. Nineteen healthy subjects served as controls. The primary end points were cardiovascular (CV) events defined by CV death, rehospitalization due to heart failure, and heart transplantation. During the follow-up period (median duration, 11.2 months; 25{sup th}-75{sup th} percentile, 7.8-21.9 months), the primary end points occurred in 19 patients (16.2%). The ECV (per 3% and 1% increase) was associated with a hazard ratio of 1.80 and 1.22 (95% confidence interval [CI], 1.48-2.20 and 1.14-1.30, respectively; p < 0.001) for the CV events. Multivariable analysis also indicated that ECV was an independent prognostic factor and had a higher prognostic value (Harrell's c statistic, 0.88) than LGE quantification values (0.77) or midwall LGE (0.80). CMR-based ECV independently predicts the clinical outcome in NIDCM patients. (orig.)

  13. Combination of five clinical data as prognostic factors of mortality after ischemic stroke

    Directory of Open Access Journals (Sweden)

    Rizaldy Taslim Pinzon

    2017-04-01

    Age, high random blood glucose level, complications, metabolic encephalopathy risk and the use of ventilators are associated with mortality after ischemic stroke. The predictive mortality score can be used to assess the prognosis of patients with ischemic stroke.

  14. Analysis of multi-factors affecting symptomatic intracranial hemorrhage in intraarterial thrombolysis with urokinase for acute ischemic stroke

    International Nuclear Information System (INIS)

    Qiao Qianlin; Zhou Shi; Wang Xuejian; Wu Qinghua; Song Jie

    2005-01-01

    Objective: To explore the causes and preventive measures of symptomatic intracranial hemorrhage in 217 patients with acute cerebral ischemic stroke treated with local intra-arterial urokinase. Methods: From February 1999 to June 2004, 217 patients were treated for acute ischemic stroke with local intra-arterial urokinase in our hospital. Factors associated with symptomatic intracranial hemorrhage of intra-arterial thrombolysis were analyzed by Stepwise logistic regression to identify some factors relating the prediction symptomatic intracranial hemorrhage. Results: Symptomatic intracranial hemorrhage occurred in 8 cases (3.7%). Predictors of the symptomatic intracranial hemorrhage were the elevated systolic blood pressure before therapy (odds ratio, 1.096; 95% CI, 1.006 to 1.194) and urokinase (UK) treatment (odds ratio, 1.068 ; 95% CL, 1.053 to 1.247). Risk of secondary symptomatic intracranial hemorrhage was increased with elevated systolic blood pressure. Other factors like age, initial treating time, NIHSS, diabetes and collateral circulation did not predict the symptomatic intracranial hemorrhage respectively. Conclusions: Predictors of symptomatic intracranial hemorrhage after local intra-arterial infusion of urokinase for acute ischemic stroke were the elevated systolic blood pressure before therapy and urokinase (UK) treatment. (authors)

  15. DRAGON score predicts functional outcomes in acute ischemic stroke patients receiving both intravenous tissue plasminogen activator and endovascular therapy.

    Science.gov (United States)

    Wang, Arthur; Pednekar, Noorie; Lehrer, Rachel; Todo, Akira; Sahni, Ramandeep; Marks, Stephen; Stiefel, Michael F

    2017-01-01

    The DRAGON score, which includes clinical and computed tomographic (CT) scan parameters, predicts functional outcomes in ischemic stroke patients treated with intravenous tissue plasminogen activator (IV tPA). We assessed the utility of the DRAGON score in predicting functional outcome in stroke patients receiving both IV tPA and endovascular therapy. A retrospective chart review of patients treated at our institution from February 2009 to October 2015 was conducted. All patients with computed tomography angiography (CTA) proven large vessel occlusions (LVO) who underwent intravenous thrombolysis and endovascular therapy were included. Baseline DRAGON scores and modified Rankin Score (mRS) at the time of hospital discharge was calculated. Good outcome was defined as mRS ≤3. Fifty-eight patients with LVO of the anterior circulation were studied. The mean DRAGON score of patients on admission was 5.3 (range, 3-8). All patients received IV tPA and endovascular therapy. Multivariate analysis demonstrated that DRAGON scores ≥7 was associated with higher mRS ( P DRAGON scores ≤6. Patients with DRAGON scores of 7 and 8 on admission had a mortality rate of 3.8% and 40%, respectively. The DRAGON score can help predict better functional outcomes in ischemic stroke patients receiving both IV tPA and endovascular therapy. This data supports the use of the DRAGON score in selecting patients who could potentially benefit from more invasive therapies such as endovascular treatment. Larger prospective studies are warranted to further validate these results.

  16. Genetic variation in ABC transporter A1 contributes to HDL cholesterol in the general population

    DEFF Research Database (Denmark)

    Frikke-Schmidt, Ruth; Nordestgaard, Børge G; Jensen, Gorm B

    2004-01-01

    Homozygosity for mutations in ABC transporter A1 (ABCA1) causes Tangier disease, a rare HDL-deficiency syndrome. Whether heterozygosity for genetic variation in ABCA1 also contributes to HDL cholesterol (HDL-C) levels in the general population is presently unclear. We determined whether mutations...... or single-nucleotide polymorphisms (SNPs) in ABCA1 were overrepresented in individuals with the lowest 1% (n=95) or highest 1% (n=95) HDL-C levels in the general population by screening the core promoter and coding region of ABCA1. For all nonsynonymous SNPs identified, we determined the effect of genotype...... on lipid traits in 9,259 individuals from the general population. Heterozygosity for ABCA1 mutations was identified in 10% of individuals with low HDL-C only. Three of 6 nonsynonymous SNPs (V771M, V825I, and R1587K) were associated with increases or decreases in HDL-C in women in the general population...

  17. Usefulness of cardiometabolic index for the estimation of ischemic stroke risk among general population in rural China.

    Science.gov (United States)

    Wang, Haoyu; Chen, Yintao; Guo, Xiaofan; Chang, Ye; Sun, Yingxian

    2017-11-01

    Cardiometabolic index (CMI) has been recognized as a novel and practical marker for the assessment of cardiometabolic risk as it is independently related to diabetes and atherosclerotic progression. This study tested the hypothesis that CMI represents a risk of ischemic stroke in a general population of rural China. From July 2012 to August 2013, we examined data from a large cross-sectional study of 11,345 participants (mean age 53.8 years; 60.8% females) who underwent biochemical determinations and anthropometric measurements in rural areas of northeast China. Ischemic stroke was documented as a history of cerebrovascular events and verified by medical record review. The prevalence of ischemic stroke was given to 3.1% of females and 3.2% of males. The cardio-metabolic profile was notably more adverse in ischemic stroke groups, irrespective of gender. A dose-response manner was detected for the prevalence of ischemic stroke, exhibiting a significant increase from the lowest to the highest quartiles of CMI (1.2% to 6.4% in females, P for trenddiscrimination power of CMI in predicting ischemic stroke was relatively higher for females (AUC: 0.685) than males (AUC: 0.573). The strong and independent association of CMI with ischemic stroke in females, in comparison with the much lesser degree in males, provides further insight to better stratify by sex in investigations of ischemic stroke and solidly corroborates the potential role of ischemic stroke prevention targeted at CMI.

  18. Genetic variation in WRN and ischemic stroke

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Frikke-Schmidt, Ruth; Nordestgaard, Børge G.

    2017-01-01

    trends for ischemic cerebrovascular disease (P = 0.06). In meta-analyses including 59,190 individuals in 5 studies, the hazard ratio for ischemic stroke for C1367R TT homozygotes versus CC/CT was 1.14 (1.04–1.25; P = 0.008). Conclusions This study suggests that common genetic variation in WRN......Background Werner syndrome, a premature genetic aging syndrome, shares many clinical features reminiscent of normal physiological aging, and ischemic vascular disease is a frequent cause of death. We tested the hypothesis that genetic variation in the WRN gene was associated with risk of ischemic...... vascular disease in the general population. Methods We included 58,284 participants from two general population cohorts, the Copenhagen City Heart Study (CCHS) and the Copenhagen General Population Study (CGPS). Of these, 6,312 developed ischemic vascular disease during follow-up. In the CCHS (n = 10...

  19. Variations of CHI3L1, levels of the encoded glycoprotein YKL-40 and prediction of fatal and non-fatal ischemic stroke

    DEFF Research Database (Denmark)

    Rathcke, Camilla Noelle; Thomsen, Stine Brinkloev; Linneberg, Allan

    2012-01-01

    BACKGROUND: Polymorphisms of CHI3L1 are associated with inter-individual YKL-40 levels and YKL-40 is associated with an increased mortality and is elevated in patients with cardiovascular disease. We investigated the association between single nucleotide polymorphisms (SNPs) of CHI3L1, serum YKL-40...... levels and all-cause and cardiovascular mortality and first-time incidence of myocardial infarction, ischemic heart disease (IHD) and stroke. METHODOLOGY/PRINCIPAL FINDINGS: 12 SNPs of CHI3L1 were genotyped and serum YKL-40 was measured in 2656 Danes representative of the general population. Median...

  20. Changes of resting cerebral activities in subacute ischemic stroke patients

    Directory of Open Access Journals (Sweden)

    Ping Wu

    2015-01-01

    Full Text Available This study aimed to detect the difference in resting cerebral activities between ischemic stroke patients and healthy participants, define the abnormal site, and provide new evidence for pathological mechanisms, clinical diagnosis, prognosis prediction and efficacy evaluation of ischemic stroke. At present, the majority of functional magnetic resonance imaging studies focus on the motor dysfunction and the acute stage of ischemic stroke. This study recruited 15 right-handed ischemic stroke patients at subacute stage (15 days to 11.5 weeks and 15 age-matched healthy participants. A resting-state functional magnetic resonance imaging scan was performed on each subject to detect cerebral activity. Regional homogeneity analysis was used to investigate the difference in cerebral activities between ischemic stroke patients and healthy participants. The results showed that the ischemic stroke patients had lower regional homogeneity in anterior cingulate and left cerebrum and higher regional homogeneity in cerebellum, left precuneus and left frontal lobe, compared with healthy participants. The experimental findings demonstrate that the areas in which regional homogeneity was different between ischemic stroke patients and healthy participants are in the cerebellum, left precuneus, left triangle inferior frontal gyrus, left inferior temporal gyrus and anterior cingulate. These locations, related to the motor, sensory and emotion areas, are likely potential targets for the neural regeneration of subacute ischemic stroke patients.

  1. Thrombophilia testing in young patients with ischemic stroke.

    Science.gov (United States)

    Pahus, Sidse Høst; Hansen, Anette Tarp; Hvas, Anne-Mette

    2016-01-01

    The possible significance of thrombophilia in ischemic stroke remains controversial. We aimed to study inherited and acquired thrombophilias as risk factors for ischemic stroke, transient ischemic attack (TIA) and amaurosis fugax in young patients. We included patients aged 18 to 50 years with ischemic stroke, TIA or amaurosis fugax referred to thrombophilia investigation at Aarhus University Hospital, Denmark from 1 January 2004 to 31 December 2012 (N=685). Clinical information was obtained from the Danish Stroke Registry and medical records. Thrombophilia investigation results were obtained from the laboratory information system. Absolute thrombophilia prevalences and associated odds ratios (OR) with 95% confidence intervals (95% CI) were reported for ischemic stroke (N=377) and TIA or amaurosis fugax (N=308). Thrombophilia prevalences for the general population were obtained from published data. No strong associations were found between thrombophilia and ischemic stroke, but patients with persistent presence of lupus anticoagulant (3%) had an OR at 2.66 (95% CI 0.84-9.15) for ischemic stroke. A significantly higher risk of TIA/amaurosis fugax was found for factor V Leiden heterozygote (12%) (OR: 1.99 (95% CI 1.14-3.28)). No other inherited or acquired thrombophilia was associated with ischemic stroke, TIA or amaurosis fugax. In young patients, thrombophilia did not infer an increased risk of ischemic stroke. Only factor V Leiden heterozygote patients had an increased risk of TIA/amaurosis fugax, and persistent presence of lupus anticoagulant was likely associated with ischemic stroke. We suggest the testing restricted to investigation of persistent presence of lupus anticoagulant. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. IMB2026791, a Xanthone, Stimulates Cholesterol Efflux by Increasing the Binding of Apolipoprotein A-I to ATP-Binding Cassette Transporter A1

    Directory of Open Access Journals (Sweden)

    Zijian Xie

    2012-03-01

    Full Text Available It is known that the ATP-binding cassette transporter A1 (ABCA1 plays a major role in cholesterol homeostasis and high density lipoprotein (HDL metabolism. Several laboratories have demonstrated that ABCA1 binding to lipid-poor apolipoprotein A-I (apoA-I will mediate the assembly of nascent HDL and cellular cholesterol efflux, which suggests a possible receptor-ligand interaction between ABCA1 and apoA-I. In this study, a cell-based-ELISA-like high-throughput screening (HTS method was developed to identify the synthetic and natural compounds that can regulate binding activity of ABCA1 to apoA-I. The cell-based-ELISA-like high-throughput screen was conducted in a 96-well format using Chinese hamster ovary (CHO cells stably transfected with ABCA1 pIRE2-EGFP (Enhanced Green Fluorecence Protein expression vector and the known ABCA1 inhibitor glibenclamide as the antagonist control. From 2,600 compounds, a xanthone compound (IMB 2026791 was selected using this HTS assay, and it was proved as an apoA-I binding agonist to ABCA1 by a flow cytometry assay and western blot analysis. The [3H] cholesterol efflux assay of IMB2026791 treated ABCA1-CHO cells and PMA induced THP-1 macrophages (human acute monocytic leukemia cell further confirmed the compound as an accelerator of cholesterol efflux in a dose-dependent manner with an EC50 of 25.23 μM.

  3. Spatio-Temporal Variation and Prediction of Ischemic Heart Disease Hospitalizations in Shenzhen, China

    Directory of Open Access Journals (Sweden)

    Yanxia Wang

    2014-05-01

    Full Text Available Ischemic heart disease (IHD is a leading cause of death worldwide. Urban public health and medical management in Shenzhen, an international city in the developing country of China, is challenged by an increasing burden of IHD. This study analyzed the spatio-temporal variation of IHD hospital admissions from 2003 to 2012 utilizing spatial statistics, spatial analysis, and space-time scan statistics. The spatial statistics and spatial analysis measured the incidence rate (hospital admissions per 1,000 residents and the standardized rate (the observed cases standardized by the expected cases of IHD at the district level to determine the spatio-temporal distribution and identify patterns of change. The space-time scan statistics was used to identify spatio-temporal clusters of IHD hospital admissions at the district level. The other objective of this study was to forecast the IHD hospital admissions over the next three years (2013–2015 to predict the IHD incidence rates and the varying burdens of IHD-related medical services among the districts in Shenzhen. The results show that the highest hospital admissions, incidence rates, and standardized rates of IHD are in Futian. From 2003 to 2012, the IHD hospital admissions exhibited similar mean centers and directional distributions, with a slight increase in admissions toward the north in accordance with the movement of the total population. The incidence rates of IHD exhibited a gradual increase from 2003 to 2012 for all districts in Shenzhen, which may be the result of the rapid development of the economy and the increasing traffic pollution. In addition, some neighboring areas exhibited similar temporal change patterns, which were also detected by the spatio-temporal cluster analysis. Futian and Dapeng would have the highest and the lowest hospital admissions, respectively, although these districts have the highest incidence rates among all of the districts from 2013 to 2015 based on the prediction

  4. Advances of 11C-flumazenil receptor imaging in ischemic penumbra

    International Nuclear Information System (INIS)

    Zhang Jun

    2004-01-01

    The ischemic penumbra is the target of therapy for ischemic stroke patients, so it is extremely important to investigate an imaging technique that may identify accurately the viability of cerebral tissues early. The neuroreceptor imaging with positron emission tomography has achieved some successes in this study field, in particular, the 11 C-flumazenil receptor imaging, which can not only differentiate between the neurons of functional impairment and those of morphological destruction, and then distinguish the ischemic penumbra from the irreversible damage tissues, but predict the malignant course of cerebral infarction. Consequently, these will help to select the patients benefiting from the intervention therapy and plan effectively the therapeutic strategies. (authors)

  5. Thrombolysis with Intravenous Tissue Plasminogen Activator (rt-PA) Predicts Favorable Discharge Disposition in Patients with Acute Ischemic Stroke

    Science.gov (United States)

    Ifejika-Jones, Nneka L.; Harun, Nusrat; Mohammed-Rajput, Nareesa A.; Noser, Elizabeth A.; Grotta, James C.

    2011-01-01

    Background and Purpose Acute ischemic stroke patients receiving IV tissue plasminogen activator (rt-PA) within 3 hours of symptom onset are 30% more likely to have minimal disability at three months. During hospitalization, short-term disability is subjectively measured by discharge disposition, whether to home, Inpatient Rehabilitation (IR), Skilled Nursing Facility (SNF) or Subacute Care (Sub). There are no studies assessing the role of rt-PA use as a predictor of post-stroke disposition. Methods Retrospective analysis of all ischemic stroke patients admitted to the University of Texas Houston Medical School (UTHMS) Stroke Service between Jan 2004 and Oct 2009. Baseline demographics and National Institute of Health Stroke Scale (NIHSS) score were collected. Cerebrovascular disease risk factors were used for risk stratification. Results Home vs. IR, SNF, Sub Of 2225 acute ischemic stroke patients, 1019 were discharged home, 1206 to another level of care. Patients who received rt-PA therapy were 1.9 times more likely to be discharged home (P = stroke patients, 719 patients were discharged to acute IR, 371 were discharged to SNF, 116 to Sub. There were no differences in disposition between patients who received rt-PA therapy. Conclusions Stroke patients who receive IV rt-PA for acute ischemic stroke are more 1.9 times more likely to be discharged directly home after hospitalization. This study is limited by its retrospective nature and the undetermined role of psychosocial factors related to discharge. PMID:21293014

  6. Electroencephalogram and magnetic resonance imaging comparison as a predicting factor for neurodevelopmental outcome in hypoxic ischemic encephalopathy infant treated with hypothermia

    Directory of Open Access Journals (Sweden)

    Francesca Del Balzo

    2014-10-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE is an important cause of acute neurological damage in newborns at (or near term. Several trials in recent years have shown that moderate hypothermia by total body cooling or selective head is an effective intervention to reduce mortality and major disability in infants survived a perinatal hypoxic-ischemic attack. Follow-up in these patients is very important to establish neurodevelopmental outcome, and specific markers can lead us to detect predicting sign for good or poor outcome. We reported a few cases of newborn with HIE treated with hypothermia, in whom the comparison between electroencephalogram (EEG and magnetic resonance imaging (MRI represents the first marker for neurodevelopment outcome prediction. The continuous EEG monitoring showed a depressed EEG activity with diffuse burst depression in 7 patients. No epileptic abnormalities were registered. In 10 out of 20 patients no abnormalities of the background activity and no epileptic abnormalities were observed. We found that a depressed EEG activity during the first 72 h of life and a diffused alteration of basal ganglia at MRI were correlated with a poor neurodevelopmental outcome at 18 months of follow-up.

  7. Renal impairment in stroke patients: A comparison between the haemorrhagic and ischemic variants [version 1; referees: 2 approved, 1 not approved

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    Pratyush Shrestha

    2017-08-01

    Full Text Available Background: Renal impairment is regularly seen in hospitalized stroke patients, affecting the outcome of patients, as well as causing difficulties in their management. A prospective cohort study was conducted to assess the trend of renal function in hospitalized ischemic and haemorrhagic stroke patients. The incidence of renal impairment in these subgroups, the contributing factors and the need for renal replacement in renal impaired patients was evaluated. Methods: Alternate day renal function testing was performed in hospitalized stroke patients. Estimated glomerular filtration rate (e-GFR was calculated and the trend of renal function in the two stroke subgroups (haemorrhagic and ischemic was assessed, with renal impairment defined as e-GFR < 60mL/ minute per 1.73m2. Results: Among 52 patients, 25 had haemorrhagic stroke (mean age 59.81 ± 14.67 and 27 had ischemic stroke (mean age 56.12 ± 13.08. The mean e-GFR (mL/minute per 1.732m2 at admission in the haemorrhagic stroke subgroup was 64.79 ± 25.85 compared to 86.04 ± 26.09 in the ischemic stroke subgroup (p=0.005. Sixteen out of 25 (64% patients in the haemorrhagic stroke subgroup and 9 out of 27 (33.3% patients in the ischemic subgroup developed renal impairment (p=0.27. The location of the bleed (p=0.8, volume of hematoma (p=0.966 and surgical intervention (p=0.4 did not predispose the patients to renal impairment. One out of 16 patients with haemorrhagic stroke (who eventually died, and 2 out of 9 patients with ischemic stroke required renal replacement. Conclusion: Renal impairment is commonly seen in stroke patients, more so in patients who suffered haemorrhagic strokes.  The impairment, however, is transient and rarely requires renal replacement therapy.

  8. Discovery of molecular mechanism of a clinical herbal formula upregulating serum HDL-c levels in treatment of metabolic syndrome by in vivo and computational studies.

    Science.gov (United States)

    Chen, Meimei; Yang, Fafu; Kang, Jie; Gan, Huijuan; Lai, Xinmei; Gao, Yuxing

    2018-01-15

    Decreased HDL cholesterol (HDL-c) is considered as an independent risk factor of cardiovascular disease in metabolic syndrome (Mets). Wendan decoction (WDD), a famous clinical traditional Chinese medicine formula in Mets in China, which can obviously up-regulate serum HDL-c levels in Mets. However, till now, the molecular mechanism of up-regulation still remained unclear. In this study, an integrated approach that combined serum ABCA1 in vivo assay, QSAR modeling and molecular docking was developed to explore the molecular mechanism and chemical substance basis of WDD upregulating HDL-c levels. Compared with Mets model group, serum ABCA1 and HDL-c levels intervened by two different doses of WDD for two weeks were significantly up-regulated. Then, kohonen and LDA were applied to develop QSAR models for ABCA1 up-regulators based flavonoids. The derived QSAR model produced the overall accuracy of 100%, a very powerful tool for screening ABCA1 up-regulators. The QSAR model prediction revealed 67 flavonoids in WDD were ABCA1 up-regulators. Finally, they were subjected to the molecular docking to understand their roles in up-regulating ABCA1 expression, which led to discovery of 23 ABCA1 up-regulators targeting LXR beta. Overall, QSAR modeling and docking studies well accounted for the observed in vivo activities of ABCA1 affected by WDD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Prdx6 Upregulation by Curcumin Attenuates Ischemic Oxidative Damage via SP1 in Rats after Stroke

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    Gongwei Jia

    2017-01-01

    Full Text Available Background. The role of Peroxiredoxin 6 (Prdx6 in brain ischemia remains unclear. Curcumin (Cur treatment elicits neuroprotective effects against cerebral ischemic injury, and the associated mechanisms may involve Prdx6. In this study, we investigated whether Prdx6 and the transcription factor specific protein 1 (SP1 were involved in the antioxidant effect of Cur after stoke. Methods. Focal cerebral ischemic injury was induced by transient middle cerebral artery occlusion for 2 hours in male Sprague-Dawley rats treated with or without Prdx6 siRNA. Expression of Prdx6 in the penumbra was assessed by Real-Time PCR (RT-PCR, Western blot analysis, and immunoflourescent staining. In addition, infarct volume, neurological deficit score, and oxidative stress were evaluated. Prdx6 levels were also determined in the presence and absence of SP1 antagonist mithramycin A (MTM-A. Results. Cur treatment upregulated Prdx6 protein expression and the number of Prdx6-positive neuronal cells 24 hours after reperfusion. Cur treatment also attenuated oxidative stress and induced neuroprotective effects against ischemic damage, whereas the beneficial effects of Cur treatment were lost in animals treated with Prdx6-siRNA. Prdx6 upregulation by Cur treatment was abolished by SP1 antagonists MTM. Conclusions. Prdx6 upregulation by Cur treatment attenuates ischemic oxidative damage through SP1 induction in rats after stroke. This represents a novel mechanism of Cur-induced neuroprotection against cerebral ischemia.

  10. The predictive value of thyroid hormone levels on the neurological outcomes of patients with acute ischemic stroke

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    Guo-dong CHEN

    2015-03-01

    Full Text Available Objective To explore the correlation between thyroid hormone levels in patients with acute ischemic stroke and the severity of disease and short-term prognosis. Methods According to the level of serum total triiodothyronine (TT3, 98 patients who presented first acute ischemic stroke and without history of thyroid abnormality were divided into low TT3 group and normal TT3 group. Thyroid hormone levels and neurological function defect of those patients were tested, and their neural functional recovery after 3 months was evaluated.  Results Low TT3 group had more severe neural function defect compared to normal TT3 group (χ2 = 58.134, P = 0.000. There were no significant differences on total thyroxine (TT4; t = 1.636, P = 0.105 and thyroid stimulating hormone (TSH; t = 1.059, P = 0.292 between 2 groups. There was a significantly negative correlation between TT3 levels and National Insititute of Health Stroke Scale (NIHSS score on admission (r = -0.672, P = 0.000. Patients with low TT3 showed a significantly smaller percentage of neurological function improvement on both NIHSS ( χ2 = 8.993, P = 0.003 and modified Rankin Scale (mRS; χ2 = 6.247, P = 0.012 scores compared to those with normal TT3 at 90 d after onset.  Conclusions Low T3 level is associated with the severity of acute ischemic stroke and neural functional recovery, suggesting serum T3 level may be a predictor of neural function improvement in patients with acute ischemic stroke. DOI: 10.3969/j.issn.1672-6731.2015.02.009

  11. Neuroprotective effects of ginsenoside Rg1-induced neural stem cell transplantation on hypoxic-ischemic encephalopathy

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    Ying-bo Li

    2015-01-01

    Full Text Available Ginsenoside Rg1 is the major pharmacologically active component of ginseng, and is reported to have various therapeutic actions. To determine whether it induces the differentiation of neural stem cells, and whether neural stem cell transplantation after induction has therapeutic effects on hypoxic-ischemic encephalopathy, we cultured neural stem cells in 10-80 µM ginsenoside Rg1. Immunohistochemistry revealed that of the concentrations tested, 20 mM ginsenoside Rg1 had the greatest differentiation-inducing effect and was the concentration used for subsequent experiments. Whole-cell patch clamp showed that neural stem cells induced by 20 µM ginsenoside Rg1 were more mature than non-induced cells. We then established neonatal rat models of hypoxic-ischemic encephalopathy using the suture method, and ginsenoside Rg1-induced neural stem cells were transplanted via intracerebroventricular injection. These tests confirmed that neural stem cells induced by ginsenoside had fewer pathological lesions and had a significantly better behavioral capacity than model rats that received saline. Transplanted neural stem cells expressed neuron-specific enolase, and were mainly distributed in the hippocampus and cerebral cortex. The present data suggest that ginsenoside Rg1-induced neural stem cells can promote the partial recovery of complicated brain functions in models of hypoxic-ischemic encephalopathy.

  12. Low density lipoprotein receptor-related protein 1 expression correlates with cholesteryl ester accumulation in the myocardium of ischemic cardiomyopathy patients

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    Cal Roi

    2012-08-01

    Full Text Available Abstract Our hypothesis was that overexpression of certain lipoprotein receptors might be related to lipid accumulation in the human ischemic myocardium. Intramyocardial lipid overload contributes to contractile dysfunction and arrhythmias in cardiomyopathy. Thus, the purpose of this study was to assess the effect of hypercholesterolemic LDL and hypertrigliceridemic VLDL dose on LRP1 expression in cardiomyocytes, as well as the potential correlation between LRP1 expression and neutral lipid accumulation in the left ventricle tissue from ischemic cardiomyopathy patients. Cell culture experiments include control and LRP1-deficient cardiomyocytes exposed to lipoproteins under normoxic and hypoxic conditions. Explanted hearts from 18 ICM patients and eight non-diseased hearts (CNT were included. Low density lipoprotein receptor-related protein 1 (LRP1, very low density lipoprotein receptor (VLDLR and low density lipoprotein receptor (LDLR expression was analyzed by real time PCR and Western blotting. Cholesteryl ester (CE, triglyceride (TG and free cholesterol (FC content was assess by thin layer chromatography following lipid extraction. Western blotting experiments showed that protein levels of LRP1, VLDLR and HIF-1α were significantly upregulated in ischemic hearts. Immunohistochemistry and confocal microscopy analysis showed that LRP1 and HIF-1α were upregulated in cardiomyocytes of ICM patients. In vitro studies showed that VLDL, LDL and hypoxia exerted an upregulatory effect on LRP1 expression and that LRP1 played a major role in cholesteryl ester accumulation from lipoproteins in cardiomyocytes. Myocardial CE accumulation strongly correlated with LRP1 levels in ischemic hearts. Taken together, our results suggest that LRP1 upregulation is key for myocardial cholesterol ester accumulation in ischemic human hearts and that LRP1 may be a target to prevent the deleterious effects of myocardial cholesterol accumulation in ischemic cardiomyopathy.

  13. Transcranial Doppler ultrasonography predicts cardiovascular events after TIA

    International Nuclear Information System (INIS)

    Holzer, Katrin; Sadikovic, Suwad; Esposito, Lorena; Bockelbrink, Angelina; Sander, Dirk; Hemmer, Bernhard; Poppert, Holger

    2009-01-01

    Transient ischemic attack (TIA) patients are at high vascular risk. We assessed the value of extracranial (ECD) and transcranial (TCD) Doppler and duplex ultrasonography to predict clinical outcome after TIA. 176 consecutive TIA patients admitted to the Stroke Unit were recruited in the study. All patients received diffusion-weighted imaging, standardized ECD and TCD. At a median follow-up of 27 months, new vascular events were recorded. 22 (13.8%) patients experienced an ischemic stroke or TIA, 5 (3.1%) a myocardial infarction or acute coronary syndrome, and 5 (3.1%) underwent arterial revascularization. ECD revealed extracranial ≥ 50% stenosis or occlusions in 34 (19.3%) patients, TCD showed intracranial stenosis in 15 (9.2%) and collateral flow patterns due to extracranial stenosis in 5 (3.1%) cases. Multivariate analysis identified these abnormal ECD and TCD findings as predictors of new cerebral ischemic events (ECD: hazard ratio (HR) 4.30, 95% confidence interval (CI) 1.75 to 10.57, P = 0.01; TCD: HR 4.73, 95% CI 1.86 to 12.04, P = 0.01). Abnormal TCD findings were also predictive of cardiovascular ischemic events (HR 18.51, 95% CI 3.49 to 98.24, P = 0.001). TIA patients with abnormal TCD findings are at high risk to develop further cerebral and cardiovascular ischemic events

  14. A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration.

    Science.gov (United States)

    Rivera, A; White, K; Stöhr, H; Steiner, K; Hemmrich, N; Grimm, T; Jurklies, B; Lorenz, B; Scholl, H P; Apfelstedt-Sylla, E; Weber, B H

    2000-10-01

    Stargardt disease (STGD) is a common autosomal recessive maculopathy of early and young-adult onset and is caused by alterations in the gene encoding the photoreceptor-specific ATP-binding cassette (ABC) transporter (ABCA4). We have studied 144 patients with STGD and 220 unaffected individuals ascertained from the German population, to complete a comprehensive, population-specific survey of the sequence variation in the ABCA4 gene. In addition, we have assessed the proposed role for ABCA4 in age-related macular degeneration (AMD), a common cause of late-onset blindness, by studying 200 affected individuals with late-stage disease. Using a screening strategy based primarily on denaturing gradient gel electrophoresis, we have identified in the three study groups a total of 127 unique alterations, of which 90 have not been previously reported, and have classified 72 as probable pathogenic mutations. Of the 288 STGD chromosomes studied, mutations were identified in 166, resulting in a detection rate of approximately 58%. Eight different alleles account for 61% of the identified disease alleles, and at least one of these, the L541P-A1038V complex allele, appears to be a founder mutation in the German population. When the group with AMD and the control group were analyzed with the same methodology, 18 patients with AMD and 12 controls were found to harbor possible disease-associated alterations. This represents no significant difference between the two groups; however, for detection of modest effects of rare alleles in complex diseases, the analysis of larger cohorts of patients may be required.

  15. TRIB1 and GCKR polymorphisms, lipid levels, and risk of ischemic heart disease in the general population

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Tybjærg-Hansen, Anne

    2011-01-01

    The goal of this study was to test whether TRIB1-rs2954029 and GCKR-rs1260326 associate with lipid levels and risk of ischemic heart disease (IHD) and myocardial infarction (MI) in the general population.......The goal of this study was to test whether TRIB1-rs2954029 and GCKR-rs1260326 associate with lipid levels and risk of ischemic heart disease (IHD) and myocardial infarction (MI) in the general population....

  16. The value of myocardial perfusion imaging in differentiating between idiopathic dilated cardiomyopathy from the ischemic form

    International Nuclear Information System (INIS)

    Fad, A.; Emami, F.; Eftekhari, M.; Saghari, M.; Fallahi, B.; Beiki, D.; Tkavar, A.

    2004-01-01

    Introduction: differentiating between ischemic cardiomyopathy and idiopathic dilated cardiomyopathy is important as coronary revascularization can improve prognosis in the ischemic subgroup. Due to inherent problems of coronary angiography in patients with depressed ejection fraction introducing a noninvasive tool to diagnose those who will benefit from angiography seems to be rewarding. We examined usefulness of myocardial perfusion scan in this group of patients. Materials and methods: study was performed on 64 patients (62 male and 2 female) aged 57.1 ± 6.7 y (mean ± SD) all with dilation of the left ventricular cavity and ejection fraction less than 40 % by echocardiography. Myocardial perfusion scan was performed in stress and rest phases. All the patients had coronary angiography which was used as the gold standard test. On each set of images, heart was arbitrary divided into 17 segments and perfusion abnormality in each segment was scored by a 5 grade scoring system (0-4). Summed stress Score was used as the scan criteria to differentiate dilated ischemic from idiopathic cardiomyopathy. Scores more than 17 were considered ischemic, and less than that, idiopathic. Results were compared with angiography. Results: from total 40 cases of ischemic cardiomyopathy (proved by angiography) 39 were correctly diagnosed by scan and only one case was mis categorized as idiopathic dilated cardiomyopathy . All 24 cases of idiopathic dilated cardiomyopathy were correctly diagnosed by scintigraphy. Sensitivity, specificity, positive predictive value, and negative predictive value of myocardial perfusion imaging for discrimination between ischemic and idiopathic dilated cardiomyopathy were 97.5 %, 100 %, 100 %, and 96 % respectively. Conclusion: Considering excellent accuracy of myocardial perfusion scan with scoring system in discrimination of ischemic dilated cardiomyopathy from idiopathic cardiomyopathy, this noninvasive test could be considered the main diagnostic test

  17. Electroacupuncture preconditioning reduces cerebral ischemic injury via BDNF and SDF-1α in mice

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    Kim Ji Hyun

    2013-01-01

    Full Text Available Abstract Background This study was designed to determine if electroacupuncture (EA preconditioning improves tissue outcome and functional outcome following experimentally induced cerebral ischemia in mice. In addition, we investigated whether the expression of brain-derived neurotrophic factor (BDNF and stromal cell derived factor-1α (SDF-1α and infarct volume were related with improvement in neurological and motor function by interventions in this study. Methods After treatment with EA at the acupoints ‘Baihui (GV20’ and ‘Dazhui (GV14’ for 20 min, BDNF was assessed in the cortical tissues based on Western blot and the SDF-1α and vascular endothelial growth factor (VEGF levels in the plasma determined by ELISA. To assess the protective effects of EA against ischemic injury, the mice received once a day 20 min EA preconditioning for three days prior to the ischemic event. Focal cerebral ischemia was then induced by photothrombotic cortical ischemia. Infarct volumes, neurobehavioral deficit and motor deficit were evaluated 24 h after focal cerebral ischemia. Results The expression of BDNF protein increased significantly from 6 h, reaching a plateau at 12 h after the end of EA treatment in the cerebral cortex. Furthermore, SDF-1α, not VEGF, increased singnificantly from 12 h to 48 h after EA stimulation in the plasma. Moreover, EA preconditioning reduced the infarct volume by 43.5% when compared to control mice at 24 h after photothrombotic cortical ischemia. Consistent with a smaller infarct size, EA preconditioning showed prominent improvement of neurological function and motor function such as vestibule-motor function, sensori-motor function and asymmetric forelimb use. The expression of BDNF colocalized within neurons and SDF-1α colocalized within the cerebral vascular endothelium was observed throughout the ischemic cortex by EA. Conclusions Pretreatment with EA increased the production of BDNF and SDF-1α, which elicited

  18. Presentation of Complex Homozygous Allele in ABCA4 Gene in a Patient with Retinitis Pigmentosa

    Directory of Open Access Journals (Sweden)

    Māreta Audere

    2015-01-01

    Full Text Available Retinitis pigmentosa is a degenerative retinal disease characterized by progressive photoreceptor damage, which causes loss of peripheral and night vision and the development of tunnel vision and may result in loss of central vision. This study describes a patient with retinitis pigmentosa caused by a mutation in the ABCA4 gene with complex allele c.1622T>C, p.L541P; c.3113C>T, p.A1038V in homozygous state.

  19. Atrial fibrillation is not uncommon among patients with ischemic stroke and transient ischemic stroke in China.

    Science.gov (United States)

    Yang, Xiaomeng; Li, Shuya; Zhao, Xingquan; Liu, Liping; Jiang, Yong; Li, Zixiao; Wang, Yilong; Wang, Yongjun

    2017-12-04

    Atrial fibrillation (AF) is reported to be a less frequent cause of ischemic stroke in China than in Europe and North America, but it is not clear whether this is due to underestimation. Our aim was to define the true frequency of AF-associated stroke, to determine the yield of 6-day Holter ECG to detect AF in Chinese stroke patients, and to elucidate predictors of newly detected AF. Patients with acute ischemic stroke or transient ischemic attack (TIA) were enrolled in a prospective, multicenter cohort study of 6-day Holter monitoring within 7 days after stroke onset at 20 sites in China between 2013 and 2015. Independent predictors of newly-detected AF were determined by multivariate analysis. Among 1511 patients with ischemic stroke and TIA (mean age 63 years, 33.1% women), 305 (20.2%) had either previously known (196, 13.0%) or AF newly-detected by electrocardiography (53, 3.5%) or by 6-day Holter monitoring (56/1262, 4.4%). A history of heart failure (OR = 4.70, 95%CI, 1.64-13.5), advanced age (OR = 1.06, 95%CI, 1.04-1.09), NIHSS at admission (OR = 1.06, 95%CI, 1.02-1.10), blood high density lipoprotein (HDL) (OR = 1.52, 95%CI, 1.09-2.13), together with blood triglycerides (OR = 0.64, 95%CI, 0.45-0.91) were independently associated with newly-detected AF. Contrary to previous reports, AF-associated stroke is frequent (20%) in China if systemically sought. Prolonged noninvasive cardiac rhythm monitoring importantly increases AF detection in patients with recent ischemic stroke and TIA in China. Advanced age, history of heart failure, and higher admission NIHSS and higher level of HDL were independent indicators of newly-detected AF. NCT02156765 (June 5, 2014).

  20. Thrombus length discrepancy on dual-phase CT can predict clinical outcome in acute ischemic stroke

    International Nuclear Information System (INIS)

    Park, Mina; Kim, Kyung-eun; Lee, Seung-Koo; Shin, Na-Young; Lim, Soo Mee; Song, Dongbeom; Heo, Ji Hoe; Kim, Jin Woo; Oh, Se Won

    2016-01-01

    The thrombus length may be overestimated on early arterial computed tomography angiography (CTA) depending on the collateral status. We evaluated the value of a grading system based on the thrombus length discrepancy on dual-phase CT in outcome prediction. Forty-eight acute ischemic stroke patients with M1 occlusion were included. Dual-phase CT protocol encompassed non-contrast enhanced CT, CTA with a bolus tracking technique, and delayed contrast enhanced CT (CECT) performed 40s after contrast injection. The thrombus length discrepancy between CTA and CECT was graded by using a three-point scale: G0 = no difference; G1 = no difference in thrombus length, but in attenuation distal to thrombus; G2 = difference in thrombus length. Univariate and multivariate analyses were performed to define independent predictors of poor clinical outcome at 3 months. The thrombus discrepancy grade showed significant linear relationships with both the collateral status (P = 0.008) and the presence of antegrade flow on DSA (P = 0.010) with good interobserver agreement (κ = 0.868). In a multivariate model, the presence of thrombus length discrepancy (G2) was an independent predictor of poor clinical outcome [odds ratio = 11.474 (1.350-97.547); P =0.025]. The presence of thrombus length discrepancy on dual-phase CT may be a useful predictor of unfavourable clinical outcome in acute M1 occlusion patients. (orig.)

  1. The association between high on-treatment platelet reactivity and early recurrence of ischemic events after minor stroke or TIA.

    Science.gov (United States)

    Rao, Zilong; Zheng, Huaguang; Wang, Fei; Wang, Anxin; Liu, Liping; Dong, Kehui; Zhao, Xingquan; Wang, Yilong; Cao, Yibin

    2017-08-01

    To evaluate the role of HTPR in predicting early recurrence of ischemic events in patients with minor ischemic stroke or high-risk TIA. From January 2014 to September 2014, a single center continuously enrolled patients with minor ischemic stroke or high-risk TIA and gave them antiplatelet therapy consisting of aspirin with clopidogrel. HTPR was assessed by TEG after 7 days of antiplatelet therapy and detected CYP2C19 genotype. The incidence of recurrent ischemic events was assessed 3 months after onset. The incidence of recurrent ischemic events was compared between the HTPR and NTPR groups with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to determine the risk factors associated with recurrent ischemic events. We enrolled 278 eligible patients with minor ischemic stroke or high-risk TIA. Through TEG testing, patients with HTPR were 22.7%, and carriers were not associated with HTPR to ADP by TEG-ADP(%) (p = 0.193). A total of 265 patients completed 3 months of follow-up, and Kaplan-Meier analysis showed that patients with HTPR had a higher percentage of recurrent ischemic events compared with patients with NTPR (p = 0.002). In multivariate Cox proportional hazards models, history of ischemic stroke or TIA (HR 4.45, 95% CI 1.77-11.16, p = 0.001) and HTPR (HR 3.34, 95% CI 1.41-7.91, p = 0.006) was independently associated with recurrent ischemic events. In patients with minor stroke or TIA, the prevalence of HTPR was 22.7%, and HTPR was independently associated with recurrent ischemic events.

  2. Identification of a Novel Mutation in the ABCA4 Gene in a Chinese Family with Retinitis Pigmentosa Using Exome Sequencing.

    Science.gov (United States)

    Huang, Xiangjun; Yuan, Lamei; Xu, Hongbo; Zheng, Wen; Cao, Yanna; Yi, Junhui; Guo, Yi; Yang, Zhijian; Li, Yu; Deng, Hao

    2018-02-05

    Retinitis pigmentosa (RP) is a group of hereditary, degenerative retinal disorders characterized by progressive retinal dysfunction, outer retina cell loss, and retinal tissue atrophy. It eventually leads to tunnel vision and legal, or total blindness. Here we aimed to reveal the causal gene and mutation contributing to the development of autosomal recessive RP (arRP) in a consanguineous family. A novel homozygous mutation, c.4845delT (p.K1616Rfs*46), in the ATP-binding cassette subfamily A member 4gene ( ABCA4 ) was identified. It may reduce ABCA4 protein activity, leading to progressive degeneration of both rod and cone photoreceptors. The study extends the arRP genotypic spectrum and confirms a genotype-phenotype relationship. This study may also disclose some new clues for RP genetic causes and pathogenesis, as well as clinical and genetic diagnosis. The research findings may contribute to improvement in clinical care, therapy, genetic screening, and counseling. ©2018 The Author(s).

  3. Web-based tool for dynamic functional outcome after acute ischemic stroke and comparison with existing models.

    Science.gov (United States)

    Ji, Ruijun; Du, Wanliang; Shen, Haipeng; Pan, Yuesong; Wang, Penglian; Liu, Gaifen; Wang, Yilong; Li, Hao; Zhao, Xingquan; Wang, Yongjun

    2014-11-25

    Acute ischemic stroke (AIS) is one of the leading causes of death and adult disability worldwide. In the present study, we aimed to develop a web-based risk model for predicting dynamic functional status at discharge, 3-month, 6-month, and 1-year after acute ischemic stroke (Dynamic Functional Status after Acute Ischemic Stroke, DFS-AIS). The DFS-AIS was developed based on the China National Stroke Registry (CNSR), in which eligible patients were randomly divided into derivation (60%) and validation (40%) cohorts. Good functional outcome was defined as modified Rankin Scale (mRS) score ≤ 2 at discharge, 3-month, 6-month, and 1-year after AIS, respectively. Independent predictors of each outcome measure were obtained using multivariable logistic regression. The area under the receiver operating characteristic curve (AUROC) and plot of observed and predicted risk were used to assess model discrimination and calibration. A total of 12,026 patients were included and the median age was 67 (interquartile range: 57-75). The proportion of patients with good functional outcome at discharge, 3-month, 6-month, and 1-year after AIS was 67.9%, 66.5%, 66.9% and 66.9%, respectively. Age, gender, medical history of diabetes mellitus, stroke or transient ischemic attack, current smoking and atrial fibrillation, pre-stroke dependence, pre-stroke statins using, admission National Institutes of Health Stroke Scale score, admission blood glucose were identified as independent predictors of functional outcome at different time points after AIS. The DFS-AIS was developed from sets of predictors of mRS ≤ 2 at different time points following AIS. The DFS-AIS demonstrated good discrimination in the derivation and validation cohorts (AUROC range: 0.837-0.845). Plots of observed versus predicted likelihood showed excellent calibration in the derivation and validation cohorts (all r = 0.99, P discrimination for good functional outcome and mortality at discharge, 3-month, 6

  4. Correlation study on cystatin C and ischemic stroke

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    CHEN Rong-bo

    2013-06-01

    Full Text Available Objective To investigate the relationship between serum cystatin C (Cys C and patients with acute ischemic stroke. Methods The clinical and laboratory data of 115 patients with acute ischemic stroke and 110 controls were recorded and analyzed. Results The serum Cys C levels of patients in ischemic stroke group [(1.15 ± 0.34 mg/L] were higher than that of the control group [(0.99 ± 0.25 mg/L]. The difference between two groups was significant after correction of age and cardiovascular risk factors (t = ? 3.889, P = 0.000. It was found that age, Cys C, homocysteine (Hcy, type 2 diabetes mellitus [hemoglobin A1c (HbA1c, fructosamine (FRU], smoking, alcohol consumption, hypertension and intima-media thickness (IMT were risk factors for ischemic stroke on univariate Logistic regression analysis. The difference of serum Cys C level between the patients and controls was significant (P = 0.000, but through covariance analysis, after adjusted other risk factors, it was not significant (P = 0.875. Conclusion The serum Cys C levels of patients in ischemic stroke group is higher than the control group. It can be used as an indicator in the acute phase of ischemic stroke. The elevation of serum Cys C is a risk factor for ischemic stroke, but not an independent risk factor.

  5. Cerebral Microbleeds and the Risk of Incident Ischemic Stroke in CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy).

    Science.gov (United States)

    Puy, Laurent; De Guio, François; Godin, Ophélia; Duering, Marco; Dichgans, Martin; Chabriat, Hugues; Jouvent, Eric

    2017-10-01

    Cerebral microbleeds are associated with an increased risk of intracerebral hemorrhage. Recent data suggest that microbleeds may also predict the risk of incident ischemic stroke. However, these results were observed in elderly individuals undertaking various medications and for whom causes of microbleeds and ischemic stroke may differ. We aimed to test the relationship between the presence of microbleeds and incident stroke in CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy)-a severe monogenic small vessel disease known to be responsible for both highly prevalent microbleeds and a high incidence of ischemic stroke in young patients. We assessed microbleeds on baseline MRI in all 378 patients from the Paris-Munich cohort study. Incident ischemic strokes were recorded during 54 months. Survival analyses were used to test the relationship between microbleeds and incident ischemic stroke. Three hundred sixty-nine patients (mean age, 51.4±11.4 years) were followed-up during a median time of 39 months (interquartile range, 19 months). The risk of incident ischemic stroke was higher in patients with microbleeds than in patients without (35.8% versus 19.6%, hazard ratio, 1.87; 95% confidence interval, 1.16-3.01; P =0.009). These results persisted after adjustment for history of ischemic stroke, age, sex, vascular risk factors, and antiplatelet agents use (hazard ratio, 1.89; 95% confidence interval, 1.10-3.26; P =0.02). The presence of microbleeds is an independent risk marker of incident ischemic stroke in CADASIL, emphasizing the need to carefully interpret MRI data. © 2017 American Heart Association, Inc.

  6. Long-term projections of temperature-related mortality risks for ischemic stroke, hemorrhagic stroke, and acute ischemic heart disease under changing climate in Beijing, China.

    Science.gov (United States)

    Li, Tiantian; Horton, Radley M; Bader, Daniel A; Liu, Fangchao; Sun, Qinghua; Kinney, Patrick L

    2018-03-01

    Changing climates have been causing variations in the number of global ischemic heart disease and stroke incidences, and will continue to affect disease occurrence in the future. To project temperature-related mortality for acute ischemic heart disease, and ischemic and hemorrhagic stroke with concomitant climate warming. We estimated the exposure-response relationship between daily cause-specific mortality and daily mean temperature in Beijing. We utilized outputs from 31 downscaled climate models and two representative concentration pathways (RCPs) for the 2020s, 2050s, and 2080s. This strategy was used to estimate future net temperature along with heat- and cold-related deaths. The results for predicted temperature-related deaths were subsequently contrasted with the baseline period. In the 2080s, using the RCP8.5 and no population variation scenarios, the net total number of annual temperature-related deaths exhibited a median value of 637 (with a range across models of 434-874) for ischemic stroke; this is an increase of approximately 100% compared with the 1980s. The median number of projected annual temperature-related deaths was 660 (with a range across models of 580-745) for hemorrhagic stroke (virtually no change compared with the 1980s), and 1683 (with a range across models of 1351-2002) for acute ischemic heart disease (a slight increase of approximately 20% compared with the 1980s). In the 2080s, the monthly death projection for hemorrhagic stroke and acute ischemic heart disease showed that the largest absolute changes occurred in summer and winter while the largest absolute changes for ischemic stroke occurred in summer. We projected that the temperature-related mortality associated with ischemic stroke will increase dramatically due to climate warming. However, projected temperature-related mortality pertaining to acute ischemic heart disease and hemorrhagic stroke should remain relatively stable over time. Copyright © 2017 Elsevier Ltd. All rights

  7. Whole-brain perfusion CT using a toggling table technique to predict final infarct volume in acute ischemic stroke.

    Science.gov (United States)

    Schrader, I; Wilk, D; Jansen, O; Riedel, C

    2013-09-01

    To evaluate how accurately final infarct volume in acute ischemic stroke can be predicted with perfusion CT (PCT) using a 64-MDCT unit and the toggling table technique. Retrospective analysis of 89 patients with acute ischemic stroke who underwent CCT, CT angiography (CTA) and PCT using the "toggling table" technique within the first three hours after symptom onset. In patients with successful thrombolytic therapy (n = 48) and in those without effective thrombolytic therapy (n = 41), the infarct volume and the volume of the penumbra on PCT were compared to the infarct size on follow-up images (CT or MRI) performed within 8 days. The feasibility of complete infarct volume prediction by 8 cm cranio-caudal coverage was evaluated. The correlation between the volume of hypoperfusion on PCT defined by cerebral blood volume reduction and final infarct volume was strongest in patients with successful thrombolytic therapy with underestimation of the definite infarct volume by 8.5 ml on average. The CBV map had the greatest prognostic value. In patients without successful thrombolytic therapy, the final infarct volume was overestimated by 12.1 ml compared to the MTT map on PCT. All infarcts were detected completely. There were no false-positive or false-negative results. Using PCT and the "toggling table" technique in acute stroke patients is helpful for the rapid and accurate quantification of the minimal final infarct and is therefore a prognostic parameter which has to be evaluated in further studies to assess its impact on therapeutic decision. ▶ Using PCT and the “toggling table technique” allows accurate quantification of the infarct core and penumbra. ▶ It is possible to record dynamic perfusion parameters quickly and easily of almost the entire supratentorial brain volume on a 64-slice MDCT unit. ▶ The technique allows identification of those patients who could profit from thrombolytic therapy outside the established time intervals. © Georg Thieme Verlag

  8. NADPH Oxidase, NOX1, Mediates Vascular Injury in Ischemic Retinopathy

    Science.gov (United States)

    Deliyanti, Devy; Rana, Indrajeetsinh; Miller, Antonia G.; Agrotis, Alex; Armani, Roksana; Szyndralewiez, Cédric; Wingler, Kirstin; Touyz, Rhian M.; Cooper, Mark E.; Jandeleit-Dahm, Karin A.; Schmidt, Harald H.H.W.

    2014-01-01

    Abstract Aims: Ischemic retinal diseases such as retinopathy of prematurity are major causes of blindness due to damage to the retinal microvasculature. Despite this clinical situation, retinopathy of prematurity is mechanistically poorly understood. Therefore, effective preventative therapies are not available. However, hypoxic-induced increases in reactive oxygen species (ROS) have been suggested to be involved with NADPH oxidases (NOX), the only known dedicated enzymatic source of ROS. Our major aim was to determine the contribution of NOX isoforms (1, 2, and 4) to a rodent model of retinopathy of prematurity. Results: Using a genetic approach, we determined that only mice with a deletion of NOX1, but not NOX2 or NOX4, were protected from retinal neovascularization and vaso-obliteration, adhesion of leukocytes, microglial accumulation, and the increased generation of proangiogenic and proinflammatory factors and ROS. We complemented these studies by showing that the specific NOX inhibitor, GKT137831, reduced vasculopathy and ROS levels in retina. The source of NOX isoforms was evaluated in retinal vascular cells and neuro-glial elements. Microglia, the immune cells of the retina, expressed NOX1, 2, and 4 and responded to hypoxia with increased ROS formation, which was reduced by GKT137831. Innovation: Our studies are the first to identify the NOX1 isoform as having an important role in the pathogenesis of retinopathy of prematurity. Conclusions: Our findings suggest that strategies targeting NOX1 have the potential to be effective treatments for a range of ischemic retinopathies. Antioxid. Redox Signal. 20, 2726–2740. PMID:24053718

  9. Analysis of prothrombotic and vascular risk factors in patients with nonarteritic anterior ischemic optic neuropathy.

    Science.gov (United States)

    Salomon, O; Huna-Baron, R; Kurtz, S; Steinberg, D M; Moisseiev, J; Rosenberg, N; Yassur, I; Vidne, O; Zivelin, A; Gitel, S; Davidson, J; Ravid, B; Seligsohn, U

    1999-04-01

    To determine whether genetic or acquired thrombophilias and other risk factors are associated with nonarteritic anterior ischemic optic neuropathy (NAION). Retrospective case-control study. Sixty-one patients with NAION diagnosed between 1984 and 1997. Ninety consecutive patients who visited the Eye Institute made up the control group. Protein C, protein S, antithrombin III, lupus anticoagulant, and three recently described prothrombotic polymorphisms (i.e., factor V G1691A, factor II G20210A, and methylenetetrahydrofolate reductase [MTHFR] C677T) were analyzed. In addition, risk factors for arteriosclerotic vascular disease were assessed. Parameters of thrombophilia. None of the thrombophilic markers (genetic and acquired) constituted a significant risk factor for NAION. Ischemic heart disease, hypercholesterolemia, and diabetes mellitus were discerned as risk factors for NAION with odds ratios of 2.9 (95% confidence interval [CI], 1.3-6.4), 2.6 (95% CI, 1.2-5.5), and 2.3 (95% CI, 1.1-4.8), respectively. Multiple logistic regression analysis indicated that ischemic heart disease and hypercholesterolemia exerted an additive risk for NAION with a combined odds ratio of 4.5 (95% CI, 1.4-14.5). However, none of these risk factors statistically predicted second eye involvement. NAION was not found to be associated with thrombophilic risk factors, yet it was related to ischemic heart disease, hypercholesterolemia, and diabetes mellitus.

  10. [Effects of exogenous high mobility group protein box 1 on angiogenesis in ischemic zone of early scald wounds of rats].

    Science.gov (United States)

    Dai, L; Guo, X; Huang, H J; Liao, X M; Luo, X Q; Li, D; Zhou, H; Gao, X C; Tan, M Y

    2018-04-20

    Objective: To observe effects of exogenous high mobility group protein box 1 (HMGB1) on angiogenesis in ischemic zone of early scald wounds of rats. Methods: Thirty-six Sprague-Dawley rats were divided into HMGB1 group and simple scald (SS) group according to the random number table, with 18 rats in each group. Comb-like copper mould was placed on the back of rats for 20 s after being immersed in 100 ℃ hot water for 3 to 5 min to make three ischemic zones of wound. Immediately after scald, rats in HMGB1 group were subcutaneously injected with 0.4 μg HMGB1 and 0.1 mL phosphate buffer solution (PBS), and rats in SS group were subcutaneously injected with 0.1 mL PBS from boarders of ischemic zone of scald wound. At post scald hour (PSH) 24, 48, and 72, 6 rats in each group were collected. Protein expressions of vascular endothelial growth factor (VEGF) in ischemic zone of wound at PSH 24, 48, and 72 and protein expressions of CD31 in ischemic zone of wound at PSH 48 and 72 were detected by immunohistochemistry. The number of microvessel in CD31 immunohistochemical sections of ischemic zone of wound at PSH 48 and 72 was calculated after observing by the microscope. The mRNA expressions of VEGF and CD31 in ischemic zone of wound were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction at PSH 24, 48, and 72. Data were processed with analysis of variance of factorial design, t test, and Bonferroni correction. Results: (1) At PSH 24, 48, and 72, protein expressions of VEGF in ischemic zone of wound of rats in HMGB1 group were significantly higher than those of rats in SS group ( t =7.496, 4.437, 5.402, P zone of wound of rats in HMGB1 group were 0.038 8±0.007 9 and 0.057 7±0.001 2 respectively, significantly higher than 0.013 4±0.004 9 and 0.030 3±0.004 0 of rats in SS group ( t =10.257, 15.055, P zone of wound of rats in HMGB1 group was obviously more than that of rats in SS group ( t =3.536, 4.000, P zone of wound of

  11. A pathophysiological role of TRPV1 in ischemic injury after transient focal cerebral ischemia in mice

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    Miyanohara, Jun [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Shirakawa, Hisashi, E-mail: shirakaw@pharm.kyoto-u.ac.jp [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Sanpei, Kazuaki [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Nakagawa, Takayuki [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital (Japan); Kaneko, Shuji [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan)

    2015-11-20

    Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel with high Ca{sup 2+} permeability, which functions as a polymodal nociceptor activated by heat, protons and several vanilloids, including capsaicin and anandamide. Although TRPV1 channels are widely distributed in the mammalian brain, their pathophysiological roles in the brain remain to be elucidated. In this study, we investigated whether TRPV1 is involved in cerebral ischemic injury using a middle cerebral artery (MCA) occlusion model in wild-type (WT) and TRPV1-knockout (KO) mice. For transient ischemia, the left MCA of C57BL/6 mice was occluded for 60 min and reperfused at 1 and 2 days after ischemia. We found that neurological and motor deficits, and infarct volumes in TRPV1-KO mice were lower than those of WT mice. Consistent with these results, intracerebroventricular injection of a TRPV1 antagonist, capsazepine (20 nmol), 30 min before the onset of ischemia attenuated neurological and motor deficits and improved infarct size without influencing cerebral blood flow in the occluded MCA territory. The protective effect of capsazepine on ischemic brain damage was not observed in TRPV1-KO mice. WT and TRPV1-KO mice did not show any differences with respect to the increased number of Iba1-positive microglia/macrophages, GFAP-positive astrocytes, and Gr1-positive neutrophils at 1 and 2 days after cerebral ischemia. Taken together, we conclude that brain TRPV1 channels are activated by ischemic stroke and cause neurological and motor deficits and infarction after brain ischemia. - Highlights: • We investigated whether TRPV1 is involved in transient ischemic brain damage in mice. • Neurological deficits and infarct volumes were lower in TRPV1-KO mice than in WT mice. • Injection of a TRPV1 antagonist, capsazepine, attenuated neurological deficits and improved infarct size. • No differences in astrocytic or microglial activation were observed between WT and TRPV1-KO mice.

