Ghrelin’s Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on β-Cell Functionality

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Antonia Diaz-Ganete

2015-01-01

Full Text Available Ghrelin is a peptidic hormone, which stimulates cell proliferation and inhibits apoptosis in several tissues, including pancreas. In preclinical stage of type 1 diabetes, proinflammatory cytokines generate a destructive environment for β-cells known as insulitis, which results in loss of β-cell mass and impaired insulin secretion, leading to diabetes. Our aim was to demonstrate that ghrelin could preserve β-cell viability, turnover rate, and insulin secretion acting as a counter balance of cytokines. In the present work we reproduced proinflammatory milieu found in insulitis stage by treating murine cell line INS-1E and rat islets with a cytokine cocktail including IL-1β, IFNγ, and TNFα and/or ghrelin. Several proteins involved in survival pathways (ERK 1/2 and Akt/PKB and apoptosis (caspases and Bcl-2 protein family and endoplasmic reticulum stress markers as well as insulin secretion were analyzed. Our results show that ghrelin alone has no remarkable effects on β-cells in basal conditions, but interestingly it activates cell survival pathways, downregulates apoptotic mediators and endoplasmic reticulum stress, and restores insulin secretion in response to glucose when beta-cells are cytokine-exposed. These data suggest a potential role of ghrelin in preventing or slowing down the transition from a preclinical to clinically established diabetes by ameliorating the effects of insulitis on β-cells.

Enfermedad cerebrovascular en Colombia Cerebrovascular disease in Colombia

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Federico A Silva

2006-10-01

Full Text Available Introducción: la enfermedad cerebrovascular constituye un problema de salud pública mundial. En Colombia es la cuarta causa de muerte en la población adulta y genera una alta discapacidad en estos pacientes. Objetivo: describir algunos resultados obtenidos por el grupo de Ciencias Neurovasculares de la Fundación Cardiovascular de Colombia. Desarrollo y conclusiones: la enfermedad cerebrovascular es una entidad con una alta prevalencia en la población colombiana y genera discapacidad mental, motora y del lenguaje. Es necesaria la implementación de unidades de cuidado neurovascular con personal entrenado, protocolos definidos, tratamientos adecuados y tecnología de punta. En Colombia deben imponerse este tipo de unidades dentro del cuidado básico de los pacientes para disminuir la morbilidad, mortalidad y discapacidad generada en estos pacientes. La Fundación Cardiovascular de Colombia es pionera en la implementación de este tipo de cuidados.Introduction: cerebrovascular disease constitutes a worldwide public health problem. In Colombia, it is the fourth leading cause of death in the adult population and generates high disability in these patients. Objective: to describe some results obtained by the Neurovascular Sciences group from the Colombian Cardiovascular Foundation. Development and conclusions: cerebrovascular disease has a high prevalence in the Colombian population and generates mental, motor, and language disabilities. The implementation of neurovascular care units with trained personnel, defined protocols, adequate treatments and high technology, are necessary. This kind of units must be imposed in Colombia as a basic care for these patients in order to decrease morbidity, mortality and disability. The Colombian Cardiovascular Foundation is pioneer in the implementation of these care units.

Bilateral cerebrovascular accidents in incontinentia pigmenti.

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Fiorillo, Loretta; Sinclair, D Barry; O'Byrne, Mary L; Krol, Alfons L

2003-07-01

Incontinentia Pigmenti is an X-linked dominant neurocutaneous disorder with central nervous system manifestations in 30% of cases, including seizures and mental retardation. Ischemic or hemorrhagic cerebrovascular accidents have been reported rarely in incontinentia pigmenti. Chart review and literature search was performed following identification of the index case. We describe a patient with incontinentia pigmenti who developed bilateral cerebrovascular accidents in the neonatal period, with resultant severe neurologic sequelae. This is the second reported case of bilateral cerebrovascular accidents in a patient with incontinentia pigmenti. This finding may be secondary to cerebrovascular anomalies, similar to those observed in the retina. Recognition of cerebrovascular accidents as a complication of incontinentia pigmenti will hopefully lead to earlier recognition and treatment.

Serum homocysteine levels in cerebrovascular accidents.

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Zongte, Zolianthanga; Shaini, L; Debbarma, Asis; Singh, Th Bhimo; Devi, S Bilasini; Singh, W Gyaneshwar

2008-04-01

Hyperhomocysteinemia has been considered an independent risk factor in the development of stroke. The present study was undertaken to evaluate serum homocysteine levels in patients with cerebrovascular accidents among the Manipuri population and to compare with the normal cases. Ninety-three cerebrovascular accident cases admitted in the hospital were enrolled for the study and twenty-seven age and sex matched individuals free from cerebrovascular diseases were taken as control group. Serum homocysteine levels were estimated by ELISA method using Axis homocysteine EIA kit manufactured by Ranbaxy Diagnostic Ltd. India. The finding suggests that hyperhomocysteinemia is associated with cerebrovascular accident with male preponderance, which increases with advancing age. However, whether hyperhomocysteinemia is the cause or the result of cerebrovascular accidents needs further investigations.

Carnosol Inhibits Pro-Inflammatory and Catabolic Mediators of Cartilage Breakdown in Human Osteoarthritic Chondrocytes and Mediates Cross-Talk between Subchondral Bone Osteoblasts and Chondrocytes.

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Christelle Sanchez

Full Text Available The aim of this work was to evaluate the effects of carnosol, a rosemary polyphenol, on pro-inflammatory and catabolic mediators of cartilage breakdown in chondrocytes and via bone-cartilage crosstalk.Osteoarthritic (OA human chondrocytes were cultured in alginate beads for 4 days in presence or absence of carnosol (6 nM to 9 μM. The production of aggrecan, matrix metalloproteinase (MMP-3, tissue inhibitor of metalloproteinase (TIMP-1, interleukin (IL-6 and nitric oxide (NO and the expression of type II collagen and ADAMTS-4 and -5 were analyzed. Human osteoblasts from sclerotic (SC or non-sclerotic (NSC subchondral bone were cultured for 3 days in presence or absence of carnosol before co-culture with chondrocytes. Chondrocyte gene expression was analyzed after 4 days of co-culture.In chondrocytes, type II collagen expression was significantly enhanced in the presence of 3 μM carnosol (p = 0.008. MMP-3, IL-6, NO production and ADAMTS-4 expression were down-regulated in a concentration-dependent manner by carnosol (p<0.01. TIMP-1 production was slightly increased at 3 μM (p = 0.02 and ADAMTS-5 expression was decreased from 0.2 to 9 μM carnosol (p<0.05. IL-6 and PGE2 production was reduced in the presence of carnosol in both SC and NSC osteoblasts while alkaline phosphatase activity was not changed. In co-culture experiments preincubation of NSC and SC osteoblasts wih carnosol resulted in similar effects to incubation with anti-IL-6 antibody, namely a significant increase in aggrecan and decrease in MMP-3, ADAMTS-4 and -5 gene expression by chondrocytes.Carnosol showed potent inhibition of pro-inflammatory and catabolic mediators of cartilage breakdown in chondrocytes. Inhibition of matrix degradation and enhancement of formation was observed in chondrocytes cocultured with subchondral osteoblasts preincubated with carnosol indicating a cross-talk between these two cellular compartments, potentially mediated via inhibition of IL-6 in

Pro-inflammatory cytokines upregulate sympathoexcitatory mechanisms in the subfornical organ of the rat

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Wei, Shun-Guang; Yu, Yang; Zhang, Zhi-Hua; Felder, Robert B.

2015-01-01

Our previous work indicated that the subfornical organ (SFO) is an important brain sensor of blood-borne pro-inflammatory cytokines, mediating their central effects on autonomic and cardiovascular function. However, the mechanisms by which SFO mediates the central effects of circulating pro-inflammatory cytokines remain unclear. We hypothesized that pro-inflammatory cytokines act within the SFO to upregulate the expression of excitatory and inflammatory mediators that drive sympathetic nerve activity. In urethane-anesthetized Sprague-Dawley rats, direct microinjection of TNF-α (25 ng) or IL-1β (25 ng) into SFO increased mean blood pressure, heart rate and renal sympathetic nerve activity within 15–20 minutes, mimicking the response to systemically administered pro-inflammatory cytokines. Pretreatment of SFO with microinjections of the angiotensin II type 1 receptor (AT1R) blocker losartan (1 µg), angiotensin-converting enzyme (ACE) inhibitor captopril (1 µg) or cyclooxygenase (COX)-2 inhibitor NS-398 (2 µg) attenuated those responses. Four hours after the SFO microinjection of TNF-α (25 ng) or IL-1β (25 ng), mRNA for ACE, AT1R, TNF-α and the p55 TNF-α receptor TNFR1, IL-1β and the IL-1R receptor, and COX-2 had increased in SFO, and mRNA for ACE, AT1R and COX-2 had increased downstream in the hypothalamic paraventricular nucleus. Confocal immunofluorescent images revealed that immunoreactivity for TNFR1 and the IL-1 receptor accessory protein, a subunit of the IL-1 receptor, co-localized with ACE, AT1R-like, COX-2 and prostaglandin E2 EP3 receptor immunoreactivity in SFO neurons. These data suggest that pro-inflammatory cytokines act within the SFO to upregulate the expression of inflammatory and excitatory mediators that drive sympathetic excitation. PMID:25776070

Seizure progression and inflammatory mediators promote pericytosis and pericyte-microglia clustering at the cerebrovasculature.

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Klement, Wendy; Garbelli, Rita; Zub, Emma; Rossini, Laura; Tassi, Laura; Girard, Benoit; Blaquiere, Marine; Bertaso, Federica; Perroy, Julie; de Bock, Frederic; Marchi, Nicola

2018-05-01

Cerebrovascular dysfunction and inflammation occur in epilepsy. Here we asked whether pericytes, a pivotal cellular component of brain capillaries, undergo pathological modifications during experimental epileptogenesis and in human epilepsy. We evaluated whether pro-inflammatory cytokines, present in the brain during seizures, contribute to pericyte morphological modifications. In vivo, unilateral intra-hippocampal kainic acid (KA) injections were performed in NG2DsRed/C57BL6 mice to induce status epilepticus (SE), epileptogenesis, and spontaneous recurrent seizures (SRS). NG2DsRed mice were used to visualize pericytes during seizure progression. The effect triggered by recombinant IL-1β, TNFα, or IL-6 on pericytes was evaluated in NG2DsRed hippocampal slices and in human-derived cell culture. Human brain specimens obtained from temporal lobe epilepsy (TLE) with or without sclerosis (HS) and focal cortical dysplasia (FCD-IIb) were evaluated for pericyte-microglial cerebrovascular assembly. A disarray of NG2DsRed + pericyte soma and ramifications was found 72 h post-SE and 1 week post-SE (epileptogenesis) in the hippocampus. Pericyte modifications topographically overlapped with IBA1 + microglia clustering around the capillaries with cases of pericytes lodged within the microglial cells. Microglial clustering around the NG2DsRed pericytes lingered at SRS. Pericyte proliferation (Ki67 + ) occurred 72 h post-SE and during epileptogenesis and returned towards control levels at SRS. Human epileptic brain tissues showed pericyte-microglia assemblies with IBA1/HLA microglial cells outlining the capillary wall in TLE-HS and FCD-IIb specimens. Inflammatory mediators contributed to pericyte modifications, in particular IL-1β elicited pericyte morphological changes and pericyte-microglia clustering in NG2DsRed hippocampal slices. Modifications also occurred when pro-inflammatory cytokines were added to an in vitro culture of pericytes. These results indicate the

The importance of balanced pro-inflammatory and anti-inflammatory mechanisms in diffuse lung disease

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Strieter Robert

2002-01-01

Full Text Available Abstract The lung responds to a variety of insults in a remarkably consistent fashion but with inconsistent outcomes that vary from complete resolution and return to normal to the destruction of normal architecture and progressive fibrosis. Increasing evidence indicates that diffuse lung disease results from an imbalance between the pro-inflammatory and anti-inflammatory mechanisms, with a persistent imbalance that favors pro-inflammatory mediators dictating the development of chronic diffuse lung disease. This review focuses on the mediators that influence this imbalance.

Higher Levels of Protective Parenting are Associated with Better Young Adult Health: Exploration of Mediation through Epigenetic Influences on Pro-Inflammatory Processes

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Steven R. H. Beach

2015-05-01

Full Text Available The current investigation was designed to examine the association of parenting during late childhood and early adolescence, a time of rapid physical development, with biological propensity for inflammation. Based on life course theory, it was hypothesized that parenting during this period of rapid growth and development would be associated with biological outcomes and self-reported health assessed in young adulthood. It was expected that association of parenting with health would be mediated either by effects on methylation of a key inflammatory factor, Tumor necrosis factor (TNF, or else by association with a pro-inflammatory shift in the distribution of mononuclear blood cells. Supporting expectations, in a sample of 398 African American youth residing in rural Georgia, followed from age 11 to age 19, parenting at ages 11-13 was associated with youth reports of better health at age 19. We found that parenting was associated with changes in TNF methylation as well as with changes in cell-type composition. However, whereas methylation of TNF was a significant mediator of the association of parenting with young adult health, variation in mononuclear white blood cell types was not a significant mediator of the association of parenting with young adult health. The current research suggests the potential value of examining the health-related effects of parenting in late childhood and early adolescence. Further examination of protection against pro-inflammatory tendencies conferred by parenting appears warranted.

Serum homocysteine levels in cerebrovascular accidents

OpenAIRE

Zongte, Zolianthanga; Shaini, L.; Debbarma, Asis; Singh, Th Bhimo; Devi, S. Bilasini; Singh, W. Gyaneshwar

2008-01-01

Hyperhomocysteinemia has been considered an independent risk factor in the development of stroke. The present study was undertaken to evaluate serum homocysteine levels in patients with cerebrovascular accidents among the Manipuri population and to compare with the normal cases. Ninety-three cerebrovascular accident cases admitted in the hospital were enrolled for the study and twenty-seven age and sex matched individuals free from cerebrovascular diseases were taken as control group. Serum h...

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

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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....

The Pro-inflammatory Effects of Glucocorticoids in the Brain

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Duque, Erica de Almeida; Munhoz, Carolina Demarchi

2016-01-01

Glucocorticoids are a class of steroid hormones derived from cholesterol. Their actions are mediated by the glucocorticoid and mineralocorticoid receptors, members of the superfamily of nuclear receptors, which, once bound to their ligands, act as transcription factors that can directly modulate gene expression. Through protein–protein interactions with other transcription factors, they can also regulate the activity of many genes in a composite or tethering way. Rapid non-genomic signaling was also demonstrated since glucocorticoids can act through membrane receptors and activate signal transduction pathways, such as protein kinases cascades, to modulate other transcriptions factors and activate or repress various target genes. By all these different mechanisms, glucocorticoids regulate numerous important functions in a large variety of cells, not only in the peripheral organs but also in the central nervous system during development and adulthood. In general, glucocorticoids are considered anti-inflammatory and protective agents due to their ability to inhibit gene expression of pro-inflammatory mediators and other possible damaging molecules. Nonetheless, recent studies have uncovered situations in which these hormones can act as pro-inflammatory agents depending on the dose, chronicity of exposure, and the structure/organ analyzed. In this review, we will provide an overview of the conditions under which these phenomena occur, a discussion that will serve as a basis for exploring the mechanistic foundation of glucocorticoids pro-inflammatory gene regulation in the brain. PMID:27445981

Inhibition of Pro-inflammatory Mediators and Cytokines by Chlorella Vulgaris Extracts.

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Sibi, G; Rabina, Santa

2016-01-01

The aim of this study was to determine the in vitro anti-inflammatory activities of solvent fractions from Chlorella vulgaris by inhibiting the production of pro-inflammatory mediators and cytokines. Methanolic extracts (80%) of C. vulgaris were prepared and partitioned with solvents of increasing polarity viz., n-hexane, chloroform, ethanol, and water. Various concentrations of the fractions were tested for cytotoxicity in RAW 264.7 cells using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and the concentrations inducing cell growth inhibition by about 50% (IC50) were chosen for further studies. Lipopolysaccharide (LPS) stimulated RAW 264.7 cells were treated with varying concentrations of C. vulgaris fractions and examined for its effects on nitric oxide (NO) production by Griess assay. The release of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) were quantified using enzyme-linked immunosorbent assay using Celecoxib and polymyxin B as positive controls. MTT assay revealed all the solvent fractions that inhibited cell growth in a dose-dependent manner. Of all the extracts, 80% methanolic extract exhibited the strongest anti-inflammatory activity by inhibiting NO production (P < 0.01), PGE2 (P < 0.05), TNF-α, and IL-6 (P < 0.001) release in LPS induced RAW 264.7 cells. Both hexane and chloroform fractions recorded a significant (P < 0.05) and dose-dependent inhibition of LPS induced inflammatory mediators and cytokines in vitro. The anti-inflammatory effect of ethanol and aqueous extracts was not significant in the study. The significant inhibition of inflammatory mediators and cytokines by fractions from C. vulgaris suggests that this microalga would be a potential source of developing anti-inflammatory agents and a good alternate for conventional steroidal and nonsteroidal anti-inflammatory drugs. C. vulgaris extracts have potential anti-inflammatory activitySolvent extraction using methanol

Cerebrovascular accidents in patients with a ventricular assist device.

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Tsukui, Hiroyuki; Abla, Adib; Teuteberg, Jeffrey J; McNamara, Dennis M; Mathier, Michael A; Cadaret, Linda M; Kormos, Robert L

2007-07-01

A cerebrovascular accident is a devastating adverse event in a patient with a ventricular assist device. The goal was to clarify the risk factors for cerebrovascular accident. Prospectively collected data, including medical history, ventricular assist device type, white blood cell count, thrombelastogram, and infection, were reviewed retrospectively in 124 patients. Thirty-one patients (25%) had 48 cerebrovascular accidents. The mean ventricular assist device support period was 228 and 89 days in patients with and without cerebrovascular accidents, respectively (P cerebrovascular accidents occurred within 4 months after implantation. Actuarial freedom from cerebrovascular accident at 6 months was 75%, 64%, 63%, and 33% with the HeartMate device (Thoratec Corp, Pleasanton, Calif), Thoratec biventricular ventricular assist device (Thoratec Corp), Thoratec left ventricular assist device (Thoratec), and Novacor device (WorldHeart, Oakland, Calif), respectively. Twenty cerebrovascular accidents (42%) occurred in patients with infections. The mean white blood cell count at the cerebrovascular accident was greater than the normal range in patients with infection (12,900/mm3) and without infection (9500/mm3). The mean maximum amplitude of the thrombelastogram in the presence of infection (63.6 mm) was higher than that in the absence of infection (60.7 mm) (P = .0309). The risk of cerebrovascular accident increases with a longer ventricular assist device support period. Infection may activate platelet function and predispose the patient to a cerebrovascular accident. An elevation of the white blood cell count may also exacerbate the risk of cerebrovascular accident even in patients without infection. Selection of device type, prevention of infection, and meticulous control of anticoagulation are key to preventing cerebrovascular accident.

Short-term alpha- or gamma-delta-enriched tocopherol oil supplementation differentially effects the expression of proinflammatory mediators: selective impacts on characteristics of protein tyrosine nitration in vivo¿.

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Protein 3’-nitrotyrosine (pNT) is an established biomarker of nitrosative cell stress in animals challenged with proinflammatory mediators like endotoxin (LPS). We determined that short-term feeding of diets supplemented with a-tocopherol- (a-T -96% a-isomer) or '- and d-enriched mixed tocopherol o...

Cre-mediated stress affects sirtuin expression levels, peroxisome biogenesis and metabolism, antioxidant and proinflammatory signaling pathways.

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Yu Xiao

Full Text Available Cre-mediated excision of loxP sites is widely used in mice to manipulate gene function in a tissue-specific manner. To analyze phenotypic alterations related to Cre-expression, we have used AMH-Cre-transgenic mice as a model system. Different Cre expression levels were obtained by investigation of C57BL/6J wild type as well as heterozygous and homozygous AMH-Cre-mice. Our results indicate that Cre-expression itself in Sertoli cells already has led to oxidative stress and lipid peroxidation (4-HNE lysine adducts, inducing PPARα/γ, peroxisome proliferation and alterations of peroxisome biogenesis (PEX5, PEX13 and PEX14 as well as metabolic proteins (ABCD1, ABCD3, MFP1, thiolase B, catalase. In addition to the strong catalase increase, a NRF2- and FOXO3-mediated antioxidative response (HMOX1 of the endoplasmic reticulum and mitochondrial SOD2 and a NF-κB activation were noted. TGFβ1 and proinflammatory cytokines like IL1, IL6 and TNFα were upregulated and stress-related signaling pathways were induced. Sertoli cell mRNA-microarray analysis revealed an increase of TNFR2-signaling components. 53BP1 recruitment and expression levels for DNA repair genes as well as for p53 were elevated and the ones for related sirtuin deacetylases affected (SIRT 1, 3-7 in Sertoli cells. Under chronic Cre-mediated DNA damage conditions a strong downregulation of Sirt1 was observed, suggesting that the decrease of this important coordinator between DNA repair and metabolic signaling might induce the repression release of major transcription factors regulating metabolic and cytokine-mediated stress pathways. Indeed, caspase-3 was activated and increased germ cell apoptosis was observed, suggesting paracrine effects. In conclusion, the observed wide stress-induced effects and metabolic alterations suggest that it is essential to use the correct control animals (Cre/Wt with matched Cre expression levels to differentiate between Cre-mediated and specific gene-knock out-mediated

Cre-Mediated Stress Affects Sirtuin Expression Levels, Peroxisome Biogenesis and Metabolism, Antioxidant and Proinflammatory Signaling Pathways

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Xiao, Yu; Karnati, Srikanth; Qian, Guofeng; Nenicu, Anca; Fan, Wei; Tchatalbachev, Svetlin; Höland, Anita; Hossain, Hamid; Guillou, Florian; Lüers, Georg H.; Baumgart-Vogt, Eveline

2012-01-01

Cre-mediated excision of loxP sites is widely used in mice to manipulate gene function in a tissue-specific manner. To analyze phenotypic alterations related to Cre-expression, we have used AMH-Cre-transgenic mice as a model system. Different Cre expression levels were obtained by investigation of C57BL/6J wild type as well as heterozygous and homozygous AMH-Cre-mice. Our results indicate that Cre-expression itself in Sertoli cells already has led to oxidative stress and lipid peroxidation (4-HNE lysine adducts), inducing PPARα/γ, peroxisome proliferation and alterations of peroxisome biogenesis (PEX5, PEX13 and PEX14) as well as metabolic proteins (ABCD1, ABCD3, MFP1, thiolase B, catalase). In addition to the strong catalase increase, a NRF2- and FOXO3-mediated antioxidative response (HMOX1 of the endoplasmic reticulum and mitochondrial SOD2) and a NF-κB activation were noted. TGFβ1 and proinflammatory cytokines like IL1, IL6 and TNFα were upregulated and stress-related signaling pathways were induced. Sertoli cell mRNA-microarray analysis revealed an increase of TNFR2-signaling components. 53BP1 recruitment and expression levels for DNA repair genes as well as for p53 were elevated and the ones for related sirtuin deacetylases affected (SIRT 1, 3-7) in Sertoli cells. Under chronic Cre-mediated DNA damage conditions a strong downregulation of Sirt1 was observed, suggesting that the decrease of this important coordinator between DNA repair and metabolic signaling might induce the repression release of major transcription factors regulating metabolic and cytokine-mediated stress pathways. Indeed, caspase-3 was activated and increased germ cell apoptosis was observed, suggesting paracrine effects. In conclusion, the observed wide stress-induced effects and metabolic alterations suggest that it is essential to use the correct control animals (Cre/Wt) with matched Cre expression levels to differentiate between Cre-mediated and specific gene-knock out-mediated

Prolonged REM sleep restriction induces metabolic syndrome-related changes: Mediation by pro-inflammatory cytokines.

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Venancio, Daniel Paulino; Suchecki, Deborah

2015-07-01

Chronic sleep restriction in human beings results in metabolic abnormalities, including changes in the control of glucose homeostasis, increased body mass and risk of cardiovascular disease. In rats, 96h of REM sleep deprivation increases caloric intake, but retards body weight gain. Moreover, this procedure increases the expression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which may be involved with the molecular mechanism proposed to mediate insulin resistance. The goal of the present study was to assess the effects of a chronic protocol of sleep restriction on parameters of energy balance (food intake and body weight), leptin plasma levels and its hypothalamic receptors and mediators of the immune system in the retroperitoneal adipose tissue (RPAT). Thirty-four Wistar rats were distributed in control (CTL) and sleep restriction groups; the latter was kept onto individual narrow platforms immersed in water for 18h/day (from 16:00h to 10:00h), for 21days (SR21). Food intake was assessed daily, after each sleep restriction period and body weight was measured daily, after the animals were taken from the sleep deprivation chambers. At the end of the 21day of sleep restriction, rats were decapitated and RPAT was obtained for morphological and immune functional assays and expression of insulin receptor substrate 1 (IRS-1) was assessed in skeletal muscle. Another subset of animals was used to evaluate blood glucose clearance. The results replicated previous findings on energy balance, e.g., increased food intake and reduced body weight gain. There was a significant reduction of RPAT mass (pmetabolic syndrome-related alterations that may be mediated by inflammation of the RPAT. Copyright © 2014 Elsevier Inc. All rights reserved.

Ambient Temperature and Cerebrovascular Hemodynamics in the Elderly.

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Pan, Wen-Chi; Eliot, Melissa N; Koutrakis, Petros; Coull, Brent A; Sorond, Farzaneh A; Wellenius, Gregory A

2015-01-01

Some prior studies have linked ambient temperature with risk of cerebrovascular events. If causal, the pathophysiologic mechanisms underlying this putative association remain unknown. Temperature-related changes in cerebral vascular function may play a role, but this hypothesis has not been previously evaluated. We evaluated the association between ambient temperature and cerebral vascular function among 432 participants ≥65 years old from the MOBILIZE Boston Study with data on cerebrovascular blood flow, cerebrovascular resistance, and cerebrovascular reactivity in the middle cerebral artery. We used linear regression models to assess the association of mean ambient temperature in the previous 1 to 28 days with cerebrovascular hemodynamics adjusting for potential confounding factors. A 10°C increase in the 21-day moving average of ambient temperature was associated with a 10.1% (95% confidence interval [CI], 2.2%, 17.3%) lower blood flow velocity, a 9.0% (95% CI, 0.7%, 18.0%) higher cerebrovascular resistance, and a 15.3% (95%CI, 2.7%, 26.4%) lower cerebral vasoreactivity. Further adjustment for ozone and fine particulate matter (PM2.5) did not materially alter the results. However, we found statistically significant interactions between ambient temperature and PM2.5 such that the association between temperature and blood flow velocity was attenuated at higher levels of PM2.5. In this elderly population, we found that ambient temperature was negatively associated with cerebral blood flow velocity and cerebrovascular vasoreactivity and positively associated with cerebrovascular resistance. Changes in vascular function may partly underlie the observed associations between ambient temperature and risk of cerebrovascular events.

Activation of Proinflammatory Responses in Cells of the Airway Mucosa by Particulate Matter: Oxidant- and Non-Oxidant-Mediated Triggering Mechanisms

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Johan Øvrevik

2015-07-01

Full Text Available Inflammation is considered to play a central role in a diverse range of disease outcomes associated with exposure to various types of inhalable particulates. The initial mechanisms through which particles trigger cellular responses leading to activation of inflammatory responses are crucial to clarify in order to understand what physico-chemical characteristics govern the inflammogenic activity of particulate matter and why some particles are more harmful than others. Recent research suggests that molecular triggering mechanisms involved in activation of proinflammatory genes and onset of inflammatory reactions by particles or soluble particle components can be categorized into direct formation of reactive oxygen species (ROS with subsequent oxidative stress, interaction with the lipid layer of cellular membranes, activation of cell surface receptors, and direct interactions with intracellular molecular targets. The present review focuses on the immediate effects and responses in cells exposed to particles and central down-stream signaling mechanisms involved in regulation of proinflammatory genes, with special emphasis on the role of oxidant and non-oxidant triggering mechanisms. Importantly, ROS act as a central second-messenger in a variety of signaling pathways. Even non-oxidant mediated triggering mechanisms are therefore also likely to activate downstream redox-regulated events.

Leptin Enhances Synthesis of Proinflammatory Mediators in Human Osteoarthritic Cartilage—Mediator Role of NO in Leptin-Induced PGE2, IL-6, and IL-8 Production

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Katriina Vuolteenaho

2009-01-01

Full Text Available Obesity is an important risk factor for osteoarthritis (OA in weight-bearing joints, but also in hand joints, pointing to an obesity-related metabolic factor that influences on the pathogenesis of OA. Leptin is an adipokine regulating energy balance, and it has recently been related also to arthritis and inflammation as a proinflammatory factor. In the present paper, the effects of leptin on human OA cartilage were studied. Leptin alone or in combination with IL-1 enhanced the expression of iNOS and COX-2, and production of NO, PGE2, IL-6, and IL-8. The results suggest that the effects of leptin are mediated through activation of transcription factor nuclear factor κB (NF-κB and mitogen-activated protein kinase (MAPK pathway c-Jun NH2-terminal kinase (JNK. Interestingly, inhibition of leptin-induced NO production with a selective iNOS inhibitor 1400 W inhibited also the production of IL-6, IL-8, and PGE2, and this was reversed by exogenously added NO-donor SNAP, suggesting that the effects of leptin on IL-6, IL-8, and PGE2 production are dependent on NO. These findings support the idea of leptin as a factor enhancing the production of proinflammatory factors in OA cartilage and as an agent contributing to the obesity-associated increased risk for osteoarthritis.

Blunt cerebrovascular injuries in trauma.

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Eastham, Shannon

2016-09-01

Blunt cerebrovascular injury (BCVI) includes trauma to the carotid or vertebral vessels and is noted in 0.1% of hospitalized trauma patients without an initial screening system in place. Several important topics must be addressed including determination of the appropriate screening population, the best modality of screening for diagnosis, treatment types, and required follow-up of blunt cerebrovascular injuries. Copyright © 2015 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Migraine, cerebrovascular disease and the metabolic syndrome

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Alexandra J Sinclair

2012-01-01

Full Text Available Evidence is emerging that migraine is not solely a headache disorder. Observations that ischemic stroke could occur in the setting of a migraine attack, and that migraine headaches could be precipitated by cerebral ischemia, initially highlighted a possibly association between migraine and cerebrovascular disease. More recently, large population-based studies that have demonstrated that migraineurs are at increased risk of stroke outside the setting of a migraine attack have prompted the concept that migraine and cerebrovascular disease are comorbid conditions. Explanations for this association are numerous and widely debated, particularly as the comorbid association does not appear to be confined to the cerebral circulation as cardiovascular and peripheral vascular disease also appear to be comorbid with migraine. A growing body of evidence has also suggested that migraineurs are more likely to be obese, hypertensive, hyperlipidemic and have impaired insulin sensitivity, all features of the metabolic syndrome. The comorbid association between migraine and cerebrovascular disease may consequently be explained by migraineurs having the metabolic syndrome and consequently being at increased risk of cerebrovascular disease. This review will summarise the salient evidence suggesting a comorbid association between migraine, cerebrovascular disease and the metabolic syndrome.

Proinflammatory Factors Mediate Paclitaxel-Induced Impairment of Learning and Memory

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Zhao Li

2018-01-01

Full Text Available The chemotherapeutic agent paclitaxel is widely used for cancer treatment. Paclitaxel treatment impairs learning and memory function, a side effect that reduces the quality of life of cancer survivors. However, the neural mechanisms underlying paclitaxel-induced impairment of learning and memory remain unclear. Paclitaxel treatment leads to proinflammatory factor release and neuronal apoptosis. Thus, we hypothesized that paclitaxel impairs learning and memory function through proinflammatory factor-induced neuronal apoptosis. Neuronal apoptosis was assessed by TUNEL assay in the hippocampus. Protein expression levels of tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β in the hippocampus tissue were analyzed by Western blot assay. Spatial learning and memory function were determined by using the Morris water maze (MWM test. Paclitaxel treatment significantly increased the escape latencies and decreased the number of crossing in the MWM test. Furthermore, paclitaxel significantly increased the number of TUNEL-positive neurons in the hippocampus. Also, paclitaxel treatment increased the expression levels of TNF-α and IL-1β in the hippocampus tissue. In addition, the TNF-α synthesis inhibitor thalidomide significantly attenuated the number of paclitaxel-induced TUNEL-positive neurons in the hippocampus and restored the impaired spatial learning and memory function in paclitaxel-treated rats. These data suggest that TNF-α is critically involved in the paclitaxel-induced impairment of learning and memory function.

Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes

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Das, Hiranmoy; Kumar, Ajay; Lin, Zhiyong; Patino, Willmar D.; Hwang, Paul M.; Feinberg, Mark W.; Majumder, Pradip K.; Jain, Mukesh K.

2006-01-01

The mechanisms regulating activation of monocytes remain incompletely understood. Herein we provide evidence that Kruppel-like factor 2 (KLF2) inhibits proinflammatory activation of monocytes. In vitro, KLF2 expression in monocytes is reduced by cytokine activation or differentiation. Consistent with this observation, KLF2 expression in circulating monocytes is reduced in patients with chronic inflammatory conditions such as coronary artery disease. Adenoviral overexpression of KLF2 inhibits the LPS-mediated induction of proinflammatory factors, cytokines, and chemokines and reduces phagocytosis. Conversely, short interfering RNA-mediated reduction in KLF2 increased inflammatory gene expression. Reconstitution of immunodeficient mice with KLF2-overexpressing monocytes significantly reduced carrageenan-induced acute paw edema formation. Mechanistically, KLF2 inhibits the transcriptional activity of both NF-κB and activator protein 1, in part by means of recruitment of transcriptional coactivator p300/CBP-associated factor. These observations identify KLF2 as a novel negative regulator of monocytic activation. PMID:16617118

The SaeR/S gene regulatory system induces a pro-inflammatory cytokine response during Staphylococcus aureus infection.

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Robert L Watkins

Full Text Available Community-associated methicillin-resistant Staphylococcus aureus accounts for a large portion of the increased staphylococcal disease incidence and can cause illness ranging from mild skin infections to rapidly fatal sepsis syndromes. Currently, we have limited understanding of S. aureus-derived mechanisms contributing to bacterial pathogenesis and host inflammation during staphylococcal disease. Herein, we characterize an influential role for the saeR/S two-component gene regulatory system in mediating cytokine induction using mouse models of S. aureus pathogenesis. Invasive S. aureus infection induced the production of localized and systemic pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-α, interferon gamma (IFN-γ, interleukin (IL-6 and IL-2. In contrast, mice infected with an isogenic saeR/S deletion mutant demonstrated significantly reduced pro-inflammatory cytokine levels. Additionally, secreted factors influenced by saeR/S elicited pro-inflammatory cytokines in human blood ex vivo. Our study further demonstrated robust saeR/S-mediated IFN-γ production during both invasive and subcutaneous skin infections. Results also indicated a critical role for saeR/S in promoting bacterial survival and enhancing host mortality during S. aureus peritonitis. Taken together, this study provides insight into specific mechanisms used by S. aureus during staphylococcal disease and characterizes a relationship between a bacterial global regulator of virulence and the production of pro-inflammatory mediators.

Cerebrovascular Accidents Associated with Sorafenib in Hepatocellular Carcinoma

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Saif, Muhammad W.; Isufi, Iris; Peccerillo, Jennifer; Syrigos, Kostas N.

2011-01-01

Sorafenib is an oral angiogenetic multikinase inhibitor approved in the treatment of renal and hepatocellular carcinoma. Bleeding and venous thrombotic events have been described with angiogenetic agents but cerebrovascular accidents are rarely reported. We report two cases of patients with hepatocellular carcinoma who developed a cerebrovascular accident while on sorafenib. Neither patient had any risk factors for the cerebrovascular events apart from gender and age in the second patient. La...

Pro-inflammatory cytokine/chemokine production by reovirus treated melanoma cells is PKR/NF-κB mediated and supports innate and adaptive anti-tumour immune priming

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Coffey Matt

2011-02-01

Full Text Available Abstract Background As well as inducing direct oncolysis, reovirus treatment of melanoma is associated with activation of innate and adaptive anti-tumour immune responses. Results Here we characterise the effects of conditioned media from reovirus-infected, dying human melanoma cells (reoTCM, in the absence of live virus, to address the immune bystander potential of reovirus therapy. In addition to RANTES, IL-8, MIP-1α and MIP-1β, reovirus-infected melanoma cells secreted eotaxin, IP-10 and the type 1 interferon IFN-β. To address the mechanisms responsible for the inflammatory composition of reoTCM, we show that IL-8 and IFN-β secretion by reovirus-infected melanoma cells was associated with activation of NF-κB and decreased by pre-treatment with small molecule inhibitors of NF-κB and PKR; specific siRNA-mediated knockdown further confirmed a role for PKR. This pro-inflammatory milieu induced a chemotactic response in isolated natural killer (NK cells, dendritic cells (DC and anti-melanoma cytotoxic T cells (CTL. Following culture in reoTCM, NK cells upregulated CD69 expression and acquired greater lytic potential against tumour targets. Furthermore, melanoma cell-loaded DC cultured in reoTCM were more effective at priming adaptive anti-tumour immunity. Conclusions These data demonstrate that the PKR- and NF-κB-dependent induction of pro-inflammatory molecules that accompanies reovirus-mediated killing can recruit and activate innate and adaptive effector cells, thus potentially altering the tumour microenvironment to support bystander immune-mediated therapy as well as direct viral oncolysis.

Protective Effects of N-Acetyl Cysteine against Diesel Exhaust Particles-Induced Intracellular ROS Generates Pro-Inflammatory Cytokines to Mediate the Vascular Permeability of Capillary-Like Endothelial Tubes

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Tseng, Chia-Yi; Chang, Jing-Fen; Wang, Jhih-Syuan; Chang, Yu-Jung; Gordon, Marion K.; Chao, Ming-Wei

2015-01-01

Exposure to diesel exhaust particles (DEP) is associated with pulmonary and cardiovascular diseases. Previous studies using in vitro endothelial tubes as a simplified model of capillaries have found that DEP-induced ROS increase vascular permeability with rearrangement or internalization of adherens junctional VE-cadherin away from the plasma membrane. This allows DEPs to penetrate into the cell and capillary lumen. In addition, pro-inflammatory cytokines are up-regulated and mediate vascular permeability in response to DEP. However, the mechanisms through which these DEP-induced pro-inflammatory cytokines increase vascular permeability remain unknown. Hence, we examined the ability of DEP to induce permeability of human umbilical vein endothelial cell tube cells to investigate these mechanisms. Furthermore, supplementation with NAC reduces ROS production following exposure to DEP. HUVEC tube cells contributed to a pro-inflammatory response to DEP-induced intracellular ROS generation. Endothelial oxidative stress induced the release of TNF-α and IL-6 from tube cells, subsequently stimulating the secretion of VEGF-A independent of HO-1. Our data suggests that DEP-induced intracellular ROS and release of the pro-inflammatory cytokines TNF- α and IL-6, which would contribute to VEGF-A secretion and disrupt cell-cell borders and increase vasculature permeability. Addition of NAC suppresses DEP-induced ROS efficiently and reduces subsequent damages by increasing endogenous glutathione. PMID:26148005

Protective Effects of N-Acetyl Cysteine against Diesel Exhaust Particles-Induced Intracellular ROS Generates Pro-Inflammatory Cytokines to Mediate the Vascular Permeability of Capillary-Like Endothelial Tubes.

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Chia-Yi Tseng

Full Text Available Exposure to diesel exhaust particles (DEP is associated with pulmonary and cardiovascular diseases. Previous studies using in vitro endothelial tubes as a simplified model of capillaries have found that DEP-induced ROS increase vascular permeability with rearrangement or internalization of adherens junctional VE-cadherin away from the plasma membrane. This allows DEPs to penetrate into the cell and capillary lumen. In addition, pro-inflammatory cytokines are up-regulated and mediate vascular permeability in response to DEP. However, the mechanisms through which these DEP-induced pro-inflammatory cytokines increase vascular permeability remain unknown. Hence, we examined the ability of DEP to induce permeability of human umbilical vein endothelial cell tube cells to investigate these mechanisms. Furthermore, supplementation with NAC reduces ROS production following exposure to DEP. HUVEC tube cells contributed to a pro-inflammatory response to DEP-induced intracellular ROS generation. Endothelial oxidative stress induced the release of TNF-α and IL-6 from tube cells, subsequently stimulating the secretion of VEGF-A independent of HO-1. Our data suggests that DEP-induced intracellular ROS and release of the pro-inflammatory cytokines TNF- α and IL-6, which would contribute to VEGF-A secretion and disrupt cell-cell borders and increase vasculature permeability. Addition of NAC suppresses DEP-induced ROS efficiently and reduces subsequent damages by increasing endogenous glutathione.

Cerebrovascular Diseases and Early Seizure

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Ayşegül Gündüz

2006-08-01

Full Text Available OBJECTIVE: Cerebrovascular disease is one of the important causes of seizures and epilepsy among the advanced age group. Seziures are found to be associated with lesion localization and size in previous studies. METHODS: Here, we aimed to detect prevelance of seizure, relation of seizure and lesion localization, and observed seizure types. RESULTS: Three hundred seventy eight patients with ischemic cerebrovascular disease or intraparenchymal hemorrhage who were followed in Cerrahpasa IVIedical School clinic were studied retrospectively and probability of seizure occurence within 1 month after stroke was evaluated. CONCLUSION: Among 378 patients hospitalized by acute stroke, 339 were diagnosed as ischemic cerebrovascular disease and 39 (10.3% had primary intraparenchymal hematoma. Seizures were observed in 16 patients (4.2%, 2 (%5.1 in intraparenchymal hematoma group and 14 (%4.1 in ischemic cerebrovascular disease. Early seizures were detected in 33% of patients with anterior cerebral artery, in 6.8% of posterior cerebral artery and in 3.3% of middle cerebral artery infarcts and in three patients out of 12 who were known to have epilepsy. Seizure types were secondarily generalised tonic-clonic seizure in nine cases (57%. Among whole group status epilepticus was observed in four patients (1.1%. Conclusion: Early seizure rates are found to be high among patients with anterior cerebral artery infarct and known epilepsy

Effect of nitric oxide-releasing derivative of indomethacin on Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

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Choe, So-Hui; Choi, Eun-Young; Hyeon, Jin-Yi; Choi, In Soon; Kim, Sung-Jo

2017-10-14

The purpose of this study was to investigate the influences of NCX 2121, a nitric oxide (NO)-releasing derivative of indomethacin, upon the generation of proinflammatory mediators using murine macrophages activated by lipopolysaccharide (LPS) isolated from Prevotella intermedia, which is one of the pathogens implicated in periodontal diseases. Inducible NO synthase (iNOS)-derived NO, IL-1β and IL-6 as well as their relevant mRNA were significantly attenuated by NCX 2121 in RAW264.7 cells activated by P. intermedia LPS. NCX 2121 was much more effective than the parental compound indomethacin in reducing these proinflammatory mediators. NCX 2121 triggered induction of heme oxygenase-1 (HO-1) in cells exposed to P. intermedia LPS, and its inhibitory influence upon P. intermedia LPS-elicited NO generation was notably blocked by SnPP treatment. NCX 2121 attenuated NF-κB-dependent SEAP release induced by P. intermedia LPS. NCX 2121 did not display inhibitory action towards IκB-α degradation triggered by LPS. Instead, it significantly diminished nuclear translocation as well as DNA-binding action of NF-κB p50 subunit elicited by P. intermedia LPS. Further, NCX 2121 significantly up-regulated SOCS1 mRNA expression in cells challenged with P. intermedia LPS. In summary, NCX 2121 down-regulates P. intermedia LPS-elicited generation of NO, IL-1β and IL-6 in murine macrophages in a mechanism that involves anti-inflammatory HO-1 induction as well as decrement of NF-κB activation, which may be associated with SOCS1 expression. NCX 2121 may have potential benefits as a host immunomodulatory agent for the therapy of periodontal disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Polybrominated diphenyl ethers enhance the production of proinflammatory cytokines by the placenta.

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Peltier, M R; Klimova, N G; Arita, Y; Gurzenda, E M; Murthy, A; Chawala, K; Lerner, V; Richardson, J; Hanna, N

2012-09-01

Polybrominated diphenyl ether(s) (PBDE) are ubiquitous environmental contaminants that bind and cross the placenta but their effects on pregnancy outcome are unclear. It is possible that environmental contaminants increase the risk of inflammation-mediated pregnancy complications such as preterm birth by promoting a proinflammatory environment at the maternal-fetal interface. We hypothesized that PBDE would reduce IL-10 production and enhance the production of proinflammatory cytokines associated with preterm labor/birth by placental explants. Second-trimester placental explants were cultured in either vehicle (control) or 2 μM PBDE mixture of congers 47, 99 and 100 for 72 h. Cultures were then stimulated with 10(6) CFU/ml heat-killed Escherichia coli for a final 24 h incubation and conditioned medium was harvested for quantification of cytokines and PGE(2). COX-2 content and viability of the treated tissues were then quantified by tissue ELISA and MTT reduction activity, respectively. PBDE pre-treatment reduced E. coli-stimulated IL-10 production and significantly increased E. coli-stimulated IL-1β secretion. PBDE exposure also increased basal and bacteria-stimulated COX-2 expression. Basal, but not bacteria-stimulated PGE(2), was also enhanced by PBDE exposure. No effect of PBDE on viability of the explants cultures was detected. In summary, pre-exposure of placental explants to congers 47, 99, and 100 enhanced the placental proinflammatory response to infection. This may increase the risk of infection-mediated preterm birth by lowering the threshold for bacteria to stimulate a proinflammatory response(s). Copyright © 2012 Elsevier Ltd. All rights reserved.

Dysregulated proinflammatory and fibrogenic phenotype of fibroblasts in cystic fibrosis.

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François Huaux

Full Text Available Morbi-mortality in cystic fibrosis (CF is mainly related to chronic lung infection and inflammation, uncontrolled tissue rearrangements and fibrosis, and yet the underlying mechanisms remain largely unknown. We evaluated inflammatory and fibrosis responses to bleomycin in F508del homozygous and wild-type mice, and phenotype of fibroblasts explanted from mouse lungs and skin. The effect of vardenafil, a cGMP-specific phosphodiesterase type 5 inhibitor, was tested in vivo and in culture. Responses of proinflammatory and fibrotic markers to bleomycin were enhanced in lungs and skin of CF mice and were prevented by treatment with vardenafil. Purified lung and skin fibroblasts from CF mice proliferated and differentiated into myofibroblasts more prominently and displayed higher sensitivity to growth factors than those recovered from wild-type littermates. Under inflammatory stimulation, mRNA and protein expression of proinflammatory mediators were higher in CF than in wild-type fibroblasts, in which CFTR expression reached similar levels to those observed in other non-epithelial cells, such as macrophages. Increased proinflammatory responses in CF fibroblasts were reduced by half with submicromolar concentrations of vardenafil. Proinflammatory and fibrogenic functions of fibroblasts are upregulated in CF and are reduced by vardenafil. This study provides compelling new support for targeting cGMP signaling pathway in CF pharmacotherapy.

Clinical analysis of 34 cases symptomatic epilepsy secondary to cerebrovascular disease

International Nuclear Information System (INIS)

Zeng Mingyu; Liu Chunfeng

2000-01-01

Objective: To investigate the relation between cerebrovascular disease and symptomatic epilepsy. Method: 786 patients suffered cerebrovascular disease were retrospectively analyzed. Result: The occurrence rate of Secondary to Cerebrovascular Disease symptomatic epilepsy Secondary to Cerebrovascular Disease was 4.3%. Those older than 60 are prone to develop Acrodynia symptomatic epilepsy. Generalized epileptic seizure were often seen. Secondary to Cerebrovascular Disease epilepsy die to cortical lesion are more easily seem than subcortical lesion. Early epilepsy is more than late epilepsy. Conclusion: The cause of symptomatic epilepsy after cerebrovascular disease is not same in different types and course of CVD. Those who developed epilepsy particularly epilepsy continua would have bad prognosis

Mapping hypercapnia-induced cerebrovascular reactivity using BOLD MRI

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Zande, F.H.R. van der; Hofman, P.A.M.; Backes, W.H. [Maastricht University Hospital, Department of Radiology, P.O. Box 5800, Maastricht (Netherlands)

2005-02-01

Severe carotid artery stenosis or occlusion may put patients at risk for ischaemic stroke. Reduced cerebrovascular reserve capacity is a possible indicator of an imminent ischaemic event and can be determined by assessment of cerebrovascular reactivity to a vasodilative stimulus. However, little is known about the distribution of cerebrovascular reactivity in healthy individuals. In 13 healthy volunteers, dynamic T{sub 2}{sup *} MR images, acquired at alternating inspiratory pCO{sub 2} levels, showed a high percentage of signal change in grey matter, with a strong linear correlation with end-tidal pCO{sub 2}. The mean percentages of signal change for grey and white matter were 5.9{+-}1.2% and 1.9{+-}0.5%, respectively. The mean time lag between CO{sub 2} stimulus and haemodynamic response was 15{+-}4 s for grey matter and 180{+-}12 s for white matter. Parameter mapping revealed a hemispherically symmetrical and homogeneous distribution of cerebrovascular reactivity over the entire grey matter. These findings indicate that it may be feasible to detect exhausted cerebrovascular autoregulation in patients with a compromised cerebral vasculature. (orig.)

Mapping hypercapnia-induced cerebrovascular reactivity using BOLD MRI

International Nuclear Information System (INIS)

Zande, F.H.R. van der; Hofman, P.A.M.; Backes, W.H.

2005-01-01

Severe carotid artery stenosis or occlusion may put patients at risk for ischaemic stroke. Reduced cerebrovascular reserve capacity is a possible indicator of an imminent ischaemic event and can be determined by assessment of cerebrovascular reactivity to a vasodilative stimulus. However, little is known about the distribution of cerebrovascular reactivity in healthy individuals. In 13 healthy volunteers, dynamic T 2 * MR images, acquired at alternating inspiratory pCO 2 levels, showed a high percentage of signal change in grey matter, with a strong linear correlation with end-tidal pCO 2 . The mean percentages of signal change for grey and white matter were 5.9±1.2% and 1.9±0.5%, respectively. The mean time lag between CO 2 stimulus and haemodynamic response was 15±4 s for grey matter and 180±12 s for white matter. Parameter mapping revealed a hemispherically symmetrical and homogeneous distribution of cerebrovascular reactivity over the entire grey matter. These findings indicate that it may be feasible to detect exhausted cerebrovascular autoregulation in patients with a compromised cerebral vasculature. (orig.)

Biomechanical Loading Modulates Proinflammatory and Bone Resorptive Mediators in Bacterial-Stimulated PDL Cells

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Andressa Vilas Boas Nogueira

2014-01-01

Full Text Available The present study aimed to evaluate in vitro whether biomechanical loading modulates proinflammatory and bone remodeling mediators production by periodontal ligament (PDL cells in the presence of bacterial challenge. Cells were seeded on BioFlex culture plates and exposed to Fusobacterium nucleatum ATCC 25586 and/or cyclic tensile strain (CTS of low (CTSL and high (CTSH magnitudes for 1 and 3 days. Synthesis of cyclooxygenase-2 (COX2 and prostaglandin E2 (PGE2 was evaluated by ELISA. Gene expression and protein secretion of osteoprotegerin (OPG and receptor activator of nuclear factor kappa-B ligand (RANKL were evaluated by quantitative RT-PCR and ELISA, respectively. F. nucleatum increased the production of COX2 and PGE2, which was further increased by CTS. F. nucleatum-induced increase of PGE2 synthesis was significantly (P<0.05 increased when CTSH was applied at 1 and 3 days. In addition, CTSH inhibited the F. nucleatum-induced upregulation of OPG at 1 and 3 days, thereby increasing the RANKL/OPG ratio. OPG and RANKL mRNA results correlated with the protein results. In summary, our findings provide original evidence that CTS can enhance bacterial-induced syntheses of molecules associated with inflammation and bone resorption by PDL cells. Therefore, biomechanical, such as orthodontic or occlusal, loading may enhance the bacterial-induced inflammation and destruction in periodontitis.

Cerebrovascular Hemodynamics in Women.

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Duque, Cristina; Feske, Steven K; Sorond, Farzaneh A

2017-12-01

Sex and gender, as biological and social factors, significantly influence health outcomes. Among the biological factors, sex differences in vascular physiology may be one specific mechanism contributing to the observed differences in clinical presentation, response to treatment, and clinical outcomes in several vascular disorders. This review focuses on the cerebrovascular bed and summarizes the existing literature on sex differences in cerebrovascular hemodynamics to highlight the knowledge deficit that exists in this domain. The available evidence is used to generate mechanistically plausible and testable hypotheses to underscore the unmet need in understanding sex-specific mechanisms as targets for more effective therapeutic and preventive strategies. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Redox-Mediated and Ionizing-Radiation-Induced Inflammatory Mediators in Prostate Cancer Development and Treatment

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Miao, Lu; Holley, Aaron K.; Zhao, Yanming; St. Clair, William H.

2014-01-01

Abstract Significance: Radiation therapy is widely used for treatment of prostate cancer. Radiation can directly damage biologically important molecules; however, most effects of radiation-mediated cell killing are derived from the generated free radicals that alter cellular redox status. Multiple proinflammatory mediators can also influence redox status in irradiated cells and the surrounding microenvironment, thereby affecting prostate cancer progression and radiotherapy efficiency. Recent Advances: Ionizing radiation (IR)–generated oxidative stress can regulate and be regulated by the production of proinflammatory mediators. Depending on the type and stage of the prostate cancer cells, these proinflammatory mediators may lead to different biological consequences ranging from cell death to development of radioresistance. Critical Issues: Tumors are heterogeneous and dynamic communication occurs between stromal and prostate cancer cells, and complicated redox-regulated mechanisms exist in the tumor microenvironment. Thus, antioxidant and anti-inflammatory strategies should be carefully evaluated for each patient at different stages of the disease to maximize therapeutic benefits while minimizing unintended side effects. Future Directions: Compared with normal cells, tumor cells are usually under higher oxidative stress and secrete more proinflammatory mediators. Thus, redox status is often less adaptive in tumor cells than in their normal counterparts. This difference can be exploited in a search for new cancer therapeutics and treatment regimes that selectively activate cell death pathways in tumor cells with minimal unintended consequences in terms of chemo- and radio-resistance in tumor cells and toxicity in normal tissues. Antioxid. Redox Signal. 20, 1481–1500. PMID:24093432

Dietary gamma oryzanol plays a significant role in the anti-inflammatory activity of rice bran oil by decreasing pro-inflammatory mediators secreted by peritoneal macrophages of rats.

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Rao, Y Poorna Chandra; Sugasini, D; Lokesh, B R

2016-10-28

Ricebran oil (RBO) is promoted as heart friendly oil because of its ability to maintain serum lipids at desirable levels. Inflammation also plays an important role on cardiovascular health. The role of minor constituents present in unsaponifiable fraction (UF) of RBO on inflammatory markers is not well understood. To evaluate this, we have taken RBO with UF (RBO-N), RBO stripped of UF (RBO-MCR) and RBO-MCR supplemented with UF from RBO (UFRBO) or Gamma-Oryzanol (γ-ORY) were added in AIN-93 diets which was then fed to Wistar rats for a period of 60 days. Groundnut oil with UF (GNO-N), UF removed GNO (GNO-MCR) and GNO-MCR supplemented with UF from RBO or γ-ORY was also used for comparison. The peritoneal macrophages from the rats were activated and pro-inflammatory mediators such as Reactive Oxygen Species (ROS), eicosanoids, cytokines, hydrolytic enzymes of lysosomal origin were monitored. The results indicated that UF of RBO and γ-ORY supplemented in the dietary oils play a significant role in reducing the secretion of pro-inflammatory mediators by macrophages. Hence γ-ORY in RBO significantly contributed to the anti-inflammatory properties of RBO. Copyright © 2016 Elsevier Inc. All rights reserved.

Proinflammatory proteins in female and male patients with primary antiphospholipid syndrome: preliminary data.

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Bećarević, Mirjana; Ignjatović, Svetlana

2016-10-01

The latest classification criteria for the diagnosis of the antiphospholipid syndrome (APS, an autoimmune disease characterized by thromboses, miscarriages and presence of antiphospholipid antibodies (Abs)) emphasized that thrombotic manifestations of APS should be without any signs of an inflammatory process. However, atherosclerosis (a chronic inflammatory response to the accumulation of lipoproteins in the walls of arteries) and APS are characterized by some similar features. We evaluated whether proinflammatory proteins were associated with the features of the primary APS (PAPS). PAPS patients without obstetric complications and with impaired lipid profile were included in the study. Antiphospholipid antibodies, TNF-alpha, and apo(a) were determined by ELISA. Complement components and hsCRP were measured by immunonephelometry. Decreased C3c was observed in female patients with increased titers of IgG anti-β2gpI (χ(2) = 3.939, P = 0.047) and in male patients with increased IgM anticardiolipin Abs (χ(2) = 4.286, P = 0.038). Pulmonary emboli were associated with interleukin (IL)-6 in male (χ(2) = 6.519, P = 0.011) and in female (χ(2) = 10.405, P = 0.001) patients. Cerebrovascular insults were associated with LDL-cholesterol (P = 0.05, 95 % CI: 1.003 - 12.739) in female and with apo(a) (P = 0.016, 95 % CI: 0.000-0.003) in male patients. Older female patients had increased LDL-cholesterol levels and frequency of myocardial infarctions. Proinflammatory proteins were associated with features of primary APS. No real gender differences in regard to proinflammatory protein levels were observed. Premenopausal state of female PAPS patients confers lower cardiovascular risk.

Anthocyanin prevents CD40-activated proinflammatory signaling in endothelial cells by regulating cholesterol distribution.