  12. A pathophysiological role of TRPV1 in ischemic injury after transient focal cerebral ischemia in mice

    International Nuclear Information System (INIS)

    Miyanohara, Jun; Shirakawa, Hisashi; Sanpei, Kazuaki; Nakagawa, Takayuki; Kaneko, Shuji

    2015-01-01

    Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel with high Ca"2"+ permeability, which functions as a polymodal nociceptor activated by heat, protons and several vanilloids, including capsaicin and anandamide. Although TRPV1 channels are widely distributed in the mammalian brain, their pathophysiological roles in the brain remain to be elucidated. In this study, we investigated whether TRPV1 is involved in cerebral ischemic injury using a middle cerebral artery (MCA) occlusion model in wild-type (WT) and TRPV1-knockout (KO) mice. For transient ischemia, the left MCA of C57BL/6 mice was occluded for 60 min and reperfused at 1 and 2 days after ischemia. We found that neurological and motor deficits, and infarct volumes in TRPV1-KO mice were lower than those of WT mice. Consistent with these results, intracerebroventricular injection of a TRPV1 antagonist, capsazepine (20 nmol), 30 min before the onset of ischemia attenuated neurological and motor deficits and improved infarct size without influencing cerebral blood flow in the occluded MCA territory. The protective effect of capsazepine on ischemic brain damage was not observed in TRPV1-KO mice. WT and TRPV1-KO mice did not show any differences with respect to the increased number of Iba1-positive microglia/macrophages, GFAP-positive astrocytes, and Gr1-positive neutrophils at 1 and 2 days after cerebral ischemia. Taken together, we conclude that brain TRPV1 channels are activated by ischemic stroke and cause neurological and motor deficits and infarction after brain ischemia. - Highlights: • We investigated whether TRPV1 is involved in transient ischemic brain damage in mice. • Neurological deficits and infarct volumes were lower in TRPV1-KO mice than in WT mice. • Injection of a TRPV1 antagonist, capsazepine, attenuated neurological deficits and improved infarct size. • No differences in astrocytic or microglial activation were observed between WT and TRPV1-KO mice.

  13. Interleukin-1beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice

    DEFF Research Database (Denmark)

    Clausen, Bettina H; Lambertsen, Kate L; Babcock, Alicia A

    2008-01-01

    BACKGROUND: Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) are expressed by microglia and infiltrating macrophages following ischemic stroke. Whereas IL-1beta is primarily neurotoxic in ischemic stroke, TNF-alpha may have neurotoxic and/or neuroprotective effects. We inv...

  14. Hyper-attenuating brain lesions on CT after ischemic stroke and thrombectomy are associated with final brain infarction.

    Science.gov (United States)

    Cabral, F B; Castro-Afonso, L H; Nakiri, G S; Monsignore, L M; Fábio, Src; Dos Santos, A C; Pontes-Neto, O M; Abud, D G

    2017-12-01

    Purpose Hyper-attenuating lesions, or contrast staining, on a non-contrast brain computed tomography (NCCT) scan have been investigated as a predictor for hemorrhagic transformation after endovascular treatment of acute ischemic stroke (AIS). However, the association of hyper-attenuating lesions and final ischemic areas are poorly investigated in this setting. The aim of the present study was to assess correlations between hyper-attenuating lesions and final brain infarcted areas after thrombectomy for AIS. Methods Data from patients with AIS of the anterior circulation who underwent endovascular treatment were retrospectively assessed. Images of the brain NCCT scans were analyzed in the first hours and late after treatment. The hyper-attenuating areas were compared to the final ischemic areas using the Alberta Stroke Program Early CT Score (ASPECTS). Results Seventy-one of the 123 patients (65.13%) treated were included. The association between the hyper-attenuating region in the post-thrombectomy CT scan and final brain ischemic area were sensitivity (58.3% to 96.9%), specificity (42.9% to 95.6%), positive predictive values (71.4% to 97.7%), negative predictive values (53.8% to 79.5%), and accuracy values (68% to 91%). The highest sensitivity values were found for the lentiform (96.9%) and caudate nuclei (80.4%) and for the internal capsule (87.5%), and the lowest values were found for the M1 (58.3%) and M6 (66.7%) cortices. Conclusions Hyper-attenuating lesions on head NCCT scans performed after endovascular treatment of AIS may predict final brain infarcted areas. The prediction appears to be higher in the deep brain regions compared with the cortical regions.

  15. The application of remote ischemic conditioning in cardiac surgery [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Zeljko J. Bosnjak

    2017-06-01

    Full Text Available Perioperative myocardial ischemia and infarction are the leading causes of morbidity and mortality following anesthesia and surgery. The discovery of endogenous cardioprotective mechanisms has led to testing of new methods to protect the human heart. These approaches have included ischemic pre-conditioning, per-conditioning, post-conditioning, and remote conditioning of the myocardium. Pre-conditioning and per-conditioning include brief and repetitive periods of sub-lethal ischemia before and during prolonged ischemia, respectively; and post-conditioning is applied at the onset of reperfusion. Remote ischemic conditioning involves transient, repetitive, non-lethal ischemia and reperfusion in one organ or tissue (remote from the heart that renders myocardium more resistant to lethal ischemia/reperfusion injury. In healthy, young hearts, many conditioning maneuvers can significantly increase the resistance of the heart against ischemia/reperfusion injury. The large multicenter clinical trials with ischemic remote conditioning have not been proven successful in cardiac surgery thus far. The lack of clinical success is due to underlying risk factors that interfere with remote ischemic conditioning and the use of cardioprotective agents that have activated the endogenous cardioprotective mechanisms prior to remote ischemic conditioning. Future preclinical research using remote ischemic conditioning will need to be conducted using comorbid models.

  16. Improving the Prediction of Spontaneous and Post-thrombolytic Recanalization in Ischemic Stroke Patients.

    Science.gov (United States)

    Vanacker, Peter; Lambrou, Dimitris; Eskandari, Ashraf; Ntaios, George; Cras, Patrick; Maeder, Philippe; Meuli, Reto; Michel, Patrik

    2015-08-01

    Endovascular treatment for acute ischemic stroke patients was recently shown to improve recanalization rates and clinical outcome in a well-defined study population. Intravenous thrombolysis (IVT) alone is insufficiently effective to recanalize in certain patients or of little value in others. Accordingly, we aimed at identifying predictors of recanalization in patients treated with or without IVT. In the observational Acute Stroke Registry and Analysis of Lausanne (ASTRAL) registry, we selected those stroke patients (1) with an arterial occlusion on computed tomography angiography (CTA) imaging, (2) who had an arterial patency assessment at 24 hours (CTA/magnetic resonance angiography/transcranial Doppler), and (3) who were treated with IVT or had no revascularization treatment. Based on 2 separate logistic regression analyses, predictors of spontaneous and post-thrombolytic recanalization were generated. Partial or complete recanalization was achieved in 121 of 210 (58%) thrombolyzed patients. Recanalization was associated with atrial fibrillation (odds ratio , 1.6; 95% confidence interval, 1.2-3.0) and absence of early ischemic changes on CT (1.1, 1.1-1.2) and inversely correlated with the presence of a significant extracranial (EC) stenosis or occlusion (.6, .3-.9). In nonthrombolyzed patients, partial or complete recanalization was significantly less frequent (37%, P < .01). The recanalization was independently associated with a history of hypercholesterolemia (2.6, 1.2-5.6) and the proximal site of the intracranial occlusion (2.5, 1.2-5.4), and inversely correlated with a decreased level of consciousness (.3, .1-.8), and EC (.3, .1-.6) and basilar artery pathology (.1, .0-.6). Various clinical findings, cardiovascular risk factors, and arterial pathology on acute CTA-based imaging are moderately associated with spontaneous and post-thrombolytic arterial recanalization at 24 hours. If confirmed in other studies, this information may influence patient selection

  17. [Association Between SNP rs6007897 of CELSR1 and Acute Ischemic Stroke in Western China Han Population: a Case-control Study].

    Science.gov (United States)

    Qin, Feng-qin; Yu, Li-hua; Hu, Wen-ting; Guo, Jian; Chen, Ning; Guo, Jiang; Fang, Jing-huan; He, Li

    2015-07-01

    To investigate the relationship between single nucleotide polymorphism (SNP) rs6007897 of CELSR1 and acute ischemic stroke in Western China Han population. All subjects (759 acute ischemic stroke patients and 786 controls) were genotyped using ligation detection reaction (LDR). We analyzed the differences between SNP rs6007897 genotypes and allele frequencies between two groups. Two genotypes (AA, AG) of rs6007897 were found in both stroke and control group. There was no statistically significance between two groups about genotype and allele frequency. After adjusting for risk factors, we found there was no significant association between rs6007897 and ischemic stroke CP = 0.797, odds ratio (OR) = 0.886, 95% confidence interval (CI) = 0.352-2.227). SNP rs6007897 of CELSR1 was not significantly associated with ischemic stroke in Western China Han population.

  18. Quantification of convection-enhanced delivery to the ischemic brain

    International Nuclear Information System (INIS)

    Haar, Peter J; Broaddus, William C; Chen, Zhi-jian; Gillies, George T; Fatouros, Panos P; Corwin, Frank D

    2010-01-01

    Convection-enhanced delivery (CED) could have clinical application in the delivery of neuroprotective agents following ischemic stroke. However, ischemic brain tissue changes such as cytotoxic edema, in which cellular swelling decreases the fractional volume of the extracellular space, would be expected to significantly alter the distribution of neuroprotective agents delivered by CED. We sought to predict and characterize these effects using the magnetic resonance contrast agent gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) as a model therapeutic agent. CED was observed using MRI in a normal rat brain and in a middle cerebral artery (MCA) occlusion rat model of brain ischemia. Gd-DTPA was infused to the caudate putamen in the normal rat (n = 6) and MCA occlusion model (n = 6). In each rat, baseline apparent diffusion coefficient images were acquired prior to infusion, and T1 maps were then acquired 13 times throughout the duration of the experiment. These T1 maps were used to compute Gd-DTPA concentrations throughout each brain. In the MCA occlusion group, CED delivered Gd-DTPA to a comparatively larger volume with lower average tissue concentrations. Following the infusion, the total content of Gd-DTPA decreased more slowly in the MCA occlusion group than in the normal group. This quantitative characterization confirms that edematous ischemic tissue changes alter the distribution of agents by CED. These findings may have important implications for CED in the treatment of brain injury, and will assist in future efforts to model the distribution of therapeutic agents

  19. [Nonfasting triglycerides and risk of ischemic stroke--secondary publication

    DEFF Research Database (Denmark)

    Freiberg, J.J.; Tybjaerg-Hansen, A.; Jensen, J.S.

    2009-01-01

    The role of triglycerides in the risk of ischemic stroke remains controversial. We tested the hypothesis that increased levels of nonfasting triglycerides are associated with ischemic stroke in the general population. Men with a nonfasting triglyceride level 5 mmol/l had a multivariable, adjusted...... hazard ratio for ischemic stroke of 2.5 (95% confidence interval: 1.3-4.8) compared with men with a nonfasting triglyceride level triglycerides is associated with risk of ischemic stroke Udgivelsesdato...

  20. Frequency of inter-atrial blocks in patients with ischemic stroke

    International Nuclear Information System (INIS)

    Manzar, A.; Iftikhar, R.; Qadir, A.

    2012-01-01

    Objective: To determine the frequency and association of Interatrial block in hospitalized patients with Ischemic Stroke. Study Design: A case control study. Place and Duration of Study: Department of medicine, Military Hospital, Rawalpindi from 1 January 2009 to 30 December 2009. Methodology: It included 64 patients, 32 cases of diagnosed ischemic stroke and 32 patients were taken as controls not suffering from ischemic stroke or ischemic heart disease. ECG findings of both selected groups were evaluated for presence or absence of interatrial block. Results: Out of 32 ischemic stroke patients, 14 (43.85%) were found to have interatrial block on electrocardiogram (ECG). Whereas only 6 (18.80%) controls were found to have interatrial block on ECG. Odds ratio was 1.66. Conclusion: Interatrial block is more frequent in ischemic stroke patients and may represent a risk factor for such stroke. (author)

  1. Nonarteritic anterior ischemic optic neuropathy: cause, effect, and management

    Directory of Open Access Journals (Sweden)

    Berry S

    2017-09-01

    Full Text Available Shauna Berry,1 Weijie V Lin,2 Ama Sadaka,1 Andrew G Lee1–7 1Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA; 2Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA; 3Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch (UTMB, Galveston, TX, USA; 4Department of Ophthalmology, 5Department of Neurology, 6Department of Neurosurgery, Weill Cornell Medicine, Houston, TX, USA; 7Department of Ophthalmology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Nonarteritic anterior ischemic optic neuropathy (NAION is the most common form of ischemic optic neuropathy and the second most common optic neuropathy. Patients are generally over the age of 50 years with vasculopathic risk factors (eg, diabetes mellitus, hypertension, and obstructive sleep apnea. The exact mechanism of NAION is not fully understood. In addition, several treatment options have been proposed. This article summarizes the current literature on the diagnosis, treatment, and management of NAION. Keywords: anterior ischemic optic neuropathy, nonarteritic anterior ischemic optic neuropathy, ischemic optic neuropathy

  2. Variants in the ATP-Binding Cassette Transporter (ABCA7), Apolipoprotein E ε4, and the Risk of Late-Onset Alzheimer Disease in African Americans

    Science.gov (United States)

    Reitz, Christiane; Jun, Gyungah; Naj, Adam; Rajbhandary, Ruchita; Vardarajan, Badri Narayan; Wang, Li-San; Valladares, Otto; Lin, Chiao-Feng; Larson, Eric B.; Graff-Radford, Neill R.; Evans, Denis; De Jager, Philip L.; Crane, Paul K.; Buxbaum, Joseph D.; Murrell, Jill R.; Raj, Towfique; Ertekin-Taner, Nilufer; Logue, Mark; Baldwin, Clinton T.; Green, Robert C.; Barnes, Lisa L.; Cantwell, Laura B.; Fallin, M. Daniele; Go, Rodney C. P.; Griffith, Patrick; Obisesan, Thomas O.; Manly, Jennifer J.; Lunetta, Kathryn L.; Kamboh, M. Ilyas; Lopez, Oscar L.; Bennett, David A.; Hendrie, Hugh; Hall, Kathleen S.; Goate, Alison M.; Byrd, Goldie S.; Kukull, Walter A.; Foroud, Tatiana M.; Haines, Jonathan L.; Farrer, Lindsay A.; Pericak-Vance, Margaret A.; Schellenberg, Gerard D.; Mayeux, Richard

    2013-01-01

    Importance Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown. Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment. Objective To identify genetic loci associated with late-onset Alzheimer disease in African Americans. Design, Setting, and Participants The Alzheimer Disease Genetics Consortium (ADGC) assembled multiple data sets representing a total of 5896 African Americans (1968 case participants, 3928 control participants) 60 years or older that were collected between 1989 and 2011 at multiple sites. The association of Alzheimer disease with genotyped and imputed single-nucleotide polymorphisms (SNPs) was assessed in case-control and in family-based data sets. Results from individual data sets were combined to perform an inverse variance–weighted meta-analysis, first with genome-wide analyses and subsequently with gene-based tests for previously reported loci. Main Outcomes and Measures Presence of Alzheimer disease according to standardized criteria. Results Genome-wide significance in fully adjusted models (sex, age, APOE genotype, population stratification) was observed for a SNP in ABCA7 (rs115550680, allele = G; frequency, 0.09 cases and 0.06 controls; odds ratio [OR], 1.79 [95% CI, 1.47-2.12]; P = 2.2 × 10–9), which is in linkage disequilibrium with SNPs previously associated with Alzheimer disease in Europeans (0.8ABCA7 was comparable with that of the APOE ε4–determining SNP rs429358 (allele = C; frequency, 0.30 cases and 0.18 controls; OR, 2.31 [95% CI, 2.19-2.42]; P = 5.5 × 10–47). Several loci previously associated with Alzheimer disease but not reaching significance in genome-wide analyses were replicated in gene-based analyses

  3. Evaluation of ischemic damage of the corticospinal tract by diffusion tensor MRI. Utility in predicting functional outcome of corona radiata infarcts

    International Nuclear Information System (INIS)

    Tanaka, Hideki; Matsuno, Akira; Okubo, Toshiyuki; Nakaguchi, Hiroshi; Murakami, Mineko; Ono, Seiichi; Takeuchi, Masato

    2011-01-01

    Motor impairment is one of the most frequent symptoms among stroke patients and often leads to post-stroke dependency, so evaluation of motor symptoms and underlining corticospinal tract (CST) damage is of prime importance. Motor impairment, ischemic lesion by diffusion weighted MRI, and clinical outcome were assessed in 15 acute to early subacute corona radiata infarct patients. Motor impairment was graded severe: limb movement synergy level, moderate: selective muscle activity possible and mild: isolated movements are well coordinated. Outcome at the time of discharge was assessed by modified Rankin Scale (mRS). Diffusion tensor MRI (GE Signa Excite system 1.5 T, Echo Planar Imaging, MPG 15) was conducted at 2.3±2.2 days from the onset of the clinical symptoms. CST was delineated 3-dimensionally with dTV.II.SR and Volume-one 1.72. CST-FA (fractional anisotropy) ratio and CST-Area % were calculated at the slice where CST-infarct overlap was maximal. CST-FA ratio and CST-Area % showed good correlation to motor impairment at presentation. Patients with severe motor impairment had lower CST-FA ratio and CSF-Area % than those with moderate or mild. CST-FA ratio was 0.73±0.22 in patients with poor clinical outcome (mRS 3-6) and 0.93±0.09 with good clinical outcome (mRS 0-2) (p=0.038). Diffusion tensor MRI is useful in evaluating ischemic CST damage and predicting functional outcome in patients with corona radiata infarcts in the acute to subacute stage. (author)

  4. Association between high homocyst(e)ine and ischemic stroke due to large- and small-artery disease but not other etiologic subtypes of ischemic stroke.

    Science.gov (United States)

    Eikelboom, J W; Hankey, G J; Anand, S S; Lofthouse, E; Staples, N; Baker, R I

    2000-05-01

    Elevated plasma homocyst(e)ine may be a causal and modifiable risk factor for ischemic stroke, but the results of previous studies have been conflicting. One possible explanation is that homocyst(e)ine may only be associated with certain pathophysiological subtypes of ischemic stroke. We conducted a case-control study of 219 hospital cases with a first-ever ischemic stroke and 205 randomly selected community control subjects stratified by age, sex, and postal code. With the use of established criteria, cases of stroke were classified by etiologic subtype in a blinded fashion. The prevalence of conventional vascular risk factors, fasting plasma homocyst(e)ine levels, vitamin levels, and nucleotide 677 methylene tetrahydrofolate reductase (MTHFR) genotypes were determined in cases and controls. Increasing homocyst(e)ine was a strong and independent risk factor for ischemic stroke (adjusted OR 2.7, 95% CI 1.4 to 5.1 for a 5-micromol/L increase in fasting plasma homocyst(e)ine from 10 to 15 micromol/L). Compared with the lowest quartile, the highest quartile of homocyst(e)ine was associated with an adjusted OR of ischemic stroke of 2.2 (95% CI 1.1 to 4.2). Mean plasma homocyst(e)ine was significantly higher in cases of ischemic stroke due to large-artery disease (14.1 micromol/L, 95% CI 12.5 to 15.9, Pine, the upper 3 quartiles were associated with an adjusted OR of ischemic stroke due to large-artery disease of 3.0 (95% CI 0.8 to 10.8) for the second quartile, 5.6 (95% CI 1.6 to 20) for the third quartile, and 8.7 (95% CI 2.4 to 32) for the fourth quartile (P for trend=0.0005). However, despite a clear association between the TT MTHFR genotype and elevated fasting plasma homocyst(e)ine, there was no association between MTHFR genotype and ischemic stroke or subtype of ischemic stroke. There is a strong, graded association between increasing plasma homocyst(e)ine and ischemic stroke caused by large-artery atherosclerosis and, to a much lesser extent, small

  5. 25-Hydroxyvitamin D and symptomatic ischemic stroke

    DEFF Research Database (Denmark)

    Brøndum-Jacobsen, Peter; Nordestgaard, Børge G; Schnohr, Peter

    2013-01-01

    City Heart Study. During 21 years of follow-up, 1,256 and 164 persons developed ischemic and hemorrhagic stroke, respectively. In a meta-analysis of ischemic stroke, we included 10 studies, 58,384 participants, and 2,644 events. RESULTS: Stepwise decreasing plasma 25-hydroxyvitamin D concentrations...

  6. Quantitative characterization of myocardial infarction by cardiovascular magnetic resonance predicts future cardiovascular events in patients with ischemic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Pauly John M

    2008-04-01

    Full Text Available Abstract Background Cardiovascular magnetic resonance (CMR can provide quantitative data of the myocardial tissue utilizing high spatial and temporal resolution along with exquisite tissue contrast. Previous studies have correlated myocardial scar tissue with the occurrence of ventricular arrhythmia. This study was conducted to evaluate whether characterization of myocardial infarction by CMR can predict cardiovascular events in patients with ischemic cardiomyopathy (ICM. Results We consecutively studied 86 patients with ICM (LVEF Conclusion Quantification of the scar volume and scar percentage by CMR is superior to LVEDV, LVESV, and LVEF in prognosticating the future likelihood of the development of cardiovascular events in patients with ICM.

  7. CT diagnosis of hypoxic ischemic encephalopathy

    International Nuclear Information System (INIS)

    Zhao Xiang; Ma Jiwei; Wu Lide

    2004-01-01

    Objective: To explore CT characteristics of hypoxic ischemic encephalopathy (HIE), and to improve the accuracy of CT diagnosis. Methods: 50 cases of neonatal asphyxia in perinatal period diagnosed as hypoxic ischemic encephalopathy by CT was analyzed. Results: The main manifestation of hypoxic ischemic encephalopathy is cerebral edema and intracranial hemorrhage. Focal or diffuse hypo-dense lesion and hyper-dense area in various location and morphology were seen on CT images. (1) Localized diffuse hypo-dense area in 1 or 2 cerebral lobe were found in 17 cases, and the lesions were localized in frontal lobe (n=6), in frontotemporal lobe (n=5), and in temporo-occipital lobe (n=6). (2) Hypo-density region involving more than three cerebral lobes were found in 18 cases, and abnormalities were found in frontotemporal and parietal lobe (n=8), accompanying with subarachnoid hemorrhage (n=2); in frontal, temporal and occipital lobe (n=6), in which cerebral hemorrhage was complicated (n=1); and in other cerebral lobe (n=4). (3) Diffuse low-density region in all cerebral lobe were found in 15 cases, in which subarachnoid hemorrhage was complicated in 4 cases, and ventricular hemorrhage was found in 2 case. Conclusion: CT imaging plays an important role in diagnosis of hypoxic ischemic encephalopathy and has shown its clinical value

  8. 1.4 times increase in atrial fibrillation-related ischemic stroke and TIA over 12years in a stroke center.

    Science.gov (United States)

    Yang, Qiong; Churilov, Leonid; Fan, Dongsheng; Davis, Stephen; Yan, Bernard

    2017-08-15

    Prevalence of atrial fibrillation (AF) has quadrupled in the past 50years in the general population. However, there is uncertainty regarding prevalence of AF over time in ischemic stroke patients given the aging population and enhanced surveillance of AF. We aimed to explore the changing prevalence of AF as well as other risk factors, stroke subtypes, investigations and pre-stroke medications among ischemic stroke and transient ischemic attack (TIA) patients. We performed a retrospective analysis of data from a prospective database of consecutive patients with acute ischemic stroke and TIA from 2004 to 2015. Trends in risk factors and other variables year by year were analyzed using logistic regression or median regression. Among 6275 patients (median age [interquartile range] 74 [62-82] years, 56% males), the prevalence of AF increased 1.4 times over 12years (from 23.3% to 32.7%, PTIA (10.9% to 13.7%) and a significant decrease in prevalence of dyslipidemia (71.8% to 49.4%). There was a 1.4 times increase in the prevalence of AF among consecutive ischemic stroke and TIA patients in the past 12years in a hospital-based registry. More active screening of the general population for AF may be warranted in order to decrease the overall stroke burden. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Relationship between hypertensive cerebral hemorrhage and ischemic lesions

    International Nuclear Information System (INIS)

    Yamaguchi, Shinya; Tsuchiya, Takashi; Yamaguchi, Takenori

    1991-01-01

    Patchy parenchymal lesions of increased intensity were frequently identified in patients with cerebral hemorrhage in T2-weighted image of high-fields MR imaging. We studied 64 patients with brain hemorrhage to determine the frequency and distribution of those lesions. We defined an area with high intensity in T2 weighted and low or iso-intensity area in T1 weighted images smaller than 1.5 cm in diameter to be 'ischemic lesion'. Ishemic lesions were found in 48 (75%) of all cases; in 25 (75%) of 32 patients with putaminal hemorrhage, in 15 (100%) of 15 with thalamic hemorrhage, in 3 (33%) of 9 with subcortical hemorrhage. Multiple ischemic lesions were more frequently seen in thalamic hemorrhage than in putaminal hemorrhage. Only 5 (10%) of 48 cases with associated ischemic lesions had a previous history related to those lesions. Multivariable regression analysis identified hypertension as the major predictor of the presence of ischemic lesions. Patients with brain hemorrhage frequently accompanied with incidental ischemic lesions, making it difficult to establish a guideline of blood pressure control for prevention of recurrent stroke. (author)

  10. [Preditive clinical factors for epileptic seizures after ischemic stroke].

    Science.gov (United States)

    Fukujima, M M; Cardeal, J O; Lima, J G

    1996-06-01

    Preditive clinical factors for epileptic seizures after ischemic stroke. Clinical features of 35 patients with ischemic stroke who developed epilepsy (Group 1) were compared with those of 35 patients with ischemic stroke without epilepsy (Group 2). The age of the patients did not differ between the groups. There were more men than women and more white than other races in both groups. Diabetes melitus, hypertension, transient ischemic attack, previous stroke, migraine, Chagas disease, cerebral embolism of cardiac origin and use of oral contraceptive did not differ between the groups. Smokers and alcohol users were more frequent in Group 1 (p < 0.05). Most patients of Group 1 presented with hemiparesis; none presented cerebellar or brainstem involvement. Perhaps strokes in smokers have some different aspects, that let them more epileptogenic than in non smokers.

  11. C-reactive protein gene C1444T polymorphism and risk of recurrent ischemic events in patients with symptomatic intracranial atherostenoses.

    Science.gov (United States)

    Arenillas, Juan F; Massot, Andreu; Alvarez-Sabín, Jose; Fernandez-Cadenas, Israel; del Rio-Espinola, Albert; Chacon, Pilar; Quintana, Manuel; Molina, Carlos A; Rovira, Alex; Montaner, Joan

    2009-01-01

    High levels of C-reactive protein (CRP) are associated with an increased risk of further ischemic events in patients with symptomatic intracranial atherosclerotic disease (ICAD). It remains unknown to which extent this increased risk might be genetically predetermined. We aimed to investigate the relationship between a common genetic polymorphism of the CRP gene and the risk of recurrent ischemic events in symptomatic ICAD patients. We studied 75 consecutive patients with a first-ever cerebral ischemic event attributable to symptomatic ICAD. Blood samples were drawn 3 months after the qualifying event. Genomic DNA was isolated and the C1444T single nucleotide polymorphism (SNP) of the CRP gene was determined. The blood concentration of CRP was also measured. Patients underwent long-term clinical follow-up to detect the occurrence of further major ischemic events. During a median follow-up time of 23 months, 18 patients (24%) suffered a major ischemic event (10 ischemic strokes, 3 transient ischemic attacks and 5 myocardial infarctions). Raised CRP levels at baseline (p = 0.02) and the presence of the T allele within the CRP C1444T SNP were associated with a higher risk of recurrent ischemic events (p = 0.02). Kaplan-Meier and multivariable Cox regression analyses adjusted for age, sex, vascular risk factors and CRP level identified that the presence of the T allele in the studied polymorphism predicted the occurrence of further ischemic events (hazard ratio 3.6, 95% confidence interval 1.2-11.1; p = 0.025). The presence of the T allele within the CRP gene C1444T polymorphism may be associated with a higher risk of further ischemic events in symptomatic ICAD patients. (c) 2009 S. Karger AG, Basel.

  12. Prognostic value of serum thioredoxin levels in ischemic stroke.

    Science.gov (United States)

    Yu, Tieer; Zhang, Wanli; Lin, Yuanshao; Li, Qian; Xue, Jie; Cai, Zhengyi; Cheng, Yifan; Shao, Bei

    2017-11-01

    Thioredoxin (Trx) is one of significant antioxidative molecules to diminish oxidative stress. Current evidence suggests that Trx is a potent antioxidant with cytoprotective functions. The aim of our study was to investigate specifically the association between serum Trx levels and acute ischemic stroke (AIS) patients. 198 AIS patients and 75 controls were enrolled to the study. Serum Trx levels were measured using an enzyme-linked immunosorbent assay (ELISA). Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS) score on admission. Clinical endpoint was functional outcome measured by Barthel Index (BI) 3 months after admission. Multivariate binary logistic regression analyses were performed to identify predictors. We found that serum Trx levels were significantly increased in patients as compared to controls. Serum Trx was an independent biomarker to predict ischemic stroke (OR, 1.264; 95% CI, 1.04-1.537; P = 0.019). In addition, there was a negative correlation between NIHSS score at admission and serum Trx levels in cardioembolic stroke patients (r = -0.422; P = 0.013). Furthermore, higher serum Trx levels in AIS patients were associated with favorable functional outcome. Serum Trx was an independent predictor for the functional outcome (OR, 0.862; 95% CI, 0.75-0.991; P = 0.037). Serum Trx might be as a biomarker of cardioembolic stroke severity. Increased serum Trx levels could be a useful tool to predict good prognosis in patients with AIS.

  13. Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yuanxue; Xu, Xiaojun; Chang, Sai; Wang, Yunjie; Xu, Yazhou; Ran, Siqi [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Huang, Zhangjian [Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009 (China); Li, Ping [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Li, Jia [National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guo Shoujing Road, Shanghai 201203 (China); Zhang, Luyong [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Saavedra, Juan M. [Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057 (United States); Liao, Hong, E-mail: liaohong56@hotmail.com [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Pang, Tao, E-mail: tpang@cpu.edu.cn [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057 (United States)

    2015-12-01

    The natural product totarol, a phenolic diterpenoid and a major constituent isolated from the sap of Podocarpus totara, has been reported to have a potent antimicrobial activity. In this study, we determined whether totarol possessed an additional neuroprotective activity in vitro and in vivo. We found that totarol prevented glutamate- and oxygen and glucose deprivation-induced neuronal death in primary rat cerebellar granule neuronal cells and cerebral cortical neurons. Totarol increased Akt and GSK-3β phosphorylation, Nrf2 and heme oxygenase-1 (HO-1) protein expressions and suppressed oxidative stress by increasing GSH and SOD activities. The PI3K/Akt inhibitor LY294002 prevented totarol neuroprotective effect by suppressing the totarol-induced changes in HO-1 expression and the activities of GSH and SOD. The HO-1 inhibitor ZnPPIX also prevented totarol-increased GSH and SOD activities. In a model of acute cerebral ischemic injury in Sprague–Dawley rats, produced by occlusion of the middle cerebral artery for 2 h followed by 22 h or 46 h of reperfusion, totarol significantly reduced infarct volume and improved the neurological deficit. In this model, totarol increased HO-1 expression and the activities of GSH and SOD. These observations suggest that totarol may be a novel activator of the Akt/HO-1 pathway protecting against ischemic stroke through reduction of oxidative stress. - Graphical abstract: It is unknown whether the natural product totarol has neuroprotective effects in vitro and in vivo. This study underscores that totarol prevents neuronal injury in vitro, not only by activating PI3K/Akt pathway, but also via induction of Nrf2, HO-1, GSH and SOD expressions. Totarol also ameliorated acute cerebral ischemic injury in a rat ischemic stroke model. The findings highlight that totarol may be exploited for protecting against ischemic stroke through Akt/HO-1 pathway. - Highlights: • Totarol protects glutamate- and OGD-induced neuronal injury in vitro.

  14. Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction

    International Nuclear Information System (INIS)

    Gao, Yuanxue; Xu, Xiaojun; Chang, Sai; Wang, Yunjie; Xu, Yazhou; Ran, Siqi; Huang, Zhangjian; Li, Ping; Li, Jia; Zhang, Luyong; Saavedra, Juan M.; Liao, Hong; Pang, Tao

    2015-01-01

    The natural product totarol, a phenolic diterpenoid and a major constituent isolated from the sap of Podocarpus totara, has been reported to have a potent antimicrobial activity. In this study, we determined whether totarol possessed an additional neuroprotective activity in vitro and in vivo. We found that totarol prevented glutamate- and oxygen and glucose deprivation-induced neuronal death in primary rat cerebellar granule neuronal cells and cerebral cortical neurons. Totarol increased Akt and GSK-3β phosphorylation, Nrf2 and heme oxygenase-1 (HO-1) protein expressions and suppressed oxidative stress by increasing GSH and SOD activities. The PI3K/Akt inhibitor LY294002 prevented totarol neuroprotective effect by suppressing the totarol-induced changes in HO-1 expression and the activities of GSH and SOD. The HO-1 inhibitor ZnPPIX also prevented totarol-increased GSH and SOD activities. In a model of acute cerebral ischemic injury in Sprague–Dawley rats, produced by occlusion of the middle cerebral artery for 2 h followed by 22 h or 46 h of reperfusion, totarol significantly reduced infarct volume and improved the neurological deficit. In this model, totarol increased HO-1 expression and the activities of GSH and SOD. These observations suggest that totarol may be a novel activator of the Akt/HO-1 pathway protecting against ischemic stroke through reduction of oxidative stress. - Graphical abstract: It is unknown whether the natural product totarol has neuroprotective effects in vitro and in vivo. This study underscores that totarol prevents neuronal injury in vitro, not only by activating PI3K/Akt pathway, but also via induction of Nrf2, HO-1, GSH and SOD expressions. Totarol also ameliorated acute cerebral ischemic injury in a rat ischemic stroke model. The findings highlight that totarol may be exploited for protecting against ischemic stroke through Akt/HO-1 pathway. - Highlights: • Totarol protects glutamate- and OGD-induced neuronal injury in vitro.

  15. Metabolic Syndrome Predicts Refractoriness to Intravenous Thrombolysis in Acute Ischemic Stroke.

    Science.gov (United States)

    Dorado, Laura; Arenillas, Juan F; López-Cancio, Elena; Hernández-Pérez, María; Pérez de la Ossa, Natalia; Gomis, Meritxell; Millán, Mònica; Granada, María Luisa; Galán, Amparo; Palomeras, Ernest; Dávalos, Antoni

    2015-11-01

    Metabolic syndrome (MetS) has been associated with higher resistance to clot lysis at 24 hours after tissue plasminogen activator (tPA) administration in patients with acute ischemic stroke. We aimed to test this hypothesis at earlier time points, when neurointerventional rescue procedures may still be indicated to achieve arterial recanalization. This is a prospective and observational study in consecutive stroke patients with MCA occlusion treated with IV tPA. MetS was diagnosed following the unified criteria of the last Joint Interim Statement 2009 participating several major organizations. The primary outcome variable was resistance to thrombolysis, defined as the absence of complete middle cerebral artery recanalization 2 hours after tPA bolus assessed by transcranial color-coded duplex or when rescue mechanical thrombectomy after IV tPA was required. Secondary outcome variables were dramatic neurological improvement (decrease in ≥10 points, or a National Institutes of Health Stroke Scale [NIHSS] score of 0-1 at 24 hours), symptomatic intracerebral hemorrhage following European-Australasian Acute Stroke Study II criteria, infarct volume at 24 hours (calculated by using the formula for irregular volumes, ABC/2), and good outcome (modified Rankin Scale score < 3) at 3 months. A total of 234 patients (median baseline NIHSS score 16 [10-20]) were included and 146 (62.4%) fulfilled MetS criteria. After multivariate analysis, MetS emerged as an independent predictor of resistance to thrombolysis (odds ratio = 2.2 [1.3-4.2], P = .01) and absence of dramatic neurological improvement (odds ratio = .5 [.28-.97], P = .04). In addition, MetS conferred poorer functional outcome, higher symptomatic intracerebral hemorrhage rate, and increased infarct volume, although these associations disappeared after adjustment for covariates. MetS predicts patients with middle cerebral artery occlusion refractory to early clot dissolution after IV tPA. This

  16. Increased expression of vascular endothelin type B and angiotensin type 1 receptors in patients with ischemic heart disease

    DEFF Research Database (Denmark)

    Dimitrijevic, Ivan; Edvinsson, Lars; Chen, Qingwen

    2009-01-01

    expression in subcutaneous arteries from patients with different degrees of ischemic heart disease. METHODS: Subcutaneous arteries were obtained, by biopsy from the abdomen, from patients undergoing coronary artery bypass graft (CABG) surgery because of ischemic heart disease (n = 15), patients with angina...... pectoris without established myocardial infarction (n = 15) and matched cardiovascular healthy controls (n = 15). Endothelin type A (ETA) and type B (ETB), and angiotensin type 1 (AT1) and type 2 (AT2) receptors expression and function were examined using immunohistochemistry, Western blot and in vitro...

  17. Elevated Plasma YKL-40 Levels and Ischemic Stroke in the General Population

    DEFF Research Database (Denmark)

    Kjaergaard, A.D.; Bojesen, S.E.; Johansen, J.S.

    2010-01-01

    inside the vessel wall. Methods: We measured plasma YKL-40 in 8,899 21- to 93-year-old participants of the Copenhagen City Heart Study 1991-1994 examination, and followed them for up to 18 years. Endpoints were ischemic stroke, ischemic cerebrovascular disease, myocardial infarction, and ischemic heart......% confidence interval, 11%-30%) for ischemic stroke, 16% (8%-24%) for ischemic cerebrovascular disease, 3% (-5%-11%) for myocardial infarction, and 7% (1%-12%) for ischemic heart disease. Interpretation: In the general population, elevated plasma YKL-40 levels are associated with increased risk of ischemic...... stroke and ischemic cerebrovascular disease, independent of plasma CRP levels. ANN NEUROL 2010;68:672-680...

  18. Automated prediction of tissue outcome after acute ischemic stroke in computed tomography perfusion images

    Science.gov (United States)

    Vos, Pieter C.; Bennink, Edwin; de Jong, Hugo; Velthuis, Birgitta K.; Viergever, Max A.; Dankbaar, Jan Willem

    2015-03-01

    Assessment of the extent of cerebral damage on admission in patients with acute ischemic stroke could play an important role in treatment decision making. Computed tomography perfusion (CTP) imaging can be used to determine the extent of damage. However, clinical application is hindered by differences among vendors and used methodology. As a result, threshold based methods and visual assessment of CTP images has not yet shown to be useful in treatment decision making and predicting clinical outcome. Preliminary results in MR studies have shown the benefit of using supervised classifiers for predicting tissue outcome, but this has not been demonstrated for CTP. We present a novel method for the automatic prediction of tissue outcome by combining multi-parametric CTP images into a tissue outcome probability map. A supervised classification scheme was developed to extract absolute and relative perfusion values from processed CTP images that are summarized by a trained classifier into a likelihood of infarction. Training was performed using follow-up CT scans of 20 acute stroke patients with complete recanalization of the vessel that was occluded on admission. Infarcted regions were annotated by expert neuroradiologists. Multiple classifiers were evaluated in a leave-one-patient-out strategy for their discriminating performance using receiver operating characteristic (ROC) statistics. Results showed that a RandomForest classifier performed optimally with an area under the ROC of 0.90 for discriminating infarct tissue. The obtained results are an improvement over existing thresholding methods and are in line with results found in literature where MR perfusion was used.

  19. Recurrent Stroke in Minor Ischemic Stroke or Transient Ischemic Attack With Metabolic Syndrome and/or Diabetes Mellitus.

    Science.gov (United States)

    Chen, Weiqi; Pan, Yuesong; Jing, Jing; Zhao, Xingquan; Liu, Liping; Meng, Xia; Wang, Yilong; Wang, Yongjun

    2017-06-01

    We aimed to determine the risk conferred by metabolic syndrome (METS) and diabetes mellitus (DM) to recurrent stroke in patients with minor ischemic stroke or transient ischemic attack from the CHANCE (Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events) trial. In total, 3044 patients were included. Patients were stratified into 4 groups: neither, METS only, DM only, or both. METS was defined using the Chinese Diabetes Society (CDS) and International Diabetes Foundation (IDF) definitions. The primary outcome was new stroke (including ischemic and hemorrhagic) at 90 days. A multivariable Cox regression model was used to assess the relationship of METS and DM status to the risk of recurrent stroke adjusted for potential covariates. Using the CDS criteria of METS, 53.2%, 17.2%, 19.8%, and 9.8% of patients were diagnosed as neither, METS only, DM only, and both, respectively. After 90 days of follow-up, there were 299 new strokes (293 ischemic, 6 hemorrhagic). Patients with DM only (16.1% versus 6.8%; adjusted hazard ratio 2.50, 95% CI 1.89-3.39) and both (17.1% versus 6.8%; adjusted hazard ratio 2.76, 95% CI 1.98-3.86) had significantly increased rates of recurrent stroke. No interaction effect of antiplatelet therapy by different METS or DM status for the risk of recurrent stroke ( P =0.82 for interaction in the fully adjusted model of CDS) was observed. Using the METS (IDF) criteria demonstrated similar results. Concurrent METS and DM was associated with an increased risk of recurrent stroke in patients with minor stroke and transient ischemic attack. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  20. Spectrum of ABCA4 (ABCR) gene mutations in Spanish patients with autosomal recessive macular dystrophies.

    Science.gov (United States)

    Paloma, E; Martínez-Mir, A; Vilageliu, L; Gonzàlez-Duarte, R; Balcells, S

    2001-06-01

    The ABCA4 gene has been involved in several forms of inherited macular dystrophy. In order to further characterize the complex genotype-phenotype relationships involving this gene, we have performed a mutation analysis of ABCA4 in 14 Spanish patients comprising eight STGD (Stargardt), four FFM (fundus flavimaculatus), and two CRD (Cone-rod dystrophy) patients. SSCP (single-strand conformation polymorphism) analysis and DNA sequencing of the coding and 5' upstream regions of this gene allowed the identification of 16 putatively pathogenic alterations, nine of which are novel. Most of these were missense changes, and no patient was found to carry two null alleles. Overall, the new data agree with a working model relating the different pathogenic phenotypes to the severity of the mutations. When considering the information presented here together with that of previous reports, a picture of the geographic distribution of three particular mutations emerges. The R212C change has been found in French, Italian, Dutch, German, and Spanish but not in British patients. In the Spanish collection, R212C was found in a CRD patient, indicating that it may be a rather severe change. In contrast, c.2588G>C, a very common mild allele in the Dutch population, is rarely found in Southern Europe. Interestingly, the c.2588G>C mutation has been found in a double mutant allele together with the missense R1055W. Finally, the newly described L1940P was found in two unrelated Spanish patients, and may be a moderate to severe allele. Copyright 2001 Wiley-Liss, Inc.

  1. Paradoxical centrally increased diffusivity in perinatal arterial ischemic stroke

    International Nuclear Information System (INIS)

    Stence, Nicholas V.; Mirsky, David M.; Deoni, Sean C.L.; Armstrong-Wells, Jennifer

    2016-01-01

    Restricted diffusion on acute MRI is the diagnostic standard for perinatal arterial ischemic stroke. In a subset of children with perinatal arterial ischemic stroke, primarily those with large infarct volumes, we noted a core of centrally increased diffusivity with a periphery of restricted diffusion. Given the paradoxical diffusion-weighted imaging (DWI) appearance observed in some children with perinatal arterial ischemic stroke, we sought to determine its significance and hypothesized that: (1) centrally increased diffusivity is associated with larger infarcts in perinatal arterial ischemic stroke and (2) this tissue is irreversibly injured (infarcted). We reviewed all perinatal arterial ischemic stroke cases in a prospective cohort study from Aug. 1, 2000, to Jan. 1, 2012. Infarct volumes were measured by drawing regions of interest around the periphery of the area of restricted diffusion on DWI. The Mann-Whitney U test was used to compare means between groups. Of 25 eligible cases, centrally increased diffusivity was seen in 4 (16%). Cases with centrally increased diffusivity had larger average infarct volumes (mean 117,182 mm 3 vs. 36,995 mm 3 ; P = 0.008), higher average apparent diffusion coefficient (ADC) values in the infarct core (1,679 x 10 -6 mm 2 /s vs. 611 x 10 -6 mm 2 /s, P < 0.0001), and higher ADC ratio (1.2 vs. 0.5, P < 0.0001). At last clinical follow-up, children with perinatal arterial ischemic stroke and centrally increased diffusivity were more often treated for ongoing seizures (75% vs. 0%; P < 0.001) than those without. Centrally increased diffusivity was associated with larger stroke volume and the involved tissue was confirmed to be infarcted on follow-up imaging. Radiologists should be aware of this unusual appearance of perinatal arterial ischemic stroke in order to avoid underestimating infarct volume or making an incorrect early diagnosis. (orig.)

  2. Paradoxical centrally increased diffusivity in perinatal arterial ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Stence, Nicholas V.; Mirsky, David M.; Deoni, Sean C.L. [University of Colorado Anschutz School of Medicine, Department of Radiology, Aurora, CO (United States); Children' s Hospital Colorado, Department of Radiology, Aurora, CO (United States); Armstrong-Wells, Jennifer [University of Colorado Anschutz School of Medicine, Department of Pediatrics (Neurology) and OB/GYN, Aurora, CO (United States); University of Colorado Hemophilia and Thrombosis Center, Aurora, CO (United States)

    2016-01-15

    Restricted diffusion on acute MRI is the diagnostic standard for perinatal arterial ischemic stroke. In a subset of children with perinatal arterial ischemic stroke, primarily those with large infarct volumes, we noted a core of centrally increased diffusivity with a periphery of restricted diffusion. Given the paradoxical diffusion-weighted imaging (DWI) appearance observed in some children with perinatal arterial ischemic stroke, we sought to determine its significance and hypothesized that: (1) centrally increased diffusivity is associated with larger infarcts in perinatal arterial ischemic stroke and (2) this tissue is irreversibly injured (infarcted). We reviewed all perinatal arterial ischemic stroke cases in a prospective cohort study from Aug. 1, 2000, to Jan. 1, 2012. Infarct volumes were measured by drawing regions of interest around the periphery of the area of restricted diffusion on DWI. The Mann-Whitney U test was used to compare means between groups. Of 25 eligible cases, centrally increased diffusivity was seen in 4 (16%). Cases with centrally increased diffusivity had larger average infarct volumes (mean 117,182 mm{sup 3} vs. 36,995 mm{sup 3}; P = 0.008), higher average apparent diffusion coefficient (ADC) values in the infarct core (1,679 x 10{sup -6} mm{sup 2}/s vs. 611 x 10{sup -6} mm{sup 2}/s, P < 0.0001), and higher ADC ratio (1.2 vs. 0.5, P < 0.0001). At last clinical follow-up, children with perinatal arterial ischemic stroke and centrally increased diffusivity were more often treated for ongoing seizures (75% vs. 0%; P < 0.001) than those without. Centrally increased diffusivity was associated with larger stroke volume and the involved tissue was confirmed to be infarcted on follow-up imaging. Radiologists should be aware of this unusual appearance of perinatal arterial ischemic stroke in order to avoid underestimating infarct volume or making an incorrect early diagnosis. (orig.)

  3. Is opium addiction a risk factor for ischemic heart disease and ischemic stroke?

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Rezvani

    2012-01-01

    Full Text Available Background: The main source of studies about effects of opium consumption on heart and brain attacks originates from Iran Therefore the aim of the present study was to assess opium addiction as a probable influencing factor for ischemic heart disease and ischemic stroke. Materials and Methods: A cross-sectional study was carried out in two Cardiology and Neurology clinics in Eastern Iran in 2011. Diagnosis of Ischemic Heart Disease (IHD and Ischemic Stroke (IS was made by Cardiologist and Stroke Neurologist respectively. The influence of gender, hypertension, diabetes, hyperlipidemia, cigarette smoking, oral and inhaled opium consumption on distribution of IHD and IS were evaluated. Results: Five hundred fifty eight patients (307 females, 251 males with mean age 56.2 years enrolled the study. On adjusted odds ratios of our whole 558 patients, only hypertension and diabetes had a significant influence on occurrence of IHD; (P = 0.000 and P = 0.000 respectively. Oral and inhaled routes of opium addiction did not have a significant effect on occurrence of IHD; [OR = 1.172, 95% CI = 0.624-2.203, P = 0.621] and [OR = 1.820, 95% CI = 0.811-4.085, P = 0.147] respectively. Hypertension and diabetes were significant risk factors of IS in our 558 patients at multivariate analysis; (P = 0.000, P = 0.020. Oral opium addiction was as significant protective factor of IS in our study group; OR = 0.211, 95% CI = 0.079-0.564, P = 0.002, while inhaled opium addiction did not have a significant effect on occurrence of IS in our patients at; OR = 1.760, 95% CI = 0.760-4.076, P = 0.187. Conclusion: Oral opium consumption is a protective factor of IS but not IHD. Inhaled opium addiction does not have a significant influence on occur r ence of IS and IHD.

  4. Is opium addiction a risk factor for ischemic heart disease and ischemic stroke?

    Science.gov (United States)

    Rezvani, Mohammad Reza; Ghandehari, Kavian

    2012-10-01

    The main source of studies about effects of opium consumption on heart and brain attacks originates from Iran Therefore the aim of the present study was to assess opium addiction as a probable influencing factor for ischemic heart disease and ischemic stroke. A cross-sectional study was carried out in two Cardiology and Neurology clinics in Eastern Iran in 2011. Diagnosis of Ischemic Heart Disease (IHD) and Ischemic Stroke (IS) was made by Cardiologist and Stroke Neurologist respectively. The influence of gender, hypertension, diabetes, hyperlipidemia, cigarette smoking, oral and inhaled opium consumption on distribution of IHD and IS were evaluated. Five hundred fifty eight patients (307 females, 251 males) with mean age 56.2 years enrolled the study. On adjusted odds ratios of our whole 558 patients, only hypertension and diabetes had a significant influence on occurrence of IHD; (P = 0.000 and P = 0.000) respectively. Oral and inhaled routes of opium addiction did not have a significant effect on occurrence of IHD; [OR = 1.172, 95% CI = 0.624-2.203, P = 0.621] and [OR = 1.820, 95% CI = 0.811-4.085, P = 0.147] respectively. Hypertension and diabetes were significant risk factors of IS in our 558 patients at multivariate analysis; (P = 0.000, P = 0.020). Oral opium addiction was as significant protective factor of IS in our study group; OR = 0.211, 95% CI = 0.079-0.564, P = 0.002, while inhaled opium addiction did not have a significant effect on occurrence of IS in our patients at; OR = 1.760, 95% CI = 0.760-4.076, P = 0.187. Oral opium consumption is a protective factor of IS but not IHD. Inhaled opium addiction does not have a significant influence on occurrence of IS and IHD.

  5. Hyperglycemia and diabetes have different impacts on outcome of ischemic and hemorrhagic stroke.

    Science.gov (United States)

    Snarska, Katarzyna K; Bachórzewska-Gajewska, Hanna; Kapica-Topczewska, Katarzyna; Drozdowski, Wiesław; Chorąży, Monika; Kułakowska, Alina; Małyszko, Jolanta

    2017-02-01

    Stroke is the second leading cause of long-term disability and death worldwide. Diabetes and hyperglycemia may impact the outcome of stroke. We examined the impact of hyperglycemia and diabetes on in-hospital death among ischemic and hemorrhagic stroke patients. Data from 766 consecutive patients with ischemic (83.15%) and hemorrhagic stroke were analyzed. Patients were classified into four groups: ischemic and diabetic; ischemic and non-diabetic; hemorrhagic and diabetic; and hemorrhagic and non-diabetic. Serum glucose was measured on admission at the emergency department together with biochemical and clinical parameters. Mean admission glucose in ischemic stroke patients with diabetes was higher than in non-diabetic ones ( p hemorrhagic stroke patients with diabetes than in those without diabetes ( p stroke and without diabetes were age, admission glucose level and estimated glomerular filtration rate (eGFR), while in diabetics they were female gender, admission glucose level, and eGFR; in patients with hemorrhagic stroke and without diabetes they were age and admission glucose levels. The cut-off value in predicting death in patients with ischemic stroke and without diabetes was above 113.5 mg/dl, while in diabetics it was above 210.5 mg/dl. Hyperglycemia on admission is associated with worsened clinical outcome and increased risk of in-hospital death in ischemic and hemorrhagic stroke patients. Diabetes increased the risk of in-hospital death in hemorrhagic stroke patients, but not in ischemic ones.

  6. Pathophysiology and Biomarkers in Acute Ischemic Stroke – A Review

    African Journals Online (AJOL)

    The pathophysiology of ischemic stroke is complex, and majorly involves excitotoxicity, oxidative stress, inflammation, blood-brain barrier dysfunction, apoptosis, etc. Several of the biomarkers are related to these pathophysiologic mechanisms and they may have applications in stroke prediction, diagnosis, assessment, ...

  7. Computer-aided diagnosis of acute ischemic stroke based on cerebral hypoperfusion using 4D CT angiography

    Science.gov (United States)

    Charbonnier, Jean-Paul; Smit, Ewoud J.; Viergever, Max A.; Velthuis, Birgitta K.; Vos, Pieter C.

    2013-02-01

    The presence of collateral blood flow is found to be a strong predictor of patient outcome after acute ischemic stroke. Collateral blood flow is defined as an alternative way to provide oxygenated blood to ischemic cerebral tissue. Assessment of collateral blood supply is currently performed by visual inspection of a Computed Tomography Angiogram (CTA) which introduces inter-observer variability and depends on the grading scale. Furthermore, variations in the arterial contrast arrival time may lead to underestimation of collateral blood supply in a CTA which exerts a negative influence on the prediction of patient outcome. In this study, the feasibility of a Computer-aided Diagnosis system is investigated capable of objectively predicting patient outcome. We present a novel automatic method for quantitative assessment of cerebral hypoperfusion in timing-invariant (i.e. delay insensitive) CTA (TI-CTA). The proposed Vessel Density Symmetry algorithm automatically generates descriptive maps based on hemispheric asymmetry of blood vessels. Intensity and symmetry based features are extracted from these descriptive maps and subjected to a best-first-search feature selection. Linear Discriminant Analysis is performed to combine selected features into a likelihood of good patient outcome. Receiver operating characteristic (ROC) analysis is conducted to evaluate the diagnostic performance of the CAD by leave-one- patient-out cross validation. A Positive Predicting Value of 1 was obtained at a sensitivity of 25% with an area under the ROC-curve of 0.86. The results show that the CAD is feasible to objectively predict patient outcome. The presented CAD could make an important contribution to acute ischemic stroke diagnosis and treatment.

  8. Preoperative Three-Dimensional Valve Analysis Predicts Recurrent Ischemic Mitral Regurgitation After Mitral Annuloplasty

    NARCIS (Netherlands)

    Bouma, Wobbe; Lai, Eric K.; Levack, Melissa M.; Shang, Eric K.; Pouch, Alison M.; Eperjesi, Thomas J.; Plappert, Theodore J.; Yushkevich, Paul A.; Mariani, Massimo A.; Khabbaz, Kamal R.; Gleason, Thomas G.; Mahmood, Feroze; Acker, Michael A.; Woo, Y. Joseph; Cheung, Albert T.; Jackson, Benjamin M.; Gorman, Joseph H.; Gorman, Robert C.

    Background. Valve repair for ischemic mitral regurgitation (IMR) with undersized annuloplasty rings is characterized by high IMR recurrence rates. Patient-specific preoperative imaging-based risk stratification for recurrent IMR would optimize results. We sought to determine if prerepair

  9. Risk factors, mortality, and timing of ischemic and hemorrhagic stroke with left ventricular assist devices.

    Science.gov (United States)

    Frontera, Jennifer A; Starling, Randall; Cho, Sung-Min; Nowacki, Amy S; Uchino, Ken; Hussain, M Shazam; Mountis, Maria; Moazami, Nader

    2017-06-01

    Stroke is a major cause of mortality after left ventricular assist device (LVAD) placement. Prospectively collected data of patients with HeartMate II (n = 332) and HeartWare (n = 70) LVADs from October 21, 2004, to May 19, 2015, were reviewed. Predictors of early (during index hospitalization) and late (post-discharge) ischemic and hemorrhagic stroke and association of stroke subtypes with mortality were assessed. Of 402 patients, 83 strokes occurred in 69 patients (17%; 0.14 events per patient-year [EPPY]): early ischemic stroke in 18/402 (4%; 0.03 EPPY), early hemorrhagic stroke in 11/402 (3%; 0.02 EPPY), late ischemic stroke in 25/402 (6%; 0.04 EPPY) and late hemorrhagic stroke in 29/402 (7%; 0.05 EPPY). Risk of stroke and death among patients with stroke was bimodal with highest risks immediately post-implant and increasing again 9-12 months later. Risk of death declined over time in patients without stroke. Modifiable stroke risk factors varied according to timing and stroke type, including tobacco use, bacteremia, pump thrombosis, pump infection, and hypertension (all p hemorrhagic stroke (adjusted odds ratio [aOR] 4.3, 95% confidence interval [CI] 1.0-17.8, p = 0.04), late ischemic stroke (aOR 3.2, 95% CI 1.1-9.0, p = 0.03), and late hemorrhagic stroke (aOR 3.7, 95% CI 1.5-9.2, p = 0.005) predicted death, whereas early ischemic stroke did not. Stroke is a leading cause and predictor of death in patients with LVADs. Risk of stroke and death among patients with stroke is bimodal, with highest risk at time of implant and increasing risk again after 9-12 months. Management of modifiable risk factors may reduce stroke and mortality rates. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  10. Can We Predict Functional Outcome in Neonates with Hypoxic Ischemic Encephalopathy by the Combination of Neuroimaging and Electroencephalography?

    Science.gov (United States)

    Nanavati, Tania; Seemaladinne, Nirupama; Regier, Michael; Yossuck, Panitan; Pergami, Paola

    2015-01-01

    Background Neonatal hypoxic ischemic encephalopathy (HIE) is a major cause of mortality, morbidity, and long-term neurological deficits. Despite the availability of neuroimaging and neurophysiological testing, tools for accurate early diagnosis and prediction of developmental outcome are still lacking. The goal of this study was to determine if combined use of magnetic resonance imaging (MRI) and electroencephalography (EEG) findings could support outcome prediction. Methods We retrospectively reviewed records of 17 HIE neonates, classified brain MRI and EEG findings based on severity, and assessed clinical outcome up to 48 months. We determined the relation between MRI/EEG findings and clinical outcome. Results We demonstrated a significant relationship between MRI findings and clinical outcome (Fisher’s exact test, p = 0.017). EEG provided no additional information about the outcome beyond that contained in the MRI score. The statistical model for outcome prediction based on random forests suggested that EEG readings at 24 hours and 72 hours could be important variables for outcome prediction, but this needs to be investigated further. Conclusion Caution should be used when discussing prognosis for neonates with mild-to-moderate HIE based on early MR imaging and EEG findings. A robust, quantitative marker of HIE severity that allows for accurate prediction of long-term outcome, particularly for mild-to-moderate cases, is still needed. PMID:25862075

  11. Cardiac rehabilitation improves the ischemic burden in patients with ischemic heart disease who are not suitable for revascularization

    Energy Technology Data Exchange (ETDEWEB)

    El Demerdash, Salah [Department of Cardiology, Ain Shams University Hospital, Cairo (Egypt); Khorshid, Hazem, E-mail: hazemkhorshid@yahoo.com [Department of Cardiology, Ain Shams University Hospital, Cairo (Egypt); Salah, Iman; Abdel-Rahman, Mohamed A. [Department of Cardiology, Ain Shams University Hospital, Cairo (Egypt); Salem, Alaa M. [Department of Internal Medicine, Medical Division, National Research Centre, Cairo (Egypt)

    2015-07-15

    Background: Ischemic heart diseases including stable angina & acute events, represent a huge burden on both the individual & the society and represent an important source of disability. Aim: We aimed to identify the effect of cardiac rehabilitation program (CRP) on the ischemic burden in patients with ischemic heart disease (IHD) unsuitable for coronary revascularization. Methods: The study included 40 patients with IHD who were not suitable for coronary revascularization either by PCI or CABG (due to unsuitable coronary anatomy, co morbidities, high surgical/procedural risk or patient preference). All patients were subjected to sophisticated CRP protocols, including patient education, nutritional, medical, psychological and sexual counseling and group smoking cessation. All patients participated in low intensity exercise program twice weekly. The patient’s symptoms, vitals and medications were evaluated at each visit and clinical and laboratory data, echocardiography and stress myocardial perfusion imaging (SPECT) were evaluated before and 3 months after the end of the study. Results: The mean age was 56.8 ± 3.1 years and only 2 patients (5%) were females. 22 (55%) patients were diabetic, 21 (53%) were hypertensive and 30 (75%) were smokers. It was found that 3 months after completion of CRP, there was a significant decrease in BMI (30.3 ± 2.9 vs. 31.2 ± 1.9, p < 0.001), and mean blood pressure (93.4 ± 11 vs. 105 ± 10.6 mmHg, p < 0.001). There was also a favorable effect on lipid profile and a significant improvement of the functional capacity in terms of NYHA functional class (2.1 ± 0.62 vs. 1.4 ± 0.6, p < 0.001). Despite that wall motion score index did not significantly change after CRP, there was a strong trend toward a better ejection fraction (53.7 ± 7.8 vs. 54.5 ± 6.3 %, p = 0.06) and significant improvement of Canadian cardiovascular class (1.42 ± 0.6 vs. 1.95 ± 0.5, p < 0.001) post CRP. Importantly, the difference between the SPECT

  12. Cardiac rehabilitation improves the ischemic burden in patients with ischemic heart disease who are not suitable for revascularization

    International Nuclear Information System (INIS)

    El Demerdash, Salah; Khorshid, Hazem; Salah, Iman; Abdel-Rahman, Mohamed A.; Salem, Alaa M.

    2015-01-01

    Background: Ischemic heart diseases including stable angina & acute events, represent a huge burden on both the individual & the society and represent an important source of disability. Aim: We aimed to identify the effect of cardiac rehabilitation program (CRP) on the ischemic burden in patients with ischemic heart disease (IHD) unsuitable for coronary revascularization. Methods: The study included 40 patients with IHD who were not suitable for coronary revascularization either by PCI or CABG (due to unsuitable coronary anatomy, co morbidities, high surgical/procedural risk or patient preference). All patients were subjected to sophisticated CRP protocols, including patient education, nutritional, medical, psychological and sexual counseling and group smoking cessation. All patients participated in low intensity exercise program twice weekly. The patient’s symptoms, vitals and medications were evaluated at each visit and clinical and laboratory data, echocardiography and stress myocardial perfusion imaging (SPECT) were evaluated before and 3 months after the end of the study. Results: The mean age was 56.8 ± 3.1 years and only 2 patients (5%) were females. 22 (55%) patients were diabetic, 21 (53%) were hypertensive and 30 (75%) were smokers. It was found that 3 months after completion of CRP, there was a significant decrease in BMI (30.3 ± 2.9 vs. 31.2 ± 1.9, p < 0.001), and mean blood pressure (93.4 ± 11 vs. 105 ± 10.6 mmHg, p < 0.001). There was also a favorable effect on lipid profile and a significant improvement of the functional capacity in terms of NYHA functional class (2.1 ± 0.62 vs. 1.4 ± 0.6, p < 0.001). Despite that wall motion score index did not significantly change after CRP, there was a strong trend toward a better ejection fraction (53.7 ± 7.8 vs. 54.5 ± 6.3 %, p = 0.06) and significant improvement of Canadian cardiovascular class (1.42 ± 0.6 vs. 1.95 ± 0.5, p < 0.001) post CRP. Importantly, the difference between the SPECT

  13. EVALUATION OF EARLY ISCHEMIC CHANGES IN STROKE PATIENTS TREATED WITH THROMBOLYTIC THERAPY

    OpenAIRE

    Kolevski Goran; Korneti-Pekevska Kostandina

    2016-01-01

    Introduction:The aim of this study is to evaluate early brain ischemic changes on CT scan in stroke patients in correlation with the clinical outcome, as well as to evaluate if there is prognostic and predictive features that can be used. Patients and methods: We examined 20 patients with acute ischemic stroke, from which 12 were male and 8 were female, at the age from 47 to 76 years. Results: The hyperdense medial artery (HMA) sign was present in 10 (50%) patients. Concerning the ASPECTS s...

  14. Absence of robust ischemic preconditioning by five 1-minute total umbilical cord occlusions in fetal sheep.

    NARCIS (Netherlands)

    Lotgering, F.K.; Bishai, J.M.; Struijk, P.C.; Blood, A.B.; Hunter, C.J.; Oberg, K.C.; Power, G.G.; Longo, L.D.

    2004-01-01

    OBJECTIVE: To determine to what extent a series of five 1-minute total umbilical cord occlusions, intended to induce ischemic preconditioning (IP), affects the physiologic responses to a 10-minute total umbilical cord occlusion (damaging insult [DI]) 1 hour later and provides cardio- and

  15. Usefulness of perfusion MR imaging in hyperacute ischemic stroke

    International Nuclear Information System (INIS)

    Park, Ji Hoon; Kim, Jae Hyoung; Shin, Tae Min; Lee, Eun Ja; Chung, Sung Hoon; Choi, Nack Cheon; Lim, Byeong Hoon; Kim, In One

    1998-01-01

    Perfusion MR imaging is a new technique for the assessment of acute ischemic stroke. The aim of this study was to evaluate the usefulness of this imaging in hyperacute ischemic stroke in comparison with conventional CT and MR imaging. Eight patients presenting the symptoms of acute ischemic stroke due to middle cerebral artery occlusion were included in this study. Within 2 hours of initial CT scan and 6 hours after the onset of stroke, perfusion MR imaging was performed in all patients using a single-section dynamic contrast-enhanced T2*-weighted imager in conjunction with conventional routine MR imaging and MR angiography. Cerebral blood volume (CBV) maps were then obtained from dynamic MR imaging data by using numerical integration techniques. The findings of CBV maps were compared with those of initial and follow-up CT or MR images. The findings of CBV maps were obviously abnormal in all patients, as compared with normal or focal subtle abnormal findings seen on initial CT and MR images. CBV in the occluded arterial territory was lower in all eight patients;two had focal regions of increased CBV within the affected territory, indicating reperfusion hyperemia. In all patients, regions of abnormal CBV were eventually converted to infarctions on follow-up images. Perfusion MR imaging was useful for the evaluation of hemodynamic change occurring during cerebral perfusion in hyperacute ischemic stroke, and prediction of the final extent of infarction. These results suggest that pertusion MR imaging can play an important role in the diagnosis and management of hyperacute ischemic stroke.=20

  16. Plasma Magnesium and the Risk of Ischemic Stroke among Women

    Science.gov (United States)

    Akarolo-Anthony, Sally N.; Jiménez, Monik C.; Chiuve, Stephanie E.; Spiegelman, Donna; Willett, Walter C.; Rexrode, Kathryn M.

    2014-01-01

    Background and Purpose Lower plasma magnesium levels may be associated with higher blood pressure and endothelial dysfunction, but sparse prospective data are available for stroke. Methods Among 32,826 participants in the Nurses’ Health Study who provided blood samples in 1989–1990, incident ischemic strokes were identified and confirmed by medical records through 2006. We conducted a nested case-control analysis of 459 cases, matched 1:1 to controls on age, race/ethnicity, smoking status, date of blood draw, fasting status, menopausal status and hormone use. We used conditional logistic regression models to estimate the multivariable adjusted association of plasma magnesium and the risk of ischemic stroke and ischemic stroke subtypes. Results Median magnesium levels did not differ between ischemic stroke cases and controls (median=0.86 mmol/l for both; p-value=0.14). Conditional on matching factors, women in the lowest magnesium quintile had a relative risk (RR) of 1.34 (95% confidence interval [CI]: 0.86–2.10, p trend=0.13) for total ischemic stroke, compared to women in the highest quintile. Additional adjustment for risk factors and confounders did not substantially alter the risk estimates for total ischemic stroke. Women with magnesium levels magnesium levels ≥0.82 mmol/l. No significant effect modification was observed by age, body mass index, hypertension or diabetes. Conclusions Lower plasma magnesium levels may contribute to higher risk of ischemic stroke among women. PMID:25116874

  17. Cerebral ischemic stroke: is gender important?

    Science.gov (United States)

    Gibson, Claire L

    2013-09-01

    Cerebral stroke continues to be a major cause of death and the leading cause of long-term disability in developed countries. Evidence reviewed here suggests that gender influences various aspects of the clinical spectrum of ischemic stroke, in terms of influencing how a patients present with ischemic stroke through to how they respond to treatment. In addition, this review focuses on discussing the various pathologic mechanisms of ischemic stroke that may differ according to gender and compares how intrinsic and hormonal mechanisms may account for such gender differences. All clinical trials to date investigating putative neuroprotective treatments for ischemic stroke have failed, and it may be that our understanding of the injury cascade initiated after ischemic injury is incomplete. Revealing aspects of the pathophysiological consequences of ischemic stroke that are gender specific may enable gender relevant and effective neuroprotective strategies to be identified. Thus, it is possible to conclude that gender does, in fact, have an important role in ischemic stroke and must be factored into experimental and clinical investigations of ischemic stroke.

  18. Serum C-reactive protein concentration and genotype in relation to ischemic stroke subtype.

    Science.gov (United States)

    Ladenvall, Claes; Jood, Katarina; Blomstrand, Christian; Nilsson, Staffan; Jern, Christina; Ladenvall, Per

    2006-08-01

    C-reactive protein (CRP) has evolved as an inflammatory risk marker of cardiovascular disease. Several single-nucleotide polymorphisms at the CRP locus have been found to be associated with CRP levels. The aim of the present study was to investigate CRP levels and genetic variants in etiological subtypes of ischemic stroke. The Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) comprises 600 consecutive ischemic stroke cases (18 to 69 years) and 600 matched controls from western Sweden. Stroke subtypes were defined by the TOAST classification. Serum CRP levels were determined by a high-sensitivity immunometric assay. CRP levels were significantly higher for all ischemic stroke subtypes compared with controls, both in the acute phase and at the 3-month follow-up. After adjustment for traditional risk factors, CRP at follow-up was related to higher odds ratios (ORs) of overall ischemic stroke (OR, 1.25; 95% CI, 1.09 to 1.43) and large-vessel disease (OR, 1.48; 95% CI, 1.09 to 2.00). The CRP -286C>T>A, 1059G>C, and 1444C>T single-nucleotide polymorphisms showed significant associations with CRP levels. However, neither CRP genotypes nor haplotypes showed an association to overall ischemic stroke. This is the first large study on CRP in different TOAST subtypes in a young ischemic stroke population. CRP levels differed between etiological subtypes of ischemic stroke both in the acute phase and at the 3-month follow-up. CRP at follow-up was associated with overall ischemic stroke and the large-vessel disease subtype. Genetic variants at the CRP locus were associated with CRP levels, but no association was detected for overall ischemic stroke.

  19. Usefulness of colonoscopy in ischemic colitis.

    Science.gov (United States)

    Lozano-Maya, M; Ponferrada-Díaz, A; González-Asanza, C; Nogales-Rincón, O; Senent-Sánchez, C; Pérez-de-Ayala, V; Jiménez-Aleixandre, P; Cos-Arregui, E; Menchén-Fernández-Pacheco, P

    2010-07-01

    the ischemic colitis is intestinal the most frequent cause of ischemia. With this work we determine the demographic and clinical characteristics, and the usefulness of the colonoscopy in the patients with ischemic colitis diagnosed in our centre in relation to a change of therapeutic attitude. retrospective study in which were selected 112 patients diagnosed with ischemic colitis by colonoscopy and biopsy, in a period of five years. It was analyzed: age, sex, reason for examination, factors of cardiovascular risk, endoscopic degree of ischemia, change in the therapeutic attitude, treatment and outcome. the average age was of 73.64 + or - 12.10 years with an equal incidence in women (50.9%) and the men (49.1%). The associated factors were the HTA (61.1%), tobacco (37.2%) and antecedents of cardiovascular episode (52.2%). The most frequent reason for colonoscopy was rectorrhagia (53.6%) followed of the abdominal pain (30.4%), being urgent the 65.3%. Colonoscopy allowed a change in the therapeutic attitude in the 50 increasing in the urgent one to the 65.75%. Global mortality was of 27.67%. The serious ischemic colitis (25%) was more frequent in men (64.3%) in urgent indication (85.71%) and attends with high mortality (53.57%). Surgical treatment in the 57.14% was made with a good evolution in the 50%, whereas the patients with mild or moderate ischemic colitis had a better prognosis (favourable evolution in 80.95%) with smaller requirement of the surgical treatment (4.76%), p change of attitude according to the result of the same one. The evidence of a serious colitis supposed an increase of the necessity of surgery and worse prognosis.

  20. Fasting and non-fasting triglycerides and risk of ischemic cardiovascular disease in Japanese men and women: the Circulatory Risk in Communities Study (CIRCS).

    Science.gov (United States)

    Iso, Hiroyasu; Imano, Hironori; Yamagishi, Kazumasa; Ohira, Tetsuya; Cui, Renzhe; Noda, Hiroyuki; Sato, Shinichi; Kiyama, Masahiko; Okada, Takeo; Hitsumoto, Shinichi; Tanigawa, Takeshi; Kitamura, Akihiko

    2014-11-01

    Non-fasting triglycerides were reported to have a greater impact on risk of ischemic cardiovascular events than fasting triglycerides. However, evidence from Asia, where the prevalence of dyslipidemia is generally lower, has been limited. We used 1975-1986 baseline surveys to investigate cohort data of 10,659 (4264 men and 6395 women) residents aged 40-69 years, initially free from ischemic heart disease and stroke, in four Japanese communities. Serum triglyceride concentrations at baseline were obtained for 2424 fasting (≥8 h after meal) and 8235 non-fasting (triglycerides were 1.71 (1.14-2.59), P for trend = 0.013, for fasting participants and 1.60 (1.25-2.05), P for trend triglycerides are predictive of risk of ischemic cardiovascular disease for Japanese men, as are non-fasting triglycerides for women. Copyright © 2014. Published by Elsevier Ireland Ltd.

  1. Fatigue, General Health, and Ischemic Heart Disease in Older Adults

    DEFF Research Database (Denmark)

    Ekmann, Anette; Petersen, Inge; Mänty, Minna Regina

    2013-01-01

    Backgrounds.Fatigue has been shown to predict ischemic heart disease (IHD) and mortality in nonsmoking middle-aged men free of cardiovascular disease. The aim of this study was to investigate the predictive value of fatigue for IHD and general health in nondisabled individuals free...... of cardiovascular disease and older than 70 years. METHODS: The study population was drawn from The Longitudinal Study of Aging Danish Twins. In total, 1,696 participants were followed up for 2-10 years by questionnaires and 10-16 years through registries. Kaplan Meier, Cox Proportional Hazard and logistic.......08-2.00) compared with participants without fatigue. CONCLUSION: We concluded that fatigue in nondisabled older adults free of cardiovascular disease is an early predictor for development of subsequent poor general health and IHD....

  2. Discrimination of acute ischemic stroke from nonischemic vertigo in patients presenting with only imbalance.

    Science.gov (United States)

    Honda, Shoji; Inatomi, Yuichiro; Yonehara, Toshiro; Hashimoto, Yoichiro; Hirano, Teruyuki; Ando, Yukio; Uchino, Makoto

    2014-01-01

    Some patients who present with an acute feeling of imbalance are experiencing an ischemic stroke that is not evident on computed tomography (CT) scans. The aim of this study was to compare ischemic stroke and nonischemic vertigo patient groups and to investigate independent factors associated with ischemic stroke. We examined 332 consecutive patients with an acute feeling of imbalance who showed no neurologic findings or responsible lesions on CT scan at the hyperacute phase. We examined their clinical backgrounds, physical findings, and laboratory examinations, with ischemic stroke diagnosed by later CT and/or magnetic resonance imaging (MRI). We identified 41 (12.3%) ischemic stroke patients. Atrial fibrillation (odds ratio 4.1; 95% confidence interval 1.4-11.5), white blood cell count (10(3)/μL, 1.4; 1.2-1.6), head and/or neck pain (4.6; 2.1-10.3), first attack of imbalance feeling (3.3; 1.1-12.2), and dizziness (3.7; 1.7-8.3) were significant and independent factors associated with ischemic stroke among patients with an acute feeling of imbalance. We used these factors to calculate an "imbalance score"; 1 point was given for the presence of each factor and a score of 3-5 points was independently associated with ischemic stroke. An awareness of these factors may indicate that further examinations including MRI are necessary to rule out ischemic stroke. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  3. Prominent deep medullary veins: a predictive biomarker for stroke risk from transient ischemic attack?

    Science.gov (United States)

    Duan, Yang; Xu, Zhihua; Li, Hongyi; Cai, Xiaonan; Chang, Cancan; Yang, Benqiang

    2018-05-01

    Background Deep medullary veins (DMVs) are a biomarker of severity and prognosis in patients with acute cerebral infarction. However, their clinical significance remains unclear in patients with transient ischemic attack (TIA). Purpose To determine whether prominent deep medullary veins (PDMVs) are a predictive biomarker for stroke risk after TIA. Material and Methods Clinical and imaging data of 49 patients with TIA and 49 sex- and age-matched controls were studied. PDMVs were defined as DMVs with a score of 3 (TDMVs) or asymmetric DMVs (ADMVs), and the relationship between PDMVs and clinical features was analyzed. The DMV score based on susceptibility weighted imaging (SWI) ranged from 0 (not visible) to 3 (very prominent) and was calculated for both hemispheres separately. A different score in each hemisphere was defined as ADMVs and an equal score was defined as symmetric DMVs. The asymmetry and score of DMVs were compared between the two groups and with respect to the time from TIA onset to imaging analysis. Results Agreement between neuroradiologists for the DMV asymmetry/score on SWI was excellent. The frequency of ADMVs and TDMVs was significantly higher in patients with TIA than controls ( P  0.05); PDMVs were not correlated with age, blood pressure, or diabetes. However, PDMVs were associated with the ABCD2 score (≥4), clinical symptoms, and duration of TIA (≥10 min). Conclusion Prominent deep medullary veins is a predictive biomarker for the risk of stroke in many patients having suffered from TIA.

  4. Presence of diabetic microvascular complications does not incrementally increase risk of ischemic stroke in diabetic patients with atrial fibrillation

    Science.gov (United States)

    Chou, Annie Y.; Liu, Chia-Jen; Chao, Tze-Fan; Wang, Kang-Ling; Tuan, Ta-Chuan; Chen, Tzeng-Ji; Chen, Shih-Ann

    2016-01-01

    Abstract Conventional stroke risk prediction tools used in atrial fibrillation (AF) incorporate the presence of diabetes mellitus (DM) as a risk factor. However, it is unknown whether this risk is homogenous or dependent on the presence of diabetic microvascular complications, such as diabetic retinopathy, nephropathy, and neuropathy. The present study examined the risk of ischemic stroke in diabetic patients with and without microvascular complications. The present study used the National Health Insurance Research Database in Taiwan with detailed healthcare data on all-comers to the Taiwanese medical system from January 1, 1996 to December 31, 2011. AF and DM were identified when listed as discharge diagnoses or confirmed more than twice in the outpatient department. Patients on antithrombotic agents were excluded. The clinical endpoint was ischemic stroke. Among the 50,180 AF patients with DM, the majority had no microvascular complications (72.7%), while 2.6% had diabetic retinopathy, 8.4% had diabetic nephropathy, and 16.1% had diabetic neuropathy. Ischemic stroke occurred in 6003 patients, with a 4.74% annual risk of ischemic stroke. When compared with DM patients without microvascular complications, those with diabetic retinopathy, nephropathy, or neuropathy had higher incidences of ischemic stroke (4.65 vs 5.07, 4.77, or 5.20 per 100 person-years, respectively). However, after adjusting for confounding factors, the differences were no longer significant. In a large nationwide AF cohort with DM, risk of ischemic stroke was similar between patients with and without microvascular complications, suggesting that risk stratification of these patients does not require inclusion of diabetic retinopathy, nephropathy, and neuropathy. PMID:27399075

  5. The Siblings With Ischemic Stroke Study (SWISS Protocol

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    Hardy John

    2002-02-01

    Full Text Available Abstract Background Family history and twins studies suggest an inherited component to ischemic stroke risk. Candidate gene association studies have been performed but have limited capacity to identify novel risk factor genes. The Siblings With Ischemic Stroke Study (SWISS aims to conduct a genome-wide scan in sibling pairs concordant or discordant for ischemic stroke to identify novel genetic risk factors through linkage analysis. Methods Screening at multiple clinical centers identifies patients (probands with radiographically confirmed ischemic stroke and a family history of at least 1 living full sibling with stroke. After giving informed consent, without violating privacy among other family members, the proband invites siblings concordant and discordant for stroke to participate. Siblings then contact the study coordinating center. The diagnosis of ischemic stroke in potentially concordant siblings is confirmed by systematic centralized review of medical records. The stroke-free status of potentially discordant siblings is confirmed by validated structured telephone interview. Blood samples for DNA analysis are taken from concordant sibling pairs and, if applicable, from 1 discordant sibling. Epstein-Barr virus-transformed lymphoblastoid cell lines are created, and a scan of the human genome is planned. Discussion Conducting adequately powered genomics studies of stroke in humans is challenging because of the heterogeneity of the stroke phenotype and the difficulty of obtaining DNA samples from clinically well-characterized members of a cohort of stroke pedigrees. The multicentered design of this study is intended to efficiently assemble a cohort of ischemic stroke pedigrees without invoking community consent or using cold-calling of pedigree members.

  6. Abca12-mediated lipid transport and Snap29-dependent trafficking of lamellar granules are crucial for epidermal morphogenesis in a zebrafish model of ichthyosis

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    Qiaoli Li

    2011-11-01

    Zebrafish (Danio rerio can serve as a model system to study heritable skin diseases. The skin is rapidly developed during the first 5–6 days of embryonic growth, accompanied by expression of skin-specific genes. Transmission electron microscopy (TEM of wild-type zebrafish at day 5 reveals a two-cell-layer epidermis separated from the underlying collagenous stroma by a basement membrane with fully developed hemidesmosomes. Scanning electron microscopy (SEM reveals an ordered surface contour of keratinocytes with discrete microridges. To gain insight into epidermal morphogenesis, we have employed morpholino-mediated knockdown of the abca12 and snap29 genes, which are crucial for secretion of lipids and intracellular trafficking of lamellar granules, respectively. Morpholinos, when placed on exon-intron junctions, were >90% effective in preventing the corresponding gene expression when injected into one- to four-cell-stage embryos. By day 3, TEM of abca12 morphants showed accumulation of lipid-containing electron-dense lamellar granules, whereas snap29 morphants showed the presence of apparently empty vesicles in the epidermis. Evaluation of epidermal morphogenesis by SEM revealed similar perturbations in both cases in the microridge architecture and the development of spicule-like protrusions on the surface of keratinocytes. These morphological findings are akin to epidermal changes in harlequin ichthyosis and CEDNIK syndrome, autosomal recessive keratinization disorders due to mutations in the ABCA12 and SNAP29 genes, respectively. The results indicate that interference of independent pathways involving lipid transport in the epidermis can result in phenotypically similar perturbations in epidermal morphogenesis, and that these fish mutants can serve as a model to study the pathomechanisms of these keratinization disorders.

  7. Effects of Ischemic Preconditioning of Different Intraoperative Ischemic Times of Vascularized Bone Graft Rabbit Models

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    Ahmad Sukari Halim

    2013-11-01

    Full Text Available BackgroundIschemic preconditioning has been shown to improve the outcomes of hypoxic tolerance of the heart, brain, lung, liver, jejunum, skin, and muscle tissues. However, to date, no report of ischemic preconditioning on vascularized bone grafts has been published.MethodsSixteen rabbits were divided into four groups with ischemic times of 2, 6, 14, and 18 hours. Half of the rabbits in each group underwent ischemic preconditioning. The osteomyocutaneous flaps consisted of the tibia bone, from which the overlying muscle and skin were raised. The technique of ischemic preconditioning involved applying a vascular clamp to the pedicle for 3 cycles of 10 minutes each. The rabbits then underwent serial plain radiography and computed tomography imaging on the first, second, fourth, and sixth postoperative weeks. Following this, all of the rabbits were sacrificed and histological examinations were performed.ResultsThe results showed that for clinical analysis of the skin flaps and bone grafts, the preconditioned groups showed better survivability. In the plain radiographs, except for two non-preconditioned rabbits with intraoperative ischemic times of 6 hours, all began to show early callus formation at the fourth week. The computed tomography findings showed more callus formation in the preconditioned groups for all of the ischemic times except for the 18-hour group. The histological findings correlated with the radiological findings. There was no statistical significance in the difference between the two groups.ConclusionsIn conclusion, ischemic preconditioning improved the survivability of skin flaps and increased callus formation during the healing process of vascularized bone grafts.

  8. Arctigenin attenuates ischemic stroke via SIRT1-dependent inhibition of NLRP3 inflammasome.

    Science.gov (United States)

    Zhang, Shimeng; Jiang, Liangjun; Che, Fengyuan; Lu, Yucheng; Xie, Zhongxiang; Wang, Hao

    2017-11-04

    Arctigenin (ARC), a phenylpropanoid dibenzylbutyrolactone lignan derived from Arctium lappa L, has been reported to protect against cerebral ischemia injury in rats, but the underlying mechanism is unclear. In this study, we investigated whether ARC ameliorated ischemic stroke by inhibiting NLRP3 inflammasome-derived neuroinflammation and whether SIRT1 signaling was involved in this process. ARC (20 mg/kg) or vehicle were intraperitoneally injected to Sprague-Dawley rats for 3 days before middle cerebral artery occlusion (MCAO) surgery performed. The infarct volume, neurological score, brain water content, neuroinflammation, NLRP3 inflammasome activation and SIRT1 protein expression were assessed. Furthermore, we also investigated whether ARC protected against cerebral ischemia via SIRT1-dependent inhibition of NLRP3 inflammasome by administrating EX527, a specific SIRT1 inhibitor, under oxygen-glucose deprivation (OGD) condition. We found that ARC pretreatment decreased infarct volume, neurological score and brain water content. Moreover, ARC treatment effectively inhibited cerebral ischemia induced NLRP3 inflammasome activation and IL-1β, IL-18 secretion both in vivo and in vitro. Futhermore, ARC treatment activated Silent information regulator 1 (SIRT1) singnaling in the brain. Importantly, suppress of SIRT1 reversed the inhibitory effect of ARC on NLRP3 inflammasome activation. Taken together our results demonstrated that ARC may confer protection against ischemic stroke by inhibiting NLRP3 inflammasome activation. The activation of SIRT1 signaling pathway may contribute to the neuroprotection of ARC in MCAO. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Self-perceived psychological stress and ischemic stroke: a case-control study

    Directory of Open Access Journals (Sweden)

    Blomstrand Christian

    2009-10-01

    Full Text Available Abstract Background A growing body of evidence suggests that psychological stress contributes to coronary artery disease. However, associations between stress and stroke are less clear. In this study, we investigated the possible association between ischemic stroke and self-perceived psychological stress, as measured by a single-item questionnaire, previously reported to be associated with myocardial infarction. Methods In the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS, 600 consecutive patients with acute ischemic stroke (aged 18 to 69 years and 600 age-matched and sex-matched population controls were recruited. Ischemic stroke subtype was determined according to Trial of Org 10172 in Acute Stroke Treatment (TOAST criteria. Self-perceived psychological stress preceding stroke was assessed retrospectively using a single-item questionnaire. Results Permanent self-perceived psychological stress during the last year or longer was independently associated with overall ischemic stroke (multivariate adjusted odds ratio (OR 3.49, 95% confidence interval (CI 2.06 to 5.93. Analyses by stroke subtype showed that this association was present for large vessel disease (OR 3.91, 95% CI 1.58 to 9.67, small vessel disease (OR 3.20, 95% CI 1.64 to 6.24, and cryptogenic stroke (OR 4.03, 95% CI 2.34 to 6.95, but not for cardioembolic stroke (OR 1.48, 95% CI 0.64 to 3.39. Conclusion In this case-control study, we found an independent association between self-perceived psychological stress and ischemic stroke. A novel finding was that this association differed by ischemic stroke subtype. Our results emphasize the need for further prospective studies addressing the potential role for psychological stress as a risk factor for ischemic stroke. In such studies ischemic stroke subtypes should be taken into consideration.

  10. Diagnosis of acute ischemic stroke based on time-to-peak and diffusion-weighted magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Maruyama, Keisuke; Eguchi, Tsuneyoshi; Sora, Shigeo; Izumi, Masafumi; Hiyama, Hirofumi [Kameda General Hospital, Kamogawa, Chiba (Japan); Ueki, Keisuke [Tokyo Univ. (Japan). Hospital

    2002-07-01

    Rapid and accurate diagnosis of the hemodynamics of the brain is essential for the treatment of acute ischemic stroke. This study investigated whether time-to-peak and diffusion-weighted magnetic resonance (MR) imaging are useful for predicting the course of stroke. Fourteen patients with non-lacunar acute ischemic stroke underwent emergent MR imaging within 24 hours from the onset followed by cerebral angiography and xenon-enhanced computed tomography (CT). Serial CT was obtained to monitor changes in the size and nature of the infarct. Volumes of the abnormal lesions demonstrated on time-to-peak (V{sub T}) or diffusion-weighted (V{sub D}) images were measured, and the ratio of V{sub T} to V{sub D} was calculated. Based on this ratio, patients were classified into three groups: Group 1 (V{sub T}/V{sub D} 0.5-1.5, n=9), Group 2 (V{sub T}/V{sub D}>1.5, n=3), and Group 3 (V{sub T}/V{sub D}<0.5, n=2). The size of the infarct detected as a low-density area on serial CT scans did not change significantly throughout the course in Group 1 patients, but showed enlargement in all three patients in Group 2. Two patients in Group 3 had major trunk occlusion followed by spontaneous reperfusion, and both developed hemorrhagic transformation. Our study showed that classification of ischemic stroke based on the V{sub T}/V{sub D} ratio was predictive of the time course of the infarct, and may be useful in selecting the initial therapeutic procedure immediately after the onset of stroke. (author)

  11. Arctigenin promotes cholesterol efflux from THP-1 macrophages through PPAR-γ/LXR-α signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Xiaolin [Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200032 (China); Li, Qian [Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai (China); Pang, Liewen; Huang, Guoqian; Huang, Jiechun; Shi, Meng; Sun, Xiaotian [Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200032 (China); Wang, Yiqing [Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200032 (China)

    2013-11-15

    Highlights: •Arctigenin enhanced cholesterol efflux in oxLDL-loaded THP-1 macrophages. •The expression of ABCA1, ABCG1 and apoE was upregulated in arctigenin-treated cells. •Arctigenin promoted the expression of PPAR-γ and LXR-α. •Inhibition of PPAR-γ or LXR-α reversed arctigenin-mediated biological effects. •Arctigenin promotes cholesterol efflux via activation of PPAR-γ/LXR-α/ABCA1 pathway. -- Abstract: Cholesterol efflux from macrophages is a critical mechanism to prevent the development of atherosclerosis. Here, we sought to investigate the effects of arctigenin, a bioactive component of Arctium lappa, on the cholesterol efflux in oxidized low-density lipoprotein (oxLDL)-loaded THP-1 macrophages. Our data showed that arctigenin significantly accelerated apolipoprotein A-I- and high-density lipoprotein-induced cholesterol efflux in both dose- and time-dependent manners. Moreover, arctigenin treatment enhanced the expression of ATP binding cassette transporter A1 (ABCA1), ABCG1, and apoE, all of which are key molecules in the initial step of cholesterol efflux, at both mRNA and protein levels. Arctigenin also caused a concentration-dependent elevation in the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and liver X receptor-alpha (LXR-α). The arctigenin-mediated induction of ABCA1, ABCG1, and apoE was abolished by specific inhibition of PPAR-γ or LXR-α using small interfering RNA technology. Our results collectively indicate that arctigenin promotes cholesterol efflux in oxLDL-loaded THP-1 macrophages through upregulation of ABCA1, ABCG1 and apoE, which is dependent on the enhanced expression of PPAR-γ and LXR-α.

  12. Arctigenin promotes cholesterol efflux from THP-1 macrophages through PPAR-γ/LXR-α signaling pathway

    International Nuclear Information System (INIS)

    Xu, Xiaolin; Li, Qian; Pang, Liewen; Huang, Guoqian; Huang, Jiechun; Shi, Meng; Sun, Xiaotian; Wang, Yiqing

    2013-01-01

    Highlights: •Arctigenin enhanced cholesterol efflux in oxLDL-loaded THP-1 macrophages. •The expression of ABCA1, ABCG1 and apoE was upregulated in arctigenin-treated cells. •Arctigenin promoted the expression of PPAR-γ and LXR-α. •Inhibition of PPAR-γ or LXR-α reversed arctigenin-mediated biological effects. •Arctigenin promotes cholesterol efflux via activation of PPAR-γ/LXR-α/ABCA1 pathway. -- Abstract: Cholesterol efflux from macrophages is a critical mechanism to prevent the development of atherosclerosis. Here, we sought to investigate the effects of arctigenin, a bioactive component of Arctium lappa, on the cholesterol efflux in oxidized low-density lipoprotein (oxLDL)-loaded THP-1 macrophages. Our data showed that arctigenin significantly accelerated apolipoprotein A-I- and high-density lipoprotein-induced cholesterol efflux in both dose- and time-dependent manners. Moreover, arctigenin treatment enhanced the expression of ATP binding cassette transporter A1 (ABCA1), ABCG1, and apoE, all of which are key molecules in the initial step of cholesterol efflux, at both mRNA and protein levels. Arctigenin also caused a concentration-dependent elevation in the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and liver X receptor-alpha (LXR-α). The arctigenin-mediated induction of ABCA1, ABCG1, and apoE was abolished by specific inhibition of PPAR-γ or LXR-α using small interfering RNA technology. Our results collectively indicate that arctigenin promotes cholesterol efflux in oxLDL-loaded THP-1 macrophages through upregulation of ABCA1, ABCG1 and apoE, which is dependent on the enhanced expression of PPAR-γ and LXR-α

  13. Heme Oxygenase-1 Gene Therapy Provides Cardioprotection Via Control of Post-Ischemic Inflammation: An Experimental Study in a Pre-Clinical Pig Model.

    Science.gov (United States)

    Hinkel, Rabea; Lange, Philipp; Petersen, Björn; Gottlieb, Elena; Ng, Judy King Man; Finger, Stefanie; Horstkotte, Jan; Lee, Seungmin; Thormann, Michael; Knorr, Maike; El-Aouni, Chiraz; Boekstegers, Peter; Reichart, Bruno; Wenzel, Philip; Niemann, Heiner; Kupatt, Christian

    2015-07-14

    Heme oxygenase-1 (HO-1) is an inducible stress-responsive enzyme converting heme to bilirubin, carbon monoxide, and free iron, which exerts anti-inflammatory and antiapoptotic effects. Although efficient cardioprotection after HO-1 overexpression has been reported in rodents, its role in attenuating post-ischemic inflammation is unclear. This study assessed the efficacy of recombinant adenoassociated virus (rAAV)-encoding human heme oxygenase-1 (hHO-1) in attenuating post-ischemic inflammation in a murine and a porcine ischemia/reperfusion model. Murine ischemia was induced by 45 min of left anterior descending occlusion, followed by 24 h of reperfusion and functional as well as fluorescent-activated cell sorting analysis. Porcine hearts were subjected to 60 min of ischemia and 24h of reperfusion before hemodynamic and histologic analyses were performed. Human microvascular endothelial cells transfected with hHO-1 displayed an attenuated interleukin-6 and intercellular adhesion molecule 1 expression, resulting in reduced monocytic THP-1 cell recruitment in vitro. In murine left anterior descending occlusion and reperfusion, the post-ischemic influx of CD45(+) leukocytes, Ly-6G(+) neutrophils, and Ly-6C(high) monocytes was further exacerbated in HO-1-deficient hearts and reversed by rAAV.hHO-1 treatment. Conversely, in our porcine model of ischemia, the post-ischemic influx of myeloperoxidase-positive neutrophils and CD14(+) monocytes was reduced by 49% and 87% after rAAV.hHO-1 transduction, similar to hHO-1 transgenic pigs. Functionally, rAAV.hHO-1 and hHO-1 transgenic left ventricles displayed a smaller loss of ejection fraction than control animals. Whereas HO-1 deficiency exacerbates post-ischemic cardiac inflammation in mice, hHO-1 gene therapy attenuates inflammation after ischemia and reperfusion in murine and porcine hearts. Regional hHO-1 gene therapy provides cardioprotection in a pre-clinical porcine ischemia/reperfusion model. Copyright © 2015 American

  14. Polymorphisms in adenosine receptor genes are associated with infarct size in patients with ischemic cardiomyopathy.

    Science.gov (United States)

    Tang, Z; Diamond, M A; Chen, J-M; Holly, T A; Bonow, R O; Dasgupta, A; Hyslop, T; Purzycki, A; Wagner, J; McNamara, D M; Kukulski, T; Wos, S; Velazquez, E J; Ardlie, K; Feldman, A M

    2007-10-01

    The goal of this experiment was to identify the presence of genetic variants in the adenosine receptor genes and assess their relationship to infarct size in a population of patients with ischemic cardiomyopathy. Adenosine receptors play an important role in protecting the heart during ischemia and in mediating the effects of ischemic preconditioning. We sequenced DNA samples from 273 individuals with ischemic cardiomyopathy and from 203 normal controls to identify the presence of genetic variants in the adenosine receptor genes. Subsequently, we analyzed the relationship between the identified genetic variants and infarct size, left ventricular size, and left ventricular function. Three variants in the 3'-untranslated region of the A(1)-adenosine gene (nt 1689 C/A, nt 2206 Tdel, nt 2683del36) and an informative polymorphism in the coding region of the A3-adenosine gene (nt 1509 A/C I248L) were associated with changes in infarct size. These results suggest that genetic variants in the adenosine receptor genes may predict the heart's response to ischemia or injury and might also influence an individual's response to adenosine therapy.

  15. Alberta Stroke Program Early CT Score-Time Score Predicts Outcome after Endovascular Therapy in Patients with Acute Ischemic Stroke: A Retrospective Single-Center Study.

    Science.gov (United States)

    Todo, Kenichi; Sakai, Nobuyuki; Kono, Tomoyuki; Hoshi, Taku; Imamura, Hirotoshi; Adachi, Hidemitsu; Yamagami, Hiroshi; Kohara, Nobuo

    2018-04-01

    Clinical outcomes after successful endovascular therapy in patients with acute ischemic stroke are associated with several factors including onset-to-reperfusion time (ORT), the National Institute of Health Stroke Scale (NIHSS) score, and the Alberta Stroke Program Early CT Score (ASPECTS). The NIHSS-time score, calculated as follows: [NIHSS score] × [onset-to-treatment time (h)] or [NIHSS score] × [ORT (h)], has been reported to predict clinical outcomes after intravenous recombinant tissue plasminogen activator therapy and endovascular therapy for acute stroke. The objective of the current study was to assess whether the combination of the ASPECTS and the ORT can predict the outcomes after endovascular therapy. The charts of 117 consecutive ischemic stroke patients with successful reperfusion after endovascular therapy were retrospectively reviewed. We analyzed the association of ORT, ASPECTS, and ASPECTS-time score with clinical outcome. ASPECTS-time score was calculated as follows: [11 - ASPECTS] × [ORT (h)]. Rates of good outcome for patients with ASPECTS-time scores of tertile values, scores 5.67 or less, scores greater than 5.67 to 10.40 or less, and scores greater than 10.40, were 66.7%, 56.4%, and 33.3%, respectively (P < .05). Ordinal logistic regression analysis showed that the ASPECTS-time score (per category increase) was an independent predictor for better outcome (common odds ratio: .374; 95% confidence interval: .150-0.930; P < .05). A lower ASPECTS-time score may predict better clinical outcomes after endovascular treatment. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. ATP-binding cassette subfamily A, member 4 intronic variants c.4773+3A>G and c.5461-10T>C cause Stargardt disease due to defective splicing.

    Science.gov (United States)

    Jonsson, Frida; Westin, Ida Maria; Österman, Lennart; Sandgren, Ola; Burstedt, Marie; Holmberg, Monica; Golovleva, Irina

    2018-02-20

    Inherited retinal dystrophies (IRDs) represent a group of progressive conditions affecting the retina. There is a great genetic heterogeneity causing IRDs, and to date, more than 260 genes are associated with IRDs. Stargardt disease, type 1 (STGD1) or macular degeneration with flecks, STGD1 represents a disease with early onset, central visual impairment, frequent appearance of yellowish flecks and mutations in the ATP-binding cassette subfamily A, member 4 (ABCA4) gene. A large number of intronic sequence variants in ABCA4 have been considered pathogenic although their functional effect was seldom demonstrated. In this study, we aimed to reveal how intronic variants present in patients with Stargardt from the same Swedish family affect splicing. The splicing of the ABCA4 gene was studied in human embryonic kidney cells, HEK293T, and in human retinal pigment epithelium cells, ARPE-19, using a minigene system containing variants c.4773+3A>G and c.5461-10T>C. We showed that both ABCA4 variants, c.4773+3A>G and c.5461-10T>C, cause aberrant splicing of the ABCA4 minigene resulting in exon skipping. We also demonstrated that splicing of ABCA4 has different outcomes depending on transfected cell type. Two intronic variants c.4773+3A>G and c.5461-10T>C, both predicted to affect splicing, are indeed disease-causing mutations due to skipping of exons 33, 34, 39 and 40 of ABCA4 gene. The experimental proof that ABCA4 mutations in STGD patients affect protein function is crucial for their inclusion to future clinical trials; therefore, functional testing of all ABCA4 intronic variants associated with Stargardt disease by minigene technology is desirable. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  17. It's All about Timing: The Involvement of Kir4.1 Channel Regulation in Acute Ischemic Stroke Pathology

    Directory of Open Access Journals (Sweden)

    Meagan Milton

    2018-02-01

    Full Text Available An acute ischemic stroke is characterized by the presence of a blood clot that limits blood flow to the brain resulting in subsequent neuronal loss. Acute stroke threatens neuronal survival, which relies heavily upon proper function of astrocytes. Neurons are more susceptible to cell death when an astrocyte is unable to carry out its normal functions in supporting the neuron in the area affected by the stroke (Rossi et al., 2007; Takano et al., 2009. For example, under normal conditions, astrocytes initially swell in response to changes in extracellular osmotic pressure and then reduce their regulatory volume in response to volume-activated potassium (K+ and chloride channels (Vella et al., 2015. This astroglial swelling may be overwhelmed, under ischemic conditions, due to the increased levels of glutamate and extracellular K+ (Lai et al., 2014; Vella et al., 2015. The increase in extracellular K+ contributes to neuronal damage and loss through the initiation of harmful secondary cascades (Nwaobi et al., 2016. Reducing the amount of extracellular K+ could, in theory, limit or prevent neuronal damage and loss resulting in an improved prognosis for individuals following ischemic stroke. Kir4.1, an inwardly rectifying K+ channel, has demonstrated an ability to regulate the rapid reuptake of this ion to return the cell to basal levels allowing it to fire again in rapid transmission (Sibille et al., 2015. Despite growing interest in this area, the underlying mechanism suggesting that neuroprotection could occur through modification of the Kir4.1 channel's activity has yet to be described. The purpose of this review is to examine the current literature and propose potential underlying mechanisms involving Kir4.1, specially the mammalian target of rapamycin (mTOR and/or autophagic pathways, in the pathogenesis of ischemic stroke. The hope is that this review will instigate further investigation of Kir4.1 as a modulator of stroke pathology.

  18. Intermittent fasting attenuates inflammasome activity in ischemic stroke.

    Science.gov (United States)

    Fann, David Yang-Wei; Santro, Tomislav; Manzanero, Silvia; Widiapradja, Alexander; Cheng, Yi-Lin; Lee, Seung-Yoon; Chunduri, Prasad; Jo, Dong-Gyu; Stranahan, Alexis M; Mattson, Mark P; Arumugam, Thiruma V

    2014-07-01

    Recent findings have revealed a novel inflammatory mechanism that contributes to tissue injury in cerebral ischemia mediated by multi-protein complexes termed inflammasomes. Intermittent fasting (IF) can decrease the levels of pro-inflammatory cytokines in the periphery and brain. Here we investigated the impact of IF (16h of food deprivation daily) for 4months on NLRP1 and NLRP3 inflammasome activities following cerebral ischemia. Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion (I/R). IF decreased the activation of NF-κB and MAPK signaling pathways, the expression of NLRP1 and NLRP3 inflammasome proteins, and both IL-1β and IL-18 in the ischemic brain tissue. These findings demonstrate that IF can attenuate the inflammatory response and tissue damage following ischemic stroke by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Post-ischemic bowel stricture: CT features in eight cases

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    Kim, Jin Sil [Dept. of Radiology, College of Medicine, Ewha Womans University, Mokdong Hospital, Seoul (Korea, Republic of); Kim, Hyun Jin; Hong, Sung Mo; Park, Seong Ho; Lee, Jong Seok; Kim, Ah Young; Ha, Hyun Kwon [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2017-11-15

    To investigate the characteristic radiologic features of post-ischemic stricture, which can then be implemented to differentiate that specific disease from other similar bowel diseases, with an emphasis on computed tomography (CT) features. Eight patients with a diagnosis of ischemic bowel disease, who were also diagnosed with post-ischemic stricture on the basis of clinical or pathologic findings, were included. Detailed clinical data was collected from the available electronic medical records. Two radiologists retrospectively reviewed all CT images. Pathologic findings were also analyzed. The mean interval between the diagnosis of ischemic bowel disease and stricture formation was 57 days. The severity of ischemic bowel disease was variable. Most post-ischemic strictures developed in the ileum (n = 5), followed by the colon (n = 2) and then the jejunum (n = 1). All colonic strictures developed in the “watershed zone.” The pathologic features of post-ischemic stricture were deep ulceration, submucosal/subserosal fibrosis and chronic transmural inflammation. The mean length of the post-ischemic stricture was 7.4 cm. All patients in this study possessed one single stricture. On contrast-enhanced CT, most strictures possessed concentric wall thickening (87.5%), with moderate enhancement (87.5%), mucosal enhancement (50%), or higher enhancement in portal phase than arterial phase (66.7%). Post-ischemic strictures develop in the ileum, jejunum and colon after an interval of several weeks. In the colonic segment, strictures mainly occur in the “watershed zone.” Typical CT findings include a single area of concentric wall thickening of medium length (mean, 7.4 cm), with moderate and higher enhancement in portal phase and vasa recta prominence.

  20. The predictive role of E/e' on ischemic stroke and atrial fibrillation in Japanese patients without atrial fibrillation.

    Science.gov (United States)

    Arai, Riku; Suzuki, Shinya; Semba, Hiroaki; Arita, Takuto; Yagi, Naoharu; Otsuka, Takayuki; Sagara, Koichi; Sasaki, Kenichi; Kano, Hiroto; Matsuno, Shunsuke; Kato, Yuko; Uejima, Tokuhisa; Oikawa, Yuji; Kunihara, Takashi; Yajima, Junji; Yamashita, Takeshi

    2018-07-01

    The predictive role of E/e' on ischemic stroke (IS) and atrial fibrillation (AF) in Japanese patients without AF are unclear. Shinken database includes all the new patients visiting the Cardiovascular Institute Hospital in Tokyo, Japan. E/e' has been routinely measured since 2007. Patients without AF for whom E/e' was measured at the initial visit between 2007 and 2014 (n=11 477, mean age 57.2 years old, men 59.5%) were divided into E/e' tertiles (11.00). During the mean follow-up period of 1.8 years, 58 IS and 140 new appearances of AF were observed. High E/e' tertile was associated with more prevalence of atherothrombotic risks. The cumulative incidence of IS events and new appearance of AF at 6 years in low, middle, and high E/e' tertiles were 0.5%, 1.4%, and 3.0%/year (log-rank test, pE/e' tertile was independently associated with IS (HR, 2.857, 95%CI 1.257-6.495, p=0.012). Although high E/e' tertile was independently associated with new appearance of AF when adjusted for coexistence of atherothrombotic risk factors (HR, 1.694, 95%CI, 1.097-2.616, p=0.017), the association was attenuated after adjustment for left atrial dimension. E/e' was significantly associated with incidence of IS and new appearance of AF in non-AF patients. Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  1. Smoking and Risk of Ischemic Stroke in Young Men.

    Science.gov (United States)

    Markidan, Janina; Cole, John W; Cronin, Carolyn A; Merino, Jose G; Phipps, Michael S; Wozniak, Marcella A; Kittner, Steven J

    2018-05-01

    There is a strong dose-response relationship between smoking and risk of ischemic stroke in young women, but there are few data examining this association in young men. We examined the dose-response relationship between the quantity of cigarettes smoked and the odds of developing an ischemic stroke in men under age 50 years. The Stroke Prevention in Young Men Study is a population-based case-control study of risk factors for ischemic stroke in men ages 15 to 49 years. The χ 2 test was used to test categorical comparisons. Logistic regression models were used to calculate the odds ratio for ischemic stroke occurrence comparing current and former smokers to never smokers. In the first model, we adjusted solely for age. In the second model, we adjusted for potential confounding factors, including age, race, education, hypertension, myocardial infarction, angina, diabetes mellitus, and body mass index. The study population consisted of 615 cases and 530 controls. The odds ratio for the current smoking group compared with never smokers was 1.88. Furthermore, when the current smoking group was stratified by number of cigarettes smoked, there was a dose-response relationship for the odds ratio, ranging from 1.46 for those smoking strong dose-response relationship between the number of cigarettes smoked daily and ischemic stroke among young men. Although complete smoking cessation is the goal, even smoking fewer cigarettes may reduce the risk of ischemic stroke in young men. © 2018 American Heart Association, Inc.

  2. Analysis of risk factors and risk assessment for ischemic stroke recurrence

    Directory of Open Access Journals (Sweden)

    Xiu-ying LONG

    2016-08-01

    Full Text Available Objective To screen the risk factors for recurrence of ischemic stroke and to assess the risk of recurrence. Methods Essen Stroke Risk Score (ESRS was used to evaluate the risk of recurrence in 176 patients with ischemic stroke (96 cases of first onset and 80 cases of recurrence. Univariate and multivariate stepwise Logistic regression analysis was used to screen risk factors for recurrence of ischemic stroke.  Results There were significant differences between first onset group and recurrence group on age, the proportion of > 75 years old, hypertension, diabetes, coronary heart disease, peripheral angiopathy, transient ischemic attack (TIA or ischemic stroke, drinking and ESRS score (P < 0.05, for all. First onset group included one case of ESRS 0 (1.04%, 8 cases of 1 (8.33%, 39 cases of 2 (40.63%, 44 cases of 3 (45.83%, 4 cases of 4 (4.17%. Recurrence group included 2 cases of ESRS 3 (2.50%, 20 cases of 4 (25% , 37 cases of 5 (46.25% , 18 cases of 6 (22.50% , 3 cases of 7 (3.75% . There was significant difference between 2 groups (Z = -11.376, P = 0.000. Logistic regression analysis showed ESRS > 3 score was independent risk factor for recurrence of ischemic stroke (OR = 31.324, 95%CI: 3.934-249.430; P = 0.001.  Conclusions ESRS > 3 score is the independent risk factor for recurrence of ischemic stroke. It is important to strengthen risk assessment of recurrence of ischemic stroke. To screen and control risk factors is the key to secondary prevention of ischemic stroke. DOI: 10.3969/j.issn.1672-6731.2016.07.011

  3. Lower Serum Caveolin-1 Is Associated with Cerebral Microbleeds in Patients with Acute Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2016-01-01

    Full Text Available Caveolin-1 (Cav-1 plays pivotal roles in the endothelial damage following stroke. The present study aimed to investigate whether serum Cav-1 level is associated with the presence of cerebral small vessel disease (cSVD in patients with acute ischemic stroke. To this end, 156 patients were consecutively enrolled. Cranial magnetic resonance imaging was analyzed to determine the surrogates of cSVD, including cerebral microbleeds (CMBs, silent lacunar infarcts (SLIs, and white matter hyperintensities (WMHs. After adjusting for potential confounders, patients with low Cav-1 level had a higher risk of CMBs than patients with high Cav-1 level (OR: 4.05, 95% CI: 1.77–9.30. However, there was no relationship between Cav-1 and the presence of SLIs or WMHs. When CMBs were stratified by location and number, a similar association was found in patients with deep or infratentorial CMBs (OR: 4.04, 95% CI: 1.59–10.25 and with multiple CMBs (OR: 3.18, 95% CI: 1.16–8.72. These results suggest lower serum Cav-1 levels may be associated with CMBs, especially those that are multiple and located in deep brain or infratentorial structures, in patients with acute ischemic stroke. Cav-1 may be involved in the pathophysiology of CMBs, and may act as a potential target for treating cSVD.

  4. Correlative study between neuron-specific enolase and blood sugar level in ischemic stroke patients

    Directory of Open Access Journals (Sweden)

    Aparna Pandey

    2011-01-01

    Full Text Available Background: A study to investigate the level of the neurobiochemical marker, Neuron-Specific Enolase (NSE, at the time of admission and its correlation with the blood sugar level in ischemic stroke patients. Patients and Methods: We investigated 90 patients with complete stroke who were admitted to the Stroke Unit of the Department of Neurology at Sri Aurobindo Institute of Medical Sciences. NSE was measured with commercially available quantitative ′sandwich′ enzyme-linked immunosorbent assay kits obtained from R and D Systems. Hyperglycemia was defined as blood glucose concentration ≥ 7 mmol / L, and measured using the glucose oxidase method immediately. Results: Significantly increased NSE and lipid profile levels were found in ischemic stroke patients as compared to the control. Hyperglycemic ischemic stroke patients had increased levels of NSE, lipid profile, and National Institute of Health stroke scale scores (NIHSS score compared to normoglycemic ischemic stroke patients. In addition the serum NSE level of hyperglycemic stroke patients was also positively correlated with the blood sugar level (r = 0.734 P < 0.001. Conclusions: Hyperglycemia predicts an increased risk of poor outcome after ischemic stroke and it is reflected by a significantly increased level of Neuron-Specific Enolase.

  5. Perceived stress and risk of ischemic heart disease: causation or bias?

    DEFF Research Database (Denmark)

    Nielsen, Naja Rod; Kristensen, Tage S; Prescott, Eva

    2006-01-01

    BACKGROUND: It is unclear whether the commonly recognized link between stress and cardiovascular disease is causal or the result of reporting bias. The objective of this study was to address the association between perceived stress and first incidence of ischemic heart disease and to evaluate...... the suggested reporting bias by addressing subdiagnoses of ischemic heart disease separately. METHODS: The 11,839 men and women who participated in the Copenhagen City Heart Study were at baseline (1981-1983) asked about their stress level. The participants were followed in nationwide registries until the year...... 2000, and fewer than 0.1% were lost to follow-up. During follow-up, 2316 individuals were diagnosed with ischemic heart disease. RESULTS: High levels of stress were associated with slightly higher risk of incident ischemic heart disease in both women (hazard ratio = 1.23; 95% confidence interval = 1...

  6. Myocardial ischemic preconditioning upregulated protein 1(Mipu1):zinc finger protein 667 - a multifunctional KRAB/C{sub 2}H{sub 2} zinc finger protein

    Energy Technology Data Exchange (ETDEWEB)

    Han, D.; Zhang, C. [Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Post-doctoral Mobile Stations for Basic Medicine, University of South China, Hengyang City, Hunan Province (China); Fan, W.J. [Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Post-doctoral Mobile Stations for Basic Medicine, University of South China, Hengyang City, Hunan Province (China); The Second Affiliated Hospital, University of South China, Hengyang City, Hunan Province (China); Pan, W.J.; Feng, D.M.; Qu, S.L.; Jiang, Z.S. [Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Post-doctoral Mobile Stations for Basic Medicine, University of South China, Hengyang City, Hunan Province (China)

    2014-10-31

    Myocardial ischemic preconditioning upregulated protein 1 (Mipu1) is a newly discovered upregulated gene produced in rats during the myocardial ischemic preconditioning process. Mipu1 cDNA contains a 1824-base pair open reading frame and encodes a 608 amino acid protein with an N-terminal Krüppel-associated box (KRAB) domain and classical zinc finger C{sub 2}H{sub 2} motifs in the C-terminus. Mipu1 protein is located in the cell nucleus. Recent studies found that Mipu1 has a protective effect on the ischemia-reperfusion injury of heart, brain, and other organs. As a nuclear factor, Mipu1 may perform its protective function through directly transcribing and repressing the expression of proapoptotic genes to repress cell apoptosis. In addition, Mipu1 also plays an important role in regulating the gene expression of downstream inflammatory mediators by inhibiting the activation of activator protein-1 and serum response element.

  7. Relationship Between Collateral Status, Contrast Transit, and Contrast Density in Acute Ischemic Stroke.

    Science.gov (United States)

    Kawano, Hiroyuki; Bivard, Andrew; Lin, Longting; Spratt, Neil J; Miteff, Ferdinand; Parsons, Mark W; Levi, Christopher R

    2016-03-01

    Collateral circulation is recognized to influence the life expectancy of the ischemic penumbra in acute ischemic stroke. The best method to quantify collateral status on acute imaging is uncertain. We aimed to determine the relationship between visual collateral status, quantitative collateral assessments, baseline computed tomographic perfusion measures, and tissue outcomes on follow-up imaging. Sixty-six consecutive patients with acute ischemic stroke clinically eligible for recanalization therapy and with M1 or M2 middle cerebral artery occlusion were evaluated. We compared the visual collateral scoring with measures of contrast peak time delay and contrast peak density. We also compared these measures for their ability to predict perfusion lesion and infarct core volumes, final infarct, and infarct growth. Shorter contrast peak time delay (P=0.041) and higher contrast peak density (P=0.002) were associated with good collateral status. Shorter contrast peak time delay correlated with higher contrast peak density (β=-4.413; P=0.037). In logistic regression analysis after adjustment for age, sex, onset-computed tomographic time, and occlusion site, higher contrast peak density was independently associated with good collateral status (P=0.009). Multiple regression analysis showed that higher contrast peak density was an independent predictor of smaller perfusion lesion volume (P=0.029), smaller ischemic core volume (P=0.044), smaller follow-up infarct volume (P=0.005), and smaller infarct growth volume (P=0.010). Visual collateral status, contrast peak density, and contrast peak time delay were inter-related, and good collateral status was strongly associated with contrast peak density. Contrast peak density in collateral vessel may be an important factor in tissue fate in acute ischemic stroke. © 2016 American Heart Association, Inc.

  8. Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy.

    Science.gov (United States)

    Liu, Xifu; Gu, Xinhua; Li, Zhaoming; Li, Xinyan; Li, Hui; Chang, Jianjie; Chen, Ping; Jin, Jing; Xi, Bing; Chen, Denghong; Lai, Donna; Graham, Robert M; Zhou, Mingdong

    2006-10-03

    We evaluated the therapeutic potential of a recombinant 61-residue neuregulin-1 (beta2a isoform) receptor-active peptide (rhNRG-1) in multiple animal models of heart disease. Activation of the erbB family of receptor tyrosine kinases by rhNRG-1 could provide a treatment option for heart failure, because neuregulin-stimulated erbB2/erbB4 heterodimerization is not only critical for myocardium formation in early heart development but prevents severe dysfunction of the adult heart and premature death. Disabled erbB-signaling is also implicated in the transition from compensatory hypertrophy to failure, whereas erbB receptor-activation promotes myocardial cell growth and survival and protects against anthracycline-induced cardiomyopathy. rhNRG-1 was administered IV to animal models of ischemic, dilated, and viral cardiomyopathy, and cardiac function and survival were evaluated. Short-term intravenous administration of rhNRG-1 to normal dogs and rats did not alter hemodynamics or cardiac contractility. In contrast, rhNRG-1 improved cardiac performance, attenuated pathological changes, and prolonged survival in rodent models of ischemic, dilated, and viral cardiomyopathy, with the survival benefits in the ischemic model being additive to those of angiotensin-converting enzyme inhibitor therapy. In addition, despite continued pacing, rhNRG-1 produced global improvements in cardiac function in a canine model of pacing-induced heart failure. These beneficial effects make rhNRG-1 promising as a broad-spectrum therapeutic for the treatment of heart failure due to a variety of common cardiac diseases.