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Xia, Min; Ling, Wenhua; Zhu, Huilian; Wang, Qing; Ma, Jing; Hou, Mengjun; Tang, Zhihong; Li, Lan; Ye, Qinyuan

2007-03-01

Intracellular tumor necrosis factor receptor-associated factors (TRAFs) translocation to lipid rafts is a key element in CD40-induced signaling. The purpose of this study was to investigate the influence of anthocyanin on CD40-mediated proinflammatory events in human endothelial cells and the underlying possible molecular mechanism. Treatment of endothelial cells with anthocyanin prevented from CD40-induced proinflammatory status, measured by production of IL-6, IL-8, and monocyte chemoattractant protein-1 through inhibiting CD40-induced nuclear factor-kappaB (NF-kappaB) activation. TRAF-2 played pivotal role in CD40-NF-kappaB pathway as TRAF-2 small interference RNA (siRNA) diminished CD40-induced NF-kappaB activation and inflammation. TRAF-2 overexpression increased CD40-mediated NF-kappaB activation. Moreover, TRAF-2 almost totally recruited to lipid rafts after stimulation by CD40 ligand and depletion of cholesterol diminished CD40-mediated NF-kappaB activation. Exposure to anthocyanin not only interrupted TRAF-2 recruitment to lipid rafts but also decreased cholesterol content in Triton X-100 insoluble lipid rafts. However, anthocyanin did not influence the interaction between CD40 ligand and CD40 receptor. Our findings suggest that anthocyanin protects from CD40-induced proinflammatory signaling by preventing TRAF-2 translocation to lipid rafts through regulation of cholesterol distribution, which thereby may represent a mechanism that would explain the anti-inflammatory response of anthocyanin.

Ischemia-modified albumin levels in cerebrovascular accidents.

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Gunduz, Abdulkadir; Turedi, Suleyman; Mentese, Ahmet; Altunayoglu, Vildan; Turan, Ibrahim; Karahan, Suleyman Caner; Topbas, Murat; Aydin, Murat; Eraydin, Ismet; Akcan, Buket

2008-10-01

Previous studies have demonstrated that ischemia-modified albumin (IMA) is a useful marker for the diagnosis of ischemic events. It was also recently demonstrated that IMA levels increase in the acute phase of cerebrovascular diseases. Yet the data regarding IMA levels in various types of cerebrovascular events are insufficient. The aim of this study was to evaluate IMA levels in various types of cerebrovascular events such as ischemic stroke, subarachnoid hemorrhage (SAH), and intracranial hemorrhage. This case-controlled study consisted of 106 consecutive patients, 43 with brain infarction (BI), 11 with brain hemorrhage (ICH), 52 with SAH, and a 43-member control group. We investigated whether there was a statistical correlation between these 3 groups and the control group. The relations among the 3 groups were also examined. Comparisons among groups were done with analysis of variance. Mean serum IMA levels were 0.280 +/- 0.045 absorbance units (ABSU) for BI patients, 0.259 +/- 0.053 ABSU for ICH patients, 0.243 +/- 0.061 ABSU for SAH patients, and 0.172 +/- 0.045 ABSU for the control group.There was a statistically significant difference between the mean IMA levels of BI, ICH, and SAH patients and the mean control patient IMA levels (P b .0001). Ischemia-modified albumin levels are high in cerebrovascular diseases. Ischemia-modified albumin measurement can also be used to distinguish SAH from BI during the acute phase of cerebrovascular event in the emergency department.

Ocurrencia de enfermedad cerebrovascular en pacientes hipertensos

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María de la Concepción Orbay Araña

2002-10-01

Full Text Available Se realizó un estudio para establecer la relación entre la hipertensión arterial esencial y la enfermedad cerebrovascular, en 19 consultorios del Médico de la Familia del Policlínico Plaza de la Revolución. Se aplicó una encuesta a pacientes reevaluados como hipertensos, confeccionándose una base de datos para tratamiento en el sistema FOXBASE versión 5.0. Aplicamos prueba de asociación entre variables cualitativas que se distribuyen en Chi cuadrado. Se identificó el comportamiento de la hipertensión arterial atendiendo a grados, los grupos etáreos, el sexo, la raza y los factores de riesgo asociados. Se estableció igualmente la relación entre el control de la hipertensión arterial y la aparición de la enfermedad cerebrovascular y encontramos un 15 % de población hipertensa, predominando la moderada (36,88 %, con mayor representación los grupos etáreos de 55 a 64 años (38,29 % y de 45 a 54 (23,16 %, del sexo femenino (55,02 % y de la raza blanca (54,04 %. La ocurrencia de enfermedad cerebrovascular estuvo representada por el 4, 35 %, correspondiente a 71 pacientes, con mayor asociación a la hipertensión arterial severa. No resultó significativamente estadística la relación entre enfermedad cerebrovascular e hipertensión arterial.A study was conducted to establish the relationship between essential arterial hypertension and cerebrovascular disease in 19 family physician offices of "Plaza de la Revolución" Polyclinic. Those patientes reevaluated as hypertensive were surveyed. A database for treatment was created in the FOXBASE system, version 5.0. A Chi square test of association among qualitative variables, which are distributed, was applied. The behavior of arterial hypertension was identified according to degrees, age groups, sex, race and the associated risk factors. The relation between the control of arterial hypertension and the appearance of cerebrovascular disease was also established. It was found a 15 % of

Depression and dementia of cerebrovascular origin

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Marmorato Paulo Germano

2002-01-01

Full Text Available We report the case of a patient who presented various psychiatric syndromes at the time of evaluation - partial complex epileptic seizures, personality change, and severe depression, which eventually progressed to dementia - resulting from multiple cerebral infarctions of probable neuro-angiopathic origin, of unknown etiology. Aspects related to depression following cerebrovascular accidents, as well as how cerebrovascular accidents can result in different disorders depending on the variables, are discussed based on the data from current literature.

Raca e mortalidade cerebrovascular no Brasil

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Paulo Andrade Lotufo

2013-12-01

Full Text Available Sendo desconhecidas as taxas de mortalidade cerebrovascular segundo raça no Brasil, foram coletadas informações de óbitos de 2010 do Sistema de Informação de Mortalidade do Ministério da Saúde. Foram calculadas as taxas de mortalidade cerebrovascular, ajustadas por idade (por 100 mil, com intervalo de confiança de 95%, por sexo e raça/cor de pele. A diferença entre brancos, pardos e negros foi significativa para homens, com taxas, respectivamente, de 44,4 (43,5;45,3, 48,2 (47,1;49,3 e 63,3 (60.6;66,6; e para mulheres, com taxa, respectivamente, de 29,0 (28,3;29,7, 33,7 (32,8;34,6 e 51,0 (48,6;53,4. Em conclusão, a mortalidade cerebrovascular no Brasil é maior entre negros.

Radiological study of cerebro-vascular accidents

International Nuclear Information System (INIS)

Misri, H.T.; Kabawe, Bassam

1991-01-01

The role of computerized tomography scanner in studying the cerebro-vascular accidents has been discussed. One hundred fifty patients with cerebro-vascular accidents were studied at Aleppo University Hospital between 1989-1990. Clinical history and physical examination were recorded, as well as, computerized tomography scanning in all cases without using the contrast media mostly. Relationship between the density of the lesion (inforctionor hemorrhage) and the time has been found. This relationship can help in forensic medicine. (author). 29 refs., 5 tabs., 2 figs

ACUTE CEREBROVASCULAR ACCIDENTS IN PREGNANCY, LABOR AND POSTPARTUM

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R. R. Arustamyan

2016-01-01

Full Text Available Background: Acute cerebrovascular accidents are rare and serious complication of pregnancy, labor and puerperium, leading to an increase in maternal and perinatal morbidity and mortality. More than 12% of maternal mortality is related to stroke. Aim: To assess the impact of pregnancy on the incidence of stroke, as well as the impact of cerebrovascular disorders on pregnancy, labor and puerperium. Materials and methods: We retrospectively and prospectively analyzed the course of pregnancy, labor and puerperium in 136 female patients with strokes of various etiologies. The diagnosis of stroke and cerebrovascular disorders was verified with magnetic resonance imaging, angiography, conventional and multiaxial computerized tomography, ophthalmoscopy, electroencephalography, electrocardiography and echocardiography (trans-thoracic and trans-esophageal, 24-hour blood pressure monitoring and electrocardiogram monitoring, ultrasound assessment of extra and intracranial vasculature with duplex scanning, cerebral angiography and laboratory assessments. Results: The analysis of 92 strokes that occurred during pregnancy, labor and postpartum showed that 38% of the cases (n=35 were caused by various cerebrovascular abnormalities. In 18.5% of the cases (n=17, acute cerebrovascular accidents occurred in patients with preeclampsia/eclampsia. Most often (84.8%, or 78/97 of cases strokes or other cerebrovascular accidents developed in II and III trimesters. The most severe cases were patients with intracranial hemorrhages (n=31. In this group, there were 5  deaths of mothers, 1  antenatal and 1  neonatal fetal deaths. In 90% of these cases (28/31, intracranial hemorrhage in pregnancy was related to manifestation of intracerebral vascular abnormality (arteriovenous malformations, arterial aneurysms, cavernomas. We observed a 4-fold rate of arteriovenous malformation ruptures during pregnancy (21 cases vs. 5. The rates of arterial aneurysm and cavernoma ruptures

Transcatheter aortic valve implantation and cerebrovascular accidents.

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Stortecky, Stefan; Wenaweser, Peter; Windecker, Stephan

2012-09-01

Transcatheter aortic valve implantation (TAVI) is an evidence-based treatment alternative for selected high-risk patients with symptomatic severe aortic stenosis as acknowledged in the most recent edition of the ESC Guidelines on Valvular Heart Disease 2012. However, periprocedural complications and in particular cerebrovascular accidents remain a matter of concern. While transcatheter heart valve technology continuously improves and the development of novel and even less invasive implantation techniques is on-going, cerebrovascular events complicating TAVI may abrogate the usual improvement in terms of prognosis and quality of life. This article describes the incidence of cerebrovascular events after cardiovascular procedures, provides an overview of the pathophysiological mechanisms as well as the impact on outcomes and provides some insights into preventive strategies as well as the acute management of these events.

Non-invasive examination method for cerebrovascular diseases

International Nuclear Information System (INIS)

Chiba, Kazuo

1979-01-01

CT is superior in the diagnosis of the characteristics and the region of cerebrovascular diseases (CVD) to the examination with RI. The RI examination can only demonstrate the cerebrovascular diseases with large area disturbance of the cerebral cortex, that passed some days after the attack. Moreover, it is difficult to detect the small lesions or the lesions localized in the deep area such as the basal nucleus and the internal capsule by this method. A slight decrease and retardation in unilateral cerebral blood flow (under 20%, within 1.5 second) found by RI-angiography does not always indicate the side of the lesion of cerebrovascular diseases. It is expected that non-invasive examination method for CVD is improved more, and that more precise estimation method for regional cerebral circulation is developed. (Tsunoda, M.)

The Hierarchy of Proinflammatory Cytokines in Ocular Inflammation.

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Da Cunha, A P; Zhang, Q; Prentiss, M; Wu, X Q; Kainz, V; Xu, Y Y; Vrouvlianis, J; Li, H; Rangaswamy, N; Leehy, B; McGee, T L; Bell, C L; Bigelow, C E; Kansara, V; Medley, Q; Huang, Q; Wu, H Y

2018-04-01

The concept of tissue-dependent cytokine hierarchy has been demonstrated in a number of diseases, but it has not been investigated in ophthalmic diseases. Here, we evaluated the functional hierarchy of interleukin-1β (IL-1β), IL-6, IL-17A, and tumor necrosis factor (TNF) in the induction of ocular inflammation. We delivered adeno-associated virus (AAV) vectors expressing IL-1β, IL-6, IL-17A, or TNF intravitreally in naïve C57/BL6 mice and compared and contrasted the inflammatory effects in the eye 5 weeks after AAV-mediated gene transfer. We also used an in vitro human system to test the effect of cytokines on barrier function. We found that IL-1β had the highest ability to initiate ocular inflammation. The continuous overexpression of IL-1β resulted in a significant upregulation of additional proinflammatory mediators in the eye. Using scanning laser ophthalmoscope and optical coherence tomography imaging techniques, we showed that a low dose of AAVIL-1β was sufficient and was as pathogenic as a high dose of TNF in inducing vascular leakage, retinal degeneration, and cellular infiltration. Furthermore, only a marginal increase in IL-1β was enough to cause cellular infiltration, thus confirming the highly pathogenic nature of IL-1β in the eye. Contrary to our expectation, IL-6 or IL-17A had minimal or no effect in the eye. To examine the clinical relevance of our findings, we used an impedance assay to show that IL-1β alone or TNF alone was able to cause primary human retinal endothelial cell barrier dysfunction in vitro. Again, IL-6 alone or IL-17A alone had no effect on barrier function; however, in the presence of IL-1β or TNF, IL-17A but not IL-6 may provide additive proinflammatory effects. Our studies demonstrate the existence of a functional hierarchy of proinflammatory cytokines in the eye, and we show that IL-1β is the most pathogenic when it is continuously expressed in the eye.

AltitudeOmics: Resetting of cerebrovascular CO2 reactivity following acclimatization to high altitude

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Jui-Lin eFan

2016-01-01

Full Text Available Previous studies reported enhanced cerebrovascular CO2 reactivity upon ascent to high altitude using linear models. However, there is evidence that this response may be sigmoidal in nature. Moreover, it was speculated that these changes at high altitude are mediated by alterations in acid-base buffering. Accordingly, we reanalyzed previously published data to assess middle cerebral blood flow velocity (MCAv responses to modified rebreathing at sea level (SL, upon ascent (ALT1 and following 16 days of acclimatization (ALT16 to 5,260 m in 21 lowlanders. Using sigmoid curve fitting of the MCAv responses to CO2, we found the amplitude (95% vs. 129%, SL vs. ALT1, 95% confidence intervals (CI [77, 112], [111, 145], respectively, P=0.024 and the slope of the sigmoid response (4.5 vs. 7.5 %/mmHg, SL vs. ALT1, 95% CIs [3.1, 5.9], [6.0, 9.0], respectively, P=0.026 to be enhanced at ALT1, which persisted with acclimatization at ALT16 (amplitude: 177%, 95% CI [139, 215], P<0.001; slope: 10.3 %/mmHg, 95% CI [8.2, 12.5], P=0.003 compared to SL. Meanwhile, the sigmoidal response midpoint was unchanged at ALT1 (SL: 36.5 mmHg; ALT1: 35.4 mmHg, 95% CIs [34.0, 39.0], [33.1, 37.7], respectively, P=0.982, while it was reduced by ~7 mmHg at ALT16 (28.6 mmHg, 95% CI [26.4, 30.8], P=0.001 vs. SL, indicating leftward shift of the cerebrovascular CO2 response to a lower arterial partial pressure of CO2 (PaCO2 following acclimatization to altitude. Sigmoid fitting revealed a leftward shift in the midpoint of the cerebrovascular response curve which could not be observed with linear fitting. These findings demonstrate that there is resetting of the cerebrovascular CO2 reactivity operating point to a lower PaCO2 following acclimatization to high altitude. This cerebrovascular resetting is likely the result of an altered acid-base buffer status resulting from prolonged exposure to the severe hypocapnia associated with ventilatory acclimatization to high altitude.

Predictive factors for cerebrovascular accidents after thoracic endovascular aortic repair.

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Mariscalco, Giovanni; Piffaretti, Gabriele; Tozzi, Matteo; Bacuzzi, Alessandro; Carrafiello, Giampaolo; Sala, Andrea; Castelli, Patrizio

2009-12-01

Cerebrovascular accidents are devastating and worrisome complications after thoracic endovascular aortic repair. The aim of this study was to determine cerebrovascular accident predictors after thoracic endovascular aortic repair. Between January 2001 and June 2008, 76 patients treated with thoracic endovascular aortic repair were prospectively enrolled. The study cohort included 61 men; mean age was 65.4 +/- 16.8 years. All patients underwent a specific neurologic assessment on an hourly basis postoperatively to detect neurologic deficits. Cerebrovascular accidents were diagnosed on the basis of physical examination, tomography scan or magnetic resonance imaging, or autopsy. Cerebrovascular accidents occurred in 8 (10.5%) patients, including 4 transient ischemic attack and 4 major strokes. Four cases were observed within the first 24-hours. Multivariable analysis revealed that anatomic incompleteness of the Willis circle (odds ratio [OR] 17.19, 95% confidence interval [CI] 2.10 to 140.66), as well as the presence of coronary artery disease (OR 6.86, 95 CI% 1.18 to 40.05), were independently associated with postoperative cerebrovascular accident development. Overall hospital mortality was 9.2%, with no significant difference for patients hit by cerebrovascular accidents (25.0% vs 7.3%, p = 0.102). Preexisting coronary artery disease, reflecting a severe diseased aorta and anomalies of Willis circle are independent cerebrovascular accident predictors after thoracic endovascular aortic repair procedures. A careful evaluation of the arch vessels and cerebral vascularization should be mandatory for patients suitable for thoracic endovascular aortic repair.

Influence of cerebrovascular disease on brain networks in prodromal and clinical Alzheimer's disease.

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Chong, Joanna Su Xian; Liu, Siwei; Loke, Yng Miin; Hilal, Saima; Ikram, Mohammad Kamran; Xu, Xin; Tan, Boon Yeow; Venketasubramanian, Narayanaswamy; Chen, Christopher Li-Hsian; Zhou, Juan

2017-11-01

Network-sensitive neuroimaging methods have been used to characterize large-scale brain network degeneration in Alzheimer's disease and its prodrome. However, few studies have investigated the combined effect of Alzheimer's disease and cerebrovascular disease on brain network degeneration. Our study sought to examine the intrinsic functional connectivity and structural covariance network changes in 235 prodromal and clinical Alzheimer's disease patients with and without cerebrovascular disease. We focused particularly on two higher-order cognitive networks-the default mode network and the executive control network. We found divergent functional connectivity and structural covariance patterns in Alzheimer's disease patients with and without cerebrovascular disease. Alzheimer's disease patients without cerebrovascular disease, but not Alzheimer's disease patients with cerebrovascular disease, showed reductions in posterior default mode network functional connectivity. By comparison, while both groups exhibited parietal reductions in executive control network functional connectivity, only Alzheimer's disease patients with cerebrovascular disease showed increases in frontal executive control network connectivity. Importantly, these distinct executive control network changes were recapitulated in prodromal Alzheimer's disease patients with and without cerebrovascular disease. Across Alzheimer's disease patients with and without cerebrovascular disease, higher default mode network functional connectivity z-scores correlated with greater hippocampal volumes while higher executive control network functional connectivity z-scores correlated with greater white matter changes. In parallel, only Alzheimer's disease patients without cerebrovascular disease showed increased default mode network structural covariance, while only Alzheimer's disease patients with cerebrovascular disease showed increased executive control network structural covariance compared to controls. Our

In-hospital Mortality from Cerebrovascular Disease in the Province of Cienfuegos

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Ada Sánchez Lozano

2014-12-01

Full Text Available Background: cerebrovascular disease is the second leading cause of death in some countries, causing 10 million annual deaths. In-hospital mortality from these diseases is high in our country. Objective: to describe mortality from cerebrovascular disease at the Dr. Gustavo Aldereguía Lima University General Hospital in Cienfuegos during 2006-2010. Methods: a retrospective case series study involving all patients (4449 diagnosed with cerebrovascular disease discharged from the Dr. Gustavo Aldereguía Lima University General Hospital from January 1st, 2006 to December 31, 2010 was conducted. The variables analyzed included age, sex, status at discharge, types of cerebrovascular disease and hospital stay. Results: in-hospital mortality from cerebrovascular disease in the study period was 23.8 %. It was higher in men than in women (24.5 % and 22.9 %, respectively. According to the type of cerebrovascular disease, mortality rate of ischemic stroke was 20 %, subarachnoid hemorrhage, 22.4 % and intraparenchymal hemorrhage, 71.2 %. Conclusions: in-hospital mortality from cerebrovascular disease in Cienfuegos shows a downward trend, though it increased in 2010. It was more common in men. Death from stroke tends to decrease and, to a lesser extent, mortality due to brain hemorrhage, which remains high. There is also an increase in subarachnoid hemorrhage.

Clinical application of SPECT and PET in cerebrovascular disease

International Nuclear Information System (INIS)

Ra, Young Shin

2003-01-01

Single photon emission computed tomography(SPECT) and positron emission tomography(PET) are modern imaging techniques that allow for both qualitative are quantitative assessment of hemodynamic changes in cerebrovascular diseases. SPECT has been becoming an indispensable method to investigate regional cerebral blood flow because equipment and isotope are easily available in most general hospitals. Acetazolamide stress SPECT has also been proved to be useful to evaluate the cerebrovascular reserve of occlusive cerebrovascular diseases and to select surgical candidate. PET has gained wide spread clinical use in the evaluation of the hemodynamic and metabolic consequences of extracranial or intracranial arterial obstructive disease despite its complexity and limited availability. PET has been established as an invaluable tool in the pathophysilogy investigation of acute ischemic stroke. The potentials, limitations, and clinical applications of SPECT and PET in various cerebrovascular diseases will be discussed in this article with reviews of literatures

Clinical application of SPECT and PET in cerebrovascular disease

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Ra, Young Shin [Ulsan University College of Medicine, Seoul (Korea, Republic of)

2003-02-01

Single photon emission computed tomography(SPECT) and positron emission tomography(PET) are modern imaging techniques that allow for both qualitative are quantitative assessment of hemodynamic changes in cerebrovascular diseases. SPECT has been becoming an indispensable method to investigate regional cerebral blood flow because equipment and isotope are easily available in most general hospitals. Acetazolamide stress SPECT has also been proved to be useful to evaluate the cerebrovascular reserve of occlusive cerebrovascular diseases and to select surgical candidate. PET has gained wide spread clinical use in the evaluation of the hemodynamic and metabolic consequences of extracranial or intracranial arterial obstructive disease despite its complexity and limited availability. PET has been established as an invaluable tool in the pathophysilogy investigation of acute ischemic stroke. The potentials, limitations, and clinical applications of SPECT and PET in various cerebrovascular diseases will be discussed in this article with reviews of literatures.

Sildenafil increases cerebrovascular reactivity: a transcranial Doppler study.

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Diomedi, M; Sallustio, F; Rizzato, B; Ferrante, F; Leone, G; Spera, E; Scarfini, M; Bernardi, G

2005-09-27

The authors performed a double-blind, placebo-controlled study in 28 patients to evaluate the effects of sildenafil on cerebral hemodynamics. A significant improvement of cerebrovascular reactivity, without any modification of other variables, was recorded 1 hour after the administration of 50 mg sildenafil. Further investigations are needed to evaluate whether cerebrovascular reactivity improvement could contribute to triggering sildenafil-induced migraine.

Association between aerobic fitness and cerebrovascular function with neurocognitive functions in healthy, young adults.

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Hwang, Jungyun; Kim, Kiyoung; Brothers, R Matthew; Castelli, Darla M; Gonzalez-Lima, F

2018-05-01

Studies of the effects of physical activity on cognition suggest that aerobic fitness can improve cognitive abilities. However, the physiological mechanisms for the cognitive benefit of aerobic fitness are less well understood. We examined the association between aerobic fitness and cerebrovascular function with neurocognitive functions in healthy, young adults. Participants aged 18-29 years underwent measurements of cerebral vasomotor reactivity (CVMR) in response to rebreathing-induced hypercapnia, maximal oxygen uptake (VO 2 max) during cycle ergometry to voluntary exhaustion, and simple- and complex-neurocognitive assessments at rest. Ten subjects were identified as having low-aerobic fitness (LF aerobic fitness (HF > 80th fitness percentile). There were no LF versus HF group differences in cerebrovascular hemodynamics during the baseline condition. Changes in middle cerebral artery blood velocity and CVMR during hypercapnia were elevated more in the HF than the LF group. Compared to the LF, the HF performed better on a complex-cognitive task assessing fluid reasoning, but not on simple attentional abilities. Statistical modeling showed that measures of VO 2 max, CVMR, and fluid reasoning were positively inter-correlated. The relationship between VO 2 max and fluid reasoning, however, did not appear to be reliably mediated by CVMR. In conclusion, a high capacity for maximal oxygen uptake among healthy, young adults was associated with greater CVMR and better fluid reasoning, implying that high-aerobic fitness may promote cerebrovascular and cognitive functioning abilities.

Comparative magnetic resonance imaging findings between gliomas and presumed cerebrovascular accidents in dogs.

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Cervera, Vicente; Mai, Wilfried; Vite, Charles H; Johnson, Victoria; Dayrell-Hart, Betsy; Seiler, Gabriela S

2011-01-01

Cerebrovascular accidents, or strokes, and gliomas are common intraaxial brain lesions in dogs. An accurate differentiation of these two lesions is necessary for prognosis and treatment decisions. The magnetic resonance (MR) imaging characteristics of 21 dogs with a presumed cerebrovascular accident and 17 with a glioma were compared. MR imaging findings were reviewed retrospectively by three observers unaware of the final diagnosis. Statistically significant differences between the appearance of gliomas and cerebrovascular accidents were identified based on lesion location, size, mass effect, perilesional edema, and appearance of the apparent diffusion coefficient map. Gliomas were predominantly located in the cerebrum (76%) compared with presumed cerebrovascular accidents that were located mainly in the cerebellum, thalamus, caudate nucleus, midbrain, and brainstem (76%). Gliomas were significantly larger compared with presumed cerebrovascular accidents and more commonly associated with mass effect and perilesional edema. Wedge-shaped lesions were seen only in 19% of presumed cerebrovascular accidents. Between the three observers, 10-47% of the presumed cerebrovascular accidents were misdiagnosed as gliomas, and 0-12% of the gliomas were misdiagnosed as cerebrovascular accidents. Diffusion weighted imaging increased the accuracy of the diagnosis for both lesions. Agreement between observers was moderate (kappa = 0.48, P < 0.01).

Oxidative stress upregulates the NMDA receptor on cerebrovascular endothelium.

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Betzen, Christian; White, Robin; Zehendner, Christoph M; Pietrowski, Eweline; Bender, Bianca; Luhmann, Heiko J; Kuhlmann, Christoph R W

2009-10-15

N-methyl-d-aspartate receptor (NMDA-R)-mediated oxidative stress has been implicated in blood-brain barrier (BBB) disruption in a variety of neuropathological diseases. Although some interactions between both phenomena have been elucidated, possible influences of reactive oxygen species (ROS) on the NMDA-R itself have so far been neglected. The objective of this study was to examine how the cerebroendothelial NMDA-R is affected by exposure to oxidative stress and to assess possible influences on BBB integrity. RT-PCR confirmed several NMDA-R subunits (NR1, NR2B-D) expressed in the bEnd3 cell line (murine cerebrovascular endothelial cells). NR1 protein expression after exposure to ROS was observed via in-cell Western. The functionality of the expressed NMDA-R was determined by measuring DiBAC fluorescence in ROS-preexposed cells upon stimulation with the specific agonist NMDA. Finally, the effects on barrier integrity were evaluated using the ECIS system to detect changes in monolayer impedance upon NMDA-R stimulation after exposure to ROS. The expression of NR1 significantly (p<0.001) increased 72 h after 30 min exposure to superoxide (+33.8+/-7.5%), peroxynitrite (+84.9+/-10.7%), or hydrogen peroxide (+92.8+/-7.6%), resulting in increased cellular response to NMDA-R stimulation and diminished monolayer impedance. We conclude that oxidative stress upregulates NMDA-R on cerebrovascular endothelium and thus heightens susceptibility to glutamate-induced BBB disruption.

Oxidative stress and proinflammatory cytokines contribute to demyelination and axonal damage in a cerebellar culture model of neuroinflammation.

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di Penta, Alessandra; Moreno, Beatriz; Reix, Stephanie; Fernandez-Diez, Begoña; Villanueva, Maite; Errea, Oihana; Escala, Nagore; Vandenbroeck, Koen; Comella, Joan X; Villoslada, Pablo

2013-01-01

Demyelination and axonal damage are critical processes in the pathogenesis of multiple sclerosis (MS). Oxidative stress and pro-inflammatory cytokines elicited by inflammation mediates tissue damage. To monitor the demyelination and axonal injury associated with microglia activation we employed a model using cerebellar organotypic cultures stimulated with lipopolysaccharide (LPS). Microglia activated by LPS released pro-inflammatory cytokines (IL-1β, IL-6 and TNFα), and increased the expression of inducible nitric oxide synthase (iNOS) and production of reactive oxygen species (ROS). This activation was associated with demyelination and axonal damage in cerebellar cultures. Axonal damage, as revealed by the presence of non-phosphorylated neurofilaments, mitochondrial accumulation in axonal spheroids, and axonal transection, was associated with stronger iNOS expression and concomitant increases in ROS. Moreover, we analyzed the contribution of pro-inflammatory cytokines and oxidative stress in demyelination and axonal degeneration using the iNOS inhibitor ethyl pyruvate, a free-scavenger and xanthine oxidase inhibitor allopurinol, as well as via blockage of pro-inflammatory cytokines using a Fc-TNFR1 construct. We found that blocking microglia activation with ethyl pyruvate or allopurinol significantly decreased axonal damage, and to a lesser extent, demyelination. Blocking TNFα significantly decreased demyelination but did not prevented axonal damage. Moreover, the most common therapy for MS, interferon-beta, was used as an example of an immunomodulator compound that can be tested in this model. In vitro, interferon-beta treatment decreased oxidative stress (iNOS and ROS levels) and the release of pro-inflammatory cytokines after LPS stimulation, reducing axonal damage. The model of neuroinflammation using cerebellar culture stimulated with endotoxin mimicked myelin and axonal damage mediated by the combination of oxidative stress and pro-inflammatory cytokines

The Sarcoglycan complex is expressed in the cerebrovascular system and is specifically regulated by astroglial Cx30 channels

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Anne-Cécile eBoulay

2015-02-01

Full Text Available Astrocytes, the most prominent glial cell type in the brain, send specialized processes called endfeet, around blood vessels and express a large molecular repertoire regulating the cerebrovascular system physiology. One of the most striking properties of astrocyte endfeet is their enrichment in gap junction protein Connexin 43 and 30 (Cx43 and Cx30 allowing in particular for direct intercellular trafficking of ions and small signaling molecules through perivascular astroglial networks. In this study, we addressed the specific role of Cx30 at the gliovascular interface. Using an inactivation mouse model for Cx30 (Cx30Δ/Δ, we showed that absence of Cx30 does not affect blood-brain barrier (BBB organization and permeability. However, it results in the cerebrovascular fraction, in a strong upregulation of Sgcg encoding γ-Sarcoglycan (SG, a member of the Dystrophin-associated protein complex (DAPC connecting cytoskeleton and the extracellular matrix. The same molecular event occurs in Cx30T5M/T5M mutated mice, where Cx30 channels are closed, demonstrating that Sgcg regulation relied on Cx30 channel functions. We further characterized the expression of other Sarcoglycan complex (SGC molecules in the cerebrovascular system and showed the presence of α-, β-, δ-, γ-, ε- and ζ- SG, as well as Sarcospan. Their expression was however not modified in Cx30Δ/Δ. These results suggest that a full SGC might be present in the cerebrovascular system, and that expression of one of its member, γ-Sarcoglycan, depends on Cx30 channels. As described in skeletal muscles, the SGC may contribute to membrane stabilization and signal transduction in the cerebrovascular system, which may therefore be regulated by Cx30 channel-mediated functions.

Edaravone Attenuates the Proinflammatory Response in Amyloid-β-Treated Microglia by Inhibiting NLRP3 Inflammasome-Mediated IL-1β Secretion

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Hong-Mei Wang

2017-10-01

Full Text Available Background/Aims: Microglial activation is an important pathological feature in the brains of patients with Alzheimer’s disease (AD, and amyloid-β (Aβ peptides play a crucial role in microglial activation. In addition, edaravone (EDA was recently shown to suppress oxidative stress and proinflammatory cytokine production in APPswePS1dE9 (APP/PS1 mice. However, the mechanism by which EDA inhibits the Aβ-induced proinflammatory response in microglia is poorly understood. Methods: The mitochondrial membrane potential (∆ψm was evaluated using JC-1 staining. Intracellular reactive oxygen species (ROS and mitochondrial ROS levels were detected using CM-H2DCFDA and MitoSOXTM Red, respectively. The levels of CD11b, NLRP3, pro-caspase-1 and manganese superoxide dismutase (SOD-2 were observed by western blotting, and the levels of interleukin-1beta (IL-1β in culture supernatants were quantified using an ELISA kit. Results: Aβ induced microglia activation and mitochondrial dysfunction. In addition, mitochondrial dysfunction was associated with ROS accumulation and activation of the NLRP3 inflammasome. Importantly, Aβ induced activation of the NLRP3 inflammasome, leading to caspase-1 activation and IL-1β release in microglia. Moreover, EDA obviously attenuated the depolarization of ∆ψm, reduced mitochondria-derived ROS production and increased SOD-2 activity, resulting in the suppression of NLRP3 inflammasome-mediated IL-1β secretion in Aβ-treated microglia. Conclusion: EDA is a mitochondria-targeted antioxidant and exhibits anti-inflammatory effects on Aβ-treated microglia.

[Early management of cerebrovascular accidents].

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Libot, Jérômie; Guillon, Benoit

2013-01-01

A cerebrovascular accident requires urgent diagnosis and treatment.The management of a stroke must be early and adapted in order to improve the overall clinical outcome and lower the risk of mortality.

Histamine mediates the pro-inflammatory effect of latex of Calotropis procera in rats

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Yatin M. Shivkar

2003-01-01

Full Text Available Introduction: Calotropis procera is known to produce contact dermatitis and the latex of this plant produces intense inflammation when injected locally. However, the precise mode of its pro-inflammatory effect is not known. In present study we have pharmacologically characterized the inflammation induced by latex of C. procera in a rat paw edema model and determined the role of histamine in latex-induced inflammation.

The pro-inflammatory effects of platelet contamination in plasma and mitigation strategies for avoidance

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Bercovitz, R. S.; Kelher, M. R.; Khan, S. Y.; Land, K. J.; Berry, T. H.; Silliman, C. C.

2013-01-01

Background and Objectives Plasma and platelet concentrates are disproportionately implicated in transfusion-related acute lung injury (TRALI). Platelet-derived pro-inflammatory mediators, including soluble CD40 ligand (sCD40L), accumulate during storage. We hypothesized that platelet contamination induces sCD40L generation that causes neutrophil [polymorphonuclear leucocyte (PMN)] priming and PMN-mediated cytotoxicity. Materials and Methods Plasma was untreated, centrifuged (12 500 g) or separated from leucoreduced whole blood (WBLR) prior to freezing. Platelet counts and sCD40L concentrations were measured 1–5 days post-thaw. The plasma was assayed for PMN priming activity and was used in a two-event in vitro model of PMN-mediated human pulmonary microvascular endothelial cell (HMVEC) cytotoxicity. Results Untreated plasma contained 42 ± 4.2 × 103/μl platelets, which generated sCD40L accumulation (1.6-eight-fold vs. controls). Priming activity and HMVEC cytotoxicity were directly proportional to sCD40L concentration. WBLR and centrifugation reduced platelet and sCD40L contamination, abrogating the pro-inflammatory potential. Conclusion Platelet contamination causes sCD40L accumulation in stored plasma that may contribute to TRALI. Platelet reduction is potentially the first TRALI mitigation effort in plasma manufacturing. PMID:22092073

Heterotrimeric G protein-dependent WNT-5A signaling to ERK1/2 mediates distinct aspects of microglia proinflammatory transformation

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Halleskog Carina

2012-05-01

Thus, WNT-5A-induced and G protein-dependent signaling to ERK1/2 is important for the regulation of proinflammatory responses in mouse primary microglia cells. We show for the first time that WNT-5A/G protein signaling mediates physiologically important processes in primary mammalian cells with natural receptor and G protein stochiometry. Consequently, WNT-5A emerges as an important means of astrocyte-microglia communication and we, therefore, suggest WNT-5A as a new player in neuroinflammatory conditions, such as neurodegenerative disease, hypoxia, stroke, injury and infection.

Cerebrovascular accidents associated with sorafenib in hepatocellular carcinoma.

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Saif, Muhammad W; Isufi, Iris; Peccerillo, Jennifer; Syrigos, Kostas N

2011-01-01

Sorafenib is an oral angiogenetic multikinase inhibitor approved in the treatment of renal and hepatocellular carcinoma. Bleeding and venous thrombotic events have been described with angiogenetic agents but cerebrovascular accidents are rarely reported. We report two cases of patients with hepatocellular carcinoma who developed a cerebrovascular accident while on sorafenib. Neither patient had any risk factors for the cerebrovascular events apart from gender and age in the second patient. Laboratory data were noncontributory. The head CT scan did not reveal acute abnormalities. No hemodynamically significant stenosis was visible in the carotid ultrasound, and the echocardiogram showed normal size of the heart chambers and normal systolic function of the left ventricle. Sorafenib was discontinued in both cases. Physicians should monitor patients receiving sorafenib for neurologic symptoms, and in the absence of other etiology, prompt discontinuation of this drug should be considered.

Chronic Pancreatitis Correlates With Increased Risk of Cerebrovascular Disease

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Wong, Tuck-Siu; Liao, Kuan-Fu; Lin, Chi-Ming; Lin, Cheng-Li; Chen, Wen-Chi; Lai, Shih-Wei

2016-01-01

Abstract The aim of this study is to explore whether there is a relationship between chronic pancreatitis and cerebrovascular disease in Taiwan. Using the claims data of the Taiwan National Health Insurance Program, we identified 16,672 subjects aged 20 to 84 years with a new diagnosis of chronic pancreatitis from 2000 to 2010 as the chronic pancreatitis group. We randomly selected 65,877 subjects aged 20 to 84 years without chronic pancreatitis as the nonchronic pancreatitis group. Both groups were matched by sex, age, comorbidities, and the index year of diagnosing chronic pancreatitis. The incidence of cerebrovascular disease at the end of 2011 was measured. The multivariable Cox proportional hazards regression model was used to measure the hazard ratio (HR) and 95% confidence interval (CI) for cerebrovascular disease risk associated with chronic pancreatitis and other comorbidities. The overall incidence of cerebrovascular disease was 1.24-fold greater in the chronic pancreatitis group than that in the nonchronic pancreatitis group (14.2 vs. 11.5 per 1000 person-years, 95% CI = 1.19–1.30). After controlling for confounding factors, the adjusted HR of cerebrovascular disease was 1.27 (95% CI = 1.19–1.36) for the chronic pancreatitis group as compared with the nonchronic pancreatitis group. Woman (adjusted HR = 1.41, 95% CI = 1.31–1.51), age (every 1 year, HR = 1.04, 95% CI = 1.04–1.05), atrial fibrillation (adjusted HR = 1.23, 95% CI = 1.02–1.48), chronic kidney disease (adjusted HR = 1.48, 95% CI = 1.31–1.67), chronic obstructive pulmonary disease (adjusted HR = 1.27, 95% CI = 1.16–1.40), diabetes mellitus (adjusted HR = 1.82, 95% CI = 1.72–1.92), hypertension (adjusted HR = 1.66, 95% CI = 1.56–1.76), and peripheral atherosclerosis (adjusted HR = 1.26, 95% CI = 1.06–1.51) were other factors significantly associated with cerebrovascular disease. Chronic pancreatitis is

The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells.

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Pourgholaminejad, Arash; Aghdami, Nasser; Baharvand, Hossein; Moazzeni, Seyed Mohammad

2016-09-01

Mesenchymal stem cells (MSCs), as cells with potential clinical utilities, have demonstrated preferential incorporation into inflammation sites. Immunophenotype and immunomodulatory functions of MSCs could alter by inflamed-microenvironments due to the local pro-inflammatory cytokine milieu. A major cellular mediator with specific function in promoting inflammation and pathogenicity of autoimmunity are IL-17-producing T helper 17 (Th17) cells that polarize in inflamed sites in the presence of pro-inflammatory cytokines such as Interleukin-1β (IL-1β), IL-6 and IL-23. Since MSCs are promising candidate for cell-based therapeutic strategies in inflammatory and autoimmune diseases, Th17 cell polarizing factors may alter MSCs phenotype and function. In this study, human bone-marrow-derived MSCs (BM-MSC) and adipose tissue-derived MSCs (AD-MSC) were cultured with or without IL-1β, IL-6 and IL-23 as pro-inflammatory cytokines. The surface markers and their differentiation capacity were measured in cytokine-untreated and cytokine-treated MSCs. MSCs-mediated immunomodulation was analyzed by their regulatory effects on mixed lymphocyte reaction (MLR) and the level of IL-10, TGF-β, IL-4, IFN-γ and TNF-α production as immunomodulatory cytokines. Pro-inflammatory cytokines showed no effect on MSCs morphology, immunophenotype and co-stimulatory molecules except up-regulation of CD45. Adipogenic and osteogenic differentiation capacity increased in CD45+ MSCs. Moreover, cytokine-treated MSCs preserved the suppressive ability of allogeneic T cell proliferation and produced higher level of TGF-β and lower level of IL-4. We concluded pro-inflammatory cytokines up-regulate the efficacy of MSCs in cell-based therapy of degenerative, inflammatory and autoimmune disorders. Copyright © 2016. Published by Elsevier Ltd.

Second-generation antipsychotics and risk of cerebrovascular accidents in the elderly.

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Percudani, Mauro; Barbui, Corrado; Fortino, Ida; Tansella, Michele; Petrovich, Lorenzo

2005-10-01

Concern has been recently raised for risperidone and olanzapine, possibly associated with cerebrovascular events in placebo-controlled trials conducted in elderly subjects with dementia. We investigated the relationship between exposure to second-generation antipsychotics (SGAs) and occurrence of cerebrovascular accidents in the elderly. From the regional database of hospital admissions of Lombardy, Italy, we extracted all patients aged 65 or older with cerebrovascular-related outcomes for the year 2002. From the regional database of prescriptions reimbursed by the National Health Service, we extracted all patients aged 65 or older who received antipsychotic prescriptions during 2001. The 2 databases were linked anonymously using the individual patient code. The proportions of cerebrovascular accidents were 3.31% (95% confidence interval, 2.95-3.69) in elderly subjects exclusively exposed to SGAs and 2.37% (95% confidence interval, 2.19-2.57) in elderly subjects exclusively exposed to first-generation antipsychotics. After background group differences were controlled for, exposure to SGAs significantly increased the risk of accidents. The analysis of cerebrovascular events in elderly subjects exposed to each individual SGA, in comparison with exposure to haloperidol, showed a significantly increased risk for risperidone only (adjusted odds ratio, 1.43; 95% confidence interval, 1.12-1.93). These data provide preliminary epidemiological evidence that exposure to SGAs, in comparison with exposure to first-generation antipsychotics, significantly increased the risk of cerebrovascular accidents in the elderly.

Psychological stress-induced cerebrovascular dysfunction: the role of metabolic syndrome and exercise.

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Brooks, Steven; Brnayan, Kayla W; DeVallance, Evan; Skinner, Roy; Lemaster, Kent; Sheets, J Whitney; Pitzer, Christopher R; Asano, Shinichi; Bryner, Randall W; Olfert, I Mark; Frisbee, Jefferson C; Chantler, Paul D

2018-05-01

What is the central question of this study? How does chronic stress impact cerebrovascular function and does metabolic syndrome accelerate the cerebrovascular adaptations to stress? What role does exercise training have in preventing cerebrovascular changes to stress and metabolic syndrome? What is the main finding and its importance? Stressful conditions lead to pathological adaptations of the cerebrovasculature via an oxidative nitric oxide pathway, and the presence of metabolic syndrome produces a greater susceptibility to stress-induced cerebrovascular dysfunction. The results also provide insight into the mechanisms that may contribute to the influence of stress and the role of exercise in preventing the negative actions of stress on cerebrovascular function and structure. Chronic unresolvable stress leads to the development of depression and cardiovascular disease. There is a high prevalence of depression with the metabolic syndrome (MetS), but to what extent the MetS concurrent with psychological stress affects cerebrovascular function is unknown. We investigated the differential effect of MetS on cerebrovascular structure/function in rats (16-17 weeks old) following 8 weeks of unpredictable chronic mild stress (UCMS) and whether exercise training could limit any cerebrovascular dysfunction. In healthy lean Zucker rats (LZR), UCMS decreased (28%, P stress and increased production of nitric oxide in the cerebral vessels. In conclusion, UCMS significantly impaired MCA structure and function, but the effects of UCMS were more substantial in OZR vs. LZR. Importantly, aerobic exercise when combined with UCMS prevented the MCA dysfunction through subtle shifts in nitric oxide and oxidative stress in the cerebral microvasculature. © 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.

Xanomeline suppresses excessive pro-inflammatory cytokine responses through neural signal-mediated pathways and improves survival in lethal inflammation

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Rosas-Ballina, Mauricio; Ferrer, Sergio Valdés; Dancho, Meghan; Ochani, Mahendar; Katz, David; Cheng, Kai Fan; Olofsson, Peder S.; Chavan, Sangeeta S.; Al-Abed, Yousef; Tracey, Kevin J.; Pavlov, Valentin A.

2014-01-01

Inflammatory conditions characterized by excessive immune cell activation and cytokine release, are associated with bidirectional immune system-brain communication, underlying sickness behavior and other physiological responses. The vagus nerve has an important role in this communication by conveying sensory information to the brain, and brain-derived immunoregulatory signals that suppress peripheral cytokine levels and inflammation. Brain muscarinic acetylcholine receptor (mAChR)-mediated cholinergic signaling has been implicated in this regulation. However, the possibility of controlling inflammation by peripheral administration of centrally-acting mAChR agonists is unexplored. To provide insight we used the centrally-acting M1 mAChR agonist xanomeline, previously developed in the context of Alzheimer’s disease and schizophrenia. Intraperitoneal administration of xanomeline significantly suppressed serum and splenic TNF levels, alleviated sickness behavior, and increased survival during lethal murine endotoxemia. The anti-inflammatory effects of xanomeline were brain mAChR-mediated and required intact vagus nerve and splenic nerve signaling. The anti-inflammatory efficacy of xanomeline was retained for at least 20h, associated with alterations in splenic lymphocyte, and dendritic cell proportions, and decreased splenocyte responsiveness to endotoxin. These results highlight an important role of the M1 mAChR in a neural circuitry to spleen in which brain cholinergic activation lowers peripheral pro-inflammatory cytokines to levels favoring survival. The therapeutic efficacy of xanomeline was also manifested by significantly improved survival in preclinical settings of severe sepsis. These findings are of interest for strategizing novel therapeutic approaches in inflammatory diseases. PMID:25063706

Oxidative Stress and Proinflammatory Cytokines Contribute to Demyelination and Axonal Damage in a Cerebellar Culture Model of Neuroinflammation

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di Penta, Alessandra; Moreno, Beatriz; Reix, Stephanie; Fernandez-Diez, Begoña; Villanueva, Maite; Errea, Oihana; Escala, Nagore; Vandenbroeck, Koen; Comella, Joan X.; Villoslada, Pablo

2013-01-01

Background Demyelination and axonal damage are critical processes in the pathogenesis of multiple sclerosis (MS). Oxidative stress and pro-inflammatory cytokines elicited by inflammation mediates tissue damage. Methods/Principal Findings To monitor the demyelination and axonal injury associated with microglia activation we employed a model using cerebellar organotypic cultures stimulated with lipopolysaccharide (LPS). Microglia activated by LPS released pro-inflammatory cytokines (IL-1β, IL-6 and TNFα), and increased the expression of inducible nitric oxide synthase (iNOS) and production of reactive oxygen species (ROS). This activation was associated with demyelination and axonal damage in cerebellar cultures. Axonal damage, as revealed by the presence of non-phosphorylated neurofilaments, mitochondrial accumulation in axonal spheroids, and axonal transection, was associated with stronger iNOS expression and concomitant increases in ROS. Moreover, we analyzed the contribution of pro-inflammatory cytokines and oxidative stress in demyelination and axonal degeneration using the iNOS inhibitor ethyl pyruvate, a free-scavenger and xanthine oxidase inhibitor allopurinol, as well as via blockage of pro-inflammatory cytokines using a Fc-TNFR1 construct. We found that blocking microglia activation with ethyl pyruvate or allopurinol significantly decreased axonal damage, and to a lesser extent, demyelination. Blocking TNFα significantly decreased demyelination but did not prevented axonal damage. Moreover, the most common therapy for MS, interferon-beta, was used as an example of an immunomodulator compound that can be tested in this model. In vitro, interferon-beta treatment decreased oxidative stress (iNOS and ROS levels) and the release of pro-inflammatory cytokines after LPS stimulation, reducing axonal damage. Conclusion The model of neuroinflammation using cerebellar culture stimulated with endotoxin mimicked myelin and axonal damage mediated by the combination of

Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification

DEFF Research Database (Denmark)

Nicolaides, Andrew N; Kakkos, Stavros K; Kyriacou, Efthyvoulos

2010-01-01

The purpose of this study was to determine the cerebrovascular risk stratification potential of baseline degree of stenosis, clinical features, and ultrasonic plaque characteristics in patients with asymptomatic internal carotid artery (ICA) stenosis.......The purpose of this study was to determine the cerebrovascular risk stratification potential of baseline degree of stenosis, clinical features, and ultrasonic plaque characteristics in patients with asymptomatic internal carotid artery (ICA) stenosis....

DHA suppresses Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

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Choi, Eun-Young; Jin, Ji-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

2014-04-14

Several reports have indicated that dietary intake of DHA is associated with lower prevalence of periodontitis. In the present study, we investigated the effect of DHA on the production of proinflammatory mediators in murine macrophage-like RAW264.7 cells stimulated with lipopolysaccharide (LPS) isolated from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. LPS was isolated from lyophilised P. intermedia ATCC 25,611 cells using the standard hot-phenol-water protocol. Culture supernatants were collected and assayed for NO, IL-1β and IL-6. Real-time PCR analysis was carried out to detect the expression of inducible NO synthase (iNOS), IL-1β, IL-6 and haeme oxygenase-1 (HO-1) mRNA. Immunoblot analysis was carried out to quantify the expression of iNOS and HO-1 protein and concentrations of signalling proteins. DNA-binding activities of NF-κB subunits were determined using an ELISA-based assay kit. DHA significantly attenuated the production of NO, IL-1β and IL-6 at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. DHA induced the expression of HO-1 in cells treated with P. intermedia LPS. Selective inhibition of HO-1 activity by tin protoporphyrin IX significantly mitigated the inhibitory effects of DHA on LPS-induced NO production. DHA significantly attenuated the phosphorylation of c-Jun N-terminal kinase induced by LPS. In addition, DHA suppressed the transcriptional activity of NF-κB by regulating the nuclear translocation and DNA-binding activity of NF-κB p50 subunit and inhibited the phosphorylation of signal transducer and activator of transcription 1. Further in vivo studies are needed to better evaluate the potential of DHA in humans as a therapeutic agent to treat periodontal disease.

Carrot juice ingestion attenuates high fructose-induced circulatory pro-inflammatory mediators in weanling Wistar rats.

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Mahesh, Malleswarapu; Bharathi, Munugala; Raja Gopal Reddy, Mooli; Pappu, Pranati; Putcha, Uday Kumar; Vajreswari, Ayyalasomayajula; Jeyakumar, Shanmugam M

2017-03-01

Adipose tissue, an endocrine organ, plays a vital role not only in energy homeostasis, but also in the development and/or progression of various metabolic diseases, such as insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD), via several factors and mechanisms, including inflammation. This study tested, whether carrot juice administration affected the adipose tissue development and its inflammatory status in a high fructose diet-induced rat model. For this purpose, male weanling Wistar rats were divided into four groups and fed either control or high fructose diet of AIN-93G composition with or without carrot juice ingestion for an 8 week period. Administration of carrot juice did not affect the adiposity and cell size of visceral fat depot; retroperitoneal white adipose tissue (RPWAT), which was corroborated with unaltered expression of genes involved in adipogenic and lipogenic pathways. However, it significantly reduced the high fructose diet-induced elevation of plasma free fatty acid (FFA) (P ≤ 0.05), macrophage chemoattractant protein 1 (MCP1) (P ≤ 0.01) and high sensitive C-reactive protein (hsCRP) (P ≤ 0.05) levels. Carrot juice administration attenuated the high fructose diet-induced elevation of levels of circulatory FFA and pro-inflammatory mediators; MCP1 and hsCRP without affecting the adiposity and cell size of visceral fat depot; RPWAT. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Industrial accident compensation insurance benefits on cerebrovascular and heart disease in Korea.

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Kim, Hyeong Su; Choi, Jae Wook; Chang, Soung Hoon; Lee, Kun Sei

2003-01-01

The purpose of this study is to present the importance of work-related cerebrovascular and heart disease from the viewpoint of expenses. Using the insurance benefit paid for the 4,300 cases, this study estimated the burden of insurance benefits spent on work-related cerebrovascular and heart disease. The number of cases with work-related cerebrovascular and heart disease per 100,000 insured workers were 3.36 in 1995; they were increased to 13.16 in 2000. By the days of occurrence, the estimated number of cases were 1,336 in 2001 (95% CI: 1,211-1,460 cases) and 1,769 in 2005 (CI: 1,610-1,931 cases). The estimated average insurance benefits paid per person with work-related cerebrovascular and heart disease was 75-19 million won for medical care benefit and 56 million won for other benefits except medical care. By considering the increase in insurance payment and average pay, the predicted insurance benefits for work-related cerebrovascular and heart disease was 107.9 billion won for the 2001 cohort and 192.4 billion won for the 2005 cohort. From an economic perspective, the results will be used as important evidence for the prevention and management of work-related cerebrovascular and heart disease. PMID:12923322

Mechanisms of Lethal Cerebrovascular Accidents in Turner Syndrome.

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Byard, Roger W

2016-05-01

A case of intracerebral hemorrhage in Turner syndrome is reported with an analysis of possible causes of cerebrovascular accidents in this condition. A 42-year-old woman with known Turner syndrome died soon after hospital admission having been found unconscious at her home address. At autopsy, she showed typical features of Turner syndrome with short stature, webbing of the neck, underdeveloped breasts, and an increased carrying angle of the arm. Death was due to a large left-sided intracerebral hemorrhage extending from the left basal ganglia into the white matter of the frontal lobe and lateral ventricle. Cases of unexpected death in Turner syndrome may arise from occult cerebrovascular accidents which may be hemorrhagic or nonhemorrhagic. Associated features include hypertension, vascular malformations, accelerated atherogenesis, cystic medial necrosis, and moyamoya syndrome. The possibility of Turner syndrome should be considered in cases where there has been a lethal cerebrovascular event in a younger woman. © 2016 American Academy of Forensic Sciences.

Unemployment, government healthcare spending, and cerebrovascular mortality, worldwide 1981-2009: an ecological study.

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Maruthappu, Mahiben; Shalhoub, Joseph; Tariq, Zoon; Williams, Callum; Atun, Rifat; Davies, Alun H; Zeltner, Thomas

2015-04-01

The global economic downturn has been associated with unemployment rises, reduced health spending, and worsened population health. This has raised the question of how economic variations affect health outcomes. We sought to determine the effect of changes in unemployment and government healthcare expenditure on cerebrovascular mortality globally. Data were obtained from the World Bank and World Health Organization. Multivariate regression analysis was used to assess the effect of changes in unemployment and government healthcare expenditure on cerebrovascular mortality. Country-specific differences in infrastructure and demographics were controlled for. One- to five-year lag analyses and robustness checks were conducted. Across 99 countries worldwide, between 1981 and 2009, every 1% increase in unemployment was associated with a significant increase in cerebrovascular mortality (coefficient 187, CI: 86.6-288, P = 0.0003). Every 1% rise in government healthcare expenditure, across both genders, was associated with significant decreases in cerebrovascular deaths (coefficient 869, CI: 383-1354, P = 0.0005). The association between unemployment and cerebrovascular mortality remained statistically significant for at least five years subsequent to the 1% unemployment rise, while the association between government healthcare expenditure and cerebrovascular mortality remained significant for two years. These relationships were both shown to be independent of changes in gross domestic product per capita, inflation, interest rates, urbanization, nutrition, education, and out-of-pocket spending. Rises in unemployment and reductions in government healthcare expenditure are associated with significant increases in cerebrovascular mortality globally. Clinicians may also need to consider unemployment as a possible risk factor for cerebrovascular disease mortality. © 2015 World Stroke Organization.

Cerebrovascular reserve capacity is impaired in patients with sickle cell disease

NARCIS (Netherlands)

Nur, Erfan; Kim, Yu-Sok; Truijen, Jasper; van Beers, Eduard J.; Davis, Shyrin C. A. T.; Brandjes, Dees P.; Biemond, Bart J.; van Lieshout, Johannes J.

2009-01-01

Sickle cell disease (SCD) is associated with a high incidence of ischemic stroke. SCD is characterized by hemolytic anemia, resulting in reduced nitric oxide-bioavailability, and by impaired cerebrovascular hemodynamics. Cerebrovascular CO2 responsiveness is nitric oxide dependent and has been

Beneficial effects of estrogen in a mouse model of cerebrovascular insufficiency.