  9. Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury

    OpenAIRE

    Winerdal, Max; Winerdal, Malin E.; Wang, Ying-Qing; Fredholm, Bertil B.; Winqvist, Ola; Ådén, Ulrika

    2015-01-01

    Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R−/−) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction siz...

  10. Canine study on myocardial ischemic memory with 18F-FDG PET/CT imaging

    International Nuclear Information System (INIS)

    Xie Boqia; Yang Minfu; Dou Kefei; Han Chunlei; Tian Yi; Zhang Ping; Yang Zihe; Yin Jiye; Wang Hao

    2012-01-01

    Objective: To explore whether the existence and duration of ischemia measured by dynamic 18 F-FDG PET/CT imaging correlated with the extent of myocardial ischemia in a canine model of myocardial ischemia-reperfusion. Methods: Canine coronary artery occlusion was carried out for 20 min (n=4) and for 40 min (n=4) followed by 24 h of open-artery reperfusion. All dogs underwent dynamic 18 F-FDG PET/CT and 99 Tc m -MIBI SPECT imaging at baseline and 1 h and 24 h after reperfusion.Quantitative analysis of myocardial 18 F-FDG uptake was performed using Carimas Core software,and the extraction ratio of 18 F-FDG (K) was calculated by the ratio of 18 F-FDG uptake rate in the ischemic area (k ischemia ) and normoperfused region (k normoperfused ). Echocardiographic data were also acquired between each PET/CT imaging study to detect the wall motion in the ischemic and normoperfused myocardium. Paired t test and non-parametric statistical tests, measured by SPSS 19.0, were used to analyze the data. Results: Coronary occlusion produced sustained, abnormal wall motion in the ischemic region for more than 1 h. Similar K values were demonstrated between the 20 min and 40 min groups at baseline (1.02 ±0.06 and 1.03 ±0.05, Z=-0.29, P>0.05). At 1 h after reperfusion, the reperfusion regions showed normal perfusion but with increased 18 F-FDG uptake, which was higher in the 40 min ischemic group than in the 20 min ischemic group (2.31 ±0.13 and 1.87 ±0.09, Z=-2.31, P<0.05). At 24 h after reperfusion, however, only the 40 min ischemic group showed slightly higher 18 F-FDG uptake than baseline (1.15 ± 0.02 and 1.03 ±0.05, t=4.32, P<0.05), whereas no significant difference was found in the 20 min ischemic group (1.05 ± 0.04 and 1.02 ± 0.06, t=0.87, P>0.05). Histological examination of the ischemic myocardium from both groups revealed neatly arranged cells without interstitial edema, hemorrhage nor inflammatory response. Conclusions: Myocardial 'ischemic memory' was

  11. Quantitative Measurement of Physical Activity in Acute Ischemic Stroke and Transient Ischemic Attack

    DEFF Research Database (Denmark)

    Strømmen, Anna Maria; Christensen, Thomas; Jensen, Kai

    2014-01-01

    BACKGROUND AND PURPOSE: The purpose of this study was to quantitatively measure and describe the amount and pattern of physical activity in patients within the first week after acute ischemic stroke and transient ischemic attack using accelerometers. METHODS: A total of 100 patients with acute is...

  12. Evaluation of ischemic corticospinal tract damage by diffusion tensor MRI. Its significance to predict functional outcome of corona radiata infarct

    International Nuclear Information System (INIS)

    Tanaka, Hideki

    2010-01-01

    Motor impairment is one of the most frequent symptoms among stroke patients and often leads to poststroke dependency. Recent advances of diffusion tensor MR imaging made it possible to identify corticospinal tract (CST) three-dimensionally and evaluate structural damage, so precise evaluation of the ischemic CST damage became feasible.Motor impairment, lesion size and location upon diffusion weighted MR image and clinical outcome were assessed in 23 acute to subacute capsular and corona radiata infarct patients. According to the lesion size, patients were grouped into A, maximal diameter below 15 mm and B, that above 15 mm. Motor impairment was graded severe: limb movement synergy level, moderate: selective muscle activity possible and mild: isolated movements well co-ordinated, each corresponding to Brunnstrom stage 1-3, 4-5, and 6, respectively. Outcome at the time of discharge was assessed by modified Rankin Scale (mRS), discharge destination and length of hospital stay were also registered. Diffusion tensor MR imaging was conducted in 15 corona radiata infarct patients at 2.3+-2.2 days from the onset of the clinical symptoms. CST was 3-dimensionally identified with dTV. II. SR and Volume-one 1.72 and CST-FA ratio (ipsi-/contralesional CST-FA) and CST-Area% (CST lesion free area/whole CST area) were obtained at the level where ischemic damage was most prominent and correlation of these parameters to motor impairment and clinical outcome was studied. CST-FA ratio and CST-Area% were in good correlation to motor impairment at presentation. Patients with severe motor impairment had lower CST-FA ratio and CSF-Area% than those with moderate or mild. CST-FA ratio was 0.73+-0.22 in patients with poor clinical outcome (mRS 3-6) and 0.93+-0.09 with good clinical outcome (mRS 0-2) (p=0.038). Diffusion tensor MR imaging is useful in evaluating motor impairment and predicting functional outcome of corona radiata infarct patient in the acute to subacute stage. (author)

  13. The Migraine-Ischemic Stroke Relation in Young Adults

    Directory of Open Access Journals (Sweden)

    Alessandro Pezzini

    2011-01-01

    Full Text Available In spite of the strong epidemiologic evidence linking migraine and ischemic stroke in young adults, the mechanisms explaining this association remain poorly understood. The observation that stroke occurs more frequently during the interictal phase of migraine prompts to speculation that an indirect relation between the two diseases might exist. In this regard, four major issues might be considered which may be summarized as follows: (1 the migraine-ischemic stroke relation is influenced by specific risk factors such as patent foramen ovale or endothelial dysfunction and more frequent in particular conditions like spontaneous cervical artery dissection; (2 migraine is associated with an increased prevalence of cardiovascular risk factors; (3 the link is caused by migraine-specific drugs; (4 migraine and ischemic vascular events are linked via a genetic component. In the present paper, we will review epidemiological studies, discuss potential mechanisms of migraine-induced stroke and comorbid ischemic stroke, and pose new research questions.

  14. The Migraine-Ischemic Stroke Relation in Young Adults

    Science.gov (United States)

    Pezzini, Alessandro; Del Zotto, Elisabetta; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Dalla Volta, Giorgio; Padovani, Alessandro

    2011-01-01

    In spite of the strong epidemiologic evidence linking migraine and ischemic stroke in young adults, the mechanisms explaining this association remain poorly understood. The observation that stroke occurs more frequently during the interictal phase of migraine prompts to speculation that an indirect relation between the two diseases might exist. In this regard, four major issues might be considered which may be summarized as follows: (1) the migraine-ischemic stroke relation is influenced by specific risk factors such as patent foramen ovale or endothelial dysfunction and more frequent in particular conditions like spontaneous cervical artery dissection; (2) migraine is associated with an increased prevalence of cardiovascular risk factors; (3) the link is caused by migraine-specific drugs; (4) migraine and ischemic vascular events are linked via a genetic component. In the present paper, we will review epidemiological studies, discuss potential mechanisms of migraine-induced stroke and comorbid ischemic stroke, and pose new research questions. PMID:21197470

  15. Ischemic necrosis and osteochondritis

    International Nuclear Information System (INIS)

    Weissman, S.D.

    1989-01-01

    Osteonecrosis indicates that ischemic death of the cellular constituents of bone and marrow has occurred. Historically, this first was thought to be related to sepsis in the osseous segments. However, continued studies led to the use of the term aseptic necrosis. Subsequent observations indicated that the necrotic areas of bone were not only aseptic, but were also avascular. This led to the terms ischemic necrosis, vascular necrosis and bone infarction. Ischemic necrosis of bone is discussed in this chapter. It results from a significant reduction in or obliteration of blood supply to the affected area. The various bone cells, including osteocytes, osteoclasts, and osteoblasts, usually undergo anoxic death in 12 to 48 hours after blood supply is cut off. The infarct that has thus developed in three-dimensional and can be divided into a number of zones: a central zone of cell death; an area of ischemic injury, most severe near the zone of cell death, and lessening as it moves peripherally; an area of active hyperemia and the zone of normal unaffected tissue. Once ischemic necrosis has begun, the cellular damage provokes an initial inflammatory response, which typically is characterized by vasodilatation, transudation of fluid and fibrin, and local infiltration of flammatory cells. This response can be considered the first stage in repair of the necrotic area

  16. Cytochrome P450 1B1 and 2C9 genotypes and risk of ischemic vascular disease, cancer, and chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Kaur-Knudsen, Diljit; Bojesen, Stig E; Nordestgaard, Børge G

    2012-01-01

    The aim of this review is to summarize present knowledge of genetic variation in cytochrome P450 1B1 (CYP1B1) and 2C9 (CYP2C9) genes and risk of tobacco-related cancer, female cancer, chronic obstructive pulmonary disease and ischemic vascular disease. The CYP1B1 and CYP2C9 enzymes metabolize pol...

  17. Hypercholesterolemia in patients of ischemic stroke

    International Nuclear Information System (INIS)

    Saeed, E.; Ali, R.; Din, M.J.U.; Saeed, A.; Jadoon, R.J.

    2015-01-01

    Background: Stroke is a common neurological disease that results in significant mortality and morbidity globally. Several risk factors have been identified for stroke among which hyperlipidaemia is one of the modifiable risk factors. Recent clinical trials have shown a reduction in ischemic stroke for patients taking lipid lowering medications. Therefore, the aim of this study was to find out the frequency of hypercholesterolemia in patients of ischemic stroke in Hazara region. Method: This cross sectional study was carried out in the Medical Department of Ayub Teaching Hospital, Abbottabad. Ninety patients of stroke confirmed as ischemic by CT scan brain were enrolled in the study after informed consent. The frequency of hypercholesterolemia in patients was recorded. Results: There were 55 (61.1 percentage) males. The mean age of patients was 64.4±11.5 years. The mean serum cholesterol in all patients was 4.16±1.1 mmol/l. The mean serum cholesterol of male patients was 4.3±1.2 mmol/l and 4.0±10.9 mmol/l in the case of females. Conclusions: Hypercholesterolemia could not be established as a major risk factor for stroke in our setup through this study that allude to the fact that other risk factors might be contributing more to the incidence of cerebrovascular accident in our population. (author)

  18. Gray-Matter Volume Estimate Score: A Novel Semi-Automatic Method Measuring Early Ischemic Change on CT

    OpenAIRE

    Song, Dongbeom; Lee, Kijeong; Kim, Eun Hye; Kim, Young Dae; Lee, Hye Sun; Kim, Jinkwon; Song, Tae-Jin; Ahn, Sung Soo; Nam, Hyo Suk; Heo, Ji Hoe

    2015-01-01

    Background and Purpose We developed a novel method named Gray-matter Volume Estimate Score (GRAVES), measuring early ischemic changes on Computed Tomography (CT) semi-automatically by computer software. This study aimed to compare GRAVES and Alberta Stroke Program Early CT Score (ASPECTS) with regards to outcome prediction and inter-rater agreement. Methods This was a retrospective cohort study. Among consecutive patients with ischemic stroke in the anterior circulation who received intra-art...

  19. Dolichoectasia and Small Vessel Disease in Young Patients With Transient Ischemic Attack and Stroke.

    Science.gov (United States)

    Thijs, Vincent; Grittner, Ulrike; Fazekas, Franz; McCabe, Dominick J H; Giese, Anne-Katrin; Kessler, Christof; Martus, Peter; Norrving, Bo; Ringelstein, Erich Bernd; Schmidt, Reinhold; Tanislav, Christian; Putaala, Jukka; Tatlisumak, Turgut; von Sarnowski, Bettina; Rolfs, Arndt; Enzinger, Christian

    2017-09-01

    We evaluated whether basilar dolichoectasia is associated with markers of cerebral small vessel disease in younger transient ischemic attack and ischemic stroke patients. We used data from the SIFAP1 study (Stroke in Young Fabry Patients), a large prospective, hospital-based, screening study for Fabry disease in young (ischemic attack/stroke patients in whom detailed clinical data and brain MRI were obtained, and stroke subtyping with TOAST classification (Trial of ORG 10172 in Acute Stroke Treatment) was performed. Dolichoectasia was found in 508 of 3850 (13.2%) of patients. Dolichoectasia was associated with older age (odds ratio per decade, 1.26; 95% confidence interval, 1.09-1.44), male sex (odds ratio, 1.96; 95% confidence interval, 1.59-2.42), and hypertension (odds ratio, 1.39; 95% confidence interval, 1.13-1.70). Dolichoectasia was more common in patients with small infarctions (33.9% versus 29.8% for acute lesions, P =0.065; 29.1% versus 16.5% for old lesions, P ischemic attack and ischemic stroke. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583. © 2017 American Heart Association, Inc.

  20. Genetic Variant of Kalirin Gene Is Associated with Ischemic Stroke in a Chinese Han Population

    Directory of Open Access Journals (Sweden)

    Hong Li

    2017-01-01

    Full Text Available Introduction. Ischemic stroke is a complex disorder resulting from the interplay of genetic and environmental factors. Previous studies showed that kalirin gene variations were associated with cardiovascular disease. However, the association between this gene and ischemic stroke was unknown. We performed this study to confirm if kalirin gene variation was associated with ischemic stroke. Methods. We enrolled 385 ischemic stroke patients and 362 controls from China. Three SNPs of kalirin gene were genotyped by means of ligase detection reaction-PCR method. Data was processed with SPSS and SHEsis platform. Results. SNP rs7620580 (dominant model: OR = 1.590, p = 0.002 and adjusted OR = 1.662, p = 0.014; additive model: OR = 1.490, p = 0.002 and adjusted OR = 1.636, p = 0.005; recessive model: OR = 2.686, p = 0.039 and SNP rs1708303 (dominant model: OR = 1.523, p = 0.007 and adjusted OR = 1.604, p = 0.028; additive model: OR = 1.438, p = 0.01 and adjusted OR = 1.476, p = 0.039 were associated with ischemic stroke. The GG genotype and G allele of SNP rs7620580 were associated with a risk for ischemic stroke with an adjusted OR of 3.195 and an OR of 1.446, respectively. Haplotype analysis revealed that A–T–G,G-T-A, and A-T-A haplotypes were associated with ischemic stroke. Conclusions. Our results provide evidence that kalirin gene variations were associated with ischemic stroke in the Chinese Han population.

  1. Increased Vascular Disease Mortality Risk in Prediabetic Korean Adults Is Mainly Attributable to Ischemic Stroke.

    Science.gov (United States)

    Kim, Nam Hoon; Kwon, Tae Yeon; Yu, Sungwook; Kim, Nan Hee; Choi, Kyung Mook; Baik, Sei Hyun; Park, Yousung; Kim, Sin Gon

    2017-04-01

    Prediabetes is a known risk factor for vascular diseases; however, its differential contribution to mortality risk from various vascular disease subtypes is not known. The subjects of the National Health Insurance Service in Korea (2002-2013) nationwide cohort were stratified into normal glucose tolerance (fasting glucose mortality risk for vascular disease and its subtypes-ischemic heart disease, ischemic stroke, and hemorrhagic stroke. When adjusted for age, sex, and body mass index, IFG stage 2, but not stage 1, was associated with significantly higher all-cause mortality (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.18-1.34) and vascular disease mortality (HR, 1.27; 95% CI, 1.08-1.49) compared with normal glucose tolerance. Among the vascular disease subtypes, mortality from ischemic stroke was significantly higher (HR, 1.60; 95% CI, 1.18-2.18) in subjects with IFG stage 2 but not from ischemic heart disease and hemorrhagic stroke. The ischemic stroke mortality associated with IFG stage 2 remained significantly high when adjusted other modifiable vascular disease risk factors (HR, 1.51; 95% CI: 1.10-2.09) and medical treatments (HR, 1.75; 95% CI, 1.19-2.57). Higher IFG degree (fasting glucose, 110-125 mg/dL) was associated with increased all-cause and vascular disease mortality. The increased vascular disease mortality in IFG stage 2 was attributable to ischemic stroke, but not ischemic heart disease or hemorrhagic stroke in Korean adults. © 2017 American Heart Association, Inc.

  2. Glibenclamide for the treatment of ischemic and hemorrhagic stroke.

    Science.gov (United States)

    Caffes, Nicholas; Kurland, David B; Gerzanich, Volodymyr; Simard, J Marc

    2015-03-04

    Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1-transient receptor potential melastatin 4 (Sur1-Trpm4) channels and, in some cases, microglial KATP (Sur1-Kir6.2) channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke.

  3. Glibenclamide for the Treatment of Ischemic and Hemorrhagic Stroke

    Directory of Open Access Journals (Sweden)

    Nicholas Caffes

    2015-03-01

    Full Text Available Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1–transient receptor potential melastatin 4 (Sur1–Trpm4 channels and, in some cases, microglial KATP (Sur1–Kir6.2 channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke.

  4. Relative impact of human leukocyte antigen mismatching and graft ischemic time after lung transplantation.

    Science.gov (United States)

    Brugière, Olivier; Thabut, Gabriel; Suberbielle, Caroline; Reynaud-Gaubert, Martine; Thomas, Pascal; Pison, Christophe; Saint Raymond, Christel; Mornex, Jean-François; Bertocchi, Michèle; Dromer, Claire; Velly, Jean-François; Stern, Marc; Philippe, Bruno; Dauriat, Gaëlle; Biondi, Giuseppina; Castier, Yves; Fournier, Michel

    2008-06-01

    Recent data strongly suggest that human leukocyte antigen (HLA) mismatching has a negative impact on development of bronchiolitis obliterans syndrome (BOS) and survival after lung transplantation (LTx). Because HLA matching is sometimes achieved by extending ischemic time in other solid-organ transplantation models and ischemic time is a risk factor per se for death after LTx, we sought to compare the theoretical benefit of HLA matching with the negative impact of lengthened ischemic time. In this collaborative study we compared the relative impact of HLA mismatching and ischemic time on BOS and survival in 182 LTx recipients. Using multivariate analyses, we observed a lower incidence of BOS (hazard ratio [HR] = 1.70, 95% confidence interval [CI]: 1.1 to 2.7, p = 0.03) and enhanced survival (HR = 1.91, 95% CI: 1.24 to 2.92, p = 0.01) in patients with zero or one HLA-A mismatch compared with those having two HLA-A mismatches. This beneficial effect on survival was equivalent to a reduction of ischemic time of 168 minutes. We observed a reduced incidence of BOS and a better survival rate in patients well-matched at the HLA-A locus, associated with an opposite effect of an enhanced ischemic time. This suggests that graft ischemic time should be taken into account in future studies of prospective HLA matching in LTx.

  5. Neurofibromatosis type 1 associated with vertebrobasilar dolichoectasia and pontine ischemic stroke.

    Science.gov (United States)

    Giannantoni, Nadia Mariagrazia; Broccolini, Aldobrando; Frisullo, Giovanni; Pilato, Fabio; Profice, Paolo; Morosetti, Roberta; Di Lella, Giuseppe; Zampino, Giuseppe; Della Marca, Giacomo

    2015-01-01

    Neurofibromatosis type 1 (NF1) is a heterogeneous, common, neurocutaneous disorder presenting different complications during a life span, including cerebrovascular dysplasia. To our knowledge this is the first reported case of NF1 associated with vertebrobasilar dolichoectasia and pontine ischemic stroke. We describe a 57-year-old man with NF1 who presented an acute onset right-sided facial palsy and hemiplegia, dysarthria, and gait imbalance. Magnetic resonance imaging showed an acute left paramedian pontine infarct and a hypoplastic right vertebral artery. Brain Computed Tomography Angiography revealed the occurrence of vertebrobasilar dolichoectasia. Co-occurrence of VBD and NF1 might not be merely casual and it may significantly heighten the mortality rate in this multisystem disorder. We suggest a possible role of VBD in the genesis of our patient's clinical-radiological features and prompt the early detection of asymptomatic arteriopathy in individuals with NF1 in order to ameliorate patients' quality of life and life expectancy. Copyright © 2014 by the American Society of Neuroimaging.

  6. Hypoxic-ischemic encephalopathy in neonates and infants: an evaluation with spiral CT

    International Nuclear Information System (INIS)

    Zhu Linghua

    2006-01-01

    Objective: To evaluate spiral CT imaging in the diagnosis of hypoxic-ischemic encephalopathy (HIE) in the neonates and infants. Methods: 112 children with history of asphyxia in peri-natal period and evident clinical symptoms were evaluated with Spiral CT. CT findings were studied. Results: 46 minor cases, 57 moderate cases and 9 severe cases were found out of 112 patients. Intracranial hemorrhage was revealed in 38 cases. Mortality occurred in 1 case. Conclusion: Spiral CT is helpful for evaluating brain damage and predicting prognosis in neonates with HIE. (authors)

  7. Genetically elevated C-reactive protein and ischemic vascular disease

    DEFF Research Database (Denmark)

    Zacho, J.; Tybjaerg-Hansen, A.; Jensen, J.S.

    2008-01-01

    Background: Elevated levels of C-reactive protein (CRP) are associated with increased risks of ischemic heart disease and ischemic cerebrovascular disease. We tested whether this is a causal association. Methods: We studied 10,276 persons from a general population cohort, including 1786 in whom...... ischemic heart disease developed and 741 in whom ischemic cerebrovascular disease developed. We examined another 31,992 persons from a cross-sectional general population study, of whom 2521 had ischemic heart disease and 1483 had ischemic cerebrovascular disease. Finally, we compared 2238 patients...... with ischemic heart disease with 4474 control subjects and 612 patients with ischemic cerebrovascular disease with 1224 control subjects. We measured levels of high-sensitivity CRP and conducted genotyping for four CRP polymorphisms and two apolipoprotein E polymorphisms. Results: The risk of ischemic heart...

  8. Role of brain natriuretic peptide as a novel prognostic biomarker in acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Bindu Menon

    2016-01-01

    Full Text Available Aim: We investigated to study the prognostic importance of brain natriuretic peptide (BNP in ischemic stroke. Materials and Methods: We prospectively enrolled 100 patients with acute ischemic stroke and measured plasma BNP levels and compared with age- and sex-matched healthy controls. Risk factors, biochemical parameters, lipid profile, carotid and vertebral Doppler, imaging, and cardiac evaluation were done. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS score on admission and functional disability by Barthel Index (BI at 3 months. Ischemic stroke subtype was classified according to the Oxfordshire Community Stroke Project (OCSP. Data were entered in MS Excel, and appropriate statistical analysis was done using the SPSS software version 21.0. A P = 0.05 was considered as significant. Results: Mean age of patients was 55.17 ± 11.37 years with a male:female ratio 3:1. OCSP showed total anterior circulation infarct (TACI 35, partial anterior circulation infarct 9, lacunar infarct 12, and posterior circulation infarct 44. NIHSS on admission was average 10 ± 7 and BI was 57 ± 30. BNP in patients (435 ng/ml was very high as compared to controls (<60 ng/ml (P < 0.001. There was a positive correlation between age and BNP (R2 = 0.34; P < 0.00; NIHSS and BNP (R2 = 0.255; P < 0.01, negative correlation between BI and BNP (R2 = −0.064; P < 0.01. Mean BNP levels across the OCSP showed higher values in TACI (F = 4.609 P = 0.005. Regression analysis showed that BNP can predict BI which was statistically significant. Conclusion: Plasma BNP levels was significantly elevated in patients with ischemic stroke. Our study concludes that high BNP levels are seen in large anterior circulation stroke and is a predictor for the poor functional outcome at 3 months. Determination of BNP levels as a biomarker could be helpful in predicting the outcome in stroke patients.

  9. The P2Y12 Receptor Antagonist Ticagrelor Reduces Lysosomal pH and Autofluorescence in Retinal Pigmented Epithelial Cells From the ABCA4-/- Mouse Model of Retinal Degeneration

    Directory of Open Access Journals (Sweden)

    Wennan Lu

    2018-04-01

    Full Text Available The accumulation of partially degraded lipid waste in lysosomal-related organelles may contribute to pathology in many aging diseases. The presence of these lipofuscin granules is particularly evident in the autofluorescent lysosome-associated organelles of the retinal pigmented epithelial (RPE cells, and may be related to early stages of age-related macular degeneration. While lysosomal enzymes degrade material optimally at acidic pH levels, lysosomal pH is elevated in RPE cells from the ABCA4-/- mouse model of Stargardt’s disease, an early onset retinal degeneration. Lowering lysosomal pH through cAMP-dependent pathways decreases accumulation of autofluorescent material in RPE cells in vitro, but identification of an appropriate receptor is crucial for manipulating this pathway in vivo. As the P2Y12 receptor for ADP is coupled to the inhibitory Gi protein, we asked whether blocking the P2Y12 receptor with ticagrelor could restore lysosomal acidity and reduce autofluorescence in compromised RPE cells from ABCA4-/- mice. Oral delivery of ticagrelor giving rise to clinically relevant exposure lowered lysosomal pH in these RPE cells. Ticagrelor also partially reduced autofluorescence in the RPE cells of ABCA4-/- mice. In vitro studies in ARPE-19 cells using more specific antagonists AR-C69931 and AR-C66096 confirmed the importance of the P2Y12 receptor for lowering lysosomal pH and reducing autofluorescence. These observations identify P2Y12 receptor blockade as a potential target to lower lysosomal pH and clear lysosomal waste in RPE cells.

  10. Factors Associated with Delay in Presentation to the Hospital for Young Adults with Ischemic Stroke.

    Science.gov (United States)

    Leung, Lester Y; Caplan, Louis R

    2016-01-01

    Young adults with ischemic stroke may present late to medical care, but the reasons for these delays are unknown. We sought to identify factors that predict delay in presentation. We performed a retrospective cohort study of adults aged 18-50 admitted to a single academic medical center between 2007 and 2012. Eighty six of 141 (61%) young adults with ischemic stroke presented at the health center more than 4.5 h after stroke onset. Diabetes was associated with delays in presentation (p = 0.033, relative risk (RR) 1.4 (95% CI 1.1-1.8)), whereas systemic cancer was associated with early presentations (p = 0.033, RR 0.26 (95% CI 0.044-1.6)). Individuals who were single were more likely to present late than those who were married or living with a partner (p = 0.0045, RR 1.7 (95% CI 1.3-2.2)). Individuals who were unemployed were more likely to present late than those who were employed or in school (p = 0.020, RR 1.4 (95% CI 1.1-1.8)). Age (dichotomized as 18-35 and 36-50), race, home medications, other medical conditions (including common stroke mimics in young adults), and stroke subtype were not determinants of delay in presentation, although there was a trend toward delayed presentations in women (p = 0.076) and with low stroke severity (dichotomized as National Institutes of Health Stroke Scale (NIHSS) ≤5 and NIHSS >5, p = 0.061). A majority of young adults with ischemic stroke presented outside the time window for intravenous fibrinolysis. Diabetes, single status, and unemployed status were associated with delayed presentation. © 2016 S. Karger AG, Basel.

  11. The protective effect of ischemic preconditioning on rat testis

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    Ciralik Harun

    2007-12-01

    Full Text Available Abstract Background It has been demonstrated that brief episodes of sublethal ischemia-reperfusion, so-called ischemic preconditioning, provide powerful tissue protection in different tissues such as heart, brain, skeletal muscle, lung, liver, intestine, kidney, retina, and endothelial cells. Although a recent study has claimed that there are no protective effects of ischemic preconditioning in rat testis, the protective effects of ischemic preconditioning on testicular tissue have not been investigated adequately. The present study was thus planned to investigate whether ischemic preconditioning has a protective effect on testicular tissue. Methods Rats were divided into seven groups that each contained seven rats. In group 1 (control group, only unilateral testicular ischemia was performed by creating a testicular torsion by a 720 degree clockwise rotation for 180 min. In group 2, group 3, group 4, group 5, group 6, and group 7, unilateral testicular ischemia was performed for 180 min following different periods of ischemic preconditioning. The ischemic preconditioning periods were as follows: 10 minutes of ischemia with 10 minutes of reperfusion in group 2; 20 minutes of ischemia with 10 minutes of reperfusion in group 3; 30 minutes of ischemia with 10 minutes of reperfusion in group 4; multiple preconditioning periods were used (3 × 10 min early phase transient ischemia with 10 min reperfusion in all episodes in group 5; multiple preconditioning periods were used (5, 10, and 15 min early phase transient ischemia with 10 min reperfusion in all episodes in group 6; and, multiple preconditioning periods were used (10, 20, and 30 min early phase transient ischemia with 10 min reperfusion in all episodes in group 7. After the ischemic protocols were carried out, animals were sacrificed by cervical dislocation and testicular tissue samples were taken for biochemical measurements (protein, malondialdehyde, nitric oxide and histological examination

  12. Rehabilitation Outcomes: Ischemic versus Hemorrhagic Strokes

    OpenAIRE

    Perna, Robert; Temple, Jessica

    2015-01-01

    Background. Ischemic and hemorrhagic strokes have different pathophysiologies and possibly different long-term cerebral and functional implications. Hemorrhagic strokes expose the brain to irritating effects of blood and ischemic strokes reflect localized or diffuse cerebral vascular pathology. Methods. Participants were individuals who suffered either an ischemic (n = 172) or hemorrhagic stroke (n = 112) within the past six months and were involved in a postacute neurorehabilitation program....

  13. The Migraine-Ischemic Stroke Relation in Young Adults

    OpenAIRE

    Pezzini, Alessandro; Del Zotto, Elisabetta; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Dalla Volta, Giorgio; Padovani, Alessandro

    2010-01-01

    In spite of the strong epidemiologic evidence linking migraine and ischemic stroke in young adults, the mechanisms explaining this association remain poorly understood. The observation that stroke occurs more frequently during the interictal phase of migraine prompts to speculation that an indirect relation between the two diseases might exist. In this regard, four major issues might be considered which may be summarized as follows: (1) the migraine-ischemic stroke relation is influenced by s...

  14. Obesity increases risk of ischemic stroke in young adults.

    Science.gov (United States)

    Mitchell, Andrew B; Cole, John W; McArdle, Patrick F; Cheng, Yu-Ching; Ryan, Kathleen A; Sparks, Mary J; Mitchell, Braxton D; Kittner, Steven J

    2015-06-01

    Body mass index has been associated with ischemic stroke in older populations, but its association with stroke in younger populations is not known. In light of the current obesity epidemic in the United States, the potential impact of obesity on stroke risk in young adults deserves attention. A population-based case-control study design with 1201 cases and 1154 controls was used to investigate the relationship of obesity and young onset ischemic stroke. Stroke cases were between the ages of 15 and 49 years. Logistic regression analysis was used to evaluate the association between body mass index and ischemic stroke with and without adjustment for comorbid conditions associated with stroke. In analyses adjusted for age, sex, and ethnicity, obesity (body mass index >30 kg/m(2)) was associated with an increased stroke risk (odds ratio, 1.57; 95% confidence interval, 1.28-1.94) although this increased risk was highly attenuated and not statistically significant after adjustment for smoking, hypertension, and diabetes mellitus. These results indicate that obesity is a risk factor for young onset ischemic stroke and suggest that this association may be partially mediated through hypertension, diabetes mellitus, or other variables associated with these conditions. © 2015 American Heart Association, Inc.

  15. Delayed treatment with ADAMTS13 ameliorates cerebral ischemic injury without hemorrhagic complication.

    Science.gov (United States)

    Nakano, Takafumi; Irie, Keiichi; Hayakawa, Kazuhide; Sano, Kazunori; Nakamura, Yoshihiko; Tanaka, Masayoshi; Yamashita, Yuta; Satho, Tomomitsu; Fujioka, Masayuki; Muroi, Carl; Matsuo, Koichi; Ishikura, Hiroyasu; Futagami, Kojiro; Mishima, Kenichi

    2015-10-22

    Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke. However, delayed tPA treatment increases the risk of cerebral hemorrhage and can result in exacerbation of nerve injury. ADAMTS13, a von Willebrand factor (VWF) cleaving protease, has a protective effect against ischemic brain injury and may reduce bleeding risk by cleaving VWF. We examined whether ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA in mice subjected to middle cerebral artery occlusion (MCAO). ADAMTS13 (0.1mg/kg) or tPA (10mg/kg) was administered i.v., immediately after reperfusion of after 2-h or 4-h MCAO for comparison of the therapeutic time windows in ischemic stroke. Infarct volume, hemorrhagic volume, plasma high-mobility group box1 (HMGB1) levels and cerebral blood flow were measured 24h after MCAO. Both ADAMTS13 and tPA improved the infarct volume without hemorrhagic complications in 2-h MCAO mice. On the other hand, ADAMTS13 reduced the infarct volume and plasma HMGB1 levels, and improved cerebral blood flow without hemorrhagic complications in 4-h MCAO mice, but tPA was not effective and these animals showed massive intracerebral hemorrhage. These results indicated that ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA, and ADAMTS13 may be useful as a new therapeutic agent for ischemic stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Putative role of ischemic postconditioning in a rat model of limb ischemia and reperfusion: involvement of hypoxia-inducible factor-1α expression

    Energy Technology Data Exchange (ETDEWEB)

    Wang, T. [Department of Anesthesiology, Shuyang People' s Hospital, JiangSu (China); Zhou, Y.T. [Department of General Surgery, Shuyang People' s Hospital, JiangSu (China); Chen, X.N. [Institute of Pathophysiology, School of Basic Medical Sciences, LanZhou University, Lanzhou, Gansu (China); Zhu, A.X. [Department of Pharmacy, Shuyang People' s Hospital, JiangSu (China)

    2014-07-25

    Hypoxia-inducible factor-1α (HIF-1α) is one of the most potent angiogenic growth factors. It improves angiogenesis and tissue perfusion in ischemic skeletal muscle. In the present study, we tested the hypothesis that ischemic postconditioning is effective for salvaging ischemic skeletal muscle resulting from limb ischemia-reperfusion injury, and that the mechanism involves expression of HIF-1α. Wistar rats were randomly divided into three groups (n=36 each): sham-operated (group S), hindlimb ischemia-reperfusion (group IR), and ischemic postconditioning (group IPO). Each group was divided into subgroups (n=6) according to reperfusion time: immediate (0 h, T{sub 0}), 1 h (T{sub 1}), 3 h (T{sub 3}), 6 h (T{sub 6}), 12 h (T{sub 12}), and 24 h (T{sub 24}). In the IPO group, three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were carried out before reperfusion. At all reperfusion times (T{sub 0}-T{sub 24}), serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities, as well as interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α) concentrations, were measured in rats after they were killed. Histological and immunohistochemical methods were used to assess the skeletal muscle damage and HIF-1α expression in skeletal muscle ischemia. In groups IR and IPO, serum LDH and CK activities and TNF-α, IL-6, and IL-10 concentrations were all significantly increased compared to group S, and HIF-1α expression was up-regulated (P<0.05 or P<0.01). In group IPO, serum LDH and CK activities and TNF-α and IL-6 concentrations were significantly decreased, IL-10 concentration was increased, HlF-1α expression was down-regulated (P<0.05 or P<0.01), and the pathological changes were reduced compared to group IR. The present study suggests that ischemic postconditioning can reduce skeletal muscle damage caused by limb ischemia-reperfusion and that its mechanisms may be related to the involvement of HlF-1α in the limb ischemia-reperfusion injury

  17. Pharmacokinetic Study of Piracetam in Focal Cerebral Ischemic Rats.

    Science.gov (United States)

    Paliwal, Pankaj; Dash, Debabrata; Krishnamurthy, Sairam

    2018-04-01

    Cerebral ischemia affects hepatic enzymes and brain permeability extensively. Piracetam was investigated up to phase III of clinical trials and there is lack of data on brain penetration in cerebral ischemic condition. Thus, knowledge of the pharmacokinetics and brain penetration of piracetam during ischemic condition would aid to improve pharmacotherapeutics in ischemic stroke. Focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h in male Wistar rats followed by reperfusion. After 24 h of middle cerebral artery occlusion or 22 h of reperfusion, piracetam was administered for pharmacokinetic, brain penetration, and pharmacological experiments. In pharmacokinetic study, blood samples were collected at different time points after 200-mg/kg (oral) and 75-mg/kg (intravenous) administration of piracetam through right external jugular vein cannulation. In brain penetration study, the cerebrospinal fluid, systemic blood, portal blood, and brain samples were collected at pre-designated time points after 200-mg/kg oral administration of piracetam. In a separate experiment, the pharmacological effect of the single oral dose of piracetam in middle cerebral artery occlusion was assessed at a dose of 200 mg/kg. All the pharmacokinetic parameters of piracetam including area under curve (AUC 0-24 ), maximum plasma concentration (C max ), time to reach the maximum plasma concentration (t max ), elimination half-life (t 1/2 ), volume of distribution (V z ), total body clearance, mean residence time, and bioavailability were found to be similar in ischemic stroke condition except for brain penetration. Piracetam exposure (AUC 0-2 ) in brain and CSF were found to be 2.4- and 3.1-fold higher, respectively, in ischemic stroke compared to control rats. Piracetam significantly reduced infarct volume by 35.77% caused by middle cerebral artery occlusion. There was no change in the pharmacokinetic parameters of piracetam in the ischemic stroke model except for

  18. Epistasis Analysis for Estrogen Metabolic and Signaling Pathway Genes on Young Ischemic Stroke Patients

    Science.gov (United States)

    Hsieh, Yi-Chen; Jeng, Jiann-Shing; Lin, Huey-Juan; Hu, Chaur-Jong; Yu, Chia-Chen; Lien, Li-Ming; Peng, Giia-Sheun; Chen, Chin-I; Tang, Sung-Chun; Chi, Nai-Fang; Tseng, Hung-Pin; Chern, Chang-Ming; Hsieh, Fang-I; Bai, Chyi-Huey; Chen, Yi-Rhu; Chiou, Hung-Yi; Jeng, Jiann-Shing; Tang, Sung-Chun; Yeh, Shin-Joe; Tsai, Li-Kai; Kong, Shin; Lien, Li-Ming; Chiu, Hou-Chang; Chen, Wei-Hung; Bai, Chyi-Huey; Huang, Tzu-Hsuan; Chi-Ieong, Lau; Wu, Ya-Ying; Yuan, Rey-Yue; Hu, Chaur-Jong; Sheu, Jau- Jiuan; Yu, Jia-Ming; Ho, Chun-Sum; Chen, Chin-I; Sung, Jia-Ying; Weng, Hsing-Yu; Han, Yu-Hsuan; Huang, Chun-Ping; Chung, Wen-Ting; Ke, Der-Shin; Lin, Huey-Juan; Chang, Chia-Yu; Yeh, Poh-Shiow; Lin, Kao-Chang; Cheng, Tain-Junn; Chou, Chih-Ho; Yang, Chun-Ming; Peng, Giia-Sheun; Lin, Jiann-Chyun; Hsu, Yaw-Don; Denq, Jong-Chyou; Lee, Jiunn-Tay; Hsu, Chang-Hung; Lin, Chun-Chieh; Yen, Che-Hung; Cheng, Chun-An; Sung, Yueh-Feng; Chen, Yuan-Liang; Lien, Ming-Tung; Chou, Chung-Hsing; Liu, Chia-Chen; Yang, Fu-Chi; Wu, Yi-Chung; Tso, An-Chen; Lai, Yu- Hua; Chiang, Chun-I; Tsai, Chia-Kuang; Liu, Meng-Ta; Lin, Ying-Che; Hsu, Yu-Chuan; Chen, Chih-Hung; Sung, Pi-Shan; Chern, Chang-Ming; Hu, Han-Hwa; Wong, Wen-Jang; Luk, Yun-On; Hsu, Li-Chi; Chung, Chih-Ping; Tseng, Hung-Pin; Liu, Chin-Hsiung; Lin, Chun-Liang; Lin, Hung-Chih; Hu, Chaur-Jong

    2012-01-01

    Background Endogenous estrogens play an important role in the overall cardiocirculatory system. However, there are no studies exploring the hormone metabolism and signaling pathway genes together on ischemic stroke, including sulfotransferase family 1E (SULT1E1), catechol-O-methyl-transferase (COMT), and estrogen receptor α (ESR1). Methods A case-control study was conducted on 305 young ischemic stroke subjects aged ≦ 50 years and 309 age-matched healthy controls. SULT1E1 -64G/A, COMT Val158Met, ESR1 c.454−397 T/C and c.454−351 A/G genes were genotyped and compared between cases and controls to identify single nucleotide polymorphisms associated with ischemic stroke susceptibility. Gene-gene interaction effects were analyzed using entropy-based multifactor dimensionality reduction (MDR), classification and regression tree (CART), and traditional multiple regression models. Results COMT Val158Met polymorphism showed a significant association with susceptibility of young ischemic stroke among females. There was a two-way interaction between SULT1E1 -64G/A and COMT Val158Met in both MDR and CART analysis. The logistic regression model also showed there was a significant interaction effect between SULT1E1 -64G/A and COMT Val158Met on ischemic stroke of the young (P for interaction = 0.0171). We further found that lower estradiol level could increase the risk of young ischemic stroke for those who carry either SULT1E1 or COMT risk genotypes, showing a significant interaction effect (P for interaction = 0.0174). Conclusions Our findings support that a significant epistasis effect exists among estrogen metabolic and signaling pathway genes and gene-environment interactions on young ischemic stroke subjects. PMID:23112845

  19. Characteristic adverse events and their incidence among patients participating in acute ischemic stroke trials.

    Science.gov (United States)

    Hesse, Kerrick; Fulton, Rachael L; Abdul-Rahim, Azmil H; Lees, Kennedy R

    2014-09-01

    Adverse events (AE) in trial populations present a major burden to researchers and patients, yet most events are unrelated to investigational treatment. We aimed to develop a coherent list of expected AEs, whose incidence can be predicted by patient characteristics that will inform future trials and perhaps general poststroke care. We analyzed raw AE data from patients participating in acute ischemic stroke trials. We identified events that occurred with a lower 99% confidence bound greater than nil. Among these, we applied receiver operating characteristic principles to select the fewest types of events that together represented the greatest number of reports. Using ordinal logistic regression, we modeled the incidence of these events as a function of patient age, sex, baseline National Institutes of Health Stroke Scale, and multimorbidity status, defining Ppatients, reporting 21 217 AEs. Among 756 types of AEs, 132 accounted for 82.7%, of which 80% began within 10 days after stroke. Right hemisphere (odds ratio [OR], 1.67), increasing baseline National Institutes of Health Stroke Scale (OR, 1.11), multimorbidity status (OR, 1.09 per disease), patient age (OR, 1.01 per year), height (OR, 1.01 per centimeter), diastolic blood pressure (OR, 0.99 per mm Hg), and smoking (OR, 0.82) were independently associated with developing more AEs but together explained only 13% of the variation. A list of 132 expected AEs after acute ischemic stroke may be used to simplify interpretation and reporting of complications. AEs can be modestly predicted by patient characteristics, facilitating stratification of patients by risk for poststroke complications. © 2014 American Heart Association, Inc.

  20. Extracranial cerebral arterial atherosclerosis in Iranian patients suffering ischemic strokes

    Directory of Open Access Journals (Sweden)

    Sayed Ali Mousavi

    2006-12-01

    Full Text Available BACKGROUND: To determine the distribution and severity of extracranial carotid arterial atherosclerosis in Iranian patients with ischemic stroke. METHODS: 328 patients with ischemic stroke were included in this study. Doppler ultrasound was used for evaluation of atherosclerosis in extracranial carotid arteries. The NASCET criteria were used to measure carotid stenosis. RESULTS: Ninety of 328 patients (27.4% were found to have atherosclerotic plaques; 40 of these patients were women and 50 were men. Sixty-eight patients (20.7% had artery stenosis <50%, 13 patients (3.95% had 50-70 % artery stenosis and 6 (1.8% had >70% artery stenosis. CONCLUSIONS: Extracranial atherosclerosis is not rare in Iranian patients with ischemic stroke, but most carotid artery lesions were plaques with <50% stenosis. KEY WORDS: Atherosclerosis, ischemic stroke, carotid stenosis.

  1. [1-11C]octanoate as a PET tracer for studying ischemic stroke. Evaluation in a canine model of thromboembolic stroke with positron emission tomography

    International Nuclear Information System (INIS)

    Kuge, Yuji; Kawashima, Hidefumi; Minematsu, Kazuo

    2000-01-01

    Octanoate is taken up by the brain and converted in astrocytes to glutamine through the TCA cycle after β-oxidation. Consequently, [1- 11 C]octanoate might serve as a useful positron emission tomography (PET) probe for studying cerebral oxidative metabolism and/or astroglial functions. The present study attempted to evaluate the utility of using [1- 11 C]octanoate as a PET tracer for imaging and evaluating the pathophysiology of ischemic stroke. We used a canine model of thromboembolic stroke. Five male beagle dogs were implanted with an indwelling catheter in the left internal carotid artery. A single autologous blood clot was injected into the left internal carotid artery through the catheter. The brain distribution of [1- 11 C]octanoate and cerebral blood flow (CBF) were determined 24 h after insult using a high resolution PET scanner. Post mortem brain regions unstained with 2, 3, 5-triphenyltetrazolium chloride (TTC) were defined as infarcts. In the region of an infarct, accumulation of [1- 11 C]octanoate decreased concurrently with CBF reduction. In contrast, normal accumulation of [1- 11 C]octanoate was observed in ischemic but vital regions, suggesting that an increased accumulation of [1- 11 C]octanoate relative to CBF takes place in these regions. In conclusion, [1- 11 C]octanoate accumulated in ischemic but vital regions, indicating that [1- 11 C]octanoate is a potentially useful PET tracer for imaging and evaluating the pathophysiology of ischemic stroke. (author)

  2. Comparison of characteristics and healing course of diabetic foot ulcers by etiological classification: neuropathic, ischemic, and neuro-ischemic type.

    Science.gov (United States)

    Yotsu, Rie Roselyne; Pham, Ngoc Minh; Oe, Makoto; Nagase, Takeshi; Sanada, Hiromi; Hara, Hisao; Fukuda, Shoji; Fujitani, Junko; Yamamoto-Honda, Ritsuko; Kajio, Hiroshi; Noda, Mitsuhiko; Tamaki, Takeshi

    2014-01-01

    To identify differences in the characteristics of patients with diabetic foot ulcers (DFUs) according to their etiological classification and to compare their healing time. Over a 4.5-year period, 73 patients with DFUs were recruited. DFUs were etiologically classified as being of neuropathic, ischemic, or neuro-ischemic origin. Descriptive analyses were performed to characterize study subjects, foot-related factors, and healing outcome and time. Duration of healing was assessed using the Kaplan-Meier method. Healing time among the three types was compared using the log rank test. The number of patients manifesting neuropathic, ischemic, and neuro-ischemic ulcers was 30, 20, and 14, respectively. Differences were identified for age, diabetes duration, body mass index, hypertension, and estimated glomerular filtration rate. Patients with neuro-ischemic ulcers had better ankle-brachial index, skin perfusion pressure (SPP), and transcutaneous oxygen pressure values compared to those with ischemic ulcers. The average time in which 50% of patients had healed wounds was 70, 113, and 233 days for neuropathic, neuro-ischemic, and ischemic ulcers, respectively. Main factors associated with healing were age and SPP values. Based on the etiological ulcer type, DFU healing course and several patient factors differed. Failure to consider the differences in DFU etiology may have led to heterogeneity of results in previous studies on DFUs. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Predictors of migraine subtypes in young adults with ischemic stroke: the italian project on stroke in young adults.

    Science.gov (United States)

    Pezzini, Alessandro; Grassi, Mario; Lodigiani, Corrado; Patella, Rosalba; Gandolfo, Carlo; Casoni, Federica; Musolino, Rossella; Calabrò, Rocco Salvatore; Bovi, Paolo; Adami, Alessandro; Delodovici, Maria Luisa; Del Zotto, Elisabetta; Rota, Lidia Luciana; Rasura, Maurizia; Del Sette, Massimo; Giossi, Alessia; Volonghi, Irene; Zini, Andrea; Cerrato, Paolo; Costa, Paolo; Magoni, Mauro; Iacoviello, Licia; Padovani, Alessandro

    2011-01-01

    the mechanisms underlying the relationship between migraine and ischemic stroke remain uncertain. The aim of the present study was to investigate the predictive value of major cardiovascular risk factors, cardiac interatrial abnormalities, and additional biological markers on migraine subtypes in young adults with ischemic stroke. ischemic stroke patients aged 45 years or younger were consecutively enrolled as part of the Italian Project on Stroke in Young Adults. A comprehensive evaluation was performed including assessment of self-reported migraine and cardiovascular risk factors, interatrial right-to-left shunt, and genotyping to detect factor V Leiden and the G20210A mutation in the prothrombin gene. nine hundred eighty-one patients (mean age, 36.0 ± 7.6 years; 50.7% women) were included. The risk of migraine with aura increased with decreasing number of cardiovascular risk factors (OR, 0.50; 95% CI, 0.24-0.99 for 2 factors or more), increasing number of thrombophilic variants (OR, 2.21; 95% CI, 1.05-4.68 for carriers of at least 1 of the 2), and the presence of right-to-left shunt (OR, 2.41; 95% CI, 1.37-3.45), as compared to patients without migraine. None of these factors had influence on the risk of migraine without aura. in young adults with ischemic stroke, low cardiovascular risk profile, right-to-left shunt, and an underlying procoagulant state are predictors of migraine with aura. The biological effects of these factors should be considered in future studies aimed at investigating the mechanisms linking migraine to brain ischemia.

  4. Ankle-brachial index and brachial-ankle pulse wave velocity are risk factors for ischemic stroke in patients with Type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Ting Li

    2017-01-01

    Full Text Available The incidence of ischemic stroke in patients with diabetes is increasing. While brachial-ankle pulse wave velocity (BaPWV and ankle-brachial index (ABI are known to be associated with ischemic cardiovascular and cerebrovascular diseases, whether these measures predict the risk of ischemic cerebrovascular disease in diabetic patients remains unclear. 117 patients with type 2 diabetes were enrolled in this study. According to the results of head magnetic resonance imaging, the patients were divided into a diabetes-only group (n = 55 and a diabetes and ischemic stroke group (n = 62. We then performed ABI and BaPWV examinations for all patients. Compared with the diabetes-only group, we found decreased ABI and increased BaPWV in the diabetes and ischemic stroke group. Multivariate logistic regression analyses revealed that BaPWV and ABI were risk factors for ischemic stroke in patients with type 2 diabetes. Our findings indicate that decreased ABI and increased BaPWV are objective indicators of increased risk of ischemic stroke in patients with type 2 diabetes.

  5. Smoking Cessation Intervention After Ischemic Stroke or Transient Ischemic Attack. A Randomized Controlled Pilot Trial

    DEFF Research Database (Denmark)

    Brunner Frandsen, Nicole; Sørensen, Margit; Hyldahl, Tanja Kirstine

    2012-01-01

    BACKGROUND: Smoking cessation is widely recommended for secondary stroke prevention. However, little is known about the efficacy of smoking cessation intervention after stroke or transient ischemic attack (TIA). METHODS: Ninety-four smokers under age 76, admitted with ischemic stroke or TIA were ...

  6. Heparin monotherapy or bivalirudin during percutaneous coronary intervention in patients with non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease: results from the Evaluation of Drug-Eluting Stents and Ischemic Events registry.

    Science.gov (United States)

    Bangalore, Sripal; Pencina, Michael J; Kleiman, Neal S; Cohen, David J

    2014-06-01

    The use of bivalirudin versus unfractionated heparin monotherapy in patients without ST-segment-elevation myocardial infarction is not well defined. The study population consisted of patients enrolled in the Evaluation of Drug-Eluting Stents and Ischemic Events (EVENT) registry with either non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease, who underwent percutaneous coronary intervention with either unfractionated heparin or bivalirudin monotherapy. Propensity score matching was used to adjust for baseline characteristics. The primary bleeding (in-hospital composite bleeding-access site bleeding, thrombolysis in myocardial infarction major/minor bleeding, or transfusion) and primary (in-hospital death/myocardial infarction) and secondary ischemic outcomes (death/myocardial infarction/unplanned repeat revascularization at 12 months) were evaluated. Propensity score matching yielded 1036 patients with non-ST-segment-elevation acute coronary syndromes and 2062 patients with stable ischemic heart disease. For the non-ST-segment-elevation acute coronary syndrome cohort, bivalirudin use was associated with lower bleeding (difference, -3.3% [-0.8% to -5.8%]; P=0.01; number need to treat=30) without increase in either primary (difference, 1.2% [4.1% to -1.8%]; P=0.45) or secondary ischemic outcomes, including stent thrombosis (difference, 0.0% [1.3% to -1.3%]; P=1.00). Similarly, in the stable ischemic heart disease cohort, bivalirudin use was associated with lower bleeding (difference, -1.8% [-0.4% to -3.3%]; P=0.01; number need to treat=53) without increase in either primary (difference, 0.4% [2.3% to -1.5%]; P=0.70) or secondary ischemic outcomes, including stent thrombosis (difference, 0.0% [0.7% to -0.7%]; P=1.00) when compared with unfractionated heparin monotherapy. Among patients with non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease undergoing percutaneous coronary intervention, bivalirudin use

  7. Long-term deficits in episodic memory after ischemic stroke: evaluation and prediction of verbal and visual memory performance based on lesion characteristics

    NARCIS (Netherlands)

    Schouten, Eveline A.; Schiemanck, Sven K.; Brand, Nico; Post, Marcel W. M.

    2009-01-01

    We investigated the relationship between ischemic lesion characteristics (hemispheric side, cortical and subcortical level, volume) and memory performance, 1 year after stroke. Verbal and visual memory of 86 patients with stroke were assessed with Rey Auditory-Verbal Learning Test and the Doors

  8. Celecoxib sensitizes imatinib-resistant K562 cells to imatinib by inhibiting MRP1-5, ABCA2 and ABCG2 transporters via Wnt and Ras signaling pathways.

    Science.gov (United States)

    Dharmapuri, Gangappa; Doneti, Ravinder; Philip, Gundala Harold; Kalle, Arunasree M

    2015-07-01

    Imatinib mesylate, a tyrosine kinase inhibitor, is very effective in the treatment of chronic myeloid leukemia (CML). However, development of resistance to imatinib therapy is also a very common mechanism observed with long-term administration of the drug. Our previous studies have highlighted the role of cyclooxygenase-2 (COX-2) in regulating the expression of multidrug resistant protein-1 (MDR1), P-gp, in imatinib-resistant K562 cells (IR-K562) via PGE2-cAMP-PKC-NF-κB pathway and inhibition of COX-2 by celecoxib, a COX-2 specific inhibitor, inhibits this pathway and reverses the drug resistance. Studies have identified that not only MDR1 but other ATP-binding cassette transport proteins (ABC transporters) are involved in the development of imatinib resistance. Here, we tried to study the role of COX-2 in the regulation of other ABC transporters such as MRP1, MRP2, MRP3, ABCA2 and ABCG2 that have been already implicated in imatinib resistance development. The results of the study clearly indicated that overexpression of COX-2 lead to upregulation of MRP family proteins in IR-K562 cells and celecoxib down-regulated the ABC transporters through Wnt and MEK signaling pathways. The study signifies that celecoxib in combination with the imatinib can be a good alternate treatment strategy for the reversal of imatinib resistance. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans.

    Science.gov (United States)

    Reitz, Christiane; Jun, Gyungah; Naj, Adam; Rajbhandary, Ruchita; Vardarajan, Badri Narayan; Wang, Li-San; Valladares, Otto; Lin, Chiao-Feng; Larson, Eric B; Graff-Radford, Neill R; Evans, Denis; De Jager, Philip L; Crane, Paul K; Buxbaum, Joseph D; Murrell, Jill R; Raj, Towfique; Ertekin-Taner, Nilufer; Logue, Mark; Baldwin, Clinton T; Green, Robert C; Barnes, Lisa L; Cantwell, Laura B; Fallin, M Daniele; Go, Rodney C P; Griffith, Patrick; Obisesan, Thomas O; Manly, Jennifer J; Lunetta, Kathryn L; Kamboh, M Ilyas; Lopez, Oscar L; Bennett, David A; Hendrie, Hugh; Hall, Kathleen S; Goate, Alison M; Byrd, Goldie S; Kukull, Walter A; Foroud, Tatiana M; Haines, Jonathan L; Farrer, Lindsay A; Pericak-Vance, Margaret A; Schellenberg, Gerard D; Mayeux, Richard

    2013-04-10

    Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown. Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment. To identify genetic loci associated with late-onset Alzheimer disease in African Americans. The Alzheimer Disease Genetics Consortium (ADGC) assembled multiple data sets representing a total of 5896 African Americans (1968 case participants, 3928 control participants) 60 years or older that were collected between 1989 and 2011 at multiple sites. The association of Alzheimer disease with genotyped and imputed single-nucleotide polymorphisms (SNPs) was assessed in case-control and in family-based data sets. Results from individual data sets were combined to perform an inverse variance-weighted meta-analysis, first with genome-wide analyses and subsequently with gene-based tests for previously reported loci. Presence of Alzheimer disease according to standardized criteria. Genome-wide significance in fully adjusted models (sex, age, APOE genotype, population stratification) was observed for a SNP in ABCA7 (rs115550680, allele = G; frequency, 0.09 cases and 0.06 controls; odds ratio [OR], 1.79 [95% CI, 1.47-2.12]; P = 2.2 × 10(-9)), which is in linkage disequilibrium with SNPs previously associated with Alzheimer disease in Europeans (0.8 Alzheimer disease but not reaching significance in genome-wide analyses were replicated in gene-based analyses accounting for linkage disequilibrium between markers and correcting for number of tests performed per gene (CR1, BIN1, EPHA1, CD33; 0.0005 Alzheimer disease was significantly associated with variants in ABCA7 and with other genes that have been associated with Alzheimer disease in individuals of European ancestry. Replication and functional

  10. Cerebrospinal fluid and plasma concentration of soluble intercellular adhesion molecule1, vascular cell adhesion molecule1 and endothelial leukocyte adhesion molecule in patients with acute ischemic b

    Directory of Open Access Journals (Sweden)

    Selaković Vesna M.

    2003-01-01

    Full Text Available Background. Leukocyte migration into the ischemic area is a complex process controlled by adhesion molecules (AM in leukocytes and endothelium, by migratory capacity of leukocytes and the presence of hemotaxic agents in the tissue. In this research it was supposed that in the blood and cerebrospinal fluid (CSF of patients in the acute phase of ischemic brain disease (IBD there were relevant changes in the concentration of soluble AM (sICAM-1 sVCAM-1 and sE-selectin, that could have been the indicators of the intensity of damaging processes in central nervous system (CNS. Methods. The study included 45 IBD patients, 15 with transient ischemic attack (TIA 15 with reversible ischemic attack (RIA, and 15 with brain infarction (BI of both sexes, mean age 66±7. Control group consisted of 15 patients with radicular lesions of discal origin, subjected to diagnostic radiculography without the signs of interruption in the passage of CSF. Changes of selected biochemical parameters were determined in all patients in frame 72 hours since the occurence of an ischemic episode. Concentrations of soluble AM were determined in plasma and CSF by ELISA. Total number of leukocytes (TNL in peripheral blood was determined by hematological analyzer. Results. The results showed that during the first 72 hrs of IBD significant increases occured in TNL and that the increase was progressive compared to the severeness of the disease. Significant increase of soluble AM concentration was shown in plasma of IBD patients. The increase was highest in BI somewhat lower in RIA and the lowest in TIA patients compared to the control. In CSF concentrations of sICAM-1, sVCAM-1 and sE-selectin demonstrated similar increasing trend as in plasma. Conclusion. TNL, as well as the soluble AM concentrations in plasma and CSF, were increased during the acute IBD phase and progressive in relation to the severeness of the disease, so that they might have been the indicators of CNS inflammatory

  11. Magnetic resonance imaging in acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Ohta, Kouichi [Mito Red Cross Hospital (Japan)

    2000-01-01

    This paper summarizes current MRI technology used in the diagnosis of acute cerebral infarction and discusses tasks for further improvement of MRI technology. First, the principles and methods of MRI imaging are described in terms of 1) diffusion-weighted imaging (DWI) and ADC maps, 2) perfusion imaging, 3) the fluid-attenuated inversion recovery (FLAIR) method, and 4) MR angiography (MRA). Then, the actual use of MRI in the early phase of ischemic cerebrovascular disorders is discussed focusing on general MRI procedures, cases in which an ischemic lesion dose not yield a high signal with DWI in the acute phase, and chronological changes in DWI signal strength and ADC. Third, chronological changes in acute cerebrovascular disorder in an animal model of local cerebral ischemia are summarized in terms of expansion of reduced ADC areas and ischemic penumbras in the acute phase of cerebral ischemia. Finally, chronological changes in acute ischemic disorders in patients with cerebrovascular disorders are assessed by reviewing the development of reduced ADC and expansion of DWI lesions. Whether MRI can identify cerebral tissues that can be rescued by the reperfusion method by examining the mismatchs between perfusion images and DWI, relative CBV, and ADC is also discussed. (K.H.)