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Naohito Kitamura

Full Text Available BACKGROUND: The M(5 muscarinic acetylcholine receptor is known to play a crucial role in mediating acetylcholine dependent dilation of cerebral blood vessels. Previously, we reported that male M(5 muscarinic acetylcholine knockout mice (M5R(-/- mice suffer from a constitutive constriction of cerebral arteries, reduced cerebral blood flow, dendritic atrophy, and short-term memory loss, without necrosis and/or inflammation in the brain. METHODOLOGY/PRINCIPAL FINDINGS: We employed the Magnetic Resonance Angiography to study the area of the basilar artery in male and female M5R(-/- mice. Here we show that female M5R(-/- mice did not show the reduction in vascular area observed in male M5R(-/- mice. However, ovariectomized female M5R(-/- mice displayed phenotypic changes similar to male M5R(-/- mice, strongly suggesting that estrogen plays a key role in the observed gender differences. We found that 17beta-estradiol (E2 induced nitric oxide release and ERK activation in a conditional immortalized mouse brain cerebrovascular endothelial cell line. Agonists of ERalpha, ERbeta, and GPR30 promoted ERK activation in this cell line. Moreover, in vivo magnetic resonance imaging studies showed that the cross section of the basilar artery was restored to normal in male M5R(-/- mice treated with E2. Treatment with E2 also improved the performance of male M5R(-/- mice in a cognitive test and reduced the atrophy of neural dendrites in the cerebral cortex and hippocampus. M5R(-/- mice also showed astrocyte swelling in cortex and hippocampus using the three-dimensional reconstruction of electron microscope images. This phenotype was reversed by E2 treatment, similar to the observed deficits in dendrite morphology and the number of synapses. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that M5R(-/- mice represent an excellent novel model system to study the beneficial effects of estrogen on cerebrovascular function and cognition. E2 may offer new therapeutic

Auditory Dysfunction in Patients with Cerebrovascular Disease

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Sadaharu Tabuchi

2014-01-01

Full Text Available Auditory dysfunction is a common clinical symptom that can induce profound effects on the quality of life of those affected. Cerebrovascular disease (CVD is the most prevalent neurological disorder today, but it has generally been considered a rare cause of auditory dysfunction. However, a substantial proportion of patients with stroke might have auditory dysfunction that has been underestimated due to difficulties with evaluation. The present study reviews relationships between auditory dysfunction and types of CVD including cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, cerebrovascular malformation, moyamoya disease, and superficial siderosis. Recent advances in the etiology, anatomy, and strategies to diagnose and treat these conditions are described. The numbers of patients with CVD accompanied by auditory dysfunction will increase as the population ages. Cerebrovascular diseases often include the auditory system, resulting in various types of auditory dysfunctions, such as unilateral or bilateral deafness, cortical deafness, pure word deafness, auditory agnosia, and auditory hallucinations, some of which are subtle and can only be detected by precise psychoacoustic and electrophysiological testing. The contribution of CVD to auditory dysfunction needs to be understood because CVD can be fatal if overlooked.

Apathy due to cerebrovascular accidents successfully treated with methylphenidate: a case series.

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Spiegel, David R; Kim, Jeffrey; Greene, Krista; Conner, Cheryl; Zamfir, Dan

2009-01-01

Apathy has been observed in various types of neuropsychiatric illness, including degenerative, traumatic, and cerebrovascular. In this article, the authors describe the neurobiology of cerebrovascular induced apathy and its treatment.

CD54-Mediated Interaction with Pro-inflammatory Macrophages Increases the Immunosuppressive Function of Human Mesenchymal Stromal Cells

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Nicolas Espagnolle

2017-04-01

Full Text Available Summary: Mesenchymal stromal cells (MSCs sense and modulate inflammation and represent potential clinical treatment for immune disorders. However, many details of the bidirectional interaction of MSCs and the innate immune compartment are still unsolved. Here we describe an unconventional but functional interaction between pro-inflammatory classically activated macrophages (M1MΦ and MSCs, with CD54 playing a central role. CD54 was upregulated and enriched specifically at the contact area between M1MФ and MSCs. Moreover, the specific interaction induced calcium signaling and increased the immunosuppressive capacities of MSCs dependent on CD54 mediation. Our data demonstrate that MSCs can detect an inflammatory microenvironment via a direct and physical interaction with innate immune cells. This finding opens different perspectives for MSC-based cell therapy. : Mesenchymal stromal cells (MSCs are promising for cell-based therapy in inflammatory disorders by switching off the immune response. Varin and colleagues demonstrate that MSCs and inflammatory macrophages communicate via an unconventional but functional interaction that strongly increases the immunosuppressive capacities of MSCs. This new communication between the innate immune system and MSCs opens new perspectives for MSC-based cell therapy. Keywords: macrophages, bone marrow mesenchymal stromal cells, functional interaction, CD54, immunosuppression, indoleamine 2,3-dioxygenase, cell therapy

Brain and Peripheral Atypical Inflammatory Mediators Potentiate Neuroinflammation and Neurodegeneration.

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Kempuraj, Duraisamy; Thangavel, Ramasamy; Selvakumar, Govindhasamy P; Zaheer, Smita; Ahmed, Mohammad E; Raikwar, Sudhanshu P; Zahoor, Haris; Saeed, Daniyal; Natteru, Prashant A; Iyer, Shankar; Zaheer, Asgar

2017-01-01

Neuroinflammatory response is primarily a protective mechanism in the brain. However, excessive and chronic inflammatory responses can lead to deleterious effects involving immune cells, brain cells and signaling molecules. Neuroinflammation induces and accelerates pathogenesis of Parkinson's disease (PD), Alzheimer's disease (AD) and Multiple sclerosis (MS). Neuroinflammatory pathways are indicated as novel therapeutic targets for these diseases. Mast cells are immune cells of hematopoietic origin that regulate inflammation and upon activation release many proinflammatory mediators in systemic and central nervous system (CNS) inflammatory conditions. In addition, inflammatory mediators released from activated glial cells induce neurodegeneration in the brain. Systemic inflammation-derived proinflammatory cytokines/chemokines and other factors cause a breach in the blood brain-barrier (BBB) thereby allowing for the entry of immune/inflammatory cells including mast cell progenitors, mast cells and proinflammatory cytokines and chemokines into the brain. These peripheral-derived factors and intrinsically generated cytokines/chemokines, α-synuclein, corticotropin-releasing hormone (CRH), substance P (SP), beta amyloid 1-42 (Aβ1-42) peptide and amyloid precursor proteins can activate glial cells, T-cells and mast cells in the brain can induce additional release of inflammatory and neurotoxic molecules contributing to chronic neuroinflammation and neuronal death. The glia maturation factor (GMF), a proinflammatory protein discovered in our laboratory released from glia, activates mast cells to release inflammatory cytokines and chemokines. Chronic increase in the proinflammatory mediators induces neurotoxic Aβ and plaque formation in AD brains and neurodegeneration in PD brains. Glial cells, mast cells and T-cells can reactivate each other in neuroinflammatory conditions in the brain and augment neuroinflammation. Further, inflammatory mediators from the brain can

Operative volume and outcomes of cerebrovascular neurosurgery in children.

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Bekelis, Kimon; Connolly, Ian D; Do, Huy M; Choudhri, Omar

2016-11-01

OBJECTIVE The impact of procedural volume on the outcomes of cerebrovascular surgery in children has not been determined. In this study, the authors investigated the association of operative volume on the outcomes of cerebrovascular neurosurgery in pediatric patients. METHODS The authors performed a cohort study of all pediatric patients who underwent a cerebrovascular procedure between 2003 and 2012 and were registered in the Kids' Inpatient Database (KID). To control for confounding, the authors used multivariable regression models, propensity-score conditioning, and mixed-effects analysis to account for clustering at the hospital level. RESULTS During the study period, 1875 pediatric patients in the KID underwent cerebrovascular neurosurgery and met the inclusion criteria for the study; 204 patients (10.9%) underwent aneurysm clipping, 446 (23.8%) underwent coil insertion for an aneurysm, 827 (44.1%) underwent craniotomy for arteriovenous malformation resection, and 398 (21.2%) underwent bypass surgery for moyamoya disease. Mixed-effects multivariable regression analysis revealed that higher procedural volume was associated with fewer inpatient deaths (OR 0.58; 95% CI 0.40-0.85), a lower rate of discharges to a facility (OR 0.87; 95% CI 0.82-0.92), and shorter length of stay (adjusted difference -0.22; 95% CI -0.32 to -0.12). The results in propensity-adjusted multivariable models were robust. CONCLUSIONS In a national all-payer cohort of pediatric patients who underwent a cerebrovascular procedure, the authors found that higher procedural volume was associated with fewer deaths, a lower rate of discharges to a facility, and decreased lengths of stay. Regionalization initiatives should include directing children with such rare pathologies to a center of excellence.

Results of CT brain examinations in cerebrovascular emergency

International Nuclear Information System (INIS)

Pinta, Z.; Dolansky, J.; Sorfova, J.; Jerie, T.

1987-01-01

Experience is briefly reported with CT (computerized tomography) diagnosis of cerebrovascular emergencies. It is pointed out that the introduction of computerized tomography greatly improved and made more accurate the diagnosis of focal ischemias and revealed significant differences in the foci of ischemia in hypertension patients and atherosclerosis patients without hypertension, and showed a higher incidence of intracerebral and subarachnoidal hemorrhages than previously thought. It is believed that knowledge gained thanks to CT (computerized tomography) will be of benefit to the primary and secondary prevention of cerebrovascular ischemias. (L.O.). 1 fig., 5 refs

A meta-analysis of cerebrovascular disease and hyperhomocysteinaemia

DEFF Research Database (Denmark)

Nielsen, G M; Tvedegaard, K C; Andersen, Niels Trolle

2000-01-01

Hyperhomocysteinaemia has been identified as a risk factor for stroke and cerebrovascular disease in several studies. To evaluate the evidence we performed a meta-analysis. We found 21 studies searching Medline from 1966-July 1999 using the key words homocysteine, homocystine and cerebrovascular...... was used. The reports on 8 cross-sectional and 4 longitudinal studies gave data on the mean and standard deviations of plasma or serum homocysteine for both cases and controls, and these studies were included in the meta-analysis. The results of the 5 excluded studies all pointed to a positive relationship...

CT, MRI and MRA of cerebrovascular malformations (report of 16 cases)

International Nuclear Information System (INIS)

Ding Qingguo; Hu Chunhong; Guo Liang; Ding Yi

2000-01-01

Objective: To evaluate the value of CT, MRI and MRA in cerebrovascular malformations. Methods: 16 cases of cerebrovascular malformations were confirmed by angiography and pathology, including 12 cases of arteriovenous malformations, 4 cases of cavernous angiomas. All of these cases were performed with CT, MRI non-contrast scan and 3D-TOF MRA. Results: CT appearances of AVM were mixed density with hypo-density, iso-density or hyper-density. Some had calcification or acute hemorrhage. MRI scan showed the dilated and tortuous nidus of AVMs on T 1 WI and T 2 WI. The appearances of hemorrhage were variable. Feeding arteries and draining veins were showed clearly on MRA. The typical sign of cavernous angiomas was mixed signals with hypointensity ring on MRI, while MRA could not provide much information. Conclusions: CT, MRI and MRA had different value in diagnosis of cerebrovascular malformations. CT combined with MRI and MRA could sharply improve the accuracy of diagnosis, and aid in the comprehensive evaluation of cerebrovascular malformations

Nutritionally Mediated Oxidative Stress and Inflammation

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Alexandra Muñoz

2013-01-01

Full Text Available There are many sources of nutritionally mediated oxidative stress that trigger inflammatory cascades along short and long time frames. These events are primarily mediated via NFκB. On the short-term scale postprandial inflammation is characterized by an increase in circulating levels of IL-6 and TNF-α and is mirrored on the long-term by proinflammatory gene expression changes in the adipocytes and peripheral blood mononuclear cells (PBMCs of obese individuals. Specifically the upregulation of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CXCL2/MIP-2α, and CXCL3/MIP-2β is noted because these changes have been observed in both adipocytes and PBMC of obese humans. In comparing numerous human intervention studies it is clear that pro-inflammatory and anti-inflammatory consumption choices mediate gene expression in humans adipocytes and peripheral blood mononuclear cells. Arachidonic acid and saturated fatty acids (SFAs both demonstrate an ability to increase pro-inflammatory IL-8 along with numerous other inflammatory factors including IL-6, TNFα, IL-1β, and CXCL1 for arachidonic acid and IGB2 and CTSS for SFA. Antioxidant rich foods including olive oil, fruits, and vegetables all demonstrate an ability to lower levels of IL-6 in PBMCs. Thus, dietary choices play a complex role in the mediation of unavoidable oxidative stress and can serve to exacerbate or dampen the level of inflammation.

Non-proinflammatory and responsive nanoplatforms for targeted treatment of atherosclerosis.

Science.gov (United States)

Dou, Yin; Chen, Yue; Zhang, Xiangjun; Xu, Xiaoqiu; Chen, Yidan; Guo, Jiawei; Zhang, Dinglin; Wang, Ruibing; Li, Xiaohui; Zhang, Jianxiang

2017-10-01

Atherosclerosis is the leading cause of many fatal cardiovascular and cerebrovascular diseases. Whereas nanomedicines are promising for targeted therapy of atherosclerosis, great challenges remain in development of effective, safe, and translational nanotherapies for its treatment. Herein we hypothesize that non-proinflammatory nanomaterials sensitive to low pH or high reactive oxygen species (ROS) may serve as effective platforms for triggerable delivery of anti-atherosclerotic therapeutics in cellular and tissue microenvironments of inflammation. To demonstrate this hypothesis, an acid-labile material of acetalated β-cyclodextrin (β-CD) (Ac-bCD) and a ROS-sensitive β-CD material (Ox-bCD) were separately synthesized by chemical modification of β-CD, which were formed into responsive nanoparticles (NPs). Ac-bCD NP was rapidly hydrolyzed in mildly acidic buffers, while hydrolysis of Ox-bCD NP was selectively accelerated by H 2 O 2 . Using an anti-atherosclerotic drug rapamycin (RAP), we found stimuli-responsive release of therapeutic molecules from Ac-bCD and Ox-bCD nanotherapies. Compared with non-responsive poly(lactide-co-glycolide) (PLGA)-based NP, Ac-bCD and Ox-bCD NPs showed negligible inflammatory responses in vitro and in vivo. By endocytosis in cells and intracellularly releasing cargo molecules in macrophages, responsive nanotherapies effectively inhibited macrophage proliferation and suppressed foam cell formation. After intraperitoneal (i.p.) delivery in apolipoprotein E-deficient (ApoE -/- ) mice, fluorescence imaging showed accumulation of NPs in atherosclerotic plaques. Flow cytometry analysis indicated that the lymphatic translocation mediated by neutrophils and monocytes/macrophages may contribute to atherosclerosis targeting of i.p. administered NPs, in addition to targeting via the leaky blood vessels. Correspondingly, i.p. treatment with different nanotherapies afforded desirable efficacies. Particularly, both pH and ROS

l-arginine and l-NMMA for assessing cerebral endothelial dysfunction in ischaemic cerebrovascular disease

DEFF Research Database (Denmark)

Karlsson, William K; Sørensen, Caspar G; Kruuse, Christina

2017-01-01

Endothelial dysfunction (ED), in particular cerebral ED, may be an essential biomarker for ischaemic cerebrovascular disease. However, there is no consensus on methods to best estimate cerebral ED. In this systematic review, we evaluate the use of l-arginine and NG -monomethyl-l-arginine (l......-NMMA) for assessment of cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was done. We included studies investigating cerebrovascular response to l-arginine or l-NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular disease. Seven studies (315 subjects) were eligible...... cerebrovascular disease. Inconsistencies in results were most likely due to variations in methods and included subject populations. In order to use cerebral ED as a prognostic marker, further studies are required to evaluate the association to cerebrovascular disease....

Risk factors of cerebrovascular diseases and their intervention and management

Directory of Open Access Journals (Sweden)

En XU

2015-01-01

Full Text Available Cerebrovascular diseases are important causes of clinical death and disability because of high prevalence and morbidity and easy to recurrence. A number of risk factors have involved in the progress of cerebrovascular diseases, which include uncontrolled and controlled risk factors. The former refers to old age, gender, low birth weight, race/ethnicity, genetic factors, etc. The latter includes hypertension, diabetes mellitus, atrial fibrillation and other cardiac diseases, dyslipidemia, asymptomatic carotid stenosis, obesity, smoking, unhealthy lifestyle, alcoholism, metabolic syndrome, hyperhomocysteinemia, etc. Meanwhile, hypertension is the most important one in the above-mentioned risk factors. It would effectively reduce or postpone the onset of cerebrovascular diseases through proper intervention and management on those risk factors. DOI: 10.3969/j.issn.1672-6731.2015.01.006

Relationship of Aphasia and Topography of Cerebrovascular Territories

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K. Ghandehari

2004-10-01

Full Text Available Aphasia is a common manifestation of stroke and evaluation of relationships of aphasia and brain topography could lead to better understanding of cognitive neurophysiology.Consecutive 100 stroke patients with aphasia admitted in Valie Asr hospital, Khorasan in 2003 enrulled in this prospective study. Diagnosis of stroke and aphasia was made by a neurolosist and topography of involved cerebrovascular territories confirmed by topographic maps of brain in CT scan. Global, Broca and Wernicke subtypes of aphasia constituted 52%, 40% and 6% of the cases respectively. Based on the usual nourishment of Broca and Wernicke areas by anterior and posterior cortical branches of the middle cerebral artery, 79% of Global, 47% of Broca and 50% of Wernicke aphasias had a compatible infarct topography. Other cases had no congruent infarct topography with involved linguistic area of their brain. Specific cerebrovascular topography for subtypes of aphasia in stroke patients was not found. The effects of cerebrovascular lesions on linguistic functions are not predictable by their topography in CT scan.

Bojesodok-eum, a Herbal Prescription, Ameliorates Acute Inflammation in Association with the Inhibition of NF-κB-Mediated Nitric Oxide and ProInflammatory Cytokine Production

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Kook Ho Sohn

2012-01-01

Full Text Available Bojesodok-eum (BSE is a herbal prescription consisting of Coptidis Rhizoma and Scutellariae Radix as main components. This paper investigated the effects of BSE on the induction of nitric oxide (NO, prostaglandin E2 (PGE2, and proinflammatory cytokines that are caused by lipopolysaccharide (LPS in murine macrophage cell line and on the paw edema formation in animals. Administration of BSE (0.3 g/kg and 1 g/kg in rats significantly inhibited carrageenan-induced paw edema formation, as did dexamethasone, an anti-inflammatory positive control drug. In cell model, treatment of BSE decreased the production of NO and PGE2 in RAW264.7 cells stimulated by LPS. BSE also inhibited the expression of iNOS and COX-2 protein as well as COX activity in a concentration-dependent manner. Consistently, BSE suppressed the ability of LPS to produce TNF-α, interleukin-1β, and interleukin-6. LPS treatment induced nuclear NF-κB level and I-κBα phosphorylation, which were inhibited subsequent treatment of BSE, suggesting its repression of LPS-inducible NF-κB activation. BSE abrogated the induction of NO, PGE2, and proinflammatory cytokines, as well as iNOS and COX-2 protein expression in RAW264.7 cells stimulated by LPS as mediated with NF-κB inhibition.

In-hospital cerebrovascular complications following orthotopic liver transplantation: A retrospective study

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Liang Zhijian

2008-12-01

Full Text Available Abstract Background Cerebrovascular complications are severe events following orthotopic liver transplantation (OLT. This study aimed to observe the clinical and neuroimaging features and possible risk factors of in-hospital cerebrovascular complications in the patients who underwent OLT. Patients and methods We retrospectively reviewed 337 consecutive patients who underwent 358 OLTs. Cerebrovascular complications were determined by clinical and neuroimaging manifestations, and the possible risk factors were analyzed in the patients with intracranial hemorrhage. Results Ten of 337 (3.0% patients developed in-hospital cerebrovascular complications (8 cases experienced intracranial hemorrhage and 2 cases had cerebral infarction, and 6 of them died. The clinical presentations were similar to common stroke, but with rapid deterioration at early stage. The hematomas on brain CT scan were massive, irregular, multifocal and diffuse, and most of them were located at brain lobes and might enlarge or rebleed. Infarcts presented lacunar and multifocal lesions in basal gangliar but with possible hemorrhagic transformation. The patients with intracranial hemorrhage had older age and a more frequency of systemic infection than non-intracranial hemorrhage patients. (P = 0.011 and 0.029, respectively. Conclusion Posttransplant cerebrovascular complications have severe impact on outcome of the patients who received OLT. Older age and systemic infection may be the possible risk factors of in-hospital intracranial hemorrhage following OLT.

Impact of EPA ingestion on COX- and LOX-mediated eicosanoid synthesis in skin with and without a pro-inflammatory UVR challenge – Report of a randomised controlled study in humans

Science.gov (United States)

Pilkington, Suzanne M; Rhodes, Lesley E; Al-Aasswad, Naser M I; Massey, Karen A; Nicolaou, Anna

2014-01-01

Scope Eicosapentaenoic acid (EPA), abundant in oily fish, is reported to reduce skin inflammation and provide photoprotection, potential mechanisms include competition with arachidonic acid (AA) for metabolism by cyclooxygenases/lipoxygenases to less pro-inflammatory mediators. We thus examine impact of EPA intake on levels of AA, EPA and their resulting eicosanoids in human skin with or without ultraviolet radiation (UVR) challenge. Methods and results In a double-blind randomised controlled study, 79 females took 5 g EPA-rich or control lipid for 12 wk. Pre- and post-supplementation, red blood cell and skin polyunsaturated fatty acids were assessed by GC, and eicosanoids from unexposed and UVR-exposed skin by LC-MS/MS. Active supplementation increased red blood cell and dermal EPA versus control (both p skin (p skin; 12-hydroxyeicosatetraenoic acids:12-HEPE was lower in UVR-exposed skin (3:1 versus 11:1; p skin EPA:AA content, shifting eicosanoid synthesis towards less pro-inflammatory species, and promoting a regulatory milieu under basal conditions and in response to inflammatory insult. PMID:24311515

Globular adiponectin induces a pro-inflammatory response in human astrocytic cells

International Nuclear Information System (INIS)

Wan, Zhongxiao; Mah, Dorrian; Simtchouk, Svetlana; Klegeris, Andis; Little, Jonathan P.

2014-01-01

Highlights: • Adiponectin receptors are expressed in human astrocytes. • Globular adiponectin induces secretion of IL-6 and MCP-1 from cultured astrocytes. • Adiponectin may play a pro-inflammatory role in astrocytes. - Abstract: Neuroinflammation, mediated in part by activated brain astrocytes, plays a critical role in the development of neurodegenerative disorders, including Alzheimer’s disease (AD). Adiponectin is the most abundant adipokine secreted from adipose tissue and has been reported to exert both anti- and pro-inflammatory effects in peripheral tissues; however, the effects of adiponectin on astrocytes remain unknown. Shifts in peripheral concentrations of adipokines, including adiponectin, could contribute to the observed link between midlife adiposity and increased AD risk. The aim of the present study was to characterize the effects of globular adiponectin (gAd) on pro-inflammatory cytokine mRNA expression and secretion in human U373 MG astrocytic cells and to explore the potential involvement of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphatidylinositide 3-kinases (PI3 K) signaling pathways in these processes. We demonstrated expression of adiponectin receptor 1 (adipoR1) and adipoR2 in U373 MG cells and primary human astrocytes. gAd induced secretion of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and gene expression of IL-6, MCP-1, IL-1β and IL-8 in U373 MG cells. Using specific inhibitors, we found that NF-κB, p38MAPK and ERK1/2 pathways are involved in gAd-induced induction of cytokines with ERK1/2 contributing the most. These findings provide evidence that gAd may induce a pro-inflammatory phenotype in human astrocytes

Globular adiponectin induces a pro-inflammatory response in human astrocytic cells

Energy Technology Data Exchange (ETDEWEB)

Wan, Zhongxiao; Mah, Dorrian; Simtchouk, Svetlana [School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, BC (Canada); Klegeris, Andis [Department of Biology, University of British Columbia Okanagan, Kelowna, BC (Canada); Little, Jonathan P., E-mail: jonathan.little@ubc.ca [School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, BC (Canada)

2014-03-28

Highlights: • Adiponectin receptors are expressed in human astrocytes. • Globular adiponectin induces secretion of IL-6 and MCP-1 from cultured astrocytes. • Adiponectin may play a pro-inflammatory role in astrocytes. - Abstract: Neuroinflammation, mediated in part by activated brain astrocytes, plays a critical role in the development of neurodegenerative disorders, including Alzheimer’s disease (AD). Adiponectin is the most abundant adipokine secreted from adipose tissue and has been reported to exert both anti- and pro-inflammatory effects in peripheral tissues; however, the effects of adiponectin on astrocytes remain unknown. Shifts in peripheral concentrations of adipokines, including adiponectin, could contribute to the observed link between midlife adiposity and increased AD risk. The aim of the present study was to characterize the effects of globular adiponectin (gAd) on pro-inflammatory cytokine mRNA expression and secretion in human U373 MG astrocytic cells and to explore the potential involvement of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphatidylinositide 3-kinases (PI3 K) signaling pathways in these processes. We demonstrated expression of adiponectin receptor 1 (adipoR1) and adipoR2 in U373 MG cells and primary human astrocytes. gAd induced secretion of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and gene expression of IL-6, MCP-1, IL-1β and IL-8 in U373 MG cells. Using specific inhibitors, we found that NF-κB, p38MAPK and ERK1/2 pathways are involved in gAd-induced induction of cytokines with ERK1/2 contributing the most. These findings provide evidence that gAd may induce a pro-inflammatory phenotype in human astrocytes.

Autumn Weather and Winter Increase in Cerebrovascular Disease Mortality

LENUS (Irish Health Repository)

McDonagh, R

2016-11-01

Mortality from cerebrovascular disease increases in winter but the cause is unclear. Ireland’s oceanic climate means that it infrequently experiences extremes of weather. We examined how weather patterns relate to stroke mortality in Ireland. Seasonal data for Sunshine (% of average), Rainfall (% of average) and Temperature (degrees Celsius above average) were collected for autumn (September-November) and winter (December-February) using official Irish Meteorological Office data. National cerebrovascular mortality data was obtained from Quarterly Vital Statistics. Excess winter deaths were calculated by subtracting (nadir) 3rd quarter mortality data from subsequent 1st quarter data. Data for 12 years were analysed, 2002-2014. Mean winter mortality excess was 24.7%. Winter mortality correlated with temperature (r=.60, p=0.04). Rise in winter mortality correlated strongly with the weather in the preceding autumn (Rainfall: r=-0.19 p=0.53, Temperature: r=-0.60, p=0.03, Sunshine, r=0.58, p=0.04). Winter cerebrovascular disease mortality appears higher following cool, sunny autum

[Direct economic burden of cerebrovascular disease, during 1993-2008 in China].

Science.gov (United States)

Lu, Jing; Xu, Ling; Zhai, Yi; Zhang, Yaoguang; Lyu, Yuebin; Shi, Xiaoming

2014-11-01

To evaluate the status and trend of direct economic burden on cerebrovascular disease, from 1993 to 2008 in China. Using two-step model to calculate the economic cost with related trend of cerebrovascular disease within the population among the over 30-year-olds, from 1993 to 2008. Data was gathered from the National Health Service Surveys Analysis Reports of 1993, 1998, 2003 and 2008, that including both direct outpatient and inpatient cost. There appeared a significant increase on the burden of cerebrovascular diseases in the period of 15 years, with direct economic cost increasing from 8.473 billion to 103.125 billion RMB. In fact, the actual increase was 5.3 times, without the influence of the price. The average annual growth rate was 13.1%, exceeding the rate of total expenditure on health and GDP during the same time span. In addition, the growth rate in 2003-2008 was the fastest, which appeared to be 19.8%. Burden that caused by cerebrovascular disease on individuals and the whole society was heavy which warrented further theoratical and practical studies on it.

Diamox-enhanced brain SPECT in cerebrovascular diseases

International Nuclear Information System (INIS)

Choi, Yun Young

2007-01-01

Acute event in cerebrovascular disease is the second most common cause of death in Korea following cancer, and it can also cause serious neurologic deficits. Understanding of perfusion status is important for clinical applications in management of patients with cerebrovascular diseases, and then the attacks of ischemic neurologic symptoms and the risk of acute events can be reduced. Therefore, the normal vascular anatomy of brain, various clinical applications of acetazolamide-enhanced brain perfusion SPECT, including meaning and role of assessment of vascular reserve in carotid stenosis before procedure, in pediatric Moyamoya disease before and after operation, in prediction of development of hyperperfusion syndrome before procedure, and in prediction of vasospasm and of prognosis in subarachnoid hemorrhage were reviewed in this paper

HM-PAO SPECT in the diagnosis of cerebrovascular disease

International Nuclear Information System (INIS)

Cordes, M.; Rummeny, E.; Reissmann, M.; Fox, K.; Panitz, N.; Pfannenstiel, P.

1987-01-01

Single photon emission computed tomography (SPECT) after injection of 99m-Tc-HM-PAO was used to examine 34 patients whose clinical findings could not exclude a cerebrovascular disease. In all patients an X-ray computed tomography examination was inconclusive for the clinical-neurological findings. The regional cerebral bloodflow was pathologically disturbed in 10 of 34 patients in the HM-PAO SPECT examination. The detection of the regional cerebral bloodflow with HM-PAO SPECT is helpful in the diagnosis of cerebrovascular disease. (orig.) [de

Cerebral blood flow in sickle cell cerebrovascular disease

International Nuclear Information System (INIS)

Huttenlocher, P.R.; Moohr, J.W.; Johns, L.; Brown, F.D.

1984-01-01

Cerebral blood flow (CBF) has been studied by the xenon-133 ( 133 Xe) inhalation method in 16 children with suspected sickle cell cerebrovascular disease. Abnormalities consisting of decreases in total, hemispheral, or regional CBF were found in 17 of 26 studies. Eleven studies performed immediately after stroke, transient ischemic attack, or depression of state of alertness showed abnormalities. In addition to confirming regional cerebrovascular insufficiency in children with stroke due to major cerebral artery occlusion, the method detected diffuse decrease in CBF in children with stupor, coma, and seizures who had normal angiographic findings. In contrast, six of seven studies obtained after exchange transfusion or during maintenance on hypertransfusion therapy showed normal findings. The difference between results in patients with acute neurologic disturbances and those receiving transfusion therapy was statistically significant (P less than .005). The data indicate that the 133 Xe method reliably demonstrates cerebrovascular impairment in sickle cell disease. They also suggest that CBF changes in patients with sickle cell disease can be reversed by exchange transfusion and by hypertransfusion therapy. The 133 Xe CBF method may be useful for following up children with sickle cell disease who are at high risk for recurrent stroke

Dichotic auditory-verbal memory in adults with cerebro-vascular accident

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Samaneh Yekta

2014-01-01

Full Text Available Background and Aim: Cerebrovascular accident is a neurological disorder involves central nervous system. Studies have shown that it affects the outputs of behavioral auditory tests such as dichotic auditory verbal memory test. The purpose of this study was to compare this memory test results between patients with cerebrovascular accident and normal subjects.Methods: This cross-sectional study was conducted on 20 patients with cerebrovascular accident aged 50-70 years and 20 controls matched for age and gender in Emam Khomeini Hospital, Tehran, Iran. Dichotic auditory verbal memory test was performed on each subject.Results: The mean score in the two groups was significantly different (p<0.0001. The results indicated that the right-ear score was significantly greater than the left-ear score in normal subjects (p<0.0001 and in patients with right hemisphere lesion (p<0.0001. The right-ear and left-ear scores were not significantly different in patients with left hemisphere lesion (p=0.0860.Conclusion: Among other methods, Dichotic auditory verbal memory test is a beneficial test in assessing the central auditory nervous system of patients with cerebrovascular accident. It seems that it is sensitive to the damages occur following temporal lobe strokes.

LRP1 in Brain Vascular Smooth Muscle Cells Mediates Local Clearance of Alzheimer's Amyloid-β

OpenAIRE

Kanekiyo, Takahisa; Liu, Chia-Chen; Shinohara, Mitsuru; Li, Jie; Bu, Guojun

2012-01-01

Impaired clearance of amyloid-β (Aβ) is a major pathogenic event for Alzheimer’s disease (AD). Aβ depositions in brain parenchyma as senile plaques and along cerebrovasculature as cerebral amyloid angiopathy (CAA) are hallmarks of AD. A major pathway that mediates brain Aβ clearance is the cerebrovascular system where Aβ is eliminated through the blood-brain barrier (BBB) and/or degraded by cerebrovascular cells along the interstitial fluid drainage pathway. An Aβ clearance receptor, the low-...

Neuropsychological evaluation of children after ischemic cerebrovascular disease

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Guimarães Inês Elcione

2002-01-01

Full Text Available The purpose of this study is to associate neuropsychological evaluation with neuroimaging results in children with cerebral tomography indicating ischemic cerebrovascular disease (ICVD. Neuroimaging, neurological exams and neuropsychological instruments were used to evaluate five children. The study revealed that the cognitive and perceptive skills in two children were normal and motor sequele in four cases. The rhythm, visual and speech receptive skills remained unchanged. In four cases the SPECT exam showed regions with hypoperfusion and in four cases the EEG was normal. Neuropsychological, neurological and image indication some degree of sequele demonstrating the importance of follow up of children who had suffered cerebrovascular disease.

The complex contribution of NOS interneurons in the physiology of cerebrovascular regulation

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Sonia eDuchemin

2012-08-01

Full Text Available Following the discovery of the vasorelaxant properties of nitric oxide (NO by Furchgott and Ignarro, the finding by Bredt and coll. of a constitutively expressed NO synthase in neurons (nNOS led to the presumption that neuronal NO may control cerebrovascular functions. Consequently, numerous studies have sought to determine whether neuraly-derived NO is involved in the regulation of cerebral blood flow. Anatomically, axons, dendrites or somata of NO neurons have been found to contact the basement membrane of blood vessels or perivascular astrocytes in all segments of the cortical microcirculation. Functionally, various experimental approaches support a role of neuronal NO in the maintenance of resting cerebral blood flow as well as in the vascular response to neuronal activity. Since decades, it has been assumed that neuronal NO simply diffuses to the local blood vessels and produce vasodilation through a cGMP-PKG dependent mechanism. However, NO is not the sole mediator of vasodilation in the cerebral microcirculation and is known to interact with a myriad of signaling pathways also involved in vascular control. In addition, cerebrovascular regulation is the result of a complex orchestration between all components of the neurovascular unit (i.e. neuronal, glial and vascular cells also known to produce NO. In this review article, the role of NO interneuron in the regulation of cortical microcirculation will be discussed in the context of the neurovascular unit.

Pioglitazone improves reversal learning and exerts mixed cerebrovascular effects in a mouse model of Alzheimer's disease with combined amyloid-β and cerebrovascular pathology.

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Panayiota Papadopoulos

Full Text Available Animal models of Alzheimer's disease (AD are invaluable in dissecting the pathogenic mechanisms and assessing the efficacy of potential new therapies. Here, we used the peroxisome proliferator-activated receptor gamma agonist pioglitazone in an attempt to rescue the pathogenic phenotype in adult (12 months and aged (>18 months bitransgenic A/T mice that overexpress a mutated human amyloid precursor protein (APPSwe,Ind and a constitutively active form of transforming growth factor-β1 (TGF-β1. A/T mice recapitulate the AD-related cognitive deficits, amyloid beta (Aβ and cerebrovascular pathologies, as well as the altered metabolic and vascular coupling responses to increased neuronal activity. Pioglitazone normalized neurometabolic and neurovascular coupling responses to sensory stimulation, and reduced cortical astroglial and hippocampal microglial activation in both age groups. Spatial learning and memory deficits in the Morris water maze were not rescued by pioglitazone, but reversal learning was improved in the adult cohort notwithstanding a progressing Aβ pathology. While pioglitazone preserved the constitutive nitric oxide synthesis in the vessel wall, it unexpectedly failed to restore cerebrovascular reactivity in A/T mice and even exacerbated the dilatory deficits. These data demonstrate pioglitazone's efficacy on selective AD hallmarks in a complex AD mouse model of comorbid amyloidosis and cerebrovascular pathology. They further suggest a potential benefit of pioglitazone in managing neuroinflammation, cerebral perfusion and glucose metabolism in AD patients devoid of cerebrovascular pathology.

Combination of roflumilast with a beta-2 adrenergic receptor agonist inhibits proinflammatory and profibrotic mediator release from human lung fibroblasts

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Tannheimer Stacey L

2012-03-01

of the transcription factor cAMP response element-binding protein (CREB, an effect that was protein kinase A-dependent. Inhibition of protein kinase A was also found to reverse the inhibition of indacaterol and roflumilast on CTGF. Conclusions These results demonstrate that addition of roflumilast to a LABA inhibits primary fibroblast/myofibroblast function and therapeutically this may impact lung fibroblast proinflammatory and profibrotic mediator release which contributes to small airway remodeling and airway obstruction in COPD.

Revisión actualizada sobre enfermedad cerebrovascular: estudio de un caso

OpenAIRE

Bardají Fandos, Teodosia

2003-01-01

La enfermedad cerebrovascular (ECV), también denominada accidente cerebrovascular (ACV)o ictus, representa el 90% de las enfermedades neurológicas y constituye la tercera causa de muerte en la mayoría de los países desarrollados; en España representa la primera causa de muerte en mujeres de 75 años o más de edad.

Cerebrovascular disease in Utah, 1968--1971.

Science.gov (United States)

Lyon, J L; Bishop, C T; Nielsen, N S

1981-01-01

Utah mortality rates for cerebrovascular disease (ICD numbers 430--438) are 13% below U.S. rates. About 70% of Utahns are members of the Church of Jesus Christ of Latter-day Saints, commonly called Mormons of LDS, which proscribes use of tobacco and alcohol. Other studies on this group have found significantly lower occurrence of many cancers and ischemic heart disease. We tested the hypothesis that Utah's lower cerebrovascular disease (CBVD) mortality was contributed by the LDS population. We classified by religion all CBVD deaths (2,521) (except subarachnoid hemorrhage and cerebral embolism) occurring in the state in 1968--1971. No significant difference was found between LDS and non-LDS, but both groups had mortality rates below U.S. expectation. Although recent studies have reported smoking to be a risk factor for CBVD, we found no consistent difference between the LDS and non-LDS, even in the younger age groups. The results do not support the hypothesis that tobacco is an important etiologic agent in CBVD mortality.

Aspirin Allergy Desensitization in Cerebrovascular Disease

Science.gov (United States)

Zuckerman, Scott L; Seder, David B; Tsujiura, Crystiana; Cushing, Deborah; Gallup, Holly; Mocco, J; Hanel, Richard A; Ecker, Robert D

2014-01-01

Summary Aspirin (ASA) is the mainstay of treatment in cerebrovascular and systemic vascular disease. ASA hypersensitivity can pose a challenge to achieving optimum medical management prior to and after neurointerventional treatment. Desensitization to ASA is well described in the allergy and cardiovascular literature, but there are no similar discussions specific to neurointervention. The purpose of our study was to describe our experience with ASA hypersensitivity management and review the relevant literature. Two cases of patients with symptomatic cerebrovascular disease requiring neurointervention who were successfully desensitized to their ASA hypersensitivity prior to treatment are described. The subsequent literature is reviewed. Several ASA desensitization protocols exist and have been proven to successfully treat ASA hypersensitivity and allow for ASA therapy to be safely initiated. We describe several previously published protocols. ASA desensitization is a safe and simple way to manage ASA hypersensitivity. We provide comprehensive management guidelines for the neurointerventionalist engaging in ASA desensitization. PMID:24556294

Positron emission tomography in cerebrovascular disease

International Nuclear Information System (INIS)

Powers, W.J.

1988-01-01

This paper reviews and discusses those aspects of PET that are relevant to its current and future role in the clinical care of individual patients with ischemic cerebrovascular disease. In making a judgement about the value of any diagnostic test in the management of patients with a specific disease, one must decide what criteria to apply. It is tempting to conclude that any test that provides accurate data related to the pathophysiology of the disease under consideration must be clinically useful. This is not necessarily the case, however, if the data do not lead to better patient care by reducing either morbidity and mortality or expense. Such is currently the case for PET in human cerebrovascular disease. The data that PET can provide on CBF, CBV, OEF, and CMRO 2 are accurate and are directly related to the pathophysiology of cerebral ischemia. As yet, however, there is no evidence that the application of these data leads to improvements in patient care

Promotor polymorphisms in leukotriene C4 synthase and risk of ischemic cerebrovascular disease

DEFF Research Database (Denmark)

Freiberg, J.J.; Tybjaerg-Hansen, A.; Sillesen, H.

2008-01-01

OBJECTIVE: Cysteinyl leukotrienes are involved in inflammation and possibly in early carotid atherosclerosis. We tested the hypothesis that the -444 A/C and -1072 G/A polymorphisms of the leukotriene C(4) synthase associate with risk of ischemic cerebrovascular disease. METHODS AND RESULTS: We...... genotyped 10 592 individuals from the Danish general population, the Copenhagen City Heart Study. During 24 years of follow-up, 557 individuals developed ischemic cerebrovascular disease. The allele frequency was 0.07 for -1072 A and 0.29 for -444 C. Cumulative incidence for ischemic cerebrovascular disease...... was higher for -1072 AA versus GG genotype (log-rank: P=0.002), and lower for -444 CC versus AA genotype (log-rank: P=0.008). Combined genotypes showed corresponding cumulative incidence differences (log-rank: P=0.003). Multifactorially adjusted hazard ratios for ischemic cerebrovascular disease were 2...

Dietary Curcumin Ameliorates Aging-Related Cerebrovascular Dysfunction through the AMPK/Uncoupling Protein 2 Pathway

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Yunfei Pu

2013-11-01

Full Text Available Background/Aims: Age-related cerebrovascular dysfunction contributes to stroke, cerebral amyloid angiopathy, cognitive decline and neurodegenerative diseases. One pathogenic mechanism underlying this effect is increased oxidative stress. Up-regulation of mitochondrial uncoupling protein 2 (UCP2 plays a crucial role in regulating reactive oxygen species (ROS production. Dietary patterns are widely recognized as contributors to cardiovascular and cerebrovascular disease. In this study, we tested the hypothesis that dietary curcumin, which has an antioxidant effect, can improve aging-related cerebrovascular dysfunction via UCP2 up-regulation. Methods: The 24-month-old male rodents used in this study, including male Sprague Dawley (SD rats and UCP2 knockout (UCP2-/- and matched wild type mice, were given dietary curcumin (0.2%. The young control rodents were 6-month-old. Rodent cerebral artery vasorelaxation was detected by wire myograph. The AMPK/UCP2 pathway and p-eNOS in cerebrovascular and endothelial cells were observed by immunoblotting. Results: Dietary curcumin administration for one month remarkably restored the impaired cerebrovascular endothelium-dependent vasorelaxation in aging SD rats. In cerebral arteries from aging SD rats and cultured endothelial cells, curcumin promoted eNOS and AMPK phosphorylation, up-regulated UCP2 and reduced ROS production. These effects of curcumin were abolished by either AMPK or UCP2 inhibition. Chronic dietary curcumin significantly reduced ROS production and improved cerebrovascular endothelium-dependent relaxation in aging wild type mice but not in aging UCP2-/- mice. Conclusions: Curcumin improves aging-related cerebrovascular dysfunction via the AMPK/UCP2 pathway.

Associations of cerebrovascular metabolism genotypes with neuropsychiatric symptoms and age at onset of Alzheimer’s disease dementia

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Fabricio F. de Oliveira

Full Text Available Objective: To study associations of cerebrovascular metabolism genotypes and haplotypes with age at Alzheimer’s disease dementia (AD onset and with neuropsychiatric symptoms according to each dementia stage. Methods: Consecutive outpatients with late-onset AD were assessed for age at dementia onset and Neuropsychiatric Inventory scores according to Clinical Dementia Rating scores, apolipoprotein E gene (APOE haplotypes, angiotensin-converting enzyme gene (ACE variants rs1800764 and rs4291, low-density lipoprotein cholesterol receptor gene (LDLR variants rs11669576 and rs5930, cholesteryl ester transfer protein gene (CETP variants I422V and TaqIB, and liver X receptor beta gene (NR1H2 polymorphism rs2695121. Results: Considering 201 patients, only APOE-ɛ4 carriers had earlier dementia onset in multiple correlations, as well as less apathy, more delusions, and more aberrant motor behavior. Both ACE polymorphisms were associated with less intense frontally mediated behaviors. Regarding LDLR variants, carriers of the A allele of rs11669576 had less anxiety and more aberrant motor behavior, whereas carriers of the A allele of rs5930 had less delusions, less anxiety, more apathy, and more irritability. CETP variants that included G alleles of I422V and TaqIB were mostly associated with less intense frontally mediated behaviors, while severely impaired carriers of the T allele of rs2695121 had more anxiety and more aberrant motor behavior. Conclusion: Though only APOE haplotypes affected AD onset, cerebrovascular metabolism genotypes were associated with differences in several neuropsychiatric manifestations of AD.

Proinflammatory effects and oxidative stress within human bronchial epithelial cells exposed to atmospheric particulate matter (PM2.5 and PM>2.5) collected from Cotonou, Benin

International Nuclear Information System (INIS)

Cachon, Boris Fresnel; Firmin, Stéphane; Verdin, Anthony; Ayi-Fanou, Lucie

2014-01-01

After particulate matter (PM) collection in Cotonou (Benin), a complete physicochemical characterization of PM 2.5 and PM >2.5 was led. Then, their adverse health effects were evaluated by using in vitro culture of human lung cells. BEAS-2B (bronchial epithelial cells) were intoxicated during short-term exposure at increasing PM concentrations (1.5–96 μg/cm 2 ) to determine global cytotoxicity. Hence, cells were exposed to 3 and 12 μg/cm 2 to investigate the potential biological imbalance generated by PM toxicity. Our findings showed the ability of both PM to induce oxidative stress and to cause inflammatory cytokines/chemokines gene expression and secretion. Furthermore, PM were able to induce gene expression of enzymes involved in the xenobiotic metabolism pathway. Strong correlations between gene expression of metabolizing enzymes, proinflammatory responses and cell cycle alteration were found, as well as between proinflammatory responses and cell viability. Stress oxidant parameters were highly correlated with expression and protein secretion of inflammatory mediators. Highlights: • The aim of this study was to investigate the toxic potential of collected particles. • Toxicological effects were determined by using human bronchial epithelial cells. • Both particles induced oxidative stress, proinflammatory response and cell alterations. • Metabolizing enzymes were linked to proinflammatory responses and cell alterations. • Oxidative stress was highly correlated to the proinflammatory mediators. -- This study evidences the toxic potential of African fine and coarse particulate matters on respiratory epithelial cells

Induction of intestinal pro-inflammatory immune responses by lipoteichoic acid

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Zadeh Mojgan

2012-03-01

Full Text Available Abstract Background The cellular and molecular mechanisms of inflammatory bowel disease are not fully understood; however, data indicate that uncontrolled chronic inflammation induced by bacterial gene products, including lipoteichoic acid (LTA, may trigger colonic inflammation resulting in disease pathogenesis. LTA is a constituent glycolipid of Gram-positive bacteria that shares many inflammatory properties with lipopolysaccharide and plays a critical role in the pathogenesis of severe inflammatory responses via Toll-like receptor 2. Accordingly, we elucidate the role of LTA in immune stimulation and induced colitis in vivo. Methods To better understand the molecular mechanisms utilized by the intestinal microbiota and their gene products to induce or subvert inflammation, specifically the effect(s of altered surface layer protein expression on the LTA-mediated pro-inflammatory response, the Lactobacillus acidophilus surface layer protein (Slp genes encoding SlpB and SlpX were deleted resulting in a SlpB- and SlpX- mutant that continued to express SlpA (assigned as NCK2031. Results Our data show profound activation of dendritic cells by NCK2031, wild-type L. acidophilus (NCK56, and purified Staphylococcus aureus-LTA. In contrary to the LTA-deficient strain NCK2025, the LTA-expressing strains NCK2031 and NCK56, as well as S. aureus-LTA, induce pro-inflammatory innate and T cell immune responses in vivo. Additionally, neither NCK2031 nor S. aureus-LTA supplemented in drinking water protected mice from DSS-colitis, but instead, induced significant intestinal inflammation resulting in severe colitis and tissue destruction. Conclusions These findings suggest that directed alteration of two of the L. acidophilus NCFM-Slps did not ameliorate LTA-induced pro-inflammatory signals and subsequent colitis.

Clinical observation of cerebrovascular diseases current in Chernobyl accident liquidators

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Golovchenko, Yu.Yi.; Usatenko, O.G.; Romanenko, N.Yi.

1999-01-01

The results of the clinical follow up study (1993-1997) of cerebrovascular diseases development in the Chernobyl accident liquidators are presented. The syndrome of autonomous nervous system dysfunction following to an exposure to the Chernobyl accident consequences factors promotes to fast development of atherosclerosis and arterial hypertension. On the base of an analysis of the data obtained it was established that the primary diencephalic structures damage resulted in severe changes of different metabolic system, particularly in the cerebrovascular disorders development

Improved Metabolic Control in Diabetes, HSP60, and Proinflammatory Mediators

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Claudio Blasi

2012-01-01

Full Text Available The diabetes-atherosclerosis relationship remains to be fully defined. Repeated prolonged hyperglycemia, increased ROS production and endothelial dysfunction are important factors. One theory is that increased blood levels of heat shock protein (HSP60 are proinflammatory, through activation of innate immunity, and contribute to the progression of vascular disease. It was hypothesized that improvement of diabetes control in patients presenting with metabolic syndrome would lower HSP60, and anti-HSP60 antibody levels and decrease inflammatory markers. Paired sera of 17 Italian patients, before and after intensive treatment, were assayed for cytokines, HSP60 and anti-HSP60 antibodies. As expected, intensive treatment was associated with a decrease in HgbA1C (P<0.001 and BMI (P<0.001. After treatment, there was a significant decrease in IL-6 (P<0.05. HSP60 levels were before treatment −6.9+1.9, after treatment −7.1+2.0 ng/mL (P=ns. Overall HSP60 concentrations were lower than published reports. Anti-HSP60 antibody titers were high and did not decrease with treatment. In conclusion, improvement of diabetic control did not alter HSP60 concentrations or antiHSP60 antibody titers, but led to a reduction of IL-6 levels.

Neuroprotection of Scutellarin is mediated by inhibition of microglial inflammatory activation.

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Wang, S; Wang, H; Guo, H; Kang, L; Gao, X; Hu, L

2011-06-30

Inhibition of microglial over-reaction and the inflammatory processes may represent a therapeutic target to alleviate the progression of neurological diseases, such as neurodegenerative diseases and stroke. Scutellarin is the major active component of Erigeron breviscapus (Vant.) Hand-Mazz, a herbal medicine in treatment of cerebrovascular diseases for a long time in the Orient. In this study, we explored the mechanisms of neuroprotection by Scutellarin, particularly its anti-inflammatory effects in microglia. We observed that Scutellarin inhibited lipopolysaccharide (LPS)-induced production of proinflammatory mediators such as nitric oxide (NO), tumor necrosis factor α (TNFα), interleukin-1β (IL-1β) and reactive oxygen species (ROS), suppressed LPS-stimulated inducible nitric oxide synthase (iNOS), TNFα, and IL-1β mRNA expression in rat primary microglia or BV-2 mouse microglial cell line. Scutellarin inhibited LPS-induced nuclear translocation and DNA binding activity of nuclear factor κB (NF-κB). It repressed the LPS-induced c-Jun N-terminal kinase (JNK) and p38 phosphorylation without affecting the activity of extracellular signal regulated kinase (ERK) mitogen-activated protein kinase. Moreover, Scutellarin also inhibited interferon-γ (IFN-γ)-induced NO production, iNOS mRNA expression and transcription factor signal transducer and activator of transcription 1α (STAT1α) activation. Concomitantly, conditioned media from Scutellarin pretreated BV-2 cells significantly reduced neurotoxicity compared with conditioned media from LPS treated alone. Together, the present study reported the anti-inflammatory activity of Scutellarin in microglial cells along with their underlying molecular mechanisms, and suggested Scutellarin might have therapeutic potential for various microglia mediated neuroinflammation. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Influence of cerebrovascular arteriosclerosis on cerebral oxygenation during exercise

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Nagayama, Osamu; Koike, Akira; Hoshimoto, Masayo; Yamaguchi, Kaori; Tajima, Akihiko; Goda, Ayumi; Uejima, Tokuhisa; Aizawa, Tadanori; Itoh, Haruki

2007-01-01

Although it is assumed that cerebral oxygenation during exercise is influenced by both cardiopulmonary function and cerebrovascular arteriosclerosis, the latter factor has not been fully clarified. In the present study the relationship between the degree of cerebrovascular arteriosclerosis and cerebral oxygenation during exercise was investigated. A total of 109 patients (69 patients with coronary artery disease, 40 patients with hypertensive heart disease) (61.7±9.7 years) performed a symptom-limited exercise test with respiratory gas measurements (CPX). From the respiratory gas analysis, peak O 2 uptake (VO 2 ), the slope of the increase in VO 2 to the increase in work rate (ΔVO 2 /ΔWR), and the slope of the increase in ventilation to the increase in CO 2 output (VE/VCO 2 slope) were calculated. Oxyhemoglobin (O 2 Hb) at the forehead was monitored using near-infrared spectroscopy. The brain ischemic score was counted based upon fluid-attenuated inversion recovery images of magnetic resonance imaging and expressed from 0 to 4. When compared with patients with a lower ischemic score ( 2 Hb during exercise (-1.08±2.7 vs 0.77±4.1 μmol/L, p=0.011). Of brain ischemic score, left ventricular ejection fraction, peak VO 2 , ΔVO 2 /ΔWR, and the VE/VCO 2 slope, ΔVO 2 /ΔWR was found to be the sole independent index determining cerebral O 2 Hb during exercise. The CPX parameters were also significantly related to the degree of cerebrovascular arteriosclerosis. Although cerebral oxygenation during exercise is mainly related to cardiopulmonary function, the degree of cerebrovascular arteriosclerosis partly influences cerebral oxygenation in patients with risk factors for atherosclerosis. (author)

Positron emission tomography of cerebrovascular disorders

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Tanaka, Makoto; Hirai, Shunsaku; Kondo, Susumu; Ishiguro, Koji; Yamazaki, Tsuneo

1989-01-01

The pathogenesis of cerebrovascular disorders which present PET findings significantly different from those by XCT were studied. The PET study was performed using a steady state method of 15 O 2 and C 15 O 2 inhalation. The XCT was obtained simultaneously. Seventeen cases with marked discrepancies between XCT and PET findings were selected from 50 cases with cerebrovascular disorders. Twenty-two findings, shown by PET but not by XCT, from the 17 cases were classified into three major groups on the basis of pathogenesis. Group I was composed of nine cases suffering from ischemic stroke either without any cerebral cortical structural abnormalities or with an organic lesion not revealed by XCT. Ischemic penumbra or allied mechanism may explain the discrepancy in this group. Perfusion and metabolic decreases in the 11 patients in Group II were caused by the transneuronal effects (diaschisis) of stroke; cortical effect of a small white matter infarction; cortical effect of thalamic hemorrhage; and an effect of a cerebral hemispheric lesion on the contralateral cerebellar hemisphere (crossed cerebellar diaschisis). Group III consisted of two cases studied in a period of prominent fogging effect. Regional cerebral blood flow (CBF) and metabolic rates of oxygen (CMRO 2 ) of the cerebral cortex or cerebellar hemisphere were measured in the area where perfusional and/or metabolic changes were demonstrated and in the corresponding area in the contralateral hemisphere. Reduction rates of CBF and CMRO 2 in the former to those in the latter were calculated. Evaluation of the functional images in PET depends primarily on visual and qualitative analyses. The comparison of radioactivities in a diseased region and in a reference region can inform a semiquantitative parameter in SPECT. The reduction rates of CBF and CMRO 2 in PET will serve as a good guide to evaluate the parameter in SPECT of cerebrovascular disorders. (J.P.N.)

Antioxidants and Dementia Risk: Consideration through a Cerebrovascular Perspective

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Virginie Lam

2016-12-01

Full Text Available A number of natural and chemical compounds that exert anti-oxidative properties are demonstrated to be beneficial for brain and cognitive function, and some are reported to reduce the risk of dementia. However, the detailed mechanisms by which those anti-oxidative compounds show positive effects on cognition and dementia are still unclear. An emerging body of evidence suggests that the integrity of the cerebrovascular blood-brain barrier (BBB is centrally involved in the onset and progression of cognitive impairment and dementia. While recent studies revealed that some anti-oxidative agents appear to be protective against the disruption of BBB integrity and structure, few studies considered the neuroprotective effects of antioxidants in the context of cerebrovascular integrity. Therefore, in this review, we examine the mechanistic insights of antioxidants as a pleiotropic agent for cognitive impairment and dementia through a cerebrovascular axis by primarily focusing on the current available data from physiological studies. Conclusively, there is a compelling body of evidence that suggest antioxidants may prevent cognitive decline and dementia by protecting the integrity and function of BBB and, indeed, further studies are needed to directly examine these effects in addition to underlying molecular mechanisms.

Abnormal Cerebrovascular Reactivity in Patients with Parkinson’s Disease

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Carlos Henrique Ferreira Camargo

2015-01-01

Full Text Available Background. Orthostatic hypotension (OH is an important nonmotor manifestation of Parkinson’s disease (PD. Changes in cerebrovascular reactivity may contribute to this manifestation and can be monitored using transcranial Doppler. Objective. To identify possible changes in cerebrovascular reactivity in patients with OH. Methods. Twenty-two individuals were selected and divided into three groups: with and without OH and controls. Transcranial Doppler was used to assess basal mean blood flow velocity, postapnea mean blood flow velocity, percentage increase in mean blood flow velocity, and cerebrovascular reactivity as measured by the breath-holding index. Results. PD patients had lower values of basal velocity (p=0.019, postapnea velocity (p=0.0015, percentage increase in velocity (p=0.039, and breath-holding index (p=0.04 than the controls. Patients with OH had higher values of basal velocity (p=0.09 and postapnea velocity (p=0.19 but lower values of percentage increase in velocity (p=0.22 and breath-holding index (p=0.32 than patients without OH. Conclusions. PD patients present with abnormalities in a compensatory mechanism that regulates cerebral blood flow. OH could be an indicator of these abnormalities.