  12. Mortality study for a decade: ischemic stroke in the elderly.

    Directory of Open Access Journals (Sweden)

    Javier J. García Zacarías

    2014-09-01

    Full Text Available Cerebrovascular diseases are among the top three causes of death in Cuba and the world, about 80 % of these patients belong to Ischemic Stroke. The objective of this paper is to describe the clinical and developmental profile of patients who died of Ischemic Stroke. A descriptive, prospective research, cross- sectional study was made, the sample included all deaths from ischemic stroke at the University Hospital "Camilo Cienfuegos" Sancti Spiritus, between January 1st, 2001 and December 31, 2010, and persons over 60 years of age with necropsy performed. Atherothrombotic stroke was the most frequent category, the highest mortality rates were observed in persons over 80 years of age and in females, hypertension, ischemic heart disease and transient ischemic attack were the main significant medical history; most patients were admitted in the stroke unit and died in Middle Progressive Care, cerebral edema and intracranial hypertension and hypostatic bronchopne umonia were complications and specific main causes of most frequent death. Value of cerebral edema and hypostatic bronchopneumonia as clinical complications and causes of death in patients investigated is confirmed.

  13. Lipoprotein (a) as a risk factor for ischemic stroke: a meta-analysis.

    Science.gov (United States)

    Nave, Alexander H; Lange, Kristin S; Leonards, Christopher O; Siegerink, Bob; Doehner, Wolfram; Landmesser, Ulf; Steinhagen-Thiessen, Elisabeth; Endres, Matthias; Ebinger, Martin

    2015-10-01

    Lipoprotein (a) [Lp(a)] harbors atherogenic potential but its role as a risk factor for ischemic stroke remains controversial. We conducted a meta-analysis to determine the relative strength of the association between Lp(a) and ischemic stroke and identify potential subgroup-specific risk differences. A systematic search using the MeSH terms "lipoproteins" OR "lipoprotein a" AND "stroke" was performed in PubMed and ScienceDirect for case-control studies from June 2006 and prospective cohort studies from April 2009 until December 20th 2014. Data from eligible papers published before these dates were reviewed and extracted from previous meta-analyses. Studies that assessed the relationship between Lp(a) levels and ischemic stroke and reported generic data-i.e. odds ratio [OR], hazard ratio, or risk ratio [RR]-were eligible for inclusion. Studies that not distinguish between ischemic and hemorrhagic stroke and transient ischemic attack were excluded. Random effects meta-analyses with mixed-effects meta-regression were performed by pooling adjusted OR or RR. A total of 20 articles comprising 90,904 subjects and 5029 stroke events were eligible for the meta-analysis. Comparing high with low Lp(a) levels, the pooled estimated OR was 1.41 (95% CI, 1.26-1.57) for case-control studies (n = 11) and the pooled estimated RR was 1.29 (95% CI, 1.06-1.58) for prospective studies (n = 9). Sex-specific differences in RR were inconsistent between case-control and prospective studies. Study populations with a mean age of ≤55 years had an increased RR compared to older study populations. Reported Lp(a) contrast levels and ischemic stroke subtype significantly contributed to the heterogeneity observed in the analyses. Elevated Lp(a) is an independent risk factor for ischemic stroke and may be especially relevant for young stroke patients. Sex-specific risk differences remain conflicting. Further studies in these subgroups may be warranted. Copyright © 2015 Elsevier Ireland Ltd. All

  14. Diffusion MR Imaging of Postoperative Bilateral Acute Ischemic Optic Neuropathy

    International Nuclear Information System (INIS)

    Kannan, Anusha; Srinivasan, Sivasubramanian

    2012-01-01

    We read with great interest, the case report on ischemic optic neuropathy (1). We would like to add a few points concerning the blood supply of the optic nerve and the correlation with the development of post-operative ischemic neuropathy. Actually, the perioperative or post-operative vision loss (postoperative ischemic neuropathy) is most likely due to ischemic optic neuropathy. Ischemic optic neuropathy (2) is classified as an anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION). This classification is based on the fact that blood supply (2) to the anterior segment of the optic nerve (part of the optic nerve in the scleral canal and the optic disc) is supplied by short posterior ciliary vessels or anastamotic ring branches around the optic nerve. The posterior part of the optic canal is relatively less perfused, and is supplied by ophthalmic artery and central fibres are perfused by a central retinal artery. So, in the post-operative period, the posterior part of the optic nerve is more vulnerable for ischemia, especially, after major surgeries (3), one of the theories being hypotension or anaemia (2) and resultant decreased perfusion. The onset of PION is slower than the anterior ischemic optic neuropathy. AION on the other hand, is usually spontaneous (idiopathic) or due to arteritis, and is usually sudden in its onset. The reported case is most likely a case of PION. The role of imaging, especially the diffusion weighted magnetic resonance imaging, is very important because the ophthalmoscopic findings in early stages of PION is normal, and it may delay the diagnosis. On the other hand, edema of the disc is usually seen in the early stages of AION.

  15. Diffusion MR Imaging of Postoperative Bilateral Acute Ischemic Optic Neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Kannan, Anusha; Srinivasan, Sivasubramanian [Khoo Teck Puat Hospital, Singapore (Singapore)

    2012-09-15

    We read with great interest, the case report on ischemic optic neuropathy (1). We would like to add a few points concerning the blood supply of the optic nerve and the correlation with the development of post-operative ischemic neuropathy. Actually, the perioperative or post-operative vision loss (postoperative ischemic neuropathy) is most likely due to ischemic optic neuropathy. Ischemic optic neuropathy (2) is classified as an anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION). This classification is based on the fact that blood supply (2) to the anterior segment of the optic nerve (part of the optic nerve in the scleral canal and the optic disc) is supplied by short posterior ciliary vessels or anastamotic ring branches around the optic nerve. The posterior part of the optic canal is relatively less perfused, and is supplied by ophthalmic artery and central fibres are perfused by a central retinal artery. So, in the post-operative period, the posterior part of the optic nerve is more vulnerable for ischemia, especially, after major surgeries (3), one of the theories being hypotension or anaemia (2) and resultant decreased perfusion. The onset of PION is slower than the anterior ischemic optic neuropathy. AION on the other hand, is usually spontaneous (idiopathic) or due to arteritis, and is usually sudden in its onset. The reported case is most likely a case of PION. The role of imaging, especially the diffusion weighted magnetic resonance imaging, is very important because the ophthalmoscopic findings in early stages of PION is normal, and it may delay the diagnosis. On the other hand, edema of the disc is usually seen in the early stages of AION.

  16. Randomized Controlled Trial of Early Versus Delayed Statin Therapy in Patients With Acute Ischemic Stroke: ASSORT Trial (Administration of Statin on Acute Ischemic Stroke Patient).

    Science.gov (United States)

    Yoshimura, Shinichi; Uchida, Kazutaka; Daimon, Takashi; Takashima, Ryuzo; Kimura, Kazuhiro; Morimoto, Takeshi

    2017-11-01

    Several studies suggested that statins during hospitalization were associated with better disability outcomes in patients with acute ischemic stroke, but only 1 small randomized trial is available. We conducted a multicenter, open-label, randomized controlled trial in patients with acute ischemic strokes in 11 hospitals in Japan. Patients with acute ischemic stroke and dyslipidemia randomly received statins within 24 hours after admission in the early group or on the seventh day in the delayed group, in a 1:1 ratio. Statins were administered for 12 weeks. The primary outcome was patient disability assessed by modified Rankin Scale at 90 days. A total of 257 patients were randomized and analyzed (early 131, delayed 126). At 90 days, modified Rankin Scale score distribution did not differ between groups ( P =0.68), and the adjusted common odds ratio of the early statin group was 0.84 (95% confidence interval, 0.53-1.3; P =0.46) compared with the delayed statin group. There were 3 deaths at 90 days (2 in the early group, 1 in the delayed group) because of malignancy. Ischemic stroke recurred in 9 patients (6.9%) in the early group and 5 patients (4.0%) in the delayed group. The safety profile was similar between groups. Our randomized trial involving patients with acute ischemic stroke and dyslipidemia did not show any superiority of early statin therapy within 24 hours of admission compared with delayed statin therapy 7 days after admission to alleviate the degree of disability at 90 days after onset. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02549846. © 2017 American Heart Association, Inc.

  17. Gender and post-ischemic recovery of hypertrophied rat hearts

    Directory of Open Access Journals (Sweden)

    Popov Kirill M

    2006-03-01

    Full Text Available Abstract Background Gender influences the cardiac response to prolonged increases in workload, with differences at structural, functional, and molecular levels. However, it is unknown if post-ischemic function or metabolism of female hypertrophied hearts differ from male hypertrophied hearts. Thus, we tested the hypothesis that gender influences post-ischemic function of pressure-overload hypertrophied hearts and determined if the effect of gender on post-ischemic outcome could be explained by differences in metabolism, especially the catabolic fate of glucose. Methods Function and metabolism of isolated working hearts from sham-operated and aortic-constricted male and female Sprague-Dawley rats before and after 20 min of no-flow ischemia (N = 17 to 27 per group were compared. Parallel series of hearts were perfused with Krebs-Henseleit solution containing 5.5 mM [5-3H/U-14C]-glucose, 1.2 mM [1-14C]-palmitate, 0.5 mM [U-14C]-lactate, and 100 mU/L insulin to measure glycolysis and glucose oxidation in one series and oxidation of palmitate and lactate in the second. Statistical analysis was performed using two-way analysis of variance. The sequential rejective Bonferroni procedure was used to correct for multiple comparisons and tests. Results Female gender negatively influenced post-ischemic function of non-hypertrophied hearts, but did not significantly influence function of hypertrophied hearts after ischemia such that mass-corrected hypertrophied heart function did not differ between genders. Before ischemia, glycolysis was accelerated in hypertrophied hearts, but to a greater extent in males, and did not differ between male and female non-hypertrophied hearts. Glycolysis fell in all groups after ischemia, except in non-hypertrophied female hearts, with the reduction in glycolysis after ischemia being greatest in males. Post-ischemic glycolytic rates were, therefore, similarly accelerated in hypertrophied male and female hearts and higher in

  18. Phenotypic Progression of Stargardt Disease in a Large Consanguineous Tunisian Family Harboring New ABCA4 Mutations

    Directory of Open Access Journals (Sweden)

    Yousra Falfoul

    2018-01-01

    Full Text Available To assess the progression of Stargardt (STGD disease over nine years in two branches of a large consanguineous Tunisian family. Initially, different phenotypes were observed with clinical intra- and interfamilial variations. At presentation, four different retinal phenotypes were observed. In phenotype 1, bull’s eye maculopathy and slight alteration of photopic responses in full-field electroretinography were observed in the youngest child. In phenotype 2, macular atrophy and yellow white were observed in two brothers. In phenotype 3, diffuse macular, peripapillary, and peripheral RPE atrophy and hyperfluorescent dots were observed in two sisters. In phenotype 4, Stargardt disease-fundus flavimaculatus phenotype was observed in two cousins with later age of onset. After a progression of 9 years, all seven patients displayed the same phenotype 3 with advanced stage STGD and diffuse atrophy. WES and MLPA identified two ABCA4 mutations M1: c.[(?_4635_(5714+?dup; (?_6148_(6479_+? del] and M2: c.[2041C>T], p.[R681∗]. In one branch, the three affected patients had M1/M1 causal mutations and in the other branch the two affected patients had M1/M2 causal mutations. After 9-year follow-up, all patients showed the same phenotypic evolution, confirming the progressive nature of the disease. Genetic variations in the two branches made no difference to similar end-stage disease.

  19. Aspirin and the risk of cardiovascular events in atherosclerosis patients with and without prior ischemic events.

    Science.gov (United States)

    Bavry, Anthony A; Elgendy, Islam Y; Elbez, Yedid; Mahmoud, Ahmed N; Sorbets, Emmanuel; Steg, Philippe Gabriel; Bhatt, Deepak L

    2017-09-01

    The benefit of aspirin among patients with stable atherosclerosis without a prior ischemic event is not well defined. Aspirin would be of benefit in outpatients with atherosclerosis with prior ischemic events, but not in those without ischemic events. Subjects from the Reduction of Atherothrombosis for Continued Health registry were divided according to prior ischemic event (n =21 724) vs stable atherosclerosis, but no prior ischemic event (n = 11 872). Analyses were propensity score matched. Aspirin use was updated at each clinic visit and considered as a time-varying covariate. The primary outcome was the first occurrence of cardiovascular death, myocardial infarction, or stroke. In the group with a prior ischemic event, aspirin use was associated with a marginally lower risk of the primary outcome at a median of 41 months (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.65-1.01, P = 0.06). In the group without a prior ischemic event, aspirin use was not associated with a lower risk of the primary outcome at a median of 36 months (HR: 1.03, 95% CI: 0.73-1.45, P = 0.86). In this observational analysis of outpatients with stable atherosclerosis, aspirin was marginally beneficial among patients with a prior ischemic event; however, there was no apparent benefit among those with no prior ischemic event. © 2017 Wiley Periodicals, Inc.

  20. Neighborhood disadvantage and ischemic stroke: the Cardiovascular Health Study (CHS).

    Science.gov (United States)

    Brown, Arleen F; Liang, Li-Jung; Vassar, Stefanie D; Stein-Merkin, Sharon; Longstreth, W T; Ovbiagele, Bruce; Yan, Tingjian; Escarce, José J

    2011-12-01

    Neighborhood characteristics may influence the risk of stroke and contribute to socioeconomic disparities in stroke incidence. The objectives of this study were to examine the relationship between neighborhood socioeconomic status and incident ischemic stroke and examine potential mediators of these associations. We analyzed data from 3834 whites and 785 blacks enrolled in the Cardiovascular Health Study, a multicenter, population-based, longitudinal study of adults ages≥65 years from 4 US counties. The primary outcome was adjudicated incident ischemic stroke. Neighborhood socioeconomic status was measured using a composite of 6 census tract variables. Race-stratified multilevel Cox proportional hazard models were constructed adjusted for sociodemographic, behavioral, and biological risk factors. Among whites, in models adjusted for sociodemographic characteristics, stroke hazard was significantly higher among residents of neighborhoods in the lowest compared with the highest neighborhood socioeconomic status quartile (hazard ratio, 1.32; 95% CI, 1.01-1.72) with greater attenuation of the hazard ratio after adjustment for biological risk factors (hazard ratio, 1.16; 0.88-1.52) than for behavioral risk factors (hazard ratio, 1.30; 0.99-1.70). Among blacks, we found no significant associations between neighborhood socioeconomic status and ischemic stroke. Higher risk of incident ischemic stroke was observed in the most disadvantaged neighborhoods among whites, but not among blacks. The relationship between neighborhood socioeconomic status and stroke among whites appears to be mediated more strongly by biological than behavioral risk factors.

  1. Risk of ischemic stroke after atrial fibrillation diagnosis: A national sample cohort.

    Directory of Open Access Journals (Sweden)

    Mi Kyoung Son

    Full Text Available Atrial fibrillation (AF is a major risk factor for ischemic stroke and associated with a 5-fold higher risk of stroke. In this retrospective cohort study, the incidence of and risk factors for ischemic stroke in patients with AF were identified. All patients (≥30 years old without previous stroke who were diagnosed with AF in 2007-2013 were selected from the National Health Insurance Service-National Sample Cohort. To identify factors that influenced ischemic stroke risk, Cox proportional hazard regression analysis was conducted. During a mean follow-up duration of 3.2 years, 1022 (9.6% patients were diagnosed with ischemic stroke. The overall incidence rate of ischemic stroke was 30.8/1000 person-years. Of all the ischemic stroke that occurred during the follow-up period, 61.0% occurred within 1-year after AF diagnosis. Of the patients with CHA2DS2-VASc score of ≥2, only 13.6% were receiving warfarin therapy within 30 days after AF diagnosis. Relative to no antithrombotic therapy, warfarin treatment for >90 days before the index event (ischemic stroke in stroke patients and death/study end in non-stroke patients associated with decreased ischemic stroke risk (Hazard Ratio = 0.41, 95%confidence intervals = 0.32-0.53. Heart failure, hypertension, and diabetes mellitus associated with greater ischemic stroke risk. AF patients in Korea had a higher ischemic stroke incidence rate than patients in other countries and ischemic stroke commonly occurred at early phase after AF diagnosis. Long-term (>90 days continuous warfarin treatment may be beneficial for AF patients. However, warfarin treatment rates were very low. To prevent stroke, programs that actively detect AF and provide anticoagulation therapy are needed.

  2. Protective effects of incensole acetate on cerebral ischemic injury.

    Science.gov (United States)

    Moussaieff, Arieh; Yu, Jin; Zhu, Hong; Gattoni-Celli, Sebastiano; Shohami, Esther; Kindy, Mark S

    2012-03-14

    The resin of Boswellia species is a major anti-inflammatory agent that has been used for centuries to treat various conditions including injuries and inflammatory conditions. Incensole acetate (IA), a major constituent of this resin, has been shown to inhibit NF-κB activation and concomitant inflammation, as well as the neurological deficit following head trauma. Here, we show that IA protects against ischemic neuronal damage and reperfusion injury in mice, attenuating the inflammatory nature of ischemic damage. IA given post-ischemia, reduced infarct volumes and improved neurological activities in the mouse model of ischemic injury in a dose dependent fashion. The protection from damage was accompanied by inhibition of TNF-α, IL-1β and TGF-β expression, as well as NF-κB activation following injury. In addition, IA is shown to have a therapeutic window of treatment up to 6h after ischemic injury. Finally, the protective effects of IA were partially mediated by TRPV3 channels as determined by the TRPV3 deficient mice and channel blocker studies. This study suggests that the anti-inflammatory and neuroprotective activities of IA may serve as a novel therapeutic treatment for ischemic and reperfusion injury, and as a tool in the ongoing research of mechanisms for neurological damage. Published by Elsevier B.V.

  3. Observed and predicted reduction of ischemic cardiovascular events in the Simvastatin and Ezetimibe in Aortic Stenosis trial

    DEFF Research Database (Denmark)

    Holme, Ingar; Boman, Kurt; Brudi, Philippe

    2010-01-01

    In the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial, combined ezetimibe (10 mg) and simvastatin (40 mg) decreased low-density lipoprotein cholesterol levels by 50% and ischemic cardiovascular event (ICE) risk by 22% compared to placebo. A larger decrease in ICE risk might have been...... expected for the degree of lipid-lowering observed. This analysis investigated relations between changes in lipoprotein components (LCs), and ICE risk decrease in the SEAS trial in all patients, by severity of aortic stenosis (AS), and compared to results of other clinical trials. A total of 1,570 patients...

  4. Occurrence and predictors of persistent impaired glucose tolerance after acute ischemic stroke or transient ischemic attack

    NARCIS (Netherlands)

    S. Fonville (Susanne); H.M. den Hertog (Heleen); A.A.M. Zandbergen (Adrienne); P.J. Koudstaal (Peter Jan); H.F. Lingsma (Hester)

    2014-01-01

    textabstractBackground Impaired glucose tolerance is often present in patients with a transient ischemic attack (TIA) or ischemic stroke and doubles the risk of recurrent stroke. This impaired glucose tolerance can be transient, reflecting an acute stress response, or persistent, representing

  5. Association of ATP-Binding Cassette Transporter A1 Gene Polymorphisms in Type 2 Diabetes Mellitus among Malaysians

    OpenAIRE

    Haghvirdizadeh, Polin; Ramachandran, Vasudevan; Etemad, Ali; Heidari, Farzad; Ghodsian, Nooshin; Bin Ismail, Norzian; Ismail, Patimah

    2015-01-01

    Background. Type 2 diabetes mellitus (T2DM) is a complex polygenic disorder characterized by impaired insulin resistance, insulin secretion, and dysregulation of lipid and protein metabolism with environmental and genetic factors. ATP-binding cassette transporter A1 (ABCA1) gene polymorphisms are reported as the one of the genetic risk factors for T2DM in various populations with conflicting results. This study was conducted based on PCR-HRM to determine the frequency of ABCA1 gene by rs22308...

  6. An unfavorable dietary pattern is associated with symptomatic ischemic stroke and carotid atherosclerosis.

    Science.gov (United States)

    Mahe, Guillaume; Ronziere, Thomas; Laviolle, Bruno; Golfier, Véronique; Cochery, Thomas; De Bray, Jean-Michel; Paillard, François

    2010-07-01

    Ischemic strokes represent more than 80% of total strokes in Western countries. The influence of dietary factors on ischemic stroke risk is debated mainly because available data are limited. Our objective was to compare the dietary pattern of symptomatic ischemic stroke patients under 65 years old with control subjects using a validated 14-item food frequency questionnaire (FFQ). We also compared symptomatic ischemic stroke patients with carotid atherosclerosis with those without according to the presence or the absence of carotid plaque defined by duplex scanning. This was a case-control multi-center study that took place in one University hospital and two general hospitals in France. One hundred twenty-four symptomatic ischemic stroke patients (confirmation by a neurologist and imaging; 66% smokers) and 50 controls (34% smokers) without any known cardiovascular disease or previous nutritional advice were included. The main outcome measure(s) were intake scores for saturated (SFA), monounsaturated (MUFA), Omega-3 polyunsaturated (Omega-3 PUFA), and Omega-6 polyunsaturated fatty acids (Omega-6PUFA). Fruit and vegetables and an overall cardiovascular dietary score were evaluated with the FFQ. The overall cardiovascular score is calculated as (MUFA + Omega-3 PUFA + fruits and vegetables) - (SFA) scores. Compared with controls, ischemic stroke patients had a higher SFA score (6.6 +/- 3.0 vs 4.9 +/- 2.7; P vs 1.5 +/- 1.2; P vs 2.2 +/- 1.5; P = .013), Omega-6PUFA (2.6 +/- 2.5 vs 3.9 +/- 2.7; P = .002), fruit and vegetables (2.9 +/- 1.7 vs 3.8 +/- 1.6; P = .005), and a lower overall dietary score (-1.2 +/- 5.0 vs 2.5 +/- 4.4; P stroke patients with carotid atherosclerosis (n = 54) had a worse overall cardiovascular dietary score than those without (n = 68): -2.2 +/- 4.4 vs -0.2 +/- 5.2; P = .024. Compared with controls, ischemic stroke patients, especially those with carotid atherosclerosis, have an unfavorable dietary pattern (high SFA, low fruit and vegetables, and

  7. Substitution of Linoleic Acid for Other Macronutrients and the Risk of Ischemic Stroke.

    Science.gov (United States)

    Venø, Stine K; Schmidt, Erik B; Jakobsen, Marianne U; Lundbye-Christensen, Søren; Bach, Flemming W; Overvad, Kim

    2017-12-01

    Ischemic stroke is a major health problem worldwide, but the influence of dietary factors on stroke risk is not well known. This study aimed to investigate the risk of ischemic stroke and its subtypes with a higher intake from linoleic acid and a concomitant lower intake from saturated fatty acids, monounsaturated fatty acids, or glycemic carbohydrates. In the Danish prospective Diet, Cancer, and Health Study of 57 053 participants aged 50 to 64 years at baseline, information on diet was collected using a validated semiquantitative food frequency questionnaire. Information on ischemic stroke was obtained from the Danish National Patient Register, and cases were all validated and subclassified according to the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification. Substitution of linoleic acid for saturated fatty acid, monounsaturated fatty acid, or glycemic carbohydrates was investigated in relation to the risk of ischemic stroke and subtypes. Cox proportional hazards regression was used to estimate the associations with ischemic stroke adjusting for appropriate confounders. During 13.5 years of follow-up 1879 participants developed ischemic stroke. A slightly lower risk of ischemic stroke was found with a 5% higher intake of linoleic acid and a concomitant lower intake of saturated fatty acid (hazard ratio, 0.98; 95% confidence interval, 0.83-1.16), monounsaturated fatty acid (hazard ratio, 0.80; 95% confidence interval, 0.63-1.02), and glycemic carbohydrates (hazard ratio, 0.92; 95% confidence interval, 0.78-1.09), although not statistically significant. Similar patterns of association were found for large-artery atherosclerosis and small-vessel occlusions. This study suggests that replacing saturated fatty acid, glycemic carbohydrate, or monounsaturated fatty acid with linoleic acid may be associated with a lower risk of ischemic stroke. © 2017 American Heart Association, Inc.

  8. Variation in mortality of ischemic and hemorrhagic strokes in relation to high temperature

    Science.gov (United States)

    Lim, Youn-Hee; Kim, Ho; Hong, Yun-Chul

    2013-01-01

    Outdoor temperature has been reported to have a significant influence on the seasonal variations of stroke mortality, but few studies have investigated the effect of high temperature on the mortality of ischemic and hemorrhagic strokes. The main study goal was to examine the effect of temperature, particularly high temperature, on ischemic and hemorrhagic strokes. We investigated the association between outdoor temperature and stroke mortality in four metropolitan cities in Korea during 1992-2007. We used time series analysis of the age-adjusted mortality rate for ischemic and hemorrhagic stroke deaths by using generalized additive and generalized linear models, and estimated the percentage change of mortality rate associated with a 1°C increase of mean temperature. The temperature-responses for the hemorrhagic and ischemic stroke mortality differed, particularly in the range of high temperature. The estimated percentage change of ischemic stroke mortality above a threshold temperature was 5.4 % (95 % CI, 3.9-6.9 %) in Seoul, 4.1 % (95 % CI, 1.6-6.6 %) in Incheon, 2.3 % (-0.2 to 5.0 %) in Daegu and 3.6 % (0.7-6.6 %) in Busan, after controlling for daily mean humidity, mean air pressure, day of the week, season, and year. Additional adjustment of air pollution concentrations in the model did not change the effects. Hemorrhagic stroke mortality risk significantly decreased with increasing temperature without a threshold in the four cities after adjusting for confounders. These findings suggest that the mortality of hemorrhagic and ischemic strokes show different patterns in relation to outdoor temperature. High temperature was harmful for ischemic stroke but not for hemorrhagic stroke. The risk of high temperature to ischemic stroke did not differ by age or gender.

  9. Role of Endogenous Opioid System in Ischemic-Induced Late Preconditioning.

    Directory of Open Access Journals (Sweden)

    Jan Fraessdorf

    Full Text Available Opioid receptors (OR are involved in myocardial late preconditioning (LPC induced by morphine and δ1-opioid receptor (δ1-OR agonists. The role of OR in ischemic-induced LPC is unknown. We investigated whether 1 OR are involved in the trigger and/or mediation phase of LPC and 2 a time course effect on the expression of different opioid receptors and their endogenous ligands exists.Male Wistar rats were randomly allocated to four groups (each group n = 8. Awake animals were ischemic preconditioned by a 5 minutes coronary occlusion. 24 hours later, anesthetized animals underwent 25 minutes coronary occlusion followed by 2 hours of reperfusion. The role of OR was investigated by treatment with intraperitoneal naloxone (Nal 10 minutes prior to LPC (Nal-LPC; trigger phase or 10 min prior to sustained ischemia (LPC-Nal; mediation phase.LPC reduced infarct size from 61±10% in controls to 25±9% (P<0.001. Naloxone during trigger or mediation phase completely abolished LPC-induced cardioprotection (59±9% and 62±9%; P<0.001 vs. LPC. 8, 12 and 24 hours after the ischemic stimulus, expression of δ-OR in the heart was increased, whereas μ-opioid receptor (μ-OR and κ-opioid receptor (κ-OR were not. Plasma concentrations of β-endorphin and leu-enkephalin but not dynorphin were increased by LPC.Ischemic LPC is triggererd and mediated by OR. Expression of δ-OR and plasma levels of endogenous opioid peptides are increased after ischemic LPC.

  10. Noninvasive quantitative assessment of cerebral blood flow (CBF) using Tc-99m ECD SPECT with adjunctive radionuclide angiography in ischemic stroke

    International Nuclear Information System (INIS)

    Yim, Jun Sung; Choi, Yun Young; Kim, Seung Hyun; Kim, Myung Ho; Cho, Suk Shin

    1999-01-01

    Quantitative CBF measurements are essential for diagnosing ischemic lesion, evaluating the therapeutic effects and predicting the prognosis of cerebral ischemia. Even though several methods have been introduced, these techniques are too cumbersome and invasive to be applied to routine studies. In this study, a non-invasive simple method for the quantitative angiography. Fifteen normal controls and 27 patients with unilateral carotid ischemic stoke were selected. Brain perfusion index (BPI) of each hemisphere was measured in each subject by acquisition of serial radionuclide angiography after injection of 20mCi of Tc-99m ECD. With Lassen's correction algorithm of curve-linear relationship between the brain activity and blood flow, rCBF on transaxial SPECT slice corresponding with MRI lesion sites (ischemic core, border zone and contralateral mirror locus) were calculated. BPI values for normal controls showed a significant negative correlation with advantage age (r=-0.64, p=0.021) and hemisphric BPI were 11.02±1.6 and 7.8±1.4 for normal controls and patient, respectively. Significant differences were observed between two groups (p=0.0012). rCBF obtained from core zone (12±2.5 ml/100/min), boneder zone (29.2±8.1) and contralateral mirror locus (52.1±15.1) were clearly defined in each subject of patient group. Measurement of BPI and rCBF using Tc-99m ECD SPECT with adjunctive radionuclide angiography could be an useful, simple and non-invasive method in evaluation of the cerebral flood in the ischemic stroke

  11. Predictors of long-term recurrent vascular events after ischemic stroke at young age: the Italian Project on Stroke in Young Adults.

    Science.gov (United States)

    Pezzini, Alessandro; Grassi, Mario; Lodigiani, Corrado; Patella, Rosalba; Gandolfo, Carlo; Zini, Andrea; Delodovici, Maria Luisa; Paciaroni, Maurizio; Del Sette, Massimo; Toriello, Antonella; Musolino, Rossella; Calabrò, Rocco Salvatore; Bovi, Paolo; Adami, Alessandro; Silvestrelli, Giorgio; Sessa, Maria; Cavallini, Anna; Marcheselli, Simona; Bonifati, Domenico Marco; Checcarelli, Nicoletta; Tancredi, Lucia; Chiti, Alberto; Del Zotto, Elisabetta; Spalloni, Alessandra; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Giacalone, Giacomo; Ferrazzi, Paola; Poli, Loris; Morotti, Andrea; Rasura, Maurizia; Simone, Anna Maria; Gamba, Massimo; Cerrato, Paolo; Micieli, Giuseppe; Melis, Maurizio; Massucco, Davide; De Giuli, Valeria; Iacoviello, Licia; Padovani, Alessandro

    2014-04-22

    Data on long-term risk and predictors of recurrent thrombotic events after ischemic stroke at a young age are limited. We followed 1867 patients with first-ever ischemic stroke who were 18 to 45 years of age (mean age, 36.8±7.1 years; women, 49.0%), as part of the Italian Project on Stroke in Young Adults (IPSYS). Median follow-up was 40 months (25th to 75th percentile, 53). The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. One hundred sixty-three patients had recurrent thrombotic events (average rate, 2.26 per 100 person-years at risk). At 10 years, cumulative risk was 14.7% (95% confidence interval, 12.2%-17.9%) for primary end point, 14.0% (95% confidence interval, 11.4%-17.1%) for brain ischemia, and 0.7% (95% confidence interval, 0.4%-1.3%) for myocardial infarction or other arterial events. Familial history of stroke, migraine with aura, circulating antiphospholipid antibodies, discontinuation of antiplatelet and antihypertensive medications, and any increase of 1 traditional vascular risk factor were independent predictors of the composite end point in multivariable Cox proportional hazards analysis. A point-scoring system for each variable was generated by their β-coefficients, and a predictive score (IPSYS score) was calculated as the sum of the weighted scores. The area under the receiver operating characteristic curve of the 0- to 5-year score was 0.66 (95% confidence interval, 0.61-0.71; mean, 10-fold internally cross-validated area under the receiver operating characteristic curve, 0.65). Among patients with ischemic stroke aged 18 to 45 years, the long-term risk of recurrent thrombotic events is associated with modifiable, age-specific risk factors. The IPSYS score may serve as a simple tool for risk estimation.

  12. Effect of X-Ray Attenuation of Arterial Obstructions on Intravenous Thrombolysis and Outcome after Ischemic Stroke.

    Directory of Open Access Journals (Sweden)

    Grant Mair

    Full Text Available To assess whether the x-ray attenuation of intra-arterial obstruction measured on non-contrast CT in ischemic stroke can predict response to thrombolysis and subsequent functional outcome.The Third International Stroke Trial (IST-3 was a multicenter randomized-controlled trial of intravenous thrombolysis (rt-PA given within six hours of ischemic stroke. Ethical approval and informed consent were obtained. In a subgroup of 109 IST-3 patients (38 men, median age 82 years, a single reader, masked to all clinical and other imaging data, manually measured x-ray attenuation (Hounsfield Units, HU on non-contrast CT at the location of angiographically-proven intra-arterial obstructions, pre-randomization and at 24-48 hour follow-up. We calculated change in attenuation between scans. We assessed the impact of pre-randomization arterial obstruction attenuation on six-month functional outcome.Most arterial obstructions (64/109, 59% were hyperattenuating (mean 51.0 HU. Compared with control, treatment with rt-PA was associated with a greater, but non-significant, reduction in obstruction attenuation at follow-up (-8.0 HU versus -1.4 HU in patients allocated control, p = 0.117. In multivariable ordinal regression analysis controlled for patient age, stroke severity, location and extent of obstruction, time from stroke onset to baseline scan and rt-PA treatment allocation, the attenuation of pre-randomization arterial obstruction was not independently associated with six-month outcome (odds ratio = 0.99, 95% confidence interval = 0.94-1.03, p = 0.516.In ischemic stroke, the x-ray attenuation of the arterial obstruction may decline more rapidly from baseline to 24-48 hours following treatment with thrombolysis but we found no evidence that baseline arterial obstruction attenuation predicts six-month outcome.

  13. Prediction of early recurrent thromboembolic event and major bleeding in patients with acute stroke and atrial fibrillation by a risk stratification schema: the ALESSA score study

    OpenAIRE

    Paciaroni, Maurizio; Agnelli, Giancarlo; Caso, Valeria; Tsivgoulis, Georgios; Furie, Karen L; Tadi, Prasanna; Becattini, Cecilia; Falocci, Nicola; Zedde, Marialuisa; Abdul-Rahim, Azmil H.; Lees, Kennedy R.; Alberti, Andrea; Venti, Michele; Acciarresi, Monica; D'Amore, Cataldo

    2017-01-01

    Background and Purposes—This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation.\\ud \\ud Methods—The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00–1.11) and severe atrial enlar...

  14. Whole Grain Consumption and Risk of Ischemic Stroke: Results From 2 Prospective Cohort Studies.

    Science.gov (United States)

    Juan, Juan; Liu, Gang; Willett, Walter C; Hu, Frank B; Rexrode, Kathryn M; Sun, Qi

    2017-12-01

    Higher intake of whole grains may exert cardiometabolic benefits, although findings on stroke risk are inconclusive. The potentially differential effects of individual whole grain foods on ischemic stroke have not been examined. We analyzed whole grain consumption in relation to ischemic stroke among 71 750 women from the Nurses' Health Study and 42 823 men from the Health Professionals Follow-up Study who were free of cardiovascular disease, diabetes mellitus, and cancer at baseline (1984 and 1986, respectively) through 2010 using a Cox proportional hazards model. Validated semiquantitative food frequency questionnaires were used to assess consumption of whole grain intake, including whole grain cold breakfast cereal, dark bread, oatmeal, brown rice, popcorn, bran, and germ. Self-reported incident cases of ischemic stroke were confirmed through medical record review. During 2 820 128 person-years of follow-up in the 2 cohorts, 2458 cases of ischemic stroke were identified and confirmed. Intake of total whole grains was not associated with risk of ischemic stroke after adjustment for covariates: the pooled hazard ratio (95% confidence interval) comparing extreme intake levels was 1.04 (0.91-1.19). However, intake of whole grain cold breakfast cereal and total bran was inversely associated with ischemic stroke after multivariate adjustment: the pooled hazard ratios (95% confidence intervals) were 0.88 (0.80-0.96; P trend =0.008) and 0.89 (0.79-1.00; P trend =0.004), respectively. Other whole grain foods were not associated with a lower risk of ischemic stroke. Although overall consumption of whole grains was not associated with lower risk of ischemic stroke, greater consumption of whole grain cold breakfast cereal and bran was significantly associated with a lower risk of ischemic stroke. More studies are needed to replicate these associations between individual whole grain foods and risk of ischemic stroke among other populations. © 2017 American Heart

  15. High expression of arachidonate 15-lipoxygenase and proinflammatory markers in human ischemic heart tissue

    International Nuclear Information System (INIS)

    Magnusson, Lisa U.; Lundqvist, Annika; Asp, Julia; Synnergren, Jane; Johansson, Cecilia Thalén; Palmqvist, Lars; Jeppsson, Anders; Hultén, Lillemor Mattsson

    2012-01-01

    Highlights: ► We found a 17-fold upregulation of ALOX15 in the ischemic heart. ► Incubation of human muscle cells in hypoxia showed a 22-fold upregulation of ALOX15. ► We observed increased levels of proinflammatory markers in ischemic heart tissue. ► Suggesting a link between ischemia and inflammation in ischemic heart biopsies. -- Abstract: A common feature of the ischemic heart and atherosclerotic plaques is the presence of hypoxia (insufficient levels of oxygen in the tissue). Hypoxia has pronounced effects on almost every aspect of cell physiology, and the nuclear transcription factor hypoxia inducible factor-1α (HIF-1α) regulates adaptive responses to low concentrations of oxygen in mammalian cells. In our recent work, we observed that hypoxia increases the proinflammatory enzyme arachidonate 15-lipoxygenase (ALOX15B) in human carotid plaques. ALOX15 has recently been shown to be present in the human myocardium, but the effect of ischemia on its expression has not been investigated. Here we test the hypothesis that ischemia of the heart leads to increased expression of ALOX15, and found an almost 2-fold increase in HIF-1α mRNA expression and a 17-fold upregulation of ALOX15 mRNA expression in the ischemic heart biopsies from patients undergoing coronary bypass surgery compared with non ischemic heart tissue. To investigate the effect of low oxygen concentration on ALOX15 we incubated human vascular muscle cells in hypoxia and showed that expression of ALOX15 increased 22-fold compared with cells incubated in normoxic conditions. We also observed increased mRNA levels of proinflammatory markers in ischemic heart tissue compared with non-ischemic controls. In summary, we demonstrate increased ALOX15 in human ischemic heart biopsies. Furthermore we demonstrate that hypoxia increases ALOX15 in human muscle cells. Our results yield important insights into the underlying association between hypoxia and inflammation in the human ischemic heart disease.

  16. Immunomodulators and microRNAs as neurorestorative therapy for ischemic stroke

    Directory of Open Access Journals (Sweden)

    Bridget Martinez

    2017-01-01

    Full Text Available Most of all strokes are ischemic due to occlusion of a vessel, and comprise two main types, thrombotic and embolic. Inflammation and immune response play an important role in the outcome of ischemic stroke. Pharmaceutical and cell-based therapies with immunomodulatory properties could be of benefit in treating ischemic stroke. Possible changes in microRNAs brought about by immunomodulatory treatments may be important. The pharmaceutical studies described in this review have identified several differentially regulated miRNAs associated with disregulation of mRNA targets or the upregulation of several neuroprotective genes, thereby highlighting the potential neuroprotective roles of specific miRNAs such as miR-762, -1892, -200a, -145. MiR-124, -711, -145 are the strongly associated miRNAs predicted to mediate anti-inflammatory pathways and microglia/macrophage M2-like activation phenotype. The cell-based therapy studies reviewed have mainly utilized mesenchymal stem cells or human umbilical cord blood cells and shown to improve functional and neurological outcomes in stroke animals. MiR-145 and miR-133b were implicated in nerve cell remodeling and functional recovery after stroke. Human umbilical cord blood cells decreased proinflammatory factors and promoted M2 macrophage polarization in stroke diabetic animals.

  17. Lipid profiles and ischemic stroke risk: variations by sex within racial/ethnic groups

    Directory of Open Access Journals (Sweden)

    Gezmu T

    2014-05-01

    Full Text Available Tefera Gezmu,1 Dona Schneider,1 Kitaw Demissie,2 Yong Lin,2 Christine Giordano,3 Martin S Gizzi4 1Edward J. Bloustein School of Planning and Public Policy, Rutgers, the State University of New Jersey, New Brunswick, NJ, 2Rutgers School of Public Health, Department of Epidemiology, Piscataway, NJ, 3Rutgers New Jersey Medical School, Newark, NJ, 4New Jersey Neuroscience Institute at JFK Medical Center and Seton Hall University, Edison, NJ, USA Abstract: Evidence implicates lipid abnormalities as important but modifiable risk factors for stroke. This study assesses whether hypercholesterolemia can be used to predict the risk for etiologic subtypes of ischemic stroke between sexes within racial/ethnic groups. Data elements related to stroke risk, diagnosis, and outcomes were abstracted from the medical records of 3,290 acute stroke admissions between 2006 and 2010 at a regional stroke center. Sex comparison within racial/ethnic groups revealed that South Asian and Hispanic men had a higher proportion of ischemic stroke than women, while the inverse was true for Whites and African Americans (P=0.0014. All women, except South Asian women, had higher mean plasma total cholesterol and higher blood circulating low-density lipoprotein levels (≥100 mg/dL than men at the time of their admissions. The incidence of large-artery atherosclerosis (LAA was more common among women than men, except among Hispanics, where men tended to have higher incidences. A regression analysis that considered patients diagnosed with either LAA or small-artery occlusion etiologic subtype as the outcomes and high-density lipoproteins and triglycerides as predictors showed inconsistent associations between lipid profiles and the incidence of these subtypes between the sexes within racial/ethnic groups. In conclusion, our investigation suggests that women stroke patients may be at increased risk for stroke etiologic subtype LAA than men. Although the higher prevalence of stroke

  18. Effect of sample size on multi-parametric prediction of tissue outcome in acute ischemic stroke using a random forest classifier

    Science.gov (United States)

    Forkert, Nils Daniel; Fiehler, Jens

    2015-03-01

    The tissue outcome prediction in acute ischemic stroke patients is highly relevant for clinical and research purposes. It has been shown that the combined analysis of diffusion and perfusion MRI datasets using high-level machine learning techniques leads to an improved prediction of final infarction compared to single perfusion parameter thresholding. However, most high-level classifiers require a previous training and, until now, it is ambiguous how many subjects are required for this, which is the focus of this work. 23 MRI datasets of acute stroke patients with known tissue outcome were used in this work. Relative values of diffusion and perfusion parameters as well as the binary tissue outcome were extracted on a voxel-by- voxel level for all patients and used for training of a random forest classifier. The number of patients used for training set definition was iteratively and randomly reduced from using all 22 other patients to only one other patient. Thus, 22 tissue outcome predictions were generated for each patient using the trained random forest classifiers and compared to the known tissue outcome using the Dice coefficient. Overall, a logarithmic relation between the number of patients used for training set definition and tissue outcome prediction accuracy was found. Quantitatively, a mean Dice coefficient of 0.45 was found for the prediction using the training set consisting of the voxel information from only one other patient, which increases to 0.53 if using all other patients (n=22). Based on extrapolation, 50-100 patients appear to be a reasonable tradeoff between tissue outcome prediction accuracy and effort required for data acquisition and preparation.

  19. Impaired mitochondrial function in chronically ischemic human heart

    DEFF Research Database (Denmark)

    Stride, Nis Ottesen; Larsen, Steen; Hey-Mogensen, Martin

    2013-01-01

    , and finally to assess myocardial antioxidant levels. Mitochondrial respiration in biopsies from ischemic and nonischemic regions from the left ventricle of the same heart was compared in nine human subjects. Maximal oxidative phosphorylation capacity in fresh muscle fibers was lower in ischemic compared.......05), and the levels of antioxidant protein expression was lower. Diminished mitochondrial respiration capacity and excessive ROS production demonstrate an impaired mitochondrial function in ischemic human heart muscle. No chronic ischemic preconditioning effect was found....

  20. Clinical neurological characteristics of ischemic stroke subtypes in acute phase

    Directory of Open Access Journals (Sweden)

    S. I. Shkrobot

    2018-02-01

    Full Text Available Objectives. The aim of the present study was to clarify clinical neurological characteristics and different ischemic stroke subtypes unfavorable course predictors in acute phase. Material and Methods. 482 patients with different ischemic stroke subtypes were observed. Among them there were 125 (25.9 % with cardioembolic infarct (CEI, 119 (24.7 % with large artery atherosclerosis (LAAS infarct, 122 (25.3 % with lacunar stroke (LAC, 116 (24.1 % with stroke of undetermined etiology (UDE. The comparative analysis of clinical picture was performed. The predictors of unfavorable course of acute phase were established. Results. We have found out that severe neurological deficit, high mortality and the worst functional outcome during the first 14 days were observed in patients with CEI and LAAS. The highest frequency of early neurological deterioration (END was detected at LAC (in 22.7 % of patients. There was a relationship between END and presence of transient ischemic attack (TIA in past medical history, the level of systolic blood pressure (SBP at the beginning of the disease and the degree of carotid arteries stenosis on the side of lesion. The patients with LAC had mild neurological deficit and better prognosis compared with other ischemic stroke subtypes. Among the clinical factors that have impact on the CEI, LAAS and UDE acute phase course were: the size of lesion, the level of consciousness on the 1st day, the baseline SBP, patient’s age. At LAAS, the presence of transient ischemic attack (TIA in past medical history and low SBP in the onset of the disease (less than140 mm Hg has an additional prognostic value for an unfavorable functional outcome. The severity of LAC in acute period depended on its localization and size. Localization of LAC in the internal capsule, thalamus and pons were characterized by the highest severity. Conclusions. Clinical neurological features of ischemic stroke depend on its subtype and have some prognostic value

  1. MRI in ischemic heart disease

    International Nuclear Information System (INIS)

    Hazirolan, T.

    2012-01-01

    Full text: The role of magnetic resonance imaging in the evaluation of ischemic heart disease has increased over the last years. Cardiac MRI is the only imaging modality that provides 'one stop shop' assessment. Information about ventricular function, myocardial ischemia and myocardial viability can be obtained in a single cardiac MRI session. Additionally, Cardiac MRI has become a gold standard method in evaluation of myocardial viability and in assessment of ventricular mass and function. As a result, cardiac MRI enable radiologist to comprehensively assess ischemic heart disease. The aim of this presentation is to provide the reader a state-of-the art on how the newest cardiac MRI techniques can be used to study ischemic heart disease patients.

  2. Short Telomere Length and Ischemic Heart Disease

    DEFF Research Database (Denmark)

    Madrid, Alexander Scheller; Rode, Line; Nordestgaard, Børge Grønne

    2016-01-01

    are associated with high risk of ischemic heart disease using a Mendelian randomization approach free of reverse causation and of most confounding. METHODS: We genotyped 3 genetic variants in OBFC1 (oligonucleotide/oligosaccharide binding fold containing 1), TERT (telomerase reverse transcriptase), and TERC...

  3. Cosegregation and functional analysis of mutant ABCR (ABCA4) alleles in families that manifest both Stargardt disease and age-related macular degeneration.

    Science.gov (United States)

    Shroyer, N F; Lewis, R A; Yatsenko, A N; Wensel, T G; Lupski, J R

    2001-11-01

    Mutations in ABCR (ABCA4) have been reported to cause a spectrum of autosomal recessively inherited retinopathies, including Stargardt disease (STGD), cone-rod dystrophy and retinitis pigmentosa. Individuals heterozygous for ABCR mutations may be predisposed to develop the multifactorial disorder age-related macular degeneration (AMD). We hypothesized that some carriers of STGD alleles have an increased risk to develop AMD. We tested this hypothesis in a cohort of families that manifest both STGD and AMD. With a direct-sequencing mutation detection strategy, we found that AMD-affected relatives of STGD patients are more likely to be carriers of pathogenic STGD alleles than predicted based on chance alone. We further investigated the role of AMD-associated ABCR mutations by testing for expression and ATP-binding defects in an in vitro biochemical assay. We found that mutations associated with AMD have a range of assayable defects ranging from no detectable defect to apparent null alleles. Of the 21 missense ABCR mutations reported in patients with AMD, 16 (76%) show abnormalities in protein expression, ATP-binding or ATPase activity. We infer that carrier relatives of STGD patients are predisposed to develop AMD.

  4. Transient Ischemic Attack and Ischemic Stroke in Danon Disease with Formation of Left Ventricular Apical Thrombus despite Normal Systolic Function

    Directory of Open Access Journals (Sweden)

    Takeshi Tsuda

    2017-01-01

    Full Text Available Danon disease is a rare X-linked dominant skeletal and cardiac muscle disorder presenting with hypertrophic cardiomyopathy, Wolf-Parkinson-White syndrome, skeletal myopathy, and mild intellectual disability. Early morbidity and mortality due to heart failure or sudden death are known in Danon disease, more in males than in females. Here, we present a 17-year-old female adolescent with Danon disease and severe concentric hypertrophy with normal left ventricular (LV systolic function, who has been complaining of intermittent headache and weakness for about 3 years, initially diagnosed with hemiplegic migraine. Subsequently, her neurological manifestation progressed to transient ischemic attack (TIA and eventually to ischemic stroke confirmed by CT scan with 1-day history of expressive aphasia followed by persistent left side weakness and numbness. Detailed echocardiogram for the first time revealed a small LV apical thrombus with unchanged severe biventricular hypertrophy and normal systolic function. This unexpected LV apical thrombus may be associated with a wide spectrum of neurological deficits ranging from TIA to ischemic stroke in Danon disease. Possibility of cerebral ischemic events should be suspected in Danon disease when presenting with neurological deficits even with normal systolic function. Careful assessment for LV apical thrombus is warranted in such cases.

  5. Effect of pre-stroke use of ACE inhibitors on ischemic stroke severity

    Directory of Open Access Journals (Sweden)

    Caplan Louis

    2005-06-01

    Full Text Available Abstract Background Recent trials suggest that angiotensin-converting enzyme inhibitors (ACEI are effective in prevention of ischemic stroke, as measured by reduced stroke incidence. We aimed to compare stroke severity between stroke patients who were taking ACEI before their stroke onset and those who were not, to examine the effects of pretreatment with ACEI on ischemic stroke severity. Methods We retrospectively studied 126 consecutive patients presenting within 24 hours of ischemic stroke onset, as confirmed by diffusion-weighted magnetic resonance imaging (DWI. We calculated the NIHSS score at presentation, as the primary measure of clinical stroke severity, and categorized stroke severity as mild (NIHSS [less than or equal to] 7, moderate (NIHSS 8–13 or severe (NIHSS [greater than or equal to] 14. We analyzed demographic data, risk-factor profile, blood pressure (BP and medications on admissions, and determined stroke mechanism according to TOAST criteria. We also measured the volumes of admission diffusion- and perfusion-weighted (DWI /PWI magnetic resonance imaging lesions, as a secondary measure of ischemic tissue volume. We compared these variables among patients on ACEI and those who were not. Results Thirty- three patients (26% were on ACE-inhibitors. The overall median baseline NIHSS score was 5.5 (range 2–21 among ACEI-treated patients vs. 9 (range 1–36 in non-ACEI patients (p = 0.036. Patients on ACEI prior to their stroke had more mild and less severe strokes, and smaller DWI and PWI lesion volumes compared to non-ACEI treated patients. However, none of these differences were significant. Predictably, a higher percentage of patients on ACEI had a history of heart failure (p = 0.03. Age, time-to-imaging or neurological evaluation, risk-factor profile, concomitant therapy with lipid lowering, other antihypertensives or antithrombotic agents, or admission BP were comparable between the two groups. Conclusion Our results

  6. Is endothelial microvascular function equally impaired among patients with chronic Chagas and ischemic cardiomyopathy?

    Science.gov (United States)

    Borges, Juliana Pereira; Mendes, Fernanda de Souza Nogueira Sardinha; Lopes, Gabriella de Oliveira; Sousa, Andréa Silvestre de; Mediano, Mauro Felippe Felix; Tibiriçá, Eduardo

    2018-08-15

    Chronic Chagas cardiomyopathy (CCC) and cardiomyopathies due to other etiologies involve differences in pathophysiological pathways that are still unclear. Systemic microvascular abnormalities are associated with the pathogenesis of ischemic heart disease. However, systemic microvascular endothelial function in CCC remains to be elucidated. Thus, we compared the microvascular endothelial function of patients presenting with CCC to those with ischemic cardiomyopathy disease. Microvascular reactivity was assessed in 21 patients with cardiomyopathy secondary to Chagas disease, 21 patients with cardiomyopathy secondary to ischemic disease and 21 healthy controls. Microvascular blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with iontophoresis of acetylcholine (ACh). Peak increase in forearm blood flow with ACh iontophoresis in relation to baseline was greater in healthy controls than in patients with heart disease (controls: 162.7 ± 58.4% vs. ischemic heart disease: 74.1 ± 48.3% and Chagas: 85.1 ± 68.1%; p < 0.0001). Patients with Chagas and ischemic cardiomyopathy presented similar ACh-induced changes from baseline in skin blood flow (p = 0.55). Endothelial microvascular function was equally impaired among patients with CCC and ischemic cardiomyopathy. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Agonist of inward rectifier K+ channels enhances the protection of ischemic postconditioning in isolated rat hearts.

    Science.gov (United States)

    Liao, Z; Feng, Z; Long, C

    2014-07-01

    Selective inhibition of inward rectifier K + channels could abolish the protection mediated by ischemic preconditioning, but the roles of these channels in ischemic postconditioning have not been well characterized. Our study aims to evaluate the effect of inward rectifier K + channels on the protection induced by ischemic postconditioning. Langendorff-perfused rat hearts (n=8 per group) were split into four groups: postconditioning hearts (IPO group); ischemic postconditioning with BaCl 2 hearts (PB group); ischemic postconditioning with zacopride hearts (PZ group); and without ischemic postconditioning (CON group). After suffering 30 minutes of global ischemia, groups IPO, PB and PZ went through 10 seconds of ischemic postconditioning with three different perfusates: respectively, Krebs-Henseleit buffer (IPO group); 20 μmol/L BaCl 2 (antagonist of the channel, PB group); 1 μmol/L zacopride (agonist of the channel, PZ group). At the end of reperfusion, the myocardial performance was better preserved in the PZ group than the other three groups. The PB group showed no significant differences from the CON group. Our study has shown that the I K1 channel agonist zacopride is associated with the enhancement of ischemic postconditioning. © The Author(s) 2014.

  8. Estrogen-IGF-1 interactions in neuroprotection: Ischemic Stroke as a case study

    Science.gov (United States)

    Sohrabji, Farida

    2014-01-01

    The steroid hormone 17b-estradiol and the peptide hormone insulin-like growth factor (IGF)-1 independently exert neuroprotective actions in neurologic diseases such as stroke. Only a few studies have directly addressed the interaction between the two hormone systems, however, there is a large literature that indicates potentially greater interactions between the 17b-estradiol and IGF-1 systems. The present review focuses on key issues related to this interaction including IGF-1 and sex differences and common activation of second messenger systems. Using ischemic stroke as a case study, this review also focuses on independent and cooperative actions of estrogen and IGF-1 on neuroprotection, blood brain barrier integrity, angiogenesis, inflammation and post-stroke epilepsy. Finally, the review also focuses on the astrocyte, a key mediator of post stroke repair, as a local source of 17b-estradiol and IGF-1. This review thus highlights areas where significant new research is needed to clarify the interactions between these two neuroprotectants. PMID:24882635

  9. Arterial Stiffness and Functional Outcome in Acute Ischemic Stroke

    OpenAIRE

    Lee, Yeong-Bae; Park, Joo-Hwan; Kim, Eunja; Kang, Chang-Ki; Park, Hyeon-Mi

    2014-01-01

    Objective Arterial stiffness is a common change associated with aging and can be evaluated by measuring pulse wave velocity (PWV) between sites in the arterial tree, with the stiffer artery having the higher PWV. Arterial stiffness is associated with the risk of stroke in the general population and of fatal stroke in hypertensive patients. This study is to clarify whether PWV value predicts functional outcome of acute ischemic stroke. Methods One hundred patients were enrolled with a diagnosi...

  10. Functional reconstruction of ischemic contracture in the

    Directory of Open Access Journals (Sweden)

    TANG Hao

    2011-04-01

    Full Text Available 【Abstract】Objective: To discuss the method of functional reconstruction of ischemic contracture in the lower limb and propose a classification protocol for ischemic contracture in the lower limb based on its severity and prognosis. Methods: A total of 42 patients with ischemic contracture in the lower limb were included in this study. According to different types of disturbance and degrees of severity, surgical reconstructions consisting of nerve decompression, tendon lengthening or transfer, intrinsic foot muscle release and sural-tibial nerve anastomosis were performed in every patient. Results: Postoperatively, all patients were able to walk on flat ground. Drop foot was corrected in 10 patients, and 5 patients still felt some difficulty during stair activity. Split Achilles tendon transfer to flexor hallucis longus tendon was performed in 12 patients, and their walking stability was improved. Seven patients accepted ipsilateral suraltibial nerve anastomosis, and sensitivity recovery reached to S2 in 2 patients and S3 in 5 patients. Conclusions: Ischemic contracture in the lower limb is a devastating complication after lower limb trauma. The prevention of contracture is much more important than the treatment of an established contracture. Split Achilles tendon transfer to flexor hallucis longus tendon and sural-tibial nerve anastomosis, which was initially implemented by us, could improve the functional recovery of ischemic contracture in lower limbs, and thus provides a new alternative for functional reconstruction of ischemic contracture in the lower limb. Key words: Ischemic contracture; Classification; Recovery of function

  11. The Neuroprotective Effect Of Electro-Acupuncture Against Ischemic ...

    African Journals Online (AJOL)

    The Neuroprotective Effect Of Electro-Acupuncture Against Ischemic Stroke In Animal Model: A Review. ... Conclusion: An awareness of the benefits of acupuncture might lead more patients into accepting acupuncture therapy for the management of patients with ischemic stroke and patients with high risk of ischemic stroke.

  12. Management of hypertension in the setting of acute ischemic stroke.

    Science.gov (United States)

    Heitsch, Laura; Jauch, Edward C

    2007-12-01

    The optimal management of blood pressure in the first 24 hours of ischemic stroke remains a controversial topic. Most patients are hypertensive at presentation and subsequently experience a spontaneous decline in blood pressure. Decreasing penumbral blood flow and exacerbating vasogenic edema are significant concerns in whether to treat blood pressure elevations. Although an initially elevated blood pressure has been associated with poor outcome, attempts to acutely lower blood pressure are also associated with worsened outcomes. Thus, the current approach in acute ischemic stroke is permissive hypertension, in which antihypertensive treatment is warranted in patients with systolic blood pressure greater than 220 mm Hg, receiving thrombolytic therapy, or with concomitant medical issues. The use of predictable and titratable medications that judiciously reduce (approximately 10% to 15%) the initial presenting mean arterial pressure is recommended in these situations. Future study must define optimal blood pressure goals, likely on an individual basis.