Protective effects of methanolic extract of Adhatoda vasica Nees leaf in collagen-induced arthritis by modulation of synovial toll-like receptor-2 expression and release of pro-inflammatory mediators

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Rana Adhikary

2016-03-01

Full Text Available RA associated with oxidative stress and chronic inflammation has been a major health problem among the population worldwide. In this study protective effect of methanolic extract of Adhatoda vasica leaf (AVE was evaluated on Collagen-induced arthritis in male Swiss albino mice. Post oral administration of AVE at 50, 100 and 200 mg/kg body weight doses decreased the arthritic index and footpad swelling. AVE administration diminished pro-inflammatory cytokines in serum and synovial tissues. Reduced chemokines and neutrophil infiltration in synovial tissues after AVE administration dictated its protective effect against RA. Decreased LPO content and SOD activity along with concomitant rise in GSH and CAT activities from liver, spleen and synovial tissues indicated regulation of oxidative stress by AVE. In addition decreased CRP in serum along with suppressed TLR-2 expression in CIA mice after AVE treatment was also observed. Protective effect of AVE in RA is further supported from histopathological studies which showed improvement during bone damage. In conclusion this study demonstrated A. vasica is capable of regulating oxidative stress during CIA and therefore down regulated local and systemic release of pro-inflammatory mediators, which might be linked to mechanism of decreasing synovial TLR-2 expression via downregulating release of its regular endogenous ligands like CRP.

Effects of Dietary Nitrates on Systemic and Cerebrovascular Hemodynamics

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Vernon Bond

2013-01-01

Full Text Available Cerebral blood flow dysregulation is often associated with hypertension. We hypothesized that a beetroot juice (BRJ treatment could decrease blood pressure and cerebrovascular resistance (CVR. We subjected 12 healthy females to control and BRJ treatments. Cerebrovascular resistance index (CVRI, systolic blood pressure (SBP, total vascular resistance (TVR, and the heart rate-systolic pressure product (RPP measured at rest and at two exercise workloads were lower after the BRJ treatment. CVRI, SBP, and RPP were lower without a lower TVR at the highest exercise level. These findings suggest improved systemic and cerebral hemodynamics that could translate into a dietary treatment for hypertension.

Results of CT brain examinations in cerebrovascular emergency. [computerized tomography

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Pinta, Z; Dolansky, J; Sorfova, J; Jerie, T

1987-07-01

Experience is briefly reported with CT (computerized tomography) diagnosis of cerebrovascular emergencies. It is pointed out that the introduction of computerized tomography greatly improved and made more accurate the diagnosis of focal ischemias and revealed significant differences in the foci of ischemia in hypertension patients and atherosclerosis patients without hypertension, and showed a higher incidence of intracerebral and subarachnoidal hemorrhages than previously thought. It is believed that knowledge gained thanks to CT (computerized tomography) will be of benefit to the primary and secondary prevention of cerebrovascular ischemias. (L.O.). 1 fig., 5 refs.

Suppression of pro-inflammatory T-cell responses by human mesothelial cells.

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Lin, Chan-Yu; Kift-Morgan, Ann; Moser, Bernhard; Topley, Nicholas; Eberl, Matthias

2013-07-01

Human γδ T cells reactive to the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) contribute to acute inflammatory responses. We have previously shown that peritoneal dialysis (PD)-associated infections with HMB-PP producing bacteria are characterized by locally elevated γδ T-cell frequencies and poorer clinical outcome compared with HMB-PP negative infections, implying that γδ T cells may be of diagnostic, prognostic and therapeutic value in acute disease. The regulation by local tissue cells of these potentially detrimental γδ T-cell responses remains to be investigated. Freshly isolated γδ or αβ T cells were cultured with primary mesothelial cells derived from omental tissue, or with mesothelial cell-conditioned medium. Stimulation of cytokine production and proliferation by peripheral T cells in response to HMB-PP or CD3/CD28 beads was assessed by flow cytometry. Resting mesothelial cells were potent suppressors of pro-inflammatory γδ T cells as well as CD4+ and CD8+ αβ T cells. The suppression of γδ T-cell responses was mediated through soluble factors released by primary mesothelial cells and could be counteracted by SB-431542, a selective inhibitor of TGF-β and activin signalling. Recombinant TGF-β1 but not activin-A mimicked the mesothelial cell-mediated suppression of γδ T-cell responses to HMB-PP. The present findings indicate an important regulatory function of mesothelial cells in the peritoneal cavity by dampening pro-inflammatory T-cell responses, which may help preserve the tissue integrity of the peritoneal membrane in the steady state and possibly during the resolution of acute inflammation.

[Effect of Chinese drugs for activating blood circulation and removing blood stasis on carotid atherosclerosis and ischemic cerebrovascular events].

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Lu, Yan; Li, Tao

2014-03-01

To explore the effect of Chinese drugs for activating blood circulation and removing blood stasis (CDABCRBS) on carotid atherosclerotic plaque and long-term ischemic cerebrovascular events. By using open and control method, effect of 4 groups of platelet antagonists, platelet antagonists + CDABCRBS, platelet antagonists +atorvastatin, platelet antagonists +atorvastatin +CDABCRBS on carotid atherosclerotic plaque and long-term ischemic cerebrovascular events of 90 cerebral infarction patients were analyzed. Through survival analysis, there was no statistical difference in the effect of the 4 interventions on the variation of carotid stenosis rates or ischemic cerebrovascular events (P > 0.05). The occurrence of ischemic cerebrovascular events could be postponed by about 4 months in those treated with platelet antagonists + CDABCRBS and platelet antagonists + atorvastatin +CDABCRBS. By multivariate Logistic analysis, age, hypertension, and clopidogrel were associated with stenosis of extracranial carotid arteries (P cerebrovascular accidents (P cerebrovascular events. CDABCRBS could effectively prolong the occurrence time of ischemic cerebrovascular events.

L-arginine and L-NMMA for Assessing Cerebral Endothelial Dysfunction in Ischemic Cerebrovascular Disease: A Systematic Review

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Karlsson, William Kristian; Sørensen, Caspar Godthaab; Kruuse, Christina

2017-01-01

Endothelial dysfunction (ED), in particular cerebral ED, may be an essential biomarker for ischaemic cerebrovascular disease. However, there is no consensus on methods to best estimate cerebral ED. In this systematic review, we evaluate the use of l-arginine and NG -monomethyl-l-arginine (l......-NMMA) for assessment of cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was done. We included studies investigating cerebrovascular response to l-arginine or l-NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular disease. Seven studies (315 subjects) were eligible...... cerebrovascular disease. Inconsistencies in results were most likely due to variations in methods and included subject populations. In order to use cerebral ED as a prognostic marker, further studies are required to evaluate the association to cerebrovascular disease....

Cognitive performance correlates with cerebrovascular impairments in multi-infarct dementia

International Nuclear Information System (INIS)

Judd, B.W.; Meyer, J.S.; Rogers, R.L.; Gandhi, S.; Tanahashi, N.; Mortel, K.F.; Tawaklna, T.

1986-01-01

Cerebral blood flow (CBF) was measured by the 133 Xe inhalation method in patients with multi-infarct dementia (MID, N = 26), Alzheimer's dementia (AD, N = 19), and among age-matched, neurologically normal, healthy volunteers (N = 26). Cognitive performance was assessed in all subjects using the Cognitive Capacity Screening Examination (CCSE). Cerebral vasomotor responses were calculated from differences in values of mean hemispheric gray matter blood flow (Delta CBF) measured during inhalation of 100% oxygen (hyperoxia) compared with CBF measured while breathing room air. Significant correlations were found between CCSE performance and vasomotor responsiveness in patients with MID (P less than .01), but not in patients with AD or in neurologically normal volunteers. Loss of vasomotor responsiveness is an indicator of cerebrovascular disease with rigidity and/or loss of reactivity of cerebral vessels, which impairs cerebrovascular responses to situational demands and predisposes to cerebral ischemia. Loss of cerebral vasomotor responsiveness among MID patients, which is a biologic marker of cerebrovascular disease, provides confirmatory evidence of the vascular etiology of MID and assists in separating MID from AD patients

Ambulatory versus home versus clinic blood pressure: the association with subclinical cerebrovascular diseases: the Ohasama Study.

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Hara, Azusa; Tanaka, Kazushi; Ohkubo, Takayoshi; Kondo, Takeo; Kikuya, Masahiro; Metoki, Hirohito; Hashimoto, Takanao; Satoh, Michihiro; Inoue, Ryusuke; Asayama, Kei; Obara, Taku; Hirose, Takuo; Izumi, Shin-Ichi; Satoh, Hiroshi; Imai, Yutaka

2012-01-01

The usefulness of ambulatory, home, and casual/clinic blood pressure measurements to predict subclinical cerebrovascular diseases (silent cerebrovascular lesions and carotid atherosclerosis) was compared in a general population. Data on ambulatory, home, and casual/clinic blood pressures and brain MRI to detect silent cerebrovascular lesions were obtained in 1007 subjects aged ≥55 years in a general population of Ohasama, Japan. Of the 1007 subjects, 583 underwent evaluation of the extent of carotid atherosclerosis. Twenty-four-hour, daytime, and nighttime ambulatory and home blood pressure levels were closely associated with the risk of silent cerebrovascular lesions and carotid atherosclerosis (all Ppressure values were simultaneously included in the same regression model, each of the ambulatory blood pressure values remained a significant predictor of silent cerebrovascular lesions, whereas home blood pressure lost its predictive value. Of the ambulatory blood pressure values, nighttime blood pressure was the strongest predictor of silent cerebrovascular lesions. The home blood pressure value was more closely associated with the risk of carotid atherosclerosis than any of the ambulatory blood pressure values when home and one of the ambulatory blood pressure values were simultaneously included in the same regression model. The casual/clinic blood pressure value had no significant association with the risk of subclinical cerebrovascular diseases. Although the clinical indications for ambulatory blood pressure monitoring and home blood pressure measurements may overlap, the clinical significance of each method for predicting target organ damage may differ for different target organs.

Advances in endovascular therapy for ischemic cerebrovascular diseases

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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

c-Myc is essential to prevent endothelial pro-inflammatory senescent phenotype.

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Victoria Florea

Full Text Available The proto-oncogene c-Myc is vital for vascular development and promotes tumor angiogenesis, but the mechanisms by which it controls blood vessel growth remain unclear. In the present work we investigated the effects of c-Myc knockdown in endothelial cell functions essential for angiogenesis to define its role in the vasculature. We provide the first evidence that reduction in c-Myc expression in endothelial cells leads to a pro-inflammatory senescent phenotype, features typically observed during vascular aging and pathologies associated with endothelial dysfunction. c-Myc knockdown in human umbilical vein endothelial cells using lentivirus expressing specific anti-c-Myc shRNA reduced proliferation and tube formation. These functional defects were associated with morphological changes, increase in senescence-associated-β-galactosidase activity, upregulation of cell cycle inhibitors and accumulation of c-Myc-deficient cells in G1-phase, indicating that c-Myc knockdown in endothelial cells induces senescence. Gene expression analysis of c-Myc-deficient endothelial cells showed that senescent phenotype was accompanied by significant upregulation of growth factors, adhesion molecules, extracellular-matrix components and remodeling proteins, and a cluster of pro-inflammatory mediators, which include Angptl4, Cxcl12, Mdk, Tgfb2 and Tnfsf15. At the peak of expression of these cytokines, transcription factors known to be involved in growth control (E2f1, Id1 and Myb were downregulated, while those involved in inflammatory responses (RelB, Stat1, Stat2 and Stat4 were upregulated. Our results demonstrate a novel role for c-Myc in the prevention of vascular pro-inflammatory phenotype, supporting an important physiological function as a central regulator of inflammation and endothelial dysfunction.

Elaeocarpusin Inhibits Mast Cell-Mediated Allergic Inflammation

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Min-Jong Kim

2018-06-01

Full Text Available Mast cells are major effector cells for allergic responses that act by releasing inflammatory mediators, such as histamine and pro-inflammatory cytokines. Accordingly, different strategies have been pursued to develop anti-allergic and anti-inflammatory candidates by regulating the function of mast cells. The purpose of this study was to determine the effectiveness of elaeocarpusin (EL on mast cell-mediated allergic inflammation. We isolated EL from Elaeocarpus sylvestris L. (Elaeocarpaceae, which is known to possess anti-inflammatory properties. For this study, various sources of mast cells and mouse anaphylaxis models were used. EL suppressed the induction of markers for mast cell degranulation, such as histamine and β-hexosaminidase, by reducing intracellular calcium levels. Expression of pro-inflammatory cytokines, such as tumor necrosis factor-α and IL-4, was significantly decreased in activated mast cells by EL. This inhibitory effect was related to inhibition of the phosphorylation of Fyn, Lyn, Syk, and Akt, and the nuclear translocation of nuclear factor-κB. To confirm the effect of EL in vivo, immunoglobulin E-mediated passive cutaneous anaphylaxis (PCA and ovalbumin-induced active systemic anaphylaxis (ASA models were induced. EL reduced the PCA reaction in a dose dependent manner. In addition, EL attenuated ASA reactions such as hypothemia, histamine release, and IgE production. Our results suggest that EL is a potential therapeutic candidate for allergic inflammatory diseases that acts via the inhibition of mast cell degranulation and expression of proinflammatory cytokines.

Identification of a novel proinflammatory human skin-homing Vγ9Vδ2 T cell subset with a potential role in psoriasis.

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Laggner, Ute; Di Meglio, Paola; Perera, Gayathri K; Hundhausen, Christian; Lacy, Katie E; Ali, Niwa; Smith, Catherine H; Hayday, Adrian C; Nickoloff, Brian J; Nestle, Frank O

2011-09-01

γδ T cells mediate rapid tissue responses in murine skin and participate in cutaneous immune regulation including protection against cancer. The role of human γδ cells in cutaneous homeostasis and pathology is characterized poorly. In this study, we show in vivo evidence that human blood contains a distinct subset of proinflammatory cutaneous lymphocyte Ag and CCR6-positive Vγ9Vδ2 T cells, which is rapidly recruited into perturbed human skin. Vγ9Vδ2 T cells produced an array of proinflammatory mediators including IL-17A and activated keratinocytes in a TNF-α- and IFN-γ-dependent manner. Examination of the common inflammatory skin disease psoriasis revealed a striking reduction of circulating Vγ9Vδ2 T cells in psoriasis patients compared with healthy controls and atopic dermatitis patients. Decreased numbers of circulating Vγ9Vδ2 T cells normalized after successful treatment with psoriasis-targeted therapy. Taken together with the increased presence of Vγ9Vδ2 T cells in psoriatic skin, these data indicate redistribution of Vγ9Vδ2 T cells from the blood to the skin compartment in psoriasis. In summary, we report a novel human proinflammatory γδ T cell involved in skin immune surveillance with immediate response characteristics and with potential clinical relevance in inflammatory skin disease.

The effects of natalizumab on inflammatory mediators in multiple sclerosis: prospects for treatment-sensitive biomarkers

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Khademi, M.; Bornsen, L.; Rafatnia, F.

2009-01-01

BACKGROUND: Natalizumab affects systemic cytokine expressions and clinical course in relapsing-remitting multiple sclerosis (RRMS). We analyzed levels of inflammatory cytokines in cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMCs), levels of matrix metalloproteinase (MMP...... showed the same deviations of mediators as those in relapse after natalizumab treatment. The open label clinical outcome measures were either stable or improved during therapy. CONCLUSIONS: Natalizumab attenuates pro-inflammatory mediators intrathecally and the reduced pro-inflammatory milieu may allow...... increased production of the anti-inflammatory mediator IL-10. The increased systemic cytokines may impede the improvement of certain clinical measures like fatigue. The affected mediators seem to be sensitive to an immune-modifying treatment which could be used as biomarkers for this therapy Udgivelsesdato...

NCX 4040, a nitric oxide-donating aspirin derivative, inhibits Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

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Choi, Eun-Young; Choe, So-Hui; Hyeon, Jin-Yi; Park, Hae Ryoun; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

2015-12-05

In this study, the effects and underlying mechanisms of NCX 4040, a nitric oxide (NO)-donating aspirin derivative, on the production of proinflammatory mediators were examined using murine macrophages exposed to lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in the etiology of periodontal disease. NCX 4040 significantly reduced P. intermedia LPS-induced production of inducible NO synthase (iNOS)-derived NO, IL-1β and IL-6 as well as their mRNA expression in RAW264.7 cells. Notably, NCX 4040 was much more effective than the parental compound aspirin in reducing LPS-induced production of inflammatory mediators. NCX 4040 induced the expression of heme oxygenase-1 (HO-1) in cells treated with P. intermedia LPS, and the suppressive effect of NCX 4040 on LPS-induced NO production was significantly reversed by SnPP, a competitive HO-1 inhibitor. NCX 4040 did not influence LPS-induced phosphorylation of JNK and p38. IκB-α degradation as well as nuclear translocation and DNA-binding activities of NF-κB p65 and p50 subunits induced by P. intermedia LPS were significantly reduced by NCX 4040. Besides, LPS-induced phosphorylation of STAT1 and STAT3 was significantly down-regulated by NCX 4040. Further, NCX 4040 elevated the SOCS1 mRNA in cells stimulated with LPS. This study indicates that NCX 4040 inhibits P. intermedia LPS-induced production of NO, IL-1β and IL-6 in murine macrophages through anti-inflammatory HO-1 induction and suppression of NF-κB, STAT1 and STAT3 activation, which is associated with the activation of SOCS1 signaling. NCX 4040 could potentially be a promising tool in the treatment of periodontal disease, although further studies are required to verify this. Copyright © 2015 Elsevier B.V. All rights reserved.

Crosstalk between HDAC6 and Nox2-based NADPH oxidase mediates HIV-1 Tat-induced pro-inflammatory responses in astrocytes

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Gi Soo Youn

2017-08-01

Full Text Available Histone deacetylase 6 (HDAC6 likely is important in inflammatory diseases. However, how HDAC6 exerts its effect on inflammatory processes remains unclear. HIV-1 transactivator of transcription (Tat activates NADPH oxidase resulting in generation of reactive oxygen species (ROS, leading to extensive neuro-inflammation in the central nervous system. We investigated the correlation of HDAC6 and NADPH oxidase in HIV-1 Tat-stimulated astrocytes. HDAC6 knockdown attenuated HIV-1 Tat-induced ROS generation and NADPH oxidase activation. HDAC6 knockdown suppressed HIV-1 Tat-induced expression of NADPH oxidase subunits, such as Nox2, p47phox, and p22phox. Specific inhibition of HDAC6 using tubastatin A suppressed HIV-1 Tat-induced ROS generation and activation of NADPH oxidase. N-acetyl cysteine, diphenyl iodonium, and apocynin suppressed HIV-1 Tat-induced expression of HDAC6 and the pro-inflammatory chemokines CCL2, CXCL8, and CXCL10. Nox2 knockdown attenuated HIV-1 Tat-induced HDAC6 expression and subsequent expression of chemokines. The collective results point to the potential crosstalk between HDAC6 and NADPH oxidase, which could be a combined therapeutic target for relief of HIV-1 Tat-mediated neuro-inflammation. Keywords: HIV-1 Tat, HDAC6, NADPH oxidase, ROS, Inflammation, Astrocytes

Imaging neurochemistry of cerebrovascular disease with PET and SPECT

International Nuclear Information System (INIS)

Hatazawa, J.; Shimosegawa, E.

1998-01-01

Pathophysiology od cerebrovascular disease has been studied by measuring cerebral blood flow and energy metabolism using single photon emission computed tomography (SPECT) and positron emission tomography (PET). These parameters are measures for brain tissue consisting of heterogeneous components such as neurons, glial cells, and blood vessels. It is still difficult to evaluate brain damages specifically involving either neurons or other components. Several trials were recently conducted to visualize neuron-specific injury in cerebrovascular disease by means of 11 C flumazenil for PET and 123 I-iomazenil for SPECT. These tracers selectively bind to central benzodiazepine receptor which is purely neuronal. A reduced accumulation of these ligands was found in the area surrounding the complete infarction and in the cortex remote from putaminal hemorrhage, indicating the existence of neuron specific injury not visualized by CT and MR. Neurological deficits were well correlated with the loss of cortical accumulation of these ligands. These preliminary studies indicated a potential of neurochemical imaging in cerebrovascular disease. Vulnerability to ischemia which may differ among brain tissue components, among subpopulations of neurons, and among pre-synaptic and post-synaptic functions can be more precisely examined. Neurochemical imaging can be also applied to reveal releases and re-organization of each neurotransmitter-acceptor system after stroke

Imaging neurochemistry of cerebrovascular disease with PET and SPECT

Energy Technology Data Exchange (ETDEWEB)

Hatazawa, J.; Shimosegawa, E. [Akita Research Institute of Brain and Blood Vessels, Akita (Japan). Dept. of Radiology and Nuclear Medicine

1998-09-01

Pathophysiology od cerebrovascular disease has been studied by measuring cerebral blood flow and energy metabolism using single photon emission computed tomography (SPECT) and positron emission tomography (PET). These parameters are measures for brain tissue consisting of heterogeneous components such as neurons, glial cells, and blood vessels. It is still difficult to evaluate brain damages specifically involving either neurons or other components. Several trials were recently conducted to visualize neuron-specific injury in cerebrovascular disease by means of {sup 11}C flumazenil for PET and {sup 123}I-iomazenil for SPECT. These tracers selectively bind to central benzodiazepine receptor which is purely neuronal. A reduced accumulation of these ligands was found in the area surrounding the complete infarction and in the cortex remote from putaminal hemorrhage, indicating the existence of neuron specific injury not visualized by CT and MR. Neurological deficits were well correlated with the loss of cortical accumulation of these ligands. These preliminary studies indicated a potential of neurochemical imaging in cerebrovascular disease. Vulnerability to ischemia which may differ among brain tissue components, among subpopulations of neurons, and among pre-synaptic and post-synaptic functions can be more precisely examined. Neurochemical imaging can be also applied to reveal releases and re-organization of each neurotransmitter-acceptor system after stroke.

Effect of high-intensity training on endothelial function in patients with cardiovascular and cerebrovascular disease

DEFF Research Database (Denmark)

Kolmos, Mia; Krawcyk, Rikke Steen; Kruuse, Christina

2016-01-01

OBJECTIVES: Exercise improves endothelial dysfunction, the key manifestation of cardiovascular and cerebrovascular disease, and is recommended in both cardiovascular and cerebrovascular rehabilitation. Disagreement remains, however, on the role of intensity of exercise. The purpose of this review...

N(6)-(2-Hydroxyethyl)adenosine in the Medicinal Mushroom Cordyceps cicadae Attenuates Lipopolysaccharide-Stimulated Pro-inflammatory Responses by Suppressing TLR4-Mediated NF-κB Signaling Pathways.

Science.gov (United States)

Lu, Meng-Ying; Chen, Chin-Chu; Lee, Li-Ya; Lin, Ting-Wei; Kuo, Chia-Feng

2015-10-23

Natural products play an important role in promoting health with relation to the prevention of chronic inflammation. N(6)-(2-Hydroxyethyl)adenosine (HEA), a physiologically active compound in the medicinal mushroom Cordyceps cicadae, has been identified as a Ca(2+) antagonist and shown to control circulation and possess sedative activity in pharmacological tests. The fruiting body of C. cicadae has been widely applied in Chinese medicine. However, neither the anti-inflammatory activities of HEA nor the fruiting bodies of C. cicadae have been carefully examined. In this study, we first cultured the fruiting bodies of C. cicadae and then investigated the anti-inflammatory activities of water and methanol extracts of wild and artificially cultured C. cicadae fruiting bodies. Next, we determined the amount of three bioactive compounds, adenosine, cordycepin, and HEA, in the extracts and evaluated their synergistic anti-inflammatory effects. Moreover, the possible mechanism involved in anti-inflammatory action of HEA isolated from C. cicadae was investigated. The results indicate that cordycepin is more potent than adenosine and HEA in suppressing the lipopolysaccharide (LPS)-stimulated release of pro-inflammatory cytokines by RAW 264.7 macrophages; however, no synergistic effect was observed with these three compounds. HEA attenuated the LPS-induced pro-inflammatory responses by suppressing the toll-like receptor (TLR)4-mediated nuclear factor-κB (NF-κB) signaling pathway. This result will support the use of HEA as an anti-inflammatory agent and C. cicadae fruiting bodies as an anti-inflammatory mushroom.

The effect of kineziotape on ankle joint in patients with cerebrovascular accident - objectivisation by a footscan

OpenAIRE

Veličková, Barbora

2013-01-01

BACHELOR THESIS ABSTRACT Name and surname: Barbora Veličková Supervisor: Bc. Tereza Chalupská Opponent: Title: The effect of kineziotape on ankle joint in patients with cerebrovascular accident - objectivisation by a footscan Key words: kineziotaping, ankle joint, cerebrovascular accident, Footscan® Abstract: This bachelor thesis is focused on on the effect of kineziotape on ankle joint in patients with cerebrovascular accident. The bachelor thesis consists of theoretical and practical part. ...

Clinical validation of nursing outcome mobility in patients with cerebrovascular accidents.

Science.gov (United States)

Moreira, Rafaella Pessoa; Araujo, Thelma Leite de; Lopes, Marcos Venicios de Oliveira; Cavalcante, Tahissa Frota; Guedes, Nirla Gomes; Chaves, Emília Soares; Portela, Regiane Campos; Holanda, Rose-Eloise

2016-12-15

To clinically validate the nursing outcome Mobility in patients with cerebrovascular accidents. Descriptive study, conducted in July 2011, with 38 outpatients, in northeastern Brazil. Data collection took place by evaluating two pairs of specialist nurses, where one pair used the instrument containing the constitutive and operational definitions of the indicators and magnitudes of the Mobility Outcome and the other pair without such definitions. When analyzing the evaluations among nurses, all indicators showed significant differences by the Friedman test (p cerebrovascular accident patient's mobility state.

SYSTOLIC HYPERTENSION. IMPACT ON CEREBROVASCULAR DISEASE

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Juan Eloy Cruz Quesada

2011-08-01

Full Text Available Background: Atherosclerosis is a multifactor process in which several risk factors are involved. It is the leading cause of death and morbidity in hospital admitted patients, and it may cause a marked decrease in blood flow to all organs of the body.Objective: To determine the impact of systolic hypertension on cerebrovascular disease.Methods: A cross-sectional, observational and analytical study was conducted in 59 death patients who suffered from hypertension. Cerebral arteries were analyzed and atherosclerotic lesion and its variety were quantified by using the atherometric system. The different types of hypertension were considered. Statistical (central tendency measures and comparative (comparison test based on Student’s arithmetic t-test procedures were used.Results: Recent strokes were more frequent in systodiastolic hypertensive patients. There was no significant difference in the injury onset age for both sexes, but women with systolic hypertension were significantly more damaged (from a morphometric point of view. Significant correlation for both groups of hypertensive patients was observed between type of stroke and atherometric system variables.Conclusions: Systolic hypertension is an important factor in the genesis of cerebrovascular disease and is associated with the progression of atherosclerotic plaque.

Asymptomatic Extracranial Artery Stenosis and the Risk of Cardiovascular and Cerebrovascular Diseases

OpenAIRE

Wang, Dandan; Wang, Jing; Jin, Cheng; Ji, Ruijun; Wang, Anxin; Li, Xin; Gao, Xiang; Wu, Shouling; Zhou, Yong; Zhao, Xingquan

2016-01-01

Asymptomatic extracranial artery stenosis (ECAS) is a well-known risk factor for stroke events, but it remains unclear whether it has the same role in predicting cardiovascular and cerebrovascular diseases, especially in China. We investigated the potential associations between ECAS, carotid plaque and carotid intima-media thickness and the new occurrence of cardiovascular and cerebrovascular diseases in the study. Out of 5440 study participants, 364 showed an asymptomatic ECAS at baseline, a...

Doença cerebrovascular na infância: II. Aspectos clínicos em 42 casos Cerebrovascular disease in children: II. Clinical aspects in 42 cases

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MARIA VALERIANA L. MOURA-RIBEIRO

1999-09-01

Full Text Available Entre 1990 e 1998 foram analisadas, do ponto de vista clínico, 42 crianças com diagnóstico de doença cerebrovascular, internadas no Hospital das Clínicas da FCM-UNICAMP. O distúrbio cerebrovascular mais frequente foi do tipo isquêmico com acometimento predominante da artéria cerebral média, sendo o quadro clínico agudo caracterizado por manifestações epilépticas e alterações motoras, principalmente em crianças de idade precoce. A avaliação do seguimento das crianças mostrou predomínio de sequelas motoras.We report the findings recorded in 42 children suffering cerebrovascular disease and assisted at the Hospital das Clínicas FCM-UNICAMP, over a 8 years period (January 1990 until April 1998. The ischemic type was the most common, and involvement of the middle cerebral artery, sudden onset of clinical manifestation with seizures and motor disability were more common in early aged children. Motor sequelae predominated in the follow-up of these children.

Costunolide inhibits proinflammatory cytokines and iNOS in activated murine BV2 microglia.

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Rayan, Nirmala Arul; Baby, Nimmi; Pitchai, Daisy; Indraswari, Fransisca; Ling, Eng-Ang; Lu, Jia; Dheen, Thameem

2011-06-01

Costunolide, a sesquiterpene lactone present in Costus speciosus root exerts a variety of pharmacological activity but its effects on neuroinflammation have not been studied. Microglia, the resident phagocytic cells in the central nervous system respond to neuroinflammation and their overwhelming response in turn aggravate brain damage during infection, ischemia and neurodegenerative diseases. In this study, we report the effect of Costunolide on the production of proinflammatory mediators and mechanisms involved in BV2 microglial cells stimulated with LPS. Costunolide attenuated the expression of tumour necrosis factor-alpha, interleukin-1,6, inducible nitric oxide synthase, monocyte chemotactic protein 1 and cyclooxygenase 2 in activated microglia. This Costunolide-mediated inhibition was correspondent with the inhibition of NFkappaB activation. It has been further shown that Costunolide suppressed MAPK pathway activation by inducing MKP-1 production. Collectively our results suggest that Costunolide shows an ability to inhibit expression of multiple neuroinflammatory mediators and this is attributable to the compounds inhibition of NFkappaB and MAPK activation. This novel role of Costunolide upon investigation may aid in developing better therapeutic strategies for treatment of neuroinflammatory diseases.

Clinical utility of carotid and transcranial ultrasound in cerebrovascular diseases

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Figueiredo L

2014-08-01

Full Text Available Lívia Figueiredo, Viviane F Zétola, Marcos C Lange Neurology Division, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil Abstract: Carotid and transcranial (CTU ultrasound is a useful tool in a number of clinical settings, particularly in cerebrovascular diseases. CTU is the only method that provides real-time determination of velocity and the spectral waveform of blood flow in the extracranial and basal intracranial arteries, and is effective in the detection of stenosis and occlusion. When transcranial ultrasound is considered, CTU is the only method that allows visualization of microembolic signals in the intracranial arteries. CTU makes a rapid differential diagnosis possible, improving therapeutic decision-making in acute stroke and determining the risk of recurrence and prognosis based on its findings. It is also the standard of care in children with sickle cell disease, when selecting patients for chronic blood transfusion, and for reducing the risk of ischemic stroke in these patients. CTU has some advantages, ie, relative simplicity in terms of interpretation and performance, and affordability, noninvasiveness, and portability. The main concern with ultrasound is that it is an operator-dependent tool and requires a high level of expertise and knowledge of three-dimensional cerebrovascular anatomy for correct interpretation of sonograms. The most significant limitation of intracranial evaluation by transcranial ultrasound is the absence of a suitable bone window in approximately 10% of patients. This paper gives an overview of the current utility and importance of CTU in the prevention and evaluation of ischemic cerebrovascular disease. Keywords: transcranial Doppler ultrasonography, Doppler ultrasonography duplex, cerebrovascular disorders, stroke

Identification of a novel pro-inflammatory human skin-homing Vγ9Vδ2 T cell subset with a potential role in psoriasis

Science.gov (United States)

LAGGNER, Ute; DI MEGLIO, Paola; PERERA, Gayathri K.; HUNDHAUSEN, Christian; LACY, Katie E.; ALI, Niwa; SMITH, Catherine H.; HAYDAY, Adrian C.; NICKOLOFF, Brian J.; NESTLE, Frank O.

2011-01-01

γδ T cells mediate rapid tissue responses in murine skin and participate in cutaneous immune regulation including protection against cancer. The role of human γδ cells in cutaneous homeostasis and pathology is poorly characterized. In this study we show in vivo evidence that human blood contains a distinct subset of pro-inflammatory cutaneous lymphocyte antigen (CLA) and C-C chemokine receptor (CCR) 6 positive Vγ9Vδ2 T cells, which is rapidly recruited into perturbed human skin. Vγ9Vδ2 T cells produced an array of pro-inflammatory mediators including IL-17A and activated keratinocytes in a TNF-α and IFN-γ dependent manner. Examination of the common inflammatory skin disease psoriasis revealed a striking reduction of circulating Vγ9Vδ2 T cells in psoriasis patients compared to healthy controls and atopic dermatitis patients. Decreased numbers of circulating Vγ9Vδ2 T cells normalized after successful treatment with psoriasis-targeted therapy. Together with the increased presence of Vγ9Vδ2 T cells in psoriatic skin, this data indicates redistribution of Vγ9Vδ2 T cells from the blood to the skin compartment in psoriasis. In summary, we report a novel human pro-inflammatory γδ T cell involved in skin immune surveillance with immediate response characteristics and with potential clinical relevance in inflammatory skin disease. PMID:21813772

Study of plasma neuropeptide levels in patients with acute cardiovascular and cerebrovascular disease

International Nuclear Information System (INIS)

Xu Youfen; Lan Suixin; Chen Yu; He Ling; Huang Yuan; Ma Yaling

2003-01-01

Objective: To explore the relationship between the dynamic changes of plasma neuropeptide (β-EP, NT, NPY) levels and the pathogenesis as well as clinical outcomes of acute cardiovascular and cerebrovascular diseases. Methods: The concentrations of serum neuropeptides (β-EP, NT, NPY) were measured on the 1 st, 3 rd, 7 th, 14 th day after the onset of disease with RIA in 103 patients with acute cardiovascular and cerebrovascular diseases (38 cases of acute cerebral infarction, 32 cases of cerebral hemorrhage, 33 cases of acute myocardial infarction and acute heart failure) and 66 controls. Results: 1. NPY, NT and β-EP levels in patients with acute cardiovascular and cerebrovascular disease were significantly higher than those in controls (p<0.01). (F=39.54, p<0.01; F=33.38, p<0.01; F=8.38, p<0.01 For β-EP, NPY and NT respectively). 2. The plasma neuropeptide levels were highest at onset and gradually lowered till to normal levels on the 14 th day. Conclusion: Plasma neuropeptide levels were closely related to the pathogenesis and clinical outcome of acute cardiovascular and cerebrovascular diseases, study of which might be useful in the clinical management of the diseases

Three-dimensional CT angiography in the diagnosis of cerebrovascular disease

International Nuclear Information System (INIS)

Eguchi, Takahiko; Nikaido, Yuji; Nakamura, Takeshi; Yoneda, Shigeru

1995-01-01

We reported the usefulness of three dimensional CT angiography (3 DCTA) in cerebrovascular disease. Twenty two of twenty three intracerebral aneurysms were visualized in 3 DCTA. 3 DTPA was especially useful for the evaluation of posterior-projection anterior communicating arteries and the distinction between a carotid-posterior communicating aneurysm and an infundibular dilatation. An anterior-projection carotid bifurcation aneurysm, which we missed in DSA, was visualized clearly in 3 DCTA. Stenotic cervical carotid artery lesions were well evaluated in 3 DCTA, including ulceration. 3 DCTA was not so useful for evaluation of intracranial artery stenosis. 3 DCTA was useful as a non-invasive method to evaluate cerebrovascular diseases. (author)

Unique cerebrovascular anomalies in Noonan syndrome with RAF1 mutation.

Science.gov (United States)

Zarate, Yuri A; Lichty, Angie W; Champion, Kristen J; Clarkson, L Kate; Holden, Kenton R; Matheus, M Gisele

2014-08-01

Noonan syndrome is a common autosomal dominant neurodevelopmental disorder caused by gain-of-function germline mutations affecting components of the Ras-MAPK pathway. The authors present the case of a 6-year-old male with Noonan syndrome, Chiari malformation type I, shunted benign external hydrocephalus in infancy, and unique cerebrovascular changes. A de novo heterozygous change in the RAF1 gene was identified. The patient underwent brain magnetic resonance imaging, computed tomography angiography, and magnetic resonance angiography to further clarify the nature of his abnormal brain vasculature. The authors compared his findings to the few cases of Noonan syndrome reported with cerebrovascular pathology. © The Author(s) 2013.

Increased Prevalence of Cerebrovascular Disease in Hospitalized Patients with Ehlers-Danlos Syndrome.

Science.gov (United States)

Kim, Sarasa T; Cloft, Harry; Flemming, Kelly D; Kallmes, David F; Lanzino, Giuseppe; Brinjikji, Waleed

2017-08-01

Small studies have suggested that Ehlers-Danlos syndrome (EDS) is associated with a number of cerebrovascular complications. We sought to determine whether a clinical diagnosis of EDS is associated with a higher prevalence of cerebrovascular diseases than the general population by performing a case-control study of hospitalized patients in the Nationwide Inpatient Sample (NIS). Using the 2000-2012 NIS, we performed a case-control study matching cases of EDS to controls without such a diagnosis. The prevalence of various cerebrovascular diseases between the 2 groups was compared, and multivariate logistic regression was used to adjust for suspected comorbidities. Between 2000 and 2012, there were a total of 9067 discharges carrying a diagnosis of EDS. On univariate analysis, patients with EDS were more likely to be hospitalized for carotid dissection (.2% versus .01%, odds ratio [OR] = 18.0, confidence interval [CI] = 2.41-135.12, P < .0001), vertebral dissection (.1% versus 0%, P = .008), cervical artery aneurysm (.1% versus .01%, OR = 9.01, CI = 1.14-71.11, P < .0001), cerebral aneurysm (.4% versus .09%, OR = 4.89, CI = 2.28-10.47, P < .0001), and cerebrovascular malformation (.1% versus .02%, OR = 5, CI = 1.10-22.85, P = .021), compared to the controls. On multivariate analysis adjusted for age, race, and comorbidities, EDS patients had significantly higher odds of carotid dissection (OR = 15.02, CI = 3.08-270.87, P < .0001), vertebral dissection (OR = 2406539.5, P = .0037), cervical artery aneurysm (OR = 11.75, CI = 2.11-220.71, P = .0026), cerebral aneurysm (OR = 5.59, CI = 2.69-13.18, P < .0001), and cerebrovascular malformation (OR = 4.67, CI = 1.20-30.87, P = .0243). Carotid and vertebral dissections, cervical and cerebral aneurysms, as well as other cerebrovascular malformations are more common in hospitalized patients with EDS compared to controls

A five-year study of particulate matter (PM2.5) and cerebrovascular diseases

International Nuclear Information System (INIS)

Leiva G, Manuel A.; Santibañez, Daniela A.; Ibarra E, Sergio; Matus C, Patricia; Seguel, Rodrigo

2013-01-01

Cerebrovascular accidents, or strokes, are the second leading cause of mortality and the leading cause of morbidity in both Chile and the rest of the world. However, the relationship between particulate matter pollution and strokes is not well characterized. The association between fine particle concentration and stroke admissions was studied. Data on hospital admissions due to cerebrovascular accidents were collected from the Ministry of Health. Air quality and meteorological data were taken from the Air Quality database of the Santiago Metropolitan Area. Santiago reported 33,624 stroke admissions between January 1, 2002 and December 30, 2006. PM2.5 concentration was markedly seasonal, increasing during the winter. This study found an association between PM2.5 exposure and hospital admissions for stroke; for every PM2.5 concentration increase of 10 μg m −3 , the risk of emergency hospital admissions for cerebrovascular causes increased by 1.29% (95% CI 0.552%–2.03%). Highlights: •Particulate matter pollution – cerebrovascular diseases relationship is not well known. •Cerebrovascular diseases are the second leading cause of mortality and the leading cause of morbidity. •PM2.5 increase 10 μg/m 3 the risk of hospital admissions for stroke causes increases by 1.29%. •The results are similar to that of other cities worldwide. -- Relationship between PM pollution and strokes is not well characterized. In Santiago the risk of the stroke increased by 1.29%; for every increase of 10 μg m −3 in PM2.5

LL-37 directs macrophage differentiation toward macrophages with a proinflammatory signature.

Science.gov (United States)

van der Does, Anne M; Beekhuizen, Henry; Ravensbergen, Bep; Vos, Tim; Ottenhoff, Tom H M; van Dissel, Jaap T; Drijfhout, Jan W; Hiemstra, Pieter S; Nibbering, Peter H

2010-08-01

The human cathelicidin LL-37 has broad-spectrum antimicrobial activity. It also participates at the interface of innate and adaptive immunity by chemoattracting immune effector cells, modulating the production of a variety of inflammatory mediators by different cell types, and regulating the differentiation of monocytes into dendritic cells. In this study, we investigated the effects of LL-37 on the differentiation of human monocytes into anti-inflammatory macrophages (MPhi-2; driven by M-CSF) versus proinflammatory macrophages (MPhi-1; driven by GM-CSF) as well as on fully differentiated MPhi-1 and MPhi-2. Results revealed that monocytes cultured with M-CSF in the presence of LL-37 resulted in macrophages displaying a proinflammatory signature, namely, low expression of CD163 and little IL-10 and profound IL-12p40 production on LPS stimulation. The effects of LL-37 on M-CSF-driven macrophage differentiation were dose- and time-dependent with maximal effects observed at 10 microg/ml when the peptide was present from the start of the cultures. The peptide enhanced the GM-CSF-driven macrophage differentiation. Exposure of fully differentiated MPhi-2 to LL-37 for 6 d resulted in macrophages that produced less IL-10 and more IL-12p40 on LPS stimulation than control MPhi-2. In contrast, LL-37 had no effect on fully differentiated MPhi-1. Peptide mapping using a set of 16 overlapping 22-mer peptides covering the complete LL-37 sequence revealed that the C-terminal portion of LL-37 is responsible for directing macrophage differentiation. Our results furthermore indicate that the effects of LL-37 on macrophage differentiation required internalization of the peptide. Together, we conclude that LL-37 directs macrophage differentiation toward macrophages with a proinflammatory signature.

Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan, inhibits type I-IV allergic inflammation and pro-inflammatory enzymes.

Science.gov (United States)

Lee, Ji Yun; Kim, Chang Jong

2010-06-01

We previously reported that arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan isolated from Forsythia koreana, exhibits anti-inflammatory, antioxidant, and analgesic effects in animal models. In addition, arctigenin inhibited eosinophil peroxidase and activated myeloperoxidase in inflamed tissues. In this study, we tested the effects of arctigenin on type I-IV allergic inflammation and pro-inflammatory enzymes in vitro and in vivo. Arctigenin significantly inhibited the heterologous passive cutaneous anaphylaxis induced by ovalbumin in mice at 15 mg/kg, p.o., and compound 48/80-induced histamine release from rat peritoneal mast cells at 10 microM. Arctigenin (15 mg/kg, p.o.) significantly inhibited reversed cutaneous anaphylaxis. Further, arctigenin (15 mg/kg, p.o.) significantly inhibited the Arthus reaction to sheep's red blood cells, decreasing the hemolysis titer, the hemagglutination titer, and the plaque-forming cell number for SRBCs. In addition, arctigenin significantly inhibited delayed type hypersensitivity at 15 mg/kg, p.o. and the formation of rosette-forming cells at 45 mg/kg, p.o. Contact dermatitis induced by picrylchloride and dinitrofluorobenzene was significantly (p arctigenin (0.3 mg/ear). Furthermore, arctigenin dose-dependently inhibited pro-inflammatory enzymes, such as cyclooxygenase-1 and 2, 5-lipoxygenase, phospholipase A2, and phosphodiesterase. Our results show that arctigenin significantly inhibited B- and T-cell mediated allergic inflammation as well as pro-inflammatory enzymes.

Myocardial stress in patients with acute cerebrovascular events

DEFF Research Database (Denmark)

Jespersen, C.M.; Hansen, J.F.

2008-01-01

Signs of myocardial involvement are common in patients with acute cerebrovascular events. ST segment deviations, abnormal left ventricular function, increased N-terminal pro-brain natriuretic peptide (NT-proBNP), prolonged QT interval, and/or raised troponins are observed in up to one third...

Proinflammatory mediators stimulate neutrophil-directed angiogenesis.

LENUS (Irish Health Repository)

McCourt, M

2012-02-03

BACKGROUND: Vascular endothelial growth factor (VEGF; vascular permeability factor) is one of the most potent proangiogenic cytokines, and it plays a central role in mediating the process of angiogenesis or new blood vessel formation. Neutrophils (PMNs) recently have been shown to produce VEGF. HYPOTHESIS: The acute inflammatory response is a potent stimulus for PMN-directed angiogenesis. METHODS: Neutrophils were isolated from healthy volunteers and stimulated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and anti-human Fas monoclonal antibody. Culture supernatants were assayed for VEGF using enzyme-linked immunosorbent assays. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs were then added to human umbilical vein endothelial cells and human microvessel endothelial cells and assessed for endothelial cell proliferation using 5-bromodeoxyuridine labeling. Tubule formation was also assessed on MATRIGEL basement membrane matrix. Neutrophils were lysed to measure total VEGF release, and VEGF expression was detected using Western blot analysis. RESULTS: Lipopolysaccharide and TNF-alpha stimulation resulted in significantly increased release of PMN VEGF (532+\\/-49 and 484+\\/-80 pg\\/mL, respectively; for all, presented as mean +\\/- SEM) compared with control experiments (32+\\/-4 pg\\/mL). Interleukin 6 and Fas had no effect. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs also resulted in significant increases (P<.005) in macrovascular and microvascular endothelial cell proliferation and tubule formation. Adding anti-human VEGF-neutralizing polyclonal antibody to stimulated PMN supernatant inhibited these effects. Total VEGF release following cell lysis and Western blot analysis suggests that the VEGF is released from an intracellular store. CONCLUSION: Activated human PMNs are directly angiogenic by releasing VEGF, and this has important implications for inflammation, capillary leak syndrome

Treadmill exercise promotes neuroprotection against cerebral ischemia–reperfusion injury via downregulation of pro-inflammatory mediators

Directory of Open Access Journals (Sweden)

Zhang Y

2016-12-01

ischemia–reperfusion injury via the downregulation of pro-inflammatory mediators. Keywords: rehabilitation, cytokine, chemokine, stroke, rat model 

Elevated cardiac troponin I predicts cardiovascular or cerebrovascular events in hypertensive patients

International Nuclear Information System (INIS)

Zhang Li'na; Cao Yanfei; Qiu Yifan

2011-01-01

Objective: Whether elevated cTnI is associated with cardiovascular or cerebrovascular events in patients with hypertension (HT) without left ventricular(LV) systolic dysfunction is not clear. Method: We measured cTnI serum level in 170 patients with essential HT without LV systolic dysfunction (LVEF 55%),renal failure,and prior cardiovascular or cerebrovascular diseases. Besides, control group of 40 normal presons was established and following up (45±38)months. Results: Level of cTnI was elevated (≥0.04 ng/ml) in 15 (8.8%) of the 170 patients and in 0 (0%) of the 40 normal controls. The rate of diabetes mellitus(DM), the cardiothoracic ratio, serum NT-proBNP value, and LV mass index were significantly higher in patients with than without elevated cTnI (DM, 9/15 versus 25/155, P 2 , P=0.0001). Kaplan-Meier analysis demonstrated that significantly fewer (P<0.000001) patients with, than without elevated cTnI remained free of events (hospitalization due to cardiovascular or cerebrovascular disease). Stepwise Cox multivariate analysis revealed that elevated cTnT (hazard ratio, 6.59, P=0.000001) and smoking (hazard ratio, 2.26, P=0.04) were independent predictors of events. Conclusion: The present findings indicate that cTnI is a biomarker and useful predictor of future cardiovascular or cerebrovascular events in hypertensive patients. (authors)

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.

Mortalidad intrahospitalaria por accidente cerebrovascular

OpenAIRE

Federico Rodríguez Lucci; Virginia Pujol Lereis; Sebastián Ameriso; Guillermo Povedano; María F. Díaz; Alejandro Hlavnicka; Néstor A. Wainsztein; Sebastián F. Ameriso

2013-01-01

La mortalidad global por accidente cerebrovascular (ACV) ha disminuido en las últimas tres décadas, probablemente debido a un mejor control de los factores de riesgo vascular. La mortalidad hospitalaria por ACV ha sido tradicionalmente estimada entre 6 y 14% en la mayoría de las series comunicadas. Sin embargo, los datos de ensayos clínicos recientes sugieren que esta cifra sería sustancialmente menor. Se revisaron datos de pacientes internados con diagnóstico de ACV del Banco de Datos de Str...

Adzuki bean ameliorates hepatic lipogenesis and proinflammatory mediator expression in mice fed a high-cholesterol and high-fat diet to induce nonalcoholic fatty liver disease.

Science.gov (United States)

Kim, Sera; Hong, Jihye; Jeon, Raok; Kim, Hyun-Sook

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) is a simple steatosis, in which fat accumulates more than 5% in the liver, and regarded as most common liver diseases worldwide. Because NAFLD can be developed to severe liver disease and correlated with metabolic disease, its importance is currently emphasized. Occurrence of NAFLD is strongly related to dietary patterns and lifestyles; therefore, the suggestion of physiologically beneficial food is essential. Based on these, adzuki beans containing anthocyanin, catechin, and adzukisaponin are suggested as a health-beneficial food. Moreover, the effects of adzuki beans on metabolic improvement are not well established through the in vivo studies. Therefore, this study hypothesized that adzuki beans can alleviate lipid accumulation and oxidative stress-mediated inflammation in high-cholesterol and high-fat diet-induced NALFD mice. To demonstrate its effects, 6-week-old C57BL/6 male mice were allocated into 4 groups and fed a normal diet (ND), a high-cholesterol and high-fat diet (HCD), and HCD with 10% and 20% adzuki bean for 10 weeks. The result shows that fasting blood glucose, serum and hepatic triglyceride and cholesterol levels, and antioxidative enzyme activity ameliorated in the adzuki bean groups (P hepatic lipogenesis, such as adiponectin, AMP-activated protein kinase α, sterol regulatory element-binding protein 1c, fatty acid synthase, carnitine palmitoyltransferase 1, 3-hydroxy-3-methyl-glutaryl-CoA reductase, and apolipoprotein B, as well as proinflammatory mediators, such as tumor necrosis factor α, nuclear factor κB, and caspase-3, improved in both experimental groups (P hepatic messenger RNA expression of lipogenic and inflammatory mediators in NAFLD. Copyright © 2016 Elsevier Inc. All rights reserved.

The diagnosis and management of cerebrovascular disease in diabetes.

Science.gov (United States)

Phipps, Michael S; Jastreboff, Ania M; Furie, Karen; Kernan, Walter N

2012-06-01

Cerebrovascular disease is a leading cause of morbidity and mortality in diabetes. Compared with nondiabetic patients, diabetic patients have at least twice the risk for stroke, earlier onset of symptoms, and worse functional outcomes. Approximately 20 % of diabetic patients will die from stroke, making it one of the leading causes of death in this population. Effective strategies for primary and secondary prevention of stroke have been developed in research cohorts that included both diabetic and nondiabetic patients. Nevertheless, prevention in diabetes has some specific considerations. In this paper, we summarize evidence to guide the diagnosis and management of stroke in diabetic patients. We propose that diabetic stroke patients should have a robust risk assessment to target interventions, like other patients with cerebrovascular disease, but with special attention to glycemic control and lifestyle modification.

Selective targeting of pro-inflammatory Th1 cells by microRNA-148a-specific antagomirs in vivo.

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Maschmeyer, Patrick; Petkau, Georg; Siracusa, Francesco; Zimmermann, Jakob; Zügel, Franziska; Kühl, Anja Andrea; Lehmann, Katrin; Schimmelpfennig, Sarah; Weber, Melanie; Haftmann, Claudia; Riedel, René; Bardua, Markus; Heinz, Gitta Anne; Tran, Cam Loan; Hoyer, Bimba Franziska; Hiepe, Falk; Herzog, Sebastian; Wittmann, Jürgen; Rajewsky, Nikolaus; Melchers, Fritz Georg; Chang, Hyun-Dong; Radbruch, Andreas; Mashreghi, Mir-Farzin

2018-05-01

In T lymphocytes, expression of miR-148a is induced by T-bet and Twist1, and is specific for pro-inflammatory Th1 cells. In these cells, miR-148a inhibits the expression of the pro-apoptotic protein Bim and promotes their survival. Here we use sequence-specific cholesterol-modified oligonucleotides against miR-148a (antagomir-148a) for the selective elimination of pro-inflammatory Th1 cells in vivo. In the murine model of transfer colitis, antagomir-148a treatment reduced the number of pro-inflammatory Th1 cells in the colon of colitic mice by 50% and inhibited miR-148a expression by 71% in the remaining Th1 cells. Expression of Bim protein in colonic Th1 cells was increased. Antagomir-148a-mediated reduction of Th1 cells resulted in a significant amelioration of colitis. The effect of antagomir-148a was selective for chronic inflammation. Antigen-specific memory Th cells that were generated by an acute immune reaction to nitrophenylacetyl-coupled chicken gamma globulin (NP-CGG) were not affected by treatment with antagomir-148a, both during the effector and the memory phase. In addition, antibody titers to NP-CGG were not altered. Thus, antagomir-148a might qualify as an effective drug to selectively deplete pro-inflammatory Th1 cells of chronic inflammation without affecting the protective immunological memory. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Deconstructing racial differences: the effects of quality of education and cerebrovascular risk factors.

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Carvalho, Janessa O; Tommet, Doug; Crane, Paul K; Thomas, Michael L; Claxton, Amy; Habeck, Christian; Manly, Jennifer J; Romero, Heather R

2015-07-01

To evaluate the effects of vascular conditions and education quality on cognition over time in White and African American (AA) older adults. We investigated cross-sectional and longitudinal racial differences in executive functioning (EF) and memory composites among Whites (n = 461) and AAs (n = 118) enrolled in a cohort study. We examined whether cerebrovascular risk factors and Shipley Vocabulary scores (a proxy for education quality) accounted for racial differences. On average, AAs had lower quality of education and more cerebrovascular risk factors including hypertension, diabetes, and obesity. AAs had lower mean EF and memory at baseline, but there were no group differences in rates of decline. Cross-sectional racial differences in EF and memory persisted after controlling for vascular disease, but disappeared when controlling for Shipley Vocabulary. Quality of education appears to be more important than cerebrovascular risk factors in explaining cross-sectional differences in memory and EF performance between White and AA older adults. Further investigation is needed regarding the relative contribution of education quality and cerebrovascular risk factors to cognitive decline among ethnically/racially diverse older adults. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

La enfermedad cerebrovascular en pacientes desde 29 días a 18 años de edad Cerebrovascular disease in patients from 29 days born to 18 years old

Directory of Open Access Journals (Sweden)

Nadia Arteche Díaz

2012-12-01

Full Text Available Introducción: la enfermedad cerebrovascular, tanto en adultos como en los niños, en los últimos años ha constituido un problema de gran interés para la comunidad médica y científica nacional e internacional. Objetivo: caracterizar la enfermedad cerebrovascular en pacientes desde 29 días de nacido hasta 18 años de edad. Material y método: se realizó una investigación descriptiva y retroprospectiva de los pacientes atendidos en la Unidad de Cuidados Intensivos del Hospital Pedriático Docente "Pepe Portilla" en Pinar del Río, en el período comprendido de julio de 2005 a junio de 2011. La muestra estuvo consituida por 20 pacientes desde 29 de días de nacidos hasta 18 años de edad. Se revisaron las historias clínicas y se realizó una encuesta. Resultados: la tasa de incidencia anual más alta fue de 2,7 por 100 000 habitantes; el grupo de edad de mayor incidencia fue el de 5 a 14 años (2,2 por 100 000 habitantes; el diagnóstico más frecuente fue la hemorragia intracraneal (65 %; la evolución de los pacientes fue favorable con el tratamiento adecuado y solo cinco pacientes fallecieron debido a la enfermedad cerebrovascular (letalidad=25 % y se realizó tratamiento quirúrgico en un paciente con aneurisma de la carótida interna derecha, presentando evolución favorable sin secuelas neurológicas. Conclusiones: el tratamiento de los pacientes pediátricos con enfermedad cerebrovascular en la provincia de Pinar del Río, requiere de la aplicación de un programa de diagnóstico y manejo integral personalizado para permitir una evolución favorable, mejorando la calidad de vida del paciente.Introduction: cerebrovascular disease, both in adults and children, has constituted a problem of interest to the medical, national and international scientific community during last years. Objective: to characterize cerebrovascular disease in patients from 29 days born to 18 years old. Material and Method: a descriptive and retrospective

A large, switchable optical clearing skull window for cerebrovascular imaging

Science.gov (United States)

Zhang, Chao; Feng, Wei; Zhao, Yanjie; Yu, Tingting; Li, Pengcheng; Xu, Tonghui; Luo, Qingming; Zhu, Dan

2018-01-01

Rationale: Intravital optical imaging is a significant method for investigating cerebrovascular structure and function. However, its imaging contrast and depth are limited by the turbid skull. Tissue optical clearing has a great potential for solving this problem. Our goal was to develop a transparent skull window, without performing a craniotomy, for use in assessing cerebrovascular structure and function. Methods: Skull optical clearing agents were topically applied to the skulls of mice to create a transparent window within 15 min. The clearing efficacy, repeatability, and safety of the skull window were then investigated. Results: Imaging through the optical clearing skull window enhanced both the contrast and the depth of intravital imaging. The skull window could be used on 2-8-month-old mice and could be expanded from regional to bi-hemispheric. In addition, the window could be repeatedly established without inducing observable inflammation and metabolic toxicity. Conclusion: We successfully developed an easy-to-handle, large, switchable, and safe optical clearing skull window. Combined with various optical imaging techniques, cerebrovascular structure and function can be observed through this optical clearing skull window. Thus, it has the potential for use in basic research on the physiopathologic processes of cortical vessels. PMID:29774069

Hospital descrlptlve epidemiology of cerebrovascular disorders in G. Almenara 1. Natlonal Hospital

OpenAIRE

Deza, Luis; Aldave, Raquel; Concha, Gina; Salazar, Luis; Carmona, Jorge; Castillo, Marco

2014-01-01

We present an epidemiological approach of a two years clinical observation study of a cohort of 208 admissions with cerebrovascular disease. This report represents part of a wider project intended to clarify the natural history of cerebrovascular diseases in Peru. We found a 70.7% of occlusions or stenosis, a 26.9% of intracerebral hemorrhages, a 1.9% of subarachnoid hemorrhage and a 0.5% of other unspecified. A mean age of onset of 62.2 years, with a very large range, probably with a later a...

CD54-Mediated Interaction with Pro-inflammatory Macrophages Increases the Immunosuppressive Function of Human Mesenchymal Stromal Cells

OpenAIRE

Espagnolle, Nicolas; Balguerie, Ad?lie; Arnaud, Emmanuelle; Senseb?, Luc; Varin, Audrey

2017-01-01

Summary: Mesenchymal stromal cells (MSCs) sense and modulate inflammation and represent potential clinical treatment for immune disorders. However, many details of the bidirectional interaction of MSCs and the innate immune compartment are still unsolved. Here we describe an unconventional but functional interaction between pro-inflammatory classically activated macrophages (M1MΦ) and MSCs, with CD54 playing a central role. CD54 was upregulated and enriched specifically at the contact area be...

Diclofenac enhances proinflammatory cytokine-induced nitric oxide production through NF-κB signaling in cultured astrocytes

International Nuclear Information System (INIS)

Kakita, Hiroki; Aoyama, Mineyoshi; Hussein, Mohamed Hamed; Kato, Shin; Suzuki, Satoshi; Ito, Tetsuya; Togari, Hajime; Asai, Kiyofumi

2009-01-01

Recently, the number of reports of encephalitis/encephalopathy associated with influenza virus has increased. In addition, the use of a non-steroidal anti-inflammatory drug, diclofenac sodium (DCF), is associated with a significant increase in the mortality rate of influenza-associated encephalopathy. Activated astrocytes are a source of nitric oxide (NO), which is largely produced by inducible NO synthase (iNOS) in response to proinflammatory cytokines. Therefore, we investigated whether DCF enhances nitric oxide production in astrocytes stimulated with proinflammatory cytokines. We stimulated cultured rat astrocytes with three cytokines, interleukin-1β, tumor necrosis factor-α and interferon-γ, and then treated the astrocytes with DCF or acetaminophen (N-acetyl-p-aminophenol: APAP). iNOS and NO production in astrocyte cultures were induced by proinflammatory cytokines. The addition of DCF augmented NO production, but the addition of APAP did not. NF-κB inhibitors SN50 and MG132 inhibited iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. Similarly, NF-κB p65 Stealth small interfering RNA suppressed iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. LDH activity and DAPI staining showed that DCF induces cell damage in cytokine-stimulated astrocytes. An iNOS inhibitor, L-NMMA, inhibited the cytokine- and DCF-induced cell damage. In conclusion, this study demonstrates that iNOS and NO are induced in astrocyte cultures by proinflammatory cytokines. Addition of DCF further augments NO production. This effect is mediated via NF-κB signaling and leads to cell damage. The enhancement of DCF on NO production may explain the significant increase in the mortality rate of influenza-associated encephalopathy in patients treated with DCF.

Side differences in cerebrovascular accidents after cardiac surgery: a statistical analysis of neurologic symptoms and possible implications for anatomic mechanisms of aortic particle embolization.

Science.gov (United States)

Boivie, Patrik; Edström, Cecilia; Engström, Karl Gunnar

2005-03-01

Aortic manipulation and particle embolization have been identified to cause cerebrovascular accidents in cardiac surgery. Recent data suggest that left-hemispheric cerebrovascular accident (right-sided symptoms) is more common, and this has been interpreted as being caused by aortic cannula stream jets. Our aim was to evaluate symptoms of cerebrovascular accident and side differences from a retrospective statistical analysis. During a 2-year period, 2641 consecutive cardiac surgery cases were analyzed. Patients positive for cerebrovascular accident were extracted from a database designed to monitor clinical symptoms. A protocol was used to confirm symptom data with the correct diagnosis in patient records. Patients were subdivided into 3 groups: control, immediate cerebrovascular accident, and delayed cerebrovascular accident. Among pooled patients, immediate and delayed cerebrovascular accidents were 3.0% and 0.9%, respectively. The expected predisposing factors behind immediate cerebrovascular accidents were significant, although the type of operation affected this search. Aortic quality was a strong predictor ( P cerebrovascular accident was unaffected by surgery group. Left-sided symptoms of immediate cerebrovascular accident were approximately twice as frequent ( P = .016) as on the contralateral side. This phenomenon was observed for pooled patients and for isolated coronary bypass procedures (n = 1882; P = .025). Immediate cerebrovascular accident and aortic calcifications are linked. The predominance of left-sided symptoms may suggest that aortic manipulation and anatomic mechanisms in the aortic arch are more likely to cause cerebrovascular accidents than effects from cannula stream jets.

Effect of SOCS1 overexpression on RPE cell activation by proinflammatory cytokines.

Science.gov (United States)

Bazewicz, Magdalena; Draganova, Dafina; Makhoul, Maya; Chtarto, Abdel; Elmaleh, Valerie; Tenenbaum, Liliane; Caspers, Laure; Bruyns, Catherine; Willermain, François

2016-09-06

The purpose of this study was to investigate the in vitro effect of Suppressor Of Cytokine Signaling 1 (SOCS1) overexpression in retinal pigment epithelium (RPE) cells on their activation by pro-inflammatory cytokines IFNγ, TNFα and IL-17. Retinal pigment epithelium cells (ARPE-19) were stably transfected with the control plasmid pIRES2-AcGFP1 or the plasmid pSOCS1-IRES2-AcGFP1. They were stimulated by IFNγ (150ng/ml), TNFα (30ng/ml) or IL-17 (100ng/ml). The levels of SOCS1 mRNA were measured by real-time PCR. Signal Transducer and Activator of Transcription 1 (STAT1) phosphorylation and IκBα expression were analysed by western Blot (WB). IL-8 secretion was analysed by ELISA and expression of MHCII molecules and ICAM-1/CD54 by flow cytometry. Our data show that SOCS1 mRNA overexpression in RPE cells prevents IFNγ-induced SOCS1 mRNA increase and IFNγ-mediated STAT1 phosphorylation. Moreover, SOCS1 overexpression in RPE cells inhibits IFNγ-induced decrease of IL-8 secretion and prevents IFNγ-induced MHC II and ICAM1/CD54 upregulation. However, SOCS1 overexpression does not affect TNFα-induced IκBα degradation nor block TNFα-induced or IL-17-induced IL-8 secretion. On the contrary, IL-17-induced secretion is increased by SOCS1 overexpression. In conclusion, SOCS1 overexpression in RPE cells inhibits some IFNγ-mediated responses that lead to uveitis development. This notion raises the possibility that SOCS1 overexpression could be a novel target for treating non-infectious uveitis. However, some proinflammatory effects of TNFα and IL-17 stimulation on RPE are not blocked by SOCS1 overexpression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The adaptor CRADD/RAIDD controls activation of endothelial cells by proinflammatory stimuli.

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Qiao, Huan; Liu, Yan; Veach, Ruth A; Wylezinski, Lukasz; Hawiger, Jacek

2014-08-08

A hallmark of inflammation, increased vascular permeability, is induced in endothelial cells by multiple agonists through stimulus-coupled assembly of the CARMA3 signalosome, which contains the adaptor protein BCL10. Previously, we reported that BCL10 in immune cells is targeted by the "death" adaptor CRADD/RAIDD (CRADD), which negatively regulates nuclear factor κB (NFκB)-dependent cytokine and chemokine expression in T cells (Lin, Q., Liu, Y., Moore, D. J., Elizer, S. K., Veach, R. A., Hawiger, J., and Ruley, H. E. (2012) J. Immunol. 188, 2493-2497). This novel anti-inflammatory CRADD-BCL10 axis prompted us to analyze CRADD expression and its potential anti-inflammatory action in non-immune cells. We focused our study on microvascular endothelial cells because they play a key role in inflammation. We found that CRADD-deficient murine endothelial cells display heightened BCL10-mediated expression of the pleotropic proinflammatory cytokine IL-6 and chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) in response to LPS and thrombin. Moreover, these agonists also induce significantly increased permeability in cradd(-/-), as compared with cradd(+/+), primary murine endothelial cells. CRADD-deficient cells displayed more F-actin polymerization with concomitant disruption of adherens junctions. In turn, increasing intracellular CRADD by delivery of a novel recombinant cell-penetrating CRADD protein (CP-CRADD) restored endothelial barrier function and suppressed the induction of IL-6 and MCP-1 evoked by LPS and thrombin. Likewise, CP-CRADD enhanced barrier function in CRADD-sufficient endothelial cells. These results indicate that depletion of endogenous CRADD compromises endothelial barrier function in response to inflammatory signals. Thus, we define a novel function for CRADD in endothelial cells as an inducible suppressor of BCL10, a key mediator of responses to proinflammatory agonists. © 2014 by The American Society for Biochemistry and Molecular Biology

Cerebrovascular Remodeling and Neuroinflammation is a Late Effect of Radiation-Induced Brain Injury in Non-Human Primates

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Andrews, Rachel N.; Metheny-Barlow, Linda J.; Peiffer, Ann M.; Hanbury, David B.; Tooze, Janet A.; Bourland, J. Daniel; Hampson, Robert E.; Deadwyler, Samuel A.; Cline, J. Mark

2017-01-01

Andrews, R. N., Metheny-Barlow, L. J., Peiffer, A. M., Hanbury, D. B., Tooze, J. A., Bourland, J. D., Hampson, R. E., Deadwyler, S. A. and Cline, J. M. Cerebrovascular Remodeling and Neuroinflammation is a Late Effect of Radiation-Induced Brain Injury in Non-Human Primates. Radiat. Res. 187, 599–611 (2017). Fractionated whole-brain irradiation (fWBI) is a mainstay of treatment for patients with intracranial neoplasia; however late-delayed radiation-induced normal tissue injury remains a major adverse consequence of treatment, with deleterious effects on quality of life for affected patients. We hypothesize that cerebrovascular injury and remodeling after fWBI results in ischemic injury to dependent white matter, which contributes to the observed cognitive dysfunction. To evaluate molecular effectors of radiation-induced brain injury (RIBI), real-time quantitative polymerase chain reaction (RT-qPCR) was performed on the dorsolateral prefrontal cortex (DLPFC, Brodmann area 46), hippocampus and temporal white matter of 4 male Rhesus macaques (age 6–11 years), which had received 40 Gray (Gy) fWBI (8 fractions of 5 Gy each, twice per week), and 3 control comparators. All fWBI animals developed neurologic impairment; humane euthanasia was elected at a median of 6 months. Radiation-induced brain injury was confirmed histopathologically in all animals, characterized by white matter degeneration and necrosis, and multifocal cerebrovascular injury consisting of perivascular edema, abnormal angiogenesis and perivascular extracellular matrix deposition. Herein we demonstrate that RIBI is associated with white matter-specific up-regulation of hypoxia-associated lactate dehydrogenase A (LDHA) and that increased gene expression of fibronectin 1 (FN1), SERPINE1 and matrix metalloprotease 2 (MMP2) may contribute to cerebrovascular remodeling in late-delayed RIBI. Additionally, vascular stability and maturation associated tumor necrosis super family member 15 (TNFSF15) and

Stress test with adenosine in cerebral perfusion imaging for the diagnosis of ischemic cerebrovascular disease

International Nuclear Information System (INIS)

Yuan Gengbiao; Kuang Anren; Chen Xuehong; Li Xihuan; Feng Jianzhong

2004-01-01

Objective: This study purpose is to evaluate cerebrovascular response and reserve capacity (CVR, CVRC) by stress test with adenosine in cerebral perfusion imaging for the diagnosis of ischemic cerebrovascular diseases. Methods There were 25 patients suffered from transient ischemia attack and 16 patients suffered from occlusive cerebral artery in this study. The rest cerebral perfusion imaging was obtained 30 minutes post-injection of 99mTC-ethylene cysteinate dimmer. After 2-5 days, adenosine stress tests were performed. Adenosine (0.14 mg/kg min) was administered intravenously 3 minutes pre-injection of 99mTC-ECD.Under same condition, the rest and stress tests of cerebral perfusion imaging were performed. By visual and semiquantitative analysis, the results of the rest/stress imaging were divided into the following four patterns: A: The stress imaging showed an expand areas of hypoperfusion, asymmetry index (AI) was decreased; B: Rest imaging was normal but new hypoperfused areas appeared with AI index declining in stress test; C: The hypoperfused areas were decreased or disappeared in size with AI index increasing in stress test; D: No changes showed in cerebral perfusion imaging patterns and Al index between rest and stress tests. AI index was ratio of radio account of interest regions than average radio account of cerebella. Results It was found that A, B, C and D type were 24%,12%,56% and 8% respectively in the group of transient ischemia attack patients, and 31%,44%, 19% and 6% respectively in the group of occlusive cerebrovascular patients. In rest test, of 41 patients of cerebrovascular disease, there were 28 cases decreased of radio uptake, moreover in stress test, there were 38 case decreased of radio uptake, positive rate were 68.29% and 92.68% respectively. Compared to X±SD of AI index of rest/stress test, it is found to increasing and being significant statistics (p<0.01, Spass 8.0 statistics software). Conclusion: Adenosinal-induced vasodilatation

Characteristics, treatment, and outcomes of periprocedural cerebrovascular accidents during electrophysiologic procedures.

Science.gov (United States)

Harb, Serge C; Thomas, George; Saliba, Walid I; Nakhoul, Georges N; Hussein, Ayman A; Duarte, Valeria E; Bhargava, Mandeep; Baranowski, Bryan; Tchou, Patrick; Dresing, Thomas; Callahan, Thomas; Kanj, Mohamed; Natale, Andrea; Lindsay, Bruce D; Wazni, Oussama M

2013-06-01

We sought to identify the characteristics, treatment, and outcomes of periprocedural cerebrovascular accident (PCVA) during electrophysiologic (EP) procedures. Periprocedural cerebrovascular accident is one of the most feared complications during EP procedures with very few data regarding its characteristics, management, and outcomes. Between January 1998 and December 2008, we reviewed 30,032 invasive EP procedures for PCVA occurrence and characteristics. Management and outcomes were also determined. Thirty-eight CVAs were identified. Twenty (53 %) were intraprocedural and 18 (47 %) postprocedural. Thirty-two (84 %) were classified as strokes and six (16 %) as transient ischemic attacks. All CVAs except one (37, 97 %) were ischemic and the vast majority occurred during ablation procedures (36, 95 %). Among the 31 patients with ischemic stroke, 11 (35 %) were treated with reperfusion (eight catheter-based therapy and three intravenous t-PA) of whom five (46 %) had complete recovery, three (27 %) had partial recovery, and three (27 %) had no recovery. No hemorrhagic transformations occurred. Periprocedural cerebrovascular accident during EP procedures is rare and is almost always ischemic. It occurs more frequently during ablation procedures. Reperfusion therapy is feasible and safe.

Diagnosis and differential diagnosis of cerebro-vascular malformations by CT

International Nuclear Information System (INIS)

Schumacher, M.; Stoeter, P.; Voigt, K.

1980-01-01

In 38 patients, the diagnosis of a cerebrovascular malformation (17 arteriovenous angiomas including one low-flow- and two venous angiomas; 10 aneurysms; 4 arteriovenous fistulae of the cavernous sinus, the tentorium and one of the Great Vein of Galen; 6 megadolical basilar arteries) was initially made by computertomographic (CT) examination, including contrast enhancement. The characteristic and pathognomonic CT findings are described and compared with those of cerebral angiography also done in these cases. The problems of differential diagnosis and the reasons for a false CT diagnosis in 5 other patients with a cerebro-vascular malformation are investigated; and the diagnostic value of cerebral angiography and CT is discussed and their complementary functions are being pointed out. (orig.) 891 MG/orig. 892 MKO [de

Characteristics of cerebrovascular accidents at time of diagnosis in a series of 98 patients with giant cell arteritis.

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Zenone, Thierry; Puget, Marie

2013-12-01

The objective of this study was to determine the characteristics of cerebrovascular accidents at time of diagnosis in patients with giant cell arteritis. Retrospective data were collected from 98 patients at a single hospital with giant cell arteritis (according to the American College of Rheumatology classification criteria) diagnosed between October 1999 and January 2012. Cerebrovascular accident was found at initial presentation in 6 patients (6.1 %, 95 % CIs 2.3-12.9). Most of them had other symptoms of giant cell arteritis when the disease began. Signs reflecting the involvement of vertebro-basilar territory were present in 3 cases. No other case of cerebrovascular accident was described during the follow-up of patient; particularly no case of cerebrovascular accident occurred once corticosteroid therapy for the treatment of giant cell arteritis had been initiated. No differences in the epidemiologic, clinical and laboratory features at the time of diagnosis between patients who had cerebrovascular accidents and the rest of the giant cell arteritis patients were observed. Prognosis was good in our survey. However, there was no case of bilateral vertebral artery occlusion, a condition associated with poor prognosis. The present study confirms that cerebrovascular accidents may be the initial manifestation of giant cell arteritis, an argument in favor of a direct effect of the vasculitis in the development of cerebrovascular accidents rather than a complication of the corticosteroid therapy. The diagnosis of giant cell arteritis should always be considered in an elderly patient with stroke and an unexplained elevation of inflammatory biomarkers.

Digital subtraction angiography in ischemic cerebrovascular accidents

Energy Technology Data Exchange (ETDEWEB)

Manelfe, C.; Bonafe, A.; Ducos de Lahitte, M.; Rascol, A.; Prere, J.; Guiraud, B.; Marc-Vergnes, J.P. (Hopital Purpan, 31 - Toulouse (France))

1983-12-29

Recent advances in computer and radiological technology have permitted reassessment of intravenous angiography in the evaluation of cerebrovascular disorders. Although digital subtraction angiography is a relatively new technique, it has rapidly gained a widespread acceptance. It has extended the use of angiography to outpatients and to people in whom conventional angiography is contraindicated. This reliable, safe, and relatively noninvasive technique offers the user two benefits: real-time subtraction and enhanced image quality. The system allows angiographic evaluation of the extracranial and intracranial vessels by means of intravenous injection of contrast material. Extracranial studies clearly demonstrate stenoses and occlusions of the major cervicocephalic arteries. Intracranial studies usually detect major cerebrovascular occlusions and provide insight into the collateral flow patterns. Intravenous digital subtraction angiography permits accurate assessment of cervicocephalic vessels after surgical repair. Although intravenous digital subtraction angiography obviates the need for conventional angiography in many cases, movements from the patients, or superimposition of vascular structures can substantially degrade the quality of the images. Digital subtraction angiography with intra-arterial injection of contrast medium will be contemplated in patients with poor intravenous digital subtraction angiography studies prior to surgery.

Digital subtraction angiography in ischemic cerebrovascular accidents

International Nuclear Information System (INIS)

Manelfe, C.; Bonafe, A.; Ducos de Lahitte, M.; Rascol, A.; Prere, J.; Guiraud, B.; Marc-Vergnes, J.P.

1983-01-01

Recent advances in computer and radiological technology have permitted reassessment of intravenous angiography in the evaluation of cerebrovascular disorders. Although digital subtraction angiography is a relatively new technique, it has rapidly gained a widespread acceptance. It has extended the use of angiography to outpatients and to people in whom conventional angiography is contraindicated. This reliable, safe, and relatively noninvasive technique offers the user two benefits: real-time subtraction and enhanced image quality. The system allows angiographic evaluation of the extracranial and intracranial vessels by means of intravenous injection of contrast material. Extracranial studies clearly demonstrate stenoses and occlusions of the major cervicocephalic arteries. Intracranial studies usually detect major cerebrovascular occlusions and provide insight into the collateral flow patterns. Intravenous digital subtraction angiography permits accurate assessment of cervicocephalic vessels after surgical repair. Although intravenous digital subtraction angiography obviates the need for conventional angiography in many cases, movements from the patients, or superimposition of vascular structures can substantially degrade the quality of the images. Digital subtraction angiography with intra-arterial injection of contrast medium will be contemplated in patients with poor intravenous digital subtraction angiography studies prior to surgery [fr

NSAIDs and cardiovascular drugs in neurodegenerative and cerebrovascular diseases

NARCIS (Netherlands)

M.D.M. Haag (Mendel)

2009-01-01

textabstractNeurodegenerative and cerebrovascular diseases are frequent in elderly populations and comprise primarily of dementia (mainly Alzheimer disease (AD)), Parkinson disease (PD) and stroke. The prevalence of these neurological disorders rises with older age. From 55 years to 90 years and

DMPD: Post-transcriptional regulation of proinflammatory proteins. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 15075353 Post-transcriptional regulation of proinflammatory proteins. Anderson P, P...l) (.csml) Show Post-transcriptional regulation of proinflammatory proteins. PubmedID 15075353 Title Post-tr...anscriptional regulation of proinflammatory proteins. Authors Anderson P, Phillip

NFAT5-Regulated Macrophage Polarization Supports the Proinflammatory Function of Macrophages and T Lymphocytes.

Science.gov (United States)

Tellechea, Mónica; Buxadé, Maria; Tejedor, Sonia; Aramburu, Jose; López-Rodríguez, Cristina

2018-01-01

Macrophages are exquisite sensors of tissue homeostasis that can rapidly switch between pro- and anti-inflammatory or regulatory modes to respond to perturbations in their microenvironment. This functional plasticity involves a precise orchestration of gene expression patterns whose transcriptional regulators have not been fully characterized. We had previously identified the transcription factor NFAT5 as an activator of TLR-induced responses, and in this study we explore its contribution to macrophage functions in different polarization settings. We found that both in classically and alternatively polarized macrophages, NFAT5 enhanced functions associated with a proinflammatory profile such as bactericidal capacity and the ability to promote Th1 polarization over Th2 responses. In this regard, NFAT5 upregulated the Th1-stimulatory cytokine IL-12 in classically activated macrophages, whereas in alternatively polarized ones it enhanced the expression of the pro-Th1 mediators Fizz-1 and arginase 1, indicating that it could promote proinflammatory readiness by regulating independent genes in differently polarized macrophages. Finally, adoptive transfer assays in vivo revealed a reduced antitumor capacity in NFAT5-deficient macrophages against syngeneic Lewis lung carcinoma and ID8 ovarian carcinoma cells, a defect that in the ID8 model was associated with a reduced accumulation of effector CD8 T cells at the tumor site. Altogether, detailed analysis of the effect of NFAT5 in pro- and anti-inflammatory macrophages uncovered its ability to regulate distinct genes under both polarization modes and revealed its predominant role in promoting proinflammatory macrophage functions. Copyright © 2017 by The American Association of Immunologists, Inc.

Mitochondrial reactive oxygen species mediate the lipopolysaccharide-induced pro-inflammatory response in human gingival fibroblasts

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Li, Xue; Wang, Xiaoxuan [Department of Periodontology, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Zheng, Ming, E-mail: zhengm@bjmu.edu.cn [Department of Physiology and Pathophysiology, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191 (China); Luan, Qing Xian, E-mail: kqluanqx@126.com [Department of Periodontology, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China)

2016-09-10

Although periodontal diseases are initiated by bacteria that colonize the tooth surface and gingival sulcus, the host response is believed to play an essential role in the breakdown of connective tissue and bone. Mitochondrial reactive oxygen species (mtROS) have been proposed to regulate the activation of the inflammatory response by the innate immune system. However, the role of mtROS in modulating the response of human gingival fibroblasts (HGFs) to immune stimulation by lipopolysaccharides (LPS) has yet to be fully elucidated. Here, we showed that LPS from Porphyromonas gingivalis stimulated HGFs to increase mtROS production, which could be inhibited by treatment with a mitochondrial-targeted exogenous antioxidant (mito-TEMPO) or transfection with manganese superoxide dismutase (MnSOD). A time-course study revealed that an increase in the concentration of mtROS preceded the expression of inflammatory cytokines in HGFs. Mito-TEMPO treatment or MnSOD transfection also significantly prevented the LPS-induced increase of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. Furthermore, suppressing LPS-induced mtROS generation inhibited the activation of p38, c-Jun N-terminal kinase, and inhibitor of nuclear factor-κB kinase, as well as the nuclear localization of nuclear factor-κB. These results demonstrate that mtROS generation is a key signaling event in the LPS-induced pro-inflammatory response of HGFs. - Highlights: • Inflammation is thought to promote pathogenic changes in periodontitis. • We investigated mtROS as a regulator of inflammation in gingival fibroblasts. • Targeted antioxidants were used to inhibit mtROS production after LPS challenge. • Inhibiting mtROS generation suppressed the secretion of pro-inflammatory cytokines. • JNK, p38, IKK, and NF-κB were shown to act as transducers of mtROS signaling.

Mitochondrial reactive oxygen species mediate the lipopolysaccharide-induced pro-inflammatory response in human gingival fibroblasts

International Nuclear Information System (INIS)

Li, Xue; Wang, Xiaoxuan; Zheng, Ming; Luan, Qing Xian

2016-01-01

Although periodontal diseases are initiated by bacteria that colonize the tooth surface and gingival sulcus, the host response is believed to play an essential role in the breakdown of connective tissue and bone. Mitochondrial reactive oxygen species (mtROS) have been proposed to regulate the activation of the inflammatory response by the innate immune system. However, the role of mtROS in modulating the response of human gingival fibroblasts (HGFs) to immune stimulation by lipopolysaccharides (LPS) has yet to be fully elucidated. Here, we showed that LPS from Porphyromonas gingivalis stimulated HGFs to increase mtROS production, which could be inhibited by treatment with a mitochondrial-targeted exogenous antioxidant (mito-TEMPO) or transfection with manganese superoxide dismutase (MnSOD). A time-course study revealed that an increase in the concentration of mtROS preceded the expression of inflammatory cytokines in HGFs. Mito-TEMPO treatment or MnSOD transfection also significantly prevented the LPS-induced increase of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. Furthermore, suppressing LPS-induced mtROS generation inhibited the activation of p38, c-Jun N-terminal kinase, and inhibitor of nuclear factor-κB kinase, as well as the nuclear localization of nuclear factor-κB. These results demonstrate that mtROS generation is a key signaling event in the LPS-induced pro-inflammatory response of HGFs. - Highlights: • Inflammation is thought to promote pathogenic changes in periodontitis. • We investigated mtROS as a regulator of inflammation in gingival fibroblasts. • Targeted antioxidants were used to inhibit mtROS production after LPS challenge. • Inhibiting mtROS generation suppressed the secretion of pro-inflammatory cytokines. • JNK, p38, IKK, and NF-κB were shown to act as transducers of mtROS signaling.

Chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and TNF-α mediated apoptosis in the kidneys of CD1 treated mice

Energy Technology Data Exchange (ETDEWEB)

Riezzo, Irene; Turillazzi, Emanuela; Bello, Stefania; Cantatore, Santina [Department of Forensic Pathology, University of Foggia, Foggia (Italy); Cerretani, Daniela [Pharmacology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena (Italy); Di Paolo, Marco [Department of Forensic Pathology, University of Pisa, Pisa (Italy); Fiaschi, Anna Ida [Pharmacology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena (Italy); Frati, Paola [Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, University of Rome Sapienza, Viale Regina Elena 336, 00161 Rome (Italy); Neri, Margherita [Department of Forensic Pathology, University of Foggia, Foggia (Italy); Pedretti, Monica [Department of Forensic Pathology, University of Pisa, Pisa (Italy); Fineschi, Vittorio, E-mail: vfinesc@tin.it [Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, University of Rome Sapienza, Viale Regina Elena 336, 00161 Rome (Italy)

2014-10-01

Nandrolone decanoate administration and strenuous exercise increase the extent of renal damage in response to renal toxic injury. We studied the role played by oxidative stress in the apoptotic response caused by nandrolone decanoate in the kidneys of strength-trained male CD1 mice. To measure cytosolic enzyme activity, glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA) were determined after nandrolone treatment. An immunohistochemical study and Western blot analysis were performed to evaluate cell apoptosis and to measure the effects of renal expression of inflammatory mediators (IL-1β, TNF-α) on the induction of apoptosis (HSP90, TUNEL). Dose-related oxidative damage in the kidneys of treated mice is shown by an increase in MDA levels and by a reduction of antioxidant enzyme GR and GPx activities, resulting in the kidney's reduced radical scavenging ability. Renal specimens of the treated group showed relevant glomeruli alterations and increased immunostaining and protein expressions, which manifested significant focal segmental glomerulosclerosis. The induction of proinflammatory cytokine expression levels was confirmed by Western blot analysis. Long-term administration of nandrolone promotes oxidative injury in the mouse kidneys. TNF-α mediated injury due to nandrolone in renal cells appears to play a role in the activation of both the intrinsic and extrinsic apoptosis pathways. - Highlights: • We analyze abuse of nandrolone decanoate in strength-trained male CD1 mice. • Nandrolone decanoate administration increases oxidative stress. • Increased cytokine expressions were observed. • Renal apoptosis was described. • Long-term administration of nandrolone promotes oxidative injury in mice kidney.

Chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and TNF-α mediated apoptosis in the kidneys of CD1 treated mice

International Nuclear Information System (INIS)

Riezzo, Irene; Turillazzi, Emanuela; Bello, Stefania; Cantatore, Santina; Cerretani, Daniela; Di Paolo, Marco; Fiaschi, Anna Ida; Frati, Paola; Neri, Margherita; Pedretti, Monica; Fineschi, Vittorio

2014-01-01

Nandrolone decanoate administration and strenuous exercise increase the extent of renal damage in response to renal toxic injury. We studied the role played by oxidative stress in the apoptotic response caused by nandrolone decanoate in the kidneys of strength-trained male CD1 mice. To measure cytosolic enzyme activity, glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA) were determined after nandrolone treatment. An immunohistochemical study and Western blot analysis were performed to evaluate cell apoptosis and to measure the effects of renal expression of inflammatory mediators (IL-1β, TNF-α) on the induction of apoptosis (HSP90, TUNEL). Dose-related oxidative damage in the kidneys of treated mice is shown by an increase in MDA levels and by a reduction of antioxidant enzyme GR and GPx activities, resulting in the kidney's reduced radical scavenging ability. Renal specimens of the treated group showed relevant glomeruli alterations and increased immunostaining and protein expressions, which manifested significant focal segmental glomerulosclerosis. The induction of proinflammatory cytokine expression levels was confirmed by Western blot analysis. Long-term administration of nandrolone promotes oxidative injury in the mouse kidneys. TNF-α mediated injury due to nandrolone in renal cells appears to play a role in the activation of both the intrinsic and extrinsic apoptosis pathways. - Highlights: • We analyze abuse of nandrolone decanoate in strength-trained male CD1 mice. • Nandrolone decanoate administration increases oxidative stress. • Increased cytokine expressions were observed. • Renal apoptosis was described. • Long-term administration of nandrolone promotes oxidative injury in mice kidney

Alcoholism: a systemic proinflammatory condition.

Science.gov (United States)

González-Reimers, Emilio; Santolaria-Fernández, Francisco; Martín-González, María Candelaria; Fernández-Rodríguez, Camino María; Quintero-Platt, Geraldine

2014-10-28

Excessive ethanol consumption affects virtually any organ, both by indirect and direct mechanisms. Considerable research in the last two decades has widened the knowledge about the paramount importance of proinflammatory cytokines and oxidative damage in the pathogenesis of many of the systemic manifestations of alcoholism. These cytokines derive primarily from activated Kupffer cells exposed to Gram-negative intestinal bacteria, which reach the liver in supra-physiological amounts due to ethanol-mediated increased gut permeability. Reactive oxygen species (ROS) that enhance the inflammatory response are generated both by activation of Kupffer cells and by the direct metabolic effects of ethanol. The effects of this increased cytokine secretion and ROS generation lie far beyond liver damage. In addition to the classic consequences of endotoxemia associated with liver cirrhosis that were described several decades ago, important research in the last ten years has shown that cytokines may also induce damage in remote organs such as brain, bone, muscle, heart, lung, gonads, peripheral nerve, and pancreas. These effects are even seen in alcoholics without significant liver disease. Therefore, alcoholism can be viewed as an inflammatory condition, a concept which opens the possibility of using new therapeutic weapons to treat some of the complications of this devastating and frequent disease. In this review we examine some of the most outstanding consequences of the altered cytokine regulation that occurs in alcoholics in organs other than the liver.

Photoperiodic Regulation of Behavioral Responsiveness to Proinflammatory Cytokines

OpenAIRE

Wen, Jarvi C.; Prendergast, Brian J.

2007-01-01

Symptoms of bacterial infection include decreases in body mass (cachexia), induction of depressive-like hedonic tone (anhedonia), decreases in food intake (anorexia), and increases in body temperature (fever). Recognition of bacteria by the innate immune system triggers the release of proinflammatory cytokines which induce these sickness behaviors via central and peripheral substrates. In Siberian hamsters, exposure to short day lengths decreases both the production of proinflammatory cytokin...

Fas activity mediates airway inflammation during mouse adenovirus type 1 respiratory infection.

Science.gov (United States)

Adkins, Laura J; Molloy, Caitlyn T; Weinberg, Jason B

2018-06-13

CD8 T cells play a key role in clearance of mouse adenovirus type 1 (MAV-1) from the lung and contribute to virus-induced airway inflammation. We tested the hypothesis that interactions between Fas ligand (FasL) and Fas mediate the antiviral and proinflammatory effects of CD8 T cells. FasL and Fas expression were increased in the lungs of C57BL/6 (B6) mice during MAV-1 respiratory infection. Viral replication and weight loss were similar in B6 and Fas-deficient (lpr) mice. Histological evidence of pulmonary inflammation was similar in B6 and lpr mice, but lung mRNA levels and airway proinflammatory cytokine concentrations were lower in MAV-1-infected lpr mice compared to infected B6 mice. Virus-induced apoptosis in lungs was not affected by Fas deficiency. Our results suggest that the proinflammatory effects of CD8 T cells during MAV-1 infection are mediated in part by Fas activation and are distinct from CD8 T cell antiviral functions. Copyright © 2018 Elsevier Inc. All rights reserved.

Cerebrovascular accidents in adult patients with congenital heart disease

NARCIS (Netherlands)

Hoffmann, A.; Chockalingam, P.; Balint, O.H.; Dadashev, A.; Dimopoulos, K.; Engel, R.; Schmid, M.; Schwerzmann, M.; Gatzoulis, M.A.; Mulder, B.J.M.; Oechslin, E.

2010-01-01

Objective To investigate the prevalence and characteristics of cerebrovascular accidents (CVA) in a large population of adults with congenital heart disease (CHD). Methods and results In a retrospective analysis of aggregated European and Canadian databases a total population of 23 153 patients with

Myelin Breakdown Mediates Age-Related Slowing in Cognitive Processing Speed in Healthy Elderly Men

Science.gov (United States)

Lu, Po H.; Lee, Grace J.; Tishler, Todd A.; Meghpara, Michael; Thompson, Paul M.; Bartzokis, George

2013-01-01

Background: To assess the hypothesis that in a sample of very healthy elderly men selected to minimize risk for Alzheimer's disease (AD) and cerebrovascular disease, myelin breakdown in late-myelinating regions mediates age-related slowing in cognitive processing speed (CPS). Materials and methods: The prefrontal lobe white matter and the genu of…

Proinflammatory cytokine levels in patients with conversion disorder.

Science.gov (United States)

Tiyekli, Utkan; Calıyurt, Okan; Tiyekli, Nimet Dilek

2013-06-01

It was aimed to evaluate the relationship between proinflammatory cytokine levels and conversion disorder both commonly known as stress regulated. Baseline proinflammatory cytokine levels-[Tumour necrosis factor alpha (TNF-α), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6)]-were evaluated with enzyme-linked immunosorbent assay in 35 conversion disorder patients and 30 healthy controls. Possible changes in proinflammatory cytokine levels were evaluated again, after their acute phase in conversion disorder patients. Statistically significant decreased serum TNF-α levels were obtained in acute phase of conversion disorder. Those levels increased after acute conversion phase. There were no statistically significant difference observed between groups in serum IL-1β and (IL-6) levels. Stress associated with conversion disorder may suppress immune function in acute conversion phase and may have diagnostic and therapeutic value.

Incidence of cerebrovascular accidents in patients undergoing minimally invasive valve surgery.

Science.gov (United States)

LaPietra, Angelo; Santana, Orlando; Mihos, Christos G; DeBeer, Steven; Rosen, Gerald P; Lamas, Gervasio A; Lamelas, Joseph

2014-07-01

Minimally invasive valve surgery has been associated with increased cerebrovascular complications. Our objective was to evaluate the incidence of cerebrovascular accidents in patients undergoing minimally invasive valve surgery. We retrospectively reviewed all the minimally invasive valve surgery performed at our institution from January 2009 to June 2012. The operative times, lengths of stay, postoperative complications, and mortality were analyzed. A total of 1501 consecutive patients were identified. The mean age was 73 ± 13 years, and 808 patients (54%) were male. Of the 1501 patients, 206 (13.7%) had a history of a cerebrovascular accident, and 225 (15%) had undergone previous heart surgery. The procedures performed were 617 isolated aortic valve replacements (41.1%), 658 isolated mitral valve operations (43.8%), 6 tricuspid valve repairs (0.4%), 216 double valve surgery (14.4%), and 4 triple valve surgery (0.3%). Femoral cannulation was used in 1359 patients (90.5%) and central cannulation in 142 (9.5%). In 1392 patients (92.7%), the aorta was clamped, and in 109 (7.3%), the surgery was performed with the heart fibrillating. The median aortic crossclamp and cardiopulmonary bypass times were 86 minutes (interquartile range [IQR], 70-107) minutes and 116 minutes (IQR, 96-143), respectively. The median intensive care unit length of stay was 47 hours (IQR, 29-74), and the median postoperative hospital length of stay was 7 days (IQR, 5-10). A total of 23 cerebrovascular accidents (1.53%) and 38 deaths (2.53%) had occurred at 30 days postoperatively. Minimally invasive valve surgery was associated with an acceptable stroke rate, regardless of the cannulation technique. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Homocysteine and cerebrovascular accidents.

Science.gov (United States)

Datta, Saikat; Pal, Salil K; Mazumdar, Hirak; Bhandari, Biswanath; Bhattacherjee, Sharmistha; Pandit, Sudipta

2009-06-01

Hyperhomocysteinaemia is rapidly emerging as an important risk factor for coronary artery disease, possibly because of its propensity to accelerate atherosclerosis. Whether it is also a risk factor for cerebrovascular accidents (CVA) is a matter of debate till now, as there are conflicting results of the various prospective studies. The present study was performed to correlate the levels of plasma homocysteine levels with that of ischaemic and haemorrhagic CVA. Forty-two cases of CVA were randomly selected over a period of one year, and their risk factors were assessed. It was observed that serum homocysteine levels were significantly raised in those with intracerebral infarcts when compared to those with intracerebral haemorrhage, although homocysteine levels didn't prove to be prognostically significant.

Incidence of cardiovascular and cerebrovascular disease in Danish men and women with a prolonged heavy alcohol intake

DEFF Research Database (Denmark)

Hvidtfeldt, Ulla Arthur; Frederiksen, M.E.; Thygesen, L.C.

2008-01-01

significant higher incidence rates than would be expected in a standard population were observed for cardiovascular diseases (e.g., ischemic heart diseases, men: SIR = 1.76; 95% CI 1.69-1.83; women: SIR = 2.44; 95% CI 2.19-2.73) and cerebrovascular diseases (e.g., hemorrhagic stroke, men: SIR = 2.71; 95% CI 2...... rates of cardio- and cerebrovascular diseases than the population in general. METHODS: The cohort comprised 19,185 subjects (15,368 men and 3,817 women) who attended outpatient clinics for alcohol abusers within the Copenhagen Hospital Corporation (1954 to 1992). Incidence rates were standardized (SIR......) according to sex, age and calendar time to compare subjects' cardio- and cerebrovascular incidence with that of the general population of Copenhagen. RESULTS: During the period 1977 to 2001 a total of 9,397 events of cardio- and cerebrovascular disease were observed. In both men and women, statistically...

Cerebrovascular accidents in adult patients with congenital heart disease

NARCIS (Netherlands)

Hoffmann, A.; Chockalingam, P.; Balint, O. H.; Dadashev, A.; Dimopoulos, K.; Engel, R.; Schmid, M.; Schwerzmann, M.; Gatzoulis, M. A.; Mulder, B.; Oechslin, E.

2010-01-01

To investigate the prevalence and characteristics of cerebrovascular accidents (CVA) in a large population of adults with congenital heart disease (CHD). In a retrospective analysis of aggregated European and Canadian databases a total population of 23 153 patients with CHD was followed up to the

Atención primaria de salud en la Enfermedad Cerebrovascular

Directory of Open Access Journals (Sweden)

Keidy Sabater Bueno

1999-01-01

Full Text Available Se realiza un estudio retrospectivo-descriptivo para evaluar las acciones de salud que el Médico de la Familia realizó sobre los pacientes con enfermedad cerebrovascular y que fallecieron por ese motivo en el Área de Salud "Carlos Verdugo", Matanzas, durante los años 1994 y 1995. Se estudiaron 50 fallecidos en entrevista médico-familiar; se obtuvieron los datos de, edad, sexo y antecedentes patológicos personales que recogieron: enfermedades crónicas y factores de riesgo; dispensarización, que recogió número de controles realizados en los últimos 12 meses que precedieron a la defunción ya fueran en consultas, visitas de terreno y visitas integrales, así como el cumplimiento del tratamiento indicado. Se encontró que se dispensarizaron en el 100 % de los fallecidos la hipertensión arterial, la cardiopatía isquémica, la obesidad y la hiperlipidemia. El 72,4 % (12 fallecidos recibió entre 1 y 3 controles en consultas. El 79,3 % (16 fallecidos recibió entre 1 y 3 controles en visitas de terreno y el 100 % se controló entre 1 y 3 ocasiones en visitas integrales a la familia. Se concluyó que el cumplimiento del tratamiento indicado para la enfermedad cerebrovascular, los factores de riesgo y enfermedades crónicas no fue satisfactorio en el grupo estudiado. Se recomienda realizar un mayor número de controles en la atención primaria a los pacientes con enfermedad cerebrovascular sobre todo cuando en la dispensarización se encuentra la asociación hipertensión arterial, hábito de fumar y mayores de 65 años.A retrospective descriptive study was conducted to evaluate the health actions taken by the family physician in connection with those patients that suffered from cerebrovascular disease and died due to this cause in the "Carlos Verdugo" health area, Matanzas, during 1994 and 1995. 50 dead patients were studied through doctor relative interviews. The following data were obtained: age, sex, personal pathological history

Cerebrovascular defects in Foxc1 mutants correlate with aberrant WNT and VEGF-A pathways downstream of retinoic acid from the meninges.

Science.gov (United States)

Mishra, Swati; Choe, Youngshik; Pleasure, Samuel J; Siegenthaler, Julie A

2016-12-01

Growth and maturation of the cerebrovasculature is a vital event in neocortical development however mechanisms that control cerebrovascular development remain poorly understood. Mutations in or deletions that include the FOXC1 gene are associated with congenital cerebrovascular anomalies and increased stroke risk in patients. Foxc1 mutant mice display severe cerebrovascular hemorrhage at late gestational ages. While these data demonstrate Foxc1 is required for cerebrovascular development, its broad expression in the brain vasculature combined with Foxc1 mutant's complex developmental defects have made it difficult to pinpoint its function(s). Using global and conditional Foxc1 mutants, we find 1) significant cerebrovascular growth defects precede cerebral hemorrhage and 2) expression of Foxc1 in neural crest-derived meninges and brain pericytes, though not endothelial cells, is required for normal cerebrovascular development. We provide evidence that reduced levels of meninges-derived retinoic acid (RA), caused by defects in meninges formation in Foxc1 mutants, is a major contributing factor to the cerebrovascular growth defects in Foxc1 mutants. We provide data that suggests that meninges-derived RA ensures adequate growth of the neocortical vasculature via regulating expression of WNT pathway proteins and neural progenitor derived-VEGF-A. Our findings offer the first evidence for a role of the meninges in brain vascular development and provide new insight into potential causes of cerebrovascular defects in patients with FOXC1 mutations. Copyright © 2016 Elsevier Inc. All rights reserved.

Human resistin stimulates the pro-inflammatory cytokines TNF-α and IL-12 in macrophages by NF-κB-dependent pathway

International Nuclear Information System (INIS)

Silswal, Nirupama; Singh, Anil K.; Aruna, Battu; Mukhopadhyay, Sangita; Ghosh, Sudip; Ehtesham, Nasreen Z.

2005-01-01

Resistin, a recently discovered 92 amino acid protein involved in the development of insulin resistance, has been associated with obesity and type 2 diabetes. The elevated serum resistin in human diabetes is often associated with a pro-inflammatory milieu. However, the role of resistin in the development of inflammation is not well understood. Addition of recombinant human resistin protein (hResistin) to macrophages (both murine and human) resulted in enhanced secretion of pro-inflammatory cytokines, TNF-α and IL-12, similar to that obtained using 5 μg/ml lipopolysaccharide. Both oligomeric and dimeric forms of hResistin were able to activate these cytokines suggesting that the inflammatory action of resistin is independent of its conformation. Heat denatured hResistin abrogated cytokine induction while treatment of recombinant resistin with polymyxin B agarose beads had no effect thereby ruling out the role of endotoxin in the recombinant hResistin mediated cytokine induction. The pro-inflammatory nature of hResistin was further evident from the ability of this protein to induce the nuclear translocation of NF-κB transcription factor as seen from electrophoretic mobility shift assays. Induction of TNF-α in U937 cells by hResistin was markedly reduced in the presence of either dominant negative IκBα plasmid or PDTC, a pharmacological inhibitor of NF-κB. A protein involved in conferring insulin resistance is also a pro-inflammatory molecule that has important implications

Association of Vegetable Nitrate Intake With Carotid Atherosclerosis and Ischemic Cerebrovascular Disease in Older Women.

Science.gov (United States)

Bondonno, Catherine P; Blekkenhorst, Lauren C; Prince, Richard L; Ivey, Kerry L; Lewis, Joshua R; Devine, Amanda; Woodman, Richard J; Lundberg, Jon O; Croft, Kevin D; Thompson, Peter L; Hodgson, Jonathan M

2017-07-01

A short-term increase in dietary nitrate (NO 3 - ) improves markers of vascular health via formation of nitric oxide and other bioactive nitrogen oxides. Whether this translates into long-term vascular disease risk reduction has yet to be examined. We investigated the association of vegetable-derived nitrate intake with common carotid artery intima-media thickness (CCA-IMT), plaque severity, and ischemic cerebrovascular disease events in elderly women (n=1226). Vegetable nitrate intake, lifestyle factors, and cardiovascular disease risk factors were determined at baseline (1998). CCA-IMT and plaque severity were measured using B-mode carotid ultrasound (2001). Complete ischemic cerebrovascular disease hospitalizations or deaths (events) over 14.5 years (15 032 person-years of follow-up) were obtained from the West Australian Data Linkage System. Higher vegetable nitrate intake was associated with a lower maximum CCA-IMT (B=-0.015, P =0.002) and lower mean CCA-IMT (B=-0.012, P =0.006). This relationship remained significant after adjustment for lifestyle and cardiovascular risk factors ( P ≤0.01). Vegetable nitrate intake was not a predictor of plaque severity. In total 186 (15%) women experienced an ischemic cerebrovascular disease event. For every 1 SD (29 mg/d) higher intake of vegetable nitrate, there was an associated 17% lower risk of 14.5-year ischemic cerebrovascular disease events in both unadjusted and fully adjusted models ( P =0.02). Independent of other risk factors, higher vegetable nitrate was associated with a lower CCA-IMT and a lower risk of an ischemic cerebrovascular disease event. © 2017 American Heart Association, Inc.

Adaptive cognitive testing in cerebrovascular disease and vascular dementia

NARCIS (Netherlands)

Wouters, Hans; de Koning, Inge; Zwinderman, Aeilko H; van Gool, Willem A; Schmand, Ben; Buiter, Maarten; Lindeboom, Robert

2009-01-01

BACKGROUND/AIMS: To examine whether brevity can be combined with precision in measuring global cognitive ability in patients with cerebrovascular disease (CVD) or vascular dementia (VaD). Longer tests (e.g. the CAMCOG) are precise but inefficient, whereas brief tests (e.g. the MMSE) are efficient

The Impact of Aging on Cardio and Cerebrovascular Diseases

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Carmine Izzo

2018-02-01

Full Text Available A growing number of evidences report that aging represents the major risk factor for the development of cardio and cerebrovascular diseases. Understanding Aging from a genetic, biochemical and physiological point of view could be helpful to design a better medical approach and to elaborate the best therapeutic strategy to adopt, without neglecting all the risk factors associated with advanced age. Of course, the better way should always be understanding risk-to-benefit ratio, maintenance of independence and reduction of symptoms. Although improvements in treatment of cardiovascular diseases in the elderly population have increased the survival rate, several studies are needed to understand the best management option to improve therapeutic outcomes. The aim of this review is to give a 360° panorama on what goes on in the fragile ecosystem of elderly, why it happens and what we can do, right now, with the tools at our disposal to slow down aging, until new discoveries on aging, cardio and cerebrovascular diseases are at hand.

Alzheimer's disease: Cerebrovascular dysfunction, oxidative stress, and advanced clinical therapies

NARCIS (Netherlands)

Marlatt, M.W.; Lucassen, P.J.; Perry, G.; Smith, M.A.; Zhu, X.

2008-01-01

Many lines of independent research have provided convergent evidence regarding oxidative stress, cerebrovascular disease, dementia, and Alzheimer's disease (AD). Clinical studies spurred by these findings engage basic and clinical communities with tangible results regarding molecular targets and

Radioiodine therapy increases the risk of cerebrovascular events in hyperthyroid and euthyroid patients

DEFF Research Database (Denmark)

la Cour, Jeppe Lerche; Jensen, Lars Thorbjoern; Vej-Hansen, Anders

2015-01-01

to radiation and is capable of inducing atherosclerosis. The objective of the study was to elucidate whether ionizing radiation from radioiodine might contribute to cerebrovascular morbidity. METHODS: In a retrospective register cohort study, 4000 hyperthyroid and 1022 euthyroid goitre patients treated...... with radioiodine between 1975 and 2008 were matched 1:4 on age and sex with random controls. The cohort was followed from the date of treatment until hospitalization due to cerebrovascular event, death, 20 years of follow-up or March 2013. Data were analyzed in competing risk models adjusting for age, sex...

The relationship between cerebrovascular disease and homocysteine, folate and vitamin B12 in serum

International Nuclear Information System (INIS)

Wang Wei; Yang Chen; Shi Yizhen; Liu Zengli

2005-01-01

To investigate the relationship between cerebrovascular disease and the serum levels of homocysteine(Hcy), folate and vitamin B 12 , the serum levels of Hcy, folate and vitamin B 12 in 148 patients with cerebrovascular disease were measured by fluorescence polarization immuno- assay and chemiluminescence and were compared with those in healthy controls. The result showed that the serum Hcy levels in patients with cerebral infarction, cerebral hemorrhage and vertebrobasilar ischemiay were significantly higher than those in healthy controls (P 12 levels were signifieantly lower (P 0.05). No significantly higher ratio of increased Hcy levels was observed in patient with complications (P> 0.05). Our conclusion is that hyperhomocysteinemia may be a new and an independent risk factor for cerebrovascular disease. The serum Hcy level is correlated with decreased levels of folate and vitamin B 12 but not obviously correlated with hypertension, diabetes and coronary heart disease. (authors)

Chronic Pancreatitis Correlates With Increased Risk of Cerebrovascular Disease: A Retrospective Population-Based Cohort Study in Taiwan.

Science.gov (United States)

Wong, Tuck-Siu; Liao, Kuan-Fu; Lin, Chi-Ming; Lin, Cheng-Li; Chen, Wen-Chi; Lai, Shih-Wei

2016-04-01

The aim of this study is to explore whether there is a relationship between chronic pancreatitis and cerebrovascular disease in Taiwan. Using the claims data of the Taiwan National Health Insurance Program, we identified 16,672 subjects aged 20 to 84 years with a new diagnosis of chronic pancreatitis from 2000 to 2010 as the chronic pancreatitis group. We randomly selected 65,877 subjects aged 20 to 84 years without chronic pancreatitis as the nonchronic pancreatitis group. Both groups were matched by sex, age, comorbidities, and the index year of diagnosing chronic pancreatitis. The incidence of cerebrovascular disease at the end of 2011 was measured. The multivariable Cox proportional hazards regression model was used to measure the hazard ratio (HR) and 95% confidence interval (CI) for cerebrovascular disease risk associated with chronic pancreatitis and other comorbidities. The overall incidence of cerebrovascular disease was 1.24-fold greater in the chronic pancreatitis group than that in the nonchronic pancreatitis group (14.2 vs. 11.5 per 1000 person-years, 95% CI = 1.19-1.30). After controlling for confounding factors, the adjusted HR of cerebrovascular disease was 1.27 (95% CI = 1.19-1.36) for the chronic pancreatitis group as compared with the nonchronic pancreatitis group. Woman (adjusted HR = 1.41, 95% CI = 1.31-1.51), age (every 1 year, HR = 1.04, 95% CI = 1.04-1.05), atrial fibrillation (adjusted HR = 1.23, 95% CI = 1.02-1.48), chronic kidney disease (adjusted HR = 1.48, 95% CI = 1.31-1.67), chronic obstructive pulmonary disease (adjusted HR = 1.27, 95% CI = 1.16-1.40), diabetes mellitus (adjusted HR = 1.82, 95% CI = 1.72-1.92), hypertension (adjusted HR = 1.66, 95% CI = 1.56-1.76), and peripheral atherosclerosis (adjusted HR = 1.26, 95% CI = 1.06-1.51) were other factors significantly associated with cerebrovascular disease. Chronic pancreatitis is associated with increased

Anatomical variations of the circle of Willis and cerebrovascular accidents in transitional Albania

Directory of Open Access Journals (Sweden)

Edlira Harizi (Shemsi

2015-12-01

Full Text Available Aim: The purpose of this study was twofold: i in a case-control design, to determine the relationship between anatomical variations of the circle of Willis and cerebrovascular accidents; ii to assess the association between anatomical variations of the circle of Willis and aneurisms among patients with subarachnoid hemorrhage. Methods: A case-control study was conducted in Albania in 2013-2014, including 100 patients with subarachnoid hemorrhage and 100 controls (individuals without cerebrovascular accidents. Patients with subarachnoid hemorrhage underwent a CT angiography procedure, whereas individuals in the control group underwent a magnetic resonance angiography procedure. Binary logistic regression was used to assess the association between cerebrovascular accidents and the anatomical variations of the circle of Willis. Conversely, Fisher’s exact test was used to compare the prevalence of aneurisms between subarachnoid hemorrhage patients with and without anatomical variations of the circle of Willis. Results: Among patients, there were 22 (22% cases with anatomical variations of the circle of Willis compared with 10 (10% individuals in the control group (P=0.033. There was no evidence of a statistically significant difference in the types of the anatomical variations of the circle of Willis between patients and controls (P=0.402. In age- and-sex adjusted logistic regression models, there was evidence of a significant positive association between cerebrovascular accidents and the anatomical variations of the circle of Willis (OR=1.87, 95%CI=1.03-4.68, P=0.048. Within the patients’ group, of the 52 cases with aneurisms, there were 22 (42.3% individuals with anatomical variations of the circle of Willis compared with no individuals with anatomical variations among the 48 patients without aneurisms (P<0.001. Conclusion: This study provides useful evidence on the association between anatomical variations of the circle of Willis and

Curcuma longa polyphenols improve insulin-mediated lipid accumulation and attenuate proinflammatory response of 3T3-L1 adipose cells during oxidative stress through regulation of key adipokines and antioxidant enzymes.

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Septembre-Malaterre, Axelle; Le Sage, Fanny; Hatia, Sarah; Catan, Aurélie; Janci, Laurent; Gonthier, Marie-Paule

2016-07-08

Plant polyphenols may exert beneficial action against obesity-related oxidative stress and inflammation which promote insulin resistance. This study evaluated the effect of polyphenols extracted from French Curcuma longa on 3T3-L1 adipose cells exposed to H2 O2 -mediated oxidative stress. We found that Curcuma longa extract exhibited high amounts of curcuminoids identified as curcumin, demethoxycurcumin, and bisdemethoxycurcumin, which exerted free radical-scavenging activities. Curcuma longa polyphenols improved insulin-mediated lipid accumulation and upregulated peroxisome proliferator-activated receptor-gamma gene expression and adiponectin secretion which decreased in H2 O2 -treated cells. Curcuminoids attenuated H2 O2 -enhanced production of pro-inflammatory molecules such as interleukin-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and nuclear factor κappa B. Moreover, they reduced intracellular levels of reactive oxygen species elevated by H2 O2 and modulated the expression of genes encoding superoxide dismutase and catalase antioxidant enzymes. Collectively, these findings highlight that Curcuma longa polyphenols protect adipose cells against oxidative stress and may improve obesity-related metabolic disorders. © 2016 BioFactors, 42(4):418-430, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

Proinflammatory Cytokine Responses in Extra-Respiratory Tissues During Severe Influenza

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Short, Kirsty R; Veeris, Rebecca; Leijten, Lonneke M; van den Brand, Judith M; Jong, Victor L; Stittelaar, Koert J; Osterhaus, Ab D M E|info:eu-repo/dai/nl/074960172; Andeweg, Arno C; van Riel, Debby

2017-01-01

Severe influenza is often associated with disease manifestations outside the respiratory tract. While proinflammatory cytokines can be detected in the lungs and blood of infected patients, the role of extra-respiratory organs in the production of proinflammatory cytokines is unknown. Here, we show

Proinflammatory Cytokine Responses in Extra-Respiratory Tissues during Severe Influenza

NARCIS (Netherlands)

Short, Kirsty R.; Veeris, Rebecca; Leijten, Lonneke M.; van den Brand, Judith M A; Jong, Victor L.; Stittelaar, Koert; Osterhaus, Ab D.M.E.; Andeweg, Arno C; Van Riel, Debby

2017-01-01

Severe influenza is often associated with disease manifestations outside the respiratory tract. While proinflammatory cytokines can be detected in the lungs and blood of infected patients, the role of extra-respiratory organs in the production of proinflammatory cytokines is unknown. Here, we show

Clinical value of serum vitamin B12 and folate in cerebrovascular disease

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Zhan Hao; Zhang Yongxue

2002-01-01

To study the clinical value of serum vitamin B 12 and folate in cerebrovascular disease, the concentration of serum vitamin B 12 and folate in 32 patients with cerebrovascular disease was measured by radioimmunoassay. The results showed that the changes in folate in all groups were not significant. The content of vitamin B 12 in multi-infarct dementia was markedly lower than that in cerebral infarction and cerebral hemorrhage. Moreover, the level of vitamin B 12 was lower in paralytic patients with muscular strength of grade 0-III. It can be concluded that serum vitamin B 12 level had association with intelligent disorder and paralytic degree

Serum uric acid level as a cardio-cerebrovascular event risk factor in middle-aged and non-obese Chinese men.