  13. Changes of plasma neuropeptide Y levels in patients with ischemic heart disease

    International Nuclear Information System (INIS)

    Cheng Guanghua; Zhang Xinlu; Yang Jun

    2001-01-01

    Objective: To study the pathophysiological significance of neuropeptide Y(NPY) in ischemic heart disease (IHD). Methods: The plasma NPY levels were measured by radioimmunoassay in 35 patients with angina pectoris (Group A), 31 patients with acute myocardial infarctions (AMI) without heart failure (Group B), 29 patients of AMI with left heart failure (Group C) and 27 normal subjects. Results: The plasma NPY levels were higher in all these patients on admission than those in controls with the highest values in the most severe patients. The NPY levels in group A decreased to normal levels on day 1. In group B a significant increase in the levels of NPY was observed on day 1. Their NPY levels decreased significantly on days 4 and 7, but never to normal levels until day 28. Considerable increase in the levels of NPY were observed in group C on days 1 and 4. The levels of NPY were extremely high in six AMI patients with acute left heart failure before death. The NPY levels began to decrease on day 7 but never to their levels on admission until day 28; at that time the NPY levels were still higher than those in controls. Conclusion: These information indicated that plasma NPY might be useful for monitoring and predicting prognosis in patients with ischemic heart disease

  14. Prevalence of Fabry disease in young patients with cryptogenic ischemic stroke.

    Science.gov (United States)

    Dubuc, Véronique; Moore, David F; Gioia, Laura C; Saposnik, Gustavo; Selchen, Daniel; Lanthier, Sylvain

    2013-11-01

    A German study diagnosed 4% of young cryptogenic ischemic stroke patients with Fabry disease, an X-linked lysosomal storage disease caused by mutations in the alpha-galactosidase A (α-GAL-A) gene resulting in an accumulation of glycosphingolipids. A lower prevalence was found in other geographic regions. To determine the prevalence of Fabry disease in a Canadian population of young cryptogenic ischemic stroke patients. Patients with cryptogenic ischemic stroke at age 16-55 were retrospectively identified in our institutional stroke database and underwent a focused clinical evaluation. We sequenced the α-GAL-A gene and measured the levels of blood globotriaosylsphingosine in subjects with mutations of undetermined pathogenicity. Fabry disease was diagnosed in patients with pathogenic mutations or increased levels of blood globotriaosylsphingosine. Ninety-three of 100 study subjects had normal α-GAL-A gene polymorphisms. Seven had mutations of undetermined pathogenicity, including one with increased globotriaosylsphingosine (prevalence, 1%; 95% confidence interval, ischemic stroke presentation as the first clinical manifestation of Fabry disease. Both Fabry patients experienced recurrent ischemic stroke. Fabry disease accounts for a small proportion of young Canadians with cryptogenic ischemic stroke. Identification of Fabry biomarkers remains a research priority to delineate stroke patients disserving routine screening. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  15. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack.

    Science.gov (United States)

    Kernan, Walter N; Viscoli, Catherine M; Furie, Karen L; Young, Lawrence H; Inzucchi, Silvio E; Gorman, Mark; Guarino, Peter D; Lovejoy, Anne M; Peduzzi, Peter N; Conwit, Robin; Brass, Lawrence M; Schwartz, Gregory G; Adams, Harold P; Berger, Leo; Carolei, Antonio; Clark, Wayne; Coull, Bruce; Ford, Gary A; Kleindorfer, Dawn; O'Leary, John R; Parsons, Mark W; Ringleb, Peter; Sen, Souvik; Spence, J David; Tanne, David; Wang, David; Winder, Toni R

    2016-04-07

    Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; Pischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).

  16. Air Pollution and Ischemic Stroke Among Young Adults.

    Science.gov (United States)

    Yitshak Sade, Maayan; Novack, Victor; Ifergane, Gal; Horev, Anat; Kloog, Itai

    2015-12-01

    Studies have demonstrated consistent associations between cardiovascular illness and particulate matter (PM) stroke received less attention. We hypothesized that air pollution, an inflammation progenitor, can be associated with stroke incidence in young patients in whom the usual risk factors for stroke are less prevalent. We aimed to evaluate the association between stroke incidence and exposure to PM stroke between 2005 and 2012. Exposure assessment was based on a hybrid model incorporating daily satellite remote sensing data at 1-km spatial resolution. We performed case-crossover analysis, stratified by personal characteristics and distance from main roads. We identified 4837 stroke cases (89.4% ischemic stroke). Interquartile range of PM ischemic stroke and increases of interquartile range average concentrations of particulate matter ischemic stroke associated with PM among young adults. This finding can be explained by the inflammatory mechanism, linking air pollution and stroke. © 2015 American Heart Association, Inc.

  17. Risk factors in various subtypes of ischemic stroke according to toast criteria

    International Nuclear Information System (INIS)

    Aquil, N.; Begum, I.; Ahmed, A.; Vohra, E.A.

    2011-01-01

    To identify the frequency of risk factors in various subtypes of acute ischemic stroke according to TOAST criteria. Study Design: Cross-sectional, observational study. Place and Duration of Study: Ziauddin Hospital, Karachi, from January to December 2007. Methodology: Patients with acute ischemic stroke were enrolled. Studied variables included demographic profile, history of risk factors, physical and neurological examination, and investigations relevant with the objectives of the study. Findings were described as frequency percentages. Proportions of risk factors against subtypes was compared using chi-square test with significance at p < 0.05. Results: Out of the 100 patients with acute ischemic stroke, mean age at presentation was 63.5 years. Risk factor distribution was hypertension in 85%, Diabetes mellitus in 49%, ischemic heart disease in 30%, dyslipedemia in 22%, smoking in 9%, atrial fibrillation in 5%, and previous history of stroke in 29%. The various subtypes of acute ischemic stroke were lacunar infarct in 43%, large artery atherosclerosis in 31%, cardioembolic type in 8%, stroke of other determined etiology in 1% and stroke of undetermined etiology in 18%. Hypertension and Diabetes were the most important risk factors in both large and small artery atherosclerosis. In patients with cardio-embolic stroke significant association was found with ischemic heart disease (p=0.01). Conclusion: Importance and relevance of risk factors evaluated for subtypes rather than ischemic stroke as a whole should be reflected in preventive efforts against the burden of ischemic stroke. (author)

  18. Modulation of microRNA Expression in Subjects with Metabolic Syndrome and Decrease of Cholesterol Efflux from Macrophages via microRNA-33-Mediated Attenuation of ATP-Binding Cassette Transporter A1 Expression by Statins.

    Directory of Open Access Journals (Sweden)

    Wei-Ming Chen

    Full Text Available Metabolic syndrome (MetS is a complicated health problem that encompasses a variety of metabolic disorders. In this study, we analyzed the relationship between the major biochemical parameters associated with MetS and circulating levels of microRNA (miR-33, miR-103, and miR-155. We found that miRNA-33 levels were positively correlated with levels of fasting blood glucose, glycosylated hemoglobin A1c, total cholesterol, LDL-cholesterol, and triacylglycerol, but negatively correlated with HDL-cholesterol levels. In the cellular study, miR-33 levels were increased in macrophages treated with high glucose and cholesterol-lowering drugs atorvastatin and pitavastatin. miR-33 has been reported to play an essential role in cholesterol homeostasis through ATP-binding cassette transporter A1 (ABCA1 regulation and reverse cholesterol transport. However, the molecular mechanism underlying the linkage between miR-33 and statin treatment remains unclear. In the present study, we investigated whether atorvastatin and pitavastatin exert their functions through the modulation of miR-33 and ABCA1-mediated cholesterol efflux from macrophages. The results showed that treatment of the statins up-regulated miR-33 expression, but down-regulated ABCA1 mRNA levels in RAW264.7 cells and bone marrow-derived macrophages. Statin-mediated ABCA1 regulation occurs at the post-transcriptional level through targeting of the 3'-UTR of the ABCA1 transcript by miR-33. Additionally, we found significant down-regulation of ABCA1 protein expression in macrophages treated with statins. Finally, we showed that high glucose and statin treatment significantly suppressed cholesterol efflux from macrophages. These findings have highlighted the complexity of statins, which may exert detrimental effects on metabolic abnormalities through regulation of miR-33 target genes.

  19. Modulation of microRNA Expression in Subjects with Metabolic Syndrome and Decrease of Cholesterol Efflux from Macrophages via microRNA-33-Mediated Attenuation of ATP-Binding Cassette Transporter A1 Expression by Statins.

    Science.gov (United States)

    Chen, Wei-Ming; Sheu, Wayne H-H; Tseng, Pei-Chi; Lee, Tzong-Shyuan; Lee, Wen-Jane; Chang, Pey-Jium; Chiang, An-Na

    2016-01-01

    Metabolic syndrome (MetS) is a complicated health problem that encompasses a variety of metabolic disorders. In this study, we analyzed the relationship between the major biochemical parameters associated with MetS and circulating levels of microRNA (miR)-33, miR-103, and miR-155. We found that miRNA-33 levels were positively correlated with levels of fasting blood glucose, glycosylated hemoglobin A1c, total cholesterol, LDL-cholesterol, and triacylglycerol, but negatively correlated with HDL-cholesterol levels. In the cellular study, miR-33 levels were increased in macrophages treated with high glucose and cholesterol-lowering drugs atorvastatin and pitavastatin. miR-33 has been reported to play an essential role in cholesterol homeostasis through ATP-binding cassette transporter A1 (ABCA1) regulation and reverse cholesterol transport. However, the molecular mechanism underlying the linkage between miR-33 and statin treatment remains unclear. In the present study, we investigated whether atorvastatin and pitavastatin exert their functions through the modulation of miR-33 and ABCA1-mediated cholesterol efflux from macrophages. The results showed that treatment of the statins up-regulated miR-33 expression, but down-regulated ABCA1 mRNA levels in RAW264.7 cells and bone marrow-derived macrophages. Statin-mediated ABCA1 regulation occurs at the post-transcriptional level through targeting of the 3'-UTR of the ABCA1 transcript by miR-33. Additionally, we found significant down-regulation of ABCA1 protein expression in macrophages treated with statins. Finally, we showed that high glucose and statin treatment significantly suppressed cholesterol efflux from macrophages. These findings have highlighted the complexity of statins, which may exert detrimental effects on metabolic abnormalities through regulation of miR-33 target genes.

  20. Prothrombin and risk of venous thromboembolism, ischemic heart disease and ischemic cerebrovascular disease in the general population

    DEFF Research Database (Denmark)

    Weischer, Maren; Juul, Klaus; Zacho, Jeppe

    2010-01-01

    OBJECTIVE: We tested the hypotheses that Prothrombin G20210A heterozygosity associate with increased risk of venous thromboembolism (VTE), ischemic heart disease (IHD), and ischemic cerebrovascular disease (ICVD) in the general population and re-tested risk of IHD and ICVD in two case......-control studies. METHODS: 9231 individuals from the Danish general population were followed for VTE (VTE=DVT+PE), deep venous thrombosis (DVT), pulmonary embolism (PE), IHD, myocardial infarction (MI), ICVD, and ischemic stroke (IS) for a median of 24 years. Case-control studies included 2461 IHD cases and 867...

  1. Genotyping microarray (gene chip) for the ABCR (ABCA4) gene.

    Science.gov (United States)

    Jaakson, K; Zernant, J; Külm, M; Hutchinson, A; Tonisson, N; Glavac, D; Ravnik-Glavac, M; Hawlina, M; Meltzer, M R; Caruso, R C; Testa, F; Maugeri, A; Hoyng, C B; Gouras, P; Simonelli, F; Lewis, R A; Lupski, J R; Cremers, F P M; Allikmets, R

    2003-11-01

    Genetic variation in the ABCR (ABCA4) gene has been associated with five distinct retinal phenotypes, including Stargardt disease/fundus flavimaculatus (STGD/FFM), cone-rod dystrophy (CRD), and age-related macular degeneration (AMD). Comparative genetic analyses of ABCR variation and diagnostics have been complicated by substantial allelic heterogeneity and by differences in screening methods. To overcome these limitations, we designed a genotyping microarray (gene chip) for ABCR that includes all approximately 400 disease-associated and other variants currently described, enabling simultaneous detection of all known ABCR variants. The ABCR genotyping microarray (the ABCR400 chip) was constructed by the arrayed primer extension (APEX) technology. Each sequence change in ABCR was included on the chip by synthesis and application of sequence-specific oligonucleotides. We validated the chip by screening 136 confirmed STGD patients and 96 healthy controls, each of whom we had analyzed previously by single strand conformation polymorphism (SSCP) technology and/or heteroduplex analysis. The microarray was >98% effective in determining the existing genetic variation and was comparable to direct sequencing in that it yielded many sequence changes undetected by SSCP. In STGD patient cohorts, the efficiency of the array to detect disease-associated alleles was between 54% and 78%, depending on the ethnic composition and degree of clinical and molecular characterization of a cohort. In addition, chip analysis suggested a high carrier frequency (up to 1:10) of ABCR variants in the general population. The ABCR genotyping microarray is a robust, cost-effective, and comprehensive screening tool for variation in one gene in which mutations are responsible for a substantial fraction of retinal disease. The ABCR chip is a prototype for the next generation of screening and diagnostic tools in ophthalmic genetics, bridging clinical and scientific research. Copyright 2003 Wiley

  2. Increased Risk of Ischemic Stroke in Young Nasopharyngeal Carcinoma Patients

    International Nuclear Information System (INIS)

    Lee, Ching-Chih; Su, Yu-Chieh; Ho, Hsu-Chueh; Hung, Shih-Kai; Lee, Moon-Sing; Chiou, Wen-Yen; Chou, Pesus; Huang, Yung-Sung

    2011-01-01

    Purpose: Radiation/chemoradiotherapy-induced carotid stenosis and cerebrovascular events in patients with nasopharyngeal carcinoma (NPC) can cause severe disability and even death. This study aimed to estimate the risk of ischemic stroke in this patient population over more than 10 years of follow-up. Methods and Materials: The study cohorts consisted of all patients hospitalized with a principal diagnosis of NPC (n = 1094), whereas patients hospitalized for an appendectomy during 1997 and 1998 (n = 4376) acted as the control group and surrogate for the general population. Cox proportional hazard model was performed as a means of comparing the stroke-free survival rate between the two cohorts after adjusting for possible confounding and risk factors. Results: Of the 292 patients with ischemic strokes, 62 (5.7%) were from the NPC cohort and 230 (5.3%) were from the control group. NPC patients ages 35–54 had a 1.66 times (95% CI, 1.16–2.86; p = 0.009) higher risk of ischemic stroke after adjusting for patient characteristics, comorbidities, geographic region, urbanization level of residence, and socioeconomic status. There was no statistical difference in ischemic stroke risk between the NPC patients and appendectomy patients ages 55–64 years (hazard ratio = 0.87; 95% CI, 0.56–1.33; p = 0.524) after adjusting for other factors. Conclusions: Young NPC patients carry a higher risk for ischemic stroke than the general population. Besides regular examinations of carotid duplex, different irradiation strategies or using new technique of radiotherapy, such as intensity modulated radiation therapy or volumetric modulated arc therapy, should be considered in young NPC patients.

  3. Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Michihiro Fujiwara

    2010-07-01

    Full Text Available Cannabis contains the psychoactive component delta9-tetrahydrocannabinol (delta9-THC, and the non-psychoactive components cannabidiol (CBD, cannabinol, and cannabigerol. It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta9-THC also mediates psychological effects through the activation of the CB1 receptor in the central nervous system. In addition to the CB1 receptor agonists, cannabis also contains therapeutically active components which are CB1 receptor independent. Of the CB1 receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.

  4. Diagnostic Accuracy of a New Cardiac Electrical Biomarker for Detection of Electrocardiogram Changes Suggestive of Acute Myocardial Ischemic Injury

    Science.gov (United States)

    Schreck, David M; Fishberg, Robert D

    2014-01-01

    Objective A new cardiac “electrical” biomarker (CEB) for detection of 12-lead electrocardiogram (ECG) changes indicative of acute myocardial ischemic injury has been identified. Objective was to test CEB diagnostic accuracy. Methods This is a blinded, observational retrospective case-control, noninferiority study. A total of 508 ECGs obtained from archived digital databases were interpreted by cardiologist and emergency physician (EP) blinded reference standards for presence of acute myocardial ischemic injury. CEB was constructed from three ECG cardiac monitoring leads using nonlinear modeling. Comparative active controls included ST voltage changes (J-point, ST area under curve) and a computerized ECG interpretive algorithm (ECGI). Training set of 141 ECGs identified CEB cutoffs by receiver-operating-characteristic (ROC) analysis. Test set of 367 ECGs was analyzed for validation. Poor-quality ECGs were excluded. Sensitivity, specificity, and negative and positive predictive values were calculated with 95% confidence intervals. Adjudication was performed by consensus. Results CEB demonstrated noninferiority to all active controls by hypothesis testing. CEB adjudication demonstrated 85.3–94.4% sensitivity, 92.5–93.0% specificity, 93.8–98.6% negative predictive value, and 74.6–83.5% positive predictive value. CEB was superior against all active controls in EP analysis, and against ST area under curve and ECGI by cardiologist. Conclusion CEB detects acute myocardial ischemic injury with high diagnostic accuracy. CEB is instantly constructed from three ECG leads on the cardiac monitor and displayed instantly allowing immediate cost-effective identification of patients with acute ischemic injury during cardiac rhythm monitoring. PMID:24118724

  5. Genetics of ischemic stroke: future clinical applications.

    Science.gov (United States)

    Wang, Michael M

    2006-11-01

    Ischemic stroke has long been thought to have a genetic component that is independent of conventional vascular risk factors. It has been estimated that over one half of stroke risk is determined by inherited genes. However, until recently, strong evidence of genetic influence on ischemic stroke has been subject to criticism because the risk factors for stroke are also inherited and because previous studies suffered from limitations imposed by this highly heterogeneous neurological disorder. Recent advances in molecular genetics have led to the identification of specific genetic loci that impart susceptibility to ischemic stroke. We review the studies of these genes and discuss the future potential applications of genetic markers on the management of ischemic stroke patients.

  6. Factor V leiden and ischemic stroke risk: the Genetics of Early Onset Stroke (GEOS) study.

    Science.gov (United States)

    Hamedani, Ali G; Cole, John W; Cheng, Yuching; Sparks, Mary J; O'Connell, Jeffrey R; Stine, Oscar C; Wozniak, Marcella A; Stern, Barney J; Mitchell, Braxton D; Kittner, Steven J

    2013-05-01

    Factor V Leiden (FVL) has been associated with ischemic stroke in children but not in adults. Although the FVL mutation is associated with increased risk for venous thrombosis, its association with ischemic stroke in young adults remains uncertain. Therefore, we examined the association between FVL and ischemic stroke in participants of the Genetics of Early Onset Stroke (GEOS) study. A population-based case control study identified 354 women and 476 men 15 to 49 years of age with first-ever ischemic stroke and 907 controls. Participant-specific data included vascular risk factors, FVL genotype and, for cases, the ischemic stroke subtype by modified Trial of ORG 10172 in Acute Stroke criteria. Logistic regression was used to calculate odds ratios for the entire population and for subgroups stratified by risk factors and ischemic stroke subtype. The frequency of the FVL mutation was similar between ischemic stroke patients (3.6%; 95% confidence interval [CI] 2.5%-5.1%) and nonstroke controls (3.8%; 95% CI 2.7%-5.2%). This frequency did not change significantly when cases were restricted to patients with stroke of undetermined etiology (4.1%; 95% CI 2.6%-6.4%). Among young adults, we found no evidence for an association between FVL and either all ischemic stroke or the subgroup with stroke of undetermined etiology. Published by Elsevier Inc.

  7. Thrombolytic utilization for ischemic stroke in US hospitals with neurology residency program.

    Science.gov (United States)

    Moradiya, Yogesh; Crystal, Howard; Valsamis, Helen; Levine, Steven R

    2013-12-03

    We aimed to compare the rates of thrombolysis utilization for acute ischemic stroke in hospitals with neurology residency (NR) to those of other teaching (OT) and nonteaching (NT) hospitals. A retrospective serial cross-sectional cohort study of a nationally representative sample of stroke patients was conducted. Accreditation Council for Graduate Medical Education-accredited NR program-affiliated hospitals in the United States were cross-matched to the hospitals in the Nationwide Inpatient Sample from 2000 to 2010. ICD-9-CM codes were used for case ascertainment. A total of 712,433 adult ischemic stroke patients from 6,839 hospital samples were included, of whom 10.1%, 29.1%, and 60.8% were treated in NR, OT, and NT hospitals, respectively. Stroke patients in NR received thrombolysis more frequently (3.74% ± 0.24% [standard error]) than in OT (2.28% ± 0.11%, p < 0.001) and NT hospitals (1.44% ± 0.06%, p < 0.001). The adjusted odds ratios (ORs) of thrombolysis rates in NR vs OT and NR vs NT increased with each decade increment in age. In multivariate analysis, NR was independently predictive of higher thrombolysis rate (adjusted OR 1.51; 95% confidence interval [CI] 1.44-1.59 [NR vs OT], and adjusted OR 1.82; 95% CI 1.73-1.91 [NR vs NT]). Acute stroke care in NR hospitals is associated with an increased thrombolytic utilization. The disparities between the thrombolysis rate in NR and that in OT and NT hospitals are greater among elderly patients.

  8. Association of ATP-Binding Cassette Transporter A1 Gene Polymorphisms in Type 2 Diabetes Mellitus among Malaysians

    Directory of Open Access Journals (Sweden)

    Polin Haghvirdizadeh

    2015-01-01

    Full Text Available Background. Type 2 diabetes mellitus (T2DM is a complex polygenic disorder characterized by impaired insulin resistance, insulin secretion, and dysregulation of lipid and protein metabolism with environmental and genetic factors. ATP-binding cassette transporter A1 (ABCA1 gene polymorphisms are reported as the one of the genetic risk factors for T2DM in various populations with conflicting results. This study was conducted based on PCR-HRM to determine the frequency of ABCA1 gene by rs2230806 (R219K, rs1800977 (C69T, and rs9282541 (R230C polymorphisms Malaysian subjects. Methods. A total of 164 T2DM and 165 controls were recruited and their genotypes for ABCA1 gene polymorphisms were determined based on the real time high resolution melting analysis. Results. There was a significant difference between the subjects in terms of age, BMI, FPG, HbA1c, HDL, LDL, and TG P<0.05. There was a significant association between HOM of R219K P=0.005, among Malaysian subjects; moreover, allele frequency revealed the significant difference in A allele of R219K P=0.003. But, there was no significant difference in genotypic and allelic frequencies of C69T and R230C polymorphism. Conclusion. R219K polymorphism of ABCA1 gene can be considered as a genetic risk factor for T2DM subjects among Malaysians.

  9. Risk factors in various subtypes of ischemic stroke according to TOAST criteria.

    Science.gov (United States)

    Aquil, Nadia; Begum, Imtiaz; Ahmed, Arshia; Vohra, Ejaz Ahmed; Soomro, Bashir Ahmed

    2011-05-01

    To identify the frequency of risk factors in various subtypes of acute ischemic stroke according to TOAST criteria. Cross-sectional, observational study. Ziauddin Hospital, Karachi, from January to December 2007. Patients with acute ischemic stroke were enrolled. Studied variables included demographic profile, history of risk factors, physical and neurological examination, and investigations relevant with the objectives of the study. Findings were described as frequency percentages. Proportions of risk factors against subtypes was compared using chi-square test with significance at p dyslipedemia in 22%, smoking in 9%, atrial fibrillation in 5%, and previous history of stroke in 29%. The various subtypes of acute ischemic stroke were lacunar infarct in 43%, large artery atherosclerosis in 31%, cardioembolic type in 8%, stroke of other determined etiology in 1% and stroke of undetermined etiology in 18%. Hypertension and Diabetes were the most important risk factors in both large and small artery atherosclerosis. In patients with cardio-embolic stroke significant association was found with ischemic heart disease (p=0.01). Importance and relevance of risk factors evaluated for subtypes rather than ischemic stroke as a whole should be reflected in preventive efforts against the burden of ischemic stroke.

  10. Polymorphisms in apolipoprotein B and risk of ischemic stroke

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Jensen, Jan Skov

    2007-01-01

    Apolipoprotein B levels associate with risk of ischemic stroke. APOB polymorphisms may influence levels of apolipoprotein B and low-density lipoprotein (LDL), but whether they associate with risk of ischemic stroke is unknown.......Apolipoprotein B levels associate with risk of ischemic stroke. APOB polymorphisms may influence levels of apolipoprotein B and low-density lipoprotein (LDL), but whether they associate with risk of ischemic stroke is unknown....

  11. Predictors of long-term survival among first-ever ischemic and hemorrhagic stroke in a Brazilian stroke cohort.

    Science.gov (United States)

    Goulart, Alessandra C; Fernandes, Tiotrefis G; Santos, Itamar S; Alencar, Airlane P; Bensenor, Isabela M; Lotufo, Paulo A

    2013-05-24

    Few studies have examined both ischemic and hemorrhagic stroke to identify prognostic factors associated to long-term stroke survival. We investigated long-term survival and predictors that could adversely influence ischemic and hemorrhagic first-ever stroke prognosis. We prospectively ascertained 665 consecutive first-ever ischemic and hemorrhagic stroke cases from "The Study of Stroke Mortality and Morbidity" (The EMMA Study) in a community hospital in São Paulo, Brazil. We evaluated cardiovascular risk factors and sociodemographic characteristics (age, gender, race and educational level). We found a lower survival rate among hemorrhagic cases compared to ischemic stroke cases at the end of 4 years of follow-up (52% vs. 44%, p = 0.04). The risk of death was two times higher among people with ischemic stroke without formal education. Also, we found consistently higher risk of death for diabetics with ischemic stroke (HR = 1.45; 95% CI = 1.07-1.97) compared to no diabetics. As expected, age equally influenced on the high risk of poor survival, regardless of stroke subtype. For ischemic stroke, the lack of formal education and diabetes were significant independent predictors of poor long-term survival.

  12. Basic and clinical research advances in ischemic stroke

    Directory of Open Access Journals (Sweden)

    Yuan-yuan MA

    2018-01-01

    Full Text Available Stroke is the most common cerebrovascular disease worldwide, which seriously affects life quality of survivals and results in huge economic burden of families and society. In terms of clinical treatment for ischemic stroke, apart from thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA, the occurrence and successful application of endovascular thrombectomy in patients of ischemic stroke is a major breakthrough. Meanwhile, many novel clinical drugs for ischemic stroke therapy have entered into clinical trials. Most of basic and clinical researches have showed promising results in ischemic stroke therapy. This review mainly summarizes the progress of research during the period of Twelfth Five-Year Plan for National Economic and Social Development on treatment of ischemic stroke, including omics technologies, gene therapy, microRNA (miRNA interference and stem cell therapy. Stem cell therapy has shown great potential since many clinical trials have been completed or are ongoing. The development and mutual transformation of basic and clinical research will provide valuable and comprehensive information for the precise treatment of ischemic stroke.

  13. Association of Childhood Body Mass Index and Change in Body Mass Index With First Adult Ischemic Stroke.

    Science.gov (United States)

    Gjærde, Line K; Gamborg, Michael; Ängquist, Lars; Truelsen, Thomas C; Sørensen, Thorkild I A; Baker, Jennifer L

    2017-11-01

    The incidence of ischemic stroke among young adults is rising and is potentially due to an increase in stroke risk factors occurring at younger ages, such as obesity. To investigate whether childhood body mass index (BMI) and change in BMI are associated with adult ischemic stroke and to assess whether the associations are age dependent or influenced by birth weight. This investigation was a population-based cohort study of schoolchildren born from 1930 to 1987, with follow-up through national health registers from 1977 to 2012 in Denmark. Participants were 307 677 individuals (8899 ischemic stroke cases) with measured weight and height at ages 7 to 13 years. The dates of the analysis were September 1, 2015, to May 27, 2016. Childhood BMI, change in BMI, and birth weight. Ischemic stroke events were divided into early (≤55 years) or late (>55 years) age at diagnosis. The study cohort comprised 307 677 participants (approximately 49% female and 51% male). During the study period, 3529 women and 5370 men experienced an ischemic stroke. At all ages from 7 to 13 years, an above-average BMI z score was positively associated with early ischemic stroke. At age 13 years, a BMI z score of 1 was associated with hazard ratios (HRs) of 1.26 (95% CI, 1.11-1.43) in women and 1.21 (95% CI, 1.10-1.33) in men. No significant associations were found for below-average BMI z scores. Among children with above-average BMI z scores at age 7 years, a score increase of 0.5 from ages 7 to 13 years was positively associated with early ischemic stroke in women (HR, 1.10; 95% CI, 1.01-1.20) and in men (HR, 1.08; 95% CI, 1.00-1.16). Similarly, among children with below-average BMI z scores at age 7 years, a score increase of 0.5 from ages 7 to 13 years was positively associated with early ischemic stroke in women (HR, 1.14; 95% CI, 1.06-1.23) and in men (HR, 1.10; 95% CI, 1.04-1.18). Adjusting for birth weight minimally affected the associations. Independent of birth weight, above

  14. Relationship between Cardiac Troponin and Thrombo-Inflammatory Molecules in Prediction of Outcome after Acute Ischemic Stroke

    DEFF Research Database (Denmark)

    Csecsei, Peter; Pusch, Gabriella; Ezer, Erzsebet

    2018-01-01

    BACKGROUND: In patients with acute ischemic stroke (AIS) without cardiovascular complications, we investigated the association of serum concentration of cardiac troponin (high-sensitivity cardiac troponin T [hs-cTnT]) with thrombo-inflammatory markers. METHODS: Thirty-five patients with first......-ever AIS were prospectively examined. Serum hs-cTnT was measured 6 and 24 hours after stroke, whereas S100B, high-sensitivity C-reactive protein (hsCRP), soluble CD40 ligand, tissue plasminogen activator (tPA), monocyte chemoattractant protein-1 (MCP-1), and P-selectin were measured 6 and 72 hours after...... stroke. Severity of stroke was assessed by the National Institutes of Health Stroke Scale (NIHSS) on admission, 24 hours later, and at discharge. RESULTS: Concentration of MCP-1 at 6 hours was higher in the serum of patients with worsened NIHSS by 24 hours (P = .009). Concentration of hs-cTnT at both 6...

  15. Olanzapine-induced ischemic colitis

    Directory of Open Access Journals (Sweden)

    Esteban Sáez-González

    Full Text Available Background: Ischemic colitis (IC is an uncommon adverse event associated with antipsychotic agents, more commonly found with phenothiazine drugs and atypical neuroleptics such as clozapine. The risk of developing ischemic colitis increases when anticholinergic drugs are associated. Case report: We report the case of a 38-year-old woman with a history of schizoaffective disorder who had been on chronic quetiapine for 3 years, and presented to the ER because of diarrhea for 5 days. Four months previously, olanzapine had been added to her psychiatric drug regimen. Physical examination revealed abdominal distension with abdominal tympanic sounds and tenderness. Emergency laboratory tests were notable for increased acute phase reagents. Tomography revealed a concentric thickening of the colonic wall in the transverse, descending and sigmoid segments, with no signs of intestinal perforation. Colonoscopy demonstrated severe mucosal involvement from the sigmoid to the hepatic flexure, with ulcerations and fibrinoid exudate. Biopsies confirmed the diagnosis of ischemic colitis. The only relevant finding in her history was the newly added drug to her baseline regimen. An adverse effect was suspected because of its anticholinergic action at the intestinal level, and the drug was withdrawn. After 6 months of follow-up clinical, laboratory and endoscopic recovery was achieved. Discussion: Antipsychotic medication should be considered as a potential cause of ischemic colitis, particularly atypical antipsychotics such as clozapine and olanzapine; despite being uncommon, this adverse event may result in high morbidity and mortality.

  16. MR imaging of ischemic penumbra

    International Nuclear Information System (INIS)

    Abe, Osamu; Aoki, Shigeki; Shirouzu, Ichiro; Kunimatsu, Akira; Hayashi, Naoto; Masumoto, Tomohiko; Mori, Harushi; Yamada, Haruyasu; Watanabe, Makoto; Masutani, Yoshitaka; Ohtomo, Kuni

    2003-01-01

    Cerebral ischemic stroke is one of the most fatal diseases despite current advances in medical science. Recent demonstration of efficacy using intravenous and intra-arterial thrombolysis demands therapeutic intervention tailored to the physiologic state of the individual tissue and stratification of patients according to the potential risks for therapies. In such an era, the role of the neuroimaging becomes increasingly important to evaluate the extent and location of tissues at risk of infarction (ischemic penumbra), to distinguish it from unsalvageable infarcted tissues or doomed hemorrhagic parenchyma. In this review, we present briefly the current role and limitation of computed tomography and conventional magnetic resonance imaging (MRI). We also present the possible applications of advanced MR techniques, such as diffusion and perfusion imaging, concentrating on the delineation or detection of ischemic penumbra

  17. A meta-analysis of adiponectin gene rs22411766 T>G polymorphism and ischemic stroke susceptibility

    Directory of Open Access Journals (Sweden)

    Xiuju Chen

    2016-01-01

    Full Text Available Several studies have investigated the correlation between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk. However, the results were not conclusive with each other. Therefore, to overcome this obstacle, we performed this meta-analysis to further explicate the adiponectin gene rs22411766 T>G polymorphism and ischemic stroke susceptibility. Case-control or cohort studies focused on adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk were electronic searched in the databases of Medline, Pubmed, Cochrane library, Excerpta Medica database(EMBASE and China National Knowledge Infrastructure (CNKI. All the potentially relevant studies were included in this meta-analysis. The association between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke was expressed by odds ratio with its confidence interval. Publication bias has been assessed by begg’s funnel plot. All the analyses have been performed by Revman 5.1 statistical software. Finally, a total of six studies with 1,345 cases and 1,421 controls were included in this meta-analysis. Our results demonstrated that there was a significant association between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk (p<0.05. People with G single nucleotide of adiponectin gene have the increased risk of developing ischemic stroke compared to T single nucleotide.

  18. Integrity of Cerebellar Fastigial Nucleus Intrinsic Neurons Is Critical for the Global Ischemic Preconditioning

    Directory of Open Access Journals (Sweden)

    Eugene V. Golanov

    2017-09-01

    Full Text Available Excitation of intrinsic neurons of cerebellar fastigial nucleus (FN renders brain tolerant to local and global ischemia. This effect reaches a maximum 72 h after the stimulation and lasts over 10 days. Comparable neuroprotection is observed following sublethal global brain ischemia, a phenomenon known as preconditioning. We hypothesized that FN may participate in the mechanisms of ischemic preconditioning as a part of the intrinsic neuroprotective mechanism. To explore potential significance of FN neurons in brain ischemic tolerance we lesioned intrinsic FN neurons with excitotoxin ibotenic acid five days before exposure to 20 min four-vessel occlusion (4-VO global ischemia while analyzing neuronal damage in Cornu Ammoni area 1 (CA1 hippocampal area one week later. In FN-lesioned animals, loss of CA1 cells was higher by 22% compared to control (phosphate buffered saline (PBS-injected animals. Moreover, lesion of FN neurons increased morbidity following global ischemia by 50%. Ablation of FN neurons also reversed salvaging effects of five-minute ischemic preconditioning on CA1 neurons and morbidity, while ablation of cerebellar dentate nucleus neurons did not change effect of ischemic preconditioning. We conclude that FN is an important part of intrinsic neuroprotective system, which participates in ischemic preconditioning and may participate in naturally occurring neuroprotection, such as “diving response”.

  19. Drug Delivery to the Ischemic Brain

    Science.gov (United States)

    Thompson, Brandon J.; Ronaldson, Patrick T.

    2014-01-01

    Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events inneurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for acute ischemic stroke treatment, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can “rescue” salvageable brain tissue and/or protect BBB integrity during ischemic stroke. One class of drugs that may enable neural cell rescue following cerebral ischemia/reperfusion injury is the HMG-CoA reductase inhibitors (i.e., statins). Understanding potential CNS drug delivery pathways for statins is critical to their utility in ischemic stroke. Here, we review molecular pathways associated with cerebral ischemia and novel approaches for delivering drugs to treat ischemic disease. Specifically, we discuss utility of endogenous BBB drug uptake transporters such as organic anion transporting polypeptides (OATPs/Oatps) and nanotechnology-based carriers for optimization of CNS drug delivery. Overall, this chapter highlights state-of-the-art technologies that may improve pharmacotherapy of cerebral ischemia. PMID:25307217

  20. ASSESSMENT OF RELATION BETWEEN MICROALBUMINURIA AND ISCHEMIC ELECTROCARDIOGRAM IN IRANIAN GENERAL POPULATION

    Directory of Open Access Journals (Sweden)

    Alireza Khosravi

    2010-12-01

    Full Text Available Abstract    BACKGROUND: Enhancement of albumin exertion in urine increases the risk of renal and ischemic heart diseases (IHD. We assessed the association of urine albumin and sub-clinical IHD in a random sample of Iranian general population.    METHODS: The random sample in general population in Isfahan County was recruited to the cross-sectional study. From the all sample blood pressure and lipid profile were assessed and morning urine spot was measured for albumin and Creatinine. Microalbuminuria was defined either Albumin-Creatinine Ratio (ACR was 30-300mg. Also, the standard 12 lead electrocardiogram (ECG was carried out for all participants. The ECG pattern was divided to two categories; normal or ECG with ischemia. The logistic regression model was determined the odds of albuminuria for ischemic changes in ECG.    RESULTS: 999 subjects, age 35-70 years, participated to study. From all, 40.8% were male. Microalbuminuria was detected in 8% and sub-clinical ECG ischemic changes were found in 23.4%. The most frequent ischemic change was T wave inversion. The mean urine albumin levels in subjects with normal ECG was 9.6±14.6 mg/ml and in ischemic group was 8.5±12.2 mg/ml and they did not have statistically different. The odds ratios of neither Albumin-Creatinine ratio nor microalbuminuria were in significant range for risk to ischemic changes in ECG of apparently healthy participants. They was consecutively OR=0.9 (0.51-1.6, OR=0.99 (0.98-1.004.     CONCLUSION: Our finding didn’t declare any association between ACR and IHD. Because of showing this association in the other study; it needs more exploration regarding to association between microalbuminuria and cardiovascular diseases incidence.      Keywords: Ischemic heart diseases, electrocardiogram, Albumin-Creatinine Ratio, Urine Albumin

  1. Large arterial occlusive strokes as a medical emergency: need to accurately predict clot location.

    Science.gov (United States)

    Vanacker, Peter; Faouzi, Mohamed; Eskandari, Ashraf; Maeder, Philippe; Meuli, Reto; Michel, Patrik

    2017-10-01

    Endovascular treatment for acute ischemic stroke with a large intracranial occlusion was recently shown to be effective. Timely knowledge of the presence, site, and extent of arterial occlusions in the ischemic territory has the potential to influence patient selection for endovascular treatment. We aimed to find predictors of large vessel occlusive strokes, on the basis of available demographic, clinical, radiological, and laboratory data in the emergency setting. Patients enrolled in ASTRAL registry with acute ischemic stroke and computed tomography (CT)-angiography within 12 h of stroke onset were selected and categorized according to occlusion site. Easily accessible variables were used in a multivariate analysis. Of 1645 patients enrolled, a significant proportion (46.2%) had a large vessel occlusion in the ischemic territory. The main clinical predictors of any arterial occlusion were in-hospital stroke [odd ratios (OR) 2.1, 95% confidence interval 1.4-3.1], higher initial National Institute of Health Stroke Scale (OR 1.1, 1.1-1.2), presence of visual field defects (OR 1.9, 1.3-2.6), dysarthria (OR 1.4, 1.0-1.9), or hemineglect (OR 2.0, 1.4-2.8) at admission and atrial fibrillation (OR 1.7, 1.2-2.3). Further, the following radiological predictors were identified: time-to-imaging (OR 0.9, 0.9-1.0), early ischemic changes (OR 2.3, 1.7-3.2), and silent lesions on CT (OR 0.7, 0.5-1.0). The area under curve for this analysis was 0.85. Looking at different occlusion sites, National Institute of Health Stroke Scale and early ischemic changes on CT were independent predictors in all subgroups. Neurological deficits, stroke risk factors, and CT findings accurately identify acute ischemic stroke patients at risk of symptomatic vessel occlusion. Predicting the presence of these occlusions may impact emergency stroke care in regions with limited access to noninvasive vascular imaging.

  2. Imaging of cerebral ischemic edema and neuronal death

    Energy Technology Data Exchange (ETDEWEB)

    Kummer, Ruediger von [Universitaetsklinikum Carl Gustav Carus, Institut fuer Diagnostische und Interventionelle Neuroradiologie, Dresden (Germany); Dzialowski, Imanuel [Elblandklinikum Meissen, Neurologische Rehabilitationsklinik Grossenhain, Meissen (Germany)

    2017-06-15

    In acute cerebral ischemia, the assessment of irreversible injury is crucial for treatment decisions and the patient's prognosis. There is still uncertainty how imaging can safely differentiate reversible from irreversible ischemic brain tissue in the acute phase of stroke. We have searched PubMed and Google Scholar for experimental and clinical papers describing the pathology and pathophysiology of cerebral ischemia under controlled conditions. Within the first 6 h of stroke onset, ischemic cell injury is subtle and hard to recognize under the microscope. Functional impairment is obvious, but can be induced by ischemic blood flow allowing recovery with flow restoration. The critical cerebral blood flow (CBF) threshold for irreversible injury is ∝15 ml/100 g x min. Below this threshold, ischemic brain tissue takes up water in case of any residual capillary flow (ionic edema). Because tissue water content is linearly related to X-ray attenuation, computed tomography (CT) can detect and measure ionic edema and, thus, determine ischemic brain infarction. In contrast, diffusion-weighted magnetic resonance imaging (DWI) detects cytotoxic edema that develops at higher thresholds of ischemic CBF and is thus highly sensitive for milder levels of brain ischemia, but not specific for irreversible brain tissue injury. CT and MRI are complimentary in the detection of ischemic stroke pathology and are valuable for treatment decisions. (orig.)

  3. Prevalence of Ex Vivo High On-treatment Platelet Reactivity on Antiplatelet Therapy after Transient Ischemic Attack or Ischemic Stroke on the PFA-100(®) and VerifyNow(®).

    LENUS (Irish Health Repository)

    Kinsella, Justin A

    2012-09-12

    BACKGROUND: The prevalence of ex vivo high on-treatment platelet reactivity (HTPR) to commonly prescribed antiplatelet regimens after transient ischemic attack (TIA) or ischemic stroke is uncertain. METHODS: Platelet function inhibition was simultaneously assessed with modified light transmission aggregometry (VerifyNow; Accumetrics Inc, San Diego, CA) and with a moderately high shear stress platelet function analyzer (PFA-100; Siemens Medical Solutions USA, Inc, Malvern, PA) in a pilot, cross-sectional study of TIA or ischemic stroke patients. Patients were assessed on aspirin-dipyridamole combination therapy (n = 51) or clopidogrel monotherapy (n = 25). RESULTS: On the VerifyNow, HTPR on aspirin was identified in 4 of 51 patients (8%) on aspirin-dipyridamole combination therapy (≥550 aspirin reaction units on the aspirin cartridge). Eleven of 25 (44%) patients had HTPR on clopidogrel (≥194 P2Y12 reaction units on the P2Y12 cartridge). On the PFA-100, 21 of 51 patients (41%) on aspirin-dipyridamole combination therapy had HTPR on the collagen-epinephrine (C-EPI) cartridge. Twenty-three of 25 patients (92%) on clopidogrel had HTPR on the collagen-adenosine diphosphate (C-ADP) cartridge. The proportion of patients with antiplatelet HTPR was lower on the VerifyNow than PFA-100 in patients on both regimens (P < .001). CONCLUSIONS: The prevalence of ex vivo antiplatelet HTPR after TIA or ischemic stroke is markedly influenced by the method used to assess platelet reactivity. The PFA-100 C-ADP cartridge is not sensitive at detecting the antiplatelet effects of clopidogrel ex vivo. Larger prospective studies with the VerifyNow and with the PFA-100 C-EPI and recently released Innovance PFA P2Y cartridges (Siemens Medical Solutions USA, Inc) in addition to newer tests of platelet function are warranted to assess whether platelet function monitoring predicts clinical outcome in ischemic cerebrovascular disease.

  4. Stable ischemic heart disease in women: current perspectives

    Directory of Open Access Journals (Sweden)

    Samad F

    2017-09-01

    Full Text Available Fatima Samad,1 Anushree Agarwal,2 Zainab Samad3 1Aurora Cardiovascular Services, Aurora Sinai/Aurora St Luke’s Medical Centers, University of Wisconsin School of Medicine and Public Health, Milwaukee, WI, 2Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, CA, 3Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC, USA Abstract: Cardiovascular disease is the leading cause of death in women accounting for 1 in every 4 female deaths. Pathophysiology of ischemic heart disease in women includes epicardial coronary artery, endothelial dysfunction, coronary vasospasm, plaque erosion and spontaneous coronary artery dissection. Angina is the most common presentation of stable ischemic heart disease (SIHD in women. Risk factors for SIHD include traditional risks such as older age, obesity (body mass index [BMI] >25 kg/m2, smoking, hypertension, dyslipidemia, cerebrovascular and peripheral vascular disease, sedentary lifestyle, family history of premature coronary artery disease, metabolic syndrome and diabetes mellitus, and nontraditional risk factors, such as gestational diabetes, insulin resistance/polycystic ovarian disease, pregnancy-induced hypertension, pre-eclampsia, eclampsia, menopause, mental stress and autoimmune diseases. Diagnostic testing can be used effectively to risk stratify women. Guidelines-directed medical therapy including aspirin, statins, beta-blocker therapy, calcium channel blockers and ranolazine should be instituted for symptom and ischemia management. Despite robust evidence regarding the adverse outcomes seen in women with ischemic heart disease, knowledge gaps exist in several areas. Future research needs to be directed toward a greater understanding of the role of nontraditional risk factors for SIHD in women, gaining deeper insights into the sex differences in therapeutic effects and formulating a sex-specific algorithm for the

  5. Thyrotoxic Atrial Fibrillation: Factors Associated with Persistence and Risk of Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Cheuk-Lik Wong

    2017-01-01

    Full Text Available Background. Atrial fibrillation (AF is one of the commonest cardiovascular manifestations of thyrotoxicosis. A significant proportion of patients have persistent AF which may have long term consequences, for example, ischemic stroke. Methods. We performed a retrospective cohort study in a regional hospital from January 2004 to June 2016 to examine the clinical characteristics and outcomes of thyrotoxic patients who presented with atrial fibrillation and to investigate possible factors associated with persistent atrial fibrillation and ischemic stoke. Results. Among 1918 patients who had a diagnosis of thyrotoxicosis, 133 (6.9% patients presented with AF. Spontaneous sinus conversion occurred in 89 (66.9% patients in which 85 (94% patients developed sinus conversion before or within 6 months after having achieved euthyroidism. The remaining 44 (33.1% had persistent AF. The rate of ischemic stroke was numerically higher among patients who had persistent AF than those with spontaneous sinus conversion (15.9% versus 10.1%; log-rank 0.442, p=0.506. Patients who sustained an ischemic stroke were older (71 ± 11 years versus 62 ± 16 years, p=0.023 and had a trend towards higher CHA2DS2-VASc score (2.9 ± 1.7 versus 2.3 ± 1.7, p=0.153. History of smoking (adjusted odds ratio 4.9, 95% CI [1.8,14.0], p=0.002, a larger left atrial diameter (adjusted odd ratio 2.6, 95% CI [1.2,5.5], p=0.014, and a relatively lower free thyroxine level at diagnosis (adjusted odd ratio 2.1, 95% CI [1.2,3.5], p=0.008 were associated with persistence of AF on multivariate analysis. Conclusion. Persistence of thyrotoxic AF occurred in one-third of patients and spontaneous sinus conversion was unlikely after six months of euthyroidism. High rate of ischemic stroke was observed among patients with persistent thyrotoxic AF and older age. Patients with factors associated with persistent AF, especially older people, should be closely monitored beyond 6 months so that

  6. Prevalence of electrocardiographic ST-T changes during acute ischemic stroke in patients without known ischemic heart disease

    DEFF Research Database (Denmark)

    Jensen, Jesper K; Bak, Søren; Flemming Høilund-Carlsen, Poul

    2008-01-01

    We evaluated characteristics and prevalence of ST-segment depression and/or T-wave inversion in the resting electrocardiogram of 244 consecutive patients with acute ischemic stroke, but without ischemic heart disease. The prevalence of ST-T changes ranged from 13% to 16% and this is what to expect...

  7. Optical Spectroscopy Approach for the Predictive Assessment of Kidney Functional Recovery Following Ischemic Injury

    Energy Technology Data Exchange (ETDEWEB)

    Raman, R N; Pivetti, C D; Rubenchik, A M; Matthews, D L; Troppmann, C; Demos, S G

    2010-02-11

    Tissue that has undergone significant yet unknown amount of ischemic injury is frequently encountered in organ transplantation and trauma clinics. With no reliable real-time method of assessing the degree of injury incurred in tissue, surgeons generally rely on visual observation which is subjective. In this work, we investigate the use of optical spectroscopy methods as a potentially more reliable approach. Previous work by various groups was strongly suggestive that tissue autofluorescence from NADH obtained under UV excitation is sensitive to metabolic response changes. To test and expand upon this concept, we monitored autofluorescence and light scattering intensities of injured vs. uninjured rat kidneys via multimodal imaging under 355 nm, 325 nm, and 266 nm excitation as well as scattering under 500 nm illumination. 355 nm excitation was used to probe mainly NADH, a metabolite, while 266 nm excitation was used to probe mainly tryptophan to correct for non-metabolic signal artifacts. The ratio of autofluorescence intensities derived under these two excitation wavelengths was calculated and its temporal profile was fit to a relaxation model. Time constants were extracted, and longer time constants were associated with kidney dysfunction. Analysis of both the autofluorescence and light scattering images suggests that changes in microstructure tissue morphology, blood absorption spectral characteristics, and pH contribute to the behavior of the observed signal which may be used to obtain tissue functional information and offer predictive capability.

  8. Optical spectroscopy approach for the predictive assessment of kidney functional recovery following ischemic injury

    Science.gov (United States)

    Raman, Rajesh N.; Pivetti, Christopher D.; Rubenchik, Alexander M.; Matthews, Dennis L.; Troppmann, Christoph; Demos, Stavros G.

    2010-02-01

    Tissue that has undergone significant yet unknown amount of ischemic injury is frequently encountered in organ transplantation and trauma clinics. With no reliable real-time method of assessing the degree of injury incurred in tissue, surgeons generally rely on visual observation which is subjective. In this work, we investigate the use of optical spectroscopy methods as a potentially more reliable approach. Previous work by various groups was strongly suggestive that tissue autofluorescence from NADH obtained under UV excitation is sensitive to metabolic response changes. To test and expand upon this concept, we monitored autofluorescence and light scattering intensities of injured vs. uninjured rat kidneys via multimodal imaging under 355 nm, 325 nm, and 266 nm excitation as well as scattering under 500 nm illumination. 355 nm excitation was used to probe mainly NADH, a metabolite, while 266 nm excitation was used to probe mainly tryptophan to correct for non-metabolic signal artifacts. The ratio of autofluorescence intensities derived under these two excitation wavelengths was calculated and its temporal profile was fit to a relaxation model. Time constants were extracted, and longer time constants were associated with kidney dysfunction. Analysis of both the autofluorescence and light scattering images suggests that changes in microstructure tissue morphology, blood absorption spectral characteristics, and pH contribute to the behavior of the observed signal which may be used to obtain tissue functional information and offer predictive capability.

  9. Trends in ischemic heart disease mortality in Korea, 1985-2009: an age-period-cohort analysis.

    Science.gov (United States)

    Lee, Hye Ah; Park, Hyesook

    2012-09-01

    Economic growth and development of medical technology help to improve the average life expectancy, but the western diet and rapid conversions to poor lifestyles lead an increasing risk of major chronic diseases. Coronary heart disease mortality in Korea has been on the increase, while showing a steady decline in the other industrialized countries. An age-period-cohort analysis can help understand the trends in mortality and predict the near future. We analyzed the time trends of ischemic heart disease mortality, which is on the increase, from 1985 to 2009 using an age-period-cohort model to characterize the effects of ischemic heart disease on changes in the mortality rate over time. All three effects on total ischemic heart disease mortality were statistically significant. Regarding the period effect, the mortality rate was decreased slightly in 2000 to 2004, after it had continuously increased since the late 1980s that trend was similar in both sexes. The expected age effect was noticeable, starting from the mid-60's. In addition, the age effect in women was more remarkable than that in men. Women born from the early 1900s to 1925 observed an increase in ischemic heart mortality. That cohort effect showed significance only in women. The future cohort effect might have a lasting impact on the risk of ischemic heart disease in women with the increasing elderly population, and a national prevention policy is need to establish management of high risk by considering the age-period-cohort effect.

  10. Association of inflammatory gene polymorphisms with ischemic stroke in a Chinese Han population.

    Science.gov (United States)

    Zhao, Nan; Liu, Xin; Wang, Yongqin; Liu, Xiaoqiu; Li, Jiana; Yu, Litian; Ma, Liyuan; Wang, Shuyu; Zhang, Hongye; Liu, Lisheng; Zhao, Jingbo; Wang, Xingyu

    2012-07-06

    Inflammatory mechanisms are important in stroke risk, and genetic variations in components of the inflammatory response have been implicated as risk factors for stroke. We tested the inflammatory gene polymorphisms and their association with ischemic stroke in a Chinese Han population. A total of 1,124 ischemic stroke cases and 1,163 controls were genotyped with inflammatory panel strips containing 51 selected inflammatory gene polymorphisms from 35 candidate genes. We tested the genotype-stroke association with logistic regression model. We found two single nucleotide polymorphisms (SNPs) in CCL11 were associated with ischemic stroke. After adjusting for multiple testing using false discovery rate (FDR) with a 0.20 cut-off point, CCL11 rs4795895 remained statistically significant. We further stratified the study population by their hypertension status. In the hypertensive group, CCR2 rs1799864, CCR5 rs1799987 and CCL11 rs4795895 were nominally associated with increased risk of stroke. In the non-hypertensive group, CCL11 rs3744508, LTC4S rs730012, FCER1B rs569108, TGFB1 rs1800469, LTA rs909253 and CCL11 rs4795895 were associated with ischemic stroke. After correction for multiple testing, CCR2 rs1799864 and CCR5 rs1799987 remained significant in the hypertensive group, and CCL11 rs3744508, LTC4S rs730012, FCER1B rs569108, TGFB1 rs1800469, LTA rs909253 remained significant in the non-hypertensive group. Our results indicate that inflammatory genetic variants are associated with increased risk of ischemic stroke in a Chinese Han population, particularly in non-hypertensive individuals.

  11. Modulation of Acid-sensing Ion Channel 1a by Intracellular pH and Its Role in Ischemic Stroke.

    Science.gov (United States)

    Li, Ming-Hua; Leng, Tian-Dong; Feng, Xue-Chao; Yang, Tao; Simon, Roger P; Xiong, Zhi-Gang

    2016-08-26

    An important contributor to brain ischemia is known to be extracellular acidosis, which activates acid-sensing ion channels (ASICs), a family of proton-gated sodium channels. Lines of evidence suggest that targeting ASICs may lead to novel therapeutic strategies for stroke. Investigations of the role of ASICs in ischemic brain injury have naturally focused on the role of extracellular pH in ASIC activation. By contrast, intracellular pH (pHi) has received little attention. This is a significant gap in our understanding because the ASIC response to extracellular pH is modulated by pHi, and activation of ASICs by extracellular protons is paradoxically enhanced by intracellular alkalosis. Our previous studies show that acidosis-induced cell injury in in vitro models is attenuated by intracellular acidification. However, whether pHi affects ischemic brain injury in vivo is completely unknown. Furthermore, whereas ASICs in native neurons are composed of different subunits characterized by distinct electrophysiological/pharmacological properties, the subunit-dependent modulation of ASIC activity by pHi has not been investigated. Using a combination of in vitro and in vivo ischemic brain injury models, electrophysiological, biochemical, and molecular biological approaches, we show that the intracellular alkalizing agent quinine potentiates, whereas the intracellular acidifying agent propionate inhibits, oxygen-glucose deprivation-induced cell injury in vitro and brain ischemia-induced infarct volume in vivo Moreover, we find that the potentiation of ASICs by quinine depends on the presence of the ASIC1a, ASIC2a subunits, but not ASIC1b, ASIC3 subunits. Furthermore, we have determined the amino acids in ASIC1a that are involved in the modulation of ASICs by pHi. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Meta-analysis of factor V Leiden and ischemic stroke in young adults: the importance of case ascertainment.

    Science.gov (United States)

    Hamedani, Ali G; Cole, John W; Mitchell, Braxton D; Kittner, Steven J

    2010-08-01

    The factor V Leiden mutation is associated with ischemic stroke in children but not in adults. Whether it is associated with ischemic stroke in young adults, however, is uncertain. To address this issue, we performed a meta-analysis of 18 case-control studies of ischemic stroke in adults 50 years of age and younger published before June 2009. Across all studies, factor V Leiden was detected in 154 of 2045 cases (7.5%) and 217 of 5307 controls (4.1%), yielding a fixed-effect odds ratio of 2.00 (95% CI, 1.59-2.51). However, further analyses revealed substantial heterogeneity among these studies (P=0.005 for Q-test of heterogeneity). Hypothesizing that this heterogeneity could be related to differences among studies in case selection criteria, we stratified the meta-analysis into studies for which case samples were enriched or not enriched to include cases having an increased likelihood of prothrombotic genetic involvement ("selected" ischemic stroke studies, n=9) and those that recruited cases from consecutive neurology referrals or hospitalizations ("unselected" ischemic stroke studies, n=8). Among the 9 "selected" ischemic stroke studies, factor V Leiden was more strongly associated with stroke (OR, 2.73; 95% CI, 1.98-3.75), whereas among the 8 "unselected" ischemic stroke studies, the association between factor V Leiden and stroke was substantially weaker (OR, 1.40; 95% CI, 0.998-1.95). This difference was found to be statistically significant (P=0.003 for Woolf test for heterogeneity). We conclude that factor V Leiden is associated with ischemic stroke in young adults, particularly in patient populations in which there is an increased clinical suspicion of prothrombotic state.

  13. Major Depression, C-Reactive Protein, and Incident Ischemic Heart Disease in Healthy Men and Women

    NARCIS (Netherlands)

    Surtees, Paul G.; Wainwright, Nicholas W. J.; Boekholdt, S. Matthijs; Luben, Robert N.; Wareham, Nicholas J.; Khaw, Kay-Tee

    2008-01-01

    Objective: To investigate how C-reactive protein (CRP) and major depressive disorder (MDD) relate to each other and to incident ischemic heart disease (IHD). Studies have shown that both depression and raised CRP concentration predict IHD and that elevated CRP is linked with increased risk of

  14. Cardiac insulin-like growth factor-1 and cyclins gene expression in canine models of ischemic or overpacing cardiomyopathy.

    Science.gov (United States)

    Mahmoudabady, Maryam; Mathieu, Myrielle; Touihri, Karim; Hadad, Ielham; Da Costa, Agnes Mendes; Naeije, Robert; Mc Entee, Kathleen

    2009-10-09

    Insulin-like growth factor-1 (IGF-1), transforming growth factor beta (TGFbeta) and cyclins are thought to play a role in myocardial hypertrophic response to insults. We investigated these signaling pathways in canine models of ischemic or overpacing-induced cardiomyopathy. Echocardiographic recordings and myocardial sampling for measurements of gene expressions of IGF-1, its receptor (IGF-1R), TGFbeta and of cyclins A, B, D1, D2, D3 and E, were obtained in 8 dogs with a healed myocardial infarction, 8 dogs after 7 weeks of overpacing and in 7 healthy control dogs. Ischemic cardiomyopathy was characterized by moderate left ventricular systolic dysfunction and eccentric hypertrophy, with increased expressions of IGF-1, IGF-1R and cyclins B, D1, D3 and E. Tachycardiomyopathy was characterized by severe left ventricular systolic dysfunction and dilation with no identifiable hypertrophic response. In the latter model, only IGF-1 was overexpressed while IGF-1R, cyclins B, D1, D3 and E stayed unchanged as compared to controls. The expressions of TGFbeta, cyclins A and D2 were comparable in the 3 groups. The expression of IGF-1R was correlated with the thickness of the interventricular septum, in systole and diastole, and to cyclins B, D1, D3 and E expression. These results agree with the notion that IGF-1/IGF-1R and cyclins are involved in the hypertrophic response observed in cardiomyopathies.

  15. Temporal delta wave and ischemic lesions on MRI

    International Nuclear Information System (INIS)

    Inui, Koji; Kawamoto, Hozumi; Kawakita, Masahiko; Wako, Kazuhisa; Nakashima, Hiromichi; Kamihara, Masanori; Nomura, Junichi

    1994-01-01

    The present study was designed to determine the clinical significance of a temporal low-voltage irregular delta wave (TLID) on EEG. Among 808 EEG records examined during one year at our hospital, the TLID was commonly detected in patients with clinically diagnosed ischemic brain diseases such as multiple infarction. Subsequently, a relation of the TLID to ischemic lesions on MRI was examined in 50 elderly depressive patients. It was found that there was a close correlation between the occurrence of the TLID and small ischemic lesions on MRI (p<0.001). These results suggest that the TLID is a valuable indicator of minor ischemic changes of the brain. (author)

  16. The risk of ischemic optic neuropathy post phacoemulsification cataract surgery.

    Science.gov (United States)

    Al-Madani, Mousa Victor; Al-Raqqad, Nancy Khalaf; Al-Fgarra, Naser Abdallah; Al-Thawaby, Amal Mousa; Jaafar, Ahmed Abdelra'of

    2017-01-01

    The aim was to study the risk of non arteritic ischemic optic neuropathy after phacoemulsification cataract surgery. This study was conducted at King Hussein Medical Center during the period between January 2015 and July 2016. Patients attending ophthalmology clinic complaining of decreased vision due to lens opacity were evaluated. Patients were divided into two groups. First group included patients with no medical illness and second group included patients with diabetes mellitus, hypertension or hyperlipidemia. The two groups were further divided into two subgroups. First subgroup included patients who had phacoemulsification surgery and second subgroup did not have surgery. All patients were followed up for 6 months. They were assessed by neuro-ophthalmologist looking for ischemic optic neuropathy. A total number of 568 patients were enrolled. Group 1A included patients with no medical illness who underwent surgery and group 1B did not undergo surgery. The number of patients in these two subgroups was 119 and 103 respectively. Number of patients in group 2A (medical illness and surgery) was 188 and number of patients in group 2B (medical illness and no surgery) was 130. The incidence of ischemic optic neuropathy was 4.3 % in group 2A, 4.2 % in group 1A, 0.8% in group 2B, and 0% in group 1B. Phacoemulsification is a risk factor for non arteritic ischemic optic neuropathy independent of the presence of medical risk factors. Suggested mechanisms would be local anaesthesia, intraocular pressure fluctuation and local intraocular inflammation.

  17. Migraine Headache and Ischemic Stroke Risk: An Updated Meta-analysis

    Science.gov (United States)

    Spector, June T.; Kahn, Susan R.; Jones, Miranda R.; Jayakumar, Monisha; Dalal, Deepan; Nazarian, Saman

    2010-01-01

    Background Observational studies, including recent large cohort studies which were unavailable for prior meta-analysis, have suggested an association between migraine headache and ischemic stroke. We performed an updated meta-analysis to quantitatively summarize the strength of association between migraine and ischemic stroke risk. Methods We systematically searched electronic databases, including MEDLINE and EMBASE, through February 2009 for studies of human subjects in the English language. Study selection using a priori selection criteria, data extraction, and assessment of study quality were conducted independently by reviewer pairs using standardized forms. Results Twenty-one (60%) of 35 studies met the selection criteria, for a total of 622,381 participants (13 case-control, 8 cohort studies) included in the meta-analysis. The pooled adjusted odds ratio of ischemic stroke comparing migraineurs to non-migraineurs using a random effects model was 2.30 (95% confidence interval [CI], 1.91-2.76). The pooled adjusted effect estimates for studies that reported relative risks and hazard ratios, respectively, were 2.41 (95% CI, 1.81-3.20) and 1.52 (95% CI, 0.99-2.35). The overall pooled effect estimate was 2.04 (95% CI, 1.72-2.43). Results were robust to sensitivity analyses excluding lower quality studies. Conclusions Migraine is associated with increased ischemic stroke risk. These findings underscore the importance of identifying high-risk migraineurs with other modifiable stroke risk factors. Future studies of the effect of migraine treatment and modifiable risk factor reduction on stroke risk in migraineurs are warranted. PMID:20493462

  18. Ischemic Stroke in Young Adults and Preexisting Psychiatric Disorders: A Nationwide Case-Control Study.

    Science.gov (United States)

    Chiu, Yu-Chuan; Bai, Ya-Mei; Su, Tung-Ping; Chen, Tzeng-Ji; Chen, Mu-Hong

    2015-09-01

    Previous studies showed that psychiatric disorders such as major depression, bipolar disorders, and alcohol misuse are associated with an increased risk of ischemic stroke. However, the link between psychiatric disorders and stroke in the young population is rarely investigated. Using the Taiwan National Health Insurance Research Database, 2063 young adults aged between 18 and 45 years with ischemic stroke and 8252 age- and sex-matched controls were enrolled in our study between 1998 and 2011. Participants who had preexisting psychiatric disorders were identified. After adjusting for preexisting physical disorders and demographic data, patients with ischemic stroke had an increased risk of having preexisting psychiatric disorders, including bipolar disorder (odds ratio [OR]: 2.23, 95% confidence interval [CI]: 1.06∼4.67), unipolar depression (OR: 2.15, 95% CI: 1.62∼2.86), anxiety disorders (OR: 2.63, 95% CI: 1.87∼3.69), and alcohol use disorders (OR: 2.86, 95% CI: 1.79∼4.57). Young ischemic stroke (age ≥30 years) was related to the risk of preexisting unipolar depression (OR: 1.49, 95% CI: 1.05∼2.11), anxiety disorders (OR: 1.99, 95% CI: 1.33∼2.97), and alcohol use disorders (OR: 2.54, 95% CI: 1.55∼4.14); very young stroke (age ischemic stroke at age younger than 45 years had a higher risk of having pre-existing bipolar disorder, unipolar depression, anxiety disorders, and alcohol use disorders than those who did not after adjusting for demographic data and stroke-related medical comorbidities.

  19. Increased risk of ischemic stroke in young patients with ankylosing spondylitis: a population-based longitudinal follow-up study.

    Science.gov (United States)

    Lin, Chia-Wei; Huang, Ya-Ping; Chiu, Yueh-Hsia; Ho, Yu-Tsun; Pan, Shin-Liang

    2014-01-01

    Prospective data on the association between ischemic stroke and ankylosing spondylitis (AS) in the young are sparse. The purpose of this population-based, age- and sex-matched longitudinal follow-up study was to investigate the risk of developing ischemic stroke in young patients with AS. A total of 4562 patients aged 18- to 45-year-old with at least two ambulatory visits in 2001 with a principal diagnosis of AS were enrolled in the AS group. The non-AS group consisted of 22810 age- and sex-matched, randomly sampled subjects without AS. The two-year ischemic stroke-free survival rate for each group were calculated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used to estimate the hazard ratio of ischemic stroke after adjusting for demographic and clinical covariates. During follow-up, 21 patients in the AS group and 53 in the non-AS group developed ischemic stroke. The ischemic stroke-free survival rate over the 2 year follow-up was lower in the AS group than the non-AS group (p = 0.0021). The crude hazard ratio of ischemic stroke for the AS group was 1.98 (95% CI, 1.20-3.29; p = 0.0079) and the adjusted hazard ratio after controlling for demographic and comorbid medical disorders was 1.93 (95% CI, 1.16-3.20; p = 0.0110). Our study showed an increased risk of developing ischemic stroke in young patients with AS.

  20. The distribution of N-isopropyl-p-iodoamphetamine in experimental ischemic brain of the mongolian gerbil

    International Nuclear Information System (INIS)

    Jinnouchi, Seishi; Hoshi, Hiroaki; Watanabe, Katsushi; Ueda, Takashi; Yamaguchi, Tadatoshi

    1988-01-01

    We studied the distribution of N-isopropyl-p-[I-131]-iodoamphetamine (IMP) in permanent and temporary ischemic brains of mongolian gerbils. For the permanent ischemic brain model, the right common carotid artery was ligated under ether anesthesia. For the temporary ischemic brain model, the right common carotid artery was clamped by a clip and recirculated at 3 hours thereafter. After given time intervals, 1.35 MBq (50 μCi) of IMP was injected intravenously into 17 gerbils (permanent ischemic brain model), 18 gerbils (temporary ischemic brain model) which had severe neurological symptoms, and 3 normal gerbils for controls. One minute, 10 minutes, 1 hour and 6 hours after the injection, gerbils were sacrified and autoradiography of the brain was performed. The activity of IMP in various parts of the brain was calculated from each autoradiogram. In permanent ischemic brains, low perfusion areas were observed in the right cerebral hemisphere, the brain stem (5 ∼ 20 % of normal value), and in the left hemisphere (40 ∼ 60 % of normal value). In temporary ischemic brains, focal areas of increased activity were observed in the right cerebral hemisphere and the thalamus from 10 minutes to 24 hours after recirculation. The high activity disappeared rapidly at 10 minutes after the injection. It seemed that this high activity represented luxury perfusion in the region with severe tissue damage. In the left hemisphere, almost complete recovery of perfusion occurred at 1 ∼ 3 days after recirculation. These results suggested the possibility of IMP to demonstrate cerebral ischemia, luxury perfusion and diaschisis. (author)

  1. Neuronal Rho GTPase Rac1 elimination confers neuroprotection in a mouse model of permanent ischemic stroke.

    Science.gov (United States)

    Karabiyik, Cansu; Fernandes, Rui; Figueiredo, Francisco Rosário; Socodato, Renato; Brakebusch, Cord; Lambertsen, Kate Lykke; Relvas, João Bettencourt; Santos, Sofia Duque

    2017-09-28

    The Rho GTPase Rac1 is a multifunctional protein involved in distinct pathways ranging from development to pathology. The aim of the present study was to unravel the contribution of neuronal Rac1 in regulating the response to brain injury induced by permanent focal cerebral ischemia (pMCAO). Our results show that pMCAO significantly increased total Rac1 levels in wild type mice, mainly through rising nuclear Rac1, while a reduction in Rac1 activation was observed. Such changes preceded cell death induced by excitotoxic stress. Pharmacological inhibition of Rac1 in primary neuronal cortical cells prevented the increase in oxidative stress induced after overactivation of glutamate receptors. However, this was not sufficient to prevent the associated neuronal cell death. In contrast, RNAi-mediated knock down of Rac1 in primary cortical neurons prevented cell death elicited by glutamate excitotoxicity and decreased the activity of NADPH oxidase. To test whether in vivo down regulation of neuronal Rac1 was neuroprotective after pMCAO, we used tamoxifen-inducible neuron-specific conditional Rac1-knockout mice. We observed a significant 50% decrease in brain infarct volume of knockout mice and a concomitant increase in HIF-1α expression compared to littermate control mice, demonstrating that ablation of Rac1 in neurons is neuroprotective. Transmission electron microscopy performed in the ischemic brain showed that lysosomes in the infarct of Rac1- knockout mice were preserved at similar levels to those of non-infarcted tissue, while littermate mice displayed a decrease in the number of lysosomes, further corroborating the notion that Rac1 ablation in neurons is neuroprotective. Our results demonstrate that Rac1 plays important roles in the ischemic pathological cascade and that modulation of its levels is of therapeutic interest. © 2017 International Society of Neuropathology.

  2. Timing of oral anticoagulant therapy in acute ischemic stroke with atrial fibrillation: study protocol for a registry-based randomised controlled trial.

    Science.gov (United States)

    Åsberg, Signild; Hijazi, Ziad; Norrving, Bo; Terént, Andreas; Öhagen, Patrik; Oldgren, Jonas

    2017-12-02

    Oral anticoagulation therapy is recommended for the prevention of recurrent ischemic stroke in patients with atrial fibrillation (AF). Current guidelines do not provide evidence-based recommendations on optimal time-point to start anticoagulation therapy after an acute ischemic stroke. Non-vitamin K antagonist oral anticoagulants (NOACs) may offer advantages compared to warfarin because of faster and more predictable onset of action and potentially a lower risk of intracerebral haemorrhage also in the acute phase after an ischemic stroke. The TIMING study aims to establish the efficacy and safety of early vs delayed initiation of NOACs in patients with acute ischemic stroke and AF. The TIMING study is a national, investigator-led, registry-based, multicentre, open-label, randomised controlled study. The Swedish Stroke Register is used for enrolment, randomisation and follow-up of 3000 patients, who are randomised (1:1) within 72 h from ischemic stroke onset to either early (≤ 4 days) or delayed (≥ 5-10 days) start of NOAC therapy. The primary outcome is the composite of recurrent ischemic stroke, symptomatic intracerebral haemorrhage, or all-cause mortality within 90 days after randomisation. Secondary outcomes include: individual components of the primary outcome at 90 and 365 days; major haemorrhagic events; functional outcome by the modified Rankin Scale at 90 days; and health economics. In an optional biomarker sub-study, blood samples will be collected after randomisation from approximately half of the patients for central analysis of cardiovascular biomarkers after study completion. The study is funded by the Swedish Medical Research Council. Enrolment of patients started in April 2017. The TIMING study addresses the ongoing clinical dilemma of when to start NOAC after an acute ischemic stroke in patients with AF. By the inclusion of a randomisation module within the Swedish Stroke Register, the advantages of a prospective randomised study design

  3. Remote Ischemic Conditioning to Protect against Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Brevoord, Daniel; Kranke, Peter; Kuijpers, Marijn; Weber, Nina; Hollmann, Markus; Preckel, Benedikt

    2012-01-01

    Background Remote ischemic conditioning is gaining interest as potential method to induce resistance against ischemia reperfusion injury in a variety of clinical settings. We performed a systematic review and meta-analysis to investigate whether remote ischemic conditioning reduces mortality, major adverse cardiovascular events, length of stay in hospital and in the intensive care unit and biomarker release in patients who suffer from or are at risk for ischemia reperfusion injury. Methods and Results Medline, EMBASE and Cochrane databases were searched for randomized clinical trials comparing remote ischemic conditioning, regardless of timing, with no conditioning. Two investigators independently selected suitable trials, assessed trial quality and extracted data. 23 studies in patients undergoing cardiac surgery (15 studies), percutaneous coronary intervention (four studies) and vascular surgery (four studies), comprising in total 1878 patients, were included in this review. Compared to no conditioning, remote ischemic conditioning did not reduce mortality (odds ratio 1.22 [95% confidence interval 0.48, 3.07]) or major adverse cardiovascular events (0.65 [0.38, 1.14]). However, the incidence of myocardial infarction was reduced with remote ischemic conditioning (0.50 [0.31, 0.82]), as was peak troponin release (standardized mean difference −0.28 [−0.47, −0.09]). Conclusion There is no evidence that remote ischemic conditioning reduces mortality associated with ischemic events; nor does it reduce major adverse cardiovascular events. However, remote ischemic conditioning did reduce the incidence of peri-procedural myocardial infarctions, as well as the release of troponin. PMID:22860077

  4. EFFICACY OF MELDONIUM IN ACUTE PERIOD OF ISCHEMIC STROKE

    Directory of Open Access Journals (Sweden)

    S. V. Kotov

    2015-01-01

    Full Text Available Background: As long as systemic thrombolysis is indicated to not more than 10% of patients with ischemic stroke, the search for medical agents for basic treatment of stroke is an important problem of today’s neurology.Aim: To evaluate efficacy of meldonium in patients with acute ischemic stroke.Materials and methods: One hundred and fourteen patients were assessed in the acute period of strokes in the internal carotid artery system. The main group included 70 patients who were given meldonium (Mildronate in addition to their basic treatment regimen. The drug was administered intravenously in daily drop infusions at dose of 10 ml of 10% solution for 10 days, thereafter they were switched to oral treatment at 250 mg daily for 2 to 3 weeks. The control group consisted of 40 patients who received only basic treatment regimen. Both groups were compatible for their age, gender distribution, severity of stroke and degree of neurologic dysfunction.Results: In the patients who were given meldonium in addition to basic treatment of ischemic stroke, neurological deficiency, assessed by NIHSS, scored significantly better than in those from the control group (3.1 ± 0.1 vs. 2.6 ± 0.17, p < 0.05. Also, they had significantly less disability on modified Rankin scale (1.3 ± 0.03 vs. 1.07 ± 0.07, p < 0.01 and more improvement in mobility as per Rivermead mobility index (3.6 ± 0.17 vs. 2.9 ± 0.25, p < 0.05.Conclusion: The addition of meldonium to the set of medical treatment in ischemic stroke patients gives positive results reflecting a decreased neurological deficiency, increased levels of mobility and daily activities.

  5. Intake of antioxidants and B vitamins is inversely associated with ischemic stroke and cerebral atherosclerosis

    Science.gov (United States)

    Choe, Hansaem; Hwang, Ji-Yun; Yun, Jin A; Kim, Ji-Myung; Song, Tae-Jin; Chang, Namsoo; Kim, Yong-Jae

    2016-01-01

    BACKGROUND/OBJECTIVES This study was conducted to examine relationships between dietary habits and intakes of antioxidants and B vitamins and the risk of ischemic stroke, and to compare dietary factors according to the presence of cerebral artery atherosclerosis and stroke subtypes. SUBJECTS/METHODS A total of 147 patients and 144 control subjects were recruited consecutively in the metropolitan area of Seoul, Korea. Sixty participants each in the case and control groups were included in analyses after 1:1 frequency matching. In addition, 117 acute ischemic stroke patients were classified into subtypes according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) guidelines. Dietary intake was measured using a semi-quantitative food frequency questionnaire composed of 111 food items and plasma lipid and homocysteine levels were analyzed. RESULTS When compared with control subjects, stroke patients had unfavorable dietary behaviors and lower intakes of fruits (73.1 ± 83.2 g vs. 230.9 ± 202.1 g, P < 0.001), vegetables (221.1 ± 209.0 g vs. 561.7 ± 306.6 g, P < 0.001), and antioxidants, including vitamins C, E, B6, β-carotene, and folate. The intakes of fruits, vegetables, vitamin C, and folate were inversely associated with the risk of ischemic stroke after adjusting for confounding factors. Intakes of vegetables, vitamins C, B6, B12, and folate per 1,000 kcal were lower in ischemic stroke with cerebral atherosclerosis than in those without. Overall vitamin B12 intake per 1,000 kcal differed according to the TOAST classification (P = 0.004), but no differences among groups existed based on the post-hoc test. CONCLUSIONS When compared with control subjects, ischemic stroke patients, particularly those with cerebral atherosclerosis, had unfavorable dietary intake, which may have contributed to the development of ischemic stroke. These results indicate that proper dietary recommendations are important for the prevention of ischemic stroke. PMID:27698959

  6. Toll-like receptor 2 deficiency leads to delayed exacerbation of ischemic injury

    Directory of Open Access Journals (Sweden)

    Bohacek Ivan

    2012-08-01

    Full Text Available Abstract Background Using a live imaging approach, we have previously shown that microglia activation after stroke is characterized by marked and long-term induction of the Toll-like receptor (TLR 2 biophotonic signals. However, the role of TLR2 (and potentially other TLRs beyond the acute innate immune response and as early neuroprotection against ischemic injury is not well understood. Methods TLR2−/− mice were subjected to transient middle cerebral artery occlusion followed by different reperfusion times. Analyses assessing microglial activation profile/innate immune response were performed using in situ hybridization, immunohistochemistry analysis, flow cytometry and inflammatory cytokine array. The effects of the TLR2 deficiency on the evolution of ischemic brain injury were analyzed using a cresyl violet staining of brain sections with appropriate lesion size estimation. Results Here we report that TLR2 deficiency markedly affects post-stroke immune response resulting in delayed exacerbation of the ischemic injury. The temporal analysis of the microglia/macrophage activation profiles in TLR2−/− mice and age-matched controls revealed reduced microglia/macrophage activation after stroke, reduced capacity of resident microglia to proliferate as well as decreased levels of monocyte chemotactic protein-1 (MCP-1 and consequently lower levels of CD45high/CD11b+ expressing cells as shown by flow cytometry analysis. Importantly, although acute ischemic lesions (24 to 72 h were smaller in TLR2−/− mice, the observed alterations in innate immune response were more pronounced at later time points (at day 7 after initial stroke, which finally resulted in delayed exacerbation of ischemic lesion leading to larger chronic infarctions as compared with wild-type mice. Moreover, our results revealed that TLR2 deficiency is associated with significant decrease in the levels of neurotrophic/anti-apoptotic factor Insulin-like growth factor-1 (IGF-1

  7. Perioperative erythropoietin protects the CNS against ischemic lesions in patients after open heart surgery.

    Science.gov (United States)

    Lakič, Nikola; Mrak, Miha; Šušteršič, Miha; Rakovec, Peter; Bunc, Matjaž

    2016-12-01

    The aim of this study was to establish erythropoietin as a protective factor against brain ischemia during open heart surgery. A total of 36 consecutive patients scheduled for revascularization heart surgery were included in the study. Of the patients 18 received 3 intravenous doses of recombinant human erythropoietin (rHuEpo, 24,000 IU) and 18 patients received a placebo. Magnetic resonance imaging (MRI) to detect new brain ischemic lesions was performed. Additionally, S100A, S100B, neuron-specific enolase A and B (NSE-A and B) and the concentration of antibodies against N‑methyl-D-aspartate receptors (NMDAR) to identify new neurological complications were determined. Patients who received rHuEpo showed no postoperative ischemic changes in the brain on MRI images. In the control group 5 (27.8 %) new ischemic lesions were found. The NMDAR antibody concentration, S100A, S100B and NSE showed no significant differences between the groups for new cerebral ischemia. High levels of lactate before and after external aortic compression (p = 0.022 and p = 0.048, respectively) and duration of operation could predict new ischemic lesions (p = 0.009). The addition of rHuEpo reduced the formation of lesions detectable by MRI in the brain and could be used clinically as neuroprotection in cardiac surgery.

  8. Molecular Mechanisms of Renal Ischemic Conditioning Strategies

    DEFF Research Database (Denmark)

    Kierulf-Lassen, Casper; Nieuwenhuijs-Moeke, Gertrude J; Krogstrup, Nicoline V

    2015-01-01

    summarizes research on the molecular mechanisms underlying both local and remote ischemic pre-, per- and postconditioning of the kidney. The different types of conditioning strategies in the kidney recruit similar powerful pro-survival mechanisms. Likewise, renal ischemic conditioning mobilizes many...

  9. Multiphasic perfusion CT in acute middle cerebral artery ischemic stroke: prediction of final infarct volume and correlation with clinical outcome

    International Nuclear Information System (INIS)

    Yi, Chin A; Na, Dong Gyu; Ryoo, Jae Wook; Moon, Chan Hong; Byun, Hong Sik; Roh, Hong Gee; Moon, Won Jin; Lee, Kwang Ho; Lee, Soo Joo

    2002-01-01

    To assess the utility of multiphasic perfusion CT in the prediction of final infarct volume, and the relationship between lesion volume revealed by CT imaging and clinical outcome in acute ischemic stroke patients who have not undergone thrombolytic therapy. Thirty-five patients underwent multiphasic perfusion CT within six hours of stroke onset. After baseline unenhanced helical CT scanning, contrast-enhanced CT scans were obtained 20, 34, 48, and 62 secs after the injection of 90 mL contrast medium at a rate of 3 mL/sec. CT peak and total perfusion maps were obtained from serial CT images, and the initial lesion volumes revealed by CT were compared with final infarct volumes and clinical scores. Overall, the lesion volumes seen on CT peak perfusion maps correlated most strongly with final infarct volumes (R2=0.819, p<0.001, slope of regression line=1.016), but individual data showed that they were less than final infarct volume in 31.4% of patients. In those who showed early clinical improvement (n=6), final infarct volume tended to be overestimated by CT peak perfusion mapping and only on total perfusion maps was there significant correlation between lesion volume and final infarct volume (R2=0.854, p=0.008). The lesion volumes depicted by CT maps showed moderate correlation with baseline clinical scores and clinical outcomes (R=0.445-0.706, p≤0.007). CT peak perfusion maps demonstrate strong correlation between lesion volume and final infarct volume, and accurately predict final infarct volume in about two-thirds of the 35 patients. The lesion volume seen on CT maps shows moderate correlation with clinical outcome

  10. Deficiency of ATP-binding cassette transporters A1 and G1 in macrophages increases inflammation and accelerates atherosclerosis in mice.

    Science.gov (United States)

    Westerterp, Marit; Murphy, Andrew J; Wang, Mi; Pagler, Tamara A; Vengrenyuk, Yuliya; Kappus, Mojdeh S; Gorman, Darren J; Nagareddy, Prabhakara R; Zhu, Xuewei; Abramowicz, Sandra; Parks, John S; Welch, Carrie; Fisher, Edward A; Wang, Nan; Yvan-Charvet, Laurent; Tall, Alan R

    2013-05-24

    Plasma high-density lipoprotein levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is attributable to the ability of high-density lipoprotein to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking. To assess the role of macrophage cholesterol efflux pathways in atherogenesis. We developed mice with efficient deletion of the ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1) in macrophages (MAC-ABC(DKO) mice) but not in hematopoietic stem or progenitor populations. MAC-ABC(DKO) bone marrow (BM) was transplanted into Ldlr(-/-) recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared with controls. On the Western-type diet, MAC-ABC(DKO) BM-transplanted Ldlr(-/-) mice had disproportionate atherosclerosis, considering they also had lower very low-density lipoprotein/low-density lipoprotein cholesterol levels than controls. ABCA1/G1-deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, Western-type diet-fed MAC-ABC(DKO) BM-transplanted Ldlr(-/-) mice displayed monocytosis and neutrophilia in the absence of hematopoietic stem and multipotential progenitor cells proliferation. Mechanistic studies revealed increased expressions of machrophage colony stimulating factor and granulocyte colony stimulating factor in splenic macrophage foam cells, driving BM monocyte and neutrophil production. These studies show that macrophage deficiency of ABCA1/G1 is proatherogenic likely by promoting plaque inflammation and uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways.

  11. Clinical Predictors of Hospital-acquired Pneumonia Associated with Acute Ischemic

    Directory of Open Access Journals (Sweden)

    Alexis Suárez Quesada

    2015-06-01

    Full Text Available Background: hospital-acquired pneumonia is a constant challenge given the current microbiological spectrum, antimicrobial resistance together with its high mortality, morbidity and hospital costs. Objective: to identify the clinical predictors of pneumonia associated with acute ischemic stroke. Methods: a prospective cohort study was conducted in 201 patients diagnosed with acute ischemic stroke consecutively admitted to the stroke unit of the General Carlos Manuel de Céspedes Teaching Hospital during the first seven days after the onset, from January 2012 through December 2013. The independent predictors of hospital-acquired pneumonia were obtained using multivariable logistic regression. Results: fifty six point seven percent were male. The mean age was 64.17 ± 14.33 years. Cases of hospital-acquired pneumonia associated with stroke accounted for 19, 9 %. Subjects who developed pneumonia were older (68.55 ± 13.51 vs. 63.08 ± 14.36 years, had a lower score in the Glasgow Coma Scale (8.00 ± 2.60 vs. 14.00 ± 2.82, and an increased number of leukocytes at admission (10.888 ± 3.487 vs. 9.233 ± 2.539 × 109/L. The following independent factors were identified: Glasgow Coma Scale ≤ 11 (OR: 26.099; 95 % CI 7.164-85.075, history of chronic obstructive pulmonary disease (OR: 8.896; 95 % CI 1.203-65.779, dysphagia (OR: 7.652; 95 % CI 2.369- 24.720, history of heart failure (OR: 4.583; 95 % CI 1.240- 16.932 and dysarthria/severe motor aphasia (OR: 4.222; 95 % CI 1.374- 12.975. Conclusions: the resulting logistic regression model is valid for predicting post-stroke pneumonia based on data routinely acquired.

  12. Peculiarities of reaction of HIF-1α protein of the hippocampus neurons in rats with experimental diabetes mellitus in the dynamics of ischemic-reperfusion damage of the brain

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    T. M. Boychuk

    2016-12-01

    Higher State Educational Establishment of Ukraine “Bukovinian State medical University”, Chernivtsi, Ukraine   Abstract Introduction. The role of the transcriptional factor Hif-1α in pathogenesis of hypoxic damages and diabetes mellitus (DM is proved, although molecular mechanisms underlying the basis of this factor dysfunction in association with DM with ischemic-reperfusion damage of the brain remain unknown. Objective. The objective of this investigation was to study the content of Hif-1α protein in the hippocampus neurons of rats with experimental DM in the dynamics of ischemic-reperfusion damage of the brain. Results. In rats without DM 20 minute ischemia with one hour reperfusion increases the content of Hif-1α protein in all the fields of the hippocampus. On the 12th day of ischemic-reperfusion period in the hippocampus CA2-CA4 fields the values of certain examined indices of the activity of Hif-1α transcriptional factor continue to increase, and in СА1field they normalize or approach to the values of animals in the control group.  In rats with DM during early post-ischemic period there are no changes of Hif-1α protein content in CA1 field, in CA2 field there are signs of its reduced activity, in CA3 field they are limited by the reaction of one index, in CA4 field they are of a similar character with those of the control rats under experimental conditions.  On the 12th day of ischemic-reperfusion period in CA1 field all the indices of activity of Hif-1α transcriptional factor increase exceeding corresponding indices by absolute values in animals of the control group under the same experimental conditions, in СА2 and СА3 fields changes of the examined parameters are limited as compared to the same ones in animals from the control group, in CA4 field values that were increased in the control group decrease. Conclusions. Diabetes mellitus restricts reaction of Hif-1α protein on ischemia-reperfusion inn the neurons of СА1-СА3 fields in

  13. Rare variants in ischemic stroke: an exome pilot study.

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    John W Cole

    Full Text Available The genetic architecture of ischemic stroke is complex and is likely to include rare or low frequency variants with high penetrance and large effect sizes. Such variants are likely to provide important insights into disease pathogenesis compared to common variants with small effect sizes. Because a significant portion of human functional variation may derive from the protein-coding portion of genes we undertook a pilot study to identify variation across the human exome (i.e., the coding exons across the entire human genome in 10 ischemic stroke cases. Our efforts focused on evaluating the feasibility and identifying the difficulties in this type of research as it applies to ischemic stroke. The cases included 8 African-Americans and 2 Caucasians selected on the basis of similar stroke subtypes and by implementing a case selection algorithm that emphasized the genetic contribution of stroke risk. Following construction of paired-end sequencing libraries, all predicted human exons in each sample were captured and sequenced. Sequencing generated an average of 25.5 million read pairs (75 bp×2 and 3.8 Gbp per sample. After passing quality filters, screening the exomes against dbSNP demonstrated an average of 2839 novel SNPs among African-Americans and 1105 among Caucasians. In an aggregate analysis, 48 genes were identified to have at least one rare variant across all stroke cases. One gene, CSN3, identified by screening our prior GWAS results in conjunction with our exome results, was found to contain an interesting coding polymorphism as well as containing excess rare variation as compared with the other genes evaluated. In conclusion, while rare coding variants may predispose to the risk of ischemic stroke, this fact has yet to be definitively proven. Our study demonstrates the complexities of such research and highlights that while exome data can be obtained, the optimal analytical methods have yet to be determined.

  14. Ischemic stroke due to embolic heart diseases and associated factors in Benin hospital setting.

    Science.gov (United States)

    Gnonlonfoun, Dieudonné; Adjien, Constant; Gnimavo, Ronald; Goudjinou, Gérard; Hotcho, Corine; Nyangui Mapaga, Jennifer; Sowanou, Arlos; Gnigone, Pupchen; Domingo, Rodrigue; Houinato, Dismand

    2018-04-15

    Poor access to cardiovascular checkups is a major cause of ignorance of embolic heart diseases as the etiology for ischemic stroke. Study ischemic strokes due to embolic heart diseases and their associated factors. It was a cross-sectional, prospective, descriptive and analytical study conducted from November 1, 2014 to August 31, 2015 on 104 patients with ischemic stroke confirmed through brain imaging. Embolic heart diseases included arrhythmia due to atrial fibrillation (AF), atrial flutter, myocardial infarction (MI), heart valve diseases and atrial septal aneurysm (ASA). The dependent variable was embolic heart disease while independent variables encompassed socio-demographic factors, patients' history, and lifestyle. Data analysis was carried out through SAS 9.3. The rate of embolic heart diseases (EHD) as etiology for ischemic stroke was 26% (28/104). AF accounted for 69% of embolic heart diseases and 22.8% of etiologies for ischemic stroke. Ischemic strokes prevalence was 3.5%, 2.5% and 1.2% respectively for heart valve diseases, MI and ASA. The associated factor was age (p=0.000). The diagnosis of a potential cardiac source of embolism is essential because of therapeutic and prognostic implications. Wherefore, there is need for cardiovascular examination particularly Holter ECG and cardiac ultrasound examination which are not always accessible to our populations. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Association of inflammatory gene polymorphisms with ischemic stroke in a Chinese Han population

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    Zhao Nan

    2012-07-01

    Full Text Available Abstract Background Inflammatory mechanisms are important in stroke risk, and genetic variations in components of the inflammatory response have been implicated as risk factors for stroke. We tested the inflammatory gene polymorphisms and their association with ischemic stroke in a Chinese Han population. Methods A total of 1,124 ischemic stroke cases and 1,163 controls were genotyped with inflammatory panel strips containing 51 selected inflammatory gene polymorphisms from 35 candidate genes. We tested the genotype-stroke association with logistic regression model. Results We found two single nucleotide polymorphisms (SNPs in CCL11 were associated with ischemic stroke. After adjusting for multiple testing using false discovery rate (FDR with a 0.20 cut-off point, CCL11 rs4795895 remained statistically significant. We further stratified the study population by their hypertension status. In the hypertensive group, CCR2 rs1799864, CCR5 rs1799987 and CCL11 rs4795895 were nominally associated with increased risk of stroke. In the non-hypertensive group, CCL11 rs3744508, LTC4S rs730012, FCER1B rs569108, TGFB1 rs1800469, LTA rs909253 and CCL11 rs4795895 were associated with ischemic stroke. After correction for multiple testing, CCR2 rs1799864 and CCR5 rs1799987 remained significant in the hypertensive group, and CCL11 rs3744508, LTC4S rs730012, FCER1B rs569108, TGFB1 rs1800469, LTA rs909253 remained significant in the non-hypertensive group. Conclusions Our results indicate that inflammatory genetic variants are associated with increased risk of ischemic stroke in a Chinese Han population, particularly in non-hypertensive individuals.

  16. Rational modulation of the innate immune system for neuroprotection in ischemic stroke

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    Diana eAmantea

    2015-04-01

    Full Text Available The innate immune system plays a dualistic role in the evolution of ischemic brain damage and has also been implicated in ischemic tolerance produced by different conditioning stimuli. Early after ischemia, perivascular astrocytes release cytokines and activate metalloproteases (MMPs that contribute to blood–brain barrier (BBB disruption and vasogenic oedema; whereas at later stages, they provide extracellular glutamate uptake, BBB regeneration and neurotrophic factors release. Similarly, early activation of microglia contributes to ischemic brain injury via the production of inflammatory cytokines, including tumor necrosis factor (TNF and interleukin (IL-1, reactive oxygen and nitrogen species and proteases. Nevertheless, microglia also contributes to the resolution of inflammation, by releasing IL-10 and tumor growth factor (TGF-beta, and to the late reparative processes by phagocytic activity and growth factors production. Indeed, after ischemia, microglia/macrophages differentiate towards several phenotypes: the M1 pro-inflammatory phenotype is classically activated via toll-like receptors or interferon-γ, whereas M2 phenotypes are alternatively activated by regulatory mediators, such as ILs 4, 10, 13 or TGF-beta. Thus, immune cells exert a dualistic role on the evolution of ischemic brain damage, since the classic phenotypes promote injury, whereas alternatively activated M2 macrophages or N2 neutrophils prompt tissue remodeling and repair.Moreover, a subdued activation of the immune system has been involved in ischemic tolerance, since different preconditioning stimuli act via modulation of inflammatory mediators, including toll-like receptors and cytokine signaling pathways. This further underscores that the immuno-modulatory approach for the treatment of ischemic stroke should be aimed at blocking the detrimental effects, while promoting the beneficial responses of the immune reaction.

  17. Increased risk of ischemic stroke after hyperosmolar hyperglycemic state: a population-based follow-up study.

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    Jen-Yu Wang

    Full Text Available BACKGROUND: Although much attention has been focused on the association between chronic hyperglycemia and cerebrovascular diseases in type 2 diabetes mellitus (DM patients, there is no data regarding the risk of ischemic stroke after a hyperosmolar hyperglycemic state (HHS attack. The objective of this study was to investigate the risk of ischemic stroke in type 2 DM patients after an HHS attack. METHODS: From 2004 to 2008, this retrospective observational study was conducted on a large cohort of Taiwanese using Taiwan's National Health Insurance Research Database (NHIRD. We identified 19,031 type 2 DM patients who were discharged with a diagnosis of HHS and 521,229 type 2 DM patients without an HHS diagnosis. Using the propensity score generated from logistic regression models, conditional on baseline covariates, we matched 19,031 type 2 DM patients with an HHS diagnosis with the same number from the comparison cohort. The one-year cumulative rate for ischemic stroke was estimated using the Kaplan-Meier method. After adjusting covariates, Cox proportional hazard regression was used to compute the adjusted one-year rate of ischemic stroke. RESULTS: Of the patients sampled, 1,810 (9.5% of the type 2 DM patients with HHS and 996 (5.2% of the comparison cohort developed ischemic stroke during the one-year follow-up period. After adjusting for covariates, the adjusted HR for developing ischemic stroke during the one-year follow-up period was 1.8 (95% C.I., 1.67 to 1.95, P<0.001 for type 2 DM patients with HHS compared with those without HHS. CONCLUSION: Although DM is a well-recognized risk factor for atherosclerosis, type 2 DM patients that have suffered a HHS attacks are at an increased risk of developing ischemic stroke compared with those without HHS.

  18. Influence of Bleeding Pattern on Ischemic Lesions After Spontaneous Hypertensive Intracerebral Hemorrhage with Intraventricular Hemorrhage.

    Science.gov (United States)

    Rivera-Lara, Lucia; Murthy, Santosh B; Nekoovaght-Tak, Saman; Ali, Hasan; McBee, Nichol; Dlugash, Rachel; Ram, Malathi; Thompson, Richard; Awad, Issam A; Hanley, Daniel F; Ziai, Wendy C

    2018-03-27

    Concomitant acute ischemic lesions are detected in up to a quarter of patients with spontaneous intracerebral hemorrhage (ICH). Influence of bleeding pattern and intraventricular hemorrhage (IVH) on risk of ischemic lesions has not been investigated. Retrospective study of all 500 patients enrolled in the CLEAR III randomized controlled trial of thrombolytic removal of obstructive IVH using external ventricular drainage. The primary outcome measure was radiologically confirmed ischemic lesions, as reported by the Safety Event Committee and confirmed by two neurologists. We assessed predictors of ischemic lesions including analysis of bleeding patterns (ICH, IVH and subarachnoid hemorrhage) on computed tomography scans (CT). Secondary outcomes were blinded assessment of mortality and modified Rankin scale (mRS) at 30 and 180 days. Ischemic lesions occurred in 23 (4.6%) during first 30 days after ICH. Independent risk factors associated with ischemic lesions in logistic regression models adjusted for confounders were higher IVH volume (p = 0.004) and persistent subarachnoid hemorrhage on CT scan (p = 0.03). Patients with initial IVH volume ≥ 15 ml had five times the odds of concomitant ischemic lesions compared to IVH volume < 15 ml. Patients with ischemic lesions had significantly higher odds of death at 1 and 6 months (but not poor outcome; mRS 4-6) compared to patients without concurrent ischemic lesions. Occurrence of ischemic lesions in the acute phase of IVH is not uncommon and is significantly associated with increased early and late mortality. Extra-parenchymal blood (larger IVH and visible subarachnoid hemorrhage) is a strong predictor for development of concomitant ischemic lesions after ICH.

  19. Arctigenin promotes cholesterol efflux from THP-1 macrophages through PPAR-γ/LXR-α signaling pathway.

    Science.gov (United States)

    Xu, Xiaolin; Li, Qian; Pang, Liewen; Huang, Guoqian; Huang, Jiechun; Shi, Meng; Sun, Xiaotian; Wang, Yiqing

    2013-11-15

    Cholesterol efflux from macrophages is a critical mechanism to prevent the development of atherosclerosis. Here, we sought to investigate the effects of arctigenin, a bioactive component of Arctium lappa, on the cholesterol efflux in oxidized low-density lipoprotein (oxLDL)-loaded THP-1 macrophages. Our data showed that arctigenin significantly accelerated apolipoprotein A-I- and high-density lipoprotein-induced cholesterol efflux in both dose- and time-dependent manners. Moreover, arctigenin treatment enhanced the expression of ATP binding cassette transporter A1 (ABCA1), ABCG1, and apoE, all of which are key molecules in the initial step of cholesterol efflux, at both mRNA and protein levels. Arctigenin also caused a concentration-dependent elevation in the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and liver X receptor-alpha (LXR-α). The arctigenin-mediated induction of ABCA1, ABCG1, and apoE was abolished by specific inhibition of PPAR-γ or LXR-α using small interfering RNA technology. Our results collectively indicate that arctigenin promotes cholesterol efflux in oxLDL-loaded THP-1 macrophages through upregulation of ABCA1, ABCG1 and apoE, which is dependent on the enhanced expression of PPAR-γ and LXR-α. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Ischemic Stroke Identification Based on EEG and EOG using 1D Convolutional Neural Network and Batch Normalization

    OpenAIRE

    Giri, Endang Purnama; Fanany, Mohamad Ivan; Arymurthy, Aniati Murni

    2016-01-01

    In 2015, stroke was the number one cause of death in Indonesia. The majority type of stroke is ischemic. The standard tool for diagnosing stroke is CT-Scan. For developing countries like Indonesia, the availability of CT-Scan is very limited and still relatively expensive. Because of the availability, another device that potential to diagnose stroke in Indonesia is EEG. Ischemic stroke occurs because of obstruction that can make the cerebral blood flow (CBF) on a person with stroke has become...

  1. Urinary albumin excretion. An independent predictor of ischemic heart disease

    DEFF Research Database (Denmark)

    Borch-Johnsen, K; Feldt-Rasmussen, B; Strandgaard, S

    1999-01-01

    Cross-sectional studies suggest that an increased urinary albumin excretion rate is associated with cardiovascular disease, dyslipidemia, and hypertension. The purpose of this study was to analyze prospectively whether the urinary albumin-to -creatinine (A/C) ratio can independently predict...... ischemic heart disease (IHD) in a population-based cohort. In 1983, urinary albumin and creatinine levels were measured, along with the conventional atherosclerotic risk factors, in 2085 consecutive participants without IHD, renal disease, urinary tract infection, or diabetes mellitus. The participants...

  2. Molecular Basis of Impaired Glycogen Metabolism during Ischemic Stroke and Hypoxia

    Science.gov (United States)

    Hossain, Mohammed Iqbal; Roulston, Carli Lorraine; Stapleton, David Ian

    2014-01-01

    Background Ischemic stroke is the combinatorial effect of many pathological processes including the loss of energy supplies, excessive intracellular calcium accumulation, oxidative stress, and inflammatory responses. The brain's ability to maintain energy demand through this process involves metabolism of glycogen, which is critical for release of stored glucose. However, regulation of glycogen metabolism in ischemic stroke remains unknown. In the present study, we investigate the role and regulation of glycogen metabolizing enzymes and their effects on the fate of glycogen during ischemic stroke. Results Ischemic stroke was induced in rats by peri-vascular application of the vasoconstrictor endothelin-1 and forebrains were collected at 1, 3, 6 and 24 hours post-stroke. Glycogen levels and the expression and activity of enzymes involved in glycogen metabolism were analyzed. We found elevated glycogen levels in the ipsilateral hemispheres compared with contralateral hemispheres at 6 and 24 hours (25% and 39% increase respectively; PGlycogen synthase activity and glycogen branching enzyme expression were found to be similar between the ipsilateral, contralateral, and sham control hemispheres. In contrast, the rate-limiting enzyme for glycogen breakdown, glycogen phosphorylase, had 58% lower activity (Pglycogen debranching enzyme expression 24 hours post-stroke was 77% (Pglycogen phosphorylase activity and increased glycogen accumulation but did not alter glycogen synthase activity. Furthermore, elevated glycogen levels provided metabolic support to astrocytes during hypoxia. Conclusion Our study has identified that glycogen breakdown is impaired during ischemic stroke, the molecular basis of which includes reduced glycogen debranching enzyme expression level together with reduced glycogen phosphorylase and PKA activity. PMID:24858129

  3. Proton NMR imaging in experimental ischemic infarction

    International Nuclear Information System (INIS)

    Buonanno, F.S.; Pykett, I.L.; Brady, T.J.; Vielma, J.; Burt, C.T.; Goldman, M.R.; Hinshaw, W.S.; Pohost, G.M.; Kistler, J.P.

    1983-01-01

    Proton nuclear magnetic resonance (NMR) images depict the distribution and concentration of mobile protons modified by the relaxation times T1 and T2. Using the steady-state-free-precession (SSFP) technique, serial coronal images were obtained sequentially over time in laboratory animals with experimental ischemic infarction. Image changes were evident as early as 2 hours after carotid artery ligation, and corresponded to areas of ischemic infarction noted pathologically. Resulting SSFP images in experimental stroke are contrasted to inversion-recovery NMR images in an illustrative patient with established cerebral infarction. Bulk T1 and T2 measurements were made in vitro in three groups of gerbils: normal, those with clinical evidence of infarction, and those clinically normal after carotid ligature. Infarcted hemispheres had significantly prolonged T1 and T2 (1.47 +/- .12 sec, 76.0 +/- 9.0 msec, respectively) when compared to the contralateral hemisphere (T1 . 1.28 +/- .05 sec, T2 . 58.7 +/- 3.9 msec) or to the other two groups. These data suggest that changes in NMR parameters occur and can be detected by NMR imaging as early as two hours after carotid artery ligation

  4. C-reactive Protein -717A>G and -286C>T>A Gene Polymorphism and Ischemic Stroke.

    Science.gov (United States)

    Liu, Yan; Geng, Pei-Liang; Yan, Fu-Qin; Chen, Tong; Wang, Wei; Tang, Xu-Dong; Zheng, Jing-Chen; Wu, Wei-Ping; Wang, Zhen-Fu

    2015-06-20

    Inflammation plays a pivotal role in the formation and progression of ischemic stroke. Recently, more and more epidemiological studies have focused on the association between C-reactive protein (CRP) -717A > G and -286C > T > A genetic polymorphisms and ischemic stroke. However, the findings of these researches are not conclusive. We performed a meta-analysis to determine whether these two polymorphisms are associated with the risk of ischemic stroke. Eligible studies were identified from the database of PubMed, Medline, Embase, Web of Science, CNKI, Weipu, and Wanfang. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Four articles were included in our study, including 1926 cases and 2678 controls for -717A > G polymorphism, 652 cases and 1103 controls for -286C > T > A polymorphism. The results of meta-analysis showed that single nucleotide polymorphism (SNP) -717A > G was not significantly associated with the risk of ischemic stroke (GG vs. AA, OR = 1.12, 95% CI = 0.83-1.50, P = 0.207; GG + GA vs. AA, OR = 1.04, 95% CI = 0.93-1.17, P = 0.533; GG vs. GA + AA, OR = 1.10, 95% CI = 0.82-1.47, P = 0.220). Meta-analysis of SNP - 286C > T > A also demonstrated no statistical evidence of a significant association with the risk of ischemic stroke (AA vs. CC, OR = 0.86, 95% CI = 0.59-1.25, P = 0.348; AA vs. CC, OR = 0.92, 95% CI = 0.80-1.06, P = 0.609; AA vs. CC, OR = 0.89, 95% CI = 0.62-1.30, P = 0.374). This meta-analysis demonstrated little evidence to support a role of CRP gene -717A > G, -286C > T > A polymorphisms in ischemic stroke predisposition. However, to draw comprehensive and more reliable conclusions, further larger studies are needed to validate the association between CRP gene polymorphisms and ischemic stroke in various ethnic groups.

  5. Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes).

    Science.gov (United States)

    Easton, J Donald; Aunes, Maria; Albers, Gregory W; Amarenco, Pierre; Bokelund-Singh, Sara; Denison, Hans; Evans, Scott R; Held, Peter; Jahreskog, Marianne; Jonasson, Jenny; Minematsu, Kazuo; Molina, Carlos A; Wang, Yongjun; Wong, K S Lawrence; Johnston, S Claiborne

    2017-09-05

    Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52-1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2

  6. Increased risk of ischemic stroke in young patients with ankylosing spondylitis: a population-based longitudinal follow-up study.

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    Chia-Wei Lin

    Full Text Available BACKGROUND: Prospective data on the association between ischemic stroke and ankylosing spondylitis (AS in the young are sparse. The purpose of this population-based, age- and sex-matched longitudinal follow-up study was to investigate the risk of developing ischemic stroke in young patients with AS. METHODS: A total of 4562 patients aged 18- to 45-year-old with at least two ambulatory visits in 2001 with a principal diagnosis of AS were enrolled in the AS group. The non-AS group consisted of 22810 age- and sex-matched, randomly sampled subjects without AS. The two-year ischemic stroke-free survival rate for each group were calculated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used to estimate the hazard ratio of ischemic stroke after adjusting for demographic and clinical covariates. RESULTS: During follow-up, 21 patients in the AS group and 53 in the non-AS group developed ischemic stroke. The ischemic stroke-free survival rate over the 2 year follow-up was lower in the AS group than the non-AS group (p = 0.0021. The crude hazard ratio of ischemic stroke for the AS group was 1.98 (95% CI, 1.20-3.29; p = 0.0079 and the adjusted hazard ratio after controlling for demographic and comorbid medical disorders was 1.93 (95% CI, 1.16-3.20; p = 0.0110. CONCLUSION: Our study showed an increased risk of developing ischemic stroke in young patients with AS.

  7. Short-Term Prognosis of Transient Ischemic Attack and Predictive Value of the ABCD2 Score in Hong Kong Chinese

    Directory of Open Access Journals (Sweden)

    Lai Hong Simon Chiu

    2014-03-01

    Full Text Available Background: Literature on prognosis of transient ischemic attack (TIA in Chinese is scarce. The short-term prognosis of TIA and the predictive value of the ABCD2 score in Hong Kong Chinese patients attending the emergency department (ED were studied to provide reference for TIA patient management in our ED. Methods: A cohort of TIA patients admitted through the ED to 13 acute public hospitals in 2006 was recruited through the centralized electronic database by the Hong Kong Hospital Authority (HA. All inpatients were e-coded by the HA according to the International Classification of Diseases, Ninth Revision (ICD9. Electronic records and hard copies were studied up to 90 days after a TIA. The stroke risk of a separate TIA cohort diagnosed by the ED was compared. Results: In the 1,000 recruited patients, the stroke risk after a TIA at days 2, 7, 30, and 90 was 0.2, 1.4, 2.9, and 4.4%, respectively. Antiplatelet agents were prescribed in 89%, warfarin in 6.9%, statin in 28.6%, antihypertensives in 39.3%, and antidiabetics in 11.9% of patients after hospitalization. Before the index TIA, the prescribed medications were 27.6, 3.7, 11.3, 27.1, and 9.7%, respectively. The accuracy of the ABCD2 score in predicting stroke risk was 0.607 at 7 days, 0.607 at 30 days, and 0.574 at 90 days. At 30 days, the p for trend across ABCD2 score levels was 0.038 (OR for every score point = 1.36, p = 0.040. Diabetes mellitus, previous stroke and carotid bruit were associated with stroke within 90 days (p = 0.038, 0.045, 0.030, respectively. A total of 45.4% of CTs of the brain showed lacunar infarcts or small vessel disease. There was an increased stroke risk at 90 days in patients with old or new infarcts on CT or MRI. Patients with carotid stenosis ≥70% had an increased stroke risk within 30 (OR = 6.335, p = 0.013 and 90 days (OR = 3.623, p = 0.050. Stroke risks at days 2, 7, 30, and 90 in the 289 TIA patients diagnosed by the ED were 0.35, 2.4, 5.2, and 6

  8. Dual Antiplatelet Therapy in Secondary Prevention of Ischemic Stroke: A Ghost from the Past or a New Frontier?

    Directory of Open Access Journals (Sweden)

    Clotilde Balucani

    2010-01-01

    Full Text Available With majority of ischemic strokes attributable to atherothrombosis and many being predictable after transient ischemic attacks (TIA, the role of early secondary prevention with antiplatelet agents is under renewed investigation. Prior major clinical trials of various secondary stroke prevention regimens pointed to a greater efficacy of dual antiplatelet agents if initiated early from symptom onset. This paper examines data and rationale behind dual antiplatelet regimens across the completed clinical trials. The safety of dual antiplatelets approach is of concern, but it could be outweighed, at least in early management, by a greater reduction in recurrence of ischemic events since this risk is “front loaded” after minor stroke or TIA. Aspirin monotherapy, though considered standard of care, is compared to aspirin-extended release dipiridamole and its combination with clopidogrel in early-phase completed and efficacy-phase ongoing clinical trials.

  9. Differential Temporal Evolution Patterns in Brain Temperature in Different Ischemic Tissues in a Monkey Model of Middle Cerebral Artery Occlusion

    Directory of Open Access Journals (Sweden)

    Zhihua Sun

    2012-01-01

    Full Text Available Brain temperature is elevated in acute ischemic stroke, especially in the ischemic penumbra (IP. We attempted to investigate the dynamic evolution of brain temperature in different ischemic regions in a monkey model of middle cerebral artery occlusion. The brain temperature of different ischemic regions was measured with proton magnetic resonance spectroscopy (1H MRS, and the evolution processes of brain temperature were compared among different ischemic regions. We found that the normal (baseline brain temperature of the monkey brain was 37.16°C. In the artery occlusion stage, the mean brain temperature of ischemic tissue was 1.16°C higher than the baseline; however, this increase was region dependent, with 1.72°C in the IP, 1.08°C in the infarct core, and 0.62°C in the oligemic region. After recanalization, the brain temperature of the infarct core showed a pattern of an initial decrease accompanied by a subsequent increase. However, the brain temperature of the IP and oligemic region showed a monotonously and slowly decreased pattern. Our study suggests that in vivo measurement of brain temperature could help to identify whether ischemic tissue survives.

  10. Age-related differences in the rate and diagnosis of 30-day readmission after hospitalization for acute ischemic stroke.

    Science.gov (United States)

    Hirayama, Atsushi; Goto, Tadahiro; Faridi, Mohammad K; Camargo, Carlos A; Hasegawa, Kohei

    2018-01-01

    Background Little is known about the association between age and readmission within 30 days after hospitalization for acute ischemic stroke. Aim To examine the age-related differences in rate and principal reason of 30-day readmissions in patients hospitalized for acute ischemic stroke. Methods In this retrospective, population-based cohort study using State Inpatient Databases from eight US states, we identified all adults hospitalized for acute ischemic stroke. We grouped the patients into four age categories: readmission within 30 days of discharge from the index hospitalization for acute ischemic stroke and the principal diagnosis of 30-day readmission. Results We identified 620,788 hospitalizations for acute ischemic stroke. The overall 30-day readmission rate was 16.6% with an increase with advanced age. Compared to patients aged readmission rate was significantly higher in age 65-74 years (OR 1.19; 95% CI 1.16-1.21), in age 75-84 years (OR 1.29; 95% CI 1.27-1.31), and in ≥ 85 years (OR 1.24; 95% CI 1.22-1.27; all Preadmission rate association between men and women (P interaction  readmissions were assigned stroke-related conditions or rehabilitation care. Compared to younger adults, older adults were more likely to present with non-stroke-related conditions (46.1% in readmission rate after acute ischemic stroke. Compared with younger adults, older adults were more likely to be readmitted for non-stroke-related conditions.

  11. Rehabilitation Outcomes: Ischemic versus Hemorrhagic Strokes.

    Science.gov (United States)

    Perna, Robert; Temple, Jessica

    2015-01-01

    Background. Ischemic and hemorrhagic strokes have different pathophysiologies and possibly different long-term cerebral and functional implications. Hemorrhagic strokes expose the brain to irritating effects of blood and ischemic strokes reflect localized or diffuse cerebral vascular pathology. Methods. Participants were individuals who suffered either an ischemic (n = 172) or hemorrhagic stroke (n = 112) within the past six months and were involved in a postacute neurorehabilitation program. Participants completed three months of postacute neurorehabilitation and the Mayo Portland Adaptability Inventory-4 (MPAI-4) at admission and discharge. Admission MPAI-4 scores and level of functioning were comparable. Results. Group ANOVA comparisons show no significant group differences at admission or discharge or difference in change scores. Both groups showed considerably reduced levels of productivity/employment after discharge as compared to preinjury levels. Conclusions. Though the pathophysiology of these types of strokes is different, both ultimately result in ischemic injuries, possibly accounting for lack of findings of differences between groups. In the present study, participants in both groups experienced similar functional levels across all three MPAI-4 domains both at admission and discharge. Limitations of this study include a highly educated sample and few outcome measures.

  12. Rehabilitation Outcomes: Ischemic versus Hemorrhagic Strokes

    Directory of Open Access Journals (Sweden)

    Robert Perna

    2015-01-01

    Full Text Available Background. Ischemic and hemorrhagic strokes have different pathophysiologies and possibly different long-term cerebral and functional implications. Hemorrhagic strokes expose the brain to irritating effects of blood and ischemic strokes reflect localized or diffuse cerebral vascular pathology. Methods. Participants were individuals who suffered either an ischemic (n=172 or hemorrhagic stroke (n=112 within the past six months and were involved in a postacute neurorehabilitation program. Participants completed three months of postacute neurorehabilitation and the Mayo Portland Adaptability Inventory-4 (MPAI-4 at admission and discharge. Admission MPAI-4 scores and level of functioning were comparable. Results. Group ANOVA comparisons show no significant group differences at admission or discharge or difference in change scores. Both groups showed considerably reduced levels of productivity/employment after discharge as compared to preinjury levels. Conclusions. Though the pathophysiology of these types of strokes is different, both ultimately result in ischemic injuries, possibly accounting for lack of findings of differences between groups. In the present study, participants in both groups experienced similar functional levels across all three MPAI-4 domains both at admission and discharge. Limitations of this study include a highly educated sample and few outcome measures.

  13. Behavior outcome after ischemic and hemorrhagic stroke, with similar brain damage, in rats.

    Science.gov (United States)

    Mestriner, Régis Gemerasca; Miguel, Patrícia Maidana; Bagatini, Pamela Brambilla; Saur, Lisiani; Boisserand, Lígia Simões Braga; Baptista, Pedro Porto Alegre; Xavier, Léder Leal; Netto, Carlos Alexandre

    2013-05-01

    Stroke causes disability and mortality worldwide and is divided into ischemic and hemorrhagic subtypes. Although clinical trials suggest distinct recovery profiles for ischemic and hemorrhagic events, this is not conclusive due to stroke heterogeneity. The aim of this study was to produce similar brain damage, using experimental models of ischemic (IS) and hemorrhagic (HS) stroke and evaluate the motor spontaneous recovery profile. We used 31 Wistar rats divided into the following groups: Sham (n=7), ischemic (IS) (n=12) or hemorrhagic (HS) (n=12). Brain ischemia or hemorrhage was induced by endotelin-1 (ET-1) and collagenase type IV-S (collagenase) microinjections, respectively. All groups were evaluated in the open field, cylinder and ladder walk behavioral tests at distinct time points as from baseline to 30 days post-surgery (30 PS). Histological and morphometric analyses were used to assess the volume of lost tissue and lesion length. Present results reveal that both forms of experimental stroke had a comparable long-term pattern of damage, since no differences were found in volume of tissue lost or lesion size 30 days after surgery. However, behavioral data showed that hemorrhagic rats were less impaired at skilled walking than ischemic ones at 15 and 30 days post-surgery. We suggest that experimentally comparable stroke design is useful because it reduces heterogeneity and facilitates the assessment of neurobiological differences related to stroke subtypes; and that spontaneous skilled walking recovery differs between experimental ischemic and hemorrhagic insults. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. New Treatments for Nonarteritic Anterior Ischemic Optic Neuropathy.