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Li, Zhi-Jun; Yi, Chen-Ju; Li, Jing; Tang, Na

2017-04-11

The role of uric acid as a risk factor for cardio-cerebrovascular diseases is controversial. In this study, we aimed to investigate the relationship between serum uric acid level and the risk of cardio-cerebrovascular events in middle-aged and non-obese Chinese men. We included 3152 participants from the health examination center of Tongji Hospital from June 2007 to June 2010. Clinical examination and medical records were collected at the annual health examination. The hazard ratios (HRs) of uric acid for cardio-cerebrovascular events were calculated by Cox proportional hazards models. Generalized additive model and threshold effect analysis were used to explore the non-linear relationship between serum uric acid level and the incidence of cardio-cerebrovascular event. The mean follow-up time was 52 months. When the participants were classified into four groups by the serum acid quarter (Q1-Q4), the HRs (95% CI) of Q2-Q4 for cardio-cerebrovascular events were 1.26 (0.83, 1.92), 1.97 (1.33, 2.91) and 2.05 (1.40, 3.01), respectively, compared with the reference (Q1). The actual incidence and conditional incidence of cardio-cerebrovascular events in the high serum acid group were higher than those in the low serum acid group, which were stratified by the turning point (sUA = 372 μmol/L). We also showed a strong prognostic accuracy of the multiple variable-based score in 3 years and 5 years, with area under the receiver operating characteristic (ROC) curve of 0.790 (0.756-0.823) and 0.777 (0.749-0.804), respectively. Serum uric acid level is a strong risk factor for cardio-cerebrovascular events.

The increase of the life quality for patients who had a cerebrovascular accident by using the MBT physiotherapy device

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Danelciuc Francisc Tadeus

2017-05-01

Full Text Available The cerebrovascular accident is a major health issue, with medical and economic consequences upon the society. The cerebrovascular accident determines the sensorial and motor impairment, the speech and postural control impairment. Some patients who had a cerebrovascular accident may have difficulties in the response to the postural perturbations. Some patients who had a cerebrovascular accident may have difficulties in the response to the postural perturbations. The recovery of the postural control and of the balance depends on the quality of the motor action in order to use the ADL and to ensure the social and professional reintegration of the patients. That is why the postural control is essential in the recovery of the patients who had a cerebrovascular accident. The current study aims at the possibilities to regain the postural control for the patients with motor deficit by an individual program of recovery sessions. The current trial aimed at finding the way in which it is possible to influence the quality of life for the patients who had a cerebrovascular accident by using the MBT physiotherapy device. The use of the MBT physiotherapy devices in the recovery programme of the postural control after the cerebrovascular accident involves the need to set up an individualized programme of kinetic therapy. According to the established deficiency, namely the average one and the slight one, the recovery programme would need the introduction of techniques and methods whose effect is to reeducate the postural function. This can be done more easily if the recovery is initiated by using the MBT physiotherapy device that can intervene in the functional recovery which corresponds to each recovery stage.

Histone deacetylase 2 is decreased in peripheral blood pro-inflammatory CD8+ T and NKT-like lymphocytes following lung transplant.

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Hodge, Greg; Hodge, Sandra; Holmes-Liew, Chien-Li; Reynolds, Paul N; Holmes, Mark

2017-02-01

Immunosuppression therapy following lung transplantation fails to prevent chronic rejection in many patients, which is associated with lack of suppression of cytotoxic mediators and pro-inflammatory cytokines in peripheral blood T and natural killer T (NKT)-like cells. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) upregulate/downregulate pro-inflammatory gene expression, respectively; however, differences in the activity of these enzymes following lung transplant are unknown. We hypothesized decreased HDAC2 expression and increased HAT expression in pro-inflammatory lymphocytes following lung transplant. Blood was collected from 18 stable lung transplant patients and 10 healthy age-matched controls. Intracellular pro-inflammatory cytokines and HAT/HDAC2 expression were determined in lymphocyte subsets following culture using flow cytometry. A loss of HDAC2 in cluster of differentiation (CD) 8+ T and NKT-like cells in transplant patients compared with controls was noted (CD8+ T: 28 ± 10 (45 ± 10), CD8+NKT-like: 30 ± 13 (54 ± 16) (mean ± SD transplant) (control)). Loss of HDAC2 was associated with an increased percentage of CD8+ T and NKT-like cells expressing perforin, granzyme b, interferon gamma (IFN-γ) and TNF-α (no change in HAT expression in any lymphocyte subset). There was a negative correlation between loss of HDAC2 expression by CD8+ T cells with cumulative dose of prednisolone and time post-transplant. Treatment with 10 mg/L theophylline + 1 µmol/L prednisolone or 2.5 ng/mL cyclosporine A synergistically upregulated HDAC2 and inhibited IFN-γ and TNF-α production by CD8+ T and NKT-like lymphocytes. HDAC2 is decreased in CD8+ T and NKT-like pro-inflammatory lymphocytes following lung transplant. Treatment options that increase HDAC2 may improve graft survival. © 2016 Asian Pacific Society of Respirology.

Anti-inflammatory activity of traditional Chinese medicinal herbs

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Min-Hsiung Pan

2011-10-01

Full Text Available Accumulating epidemiological and clinical evidence shows that inflammation is an important risk factor for various human diseases. Thus, suppressing chronic inflammation has the potential to delay, prevent, and control various chronic diseases, including cerebrovascular, cardiovascular, joint, skin, pulmonary, blood, lymph, liver, pancreatic, and intestinal diseases. Various natural products from traditional Chinese medicine (TCM have been shown to safely suppress proinflammatory pathways and control inflammation-associated disease. In vivo and/or in vitro studies have demonstrated that anti-inflammatory effects of TCM occur by inhibition of the expression of master transcription factors (for example, nuclear factor-κB (NF-κB, pro-inflammatory cytokines (for example, tumor necrosis factor-α (TNF-α, chemokines (for example, chemokine (C-C motif ligand (CCL-24, intercellular adhesion molecule expression and pro-inflammatory mediators (for example, inducible nitric oxide synthase (iNOS and cyclooxygenase 2 (COX2. However, a handful of review articles have focused on the anti-inflammatory activities of TCM and explore their possible mechanisms of action. In this review, we summarize recent research attempting to identify the anti-inflammatory constituents of TCM and their molecular targets that may create new opportunities for innovation in modern pharmacology.

Agonists for G-protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microglia.

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Wei, Li; Tokizane, Kyohei; Konishi, Hiroyuki; Yu, Hua-Rong; Kiyama, Hiroshi

2017-10-03

Several G-protein-coupled receptors (GPCRs) have been shown to be important signaling mediators between neurons and glia. In our previous screening for identification of nerve injury-associated GPCRs, G-protein-coupled receptor 84 (GPR84) mRNA showed the highest up-regulation by microglia after nerve injury. GPR84 is a pro-inflammatory receptor of macrophages in a neuropathic pain mouse model, yet its function in resident microglia in the central nervous system is poorly understood. We used endogenous, natural, and surrogate agonists for GPR84 (capric acid, embelin, and 6-OAU, respectively) and examined their effect on mouse primary cultured microglia in vitro. 6-n-Octylaminouracil (6-OAU), embelin, and capric acid rapidly induced membrane ruffling and motility in cultured microglia obtained from C57BL/6 mice, although these agonists failed to promote microglial pro-inflammatory cytokine expression. Concomitantly, 6-OAU suppressed forskolin-induced increase of cAMP in cultured microglia. Pertussis toxin, an inhibitor of Gi-coupled signaling, completely suppressed 6-OAU-induced microglial membrane ruffling and motility. In contrast, no 6-OAU-induced microglial membrane ruffling and motility was observed in microglia from DBA/2 mice, a mouse strain that does not express functional GPR84 protein due to endogenous nonsense mutation of the GPR84 gene. GPR84 mediated signaling causes microglial motility and membrane ruffling but does not promote pro-inflammatory responses. As GPR84 is a known receptor for medium-chain fatty acids, those released from damaged brain cells may be involved in the enhancement of microglial motility through GPR84 after neuronal injury.

Endogenous sex steroids and cardio- and cerebro-vascular disease in the postmenopausal period.

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Pappa, Theodora; Alevizaki, Maria

2012-08-01

Cardio- and cerebro-vascular diseases are two leading causes of death and long-term disability in postmenopausal women. The acute fall of estrogen in menopause is associated with increased cardiovascular risk. The relative contribution of androgen to this risk is also being recognized. The use of more sensitive assays for estradiol measurement and the study of receptor and carrier protein gene polymorphisms have provided some new information on the clinical relevance of endogenous sex steroids. We provide an update on the role of endogenous sex steroids on cardio- and cerebro-vascular disease in the postmenopausal period. We performed a PubMed search using the terms 'endogenous estrogen', 'androgen', 'cardiovascular disease', 'cerebro-vascular disease', 'stroke', 'carotid artery disease', and 'subclinical atherosclerosis'. The majority of studies show a beneficial effect of endogenous estrogen on the vasculature; however, there are a few studies reporting the contrary. A significant body of literature has reported associations of endogenous estrogen and androgen with early markers of atherosclerosis and metabolic parameters. Data on the relevance of endogenous sex steroids in heart disease and stroke are inconclusive. Most studies support a beneficial role of endogenous estrogens and, probably, an adverse effect of androgens in the vasculature in postmenopausal women. However, the described associations may not always be considered as causal. It is possible that circulating estrogen might represent a marker of general health status or alternatively reflect the sum of endogenous androgens aromatized in the periphery. Elucidating the role of sex steroids in cardio- and cerebro-vascular disease remains an interesting field of future research.

Cyclooxygenases 1 and 2 differentially regulate blood pressure and cerebrovascular responses to acute and chronic intermittent hypoxia: implications for sleep apnea.

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Beaudin, Andrew E; Pun, Matiram; Yang, Christina; Nicholl, David D M; Steinback, Craig D; Slater, Donna M; Wynne-Edwards, Katherine E; Hanly, Patrick J; Ahmed, Sofia B; Poulin, Marc J

2014-05-09

Obstructive sleep apnea (OSA) is associated with increased risk of cardiovascular and cerebrovascular disease resulting from intermittent hypoxia (IH)-induced inflammation. Cyclooxygenase (COX)-formed prostanoids mediate the inflammatory response, and regulate blood pressure and cerebral blood flow (CBF), but their role in blood pressure and CBF responses to IH is unknown. Therefore, this study's objective was to determine the role of prostanoids in cardiovascular and cerebrovascular responses to IH. Twelve healthy, male participants underwent three, 6-hour IH exposures. For 4 days before each IH exposure, participants ingested a placebo, indomethacin (nonselective COX inhibitor), or Celebrex(®) (selective COX-2 inhibitor) in a double-blind, randomized, crossover study design. Pre- and post-IH blood pressure, CBF, and urinary prostanoids were assessed. Additionally, blood pressure and urinary prostanoids were assessed in newly diagnosed, untreated OSA patients (n=33). Nonselective COX inhibition increased pre-IH blood pressure (P ≤ 0.04) and decreased pre-IH CBF (P=0.04) while neither physiological variable was affected by COX-2 inhibition (P ≥ 0.90). Post-IH, MAP was elevated (P ≤ 0.05) and CBF was unchanged with placebo and nonselective COX inhibition. Selective COX-2 inhibition abrogated the IH-induced MAP increase (P=0.19), but resulted in lower post-IH CBF (P=0.01). Prostanoids were unaffected by IH, except prostaglandin E2 was elevated with the placebo (P=0.02). Finally, OSA patients had elevated blood pressure (P ≤ 0.4) and COX-1 formed thromboxane A2 concentrations (P=0.02). COX-2 and COX-1 have divergent roles in modulating vascular responses to acute and chronic IH. Moreover, COX-1 inhibition may mitigate cardiovascular and cerebrovascular morbidity in OSA. www.clinicaltrials.gov. Unique identifier: NCT01280006.

Host defense peptides of thrombin modulate inflammation and coagulation in endotoxin-mediated shock and Pseudomonas aeruginosa sepsis.

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Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; Mörgelin, Matthias; van der Plas, Mariena J A; Rydengård, Victoria; Malmsten, Martin; Albiger, Barbara; Schmidtchen, Artur

2012-01-01

Gram-negative sepsis is accompanied by a disproportionate innate immune response and excessive coagulation mainly induced by endotoxins released from bacteria. Due to rising antibiotic resistance and current lack of other effective treatments there is an urgent need for new therapies. We here present a new treatment concept for sepsis and endotoxin-mediated shock, based on host defense peptides from the C-terminal part of human thrombin, found to have a broad and inhibitory effect on multiple sepsis pathologies. Thus, the peptides abrogate pro-inflammatory cytokine responses to endotoxin in vitro and in vivo. Furthermore, they interfere with coagulation by modulating contact activation and tissue factor-mediated clotting in vitro, leading to normalization of coagulation responses in vivo, a previously unknown function of host defense peptides. In a mouse model of Pseudomonas aeruginosa sepsis, the peptide GKY25, while mediating a modest antimicrobial effect, significantly inhibited the pro-inflammatory response, decreased fibrin deposition and leakage in the lungs, as well as reduced mortality. Taken together, the capacity of such thrombin-derived peptides to simultaneously modulate bacterial levels, pro-inflammatory responses, and coagulation, renders them attractive therapeutic candidates for the treatment of invasive infections and sepsis.

Host defense peptides of thrombin modulate inflammation and coagulation in endotoxin-mediated shock and Pseudomonas aeruginosa sepsis.

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Martina Kalle

Full Text Available Gram-negative sepsis is accompanied by a disproportionate innate immune response and excessive coagulation mainly induced by endotoxins released from bacteria. Due to rising antibiotic resistance and current lack of other effective treatments there is an urgent need for new therapies. We here present a new treatment concept for sepsis and endotoxin-mediated shock, based on host defense peptides from the C-terminal part of human thrombin, found to have a broad and inhibitory effect on multiple sepsis pathologies. Thus, the peptides abrogate pro-inflammatory cytokine responses to endotoxin in vitro and in vivo. Furthermore, they interfere with coagulation by modulating contact activation and tissue factor-mediated clotting in vitro, leading to normalization of coagulation responses in vivo, a previously unknown function of host defense peptides. In a mouse model of Pseudomonas aeruginosa sepsis, the peptide GKY25, while mediating a modest antimicrobial effect, significantly inhibited the pro-inflammatory response, decreased fibrin deposition and leakage in the lungs, as well as reduced mortality. Taken together, the capacity of such thrombin-derived peptides to simultaneously modulate bacterial levels, pro-inflammatory responses, and coagulation, renders them attractive therapeutic candidates for the treatment of invasive infections and sepsis.

Time series analysis of the association between ambient temperature and cerebrovascular morbidity in the elderly in Shanghai, China

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Zhang, Xian-Jing; Ma, Wei-Ping; Zhao, Nai-Qing; Wang, Xi-Ling

2016-01-01

Research on the association between ambient temperature and cerebrovascular morbidity is scarce in China. In this study, we applied mixed generalized additive model (MGAM) to daily counts of cerebrovascular disease of Shanghai residents aged 65 years or older from 2007-2011, stratified by gender. Weighted daily mean temperature up to lags of one week was smoothed by natural cubic spline, and was added into the model to assess both linear and nonlinear effects of temperature. We found that when the mean temperature increased by 1 °C, the male cases of cerebrovascular disease reduced by 0.95% (95% Confidence Interval (CI): 0.80%, 1.10%) or reduced by 0.34% (95% CI: -0.68, 1.36%) in conditions of temperature was below or above 27 °C. However, for every 1 °C increase in temperature, the female cases of cerebrovascular disease increased by 0.34% (95% CI: -0.26%, 0.94%) or decreased by 0.92% (95% CI: 0.72, 1.11%) in conditions of temperature was below or above 8 °C, respectively. Temperature and cerebrovascular morbidity is negatively associated in Shanghai. MGAM is recommended in assessing the association between environmental hazards and health outcomes in time series studies.

Mortalidad intrahospitalaria por accidente cerebrovascular

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Federico Rodríguez Lucci

2013-08-01

Full Text Available La mortalidad global por accidente cerebrovascular (ACV ha disminuido en las últimas tres décadas, probablemente debido a un mejor control de los factores de riesgo vascular. La mortalidad hospitalaria por ACV ha sido tradicionalmente estimada entre 6 y 14% en la mayoría de las series comunicadas. Sin embargo, los datos de ensayos clínicos recientes sugieren que esta cifra sería sustancialmente menor. Se revisaron datos de pacientes internados con diagnóstico de ACV del Banco de Datos de Stroke de FLENI y los registros institucionales de mortalidad entre los años 2000 y 2010. Los subtipos de ACV isquémicos se clasificaron según criterios TOAST y los ACV hemorrágicos en hematomas intrapanquimatosos, hemorragias subaracnoideas aneurismáticas, malformaciones arteriovenosas y otros hematomas intraparenquimatosos. Se analizaron 1514 pacientes, 1079 (71% con ACV isquémico (grandes vasos 39%, cardioembólicos 27%, lacunares 9%, etiología indeterminada 14%, otras etiologías 11% y 435 (29% con ACV hemorrágico (intraparenquimatosos 27%, hemorragia subaracnoidea 30%, malformaciones arteriovenosas 25% y otros hematomas espontáneos 18%. Se registraron 38 muertes intrahospitalarias (17 ACV isquémicos y 21 ACV hemorrágicos, representando una mortalidad global del 2.5% (1.7% en ACV isquémicos y 4.8% en ACV hemorrágicos. No se registraron muertes asociadas al uso de fibrinolíticos endovenosos. La mortalidad intrahospitalaria en pacientes con ACV isquémico y hemorrágico en nuestro centro fue baja. El manejo en un centro dedicado a las enfermedades neurológicas y el enfoque multidisciplinario por personal médico y no médico entrenado en el cuidado de la enfermedad cerebrovascular podrían explicar, al menos en parte, estos resultados.

SICK SINUS SYNDROME IN PATIENTS WITH ACUTE CEREBROVASCULAR ACCIDENTS

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E. K. Kazakova

2015-01-01

Full Text Available The article presents a clinical case of 2 patients with heart arrhythmias of the sick sinus syndrome type, who were implanted electriccardiac pacemakers in the acute period of cerebrovascular accidents. There were no cardiac complaints in the clinical manifestation, however, a comprehensive assessment confirmed the diagnosis of sick sinus syndrome.

Brain MRI hyperintense lesions and cerebrovascular risk factors in the elderly

International Nuclear Information System (INIS)

Iidaka, Tetsuya

1993-01-01

It is known that asymptomatic MRI lesions of the brain are found in elderly subjects, but the significance of the lesions has not been determined. In previous reports, the prevalence of MRI lesions varied from 11% to 59%, but many of the authors indicated a close relationship with cerebrovascular risk factors. We evaluated 76 elderly subjects (over 60 years old, average age ±SD was 66.7±4.5) without a history of cerebrovascular disease and dementia, and determined the prevalence of periventricular (PVH), white matter (WMH) and pontine (PH) hyperintensity and risk factors. The severity of MRI lesion was evaluated in T2-weighted images by Fazekas' scoring method of MRI hyperintense lesions. PVH, WMH and PH were graded visually from 0 to 3 by the author and these points are added to the MRI score. In T1-weighted images, we also measured the diameter of the third ventricle, frontal horn and body of the lateral ventricle. Our results were that 62% of subjects had PVH, 64% had WMH and 8% had PH. In regard to risk factors, 38% of subjects had hypertension, 17% had diabetes mellitus, 8% had ischemic heart disease. The PVH (+) group was significantly older (p<0.01) and had larger lateral ventricles (p<0.05) than the PVH (-) group. The WMH (+) group was significantly older (p<0.05) and had higher risk of cerebrovascular disease (0.05) than the WMH (-) group. The MRI score was related, but not significantly, to a history of hypertension, diabetes mellitus and ischemic heart disease. The MRI score and index of ventricular enlargement correlated with age (p<0.05). In conclusion, PVH was related to aging and cerebrovascular risk factors. Therefore, PVH and WMH were suspected to have different pathogenesis and WMH was more closely related to risk factors. Our scoring method permits evaluation and comparison of MRI lesions of different groups. (author)

Long-term exposure to ambient air pollution and mortality due to cardiovascular disease and cerebrovascular disease in Shenyang, China.

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Pengfei Zhang

Full Text Available BACKGROUND: The relationship between ambient air pollution exposure and mortality of cardiovascular and cerebrovascular diseases in human is controversial, and there is little information about how exposures to ambient air pollution contribution to the mortality of cardiovascular and cerebrovascular diseases among Chinese. The aim of the present study was to examine whether exposure to ambient-air pollution increases the risk for cardiovascular and cerebrovascular disease. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a retrospective cohort study among humans to examine the association between compound-air pollutants [particulate matter <10 µm in aerodynamic diameter (PM(10, sulfur dioxide (SO(2 and nitrogen dioxide (NO(2] and mortality in Shenyang, China, using 12 years of data (1998-2009. Also, stratified analysis by sex, age, education, and income was conducted for cardiovascular and cerebrovascular mortality. The results showed that an increase of 10 µg/m(3 in a year average concentration of PM(10 corresponds to 55% increase in the risk of a death cardiovascular disease (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.51 to 1.60 and 49% increase in cerebrovascular disease (HR, 1.49; 95% CI, 1.45 to 1.53, respectively. The corresponding figures of adjusted HR (95%CI for a 10 µg/m(3 increase in NO(2 was 2.46 (2.31 to 2.63 for cardiovascular mortality and 2.44 (2.27 to 2.62 for cerebrovascular mortality, respectively. The effects of air pollution were more evident in female that in male, and nonsmokers and residents with BMI<18.5 were more vulnerable to outdoor air pollution. CONCLUSION/SIGNIFICANCE: Long-term exposure to ambient air pollution is associated with the death of cardiovascular and cerebrovascular diseases among Chinese populations.

Screening for cerebrovascular disease in microcephalic osteodysplastic primordial dwarfism type II (MOPD II): an evidence-based proposal.

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Perry, Luke D; Robertson, Fergus; Ganesan, Vijeya

2013-04-01

Microcephalic osteodysplastic primordial dwarfism type II (OMIM 210720) is a rare autosomal recessive condition frequently associated with early-onset cerebrovascular disease. Presymptomatic detection and intervention could prevent the adverse consequences associated with this. We reviewed published cases of microcephalic osteodysplastic primordial dwarfism type II to ascertain prevalence and characteristics of cerebrovascular disease and use these data to propose an evidence-based approach to cerebrovascular screening. Of 147 cases identified, 47 had cerebrovascular disease (32%), including occlusive arteriopathy (including moyamoya) and cerebral aneurysmal disease. Occlusive disease occurred in younger individuals, and progression can be both rapid and clinically silent. A reasonable screening approach would be magnetic resonance imaging and angiography of the cervical and intracranial circulation at diagnosis, repeated at yearly intervals until 10 years, and every 2 years thereafter, unless clinical concerns occur earlier. At present it would appear that this needs to be life-long. Families and professionals should be alerted to the potential significance of neurologic symptoms and measures should be taken to maintain good vascular health in affected individuals. Copyright © 2013 Elsevier Inc. All rights reserved.

Neisseria meningitidis elicits a pro-inflammatory response involving IκBζ in a human blood-cerebrospinal fluid barrier model.

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Borkowski, Julia; Li, Li; Steinmann, Ulrike; Quednau, Natascha; Stump-Guthier, Carolin; Weiss, Christel; Findeisen, Peter; Gretz, Norbert; Ishikawa, Hiroshi; Tenenbaum, Tobias; Schroten, Horst; Schwerk, Christian

2014-09-13

The human-specific, Gram-negative bacterium Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis worldwide. The blood-cerebrospinal fluid barrier (BCSFB), which is constituted by the epithelial cells of the choroid plexus (CP), has been suggested as one of the potential entry sites of Nm into the CSF and can contribute to the inflammatory response during infectious diseases of the brain. Toll-like receptors (TLRs) are involved in mediating signal transduction caused by the pathogens. Using a recently established in vitro model of the human BCSFB based on human malignant CP papilloma (HIBCPP) cells we investigated the cellular response of HIBCPP cells challenged with the meningitis-causing Nm strain, MC58, employing transcriptome and RT-PCR analysis, cytokine bead array, and enzyme-linked immunosorbent assay (ELISA). In comparison, we analyzed the answer to the closely related unencapsulated carrier isolate Nm α14. The presence of TLRs in HIBCPP and their role during signal transduction caused by Nm was studied by RT-PCR and the use of specific agonists and mutant bacteria. We observed a stronger transcriptional response after infection with strain MC58, in particular with its capsule-deficient mutant MC58siaD-, which correlated with bacterial invasion levels. Expression evaluation and Gene Set Enrichment Analysis pointed to a NFκB-mediated pro-inflammatory immune response involving up-regulation of the transcription factor IκBζ. Infected cells secreted significant levels of pro-inflammatory chemokines and cytokines, including, among others, IL8, CXCL1-3, and the IκBζ target gene product IL6. The expression profile of pattern recognition receptors in HIBCPP cells and the response to specific agonists indicates that TLR2/TLR6, rather than TLR4 or TLR2/TLR1, is involved in the cellular reaction following Nm infection. Our data show that Nm can initiate a pro-inflammatory response in human CP epithelial cells probably involving TLR2/TLR6

Evaluation of computer tomography in cerebro-vascular disease (Strokes)

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Lee, Young Sik; Baek, Seung Yon; Rhee, Chung Sik; Kim, Hee Seup

1984-01-01

Most of cerebrovascular disease are composed of vascular occulusive changes and hemorrhage. Now a day, the computed tomography is the best way for evaluation of cerebrovascular disease including detection of nature, location, and associated changes. This study includes evaluation of computed tomography of 70 patients with cerebrovascular disease during the period of 10 months from April. 1983 to Feb. 1984 in Department of Radiology, Ewha Womans University Hospital. The results were as follows: 1. Age distribution of the total 70 patients was broad ranging from 25 years to 79 years. 78.6% of patients were over the age of 50. The male and female sex ratio was 1.4:1. 2. 4 out of 70 patients were normal and 66 patients revealed abnormal on C.T. findings; those were intracranial hemorrhage (28 patients), cerebral infarction (34 patients) and brain atrophy (4 patients). 3. In cases of cerebral infarction, the cerebral hemisphere was most common site of lesion (28 cases), and next was basal ganglia (2 cases). Most of the infarcts in cerebral hemisphere were located in the parietal and temporal lobes. 4. In cases of intracranial hemorrhage, the basal ganglia was most common site of lesion (15 cases). The next common site was cerebral hemisphere (9 cases). 6 patients of all intracranial hemorrhage were combined with intraventricular hemorrhage. Ratio of right and left was 2:3. 5. In patients with motor weakness or hemiparesis, more common findings on CT scan were cerebral infarction. In case with hemiplegia, more common CT findings were intracerebral hemorrhage. 6. Of the 40 cases thought to be cerebral infarction initially by clinical findings and spinal tap. 8 cases (20.0%) were proved to be cerebral hemorrhage by the CT scan. However, of the 22 cases thought to be cerebral hemorrhage, initially, only two cases (9.0%) were cerebral infarction

Cardiomyopathy and Cerebrovascular Accident Associated with Anabolic-Androgenic Steroid Use.

Science.gov (United States)

Mochizuki, Ronald M.; Richter, Kenneth J.

1988-01-01

A case report is presented of a 32 year-old male bodybuilder who sustained an ischemic cerebrovascular accident and showed signs of cardiomyopathy. Although no cause was found, the man had been taking steroids for 16 years. Harmful effects of steroid use are discussed. (IAH)

Intra-individual variability in cerebrovascular and respiratory chemosensitivity: Can we characterize a chemoreflex "reactivity profile"?

Science.gov (United States)

Borle, Kennedy J; Pfoh, Jamie R; Boulet, Lindsey M; Abrosimova, Maria; Tymko, Michael M; Skow, Rachel J; Varner, Amy; Day, Trevor A

2017-08-01

Intra-individual variability in the magnitude of human cerebrovascular and respiratory chemoreflex responses is largely unexplored. By comparing response magnitudes of cerebrovascular CO 2 reactivity (CVR; middle and posterior cerebral arteries; MCA, PCA), central (CCR; CO 2 ) and peripheral respiratory chemoreflexes (PCR; CO 2 and O 2 ), we tested the hypothesis that a within-individual reactivity magnitude profile could be characterized. The magnitudes of CVR and CCR were tested with hyperoxic rebreathing and PCR magnitudes were tested through transient respiratory tests (TT-CO 2 , hypercapnia; TT-N 2 , hypoxia). No significant intra-individual relationships were found between CCR vs. CVR (MCA and PCA), CCR vs. PCR (TT-N 2 or TT-CO 2 ) (r0.3) response magnitudes. Statistically significant relationships were found between MCA vs. PCA reactivity (r=0.45, Pvariability that exists in human cerebrovascular and respiratory chemoreflexes. Copyright © 2017 Elsevier B.V. All rights reserved.

Coding in Stroke and Other Cerebrovascular Diseases.

Science.gov (United States)

Korb, Pearce J; Jones, William

2017-02-01

Accurate coding is critical for clinical practice and research. Ongoing changes to diagnostic and billing codes require the clinician to stay abreast of coding updates. Payment for health care services, data sets for health services research, and reporting for medical quality improvement all require accurate administrative coding. This article provides an overview of coding principles for patients with strokes and other cerebrovascular diseases and includes an illustrative case as a review of coding principles in a patient with acute stroke.

Radiation-induced cerebrovascular disease in children

International Nuclear Information System (INIS)

Wright, T.L.; Bresnan, M.J.

1976-01-01

Radiation-induced internal carotid artery occlusion has not been well recognized previously as a cause of childhood cerebrovascular disease. A child who had received radiation as a neonate for a hemangioma involving the left orbit at the age of 6 years experienced a recurrent right-sided paresis, vascular headaches, and speech difficulties. Angiography showed a hypoplastic left carotid artery with occlusion of both the anterior and middle cerebral arteries. Collateral vessels bypassed the occluded-stenotic segments. Review of the literature showed two additional cases of large vessel occlusion in childhood associated with anastomatic telangiectatic vessel development following early radiation therapy of facial hemangioma

Cerebrovascular endothelin-1 hyper-reactivity is associated with transient receptor potential canonical channels 1 and 6 activation and delayed cerebral hypoperfusion after forebrain ischaemia in rats

DEFF Research Database (Denmark)

Johansson, S E; Andersen, X E D R; Hansen, R H

2015-01-01

. METHODS: Experimental forebrain ischaemia was induced in Wistar male rats by a two-vessel occlusion model, and the cerebral blood flow was measured by magnetic resonance imaging two days after reperfusion. In vitro vasoreactivity studies, immunofluorescence and quantitative PCR were performed on cerebral...... in the vascular smooth muscle cells was enhanced and correlated with decreased cerebral blood flow two days after forebrain ischaemia. Furthermore, under conditions when voltage-dependent calcium channels were inhibited, endothelin-1-induced cerebrovascular contraction was enhanced and this enhancement...... was presumably mediated by Ca(2+) influx via upregulated transient receptor potential canonical channels 1 and 6. CONCLUSIONS: Our data demonstrates that endothelin-1-mediated influx of extracellular Ca(2+) activates transient receptor potential canonical channels 1 and 6 in cerebral vascular smooth muscle cells...

GPBAR1/TGR5 mediates bile acid-induced cytokine expression in murine Kupffer cells.

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Guiyu Lou

Full Text Available GPBAR1/TGR5 is a novel plasma membrane-bound G protein-coupled bile acid (BA receptor. BAs are known to induce the expression of inflammatory cytokines in the liver with unknown mechanism. Here we show that without other external stimuli, TGR5 activation alone induced the expression of interleukin 1β (IL-1β and tumor necrosis factor-α (TNF-α in murine macrophage cell line RAW264.7 or murine Kupffer cells. The TGR5-mediated increase of pro-inflammatory cytokine expression was suppressed by JNK inhibition. Moreover, the induced pro-inflammatory cytokine expression in mouse liver by 1% cholic acid (CA diet was blunted in JNK-/- mice. TGR5 activation by its ligands enhanced the phosphorylation levels, DNA-binding and trans-activities of c-Jun and ATF2 transcription factors. Finally, the induced pro-inflammatory cytokine expression in Kupffer cells by TGR5 activation correlated with the suppression of Cholesterol 7α-hydroxylase (Cyp7a1 expression in murine hepatocytes. These results suggest that TGR5 mediates the BA-induced pro-inflammatory cytokine production in murine Kupffer cells through JNK-dependent pathway. This novel role of TGR5 may correlate to the suppression of Cyp7a1 expression in hepatocytes and contribute to the delicate BA feedback regulation.

Host transcription factors in the immediate pro-inflammatory response to the parasitic mite Psoroptes ovis.

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Stewart T G Burgess

Full Text Available BACKGROUND: Sheep scab, caused by infestation with the ectoparasitic mite Psoroptes ovis, results in the rapid development of cutaneous inflammation and leads to the crusted skin lesions characteristic of the disease. We described previously the global host transcriptional response to infestation with P. ovis, elucidating elements of the inflammatory processes which lead to the development of a rapid and profound immune response. However, the mechanisms by which this response is instigated remain unclear. To identify novel methods of intervention a better understanding of the early events involved in triggering the immune response is essential. The objective of this study was to gain a clearer understanding of the mechanisms and signaling pathways involved in the instigation of the immediate pro-inflammatory response. RESULTS: Through a combination of transcription factor binding site enrichment and pathway analysis we identified key roles for a number of transcription factors in the instigation of cutaneous inflammation. In particular, defined roles were elucidated for the transcription factors NF-kB and AP-1 in the orchestration of the early pro-inflammatory response, with these factors being implicated in the activation of a suite of inflammatory mediators. CONCLUSIONS: Interrogation of the host temporal response to P. ovis infestation has enabled the further identification of the mechanisms underlying the development of the immediate host pro-inflammatory response. This response involves key regulatory roles for the transcription factors NF-kB and AP-1. Pathway analysis demonstrated that the activation of these transcription factors may be triggered following a host LPS-type response, potentially involving TLR4-signalling and also lead to the intriguing possibility that this could be triggered by a P. ovis allergen.

Enfermedad cerebrovascular en mujeres: estado del arte y visión del cardiólogo

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Johanna P. Contreras

2018-01-01

Full Text Available Resumen: La enfermedad cerebrovascular tiene varias denominaciones; en la actualidad se habla globalmente de ataque cerebrovascular, términos en los que se abarcan tanto manifestaciones hemorrágicas como isquémicas. Las mujeres son una población especial, con un riesgo relevante y mayores implicaciones pronósticas. Comparado con los hombres, comorbilidades como la hipertensión y la fibrilación auricular tienen mayor impacto vital y funcional en las mujeres. En el manejo no hay consideraciones que las diferencien de manera contundente, excepto en las mujeres embarazadas que requieren un ajuste especial al tratamiento, y en algunos casos no hay suficiente información para emitir una recomendación. Abstract: Cerebrovascular disease has several names and it is currently referred to as stroke, which encompasses hemorrhagic and ischemic manifestations. Women are a special population, with a relevant risk and greater prognostic implications. Comorbidities such as hypertension and atrial fibrillation have a greater impact at a vital and functional level, compared to men. Regarding management, there are no considerations that differentiate them in a definitive way, except in pregnant women (who require a special adjustment to the treatment, and in some cases there is not enough data to issue a recommendation. Palabras clave: Ataque cerebrovascular, Embarazo, Fibrilación auricular, Keywords: Stroke, Pregnancy, Atrial fibrillation

Cuidado popular de familias con un adulto mayor sobreviviente del primer accidente cerebrovascular

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Lucero López-Díaz

2016-01-01

Full Text Available Introducción: el accidente cerebrovascular afecta a numerosas personas en el mundo y se constituye en la principal causa de muer- te. Los sobrevivientes pueden padecer discapacidad y sufrir modificaciones en las actividades cotidianas. La familia es el principal apoyo del sobreviviente y al ser parte de una misma cultura, construye acciones de cuidado en búsqueda del bienestar. Objetivo: describir las acciones del cuidado popular de las familias con un adulto mayor sobreviviente del primer accidente cerebrovascular. Método: estudio etnográfico, con observación participante y entrevistas en profundidad. Participaron siete familias bogotanas (siete adultos mayores entre los dos y diez meses posteriores al primer accidente cerebrovascular y los siete cuidadores principales respectivos. Resultados: cuidadores y adulto mayor comparten acciones de cuidado para la recuperación, relacionadas con la alimentación, el cuidado personal y la ingesta de medicamentos permeadas por la creencia religiosa, fuente de soporte y vínculo afectivo. Conclusión: conocer el cuidado popular de esta población posibilita proponer acciones culturalmente congruentes con sus valores y creencias para potencializar las ca- pacidades familiares e intermediar en los procesos de tratamiento.

MDMA ("Ecstasy") and its association with cerebrovascular accidents: preliminary findings

NARCIS (Netherlands)

Reneman, L.; Habraken, J. B.; Majoie, C. B.; Booij, J.; den Heeten, G. J.

2000-01-01

BACKGROUND AND PURPOSE: Abuse of the popular recreational drug "Ecstasy" (MDMA) has been linked to the occurrence of cerebrovascular accidents. It is known that MDMA alters brain serotonin (5-HT) concentrations and that brain postsynaptic 5-HT(2) receptors play a role in the regulation of brain

Microbubbles as drug delivery systems in cerebrovascular diseases.

Science.gov (United States)

Spinelli, Mariacarmela; Demitri, Christian; Sannino, Alessandro; Peruzzotti-Jametti, Luca; Bacigaluppi, Marco; Comi, Giancarlo; Corea, Francesco

2009-11-01

The field of neurovascular ultrasound is growing rapidly with new applications. While ultrasound contrast agents were initially used to overcome poor transcranial bone windows for identification of cerebral arteries, newgeneration microbubbles in combination with innovative contrast-specific ultrasound techniques now enable potential therapeutic procedures. This article will provide a review of recent and emerging developments along with patents in ultrasound technology and contrast-specific therapeutic techniques for cerebrovascular patients.

Selective intra-arterial digital subtraction angiography (IADSA) in cerebrovascular disease

International Nuclear Information System (INIS)

Uchino, Akira; Satoh, Yoshiyuki; Ohno, Masato

1987-01-01

Selective right transbrachial intra-arterial digital subtraction angiography (transbrachial selective IADSA) was successfully performed for 24 of 26 patients with known or suspected cerebrovascular disease, four of whom were outpatients. Catheterization failed in two elderly hypertensive men because of tortuosity of their brachial arteries, and in one woman whose aberrant right subclavian artery (SCA) prevented bilateral common carotid arterial (CCA) catheterizations. No complications occurred. One-hundred and ten ''excellent'' images were obtained by means of 118 injections for the 24 patients. Iopamidol, the contrast medium, was diluted to 50 % concentration with saline, then warmed to 37 deg C. Nearly all the injections of both CCAs and right vertebral arteries (VAs) were completed using 10 ml injections and a 5 ml/sec flow rate. The mean examination time for the three-vessel study was 29.4 minutes. Transbrachial selective IADSA thus proved to be a safe, useful, and relatively easy means of diagnosing cerebrovascular disease. (author)

Evaluating patients with ischemic cerebrovascular disease using positron emission tomography

International Nuclear Information System (INIS)

Raichle, M.E.

1982-01-01

Recent advances in nuclear medicine imaging techniques offer an important alternative for the evaluation of therapy for ischemic cerebrovascular disease. In particular, positron emission tomography (PET), with its capacity to provide quantitative measurements of brain blood flow, metabolism and biochemistry on a truly regional basis, now offers the opportunity to evaluate therapy in terms of specific changes in these parameters. By doing this PET permits one to study the problem on an individual patient basis with each subject serving as his own control. The author has been pursuing this approach in patients considered candidates for superficial temporal artery-middle cerebral artery anastomosis to bypass major stenotic or occlusive lesions of the internal carotid or middle cerebral artery. The results indicate that PET is of considerable value in establishing much more exactly the pathophysiology of certain forms of ischemic cerebrovascular disease and evaluating a form of therapy designed to correct the basic underlying defect. (Auth./C.F.)

Cerebrovascular-Reactivity Mapping Using MRI: Considerations for Alzheimer’s Disease

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J. J. Chen

2018-06-01

Full Text Available Alzheimer’s disease (AD is associated with well-established macrostructural and cellular markers, including localized brain atrophy and deposition of amyloid. However, there is growing recognition of the link between cerebrovascular dysfunction and AD, supported by continuous experimental evidence in the animal and human literature. As a result, neuroimaging studies of AD are increasingly aiming to incorporate vascular measures, exemplified by measures of cerebrovascular reactivity (CVR. CVR is a measure that is rooted in clinical practice, and as non-invasive CVR-mapping techniques become more widely available, routine CVR mapping may open up new avenues of investigation into the development of AD. This review focuses on the use of MRI to map CVR, paying specific attention to recent developments in MRI methodology and on the emerging stimulus-free approaches to CVR mapping. It also summarizes the biological basis for the vascular contribution to AD, and provides critical perspective on the choice of CVR-mapping techniques amongst frail populations.

Ibuprofen abates cypermethrin-induced expression of pro-inflammatory mediators and mitogen-activated protein kinases and averts the nigrostriatal dopaminergic neurodegeneration.

Science.gov (United States)

Singh, Ashish; Tripathi, Pratibha; Prakash, Om; Singh, Mahendra Pratap

2016-12-01

Cypermethrin induces oxidative stress, microglial activation, inflammation and apoptosis leading to Parkinsonism in rats. While ibuprofen, a non-steroidal anti-inflammatory drug, relieves from inflammation, its efficacy against cypermethrin-induced Parkinsonism has not yet been investigated. The study aimed to explore the protective role of ibuprofen in cypermethrin-induced Parkinsonism, an environmentally relevant model of Parkinson's disease (PD), along with its underlying mechanism. Animals were treated with/without cypermethrin in the presence/absence of ibuprofen. Behavioural, immunohistochemical and biochemical parameters of Parkinsonism and expression of pro-inflammatory and pro-apoptotic proteins along with mitogen-activated protein kinases (MAPKs) were determined. Ibuprofen resisted cypermethrin-induced behavioural impairments, striatal dopamine depletion, oxidative stress in the nigrostriatal tissues and loss of the nigral dopamine producing cells and increase in microglial activation along with atypical expression of pro-inflammatory and apoptotic proteins that include cyclooxygenase-2, tumour necrosis factor-α, MAPKs (c-Jun N-terminal kinase, p38 and extracellular signal-regulated kinase), B cell lymphoma 2-associated protein X, tumour suppressor protein p53, cytochrome c and caspase-3 in the nigrostriatal tissue. The results obtained thus demonstrate that ibuprofen lessens inflammation and regulates MAPKs expression thereby averts cypermethrin-induced Parkinsonism.

UBC-Nepal expedition: The use of oral antioxidants does not alter cerebrovascular function at sea level or high altitude.

Science.gov (United States)

Hansen, Alexander B; Hoiland, Ryan L; Lewis, Nia C S; Tymko, Michael M; Tremblay, Joshua C; Stembridge, Michael; Nowak-Flück, Daniela; Carter, Howard H; Bailey, Damian M; Ainslie, Philip N

2018-04-01

What is the central question of the study? Does the use of antioxidants alter cerebrovascular function and blood flow at sea level (344 m) and/or high altitude (5050 m)? What is the main finding and its importance? This is the first study to investigate whether antioxidant administration alters cerebrovascular regulation and blood flow in response to hypercapnia, acute hypoxia and chronic hypoxia in healthy humans. We demonstrate that an acute dose of antioxidants does not alter cerebrovascular function and blood flow at sea level (344 m) or after 12 days at high altitude (5050 m). Hypoxia is associated with an increase in systemic and cerebral formation of free radicals and associated reactants that may be linked to impaired cerebral vascular function and neurological sequelae. To what extent oral antioxidant prophylaxis impacts cerebrovascular function in humans throughout the course of acclimatization to the hypoxia of terrestrial high altitude has not been examined. Thus, the purpose of the present study was to examine the influence of orally ingested antioxidants at clinically relevant doses (vitamins C and E and α-lipoic acid) on cerebrovascular regulation at sea level (344 m; n = 12; female n = 2 participants) and at high altitude (5050 m; n = 9; female n = 2) in a randomized, placebo-controlled and double-blinded crossover design. Hypercapnic and hypoxic cerebrovascular reactivity tests of the internal carotid artery (ICA) were conducted at sea level, and global and regional cerebral blood flow (CBF; i.e. ICA and vertebral artery) were assessed 10-12 days after arrival at 5050 m. At sea level, acute administration of antioxidants did not alter cerebral hypoxic cerebrovascular reactivity (pre versus post: 1.5 ± 0.7 versus 1.2 ± 0.8%∆CBF/-%∆SpO2; P = 0.96) or cerebral hypercapnic cerebrovascular reactivity (pre versus post: 5.7 ± 2.0 versus 5.8 ± 1.9%∆CBF/∆mmHg; P = 0.33). Furthermore, global CBF (P = 0.43) and

The mediating role of interpersonal conflict at work in the relationship between negative affectivity and biomarkers of stress.

Science.gov (United States)

Girardi, Damiano; Falco, Alessandra; De Carlo, Alessandro; Benevene, Paula; Comar, Manola; Tongiorgi, Enrico; Bartolucci, Giovanni Battista

2015-12-01

This study examined the association between interpersonal conflict at work (ICW) and serum levels of three possible biomarkers of stress, namely the pro-inflammatory cytokines Interleukin 1 beta (IL-1β), Interleukin 12 (IL-12), and Interleukin 17 (IL-17). Additionally, this study investigated the role of negative affectivity (NA) in the relationship between ICW and the pro-inflammatory cytokines. Data from 121 employees in an Italian healthcare organization were analyzed using structural equation modeling. Results showed that ICW was positively associated with IL-1β, IL-12, and IL-17, after controlling for the effect of gender. Moreover, ICW completely mediated the relationship between NA and the pro-inflammatory cytokines IL-1β, IL-12, and IL-17. This mediating effect was significant after controlling for the effect of gender. Overall, this study suggests that work-related stress may be associated with biomarkers of inflammation, and that negative affectivity may influence the stress process affecting the exposure to psychosocial stressors.

[Descriptive study of cerebrovascular accidents in Douala, Cameroon].

Science.gov (United States)

Chiasseu, Mbeumi M T; Mbahe, S

2011-10-01

A cerebrovascular accident or stroke is a sudden-onset cerebral deficit of vascular origin lasting more than 24 hours. These events represent the second leading cause of death in the world and take a particularly heavy toll in third world countries. The purpose of this study was to describe cerebrovascular lesions (type, location, size) as well as patient age and gender in Cameroon. Brain CT-scan and MRI findings from 50 stroke patients admitted to two health centers in Douala were reviewed. Data showed that 74% of patients were over 50 years of age, the 51-60 year group being the most affected. Patients were male in 64% of cases. Ischemic stroke accounted for 60% of cases versus 40% for hemorrhagic stroke. The most affected sites were the sylvian territory site in ischemic stroke and the temporal lobe in hemorrhagic stroke, acconting for 43.3% and 35% of cases respectively. The median size of ischemic and hemorrhagic lesions were 2.81 cm3, and 26.98 cm3 respectively. Hemorrhagic stroke and lacunar infarcts were more common in this sample. Discrepancies between results at the two hospitals may be due to the use of different imaging techniques. Indeed, MRI is known to be more sensitive than CT-scan for acute detection of stroke lesions.

Cerebral blood flow measurement in cerebrovascular occlusive diseases

International Nuclear Information System (INIS)

Yanagihara, T.; Wahner, H.W.

1984-01-01

In order to evaluate cerebral blood flow (CBF) patterns among individual patients with increased statistical confidence, CBF measurements were carried out using the 133Xe-inhalation method and external head detectors. F1 values representing gray matter flow from 3 to 6 head detectors were averaged to form 16 different regions for each cerebral hemisphere. Normative values were obtained from 46 healthy volunteers, and data from individual regions were analyzed for absolute blood flow rates (ml/100g/min), for concordance between right and left hemispheres and as percent of mean hemispheric flow. CBF measurements were then carried out among 37 patients with cerebrovascular occlusive diseases, and results were compared with normative values. A high incidence of abnormal flows were detected among symptomatic patients with intracranial arterial stenosis or occlusion and those with extracranial internal carotid artery occlusion. By using the above method for data analysis, it was possible to delineate hypoperfused areas among these patients. Even though the 133Xe-inhalation method has inherent limitations, this is a practical and safe method for measurement of CBF which can provide reliable information useful for management of patients with cerebrovascular occlusive diseases, particularly when the results are presented with statistical confidence

Bacterial Endocarditis and Cerebrovascular Disease.

Science.gov (United States)

Silver, Brian; Behrouz, Réza; Silliman, Scott

2016-12-01

Cerebrovascular complications of endocarditis occur in 25-70% of patients with infective endocarditis. The cornerstone of treatment is early initiation of antibiotic treatment, which significantly reduces the risk of embolization after 1 week of treatment. In general, thrombolysis and anticoagulation of these patients should be avoided, while antiplatelet therapy may be considered in those with other indications. Endovascular treatment of acute septic emboli is uncertain, but a few case reports have demonstrated benefit. Other complications of infective endocarditis include intracerebral hemorrhage, which may be predicted by the presence of two or more cerebral microbleeds on gradient echo sequences. Intracranial mycotic aneurysms can often be managed with serial imaging and coiled if there is evidence of failure to reduce in size, or enlargement.

Ultra-sensitive molecular MRI of cerebrovascular cell activation enables early detection of chronic central nervous system disorders

International Nuclear Information System (INIS)

Montagne, Axel; Gauberti, Maxime; Jullienne, Amandine; Briens, Aurelien; Docagne, Fabian; Vivien, Denis; Maubert, Eric; Macrez, Richard; Defer, Gilles; Raynaud, Jean-Sebastien; Louin, Gaelle; Buisson, Alain; Haelewyn, Benoit

2012-01-01

Since endothelial cells can be targeted by large contrast-carrying particles, molecular imaging of cerebrovascular cell activation is highly promising to evaluate the underlying inflammation of the central nervous system (CNS). In this study, we aimed to demonstrate that molecular magnetic resonance imaging (MRI) of cerebrovascular cell activation can reveal CNS disorders in the absence of visible lesions and symptoms. To this aim, we optimized contrast carrying particles targeting vascular cell adhesion molecule-1 and MRI protocols through both in vitro and in vivo experiments. Although, pre-contrast MRI images failed to reveal the ongoing pathology, contrast-enhanced MRI revealed hypoperfusion-triggered CNS injury in vascular dementia, unmasked amyloid-induced cerebrovascular activation in Alzheimer's disease and allowed monitoring of disease activity during experimental autoimmune encephalomyelitis. Moreover, contrast-enhanced MRI revealed the cerebrovascular cell activation associated with known risk factors of CNS disorders such as peripheral inflammation, ethanol consumption, hyperglycemia and aging. By providing a dramatically higher sensitivity than previously reported methods and molecular contrast agents, the technology described in the present study opens new avenues of investigation in the field of neuro-inflammation. (authors)

Vascular remodeling versus amyloid beta-induced oxidative stress in the cerebrovascular dysfunctions associated with Alzheimer's disease.

Science.gov (United States)

Tong, Xin-Kang; Nicolakakis, Nektaria; Kocharyan, Ara; Hamel, Edith

2005-11-30

The roles of oxidative stress and structural alterations in the cerebrovascular dysfunctions associated with Alzheimer's disease (AD) were investigated in transgenic mice overexpressing amyloid precusor protein (APP+) or transforming growth factor-beta1 (TGF+). Age-related impairments and their in vitro reversibility were evaluated, and underlying pathogenic mechanisms were assessed and compared with those seen in AD brains. Vasoconstrictions to 5-HT and endothelin-1 were preserved, except in the oldest (18-21 months of age) TGF+ mice. Despite unaltered relaxations to sodium nitroprusside, acetylcholine (ACh) and calcitonin gene-related peptide-mediated dilatations were impaired, and there was an age-related deficit in the basal availability of nitric oxide (NO) that progressed more gradually in TGF+ mice. The expression and progression of these deficits were unrelated to the onset or extent of thioflavin-S-positive vessels. Manganese superoxide dismutase (SOD2) was upregulated in pial vessels and around brain microvessels of APP+ mice, pointing to a role of superoxide in the dysfunctions elicited by amyloidosis. In contrast, vascular wall remodeling associated with decreased levels of endothelial NO synthase and cyclooxygenase-2 and increased contents of vascular endothelial growth factor and collagen-I and -IV characterized TGF+ mice. Exogenous SOD or catalase normalized ACh dilatations and NO availability in vessels from aged APP+ mice but had no effect in those of TGF+ mice. Increased perivascular oxidative stress was not evidenced in AD brains, but vascular wall alterations compared well with those seen in TGF+ mice. We conclude that brain vessel remodeling and associated alterations in levels of vasoactive signaling molecules are key contributors to AD cerebrovascular dysfunctions.

[Sleep disorders in the structure of cerebrovascular diseases].

Science.gov (United States)

Iakupov, É Z; Aleksandrova, E A; Troshina, Iu V; Shebasheva, E V; Shagiakhmetova, L Ia

2014-01-01

The literature on the place and role of insomnia in cerebral blood circulation disturbances is reviewed. It is emphasized that insomnia is a modifying risk factor of cerebrovascular pathology. The syndrome of obstructive sleep apnea may be a cause of arterial hypertension. The diagnostic relevance of the complex examination of patients with sleep pathology, including polysomnographic technology, and its role in the choice of corrective measures and treatment of insomnia in whole are shown.

Digital subtraction angiography in pediatric cerebrovascular occlusive disease

International Nuclear Information System (INIS)

Faerber, E.N.; Griska, L.A.B.; Swartz, J.D.; Capitanio, M.A.; Popky, G.L.

1984-01-01

While conventional angiography has been used to demonstrate cerebrovascular occlusive disease in the past, digital subtraction angiography (DSA) is capable of showing progressive vascular involvement with ease, simplicity, and extremely low morbidity, making it particularly well suited for children and outpatients either alone or coordinated with computed tomography. The authors discuss the usefulness and advantages of DSA as demonstrated in 7 infants and children with hemiplegia, 4 of whom had sickle-cell disease

Cancer as a Proinflammatory Environment: Metastasis and Cachexia

Science.gov (United States)

Inácio Pinto, Nelson; Carnier, June; Oyama, Lila M.; Otoch, Jose Pinhata; Alcântara, Paulo Sergio; Tokeshi, Flavio; Nascimento, Claudia M.

2015-01-01

The development of the syndrome of cancer cachexia and that of metastasis are related with a poor prognostic for cancer patients. They are considered multifactorial processes associated with a proinflammatory environment, to which tumour microenvironment and other tissues from the tumour bearing individuals contribute. The aim of the present review is to address the role of ghrelin, myostatin, leptin, HIF, IL-6, TNF-α, and ANGPTL-4 in the regulation of energy balance, tumour development, and tumoural cell invasion. Hypoxia induced factor plays a prominent role in tumour macro- and microenvironment, by modulating the release of proinflammatory cytokines. PMID:26508818

Cancer as a Proinflammatory Environment: Metastasis and Cachexia

Directory of Open Access Journals (Sweden)

Nelson Inácio Pinto

2015-01-01

Full Text Available The development of the syndrome of cancer cachexia and that of metastasis are related with a poor prognostic for cancer patients. They are considered multifactorial processes associated with a proinflammatory environment, to which tumour microenvironment and other tissues from the tumour bearing individuals contribute. The aim of the present review is to address the role of ghrelin, myostatin, leptin, HIF, IL-6, TNF-α, and ANGPTL-4 in the regulation of energy balance, tumour development, and tumoural cell invasion. Hypoxia induced factor plays a prominent role in tumour macro- and microenvironment, by modulating the release of proinflammatory cytokines.

The Clinical Characteristics of Acute Cerebrovascular Accidents Resulting from Ovarian Hyperstimulation Syndrome.