    Science.gov (United States)

    Foroozan, Rod

    2017-02-01

    Despite increasing knowledge about the risk factors and clinical findings of nonarteritic anterior ischemic optic neuropathy (NAION), the treatment of this optic neuropathy has remained limited and without clear evidence-based benefit. Historical treatments of NAION are reviewed, beginning with the Ischemic Optic Neuropathy Decompression Trial. More recent treatments are placed within the historical context and illustrate the need for evidence-based therapy for ischemic optic neuropathy. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Diffusion MR Imaging of Postoperative Bilateral Acute Ischemic Optic Neuropathy

    International Nuclear Information System (INIS)

    Park, Ju Young; Lee, In Ho; Song, Chang June; Hwang, Hee Youn

    2012-01-01

    A 57-year-old woman experienced bilateral acute ischemic optic neuropathy after spine surgery. Routine MR imaging sequence, T2-weighted image, showed subtle high signal intensity on bilateral optic nerves. A contrast-enhanced T1 weighted image showed enhancement along the bilateral optic nerve sheath. Moreover, diffusion-weighted image (DWI) and an apparent diffusion coefficient map showed markedly restricted diffusion on bilateral optic nerves. Although MR findings of T2-weighted and contrast enhanced T1-weighted images may be nonspecific, the DWI finding of cytotoxic edema of bilateral optic nerves will be helpful for the diagnosis of acute ischemic optic neuropathy after spine surgery.

  16. Diffusion MR Imaging of Postoperative Bilateral Acute Ischemic Optic Neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ju Young; Lee, In Ho; Song, Chang June [Chungnam National University Hospital, Daejeon (Korea, Republic of); Hwang, Hee Youn [Eulji University Hospital, Daejeon(Korea, Republic of)

    2012-03-15

    A 57-year-old woman experienced bilateral acute ischemic optic neuropathy after spine surgery. Routine MR imaging sequence, T2-weighted image, showed subtle high signal intensity on bilateral optic nerves. A contrast-enhanced T1 weighted image showed enhancement along the bilateral optic nerve sheath. Moreover, diffusion-weighted image (DWI) and an apparent diffusion coefficient map showed markedly restricted diffusion on bilateral optic nerves. Although MR findings of T2-weighted and contrast enhanced T1-weighted images may be nonspecific, the DWI finding of cytotoxic edema of bilateral optic nerves will be helpful for the diagnosis of acute ischemic optic neuropathy after spine surgery.

  17. [Health valuations for patients with chronic ischemic heart disease].

    Science.gov (United States)

    Meder, M; Farin, E

    2011-08-01

    The study deals with the question of how patients with chronic ischemic heart disease assess different health situations that can be achieved by rehabilitation. Furthermore it examines which factors influence these health valuations and whether the predictors vary depending on the level of education. The health valuations of n = 331 patients with chronic ischemic heart disease are compiled using visual analogue scales (VAS). In addition to sociodemographic questions, generic and illness-specific scales (SF-12, MacNew) for the health-related quality of life (HRQOL) are used as potential predictors of the health valuations. Additional basic medical data were provided by the physician. Hierarchical regression analyses are conducted; the sociodemographic, medical and HRQOL variables are included stepwise. Since many variables are observed for the regression models, an imputation of missing values is made. The health dimensions "Self-care and domestic life" and "Mobility" are assigned the highest values on the VAS. The lowest preference is assigned to the dimensions "Reduction of symptoms" and "Information about the disease". The differences between the health dimensions are statistically significant. Sociodemographic variables explain up to 3.6% of the variance of health valuations, with level of education and living with a partner being the most important predictors. The medical variables included in the second step explain between 2.1 and 6.8% incremental variance; the most important predictor is the operation performed prior to rehabilitation (bypass, heart valve). The HRQOL variables in the third block provide 7.1-24.9% incremental explanation of variance, by far the highest percentage. This is mainly achieved using the 3 MacNew scales (emotional, social and physical functioning). The overall explanation of variance for the health valuations is 17.1-28.8%. For patients with a higher level of education, the total explanation of variance is about 9.2% higher on

  18. High blood pressure in acute ischemic stroke and clinical outcome.

    Science.gov (United States)

    Manabe, Yasuhiro; Kono, Syoichiro; Tanaka, Tomotaka; Narai, Hisashi; Omori, Nobuhiko

    2009-11-16

    This study aimed to evaluate the prognostic value of acute phase blood pressure in patients with acute ischemic stroke by determining whether or not it contributes to clinical outcome. We studied 515 consecutive patients admitted within the first 48 hours after the onset of ischemic strokes, employing systolic and diastolic blood pressure measurements recorded within 36 hours after admission. High blood pressure was defined when the mean of at least 2 blood pressure measurements was ≥200 mmHg systolic and/or ≥110 mmHg diastolic at 6 to 24 hours after admission or ≥180 mmHg systolic and/or ≥105 mmHg diastolic at 24 to 36 hours after admission. The high blood pressure group was found to include 16% of the patients. Age, sex, diabetes mellitus, hypercholesterolemia, atrial fibrillation, ischemic heart disease, stroke history, carotid artery stenosis, leukoaraiosis, NIH Stroke Scale (NIHSS) on admission and mortality were not significantly correlated with either the high blood pressure or non-high blood pressure group. High blood pressure on admission was significantly associated with a past history of hypertension, kidney disease, the modified Rankin Scale (mRS) on discharge and the length of stay. On logistic regression analysis, with no previous history of hypertension, diabetes mellitus, atrial fibrillation, and kidney disease were independent risk factors associated with the presence of high blood pressure [odds ratio (OR), 1.85 (95% confidence interval (CI): 1.06-3.22), 1.89 (95% CI: 1.11-3.22), and 3.31 (95% CI: 1.36-8.04), respectively]. Multi-organ injury may be presented in acute stroke patients with high blood pressure. Patients with high blood pressure had a poor functional outcome after acute ischemic stroke.

  19. [Primary emergencies: management of acute ischemic stroke].

    Science.gov (United States)

    Leys, Didier; Goldstein, Patrick

    2012-01-01

    The emergency diagnostic strategy for acute ischemic stroke consists of:--identification of stroke, based on clinical examination (sudden onset of a focal neurological deficit);--identification of the ischemic or hemorrhagic nature by MRI or CT;--determination of the early time-course (clinical examination) and the cause. In all strokes (ischemic or hemorrhagic), treatment consists of:--the same general management (treatment of a life-threatening emergency, ensuring normal biological parameters except for blood pressure, and prevention of complications);--decompressive surgery in the rare cases of intracranial hypertension. For proven ischemic stroke, other therapies consist of: rt-PA for patients admitted with 4.5 hours of stroke onset who have no contraindications, and aspirin (160 to 300 mg) for patients who are not eligible for rt-PA. These treatments should be administered within a few hours. A centralized emergency call system (phone number 15 in France) is the most effective way of achieving this objective.

  20. Paraneoplastic Ischemic Stroke: Case Report and Review

    Directory of Open Access Journals (Sweden)

    Murat Sumer

    2008-10-01

    Full Text Available OBJECTIVE: Paraneoplastic etiology is not frequent among cerebrovascular disorders. This rare disorder is interesting with different mechanisms, clinical manifestations and treatment options. Diagnosis may be overlooked for its rarity. We present a paraneoplastic ischemic stroke patient with its clinical and imaging characteristics for recalling this rare disease. CASE: A sixty years old woman with a history of ovarian and colon cancer and liver metastasis admitted with acute left sided hemiplegia. Brain magnetic resonance imaging showed multiple ischemic lesions at the same age. Laboratory findings were compatible with chronic disseminated intravascular coagulopathy. She was anticoagulated but the clinical findings were not changed. She died one month after her discharge from the hospital. CONCLUSIONS: Paraneoplastic ischemic stroke is rare and it should be recognized by the clinician to differentiate from other ischemic strokes by its different mechanisms, imaging characteristics and treatment modalities. Prognosis depends on the characteristics of the primary tumor

  1. Risk factor for hypoxic ischemic encephalopathy in children

    International Nuclear Information System (INIS)

    Butt, T.K.; Farooqui, R.; Khan, U.; Farooqui, R.

    2008-01-01

    To determine underlying risk factors in neonates with hypoxic ischemic encephalopathy. All neonates (153) with the diagnosis of Hypoxic Ischemic Encephalopathy (HIE) were included in the study. Controls (187) were selected from admissions on the same day. Possible risk factors such as maternal age, parity, antenatal monitoring, place of delivery, prolonged second stage of labour, type of delivery, type of attendant at delivery and the gestational age were noted and compared. Sixty one (39.9%) mothers of asphyxiated babies reported no antenatal visits compared to 24.1% in the control group (OR 2.1, 95% CI 1.3-3.2; p=0.002). Only 6.5% of cases were born in government hospitals (teaching and district) in comparison to 20.9% of controls (OR 3.8, 95% CI 1.9-7.6; p=0.001). In 28.1% of cases, mothers had history of prolonged 2nd stage of labour in comparison to 5.9% of controls (OR 6.3, 95% CI 3.3-11.9; p<0.001). Fifty five cases (35.9%) were delivered by unskilled birth attendants compared to 28 (14.9%) controls (OR 3.2, 95% CI 1.9-5.3; p<0.001). No significant difference was found in maternal age, maternal parity, gestational age and the mode of delivery between the two groups. Delivery by unskilled birth attendant, prolonged second stage of labour, birth in a non-government hospital setup and absence of antenatal care were significant risk factors for hypoxic ischemic encephalopathy in neonates. Improvement in antenatal and intrapartum care may be helpful in decreasing the frequency of this problem. (author)

  2. CT findings in isolated ischemic proctosigmoiditis

    International Nuclear Information System (INIS)

    Wiesner, Walter; Mortele, Koenraad J.; Ji, Hoon; Khurana, Bharti; Ros, Pablo R.; Glickman, Jonathan N.

    2002-01-01

    The purpose of our study was to describe the CT features of ischemic proctosigmoiditis in correlation with clinical, laboratory, endoscopic, and histopathologic findings. Our study included seven patients with isolated ischemic proctosigmoiditis. Patients were identified by a retrospective review of all histopathologic records of colonoscopic biopsies performed during a time period of 4 years. All patients presented with left lower abdominal quadrant pain, bloody stools, and leukocytosis, and four patients had fever at the time of presentation. Four of seven patients suffered from diarrhea, one of seven was constipated and two of seven had normal stool consistency. The CT examinations were reviewed by two authors by consensus and compared with clinical and histopathologic results as well as with the initial CT diagnosis. The CT showed a wall thickening confined to the rectum and sigmoid colon in seven of seven patients, stranding of the pararectal fat in four of seven, and stranding of the perisigmoidal fat in one of seven patients. There were no enlarged lymph nodes, but five of seven patients showed coexistent diverticulosis and in three of these patients CT findings were initially misinterpreted as sigmoid diverticulitis. Endoscopies and histopathologic analyses of endoscopic biopsies confirmed non-transmural ischemic proctosigmoiditis in all patients. Isolated ischemic proctosigmoiditis often presents with unspecific CT features and potentially misleading clinical and laboratory findings. In an elderly patient or a patient with known cardiovascular risk factors the diagnosis of ischemic proctosigmoiditis should be considered when wall thickening confined to the rectum and sigmoid colon is seen that is associated with perirectal fat stranding. (orig.)

  3. Relationship between weather conditions and admissions for ischemic stroke and subarachnoid hemorrhage.

    Science.gov (United States)

    Tarnoki, Adam D; Turker, Acar; Tarnoki, David L; Iyisoy, Mehmet S; Szilagyi, Blanka K; Duong, Hoang; Miskolczi, Laszlo

    2017-02-28

    To assess impacts of different weather conditions on hospitalizations of patients with ischemic strokes and subarachnoid hemorrhages (SAH) in South Florida. Diagnostic data of patients with spontaneous SAH and strokes were recorded between June 2010 and July 2013. Daily synchronous forecast charts were collected from the National Weather Service and the whole data were matched prospectively. The incidence rate ratio (IRR) was calculated. Increased incidence rate of ischemic stroke was consistent with the daily lowest and highest air pressure (IRR 1.03, P=0.128 and IRR 0.98, P=0.380, respectively), highest air temperature (IRR 0.99, P=0.375), and presence of hurricanes or storms (IRR 0.65, P=0.054). Increased incidence of SAH cases was consistent with daily lowest and highest air pressure (IRR 0.87, P<0.001 and IRR 1.08, P=0.019, respectively) and highest air temperature (IRR 0.98, P<0.001). Presence of hurricanes and/or tropical storms did not influence the frequency of SAH. We found no relationship between the presence of fronts and the admissions for ischemic stroke or SAH. Higher number of ischemic stroke and SAH cases can be expected with the daily lowest and highest air pressure, highest air temperature. Presence of hurricanes or tropical storms increased the risk of ischemic stroke but not the SAH. These findings can help to develop preventive health plans for cerebrovascular diseases.

  4. Relationship between vascular dysfunction in peripheral arteries and ischemic episodes during daily life in patients with ischemic heart disease and hypercholesterolemia

    DEFF Research Database (Denmark)

    Søndergaard, Eva; Møller, Jacob E; Egstrup, Kenneth

    2002-01-01

    cardiovascular risk factors. CONCLUSIONS: These results indicate a significant relationship between ischemic episodes and vascular dysfunction in patients with ischemic heart disease and hypercholesterolemia and may justify an aggressive preventive therapy targeted directly at the endothelium.......BACKGROUND: It is well established that endothelial dysfunction is present in patients with ischemic heart disease and hypercholesterolemia. Some of these patients will have signs of transient myocardial ischemia during Holter monitoring. We sought to describe the correlation between daily life...... ischemia and signs of endothelial dysfunction as assessed by means of brachial vasoreactivity. METHODS: We included in the study 131 patients with documented ischemic heart disease and a serum cholesterol level of > or =5 mmol/L before the institution of lipid-lowering treatment and dietary intervention...

  5. Is beta-thalassemia trait a protective factor against ischemic cerebrovascular accidents?

    Science.gov (United States)

    Karimi, Mehran; Borhani Haghighi, Afshin; Yazdani, Maryam; Raisi, Hamideh; Giti, Rahil; Namazee, Mohammad Reza

    2008-01-01

    In this research, we sought to determine the association between beta-thalassemia trait and ischemic cerebrovascular accident (CVA). In acase-control study, 148 patients with thromboembolic cerebrovascular events were evaluated for the presence of hypertension, diabetes mellitus, hyperlipidemia, and beta-thalassemia trait. A total of 156 age- and sex-matched patients with no cardiac or cerebrovascular diseases, serving as the control group, were also investigated for the above-mentioned risk factors. We found that 6.1% of patients with ischemic CVA and 12.2% of the control group had beta-thalassemia trait (P = .066). In male patients, the negative association between ischemic CVA and presence of beta-thalassemia trait was significant (P = .008). In patients, the prevalence of hypertension was also significantly different between those with and without beta-thalassemia trait (P = .01); those with beta-thalassemia trait had a lower mean blood pressure than those without the trait. beta-Thalassemia trait may have a protective effect against ischemic CVA that might be caused by the lower arterial blood pressure observed in those with this trait.

  6. Involvement of CCR-2 chemokine receptor activation in ischemic preconditioning and postconditioning of brain in mice.

    Science.gov (United States)

    Rehni, Ashish K; Singh, Thakur Gurjeet

    2012-10-01

    The present study has been designed to investigate the potential role of CCR-2 chemokine receptor in ischemic preconditioning as well as postconditioning induced reversal of ischemia-reperfusion injury in mouse brain. Bilateral carotid artery occlusion of 17 min followed by reperfusion for 24h was employed in present study to produce ischemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using elevated plus-maze test and Morris water maze test. Rota rod test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired memory and motor co-ordination. Three preceding episodes of bilateral carotid artery occlusion for 1 min and reperfusion of 1 min were employed to elicit ischemic preconditioning of brain, while three episodes of bilateral carotid artery occlusion for 10s and reperfusion of 10s immediately after the completion of were employed to elicit ischemic postconditioning of brain. Both prior ischemic preconditioning as well as ischemic postconditioning immediately after global cerebral ischemia prevented markedly ischemia-reperfusion-induced cerebral injury as measured in terms of infarct size, loss of memory and motor coordination. RS 102895, a selective CCR-2 chemokine receptor antagonist, attenuated the neuroprotective effect of both the ischemic preconditioning as well as postconditioning. It is concluded that the neuroprotective effect of both ischemic preconditioning as well as ischemic postconditioning may involve the activation of CCR-2 chemokine receptors. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Health behavior of patients with ischemic heart disease

    Directory of Open Access Journals (Sweden)

    Paweł Węgorowski

    2017-06-01

    Full Text Available Admission By analyzing the available scientific literature, it is possible to define ischemic heart disease as a set of disease symptoms that are a consequence of a chronic state of imbalance between the ability to supply nutrients and oxygen and the real need of myocardial cells for these substances. Adapting life-style behaviors to healthy living is a priority to prevent the onset and development of cardiovascular disease, especially ischemic heart disease, Purpose of research The aim of the study is to determine the health behavior of patients with ischemic heart disease. Materials and methods The study was conducted from 01.08.2015 to 28.12.2015 in a group of 35 people (15 women and 20 men. The research method used in the work is a diagnostic survey, the research technique used was a survey of its own author. Conclusions By analyzing the data collected, it is important to note that patients with coronary heart disease are often associated with health problems such as hypertension, diabetes and abnormal weight. The nutritional habits of the subjects studied can be described as abnormal, particularly the excessive intake of oily meat and too little fish intake. It has also been observed that most of the patients studied have familial predisposition to ischemic heart disease. Discussion Heart attacks occur mostly in people with obesity, diabetes and atherosclerosis. It is also closely related to ischemic heart disease. The health behaviors of patients suffering from Ischemic Heart Disease are moderately satisfactory and therefore the role of a nurse practitioner as a health educator is very difficult but essential in the prevention of ischemic heart disease.

  8. Association of inflammatory gene polymorphisms with ischemic stroke in a Chinese Han population

    OpenAIRE

    Zhao, Nan; Liu, Xin; Wang, Yongqin; Liu, Xiaoqiu; Li, Jiana; Yu, Litian; Ma, Liyuan; Wang, Shuyu; Zhang, Hongye; Liu, Lisheng; Zhao, Jingbo; Wang, Xingyu

    2012-01-01

    Abstract Background Inflammatory mechanisms are important in stroke risk, and genetic variations in components of the inflammatory response have been implicated as risk factors for stroke. We tested the inflammatory gene polymorphisms and their association with ischemic stroke in a Chinese Han population. Methods A total of 1,124 ischemic stroke cases and 1,163 controls were genotyped with inflammatory panel strips containing 51 selected inflammatory gene polymorphisms from 35 candidate genes...

  9. Current status and outlook of endovascular therapy for cerebral ischemic diseases

    International Nuclear Information System (INIS)

    Li Minghua; Zhao Jungong

    2005-01-01

    Improvement of diagnostic technology and increasing advent of new materials for intervention has created a new area for endovascular therapy of cerebral ischemic diseases. Current research findings have shown that endovascular thrombolysis in acute stage of cerebral infarction can accelerate the rate of re-canalization of occluded arteries and greatly decrease the morbidity and mortality of cerebral ischemic vascular diseases. Stenting of arterial stenosis can the improve of blood supply distal to the lesion, prevent recurrent cerebral ischemic stroke. As a result, endovascular thrombolysis for acute cerebral infarction and stenting for intracranial and carotid arterial stenosis are booming both at home and abroad. Proper selection of patients of acute cerebral infarction for endovascular thrombolysis with less complications could be achieved through CT perfusion, MR perfusion-weighted image (PWI) and diffusion-weighted image (DWI), non-invasive vascular imaging technology including CEMRA and CTA for confirming and demonstrating the sites and causes of cerebral ischemia, and furthermore for evaluating the survival ability and etc. The research team administered albumin and magnesium sulfate as neurological protection drug to treat rat infarction model within 6 hours of onset resulting with the same effect of decreasing the damage of ischemic cerebral tissue and without hemorrhagic complication. It is certain that hemorrhagic complication in thrombolysis is a result of multiple factors with no single drug being able to solve the problem. It is predictable that, based on semi-quantitative or quantitative parameters of CT or MRI in conjunction with PWI/DWI mismatch model rather than simply on the onset time of infarction for proper selection of patients of cerebral infarction, mechanic thrombus-disruption and/or intra-arterial thrombolysis together with intervention of neurological protection drug will be the trend for treating acute cerebral infarction in the future

  10. Ischemic stroke progress evaluation by 31P NMR-based metabonomic of human serum

    International Nuclear Information System (INIS)

    Grandizoli, Caroline W.P.S.; Barison, Andersson; Lange, Marcos C.; Novak, Felipe T. M.; Campos, Francinete R.

    2014-01-01

    In this work, chemometric analyses over 31 P{ 1H } NMR (nuclear magnetic resonance) spectra of human blood serum permitted to discriminated ischemic stroke patients from health individuals due to changes in the chemical composition of phosphorus-containing compounds. These results indicate that 31 P NMR-based metabonomic allowed insights over the mechanism triggered by ischemic stroke. (author)

  11. Parvovirus B19 Infection in Children With Arterial Ischemic Stroke.

    Science.gov (United States)

    Fullerton, Heather J; Luna, Jorge M; Wintermark, Max; Hills, Nancy K; Tokarz, Rafal; Li, Ying; Glaser, Carol; DeVeber, Gabrielle A; Lipkin, W Ian; Elkind, Mitchell S V

    2017-10-01

    Case-control studies suggest that acute infection transiently increases the risk of childhood arterial ischemic stroke. We hypothesized that an unbiased pathogen discovery approach utilizing MassTag-polymerase chain reaction would identify pathogens in the blood of childhood arterial ischemic stroke cases. The multicenter international VIPS study (Vascular Effects of Infection in Pediatric Stroke) enrolled arterial ischemic stroke cases, and stroke-free controls, aged 29 days through 18 years. Parental interview included questions on recent infections. In this pilot study, we used MassTag-polymerase chain reaction to test the plasma of the first 161 cases and 34 controls enrolled for a panel of 28 common bacterial and viral pathogens. Pathogen DNA was detected in no controls and 14 cases (8.7%): parvovirus B19 (n=10), herpesvirus 6 (n=2), adenovirus (n=1), and rhinovirus 6C (n=1). Parvovirus B19 infection was confirmed by serologies in all 10; infection was subclinical in 8. Four cases with parvovirus B19 had underlying congenital heart disease, whereas another 5 had a distinct arteriopathy involving a long-segment stenosis of the distal internal carotid and proximal middle cerebral arteries. Using MassTag-polymerase chain reaction, we detected parvovirus B19-a virus known to infect erythrocytes and endothelial cells-in some cases of childhood arterial ischemic stroke. This approach can generate new, testable hypotheses about childhood stroke pathogenesis. © 2017 American Heart Association, Inc.

  12. Mental stress-induced left ventricular dysfunction and adverse outcome in ischemic heart disease patients.

    Science.gov (United States)

    Sun, Julia L; Boyle, Stephen H; Samad, Zainab; Babyak, Michael A; Wilson, Jennifer L; Kuhn, Cynthia; Becker, Richard C; Ortel, Thomas L; Williams, Redford B; Rogers, Joseph G; O'Connor, Christopher M; Velazquez, Eric J; Jiang, Wei

    2017-04-01

    Aims Mental stress-induced myocardial ischemia (MSIMI) occurs in up to 70% of patients with clinically stable ischemic heart disease and is associated with increased risk of adverse prognosis. We aimed to examine the prognostic value of indices of MSIMI and exercise stress-induced myocardial ischemia (ESIMI) in a population of ischemic heart disease patients that was not confined by having a recent positive physical stress test. Methods and results The Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment (REMIT) study enrolled 310 subjects who underwent mental and exercise stress testing and were followed annually for a median of four years. Study endpoints included time to first and total rate of major adverse cardiovascular events, defined as all-cause mortality and hospitalizations for cardiovascular causes. Cox and negative binomial regression adjusting for age, sex, resting left ventricular ejection fraction, and heart failure status were used to examine associations of indices of MSIMI and ESIMI with study endpoints. The continuous variable of mental stress-induced left ventricular ejection fraction change was significantly associated with both endpoints (all p values mental stress, patients had a 5% increase in the probability of a major adverse cardiovascular event at the median follow-up time and a 20% increase in the number of major adverse cardiovascular events endured over the follow-up period of six years. Indices of ESIMI did not predict endpoints ( ps > 0.05). Conclusion In patients with stable ischemic heart disease, mental, but not exercise, stress-induced left ventricular ejection fraction change significantly predicts risk of future adverse cardiovascular events.

  13. Advances in endovascular therapy for ischemic cerebrovascular diseases

    Directory of Open Access Journals (Sweden)

    Jun Lu

    2016-09-01

    Full Text Available Endovascular therapy for ischemic cerebrovascular diseases has developed rapidly in recent years. The latest clinical trials of acute ischemic stroke have shown promising results with the continued advancement of concepts, techniques, and materials. Mechanical thrombectomy is recommended in the treatment of acute ischemic stroke caused by large vessel occlusion of the anterior circulation, according to the guidelines updated in Europe, USA, and China. The long-term therapeutic efficacy of endovascular stenting for carotid artery stenosis has also been proved noninferior to that of carotid endarterectomy. However, the latest clinical trials have shown that the efficacy of stenting for intracranial artery and vertebral artery stenosis is inferior to that of medical treatment alone, which needs urgent attention through further development and studies. Keywords: Ischemic cerebrovascular diseases, Interventional surgery, Progress

  14. Lack of association between a functional variant of the BRCA-1 related associated protein (BRAP) gene and ischemic stroke

    OpenAIRE

    Liao, Yi-Chu; Lin, Hsiu-Fen; Guo, Yuh-Cherng; Chen, Chung-Hung; Huang, Zhi-Zhang; Juo, Suh-Hang Hank; Lin, Ruey-Tay

    2013-01-01

    Abstract Background Atherosclerosis shares common pathogenic features with myocardial infarction (MI) and ischemic stroke. BRCA-1 associated protein (BRAP), a newly identified risk gene for MI, aggravates the inflammatory response in atherosclerosis. The aim of this study was to test the association between the BRAP gene and stroke in a Taiwanese population. Methods A total of 1,074 stroke patients and 1,936 controls were genotyped for the functional SNP rs11066001. In our previous studies, t...

  15. Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke

    DEFF Research Database (Denmark)

    Zangari, Rosalia; Zanier, Elisa R; Torgano, G

    2016-01-01

    BACKGROUND: Several lines of evidence support the involvement of the lectin pathway of complement (LP) in the pathogenesis of acute ischemic stroke. The aim of this multicenter observational study was to assess the prognostic value of different circulating LP initiators in acute stroke. METHODS......: Plasma levels of the LP initiators ficolin-1, -2, and -3 and mannose-binding lectin (MBL) were measured in 80 stroke patients at 6 h only and in 85 patients at 48 h and later. Sixty-one age- and sex-matched healthy individuals served as controls. Stroke severity was measured on admission using...... (0.45 μg/ml, p difference...

  16. Observation of 99Tcm-MIBI uptake of ischemic myocardium in dog models after left circumflex coronary artery constriction

    International Nuclear Information System (INIS)

    Cheng Guanghua; Dai Yunhai; Wu Kefang; Xu Quanfeng

    2008-01-01

    Objective: To observe 99 Tc m -MIBI uptake of ischemic myocardium at different times (1h, 4h) in dog models after left circumflex coronary artery constriction. Methods: 12 dog models of coronary artery stenosis were prepared by left circumflex coronary ligation, and were given injection of 99 Tc m -MIBI at the dosage of 185 MBq (5 mCi). Six models were sacrificed at one hour and four hours after the injection respectively. Radio-uptake in about 100 mg myocardium from both ischemic and non-ischemic sites were measured with r-counter. Results: No significant differences were found between ratios of radioactive count of ischemic over normal myocardial tissues at 1h and 4h after injection of 99 Tc m -MIBI (0.726±0.054 and 0.673±0.080, respective, t=1.3452, P >0.05). Conclusion: The extension of post-injection time would not increase 99 Tc m -MIBI uptake in ischemic myocardium. (authors)

  17. Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study.

    Science.gov (United States)

    Paciaroni, Maurizio; Agnelli, Giancarlo; Caso, Valeria; Tsivgoulis, Georgios; Furie, Karen L; Tadi, Prasanna; Becattini, Cecilia; Falocci, Nicola; Zedde, Marialuisa; Abdul-Rahim, Azmil H; Lees, Kennedy R; Alberti, Andrea; Venti, Michele; Acciarresi, Monica; D'Amore, Cataldo; Mosconi, Maria Giulia; Cimini, Ludovica Anna; Procopio, Antonio; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Cappellari, Manuel; Putaala, Jukka; Tomppo, Liisa; Tatlisumak, Turgut; Bandini, Fabio; Marcheselli, Simona; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Masotti, Luca; Vannucchi, Vieri; Sohn, Sung-Il; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Acampa, Maurizio; Martini, Giuseppe; Ntaios, George; Karagkiozi, Efstathia; Athanasakis, George; Makaritsis, Kostantinos; Vadikolias, Kostantinos; Liantinioti, Chrysoula; Chondrogianni, Maria; Mumoli, Nicola; Consoli, Domenico; Galati, Franco; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Corea, Francesco; Ageno, Walter; Bellesini, Marta; Colombo, Giovanna; Silvestrelli, Giorgio; Ciccone, Alfonso; Scoditti, Umberto; Denti, Licia; Mancuso, Michelangelo; Maccarrone, Miriam; Orlandi, Giovanni; Giannini, Nicola; Gialdini, Gino; Tassinari, Tiziana; De Lodovici, Maria Luisa; Bono, Giorgio; Rueckert, Christina; Baldi, Antonio; D'Anna, Sebastiano; Toni, Danilo; Letteri, Federica; Giuntini, Martina; Lotti, Enrico Maria; Flomin, Yuriy; Pieroni, Alessio; Kargiotis, Odysseas; Karapanayiotides, Theodore; Monaco, Serena; Baronello, Mario Maimone; Csiba, Laszló; Szabó, Lilla; Chiti, Alberto; Giorli, Elisa; Del Sette, Massimo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Michel, Patrik; Vanacker, Peter; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Gourbali, Vanessa; Yaghi, Shadi

    2017-03-01

    This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P =0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P =0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P =0.10) for major bleedings. The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P =0.009) for ischemic outcome events and 0.407 (0.275-0.540; P =0.14) for hemorrhagic outcome events. In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings. © 2017 American Heart Association, Inc.

  18. Prediction and prognosis of ventricular tachycardia recurrence after catheter ablation with remote magnetic navigation for electrical storm in patients with ischemic cardiomyopathy.

    Science.gov (United States)

    Jin, Qi; Jacobsen, Peter Karl; Pehrson, Steen; Chen, Xu

    2017-11-01

    Ventricular tachycardia (VT) recurrence after catheter ablation for electrical storm is commonly seen in patients with ischemic cardiomyopathy (ICM). We hypothesized that VT recurrence can be predicted and be related to the all-cause death after VT storm ablation guided by remote magnetic navigation (RMN) in patients with ICM. A total of 54 ICM patients (87% male; mean age, 65 ± 7.1 years) presenting with VT storm undergoing acute ablation using RMN were enrolled. Acute complete ablation success was defined as noninducibility of any sustained monomorphic VT at the end of the procedure. Early VT recurrence was defined as the occurrence of sustained VT within 1 month after the first ablation. After a mean follow-up of 17.1 months, 27 patients (50%) had freedom from VT recurrence. Sustained VT recurred in 12 patients (22%) within 1 month following the first ablation. In univariate analysis, VT recurrence was associated with incomplete procedural success (hazard ratio [HR]: 6.25, 95% confidence interval [CI]: 1.20-32.47, P = 0.029), lack of amiodarone usage before ablation (HR: 4.71, 95% CI: 1.12-19.7, P = 0.034), and a longer procedural time (HR: 1.023, 95% CI: 1.00-1.05, P = 0.05). The mortality of patients with early VT recurrence was higher than that of patients without recurrence (P storm guided by RMN is the strongest predictor of VT recurrence. ICM patients who have early recurrences after VT storm ablation are at high risk of all-cause death. © 2017 Wiley Periodicals, Inc.

  19. Intensive treadmill training in the acute phase after ischemic stroke

    DEFF Research Database (Denmark)

    Strømmen, Anna Maria; Christensen, Thomas; Jensen, Kai

    2016-01-01

    The aim of the study was to (a) assess the feasibility of intensive treadmill training in patients with acute ischemic stroke, (b) test whether physical activity of the legs during training increases with time, and (c) evaluate to what extent training sessions contribute toward the overall physical...... activity of these patients. Twenty hospitalized patients with acute ischemic stroke trained on a treadmill twice daily for 30 min for 5 days and on day 30. Physical activity was measured as activity counts (AC) from accelerometers. A total of 196 of 224 initiated training sessions were completed. Training...... with increasing number of days, with the median AC being 133% higher on day 5 than on day 1. AC in the paretic leg during 60 min of training constituted median 53% of the daytime AC. Early intensive treadmill training in acute ischemic stroke patients is thus feasible and contributes considerably toward...

  20. Increased risk of ischemic stroke in cervical cancer patients: a nationwide population-based study

    International Nuclear Information System (INIS)

    Tsai, Shiang-Jiun; Su, Yu-Chieh; Hung, Shih-Kai; Huang, Yung-Sung; Tung, Chien-Hsueh; Lee, Ching-Chih; Lee, Moon-Sing; Chiou, Wen-Yen; Lin, Hon-Yi; Hsu, Feng-Chun; Tsai, Chih-Hsin

    2013-01-01

    Increased risk of ischemic stroke has been validated for several cancers, but limited study evaluated this risk in cervical cancer patients. Our study aimed to evaluate the risk of ischemic stroke in cervical cancer patients. The study analyzed data from the 2003 to 2008 National Health Insurance Research Database (NHIRD) provided by the National Health Research Institutes in Taiwan. Totally, 893 cervical cancer patients after radiotherapy and 1786 appendectomy patients were eligible. The Kaplan-Meier method and the Cox proportional hazards model were used to assess the risk of ischemic stroke. The 5-year cumulative risk of ischemic stroke was significantly higher for the cervical cancer group than for the control group (7.8% vs 5.1%; p <0.005). The risk of stroke was higher in younger (age <51 years) than in older (age ≥51 years) cervical cancer patients (HR = 2.73, p = 0.04; HR = 1.37, p = 0.07) and in patients with more than two comorbid risk factors (5 years cumulative stroke rate of two comorbidities: 15% compared to no comorbidities: 4%). These study demonstrated cervical cancer patients had a higher risk of ischemic stroke than the general population, especially in younger patients. Strategies to reduce this risk should be assessed

  1. Ischemic stroke and transient ischemic attack in young adults: risk factors, diagnostic yield, neuroimaging, and thrombolysis.

    Science.gov (United States)

    Ji, Ruijun; Schwamm, Lee H; Pervez, Muhammad A; Singhal, Aneesh B

    2013-01-01

    Approximately 10% to 14% of ischemic strokes occur in young adults. To investigate the yield of diagnostic tests, neuroimaging findings, and treatment of ischemic strokes in young adults. We retrospectively reviewed data from our Get with the Guidelines-Stroke database from 2005 through 2010. University hospital tertiary stroke center. A total of 215 consecutive inpatients aged 18 to 45 years with ischemic stroke/transient ischemic attack. The mean (SD) age was 37.5 (7) years; 51% were male. There were high incidence rates of hypertension (20%), diabetes mellitus (11%), dyslipidemia (38%), and smoking (34%). Relevant abnormalities were shown on cerebral angiography in 136 of 203 patients, on cardiac ultrasonography in 100 of 195, on Holter monitoring in 2 of 192; and on hypercoagulable panel in 30 of 189 patients. Multiple infarcts were observed in 31% and were more prevalent in individuals younger than age 35 years. Relevant arterial lesions were frequently detected in the middle cerebral artery (23%), internal carotid artery (13%), and vertebrobasilar arteries (13%). Cardioembolic stroke occurred in 47% (including 17% with isolated patent foramen ovale), and 11% had undetermined stroke etiology. The median National Institutes of Health Stroke Scale score was 3 (interquartile range, 0-9) and 81% had good outcome at hospital discharge. Of the 29 patients receiving thrombolysis (median National Institutes of Health Stroke Scale score, 14; interquartile range, 9-17), 55% had good outcome at hospital discharge and none developed symptomatic brain hemorrhage. This study shows the contemporary profile of ischemic stroke in young adults admitted to a tertiary stroke center. Stroke etiology can be determined in nearly 90% of patients with modern diagnostic tests. The causes are heterogeneous; however, young adults have a high rate of traditional vascular risk factors. Thrombolysis appears safe and short-term outcomes are favorable.

  2. Newer concepts in the pathophysiology of ischemic heart disease.

    Science.gov (United States)

    Kirk, E S; Factor, S; Sonnenblick, E H

    1984-11-01

    Thus the thrust of these studies suggests that blood flow is the overwhelming factor in determining the consequences of the imbalance of oxygen supply and demand. Moreover, the factors that determine the requirements for tissue survival in the presence of deep ischemia are not the same as those shown for the normal myocardium in figure 1. In deep ischemia, contraction ceases, and metabolism shifts from aerobic to anaerobic pathways. Survival rather than contractile function then becomes the agenda. Not only does supply tend to overshadow demand in determining extent of transmural necrosis, but the anatomical pattern of supply precisely delineates the region at risk following a coronary occlusion as well as the ultimate extent of infarction. These views are summarized in the model presented in figures 12 and 13. The anatomic distribution of the ligated artery determines the lateral limits of the ischemic region (Fig. 12) and thus the lateral extension of necrosis (Fig. 13). The extension of the necrosis across the heart wall depends largely on the status of perfusion within the ischemic region. Extension of an infarct, should it occur, has to be explained by other mechanisms. These might include: (i) vascular obstruction in adjacent vascular systems that were not involved in the first occlusion, (ii) relative ischemia in the normal tissue surrounding the ischemic tissue due to an increased wall stress at the demarcation between contracting and noncontracting tissue, or (9) interruption of vessels supplying large interdigitations of normal tissue within the originally ischemic tissue due to changes associated with the process of infarction of ischemia. Alternatively, much that is called extension of infarction may involve more of the wall transmurally without lateral extension. Additional features of the development of myocardial infarction in figures 12 and 13 include: (i) the development of collateral vessel function resulting in an increased capacity to supply the

  3. Long-term cognitive impairment after first-ever ischemic stroke in young adults.

    Science.gov (United States)

    Schaapsmeerders, Pauline; Maaijwee, Noortje A M; van Dijk, Ewoud J; Rutten-Jacobs, Loes C A; Arntz, Renate M; Schoonderwaldt, Hennie C; Dorresteijn, Lucille D A; Kessels, Roy P C; de Leeuw, Frank-Erik

    2013-06-01

    Up to 14% of all ischemic strokes occur in young adults (young stroke, especially not on the long term. This long-term perspective is important because young patients have a long life expectancy during which they start forming a family, have an active social life, and make decisive career moves. We aimed to evaluate the long-term cognitive outcome. All consecutive patients between January 1, 1980, and November 1, 2010, with a first-ever young ischemic stroke were recruited for cognitive assessment, using a matched stroke-free population as a reference. Composite Z scores for 7 cognitive domains were calculated and the ANCOVA model was used (Bonferroni correction). A below average performance was defined as >1.0 SD below the age-adjusted mean of the controls and cognitive impairment as >1.5 SD. Two hundred seventy-seven patients and 146 matched controls completed cognitive assessment (mean follow-up, 11.0 years, SD, 8.2; age, 50.9 years, SD, 10.3). Long-term cognitive outcome after an ischemic stroke was worse in most cognitive domains compared with a nonstroke population. Up to 50% of the patients had a below average performance or cognitive impairment. Deficits in processing speed, working memory, and attention were most common. Even 11 years after ischemic stroke in young adults, a substantial proportion of patients must cope with permanent cognitive deficits. These results have implications for information given to patients and rehabilitation services.

  4. Ischemic Stroke during Pregnancy and Puerperium

    Directory of Open Access Journals (Sweden)

    Elisabetta Del Zotto

    2011-01-01

    Full Text Available Ischemic stroke during pregnancy and puerperium represents a rare occurrence but it could be a serious and stressful event for mothers, infants, and also families. Whenever it does occur, many concerns arise about the safety of the mother and the fetus in relation to common diagnostic tests and therapies leading to a more conservative approach. The physiological adaptations in the cardiovascular system and in the coagulability that accompany the pregnant state, which are more significant around delivery and in the postpartum period, likely contribute to increasing the risk of an ischemic stroke. Most of the causes of an ischemic stroke in the young may also occur in pregnant patients. Despite this, there are specific conditions related to pregnancy which may be considered when assessing this particular group of patients such as pre-eclampsia-eclampsia, choriocarcinoma, peripartum cardiomiopathy, amniotic fluid embolization, and postpartum cerebral angiopathy. This article will consider several questions related to pregnancy-associated ischemic stroke, dwelling on epidemiological and specific etiological aspects, diagnostic issue concerning the use of neuroimaging, and the related potential risks to the embryo and fetus. Therapeutic issues surrounding the use of anticoagulant and antiplatelets agents will be discussed along with the few available reports regarding the use of thrombolytic therapy during pregnancy.

  5. Safety and feasibility of post-stroke care and exercise after minor ischemic stroke or transient ischemic attack: MotiveS & MoveIT

    NARCIS (Netherlands)

    Boss, H.M.; Van Schaik, S.M.; Deijle, I.A.; de Melker, E.C.; van den Berg, B.M.; Scherder, E.J.A.; Bosboom, W.M.J.; Weinstein, H.C.; van den Berg-Vos, R.M.

    2014-01-01

    Background: Despite the beneficial effect of cardiac rehabilitation after myocardial infarction, a rehabilitation program to improve cardiorespiratory fitness and influence secondary prevention has not been implemented for ischemic stroke and transient ischemic attack (TIA). Objective: To

  6. Transient Ischemic Attack Caused by Iron Deficiency Anemia

    Directory of Open Access Journals (Sweden)

    Ufuk Emre

    2006-02-01

    Full Text Available Transient Ischemic Attack Caused by Iron Deficiency Anemia Transient ischemic attacks are episodes of transient focal ischemia involving the brain or brainstem. They are commonly two to thirty minutes in duration and lasting less than 24 hours. Anemia of iron deficiency isn’t frequently cause for transient ischemic attack. It has been reported as a risk factor for childhood ischemic strokes. In the iron deficiency anemia, T‹A may develop as result of hypercoagulable state and increased viscosity that is caused by anemic hypoxia that is result of reduce hemoglobine level, seconder thrombosis and microcytose As iron deficiency anemia has been reported so rarely in adult patients with transient ischemic attacks as a cause, we aimed to discuss the clinical and outcome features of two cases with iron deficiency anemia and transient ischemic attacks in this study. Materials and methods: Routine neurologic examination, biochemical screen, serological tests, vasculitic markers, thyroid function tests, vitamin B 12 level, cranial imaging, vertebral carotid doppler USG examination was conducted in the two patients. Anemia of iron deficiency was found as the only risk factor for TIA and the two patients were treated with replacement of iron and antiagregan therapy. Neurological examination revealed no abnormality through the two years of follow-up. The iron deficiency anemia may be cause of many neurologic problems such a irritability, lethargy, headache, development retardation except from T‹A. In the iron deficiency anemia, early diagnosis and treatment is important

  7. Risk factors for mortality and ischemic heart disease in patients with long-term type 1 diabetes

    DEFF Research Database (Denmark)

    Grauslund, Jakob; Mejnert Jørgensen, Trine; Nybo, Mads

    2010-01-01

    AIMS: The purpose of this study is to evaluate the effect of glycemic regulation, dyslipidemia, and renal dysfunction on mortality (all-cause and cardiovascular) and ischemic heart disease (IHD) in a long-term follow-up of a population-based cohort of Danish type 1 diabetic patients with at least......-density lipoprotein cholesterol (inversely), total cholesterol, creatinine, and macroalbuminuria. Furthermore, all markers except macroalbuminuria were associated with IHD. Microalbuminuria at baseline was not related to any of the endpoints. CONCLUSIONS: Glycemic regulation, dyslipidemia, and renal dysfunction were...

  8. Infection in the ischemic lower extremity.

    Science.gov (United States)

    Fry, D E; Marek, J M; Langsfeld, M

    1998-06-01

    Infections in the lower extremity of the patient with ischemia can cover a broad spectrum of different diseases. An understanding of the particular pathophysiologic circumstances in the ischemic extremity can be of great value in understanding the natural history of the disease and the potential complications that may occur. Optimizing blood flow to the extremity by using revascularization techniques is important for any patient with an ischemic lower extremity complicated by infection or ulceration. Infections in the ischemic lower extremity require local débridement and systemic antibiotics. For severe infections, such as necrotizing fasciitis or the fetid foot, more extensive local débridement and even amputation may be required. Fundamentals of managing prosthetic graft infection require removing the infected prosthesis, local wound débridement, and systemic antibiotics while attempting to preserve viability of the lower extremity using autogenous graft reconstruction.

  9. MCT1 and MCT4 Expression During Myocardial Ischemic-Reperfusion Injury in the Isolated Rat Heart

    Directory of Open Access Journals (Sweden)

    Yi Zhu

    2013-09-01

    Full Text Available Background/Aims: Myocardium ischemia-reperfusion (I/R injury can be caused by imbalances in cellular metabolism. Lactate, transported by monocarboxylate transporters (MCTs, has been implicated as a mechanism in this process. The present study was designed to investigate the expression and functional role of MCTs in rat hearts during ischemia and reperfusion. Methods: Langendorff-perfused rat hearts were subjected to 20 minutes stabilization, 30 minutes of global ischemia and 60 minutes reperfusion. Hearts were collected serially for detecting expression changes in MCT1, MCT4 during myocardial I/R injury and lactate concentration was measured. Post-ischemic left ventricular function and infract size were determined at end-point, followed by the pretreatment of D-lactate, a competitive inhibitor of MCTs. Results: MCT4 was significantly increased following global ischemia and MCT1 expression was increased during the early stages of reperfusion in isolated rat hearts, while the expression of the ancillary protein CD147 was increased during I/R injury. We determined increases in AMPK phosphorylation status, which was significantly elevated following ischemia and early reperfusion. Blocking monocarboxylate transport by competitive inhibition with D-lactate caused decreased left ventricular performance and increased infarct size. Conclusion: Increased MCT4 expression facilitates lactate extrusion during the ischemic period, while increased MCT1 may facilitate lactate transport into and out of cells simultaneously during early reperfusion, with increases in AMPK phosphorylation status during the myocardial I/R period. Lactate transport by MCTs has a profound protective effect during myocardial ischemia reperfusion injury.

  10. Seizure Severity Is Correlated With Severity of Hypoxic-Ischemic Injury in Abusive Head Trauma.

    Science.gov (United States)

    Dingman, Andra L; Stence, Nicholas V; O'Neill, Brent R; Sillau, Stefan H; Chapman, Kevin E

    2017-12-12

    The objective of this study was to characterize hypoxic-ischemic injury and seizures in abusive head trauma. We performed a retrospective study of 58 children with moderate or severe traumatic brain injury due to abusive head trauma. Continuous electroencephalograms and magnetic resonance images were scored. Electrographic seizures (51.2%) and hypoxic-ischemic injury (77.4%) were common in our cohort. Younger age was associated with electrographic seizures (no seizures: median age 13.5 months, interquartile range five to 25 months, versus seizures: 4.5 months, interquartile range 3 to 9.5 months; P = 0.001). Severity of hypoxic-ischemic injury was also associated with seizures (no seizures: median injury score 1.0, interquartile range 0 to 3, versus seizures: 4.5, interquartile range 3 to 8; P = 0.01), but traumatic injury severity was not associated with seizures (no seizures: mean injury score 3.78 ± 1.68 versus seizures: mean injury score 3.83 ± 0.95, P = 0.89). There was a correlation between hypoxic-ischemic injury severity and seizure burden when controlling for patient age (r s =0.61, P interquartile range 0 to 0.23 on magnetic resonance imaging done within two days versus median restricted diffusion ratio 0.13, interquartile range 0.01 to 0.43 on magnetic resonance imaging done after two days, P = 0.03). Electrographic seizures are common in children with moderate to severe traumatic brain injury from abusive head trauma, and therefore children with suspected abusive head trauma should be monitored with continuous electroencephalogram. Severity of hypoxic-ischemic brain injury is correlated with severity of seizures, and evidence of hypoxic-ischemic injury on magnetic resonance imaging may evolve over time. Therefore children with a high seizure burden should be reimaged to evaluate for evolving hypoxic-ischemic injury. Published by Elsevier Inc.

  11. Impact of Collateral Status Evaluated by Dynamic Computed Tomographic Angiography on Clinical Outcome in Patients With Ischemic Stroke

    NARCIS (Netherlands)

    van den Wijngaard, Ido R.; Boiten, Jelis; Holswilder, Ghislaine; Algra, Ale; Dippel, Diederik W J; Velthuis, Birgitta K.; Wermer, Marieke J H; van Walderveen, Marianne A A

    2015-01-01

    BACKGROUND AND PURPOSE—: Status of collateral circulation is a strong predictor of outcome after acute ischemic stroke. Our aim was to compare the predictive value of strategies for collateral blood flow assessment with dynamic computed tomographic angiography (CTA) and conventional single-phase CT

  12. Quantitative evaluation of perfusion magnetic resonance imaging hyper-acute ischemic stroke patients comparison with 1.5T and 3.0T units

    Energy Technology Data Exchange (ETDEWEB)

    Goo, Eun Hoe [Dept. of Radiological Science, Cheongju University, Cheongju (Korea, Republic of); Moon, Il Bong; Dong, Kyung Rae [Dept. of Radiological Technology, Gwangju Health University, Gwangju (Korea, Republic of)

    2017-02-15

    Perfusion magnetic resonance image of biological mechanism are independent of magnetic field strength in hyper acute ischemic stroke. 3.0 T magnetic field, however, does affect the SNRs (signal to noise ratio) and artifacts of PMRI (perfusion magnetic resonance image), which basically will influence the quantitative of PMRI. In this study, the effects of field strength on PMRI are analyzed. The effects of the diseases also are discussed. PMRI in WM (white matter), GM (gray matter), hyper acute ischemic stroke were companied with 1.5 T and 3.0 T on SNR. PMRI also was compared to the SI difference after setting ROI (region of interest) in left and right b side of the brain. In conclusion, the SNRs and SI of the 3.0 T PMRI showed higher than those at 1.5 T. In summary, PMRI studies at 3.0 T is provided significantly improved perfusion evaluation when comparing with 1.5 T.

  13. Quantitative evaluation of perfusion magnetic resonance imaging hyper-acute ischemic stroke patients comparison with 1.5T and 3.0T units

    International Nuclear Information System (INIS)

    Goo, Eun Hoe; Moon, Il Bong; Dong, Kyung Rae

    2017-01-01

    Perfusion magnetic resonance image of biological mechanism are independent of magnetic field strength in hyper acute ischemic stroke. 3.0 T magnetic field, however, does affect the SNRs (signal to noise ratio) and artifacts of PMRI (perfusion magnetic resonance image), which basically will influence the quantitative of PMRI. In this study, the effects of field strength on PMRI are analyzed. The effects of the diseases also are discussed. PMRI in WM (white matter), GM (gray matter), hyper acute ischemic stroke were companied with 1.5 T and 3.0 T on SNR. PMRI also was compared to the SI difference after setting ROI (region of interest) in left and right b side of the brain. In conclusion, the SNRs and SI of the 3.0 T PMRI showed higher than those at 1.5 T. In summary, PMRI studies at 3.0 T is provided significantly improved perfusion evaluation when comparing with 1.5 T

  14. Sporadic Carney complex without PRKAR1A mutation in a young patient with ischemic stroke.

    Science.gov (United States)

    Aguiar de Sousa, Diana; Gouveia, Ana Isabel; Wessling, Ana; Geraldes, Ruth; Canhão, Patrícia

    2015-03-01

    We describe a 29-year-old male, with a previous history of testicular tumor, who presented with a posterior circulation ischemic stroke associated to an atrial myxoma. Dermatologic observation disclosed spotty skin and mucosal pigmentation (lentigines), and a cutaneous myxoma was histopathologically confirmed. Although there was no family history of any of the Carney complex (CNC) features and no mutations in the PRKAR1A gene were found, these findings lead to the diagnosis of CNC. We emphasize the importance of recognizing this entity in young patients with stroke. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  15. Role of homocysteine in the ischemic stroke nad development of ischemic tolerance

    Directory of Open Access Journals (Sweden)

    Jan Lehotsky

    2016-11-01

    Full Text Available Homocysteine (Hcy is a toxic, sulfur-containing intermediate of methionine metabolism. Hyperhomocysteinemia (hHcy, as a consequence of impaired Hcy metabolism or defects in crucial co-factors that participate in its recycling, is assumed as an independent human stroke risk factor. Neural cells are sensitive to prolonged hHcy treatment, because Hcy cannot be metabolized either by the transsulfuration pathway or by the folate/vitamin B12 independent remethylation pathway. Its detrimental effect after ischemia-induced damage includes accumulation of reactive oxygen species (ROS and posttranslational modifications of proteins via homocysteinylation and thiolation. Ischemic preconditioning (IPC is an adaptive response of the CNS to sub-lethal ischemia, which elevates tissues tolerance to subsequent ischemia. The main focus of this review is on the recent data on homocysteine metabolism and mechanisms of its neurotoxicity. In this context, the review documents an increased oxidative stress and functional modification of enzymes involved in redox balance in experimentally induced hyperhomocysteinemia. It also gives an interpretation whether hyperhomocysteinemia alone or in combination with IPC affects the ischemia-induced neurodegenerative changes as well as intracellular signalling. Studies document that hHcy alone significantly increased Fluoro-Jade C- and TUNEL-positive cell neurodegeneration in the rat hippocampus as well as in the cortex. IPC, even if combined with hHcy, could still preserve the neuronal tissue from the lethal ischemic effects. This review also describes the changes in the mitogen-activated protein kinase (MAPK protein pathways following ischemic injury and IPC. These studies provide evidence for the interplay and tight integration between ERK and p38 MAPK signalling mechanisms in response to the hHcy and also in association of hHcy with ischemia/IPC challenge in the rat brain. Further investigations of the protective factors

  16. Netrin-1 Ameliorates Blood-Brain Barrier Impairment Secondary to Ischemic Stroke via the Activation of PI3K Pathway

    Directory of Open Access Journals (Sweden)

    Jian Yu

    2017-12-01

    Full Text Available Secondary impairment of blood-brain barrier (BBB occurs in the remote thalamus after ischemic stroke. Netrin-1, an axonal guidance molecule, presents bifunctional effects on blood vessels through receptor-dependent pathways. This study investigates whether netrin-1 protects BBB against secondary injury. Netrin-1 (600 ng/d for 7 days was intracerebroventricularly infused 24 h after middle cerebral artery occlusion (MCAO in hypertensive rats. Neurological function was assessed 8 and 14 days after MCAO, and the permeability of BBB in the ipsilateral thalamus was detected. The viability of brain microvascular endothelial cells was determined after being disposed with netrin-1 (50 ng/mL before oxygen-glucose deprivation (OGD. The role of netrin-1 was further explored by examining its receptors and their function. We found that netrin-1 infusion improved neurological function, attenuated secondary impairment of BBB by up-regulating the levels of tight junction proteins and diminishing extravasation of albumin, with autophagy activation 14 days after MCAO. Netrin-1 also enhanced cell survival and autophagy activity in OGD-treated cells, inhibited by UNC5H2 siRNA transfection. Furthermore, the beneficial effects of netrin-1 were suppressed by PI3K inhibitors 3-Methyladenine and LY294002. Our results showed that netrin-1 ameliorated BBB impairment secondary to ischemic stroke by promoting tight junction function and endothelial survival. PI3K-mediated autophagy activation depending on UNC5H2 receptor could be an underlying mechanism.

  17. Association between oxidized low-density lipoprotein and cognitive impairment in patients with ischemic stroke.

    Science.gov (United States)

    Wang, A; Liu, J; Meng, X; Li, J; Wang, H; Wang, Y; Su, Z; Zhang, N; Dai, L; Wang, Y; Wang, Y

    2018-01-01

    The association between oxidized low-density lipoprotein (oxLDL) and cognitive impairment is unclear. This study aimed to investigate the potential association between oxLDL and cognitive impairment among patients with acute ischemic stroke. We measured the levels of oxLDL and recorded the Mini-Mental State Examination (MMSE) score in patients with acute ischemic stroke who were recruited from the Study of Oxidative Stress in Patients with Acute Ischemic Stroke. Cognitive impairment was defined as an MMSE score of impairment was assessed by multivariate logistic or linear regression analysis. Other clinical variables of interest were also studied. A total of 3726 patients [1287 (34.54%) female] were included in this study, with a mean age of 63.62 ± 11.96 years. After adjusting for potential confounders in our logistic regression model, each SD increase in oxLDL was associated with a 26% increase in the prevalence of cognitive impairment (odds radio, 1.26; 95% confidence interval, 1.13-1.39; P impairment (all interactions, P > 0.05). Elevated levels of oxLDL were associated with a higher prevalence of cognitive impairment in patients with ischemic stroke. © 2017 EAN.

  18. Leucine-rich glioma inactivated-1 and voltage gated potassium channel autoimmune encephalitis associated with ischemic stroke; A Case Report

    Directory of Open Access Journals (Sweden)

    Marisa Patryce McGinley

    2016-05-01

    Full Text Available Autoimmune encephalitis is associated with a wide variety of antibodies and clinical presentations. Voltage gated potassium channel (VGKC antibodies are a cause of autoimmune non-paraneoplastic encephalitis characterized by memory impairment, psychiatric symptoms, and seizures. We present a case of VGKC encephalitis likely preceding an ischemic stroke. Reports of autoimmune encephalitis associated with ischemic stroke are rare. Several hypothesizes linking these two disease processes are proposed.

  19. Leucine-Rich Glioma Inactivated-1 and Voltage-Gated Potassium Channel Autoimmune Encephalitis Associated with Ischemic Stroke: A Case Report

    Science.gov (United States)

    McGinley, Marisa; Morales-Vidal, Sarkis; Ruland, Sean

    2016-01-01

    Autoimmune encephalitis is associated with a wide variety of antibodies and clinical presentations. Voltage-gated potassium channel (VGKC) antibodies are a cause of autoimmune non-paraneoplastic encephalitis characterized by memory impairment, psychiatric symptoms, and seizures. We present a case of VGKC encephalitis likely preceding an ischemic stroke. Reports of autoimmune encephalitis associated with ischemic stroke are rare. Several hypotheses linking these two disease processes are proposed. PMID:27242653

  20. Role of nuclear medicine in ischemic heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Hayashida, Kohei; Nishimura, Tsunehiko; Uehara, Toshiisa; Naito, Hiroaki; Omine, Hiromi; Kozuka, Takahiro [National Cardiovascular Center, Suita, Osaka (Japan)

    1982-08-01

    With the progress in gamma camera and computer system, nuclear medicine has been applied for diagnostic tool in ischemic heart disease. There are two devices for cardiac images; (1) Radionuclide angiocardiography (RNA) by in vivo sup(99m)Tc-RBC labeling (2) Myocardial imaging by /sup 201/Tlcl. RNA can evaluate the kinesis of wall motion of left ventricle with gated pool scan and also detect reserve of cardiac function with exercise study. Myocardial imaging at rest can identify myocardial necrosis and the imaging in exercise can detect myocardial ischemia. The elaborateness and reproducibility of cardiac image in nuclear medicine will play the great role to evaluate clinical stage of ischemic heart disease by not only imaging but also functional diagnosis.