Science.gov (United States)

Yang, Shuna; Yuan, Junliang; Qin, Wei; Li, Yue; Yang, Lei; Hu, Wenli

2017-01-01

Ovarian hyperstimulation syndrome (OHSS) is a serious complication that occurs after the ovarian-induction treatment. Acute cerebrovascular accident is one of the most dangerous manifestations of the syndrome. However, the characteristics of stroke resulting from OHSS have so far not been well summarised in any study. We reported 2 cases of acute cerebrovascular accidents secondary to OHSS. And then we performed a literature search for reports on this type of stroke, and summarised their characteristics. Thirty-six published cases of this type of stroke were reviewed. Thirty two out of 36 (88.9%) of the women were 35 years old or younger. Stroke in 28 out of 36 (77.8%) of these cases was caused by arterial thrombosis. In 17 out of 28 cases, the involved cerebral vascular branches were mainly middle cerebral artery (MCA) and internal carotid artery (ICA). The acute cerebrovascular accidents happened 7 and 9.25 days after embryo transplantation or 8 and 8.33 days after last human chorionic gonadotropin treatment respectively. The prognosis of patients was relatively good after anticoagulation and some supportive treatments. The MCA and ICA are easily involved in stroke resulting from OHSS. The young age may be a risk factor for developing stroke secondary to OHSS. Once thromboembolism develops, administering appropriate therapy is crucial. © 2017 S. Karger AG, Basel.

Impact of drinking and smoking habits on cerebrovascular disease risk among male employees.

Science.gov (United States)

Hatanaka, Yoko; Shimokata, Keiko; Osugi, Shigeki; Kaneko, Noriyo

2016-10-07

We aimed to analyze the impact of drinking and smoking behavior on the risk of developing cerebrovascular diseases among male employees aged 20-46 years. Twenty years of follow-up data of male employees enrolled in the DENSO Health Insurance Program were used for analyses. Of 29,048 male employees aged 20-46 years who were enrolled in the insurance program in 1994, 25,084 (86.4%) employees underwent annual health check-ups until 2003 without missing an appointment. Of these 25,084 employees, the data of 11,784 (40.6%) employees who self-reported drinking and smoking habits were used for analyses. The hazard ratio and 95% confidence intervals (CIs) for developing cerebrovascular disease in 2004-2013 were calculated in four risk groups categorized as per drinking and smoking behavior in the young group who were in their 20s and the middle-aged group who were in their 30s-40s in 1994. Based on their drinking behavior, participants were categorized into two groups: "not drinking or drinking sometimes" and "drinking every day." Based on their smoking behavior, participants were also categorized into two groups: "not smoking for 10 years" and "smoking for 10 years." A Cox's proportional hazard model revealed that after controlling for body mass index, systolic blood pressure, triglycerides, total cholesterol, fasting plasma glucose, and age, the hazard ratios for "smoking and drinking every day" were 3.82 (95% CI: 1.40-10.41) in the young group and 2.31 (95% CI: 1.27-4.17) in the middle-aged group. Male employees who had been drinking and smoking for 10 years had a higher risk of developing cerebrovascular diseases. To prevent cerebrovascular diseases among male employees, it may be effective to offer behavior change interventions for both drinking and smoking habits, regardless of the age group.

Inhibitors of MyD88-dependent proinflammatory cytokine production identified utilizing a novel RNA interference screening approach.

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John S Cho

2009-09-01

Full Text Available The events required to initiate host defenses against invading pathogens involve complex signaling cascades comprised of numerous adaptor molecules, kinases, and transcriptional elements, ultimately leading to the production of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha. How these signaling cascades are regulated, and the proteins and regulatory elements participating are still poorly understood.We report here the development a completely random short-hairpin RNA (shRNA library coupled with a novel forward genetic screening strategy to identify inhibitors of Toll-like receptor (TLR dependent proinflammatory responses. We developed a murine macrophage reporter cell line stably transfected with a construct expressing diphtheria toxin-A (DT-A under the control of the TNF-alpha-promoter. Stimulation of the reporter cell line with the TLR ligand lipopolysaccharide (LPS resulted in DT-A induced cell death, which could be prevented by the addition of an shRNA targeting the TLR adaptor molecule MyD88. Utilizing this cell line, we screened a completely random lentiviral short hairpin RNA (shRNA library for sequences that inhibited TLR-mediated TNF-alpha production. Recovery of shRNA sequences from surviving cells led to the identification of unique shRNA sequences that significantly inhibited TLR4-dependent TNF-alpha gene expression. Furthermore, these shRNA sequences specifically blocked TLR2 but not TLR3-dependent TNF-alpha production.Thus, we describe the generation of novel tools to facilitate large-scale forward genetic screens in mammalian cells and the identification of potent shRNA inhibitors of TLR2 and TLR4- dependent proinflammatory responses.

Dynamic computed tomography findings in cerebrovascular diseases

International Nuclear Information System (INIS)

Araki, Yutaka; Tomoda, Kaname; Kariya, Mitsumasa; Mori, Shigeru; Mitomo, Masanori.

1988-01-01

Dynamic CT was performed with 41 patients with the clinically diagnosed cerebrovascular diseases. A visual evaluation based on the dynamic CT images classified six patterns of brain parenchymal enhancement, especially four patterns of which could only be detected by dynamic CT technique. Dynamic CT was proved of great value in detecting regional cerebral tissue filled by collaterals in retrograde fashion because of the occlusion of main arteries, namely brain tissue perfusion of internal carotid occlusion disease and moyamoya disease was best understood by dynamic CT with adequate resolution. (author)

Nitric oxide synthase inhibition and cerebrovascular regulation

DEFF Research Database (Denmark)

Iadecola, C; Pelligrino, D A; Moskowitz, M A

1994-01-01

tone and may play an important role in selected vasodilator responses of the cerebral circulation. Furthermore, evidence has been presented suggesting that NO participates in the mechanisms of cerebral ischemic damage. Despite the widespread attention that NO has captured in recent years and the large......There is increasing evidence that nitric oxide (NO) is an important molecular messenger involved in a wide variety of biological processes. Recent data suggest that NO is also involved in the regulation of the cerebral circulation. Thus, NO participants in the maintenance of resting cerebrovascular...

First translational 'Think Tank' on cerebrovascular disease, cognitive impairment and dementia

NARCIS (Netherlands)

Barone, F.C.; Gustafson, D.; Crystal, H.A.; Moreno, H.; Adamski, M.G.; Arai, K.; Baird, A.E.; Balucani, C.; Brickman, A.M.; Cechetto, D.; Gorelick, P.; Biessels, G.J.; Kiliaan, A.J.; Launer, L.; Schneider, J.; Sorond, F.A.; Whitmer, R.; Wright, C.; Zhang, Z.G.

2016-01-01

As the human population continues to age, an increasing number of people will exhibit significant deficits in cognitive function and dementia. It is now recognized that cerebrovascular, metabolic and neurodegenerative diseases all play major roles in the evolution of cognitive impairment and

ROS detoxification and proinflammatory cytokines are linked by p38 MAPK signaling in a model of mature astrocyte activation.

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Adrian Nahirnyj

Full Text Available Astrocytes are the most abundant glial cell in the retinal nerve fiber layer (NFL and optic nerve head (ONH, and perform essential roles in maintaining retinal ganglion cell (RGC detoxification and homeostasis. Mature astrocytes are relatively quiescent, but rapidly undergo a phenotypic switch in response to insult, characterized by upregulation of intermediate filament proteins, loss of glutamate buffering, secretion of pro-inflammatory cytokines, and increased antioxidant production. These changes result in both positive and negative influences on RGCs. However, the mechanism regulating these responses is still unclear, and pharmacologic strategies to modulate select aspects of this switch have not been thoroughly explored. Here we describe a system for rapid culture of mature astrocytes from the adult rat retina that remain relatively quiescent, but respond robustly when challenged with oxidative damage, a key pathogenic stress associated with inner retinal injury. When primary astrocytes were exposed to reactive oxygen species (ROS we consistently observed characteristic changes in activation markers, along with increased expression of detoxifying genes, and secretion of proinflammatory cytokines. This in vitro model was then used for a pilot chemical screen to target specific aspects of this switch. Increased activity of p38α and β Mitogen Activated Protein Kinases (MAPKs were identified as a necessary signal regulating expression of MnSOD, and heme oxygenase 1 (HO-1, with consequent changes in ROS-mediated injury. Additionally, multiplex cytokine profiling detected p38 MAPK-dependent secretion of IL-6, MCP-1, and MIP-2α, which are proinflammatory signals recently implicated in damage to the inner retina. These data provide a mechanism to link increased oxidative stress to proinflammatory signaling by astrocytes, and establish this assay as a useful model to further dissect factors regulating the reactive switch.

Helical CT scan for emergent patients with cerebrovascular diseases

International Nuclear Information System (INIS)

Matsumoto, Masato; Sato, Naoki; Nakano, Masayuki; Watanabe, Youichi; Kodama, Namio

1995-01-01

We studied 44 emergent patients with cerebrovascular diseases (18 cases of subarachnoid hemorrhage, 15 of occlusive lesions, 7 of intracerebral hematoma and 4 of suspected subarachnoid hemorrhage) using helical CT scan. The helical CT scan was performed with contrast medium at a rate of 3 ml/sec with a delay of 20 sec, and was carried out before conventional angiography. The reconstruction time of 3D-CTA was within 10 min. We were able to obtain findings for the lesion on 3D-CTA before those on conventional angiography. The 3D-CTA yielded excellent images of the vascular structures and anatomical relationships of the aneurysm, its neck and parent artery, and surrounding arteries. However, it proved difficult to visualize vessels of less than 1 mm in diameter, especially the perforating arteries. In occlusive diseases, the degree of stenosis depended on the changes in CT number threshold: at present, evaluations of the lesions should be made by conventional angiography. 3D-CTA using helical CT scan can thus be applied for emergent patients with cerebrovascular diseases. Surgical simulation images of 3D-CTA were especially useful at the time of operation. (author)

Helical CT scan for emergent patients with cerebrovascular diseases

Energy Technology Data Exchange (ETDEWEB)

Matsumoto, Masato; Sato, Naoki; Nakano, Masayuki; Watanabe, Youichi; Kodama, Namio [Fukushima Medical Coll. (Japan)

1995-08-01

We studied 44 emergent patients with cerebrovascular diseases (18 cases of subarachnoid hemorrhage, 15 of occlusive lesions, 7 of intracerebral hematoma and 4 of suspected subarachnoid hemorrhage) using helical CT scan. The helical CT scan was performed with contrast medium at a rate of 3 ml/sec with a delay of 20 sec, and was carried out before conventional angiography. The reconstruction time of 3D-CTA was within 10 min. We were able to obtain findings for the lesion on 3D-CTA before those on conventional angiography. The 3D-CTA yielded excellent images of the vascular structures and anatomical relationships of the aneurysm, its neck and parent artery, and surrounding arteries. However, it proved difficult to visualize vessels of less than 1 mm in diameter, especially the perforating arteries. In occlusive diseases, the degree of stenosis depended on the changes in CT number threshold: at present, evaluations of the lesions should be made by conventional angiography. 3D-CTA using helical CT scan can thus be applied for emergent patients with cerebrovascular diseases. Surgical simulation images of 3D-CTA were especially useful at the time of operation. (author).

Anti-inflammatory effect by lentiviral-mediated overexpression of IL-10 or IL-1 receptor antagonist in rat glial cells and macrophages

NARCIS (Netherlands)

van Strien, N.M.; Mercier, D.; Drukarch, B.; Breve, J.J.P.; Poole, S.; Binnekade, R.; Bol, J.G.J.M.; Blits, B.; Verhaagen, J.; van Dam, A.M.W.

2010-01-01

Neuroinflammation, as defined by activation of local glial cells and production of various inflammatory mediators, is an important feature of many neurological disorders. Expression of pro-inflammatory mediators produced by glial cells in the central nervous system (CNS) is considered to contribute

Tomography methods for diagnostic examination of cerebrovascular disease: a comparative evaluation of SPECT, PET and MR/CT findings

International Nuclear Information System (INIS)

Reiche, W.; Kaiser, H.J.; Weiller, C.; Altehoefer, C.; Buell, U.; Isensee, C.

1991-01-01

Single Photon Emissions Computerized Tomography (SPECT), Positron Emissions Tomography (PET), Magnetic Resonance Tomography (MR), and Transmission Computerized Tomography (CT) complement each other and lead to a consideration of the cerebrovascular disease under patho-physiological aspects. Indications for the combined application of functionally oriented (SPECT/PET) and morphologically oriented (CT/MR) examination methods with cerebrovascular disease are presented. (orig./MG) [de

Activation of p38 MAPK by feline infectious peritonitis virus regulates pro-inflammatory cytokine production in primary blood-derived feline mononuclear cells.

Science.gov (United States)

Regan, Andrew D; Cohen, Rebecca D; Whittaker, Gary R

2009-02-05

Feline infectious peritonitis (FIP) is an invariably fatal disease of cats caused by systemic infection with a feline coronavirus (FCoV) termed feline infectious peritonitis virus (FIPV). The lethal pathology associated with FIP (granulomatous inflammation and T-cell lymphopenia) is thought to be mediated by aberrant modulation of the immune system due to infection of cells such as monocytes and macrophages. Overproduction of pro-inflammatory cytokines occurs in cats with FIP, and has been suggested to play a significant role in the disease process. However, the mechanism underlying this process remains unknown. Here we show that infection of primary blood-derived feline mononuclear cells by FIPV WSU 79-1146 and FIPV-DF2 leads to rapid activation of the p38 MAPK pathway and that this activation regulates production of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). FIPV-induced p38 MAPK activation and pro-inflammatory cytokine production was inhibited by the pyridinyl imidazole inhibitors SB 203580 and SC 409 in a dose-dependent manner. FIPV-induced p38 MAPK activation was observed in primary feline blood-derived mononuclear cells individually purified from multiple SPF cats, as was the inhibition of TNF-alpha production by pyridinyl imidazole inhibitors.

Transition of care for the elderly after cerebrovascular accidents--from hospital to the home.

Science.gov (United States)

Rodrigues, Rosalina Aparecida Partezani; Marques, Sueli; Kusumota, Luciana; dos Santos, Emanuella Barros; Fhon, Jack Roberto da Silva; Fabrício-Wehbe, Suzele Cristina Coelho

2013-01-01

to examine the transition of care in families caring for elderly persons who suffered the first episode of a cerebrovascular accident. an instrumental ethnographic case study was used. The sample comprised 20 subjects: 10 caregivers and 10 elderly persons aged 65 or over, of both sexes, with diagnoses of first episode of cerebrovascular accident, capable of communicating, and requiring care from a main carer in their family. The data was collected through interviews, observation, existing documentation and field notes. Qualitative analysis techniques were used to codify and classify the data and to formulate significant categories, which generated typologies of care. The central idea was the Transition of Care and showed the context in three typologies: The care process for the dependent elderly person, Strategies for the care process and Impact and acceptance of the limitations. The data indicates that caring for an elderly person after a cerebrovascular accident is a challenge for the family. The data permitted it possible to elaborate a proposal for a model for the organization of the work, with a view to holistic care delivery in the health services, forming a care network, which constitutes an advance for the area of nursing.

Monocyte Chemoattractant Protein-1 in the choroid plexus: a potential link between vascular pro-inflammatory mediators and the CNS during peripheral tissue inflammation

Science.gov (United States)

Mitchell, K.; Yang, H.-Y. T.; Berk, J. D.; Tran, J. H.; Iadarola, M. J.

2009-01-01

During peripheral tissue inflammation, inflammatory processes in the CNS can be initiated by blood-borne pro-inflammatory mediators. The choroid plexus, the site of CSF production, is a highly specialized interface between the vascular system and CNS, and thus, this structure may be an important element in communication between the vascular compartment and the CNS during peripheral tissue inflammation. We investigated the potential participation of the choroid plexus in this process during peripheral tissue inflammation by examining expression of the SCYA2 gene which codes for monocyte chemoattractant protein-1 (MCP-1). MCP-1 protein was previously reported to be induced in a variety of cells during peripheral tissue inflammation. In the basal state, SCYA2 is highly expressed in the choroid plexus as compared to other CNS tissues. During hind paw inflammation, SCYA2 expression was significantly elevated in choroid plexus, whereas it remained unchanged in a variety of brain regions. The SCYA2-expressing cells were strongly associated with the choroid plexus as vascular depletion of blood cells by whole-body saline flush did not significantly alter SCYA2 expression in the choroid plexus. In situ hybridization suggested that the SCYA2-expressing cells were localized to the choroid plexus stroma. To elucidate potential molecular mechanisms of SCYA2 increase, we examined genes in the NF-κβ signaling cascade including TNF-α, IL-1β and IκBα in choroid tissue. Given that we also detected increased levels of MCP-1 protein by ELISA, we sought to identify potential downstream targets of MCP-1 and observed altered expression levels of mRNAs encoding tight junction proteins TJP2 and claudin 5. Finally, we detected a substantial up-regulation of the transcript encoding E-selectin, a molecule which could participate in leukocyte recruitment to the choroid plexus along with MCP-1. Together, these results suggest that profound changes occur in the choroid plexus during

Development of a Delivery System for Treating Cerebrovascular Aneurysms Final Report CRADA No. TC-1440-97

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Lee, A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Derbin, J. T. [Micrus Corp., Mountain View, CA (United States)

2018-01-24

The objective of the project was to develop a system for delivering an implantable medical device used to treat cerebrovascular aneurysms, which can cause disability or hemorrhagic stroke (over 15,000 strokes in the U.S. each year are caused by ruptured aneurysms). Micrus has developed an implantable device with the potential to significantly improve the treatment of cerebrovascular aneurysms. This implantable device should significantly reduce the number of hemorrhagic strokes. LLNL has performed proof-of-concept experiments for a delivery system that could be modified to deploy the Micrus device into aneurysms. The purpose of this CRADA was to complete development of the LLNL delivery system and to integrate it with the Micrus device. The goal of the project was to develop an integrated minimally-invasive medical device for treating cerebrovascular aneurysms. The device was designed to access aneurysms through commercially-available catheters which are introduced into the patient through a small incision in the leg.

Is outdoor work associated with elevated rates of cerebrovascular disease mortality? A cohort study based on iron-ore mining.

Science.gov (United States)

Björ, Ove; Jonsson, Håkan; Damber, Lena; Burström, Lage; Nilsson, Tohr

2016-01-01

A cohort study that examined iron ore mining found negative associations between cumulative working time employed underground and several outcomes, including mortality of cerebrovascular diseases. In this cohort study, and using the same group of miners, we examined whether work in an outdoor environment could explain elevated cerebrovascular disease rates. This study was based on a Swedish iron ore mining cohort consisting of 13,000 workers. Poisson regression models were used to generate smoothed estimates of standardized mortality ratios and adjusted rate ratios, both models by cumulative exposure time in outdoor work. The adjusted rate ratio between employment classified as outdoor work ≥25 years and outdoor work 0-4 years was 1.62 (95 % CI 1.07-2.42). The subgroup underground work ≥15 years deviated most in occurrence of cerebrovascular disease mortality compared with the external reference population: SMR (0.70 (95 % CI 0.56-0.85)). Employment in outdoor environments was associated with elevated rates of cerebrovascular disease mortality. In contrast, work in tempered underground employment was associated with a protecting effect.

Suppressor of cytokine signalling-3 expression inhibits cytokine-mediated destruction of primary mouse and rat pancreatic islets and delays allograft rejection

DEFF Research Database (Denmark)

Rønn, S G; Börjesson, A; Bruun, C

2008-01-01

The pro-inflammatory cytokines IL-1 and IFNgamma are critical molecules in immune-mediated beta cell destruction leading to type 1 diabetes mellitus. Suppressor of cytokine signalling (SOCS)-3 inhibits the cytokine-mediated destruction of insulinoma-1 cells. Here we investigate the effect of SOCS...

Central respiratory chemosensitivity and cerebrovascular CO2 reactivity: a rebreathing demonstration illustrating integrative human physiology.

Science.gov (United States)

MacKay, Christina M; Skow, Rachel J; Tymko, Michael M; Boulet, Lindsey M; Davenport, Margie H; Steinback, Craig D; Ainslie, Philip N; Lemieux, Chantelle C M; Day, Trevor A

2016-03-01

One of the most effective ways of engaging students of physiology and medicine is through laboratory demonstrations and case studies that combine 1) the use of equipment, 2) problem solving, 3) visual representations, and 4) manipulation and interpretation of data. Depending on the measurements made and the type of test, laboratory demonstrations have the added benefit of being able to show multiple organ system integration. Many research techniques can also serve as effective demonstrations of integrative human physiology. The "Duffin" hyperoxic rebreathing test is often used in research settings as a test of central respiratory chemosensitivity and cerebrovascular reactivity to CO2. We aimed to demonstrate the utility of the hyperoxic rebreathing test for both respiratory and cerebrovascular responses to increases in CO2 and illustrate the integration of the respiratory and cerebrovascular systems. In the present article, methods such as spirometry, respiratory gas analysis, and transcranial Doppler ultrasound are described, and raw data traces can be adopted for discussion in a tutorial setting. If educators have these instruments available, instructions on how to carry out the test are provided so students can collect their own data. In either case, data analysis and quantification are discussed, including principles of linear regression, calculation of slope, the coefficient of determination (R(2)), and differences between plotting absolute versus normalized data. Using the hyperoxic rebreathing test as a demonstration of the complex interaction and integration between the respiratory and cerebrovascular systems provides senior undergraduate, graduate, and medical students with an advanced understanding of the integrative nature of human physiology. Copyright © 2016 The American Physiological Society.

Contribution of physical fitness, cerebrovascular reserve and cognitive stimulation to cognitive function in postmenopausal women

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Gail A Eskes

2010-10-01

Full Text Available Studies of the effects of physical fitness on cognition suggest that exercise can improve cognitive abilities in healthy older adults, as well as delay the onset of age-related cognitive decline. The mechanisms for the positive benefit of exercise and how these effects interact with other variables known to influence cognitive function (e.g., involvement in cognitive activities are less well understood. The current study examined the associations between the physical fitness, cerebrovascular blood flow regulation and involvement in cognitive activities with neuropsychological function in healthy postmenopausal women. Methods: Forty-two healthy women between the ages of 55 and 90 were recruited. Physical fitness (V˙ o2max, cerebrovascular reserve (cerebral blood flow during rest and response to an increase in end-tidal (i.e., arterial PCO2, and cognitive activity (self-reported number and hours of involvement in cognitive activities were assessed. The association of these variables with neuropsychological performance was examined through linear regression. Results: Physical fitness, cerebrovascular reserve and total number of cognitive activities (but not total hours were independent predictors of cognitive function, particularly measures of overall cognitive performance, attention and executive function. In addition, prediction of neuropsychological performance was better with multiple variables than each alone. Conclusions: Cognitive function in older adults is associated with multiple factors, including physical fitness, cerebrovascular health and cognitive stimulation. Interestingly, cognitive stimulation effects appear related more to the diversity of activities, rather than the duration of activity. Further examination of these relationships is ongoing in a prospective cohort study.

Fisetin Inhibits Hyperglycemia-Induced Proinflammatory Cytokine Production by Epigenetic Mechanisms

OpenAIRE

Hye Joo Kim; Seong Hwan Kim; Jung-Mi Yun

2012-01-01

Diabetes is characterized by a proinflammatory state, and several inflammatory processes have been associated with both type 1 and type 2 diabetes and the resulting complications. High glucose levels induce the release of proinflammatory cytokines. Fisetin, a flavonoid dietary ingredient found in the smoke tree (Cotinus coggygria), and is also widely distributed in fruits and vegetables. Fisetin is known to exert anti-inflammatory effects via inhibition of the NF-?B signaling pathway. In this...

NF-κB dependent and independent mechanisms of quartz-induced proinflammatory activation of lung epithelial cells

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Schins Roel PF

2010-05-01

Full Text Available Abstract In the initiation and progression of pulmonary inflammation, macrophages have classically been considered as a crucial cell type. However, evidence for the role of epithelial type II cells in pulmonary inflammation has been accumulating. In the current study, a combined in vivo and in vitro approach has been employed to investigate the mechanisms of quartz-induced proinflammatory activation of lung epithelial cells. In vivo, enhanced expression of the inflammation- and oxidative stress-related genes HO-1 and iNOS was found on the mRNA level in rat lungs after instillation with DQ12 respirable quartz. Activation of the classical NF-κB pathway in macrophages and type II pneumocytes was indicated by enhanced immunostaining of phospho-IκBα in these specific lung cell types. In vitro, the direct, particle-mediated effect on proinflammatory signalling in a rat lung epithelial (RLE cell line was compared to the indirect, macrophage product-mediated effect. Treatment with quartz particles induced HO-1 and COX-2 mRNA expression in RLE cells in an NF-κB independent manner. Supernatant from quartz-treated macrophages rapidly activated the NF-κB signalling pathway in RLE cells and markedly induced iNOS mRNA expression up to 2000-fold compared to non-treated control cells. Neutralisation of TNFα and IL-1β in macrophage supernatant did not reduce its ability to elicit NF-κB activation of RLE cells. In addition the effect was not modified by depletion or supplementation of intracellular glutathione. The results from the current work suggest that although both oxidative stress and NF-κB are likely involved in the inflammatory effects of toxic respirable particles, these phenomena can operate independently on the cellular level. This might have consequences for in vitro particle hazard testing, since by focusing on NF-κB signalling one might neglect alternative inflammatory pathways.

Activation of AMPK in human fetal membranes alleviates infection-induced expression of pro-inflammatory and pro-labour mediators.

Science.gov (United States)

Lim, R; Barker, G; Lappas, M

2015-04-01

In non-gestational tissues, the activation of adenosine monophosphate (AMP)-activated kinase (AMPK) is associated with potent anti-inflammatory actions. Infection and/or inflammation, by stimulating pro-inflammatory cytokines and matrix metalloproteinase (MMP)-9, play a central role in the rupture of fetal membranes. However, no studies have examined the role of AMPK in human labour. Fetal membranes, from term and preterm, were obtained from non-labouring and labouring women, and after preterm pre-labour rupture of membranes (PPROM). AMPK activity was assessed by Western blotting of phosphorylated AMPK expression. To determine the effect of AMPK activators on pro-inflammatory cytokines, fetal membranes were pre-treated with AMPK activators then stimulated with bacterial products LPS and flagellin or viral dsDNA analogue poly(I:C). Primary amnion cells were used to determine the effect of AMPK activators on IL-1β-stimulated MMP-9 expression. AMPK activity was decreased with term labour. There was no effect of preterm labour. AMPK activity was also decreased in preterm fetal membranes, in the absence of labour, with PROM compared to intact membranes. AMPK activators AICAR, phenformin and A769662 significantly decreased IL-6 and IL-8 stimulated by LPS, flagellin and poly(I:C). Primary amnion cells treated with AMPK activators significantly decreased IL-1β-induced MMP-9 expression. The decrease in AMPK activity in fetal membranes after spontaneous term labour and PPROM indicates an anti-inflammatory role for AMPK in human labour and delivery. The use of AMPK activators as possible therapeutics for threatened preterm labour would be an exciting future avenue of research. Copyright © 2015 Elsevier Ltd. All rights reserved.

4T1 Murine Mammary Carcinoma Cells Enhance Macrophage-Mediated Innate Inflammatory Responses.

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Laurence Madera

Full Text Available Tumor progression and the immune response are intricately linked. While it is known that cancers alter macrophage inflammatory responses to promote tumor progression, little is known regarding how cancers affect macrophage-dependent innate host defense. In this study, murine bone-marrow-derived macrophages (BMDM were exposed to murine carcinoma-conditioned media prior to assessment of the macrophage inflammatory response. BMDMs exposed to 4T1 mammary carcinoma-conditioned medium demonstrated enhanced production of pro-inflammatory cytokines tumor necrosis factor α, interleukin-6, and CCL2 in response to lipopolysaccharide (LPS while production of interleukin-10 remained unchanged. The increased LPS-induced production of pro-inflammatory cytokines was transient and correlated with enhanced cytokine production in response to other Toll-like receptor agonists, including peptidoglycan and flagellin. In addition, 4T1-conditioned BMDMs exhibited strengthened LPS-induced nitric oxide production and enhanced phagocytosis of Escherichia coli. 4T1-mediated augmentation of macrophage responses to LPS was partially dependent on the NFκB pathway, macrophage-colony stimulating factor, and actin polymerization, as well as the presence of 4T1-secreted extracellular vesicles. Furthermore, peritoneal macrophages obtained from 4T1 tumor-bearing mice displayed enhanced pro-inflammatory cytokine production in response to LPS. These results suggest that uptake of 4T1-secreted factors and actin-mediated ingestion of 4T1-secreted exosomes by macrophages cause a transient enhancement of innate inflammatory responses. Mammary carcinoma-mediated regulation of innate immunity may have significant implications for our understanding of host defense and cancer progression.

A TLR4/MD2 fusion protein inhibits LPS-induced pro-inflammatory signaling in hepatic stellate cells

International Nuclear Information System (INIS)

Schnabl, Bernd; Brandl, Katharina; Fink, Marina; Gross, Philipp; Taura, Kojiro; Gaebele, Erwin; Hellerbrand, Claus; Falk, Werner

2008-01-01

Activated hepatic stellate cells (HSCs) play a key role in hepatic fibrogenesis. In injured liver they are the main extracellular matrix protein producing cell type and further perpetuate hepatic injury by secretion of pro-inflammatory mediators. Since LPS-mediated signaling through toll-like receptor 4 (TLR4) has been identified as key fibrogenic signal in HSCs we aimed to test TLR4 as potential target of therapy via ligand-binding soluble receptors. Incubation of human HSCs with a fusion protein between the extracellular domain of TLR4 and MD2 which binds LPS inhibited LPS-induced NFκB and JNK activation. TLR4/MD2 abolished LPS-induced secretion of IL-6, IL-8, MCP1, and RANTES in HSCs. In addition, TLR4/MD2 fused to human IgG-Fc neutralized LPS activity. Since TLR4 mutant mice are resistant to liver fibrosis, the TLR4/MD2 soluble receptor might represent a new therapeutic molecule for liver fibrogenesis in vivo

Proinflammatory cytokine levels in fibromyalgia patients are independent of body mass index

Directory of Open Access Journals (Sweden)

Estrada Iris

2010-06-01

Full Text Available Abstract Background Fibromyalgia (FM is characterized by chronic, widespread muscular pain and tenderness and is generally associated with other somatic and psychological symptoms. Further, circulatory levels of proinflammatory cytokines (IL-1β, TNF-α, and IL-6 may be altered in FM patients, possibly in association with their symptoms. Recently, rises in BMI have been suggested to contribute to increased circulating levels of proinflammatory cytokines in FM patients. Our aim was to measure the circulatory levels of proinflammatory cytokines to determine the influence of BMI on these levels in FM patients and healthy volunteers (HVs. In Spanish FM patients (n = 64 and HVs (n = 25, we measured BMI and serum concentrations of proinflammatory cytokines by capture ELISA. Findings There were significant differences in BMI levels between FM patients (26.40 ± 4.46 and HVs (23.64 ± 3.45 and significant increase in IL-6 in FM patients (16.28 ± 8.13 vs 0.92 ± 0.32 pg/ml (P Conclusions Our analysis in FM patients of BMI as a covariate of proinflammatory cytokines levels showed that serum TNF-α and IL-6 levels are independent of BMI. Further studies are necessary to dissect these findings and their implication in future therapeutic approaches for FM patients.

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....

Effect of breath holding on cerebrovascular hemodynamics in normal pregnancy and preeclampsia

NARCIS (Netherlands)

van Veen, Teelkien R.; Panerai, Ronney B.; Haeri, Sina; Zeeman, Gerda G.; Belfort, Michael A.

2015-01-01

Preeclampsia (PE) is associated with endothelial dysfunction and impaired autonomic function, which is hypothesized to cause cerebral hemodynamic abnormalities. Our aim was to test this hypothesis by estimating the difference in the cerebrovascular response to breath holding (BH; known to cause

Suppression of Proinflammatory and Prosurvival Biomarkers in Oral Cancer Patients Consuming a Black Raspberry Phytochemical-Rich Troche.

Science.gov (United States)

Knobloch, Thomas J; Uhrig, Lana K; Pearl, Dennis K; Casto, Bruce C; Warner, Blake M; Clinton, Steven K; Sardo-Molmenti, Christine L; Ferguson, Jeanette M; Daly, Brett T; Riedl, Kenneth; Schwartz, Steven J; Vodovotz, Yael; Buchta, Anthony J; Schuller, David E; Ozer, Enver; Agrawal, Amit; Weghorst, Christopher M

2016-02-01

Black raspberries (BRB) demonstrate potent inhibition of aerodigestive tract carcinogenesis in animal models. However, translational clinical trials evaluating the ability of BRB phytochemicals to impact molecular biomarkers in the oral mucosa remain limited. The present phase 0 study addresses a fundamental question for oral cancer food-based prevention: Do BRB phytochemicals successfully reach the targeted oral tissues and reduce proinflammatory and antiapoptotic gene expression profiles? Patients with biopsy-confirmed oral squamous cell carcinomas (OSCC) administered oral troches containing freeze-dried BRB powder from the time of enrollment to the date of curative intent surgery (13.9 ± 1.27 days). Transcriptional biomarkers were evaluated in patient-matched OSCCs and noninvolved high at-risk mucosa (HARM) for BRB-associated changes. Significant expression differences between baseline OSCC and HARM tissues were confirmed using a panel of genes commonly deregulated during oral carcinogenesis. Following BRB troche administration, the expression of prosurvival genes (AURKA, BIRC5, EGFR) and proinflammatory genes (NFKB1, PTGS2) were significantly reduced. There were no BRB-associated grade 3-4 toxicities or adverse events, and 79.2% (N = 30) of patients successfully completed the study with high levels of compliance (97.2%). The BRB phytochemicals cyanidin-3-rutinoside and cyanidin-3-xylosylrutinoside were detected in all OSCC tissues analyzed, demonstrating that bioactive components were successfully reaching targeted OSCC tissues. We confirmed that hallmark antiapoptotic and proinflammatory molecular biomarkers were overexpressed in OSCCs and that their gene expression was significantly reduced following BRB troche administration. As these molecular biomarkers are fundamental to oral carcinogenesis and are modifiable, they may represent emerging biomarkers of molecular efficacy for BRB-mediated oral cancer chemoprevention. ©2015 American Association for Cancer

Melatonin mitigates thioacetamide-induced hepatic fibrosis via antioxidant activity and modulation of proinflammatory cytokines and fibrogenic genes.

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Lebda, Mohamed A; Sadek, Kadry M; Abouzed, Tarek K; Tohamy, Hossam G; El-Sayed, Yasser S

2018-01-01

The potential antifibrotic effects of melatonin against induced hepatic fibrosis were explored. Rats were allocated into four groups: placebo; thioacetamide (TAA) (200mg/kg bwt, i.p twice weekly for two months); melatonin (5mg/kgbwt, i.p daily for a week before TAA and continued for an additional two months); and melatonin plus TAA. Hepatic fibrotic changes were evaluated biochemically and histopathologically. Hepatic oxidative/antioxidative indices were assessed. The expression of hepatic proinflammatory cytokines (tumor necrosis factor-α, and interleukin-1β), fibrogenic-related genes (transforming growth factor-1β, collagen I, collagen, III, laminin, and autotaxin) and an antioxidant-related gene (thioredoxin-1) were detected by qRT-PCR. In fibrotic rats, melatonin lowered serum aspartate aminotransferase, alanine aminotransferase, and autotaxin activities, bilirubin, hepatic hydroxyproline and plasma ammonia levels. Melatonin displayed hepatoprotective and antifibrotic potential as indicated by mild hydropic degeneration of some hepatocytes and mild fibroplasia. In addition, TAA induced the depletion of glutathione, glutathione s-transferase, glutathione peroxidase, superoxide dismutase, catalase, and paraoxonase-1 (PON-1), while inducing the accumulation of malondialdehyde, protein carbonyl (C=O) and nitric oxide (NO), and DNA fragmentation. These effects were restored by melatonin pretreatment. Furthermore, melatonin markedly attenuated the expression of proinflammatory cytokines and fibrogenic genes via the upregulation of thioredoxin-1 mRNA transcripts. Melatonin exhibits potent anti-inflammatory, antioxidant and fibrosuppressive activities against TAA-induced hepatic fibrogenesis via the suppression of oxidative stress, DNA damage, proinflammatory cytokines and fibrogenic gene transcripts. In addition, we demonstrate that the antifibrotic activity of melatonin is mediated by the induction of thioredoxin-1 with attenuation of autotaxin expressions

DREAM Is Involved in the Genesis of Inflammation-Induced Prolabour Mediators in Human Myometrial and Amnion Cells

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Priyanka Goradia

2018-01-01

Full Text Available Preterm birth is the primary cause of perinatal morbidity and mortality worldwide. Inflammation induces a cascade of events leading to preterm birth by activating nuclear factor-κB (NF-κB. In nongestational tissues, downstream regulatory element antagonist modulator (DREAM regulates NF-κB activity. Our aims were to analyse DREAM expression in myometrium and fetal membranes obtained at term and preterm and to determine the effect of DREAM inhibition on prolabour mediators in primary myometrial and amnion cells. DREAM mRNA expression was significantly higher in fetal membranes obtained after spontaneous labour compared to nonlabour and in amnion from women with histological preterm chorioamnionitis when compared to amnion from women without chorioamnionitis. In primary myometrial and amnion cells, the effect of DREAM silencing by siRNA was a significant decrease in the expression of proinflammatory cytokine IL-6, the chemokines IL-8 and MCP-1, the adhesion molecule ICAM-1, MMP-9 mRNA expression and activity, and NF-κB transcriptional activity when stimulated with the proinflammatory cytokine IL-1β, the bacterial products fsl-1 or flagellin, or the viral dsRNA analogue poly(I:C. These data suggest that, in states of heightened inflammation, DREAM mRNA expression is increased and that, in myometrial and amnion cells, DREAM regulates proinflammatory and prolabour mediators which may be mediated via NF-κB.

Anton's syndrome due to cerebrovascular disease: a case report

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Maddula Mohana

2009-09-01

Full Text Available Abstract Introduction Anton's syndrome describes the condition in which patients deny their blindness despite objective evidence of visual loss, and moreover confabulate to support their stance. It is a rare extension of cortical blindness in which, in addition to the injury to the occipital cortex, other cortical centres are also affected, with patients typically behaving as if they were sighted. Case presentation We present a case report of an 83-year-old white woman with cortical blindness as a result of bilateral occipital lobe infarcts. Despite her obvious blindness, illustrated by her walking into objects, the patient expressed denial of visual loss and demonstrated confabulation in her accounts of her surroundings, consistent with a diagnosis of Anton's syndrome. Conclusions A suspicion of cortical blindness and Anton's syndrome should be considered in patients with atypical visual loss and evidence of occipital lobe injury. Cerebrovascular disease is the most common cause of Anton's syndrome, as in our patient. However, any condition that may result in cortical blindness can potentially lead to Anton's syndrome. Recovery of visual function will depend on the underlying aetiology, with cases due to occipital lobe infarction after cerebrovascular events being less likely to result in complete recovery. Management in these circumstances should accordingly focus on secondary prevention and rehabilitation.

Soluble intercellular adhesion molecule 1 and flow-mediated dilatation are related to the estimated risk of coronary heart disease independently from each other

NARCIS (Netherlands)

Witte, D.R.; Broekmans, W.M.R.; Kardinaal, A.F.M.; Klöpping-Ketelaars, I.A.A.; Poppel, G. van; Bots, M.L.; Kluft, C.; Princen, J.M.G.

2003-01-01

Background: Flow mediated dilatation (FMD) of the brachial artery and soluble intercellular adhesion molecule 1 (sICAM-1) are measures of distinct functions of the endothelium, reflecting nitric oxide (NO)-mediated and pro-inflammatory status, respectively. The comparative value of the two measures

Upregulation of proinflammatory genes in skin lesions may be the cause of keloid formation (Review)

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DONG, XIANGLIN; MAO, SHAOLIN; WEN, HAO

2013-01-01

It was previously demonstrated that the main cause behind keloid formation may be keloid fibroblast abnormalities, which are closely associated with the microenvironment of the keloid lesion. The post-traumatic and chronic inflammation of the keloid lesion area suggest that inflammatory mediators play an important role in the keloid microenvironment and are crucial for keloid fibroblast abnormalities. In this study, we hypothesized that the mechanism underlying keloid formation may involve the continuous upregulation of proinflammatory gene expression in keloid lesions. This hypothesis may explain the inflammatory response, invasive growth and recurrence following resection of keloids, as well as the selective localization of keloids in specific parts of a patient’s body and the differences in localization among different patients. PMID:24649037

Agonists for G-protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microglia

OpenAIRE

Wei, Li; Tokizane, Kyohei; Konishi, Hiroyuki; Yu, Hua-Rong; Kiyama, Hiroshi

2017-01-01

Background Several G-protein-coupled receptors (GPCRs) have been shown to be important signaling mediators between neurons and glia. In our previous screening for identification of nerve injury-associated GPCRs, G-protein-coupled receptor 84 (GPR84) mRNA showed the highest up-regulation by microglia after nerve injury. GPR84 is a pro-inflammatory receptor of macrophages in a neuropathic pain mouse model, yet its function in resident microglia in the central nervous system is poorly understood...

Research on the influence factors of the fall efficiency of the hospitalized geriatric patients with cerebrovascular diseases.

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Li, Weili; Cheng, Ruilian

2016-11-01

To investigate the fall efficiency and its influence factors of the hospitalized geriatric patients with cerebrovascular diseases. The Modified Fall Efficacy Scale (MFES), Morse Fall Risk Assessment Scales (MFS), Berg Balance Scale (BBS) and Tinetti Gait Analysis (TGA) were adopted and the combined ways of questionnaires and observation were utilized to investigate the 113 hospitalized geriatric patients with cerebrovascular diseases. The fall efficiency of the geriatric patients with cerebrovascular diseases were 7.85±2.57 scores. The two projects "walking up and down stairs" and "taking public transport means" have got the lowest scores; The two projects "stretching out the hand to the box or the drawer for taking something" and "sitting up and down to the chair" have got the highest scores. It was found that there were three factors which had significant influences on the fall efficiency, they were myodynamia of the right upper extremity, Berg balance functions and gait. For the sake of helping the geriatric patients with cerebrovascular diseases to establish the self-confidence of preventing the falls, the medical workers need to take further psychological counseling for the patients and befittingly and specifically to improve the fall efficiency of patients so as to effectively prevent the occurring of the fall on the basis of improving the balance ability and gait of patients.

Aqueous proinflammatory cytokines in acute primary angle-closure eyes

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Yao-Ming Liu

2017-05-01

Full Text Available AIM: To evaluate changes of proinflammatory cytokines in aqueous humor of patients with acute primary angle-closure (APAC and age-related cataracts. METHODS: Twenty eyes of 20 APAC patients and 15 eyes of 15 age-related cataract patients were included in this cross-sectional study. Aqueous humor samples were collected prospectively. The levels of 20 proinflammatory cytokines were evaluated in the aqueous humor of the APAC and cataract patients using the multiplex bead immunoassay technique. Clinical data were collected for correlation analysis. RESULTS: Seven of the 20 proinflammatory cytokines included in the magnetic bead panel were detectable in both APAC eyes and cataract eyes: interleukin (IL-10, IL-12, IL-15, IL-21, IL-6, chemokine (C-C motif ligand 20, and tumor necrosis factor alpha (TNF-α. IL-27 was only detectable in APAC eyes. Compared with the cataract eyes, the APAC eyes had significantly elevated concentrations of IL-12 (P=0.036, IL-15 (P=0.001, IL-6 (P=0.012, and IL-27 (only detectable in APAC eyes. Age was positively correlated with IL-12 (P=0.022 and IL-6 (P=0.037, and time elapsed between APAC onset and aqueous humor samples collection was positively correlated with IL-15 (P=0.037, IL-27 (P=0.040, and TNF-α (P=0.042. CONCLUSION: Several proinflammatory cytokines including IL-12，IL-15, IL-6 and IL-27, were elevated in the APAC eyes and may be implicated in its pathologic mechanism.

MAPK signaling pathway regulates cerebrovascular receptor expression in human cerebral arteries

DEFF Research Database (Denmark)

Ansar, Saema; Eftekhari, Sajedeh; Waldsee, Roya

2013-01-01

if the upregulation of contractile cerebrovascular receptors after 48 h of organ culture of human cerebral arteries involves MAPK pathways and if it can be prevented by a MEK1/2 inhibitor. Human cerebral arteries were obtained from patients undergoing intracranial tumor surgery. The vessels were divided into ring...

Neuroimaging correlates of cognitive functioning in cerebrovascular disease

OpenAIRE

Fernández-Andújar, Marina

2014-01-01

[spa] Los accidentes cerebrovasculares (ACV) son la tercera causa más común de muerte y la causa principal de discapacidad en adultos en los países desarrollados (Carmichael, 2012; Organización Mundial de la Salud, 2004). Concretamente, el ictus isquémico y las lesiones de sustancia blanca (LSB) frecuentemente dan lugar a múltiples secuelas neurológicas, deterioro cognitivo y alteraciones conductuales y emocionales (Gorelick et al., 2011; Troncoso et al., 2008). Los ACV son responsables de d...

Acne: a new model of immune-mediated chronic inflammatory skin disease.

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Antiga, E; Verdelli, A; Bonciani, D; Bonciolini, V; Caproni, M; Fabbri, P

2015-04-01

Acne is a chronic inflammatory disease of the sebaceous-pilosebaceous unit. Interestingly, inflammation can be detected by histopathological examination and immuohistochemical analysis even in the apparently non-inflammatory acneic lesions, such as comedones. In the last years, it has been clearly demonstrated that acne development is linked to the combination of predisposing genetic factors and environmental triggers, among which a prominent role is played by the follicular colonization by Propionibacterium acnes (P. acnes). P. acnes displays several activities able to promote the development of acne skin lesions, including the promotion of follicular hyperkeratinisation, the induction of sebogenesis, and the stimulation of an inflammatory response by the secretion of proinflammatory molecules and by the activation of innate immunity, that is followed by a P. acnes-specific adaptive immune response. In addition, P. acnes-independent inflammation mediated by androgens or by a neurogenic activation, followed by the secretion in the skin of pro-inflammatory neuropeptides, can occur in acne lesions. In conclusion, acne can be considered as a model of immune-mediated chronic inflammatory skin disease, characterized by an innate immune response that is not able to control P. acnes followed by a Th1-mediated adaptive immune response, that becomes self-maintaining independently from P. acnes itself.

Tachykinin NK₁ receptor antagonist co-administration attenuates opioid withdrawal-mediated spinal microglia and astrocyte activation.

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Tumati, Suneeta; Largent-Milnes, Tally M; Keresztes, Attila I; Yamamoto, Takashi; Vanderah, Todd W; Roeske, William R; Hruby, Victor J; Varga, Eva V

2012-06-05

Prolonged morphine treatment increases pain sensitivity in many patients. Enhanced spinal Substance P release is one of the adaptive changes associated with sustained opioid exposure. In addition to pain transmitting second order neurons, spinal microglia and astrocytes also express functionally active Tachykinin NK₁ (Substance P) receptors. In the present work we investigated the role of glial Tachykinin NK₁ receptors in morphine withdrawal-mediated spinal microglia and astrocyte activation. Our data indicate that intrathecal co-administration (6 days, twice daily) of a selective Tachykinin NK₁ receptor antagonist (N-acetyl-L-tryptophan 3,5-bis(trifluoromethyl)benzylester (L-732,138; 20 μg/injection)) attenuates spinal microglia and astrocyte marker and pro-inflammatory mediator immunoreactivity as well as hyperalgesia in withdrawn rats. Furthermore, covalent linkage of the opioid agonist with a Tachykinin NK₁ antagonist pharmacophore yielded a bivalent compound that did not augment spinal microglia or astrocyte marker or pro-inflammatory mediator immunoreactivity and did not cause paradoxical pain sensitization upon drug withdrawal. Thus, bivalent opioid/Tachykinin NK₁ receptor antagonists may provide a novel paradigm for long-term pain management.

Structure-Based Design and Synthesis of a Small Molecule that Exhibits Anti-inflammatory Activity by Inhibition of MyD88-mediated Signaling to Bacterial Toxin Exposure.

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Alam, Shahabuddin; Javor, Sacha; Degardin, Melissa; Ajami, Dariush; Rebek, Mitra; Kissner, Teri L; Waag, David M; Rebek, Julius; Saikh, Kamal U

2015-08-01

Both Gram-positive and Gram-negative pathogens or pathogen-derived components, such as staphylococcal enterotoxins (SEs) and endotoxin (LPS) exposure, activate MyD88-mediated pro-inflammatory cellular immunity for host defense. However, dysregulated MyD88-mediated signaling triggers exaggerated immune response that often leads to toxic shock and death. Previously, we reported a small molecule compound 1 mimicking BB-loop structure of MyD88 was capable of inhibiting pro-inflammatory response to SEB exposure in mice. In this study, we designed a dimeric structure compound 4210 covalently linked with compound 1 by a non-polar cyclohexane linker which strongly inhibited the production of pro-inflammatory cytokines in human primary cells to SEB (IC50 1-50 μm) or LPS extracted from Francisella tularensis, Escherichia coli, or Burkholderia mallei (IC50 10-200 μm). Consistent with cytokine inhibition, in a ligand-induced cell-based reporter assay, compound 4210 inhibited Burkholderia mallei or LPS-induced MyD88-mediated NF-kB-dependent expression of reporter activity (IC50 10-30 μm). Furthermore, results from a newly expressed MyD88 revealed that 4210 inhibited MyD88 dimer formation which is critical for pro-inflammatory signaling. Importantly, a single administration of compound 4210 in mice showed complete protection from lethal toxin challenge. Collectively, these results demonstrated that compound 4210 inhibits toxin-induced inflated pro-inflammatory immune signaling, thus displays a potential bacterial toxin therapeutic. © 2014 John Wiley & Sons A/S.

Suppressive Effect on Lipopolysaccharide-Induced Proinflammatory Mediators by Citrus aurantium L. in Macrophage RAW 264.7 Cells via NF-κB Signal Pathway

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Sang-Rim Kang

2011-01-01

Full Text Available Citrus fruits have been used as an edible fruit and a traditional medicine since ancient times. In particular, the peels of immature citrus fruits are used widely in traditional herbal medicine in Korea, as they are believed to contain bioactive components exerting anti-inflammatory activity. This study examined whether the crude methanol extract of Citrus aurantium L. (CME has a suppressive effect on inducible enzymes and proinflammatory cytokines by inhibiting the NF-κB pathway in LPS-stimulated macrophage RAW 264.7 cells. The cells were pretreated with the indicated concentrations of CME (5, 10, 20, and 50 μg/mL and then treated with LPS (1 μg/mL. The results showed that CME (10, 20, and 50 μg/mL inhibited the LPS- (1 μg/mL induced mRNA and protein expression of iNOS in macrophage Raw 264.7 cells. In addition, the expression of COX-2 was inhibited at the mRNA and protein levels by CME in a dose-dependent manner. The mRNA expression of proinflammatory cytokines, such as TNF-α and IL-6, were markedly reduced by CME (10, 20, and 50 μg/mL. Moreover, CME clearly suppressed the nuclear translocation of the NF-κB p65 subunits, which was correlated with its inhibitory effect on I-κB phosphorylation. These results suggest that CME has anti-inflammatory properties by modulating the expression of COX-2, iNOS, and proinflammatory cytokines, such as TNF-α and IL-6, in macrophage RAW 264.7 cells via the NF-κB pathway.

Cyclic mechanical stretch down-regulates cathelicidin antimicrobial peptide expression and activates a pro-inflammatory response in human bronchial epithelial cells

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Harpa Karadottir

2015-12-01

Full Text Available Mechanical ventilation (MV of patients can cause damage to bronchoalveolar epithelium, leading to a sterile inflammatory response, infection and in severe cases sepsis. Limited knowledge is available on the effects of MV on the innate immune defense system in the human lung. In this study, we demonstrate that cyclic stretch of the human bronchial epithelial cell lines VA10 and BCi NS 1.1 leads to down-regulation of cathelicidin antimicrobial peptide (CAMP gene expression. We show that treatment of VA10 cells with vitamin D3 and/or 4-phenyl butyric acid counteracted cyclic stretch mediated down-regulation of CAMP mRNA and protein expression (LL-37. Further, we observed an increase in pro-inflammatory responses in the VA10 cell line subjected to cyclic stretch. The mRNA expression of the genes encoding pro-inflammatory cytokines IL-8 and IL-1β was increased after cyclic stretching, where as a decrease in gene expression of chemokines IP-10 and RANTES was observed. Cyclic stretch enhanced oxidative stress in the VA10 cells. The mRNA expression of toll-like receptor (TLR 3, TLR5 and TLR8 was reduced, while the gene expression of TLR2 was increased in VA10 cells after cyclic stretch. In conclusion, our in vitro results indicate that cyclic stretch may differentially modulate innate immunity by down-regulation of antimicrobial peptide expression and increase in pro-inflammatory responses.

Resultados del tratamiento fisioterapéutico mediato en pacientes con enfermedad cerebrovascular Results from the immediate physiotherapeutic treatment in patients diagnosed with cerebrovascular disease

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Enrique Arce Morera

2010-12-01

Full Text Available Se realizó un estudio que comienza prospectivo, pero continúa y termina descriptivo sobre la enfermedad cerebrovascular, con los casos nuevos que fueron tratados en el Servicio de Rehabilitación Municipal de Artemisa en el año 2008, con el objetivo general de describir los resultados del tratamiento mediato. De un universo de 46 pacientes, la muestra tomada consistió en 25 pacientes, y como la población fue pequeña, se tomaron los catalogados como hemiparéticos, para comparar su evolución clínica al cabo de 6 meses de tratamiento normado e individualizado. Para comparar su grado de efectividad se utilizó la dócima de Mc Nemar o método de los 4 cuadros, utilizado en muestras pequeñas para buscar significación estadística y que los valores obtenidos no se deban al azar. En cuanto a los resultados: de los 14 casos que recibieron tratamiento de rehabilitación en etapas mediatas, 9 de ellos (63,7 % tuvieron mejoría clínica evidente al pasar al estadio de solo presentar signos neurológicos mínimos (definición operacional de variable. Hubo un predominio del grupo perteneciente al sexo masculino con un total de 30 casos, el 37 % estuvo en edades comprendidas entre 60 y 69 años, y el estadio clínico de hemiparéticos predominó de todos los casos (54,6 %.A prospective study was conducted which start and end in a descriptive way on the cerebrovascular disease with the new cases treated in the Municipal Rehabilitation Service of Artemisa municipality during 2008, with the general objective of to describe the results from the mediate treatment. From a universe including 40 patients, the sample was of 25 patients and due to the population was small; we selected those considered hemiparetic to compare its clinical course at 6 months of standardized and individualized treatment. To compare its effectiveness degree we used the McNemar's docime or the method of four pictures used in small samples to seek a statistic significance and that

Epigenetic regulation of pro-inflammatory cytokine secretion by sphingosine 1-phosphate (S1P) in acute lung injury: Role of S1P lyase.

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Ebenezer, David L; Fu, Panfeng; Suryadevara, Vidyani; Zhao, Yutong; Natarajan, Viswanathan

2017-01-01

Cellular level of sphingosine-1-phosphate (S1P), the simplest bioactive sphingolipid, is tightly regulated by its synthesis catalyzed by sphingosine kinases (SphKs) 1 & 2 and degradation mediated by S1P phosphatases, lipid phosphate phosphatases, and S1P lyase. The pleotropic actions of S1P are attributed to its unique inside-out (extracellular) signaling via G-protein-coupled S1P1-5 receptors, and intracellular receptor independent signaling. Additionally, S1P generated in the nucleus by nuclear SphK2 modulates HDAC1/2 activity, regulates histone acetylation, and transcription of pro-inflammatory genes. Here, we present data on the role of S1P lyase mediated S1P signaling in regulating LPS-induced inflammation in lung endothelium. Blocking S1P lyase expression or activity attenuated LPS-induced histone acetylation and secretion of pro-inflammatory cytokines. Degradation of S1P by S1P lyase generates Δ2-hexadecenal and ethanolamine phosphate and the long-chain fatty aldehyde produced in the cytoplasmic compartment of the endothelial cell seems to modulate histone acetylation pattern, which is different from the nuclear SphK2/S1P signaling and inhibition of HDAC1/2. These in vitro studies suggest that S1P derived long-chain fatty aldehyde may be an epigenetic regulator of pro-inflammatory genes in sepsis-induced lung inflammation. Trapping fatty aldehydes and other short chain aldehydes such as 4-hydroxynonenal derived from S1P degradation and lipid peroxidation, respectively by cell permeable agents such as phloretin or other aldehyde trapping agents may be useful in treating sepsis-induced lung inflammation via modulation of histone acetylation. . Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical significance of the dynamic changes of serum IGF-1 levels in patients with acute cerebro-vascular accident

International Nuclear Information System (INIS)

Chen Yujuan; Liu Xueyuan; Bian Weihong; Du Xinlu; Yang Hongyan

2006-01-01

Objective: To investigate the dynamic changes of serum insulin-like growth factor-1 (IGF-1) levels in patients with acute cerebrovascular accident. Methods: Serum IGF-1 levels were determined with RIA in 40 patients with cerebral infarction, 20 patients with lacunar infarcts and 40 patients with cerebral haemorrhage within 3days after onset and on d14 as well as in 30 controls. Results: The serum IGF-1 levels in patients with cerebral vascular accidents were significantly lower than those in controls (P 0.05). Conclusion: Serum levels of IGF-1 dropped markedly during the acute stage after cerebrovascular accident and the magnitude might reflect the severity of the event, IGF-1 might be capable of crossing the blood-brain barrier after cerebrovascular accident and providing some protection against nerve injury, this fact might be of potential clinical applicability. (authors)

Nutritional Improvement and Energy Intake Are Associated with Functional Recovery in Patients after Cerebrovascular Disorders.

Science.gov (United States)

Nii, Maria; Maeda, Keisuke; Wakabayashi, Hidetaka; Nishioka, Shinta; Tanaka, Atsuko

2016-01-01

Malnutrition affects the activities of daily living (ADLs) in convalescent patients with cerebrovascular disorders. We investigated the relationship between nutritional improvement, energy intake at admission, and recovery of ADLs. We evaluated 67 patients with cerebrovascular disorders admitted to our rehabilitation hospital between April 2013 and April 2015. These patients received interventions from the rehabilitation nutritional support team according to the following criteria: weight loss of 2 kg or more and body mass index of 19 kg/m(2) or lower. Exclusion criteria included a body mass index of 25 kg/m(2) or higher, duration of intervention of less than 14 days, or transfer to an acute care hospital because of clinical deterioration. We assessed nutritional status using the Geriatric Nutritional Risk Index (GNRI) and ADL using the Functional Independence Measure (FIM) score, FIM gain, and FIM efficiency. The mean age of the patients was 78.7 ± 8.0 years. The numbers of patients in each category of cerebrovascular disorder were 39 with cerebral infarction, 16 with intracerebral hemorrhage, 8 with subarachnoid hemorrhage, and 4 others. Compared with the counterpart group, the group with an improvement in GNRI had a greater gain in FIM (median 17 and 20, respectively; P = .036) and a higher FIM efficiency (.14 and .22, respectively; P = .020). Multivariate stepwise regression analysis showed that an improvement in GNRI, increasing energy intake at admission, and intracerebral hemorrhage were associated independently with greater FIM efficiency. This study suggested that nutritional improvement and energy intake at admission are associated with recovery of ADL after cerebrovascular disorders. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

PET in cerebrovascular disease; PET bei zerebrovaskulaeren Erkrankungen

Energy Technology Data Exchange (ETDEWEB)

Herholz, K. [Neurologische Universitaetsklinik der Univ. Koeln (Germany)]|[Max-Planck-Institut fuer Neurologische Forschung, Koeln (Germany)

1997-03-01

Tissue viability is of particular interest in acute cerebral ischemia because it may be preserved if reperfusion can be achieved rapidly, e.g. by acute thrombolysis. Measurements of regional cerebral blood flow (CBF) and oxygen consumption by PET can assess tissue viability, and they have substantially increased our knowledge of th pathophysiology of ischemic stroke and the associated penumbra. Widerspread clinical application in acute stroke, however, is unlikely because of the large logistic and personnel resources required. In chronic cerebrovascular disease, measurement of regional CBF and glucose metabolism, which is usually coupled, provide detailed insights in disturbance of cortical function, e.g. due to deafferentiation, and contribute to differentiation of dementia types. Chronic misery perfusion, i.e. reduced perfusion that does not match the metabolic demand of the tissue, can be demonstrated by PET. It may be found in some patients with high-grade arterial stenoses. Less severe impairment of brain perfusion can be demonstrated by measurement of the cerebrovascular reserve capacity. The most frequent clinical situations can be assessed by less demanding procedures, e.g. by SPECT. In conclusion, PET has its role in cerebrovascular disease primarily within scientific studies, where high resolution and absolute quantitation of physiological variables are essential. (orig.). 65 refs. [Deutsch] Beim akuten ischaemischen Insult ist die Vitalitaet des Gewebes von besonderem Interesse, da sie durch rasche Reperfusion, z.B. durch Thrombolyse, erhalten bleiben kann. Messungen der zerebralen Durchblutung und des Sauerstoffumsatzes mittels PET geben darueber wesentliche Aufschluesse, und sie sind wichtig fuer das Verstaendnis der Pathophysiologie ischaemischer Infarkte und der Penumbra mit kritischer Perfusion beim Menschen. Ihre breitere Anwendung in der klinischen Patientenversorgung kommt allerdings wegen des hohen Aufwandes derzeit kaum in Betracht. Bei

Proinflammatory cytokine levels in fibromyalgia patients are independent of body mass index.

Science.gov (United States)

Hernandez, Maria E; Becerril, Enrique; Perez, Mayra; Leff, Philippe; Anton, Benito; Estrada, Sergio; Estrada, Iris; Sarasa, Manuel; Serrano, Enrique; Pavon, Lenin

2010-06-03

Fibromyalgia (FM) is characterized by chronic, widespread muscular pain and tenderness and is generally associated with other somatic and psychological symptoms. Further, circulatory levels of proinflammatory cytokines (IL-1beta, TNF-alpha, and IL-6) may be altered in FM patients, possibly in association with their symptoms. Recently, rises in BMI have been suggested to contribute to increased circulating levels of proinflammatory cytokines in FM patients. Our aim was to measure the circulatory levels of proinflammatory cytokines to determine the influence of BMI on these levels in FM patients and healthy volunteers (HVs). In Spanish FM patients (n = 64) and HVs (n = 25), we measured BMI and serum concentrations of proinflammatory cytokines by capture ELISA. There were significant differences in BMI levels between FM patients (26.40 +/- 4.46) and HVs (23.64 +/- 3.45) and significant increase in IL-6 in FM patients (16.28 +/- 8.13 vs 0.92 +/- 0.32 pg/ml) (P BMI and TNF-alpha (F = 0.098, p = 0.75) or IL-6 (F = 0.221, p = 0.63) levels in FM patients. Our analysis in FM patients of BMI as a covariate of proinflammatory cytokines levels showed that serum TNF-alpha and IL-6 levels are independent of BMI. Further studies are necessary to dissect these findings and their implication in future therapeutic approaches for FM patients.

Impaired dynamic cerebrovascular response to hypercapnia predicts development of white matter hyperintensities

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Kevin Sam

2016-01-01

Conclusions: Vascular impairment in regions of NAWM that progresses to WMH consists not only of decreased magnitude of ssCVR, but also a pathological decrease in the speed of vascular response. These findings support the association between cerebrovascular dysregulation and the development of WMH.

Correlation between serum fructosamine and hyperglycemia in patients with acute cerebrovascular disease

Institute of Scientific and Technical Information of China (English)

Kaiqiu Chu; Pengpeng Liu; Lijuan Tan; Shuhua Zhou; Lisheng Ren

2006-01-01

BACKGROUND: Diabetes mellitus is one of the risk factors in patients with acute cerebral disease, and always leads to stroke or get it worse. There is often a high level of blood glucose in those patients with diabetes mellitus and cerebral disease, but it is hard to distinguish from both kinds of hyperglycemia. Serum fructosamine is said to be correlated with blood glucose.OBJECTIVE: To explore the relationship between serum fructosamine and blood glucose in patients with acute cerebrovascular disease.DESTGN: A case-controlled study.SETTINGS: Department of Clinical Laboratory, Health Department for Cadres and Department of Neurology of Affiliated Hospital, Qingdao University Medical College.PARTICIPANTS: Forty-eight inpatients and outpatients with cerebrovascular diseases were selected from the Department of Neurology, Affiliated Hospital of Qingdao University Medical College from December 2004 to April 2005. All the patients were confirmed with CT and MRI. There were 25 patients with diabetes mellitus secondary cerebrovascular diseases, who met the diagnostic standards of diabetes mellitus set by WHO,including 12 males and 13 females with an average of (60±8) years old, the course of diabetes mellitus ranged from 1 to 21 years.. The other 23 patients had no diabetes mellitus (without diabetes mellitus group), including 14 males and 9 females with an average of (62±6) years old. Meanwhile, another 50 healthy physical examinees in the hospital were selected as control group, including 26 males and 24 females with the average age of (62±5) years old. Informed content was obtained from all the participants.METHODS: Venous blood was drawn from all the participants, and content of blood glucose was assayed by means of glucose oxidase, and the concentration of serum fructosamine was determined by nitroblue tetrazolium colorimetric method. Comparison between groups was performed by the analysis of variance and q test, and the correlation was tested by linear

Influencing factors for early acute cerebrovascular accidents in patients with stroke history following off-pump coronary artery bypass grafting.

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Wang, Bin; Jia, Ming; Jia, Shijie; Wan, Jiuhe; Zhou, Xiao; Luo, Zhimin; Zhou, Ye; Zhang, Jianqun

2014-06-01

To analyse risk factors for early acute cerebrovascular accidents following off-pump coronary artery bypass grafting (OPCAB) in patients with stroke history, and to propose preventive measures to reduce the incidence of these events. A total of 468 patients with a history of stroke underwent OPCAB surgery in Beijing Anzhen Hospital of China from January 2010 to September 2012. They were retrospectively divided into two groups according to the occurrence of early acute cerebrovascular accidents within 48 hours following OPCAB. Multivariate logistic regression analysis was used to find risk or protective factors for early acute cerebrovascular accidents following the OPCAB. Fifty-two patients (11.1%) suffered from early acute cerebrovascular accidents in 468 patients, including 39 cases of cerebral infarction, two cases of cerebral haemorrhage, 11 cases of transient ischaemic attack (TIA). There were significant differences between the two groups in preoperative left ventricular ejection fraction ≤ 35%, severe bilateral carotid artery stenosis, poorly controlled hypertension, intraoperative application of Enclose® II proximal anastomotic device, postoperative acute myocardial infarction, atrial fibrillation, hypotension, ventilation time > 48h, ICU duration >48h and mortality. Multivariate logistic regression analysis showed that preoperative severe bilateral carotid stenosis (OR=6.378, 95%CI: 2.278-20.987) and preoperative left ventricular ejection fraction ≤ 35% (OR=2.737, 95%CI: 1.267-6.389), postoperative acute myocardial infarction (OR=3.644, 95%CI: 1.928-6.876), postoperative atrial fibrillation (OR=3.104, 95%CI:1.135∼8.016) and postoperative hypotension (OR=4.173, 95%CI: 1.836∼9.701) were independent risk factors for early acute cerebrovascular accidents in patients with a history of stroke following OPCAB procedures, while intraoperative application of Enclose® II proximal anastomotic device was protective factor (OR=0.556, 95%CI: 0.337-0.925). This

ANTIPLATELET THERAPY IN THE PREVENTION OF CEREBROVASCULAR ACCIDENTS

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O. V. Rodionova

2017-01-01

Full Text Available Currently the problem of preventing cerebrovascular disorders, in which antiplatelet therapy takes one of the leading places, remains relevant. The efficiency of the therapy depends on a large number of modifiable and non-modifiable factors. There are many methods to assess the severity of the response to antiplatelet therapy, but there is no common approach to the assessment of the results and their prognostic significance. Further studies of this issue are essential with the aim of individualization of antiplatelet therapy thereby increasing its efficiency and safety.

RELATIONSHIP OF ADIPOKINES AND PROINFLAMMATORY CYTOKINES AMONG ASIAN INDIANS WITH OBESITY AND YOUTH ONSET TYPE 2 DIABETES.

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Gokulakrishnan, Kuppan; Amutha, Anandakumar; Ranjani, Harish; Bibin, Subramanian Y; Balakumar, Mahalingam; Pandey, Gautam Kumar; Anjana, Ranjit Mohan; Ali, Mohammed K; Narayan, K M Venkat; Mohan, Viswanathan

2015-10-01

It is well known that inflammation is associated with diabetes, but it is unclear whether obesity mediates this association in individuals with youth-onset type 2 diabetes mellitus (T2DM-Y). We recruited individuals with T2DM-Y (age at onset obesity and categorized as: nonobese NGT (n = 100), Obese NGT (n = 50), nonobese T2DM-Y (n = 50), and obese T2DM-Y (n = 50). We compared adipokines (adiponectin and leptin) and proinflammatory cytokines (tumor necrosis factor alpha [TNF-α] and monocyte chemotactic protein-1 [MCP-1]) across groups. Compared to nonobese NGT, the other 3 groups (obese NGT, nonobese T2DM-Y, and obese T2DM-Y) were found to have lower adiponectin (7.7 vs. 5.7, 4.2, 3.8 μg/mL, Pobese T2DM-Y (141 pg/mL, Pobese T2DM, respectively. However, adjusted for same factors, leptin, TNF-α, and MCP-1 were associated with markedly higher odds (5- to 14-fold) of nonobese and obese T2DM. In young Asian Indians, leptin and proinflammatory cytokines are positively, and adiponectin negatively, associated with both nonobese and obese T2DM-Y compared to nonobese NGT individuals.

Increased Prevalence of Cerebrovascular Disease in Hospitalized Patients with Marfan Syndrome.

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Kim, Sarasa T; Cloft, Harry; Flemming, Kelly D; Kallmes, David F; Lanzino, Giuseppe; Brinjikji, Waleed

2018-02-01

Small studies have suggested that Marfan syndrome is associated with a number of cerebrovascular complications. We sought to determine whether a clinical diagnosis of Marfan syndrome is associated with a higher prevalence of cerebrovascular diseases than the general population by performing a case-control study of hospitalized patients in the Nationwide Inpatient Sample (NIS). Using the 2000-2012 NIS, we performed a case-control study matching cases of Marfan syndrome to controls without such a diagnosis. The prevalence of various cerebrovascular diseases between the 2 groups were compared, and multivariate logistic regression was used to adjust for suspected comorbidities. Between 2000 and 2012, there were a total of 13,883 discharges carrying a diagnosis of Marfan syndrome. On univariate analysis, patients with Marfan syndrome were more likely to have a primary or secondary diagnosis of hemorrhagic stroke (0.5% versus 0.3%, odds ratio [OR] = 1.56, 95% confidence interval [CI] = 1.06-2.29, P = 0.02) as well as intracranial hemorrhage (subarachnoid hemorrhage [SAH] and hemorrhagic stroke) (0.3% versus 0.2%, OR = 1.72, 95% CI = 1.05-2.82, P = 0.03). Patients hospitalized with Marfan syndrome were significantly more likely to have carotid dissection (0.3% versus 0.0%, OR = 11.69, 95% CI = 3.60-38.08, P Marfan syndrome had significantly higher odds of ischemic stroke (OR = 1.20, 95% CI = 1.02-1.43, P = 0.03), hemorrhagic stroke (OR = 1.75, 95% CI = 1.18-2.63, P = 0.005), carotid artery dissection (OR = 11.94, 95% CI = 4.23-50.03, P Marfan syndrome when compared with controls. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Terbinafine stimulates the pro-inflammatory responses in human monocytic THP-1 cells through an ERK signaling pathway.

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Mizuno, Katsuhiko; Fukami, Tatsuki; Toyoda, Yasuyuki; Nakajima, Miki; Yokoi, Tsuyoshi

2010-10-23

Oral antifungal terbinafine has been reported to cause liver injury with inflammatory responses in a small percentage of patients. However the underlying mechanism remains unknown. To examine the inflammatory reactions, we investigated whether terbinafine and other antifungal drugs increase the release of pro-inflammatory cytokines using human monocytic cells. Dose- and time-dependent changes in the mRNA expression levels and the release of interleukin (IL)-8 and tumor necrosis factor (TNF)α from human monocytic THP-1 and HL-60 cells with antifungal drugs were measured. Effects of terbinafine on the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK)1/2 were investigated. The release of IL-8 and TNFα from THP-1 and HL-60 cells was significantly increased by treatment with terbinafine but not by fluconazole, suggesting that terbinafine can stimulate monocytes and increase the pro-inflammatory cytokine release. Terbinafine also significantly increased the phosphorylation of ERK1/2 and p38 MAP kinase in THP-1 cells. Pretreatment with a MAP kinase/ERK kinase (MEK)1/2 inhibitor U0126 significantly suppressed the increase of IL-8 and TNFα levels by terbinafine treatment in THP-1 cells, but p38 MAPK inhibitor SB203580 did not. These results suggested that an ERK1/2 pathway plays an important role in the release of IL-8 and TNFα in THP-1 cells treated with terbinafine. The release of inflammatory mediators by terbinafine might be one of the mechanisms underlying immune-mediated liver injury. This in vitro method may be useful to predict adverse inflammatory reactions that lead to drug-induced liver injury. Copyright © 2010 Elsevier Inc. All rights reserved.

Outcomes With Edoxaban Versus Warfarin in Patients With Previous Cerebrovascular Events

DEFF Research Database (Denmark)

Rost, Natalia S; Giugliano, Robert P; Ruff, Christian T

2016-01-01

BACKGROUND AND PURPOSE: Patients with atrial fibrillation and previous ischemic stroke (IS)/transient ischemic attack (TIA) are at high risk of recurrent cerebrovascular events despite anticoagulation. In this prespecified subgroup analysis, we compared warfarin with edoxaban in patients with ver......BACKGROUND AND PURPOSE: Patients with atrial fibrillation and previous ischemic stroke (IS)/transient ischemic attack (TIA) are at high risk of recurrent cerebrovascular events despite anticoagulation. In this prespecified subgroup analysis, we compared warfarin with edoxaban in patients...... with versus without previous IS/TIA. METHODS: ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a double-blind trial of 21 105 patients with atrial fibrillation randomized to warfarin (international normalized ratio......). Because only HDER is approved, we focused on the comparison of HDER versus warfarin. RESULTS: Of 5973 (28.3%) patients with previous IS/TIA, 67% had CHADS2 (congestive heart failure, hypertension, age, diabetes, prior stroke/transient ischemic attack) >3 and 36% were ≥75 years. Compared with 15 132...

Clinical application of dynamic digital subtraction angiography in cerebrovascular ischemic diseases

Energy Technology Data Exchange (ETDEWEB)

Hirata, Yoshifumi; Nonaka, Nobuhito; Matsukado, Yasuhiko; Takahashi, Mutsumasa

1987-09-01

Dynamic intravenous digital subtraction angiography (IV-DSA) was performed in 37 patients with cerebrovascular ischemic diseases. The time density curve of IV-DSA was analysed, and peak time, mean transit time and mode of transit time were obtained in each patient. On the basis of these values, cerebral perfusion was classified into low, normal and high perfusion patterns. Normal perfusion pattern was noted in 40% of patients with transient ischemic attack (TIA) and 7 % of patients with cerebral infarction. Low perfusion pattern was observed in 60 % of patients with TIA and 87 % of patients with cerebral infarction. High perfusion pattern was encountered only in 7 % of patients with cerebral infarction. In ischemic patients with moyamoya disease, extremely prolonged cerebral circulation time was evidenced by the presence of a flat or uphill type of the time density curve. This finding well correlated with decreased cerebral blood flow on single photon emission tomography. These findings suggest that the analysis of dynamic DSA is very important and useful in the clinical evaluation of patients with cerebrovascular ischemic diseases.

Neurological signs in relation to type of cerebrovascular disease in vascular dementia

NARCIS (Netherlands)

Staekenborg, S.S.; van der Flier, W.M.; van Straaten, E.C.W.; Lane, R.; Barkhof, F.; Scheltens, P.

2008-01-01

BACKGROUND AND PURPOSE - The aim of this study was to describe the prevalence of a number of neurological signs in a large population of patients with vascular dementia (VaD) and to compare the relative frequency of specific neurological signs dependent on type of cerebrovascular disease. METHODS -

Oncolytic Group B Adenovirus Enadenotucirev Mediates Non-apoptotic Cell Death with Membrane Disruption and Release of Inflammatory Mediators

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Arthur Dyer

2017-03-01

Full Text Available Enadenotucirev (EnAd is a chimeric group B adenovirus isolated by bioselection from a library of adenovirus serotypes. It replicates selectively in and kills a diverse range of carcinoma cells, shows effective anticancer activity in preclinical systems, and is currently undergoing phase I/II clinical trials. EnAd kills cells more quickly than type 5 adenovirus, and speed of cytotoxicity is dose dependent. The EnAd death pathway does not involve p53, is predominantly caspase independent, and appears to involve a rapid fall in cellular ATP. Infected cells show early loss of membrane integrity; increased exposure of calreticulin; extracellular release of ATP, HSP70, and HMGB1; and influx of calcium. The virus also causes an obvious single membrane blister reminiscent of ischemic cell death by oncosis. In human tumor biopsies maintained in ex vivo culture, EnAd mediated release of pro-inflammatory mediators such as TNF-α, IL-6, and HMGB1. In accordance with this, EnAd-infected tumor cells showed potent stimulation of dendritic cells and CD4+ T cells in a mixed tumor-leukocyte reaction in vitro. Whereas many viruses have evolved for efficient propagation with minimal inflammation, bioselection of EnAd for rapid killing has yielded a virus with a short life cycle that combines potent cytotoxicity with a proinflammatory mechanism of cell death.

Loss of function mutations in the progranulin gene are related to pro-inflammatory cytokine dysregulation in frontotemporal lobar degeneration patients

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Spalletta Gianfranco

2011-06-01

Full Text Available Abstract The progranulin gene (PGRN encodes a pleiotropic molecule with anti-inflammatory actions and neuronal protective effects. Accordingly, PGRN-deficient mice have been demonstrated to develop enhanced inflammation and progressive neurodegeneration. Loss of function mutations of the PGRN gene have been also reported to cause frontotemporal lobar degeneration (FTLD, a neurodegenerative disease leading to dementia generally in the presenium. Since neurodegeneration might be negatively impacted by chronic inflammation, the possible influence of PGRN defects on inflammatory pathways appears to be of great relevance for the understanding of neurodegeneration pathogenic processes in those patients. However, no data about the inflammatory profile of PGRN-defective subjects have been so far provided. In this study, we analyzed serum levels of the pro-inflammatory mediators IL-6, TNF-α and IL-18 in FTLD patients with or without PGRN mutations, at both pre-symptomatic and symptomatic stages. We provide evidence that circulating IL-6 is increased in PGRN-mutated FTLD patients, as compared to both PGRN non-mutated FTLD patients and controls. In contrast, levels of IL-6 were not altered in asymptomatic subjects carrying the PGRN mutations. Finally, TNF-α and IL-18 serum levels did not differ among all groups of included subjects. We conclude that the profile of circulating pro-inflammatory cytokines is altered in PGRN-related symptomatic FTLD. Thus, our findings point to IL-6 as a possible specific mediator and a potential therapeutic target in this monogenic disease, suggesting that an enhanced inflammatory response might be indeed involved in its progression.

Embelin and its derivatives unravel the signaling, proinflammatory and antiatherogenic properties of GPR84 receptor.

Science.gov (United States)

Gaidarov, Ibragim; Anthony, Todd; Gatlin, Joel; Chen, Xiaohua; Mills, David; Solomon, Michelle; Han, Sangdon; Semple, Graeme; Unett, David J

2018-05-01

GPR84 is an orphan G-protein coupled receptor, expressed on monocytes, macrophages and neutrophils and is significantly upregulated by inflammatory stimuli. The physiological role of GPR84 remains largely unknown. Medium chain fatty acids (MCFA) activate the receptor and have been proposed to be its endogenous ligands, although the high concentrations of MCFAs required for receptor activation generally exceed normal physiological levels. We identified the natural product embelin as a highly potent and selective surrogate GPR84 agonist (originally disclosed in patent application WO2007027661A2, 2007) and synthesized close structural analogs with widely varying receptor activities. These tools were used to perform a comprehensive study of GPR84 signaling and function in recombinant cells and in primary human macrophages and neutrophils. Activation of recombinant GPR84 by embelin in HEK293 cells results in G i/o as well as G12/13-Rho signaling. In human macrophages, GPR84 initiates PTX sensitive Erk1/2 and Akt phosphorylation, PI-3 kinase activation, calcium flux, and release of prostaglandin E2. In addition, GPR84 signaling in macrophages elicits G i Gβγ-mediated augmentation of intracellular cAMP, rather than the decrease expected from G iα engagement. GPR84 activation drives human neutrophil chemotaxis and primes them for amplification of oxidative burst induced by FMLP and C5A. Loss of GPR84 is associated with attenuated LPS-induced release of proinflammatory mediators IL-6, KC-GROα, VEGF, MIP-2 and NGAL from peritoneal exudates. While initiating numerous proinflammatory activities in macrophages and neutrophils, GPR84 also possesses GPR109A-like antiatherosclerotic properties in macrophages. Macrophage receptor activation leads to upregulation of cholesterol transporters ABCA1 and ABCG1 and stimulates reverse cholesterol transport. These data suggest that GPR84 may be a target of therapeutic value and that distinct modes of receptor modulation (inhibition vs

Necroptotic cells release find-me signal and are engulfed without proinflammatory cytokine production.

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Wang, Qiang; Ju, Xiaoli; Zhou, Yang; Chen, Keping

2015-11-01

Necroptosis is a form of caspase-independent programmed cell death which is mediated by the RIP1-RIP3 complex. Although phagocytosis of apoptotic cells has been extensively investigated, how necroptotic cells are engulfed has remained elusive. Here, we investigated how necroptotic cells attracted and were engulfed by macrophages. We found that necroptotic cells induced the migration of THP-1 cells in a transwell migration assay. Further analysis showed that ATP released from necroptotic cells acted as a find-me signal that induced the migration of THP-1 cells. We also found that Annexin V blocked phagocytosis of necroptotic cells by macrophages. Furthermore, necroptotic cells were shown to be silently cleared by macrophages without any proinflammatory cytokine production. These data uncover an evolutionarily conserved mechanism of the find-me signal in different types of cell death and immunological consequences between apoptotic and necroptotic cells during phagocytosis.

Effect of caffeic acid phenethyl ester on Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

Science.gov (United States)

Choi, E-Y; Choe, S-H; Hyeon, J-Y; Choi, J-I; Choi, I S; Kim, S-J

2015-12-01

Caffeic acid phenethyl ester (CAPE) has numerous potentially beneficial properties, including antioxidant, immunomodulatory and anti-inflammatory activities. However, the effect of CAPE on periodontal disease has not been studied before. This study was designed to investigate the efficacy of CAPE in ameliorating the production of proinflammatory mediators in macrophages activated by lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in periodontal disease. LPS from P. intermedia ATCC 25611 was isolated by using the standard hot phenol-water method. Culture supernatants were assayed for nitric oxide (NO), interleukin (IL)-1β and IL-6. We used real-time polymerase chain reaction to quantify inducible NO synthase, IL-1β, IL-6, heme oxygenase (HO)-1 and suppressors of cytokine signaling (SOCS) 1 mRNA expression. HO-1 protein expression and levels of signaling proteins were assessed by immunoblot analysis. DNA-binding activities of NF-κB subunits were analyzed by using the enzyme-linked immunosorbent assay-based kits. CAPE exerted significant inhibitory effects on P. intermedia LPS-induced production of NO, IL-1β and IL-6 as well as their mRNA expression in RAW264.7 cells. CAPE-induced HO-1 expression in cells activated with P. intermedia LPS, and selective inhibition of HO-1 activity by tin protoporphyrin IX attenuated the inhibitory effect of CAPE on LPS-induced NO production. CAPE did not interfere with IκB-α degradation induced by P. intermedia LPS. Instead, CAPE decreased nuclear translocation of NF-κB p65 and p50 subunits induced with LPS, and lessened LPS-induced p50 binding activity. Further, CAPE showed strong inhibitory effects on LPS-induced signal transducer and activator of transcription 1 and 3 phosphorylation. Besides, CAPE significantly elevated SOCS1 mRNA expression in P. intermedia LPS-stimulated cells. Modulation of host response by CAPE may represent an attractive strategy towards the treatment of periodontal disease

Factores asociados al ataque cerebrovascular isquémico entre los años 2013 a 2016: estudio de casos y controles

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Juan-David Vega P.

2017-11-01

Full Text Available Resumen: Objetivo: Determinar los factores asociados al ataque cerebrovascular isquémico en el servicio de urgencias de la Clínica Especializada Los Andes, de la ciudad de Tunja, entre los años 2013 a 2016. Pacientes y métodos: Estudio de casos y controles; los casos correspondieron a 97 pacientes con ataque cerebrovascular isquémico (infarto cerebral isquémico y accidente isquémico transitorio y los controles a 291 pacientes sin ataque cerebrovascular isquémico que ingresaron a urgencias entre los años 2013 a 2016. Resultados: El sexo femenino correspondió al 56,7% (55 de los casos y al 54,6% de los controles (154 (p = 0,069. La media de edad en el grupo caso fue de 73,7 años [DE: 10,5 años] y en los controles de 64,5 años [DE: 11,3 años]. Los factores asociados al ataque cerebrovascular isquémico fueron: antecedente de ataque cerebrovascular isquémico [OR 7,7 IC 95% 3,2; 18 p= 0,000], tabaquismo [OR 4,4 IC 95% 1,1; 18 p= 0,022], dislipidemia [OR 3 IC 95% 1,2; 7,5 p= 0,017], edad igual o mayor a 70 años [OR 2,3 IC 95% 1,3; 4,1 p= 0,002] e hipertensión arterial [OR 1,8 IC 95% 1,06; 3,3 p= 0,029]. Conclusiones: Los factores asociados al ataque cerebrovascular isquémico fueron, en orden de importancia, antecedente de ataque cerebrovascular isquémico, tabaquismo, dislipidemia, edad igual o mayor a 70 años e hipertensión arterial. Abstract: Objective: To determine the factors associated with ischaemic cerebrovascular accidents (ICVA in the Emergency Department of the Andes Specialist Clinic of the city of Tunja, between the years 2013 and 2016. Patients and methods: A case-control study was conducted in which the cases consisted of 97 patients with ICVA (ischaemic cerebral infarction and transient ischaemic accident, and the controls were 291 patients with no ICVA, who were admitted to the Emergency Department between the years 2013 and 2016. Results: There were 56.7% (55

[Trend analysis on the death rate of ischemic heart disease and cerebrovascular disease among Xuzhou residents from 2011 to 2015].

Science.gov (United States)

Chen, P P; Lou, P A; Zhang, P; Qiao, C; Li, T; Dong, Z M

2017-07-24

Objective: To analyze the epidemiological characteristics and trend of ischemic heart disease and cerebrovascular disease mortality among Xuzhou residents from 2011 to 2015. Methods: The mortality data of the ischemic heart disease and cerebrovascular disease were obtained from the registration disease surveillance system covering the residents of the city from 2011 to 2015. Ischemic heart disease and cerebrovascular disease were identified according to the international classification of diseases (ICD-10), Ischemic heart diseases include I20 to I25 (angina pectoris, acute myocardial infarction, certain current complications following acute myocardial infarction, other acute ischemic heart diseases chronic ischemic heart disease); cerebrovascular diseases include I60 to I69 (subarachnoid hemorrhage, intracerebral hemorrhage, other non-traumatic hemorrhage, cerebral infarction, stroke not specified as hemorrhage or infarction, other cerebrovascular diseases, sequelae of cerebrovascular disease). Results: (1)From 2011 to 2015, the chronic ischemia Cardio-Cerebrovascular disease mortality of residents in Xuzhou was 261.2 per one hundred thousand (129 950/49 748 321), 269.9 per one hundred thousand(69 562/25 775 930)for male residents, 252.0 per one hundred thousand(60 388/23 972 391)for female residents, the mortality rate in men was significantly higher than that in women ( P disease mortality rate of urban residents was 243.8 per one hundred thousand(17 049/6 993 787), which was lower than the rate of rural residents (264.0 per one hundred thousand(112 901/42 754 534), P heart disease in Xuzhou city remained unchanged: 117.1 per one hundred thousand(11 416/9 747 768), 126.8 per one hundred thousand(12 177/9 600 745), 112.0 per one hundred thousand(11 184/9 986 877), 115.2 per one hundred thousand(11 697/10 151 842), 117.1 per one hundred thousand(12 019/10 261 089, P >0.05). The mortality rate of cerebrovascular disease were 154.0 per one hundred thousand(15 014

Shape and texture analysis of the carotid plaque, and its correlation with cerebral infarctions on CT, and cerebrovascular symptoms

Energy Technology Data Exchange (ETDEWEB)

Kalomiris, Konstantinos; Tegos, Thomas J; Sabetai, Michael; Nicolaides, Andrew N [Irvine Laboratory for Cardiovascular Investigations and Research, Imperial College School of Medicine at St Mary` , Praed Street, London W2 1NY (United Kingdom)

1999-12-31

This work has studied the relationship between ultrasonic texture characteristics, ultrasonic shape characteristics, cerebral infarctions on CT, and cerebrovascular symptoms, in an attempt to identify the unstable carotid plaque, i.e. the plaque associated with high prevalence of ipsilateral cerebral infarctions on CT, and cerebrovascular symptoms. The morphological features used were : the grey scale median (GSM) for the texture, and the bending energy (BE) for the shape. It has been shown that echoluscent plaques (plaques with low GSM) with irregular shape (high BE) are associated with high prevalence of ipsilateral cerebral infarctions on CT and cerebrovascular symptoms, whereas echogenic plaques (high GSM) with smooth shape (low BE) are associated with low prevalence of ipsilateral cerebral infarctions on CT and cerebrovascular symptoms. Previous work has demonstrated the significance of the GSM in identifying the unstable carotid plaques, but no attempt, to our knowledge, has been made to establish the clinical significance of the ultrasonic shape characteristics of the carotid plaque. The importance of the ultrasonic texture and shape characteristics will be established in prospective studies of patients with asymptomatic carotid plaques, aiming at the identification of patients with a high risk for stroke, and therefore for a better selection of asymptomatic patients who might benefit from a carotid endarterectomy. (authors) 5 refs., 3 figs.

Calcium-mediated signaling and calmodulin-dependent kinase regulate hepatocyte-inducible nitric oxide synthase expression.

Science.gov (United States)

Zhang, Baochun; Crankshaw, Will; Nesemeier, Ryan; Patel, Jay; Nweze, Ikenna; Lakshmanan, Jaganathan; Harbrecht, Brian G

2015-02-01

Induced nitric oxide synthase (iNOS) is induced in hepatocytes by shock and inflammatory stimuli. Excessive NO from iNOS mediates shock-induced hepatic injury and death, so understanding the regulation of iNOS will help elucidate the pathophysiology of septic shock. In vitro, cytokines induce iNOS expression through activation of signaling pathways including mitogen-activated protein kinases and nuclear factor κB. Cytokines also induce calcium (Ca(2+)) mobilization and activate calcium-mediated intracellular signaling pathways, typically through activation of calmodulin-dependent kinases (CaMK). Calcium regulates NO production in macrophages but the role of calcium and calcium-mediated signaling in hepatocyte iNOS expression has not been defined. Primary rat hepatocytes were isolated, cultured, and induced to produce NO with proinflammatory cytokines. Calcium mobilization and Ca(2+)-mediated signaling were altered with ionophore, Ca(2+) channel blockers, and inhibitors of CaMK. The Ca(2+) ionophore A23187 suppressed cytokine-stimulated NO production, whereas Ethylene glycol tetraacetic acid and nifedipine increased NO production, iNOS messenger RNA, and iNOS protein expression. Inhibition of CaMK with KN93 and CBD increased NO production but the calcineurin inhibitor FK 506 decreased iNOS expression. These data demonstrate that calcium-mediated signaling regulates hepatocyte iNOS expression and does so through a mechanism independent of calcineurin. Changes in intracellular calcium levels may regulate iNOS expression during hepatic inflammation induced by proinflammatory cytokines. Copyright © 2015 Elsevier Inc. All rights reserved.

Is outdoor work associated with elevated rates of cerebrovascular disease mortality? : a cohort study based on iron-ore mining

OpenAIRE

Björ, Ove; Jonsson, Håkan; Damber, Lena; Burström, Lage; Nilsson, Tohr

2016-01-01

BACKGROUND: A cohort study that examined iron ore mining found negative associations between cumulative working time employed underground and several outcomes, including mortality of cerebrovascular diseases. In this cohort study, and using the same group of miners, we examined whether work in an outdoor environment could explain elevated cerebrovascular disease rates. METHODS: This study was based on a Swedish iron ore mining cohort consisting of 13,000 workers. Poisson regression models wer...

TAM receptor-dependent regulation of SOCS3 and MAPKs contributes to proinflammatory cytokine downregulation following chronic NOD2 stimulation of human macrophages.

Science.gov (United States)

Zheng, Shasha; Hedl, Matija; Abraham, Clara

2015-02-15

Microbial-induced cytokine regulation is critical to intestinal immune homeostasis. Acute stimulation of nucleotide-binding oligomerization domain 2 (NOD2), the Crohn's disease-associated sensor of bacterial peptidoglycan, induces cytokines. However, cytokines are attenuated after chronic NOD2 and pattern recognition receptor stimulation of macrophages; similar attenuation is observed in intestinal macrophages. The role of Tyro3, Axl, and Mer (TAM) receptors in regulating chronic pattern recognition receptor stimulation and NOD2-induced outcomes has not been examined. Moreover, TAM receptors have been relatively less investigated in human macrophages. Whereas TAM receptors did not downregulate acute NOD2-induced cytokines in primary human macrophages, they were essential for downregulating signaling and proinflammatory cytokine secretion after chronic NOD2 and TLR4 stimulation. Axl and Mer were similarly required in mice for cytokine downregulation after chronic NOD2 stimulation in vivo and in intestinal tissues. Consistently, TAM expression was increased in human intestinal myeloid-derived cells. Chronic NOD2 stimulation led to IL-10- and TGF-β-dependent TAM upregulation in human macrophages, which, in turn, upregulated suppressor of cytokine signaling 3 expression. Restoring suppressor of cytokine signaling 3 expression under TAM knockdown conditions restored chronic NOD2-mediated proinflammatory cytokine downregulation. In contrast to the upregulated proinflammatory cytokines, attenuated IL-10 secretion was maintained in TAM-deficient macrophages upon chronic NOD2 stimulation. The level of MAPK activation in TAM-deficient macrophages after chronic NOD2 stimulation was insufficient to upregulate IL-10 secretion; however, full restoration of MAPK activation under these conditions restored c-Fos, c-Jun, musculoaponeurotic fibrosarcoma oncogene homolog K, and PU.1 binding to the IL-10 promoter and IL-10 secretion. Therefore, TAM receptors are critical for

The influence of general anesthesia on the brain in aged patients with previous ischemic cerebrovascular disease

International Nuclear Information System (INIS)

Kokubo, Yasuaki; Kayama, Takamasa; Kondo, Rei; Oki, Masato; Takaoka, Seiji

2008-01-01

Whenever we discuss the overall results of surgical treatment for unruptured cerebral aneurysms, especially in aged patients, we tend to consider advanced age or general anesthesia as causes for unfavorable results. There are no reports concerning ischemic stroke events following general anesthesia in aged patients with a prior history of cerebrovascular disease. The purpose of this study is to clarify the influence of general anesthesia on the brats in aged patients with a previous history of ischemic cerebrovascular disease. The subjects were 30 consecutive patients over 70 years of age with previous ischemic cerebrovascular disease who underwent various surgeries except brain and cardiac surgery under general anesthesia. The patients were 70 to 85 years old, with a mean age of 76. Twenty-three were men and 7 were women. Surgical procedures were 12 gastrointestinal, 6 orthopedic and 4 urogenital and others. The type of cerebrovascular disease evaluated by neuroradiologist and anesthesiologist based on MR imaging was devided as follows: 16 patients had minor stroke, 7 had transient ischemic attack/reversible ischemic neurological deficit (TIA/RIND) and 7 had asymptomatic cerebral infarction. MR angiography was also assessed to evaluate the main artery in the brain. Blood pressure and arterial blood gas (PaCO 2 ) during general anesthesia were analyzed, and the rate of systemic and neurological complications following general anesthesia were evaluated. MR angiography revealed no occlusion or severe stenosis of the main artery in the brain of any of the patients. The minimum systolic blood pressure showed less than 100 mmHg transiently for 5-20 minutes in 28 of 30 patients during general anesthesia. The minimum value was 65 mmHg maintained for 5 minutes. The minimum PaCO 2 during general anesthesia was as follows: 1 case 36 mmHg. There were no neurological complications following general anesthesia in this study. One of 30 patients (3.3%) had suffered from pneumonia

Mouse mannose-binding lectin-A and ficolin-A inhibit lipopolysaccharide-mediated pro-inflammatory responses on mast cells

DEFF Research Database (Denmark)

Ma, Ying Jie; Kang, Hee Jung; Kim, Ji Yeon

2013-01-01

It is unknown how soluble pattern-recognition receptors in blood, such as mannose-binding lectin (MBL) and ficolins, modulate mast cell-mediated inflammatory responses. We investigate how mouse MBL-A or ficolin-A regulate mouse bone marrow-derived mast cells (mBMMCs)-derived inflammatory response...... cytokine production by LPS-mediated TLR4 in mBMMCs appears to be down-regulated, indicating that mouse MBL and ficolin may have an inhibitory function toward mouse TLR4-mediated excessive inflammation on the mast cells.......It is unknown how soluble pattern-recognition receptors in blood, such as mannose-binding lectin (MBL) and ficolins, modulate mast cell-mediated inflammatory responses. We investigate how mouse MBL-A or ficolin-A regulate mouse bone marrow-derived mast cells (mBMMCs)-derived inflammatory response...

Resveratrol post-transcriptionally regulates pro-inflammatory gene expression via regulation of KSRP RNA binding activity

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Bollmann, Franziska; Art, Julia; Henke, Jenny; Schrick, Katharina; Besche, Verena; Bros, Matthias; Li, Huige; Siuda, Daniel; Handler, Norbert; Bauer, Florian; Erker, Thomas; Behnke, Felix; Mönch, Bettina; Härdle, Lorena; Hoffmann, Markus; Chen, Ching-Yi; Förstermann, Ulrich; Dirsch, Verena M.; Werz, Oliver; Kleinert, Hartmut; Pautz, Andrea

2014-01-01

Resveratrol shows beneficial effects in inflammation-based diseases like cancer, cardiovascular and chronic inflammatory diseases. Therefore, the molecular mechanisms of the anti-inflammatory resveratrol effects deserve more attention. In human epithelial DLD-1 and monocytic Mono Mac 6 cells resveratrol decreased the expression of iNOS, IL-8 and TNF-α by reducing mRNA stability without inhibition of the promoter activity. Shown by pharmacological and siRNA-mediated inhibition, the observed effects are SIRT1-independent. Target-fishing and drug responsive target stability experiments showed selective binding of resveratrol to the RNA-binding protein KSRP, a central post-transcriptional regulator of pro-inflammatory gene expression. Knockdown of KSRP expression prevented resveratrol-induced mRNA destabilization in human and murine cells. Resveratrol did not change KSRP expression, but immunoprecipitation experiments indicated that resveratrol reduces the p38 MAPK-related inhibitory KSRP threonine phosphorylation, without blocking p38 MAPK activation or activity. Mutation of the p38 MAPK target site in KSRP blocked the resveratrol effect on pro-inflammatory gene expression. In addition, resveratrol incubation enhanced KSRP-exosome interaction, which is important for mRNA degradation. Finally, resveratrol incubation enhanced its intra-cellular binding to the IL-8, iNOS and TNF-α mRNA. Therefore, modulation of KSRP mRNA binding activity and, thereby, enhancement of mRNA degradation seems to be the common denominator of many anti-inflammatory effects of resveratrol. PMID:25352548

Multifractal characterization of cerebrovascular dynamics in newborn rats

International Nuclear Information System (INIS)

Pavlov, A.N.; Semyachkina-Glushkovskaya, O.V.; Lychagov, V.V.; Abdurashitov, A.S.; Pavlova, O.N.; Sindeeva, O.A.; Sindeev, S.S.

2015-01-01

In this paper we study the cerebrovascular dynamics in newborn rats using the wavelet-based multifractal formalism in order to reveal effective markers of early pathological changes in the macro- and microcirculation at the hidden stage of the development of intracranial hemorrhage (ICH). We demonstrate that the singularity spectrum estimated with the wavelet-transform modulus maxima (WTMM) technique allows clear characterization of a reduced complexity of blood flow dynamics and changes of the correlation properties at the transformation of normal physiological processes into pathological dynamics that are essentially different at the level of large and small blood vessels

Fisetin Inhibits Hyperglycemia-Induced Proinflammatory Cytokine Production by Epigenetic Mechanisms

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Hye Joo Kim

2012-01-01

Full Text Available Diabetes is characterized by a proinflammatory state, and several inflammatory processes have been associated with both type 1 and type 2 diabetes and the resulting complications. High glucose levels induce the release of proinflammatory cytokines. Fisetin, a flavonoid dietary ingredient found in the smoke tree (Cotinus coggygria, and is also widely distributed in fruits and vegetables. Fisetin is known to exert anti-inflammatory effects via inhibition of the NF-κB signaling pathway. In this study, we analyzed the effects of fisetin on proinflammatory cytokine secretion and epigenetic regulation, in human monocytes cultured under hyperglycemic conditions. Human monocytic (THP-1 cells were cultured under control (14.5 mmol/L mannitol, normoglycemic (NG, 5.5 mmol/L glucose, or hyperglycemic (HG, 20 mmol/L glucose conditions, in the absence or presence of fisetin. Fisetin was added (3–10 μM for 48 h. While the HG condition significantly induced histone acetylation, NF-κB activation, and proinflammatory cytokine (IL-6 and TNF-α release from THP-1 cells, fisetin suppressed NF-κB activity and cytokine release. Fisetin treatment also significantly reduced CBP/p300 gene expression, as well as the levels of acetylation and HAT activity of the CBP/p300 protein, which is a known NF-κB coactivator. These results suggest that fisetin inhibits HG-induced cytokine production in monocytes, through epigenetic changes involving NF-κB. We therefore propose that fisetin supplementation be considered for diabetes prevention.

Proinflammatory Cytokines in Prostate Cancer Development and Progression Promoted by High-Fat Diet

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Hua Xu

2015-01-01

Full Text Available Background. We aimed to examine whether proinflammatory cytokines participated in prostate cancer (PCa development and progression promoted by high-fat diet (HFD. Methods. TRAMP (transgenic adenocarcinoma mouse prostate mice were randomly divided into two groups: normal diet group and HFD group. Mortality rate and tumor formation rate were examined. TRAMP mice were sacrificed and sampled on the 20th, 24th, and 28th week, respectively. Levels of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, and TNF-α, were tested by FlowCytomix. Prostate tissue of TRAMP mice was used for histology study. Results. A total of 13 deaths of TRAMP mice were observed, among which 3 (8.33% were from the normal diet group and 10 (27.78% from the HFD group. The mortality rate of TRAMP mice from HFD group was significantly higher than that of normal diet group (P=0.032. Tumor formation rate at 20th week of age of HFD group was significantly higher than that of normal diet group (P=0.045. Proinflammatory cytokines levels, including IL-1α, IL-1β, IL-6, and TNF-α, were significantly higher in HFD TRAMP mice. Conclusions. HFD could promote TRAMP mouse PCa development and progression with elevated proinflammatory cytokines levels. Proinflammatory cytokines could contribute to PCa development and progression promoted by HFD.

Krüppel-Like Factor 4 Is a Regulator of Proinflammatory Signaling in Fibroblast-Like Synoviocytes through Increased IL-6 Expression

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Xinjing Luo

2016-01-01

Full Text Available Human fibroblast-like synoviocytes play a vital role in joint synovial inflammation in rheumatoid arthritis (RA. Proinflammatory cytokines induce fibroblast-like synoviocyte activation and dysfunction. The inflammatory mediator Krüppel-like factor 4 is upregulated during inflammation and plays an important role in endothelial and macrophage activation during inflammation. However, the role of Krüppel-like factor 4 in fibroblast-like synoviocyte activation and RA inflammation remains to be defined. In this study, we identify the notion that Krüppel-like factor 4 is higher expressed in synovial tissues and fibroblast-like synoviocytes from RA patients than those from osteoarthritis patients. In vitro, the expression of Krüppel-like factor 4 in RA fibroblast-like synoviocytes is induced by proinflammatory cytokine tumor necrosis factor-α. Overexpression of Krüppel-like factor 4 in RA fibroblast-like synoviocytes robustly induced interleukin-6 production in the presence or absence of tumor necrosis factor-α. Conversely, knockdown of Krüppel-like factor 4 markedly attenuated interleukin-6 production in the presence or absence of tumor necrosis factor-α. Krüppel-like factor 4 not only can bind to and activate the interleukin-6 promoter, but also may interact directly with nuclear factor-kappa B. These results suggest that Krüppel-like factor 4 may act as a transcription factor mediating the activation of fibroblast-like synoviocytes in RA by inducing interleukin-6 expression in response to tumor necrosis factor-α.

Both direct and indirect effects account for the pro-inflammatory activity of enteropathogenic mycotoxins on the human intestinal epithelium: Stimulation of interleukin-8 secretion, potentiation of interleukin-1β effect and increase in the transepithelial passage of commensal bacteria

International Nuclear Information System (INIS)

Maresca, Marc; Yahi, Nouara; Younes-Sakr, Lama; Boyron, Marilyn; Caporiccio, Bertrand; Fantini, Jacques

2008-01-01

Mycotoxins are fungal secondary metabolites responsible of food-mediated intoxication in animals and humans. Deoxynivalenol, ochratoxin A and patulin are the best known enteropathogenic mycotoxins able to alter intestinal functions resulting in malnutrition, diarrhea, vomiting and intestinal inflammation in vivo. Although their effects on intestinal barrier and transport activities have been extensively characterized, the mechanisms responsible for their pro-inflammatory effect are still poorly understood. Here we investigated if mycotoxin-induced intestinal inflammation results from a direct and/or indirect pro-inflammatory activity of these mycotoxins on human intestinal epithelial cells, using differentiated Caco-2 cells as model and interleukin 8 (IL-8) as an indicator of intestinal inflammation. Deoxynivalenol was the only mycotoxin able to directly increase IL-8 secretion (10- to 15-fold increase). We also investigated if these mycotoxins could indirectly stimulate IL-8 secretion through: (i) a modulation of the action of pro-inflammatory molecules such as the interleukin-1beta (IL-1β), and/or (ii) an increase in the transepithelial passage of non-invasive commensal Escherichia coli. We found that deoxynivalenol, ochratoxin A and patulin all potentiated the effect of IL-1β on IL-8 secretion (ranging from 35% to 138% increase) and increased the transepithelial passage of commensal bacteria (ranging from 12- to 1544-fold increase). In addition to potentially exacerbate established intestinal inflammation, these mycotoxins may thus participate in the induction of sepsis and intestinal inflammation in vivo. Taken together, our results suggest that the pro-inflammatory activity of enteropathogenic mycotoxins is mediated by both direct and indirect effects

Fibroelastoma valvular aórtico como causa de accidente cerebrovascular embólico: Reporte de un caso

OpenAIRE

BAHAMONDES S,JUAN CARLOS; MERIÑO S,GUSTAVO; SALMAN A,JUAN; SILVA V,ABELARDO; MORA M,JAVIER

2008-01-01

Los tumores cardíacos son una causa rara de accidente cerebrovascular embólico. Comunicamos el caso de una paciente de 65 años quien debuta su historia con un accidente cerebrovascular. El estudio de fuente embólica con ecocardiografía transesofágica demostró un fibroelastoma de la válvula aórtica en el borde libre del velo no coronariano. El tumor fue extraído mediante circulación extracorpórea. El estudio anatomopatológico confirmó el diagnóstico y la paciente se encuentra en capacidad func...

IL-27 induces a pro-inflammatory response in human fetal membranes mediating preterm birth.

Science.gov (United States)

Yin, Nanlin; Wang, Hanbing; Zhang, Hua; Ge, Huisheng; Tan, Bing; Yuan, Yu; Luo, Xiaofang; Olson, David M; Baker, Philip N; Qi, Hongbo

2017-09-01

Inflammation at the maternal-fetal interface has been shown to be involved in the pathogenesis of preterm birth. Interleukin 27 (IL-27), a heterodimeric cytokine, is known to mediate an inflammatory response in some pregnancy complications. In this study, we aimed to determine whether IL-27 could induce an inflammatory reaction at the maternal-fetal interface that would mediate the onset of preterm birth. We found elevated expression of IL-27 in human peripheral serum and elevated expression of its specific receptor (wsx-1) on fetal membranes in cases of preterm birth. Moreover, the release of inflammatory markers (CXCL10, IFN-γ, MCP-1, IL-6, IL-1β and TNF-α), especially CXCL10, was markedly augmented upon stimulation of IL-27 in the fetal membranes. Additionally, IL-27 and IFN-γ cooperated to amplify the expression of CXCL10 in the fetal membranes. Moreover, the production of CXCL10 was increased in IL-27-treated fetal membrane through JNK, PI3K or Erk signaling pathways. Finally, MMP2 and MMP9 were activated by IL-27 in human fetal membranes, which may be related to the onset of preterm premature rupture of membranes (pPROM). In conclusion, for the first time, we reported that the aberrant expression of IL-27 could mediate an excessive inflammatory response in fetal membranes through the JNK, PI3K or Erk signaling pathways, which contributes to preterm birth. Copyright © 2017 Elsevier B.V. All rights reserved.

Pharmacogenetics of cerebrovascular metabolism modulators in dementia due to Alzheimer’s disease

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Fabricio Ferreira de Oliveira

2015-03-01

Full Text Available The aims of this study were to investigate risk factors for cognitive and functional decline among 193 patients with Alzheimer’s disease dementia (AD, and to conduct pharmacogenetic analysis on cerebrovascular metabolism modulators, taking into account APOE haplotypes and the genotypes of ACE, CETP, LDLR and the LXR-β gene. For all patients, later age at AD onset was the most important risk factor for faster cognitive and functional decline, while the late-life coronary heart disease risk was inversely related to cognitive decline only for carriers of APOE4+ haplotypes. Schooling was protective against cognitive decline only for women and carriers of APOE4+ haplotypes, while higher body mass index in late life was protective against cognitive decline only for men. Carriers of the APOE-ε4/ε4 haplotype had earlier AD onset, whereas genotypes of CETP and LDLR that had traditionally been associated with higher risk of AD were associated with later onset of dementia. Angiotensin-converting enzyme inhibitors caused a 50% reduction in Mini-Mental State Examination score changes, and had better disease-modifying properties than did centrally-acting angiotensin-converting enzyme inhibitors alone. Angiotensin receptor blockers had genetically mediated effects that led to faster cognitive and functional decline, while patients with genetic tendencies towards faster cognitive and functional decline had maximum benefits when they used lipophilic statins, and vice versa.

Cerebrovascular reactivity (CVR) MRI with CO2 challenge: A technical review.

Science.gov (United States)

Liu, Peiying; B De Vis, Jill; Lu, Hanzhang

2018-03-21

Cerebrovascular reactivity (CVR) is an indicator of cerebrovascular reserve and provides important information about vascular health in a range of brain conditions and diseases. Unlike steady-state vascular parameters, such as cerebral blood flow (CBF) and cerebral blood volume (CBV), CVR measures the ability of cerebral vessels to dilate or constrict in response to challenges or maneuvers. Therefore, CVR mapping requires a physiological challenge while monitoring the corresponding hemodynamic changes in the brain. The present review primarily focuses on methods that use CO2 inhalation as a physiological challenge while monitoring changes in hemodynamic MRI signals. CO2 inhalation has been increasingly used in CVR mapping in recent literature due to its potency in causing vasodilation, rapid onset and cessation of the effect, as well as advances in MRI-compatible gas delivery apparatus. In this review, we first discuss the physiological basis of CVR mapping using CO2 inhalation. We then review the methodological aspects of CVR mapping, including gas delivery apparatus, the timing paradigm of the breathing challenge, the MRI imaging sequence, and data analysis. In addition, we review alternative approaches for CVR mapping that do not require CO2 inhalation. Copyright © 2018. Published by Elsevier Inc.

Hipertensión arterial sistólica. Impacto sobre la enfermedad cerebrovascular.

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María C. Valle Campo

2011-08-01

Full Text Available Fundamento: La aterosclerosis es un proceso multifactorial sobre el cual actúan varios factores de riesgo. Constituye la principal causa de muerte y de morbilidad en ingresados hospitalarios, y puede ocasionar una acentuada disminución del flujo sanguíneo hacia todos los órganos del cuerpo humano
Objetivo: Determinar el impacto de la hipertensión arterial sistólica sobre la enfermedad cerebrovascular.
Métodos: Se realizó un estudio transversal, observacional y analítico, en 59 fallecidos hipertensos. Se analizaron las arterias cerebrales y se cuantificó la lesión aterosclerótica y su variedad, aplicándose el sistema aterométrico, teniendo en cuenta los tipos de hipertensión arterial. Se emplearon procedimientos estadísticos (medidas de tendencia central y comparativos (prueba de comparación de media aritmética basadas en el test “t” de student.
Resultados: Los infartos cerebrales recientes fueron más frecuentes en hipertensos sistodiastólicos. No hubo diferencia significativa en cuanto a la edad en el momento de aparición de las lesiones para ambos sexos, pero las mujeres con hipertensión sistólica, fueron significativamente más dañadas desde el punto de vista morfométrico. Se observó correlación significativa para ambos grupos de hipertensos entre tipo de accidente cerebrovascular y variables del sistema aterométrico. Conclusiones: La hipertensión arterial sistólica es un factor importante en la génesis de la enfermedad vasculocerebral y está asociada con la progresión de la placa de ateroma.

SYSTOLIC HYPERTENSION. IMPACT ON CEREBROVASCULAR DISEASE

Background: Atherosclerosis is a multifactor process in which several risk factors are involved. It is the leading cause of death and morbidity in hospital admitted patients, and it may cause

A pro-inflammatory role of deubiquitinating enzyme cylindromatosis (CYLD) in vascular smooth muscle cells

International Nuclear Information System (INIS)

Liu, Shuai; Lv, Jiaju; Han, Liping; Ichikawa, Tomonaga; Wang, Wenjuan; Li, Siying; Wang, Xing Li; Tang, Dongqi; Cui, Taixing

2012-01-01

Highlights: ► Cyld deficiency suppresses pro-inflammatory phenotypic switch of VSMCs. ► Cyld deficiency inhibits MAPK rather than NF-kB activity in inflamed VSMCs. ► CYLD is up-regulated in the coronary artery with neointimal hyperplasia. -- Abstract: CYLD, a deubiquitinating enzyme (DUB), is a critical regulator of diverse cellular processes, ranging from proliferation and differentiation to inflammatory responses, via regulating multiple key signaling cascades such as nuclear factor kappa B (NF-κB) pathway. CYLD has been shown to inhibit vascular lesion formation presumably through suppressing NF-κB activity in vascular cells. However, herein we report a novel role of CYLD in mediating pro-inflammatory responses in vascular smooth muscle cells (VSMCs) via a mechanism independent of NF-κB activity. Adenoviral knockdown of Cyld inhibited basal and the tumor necrosis factor alpha (TNFα)-induced mRNA expression of pro-inflammatory cytokines including monocyte chemotactic protein-1 (Mcp-1), intercellular adhesion molecule (Icam-1) and interleukin-6 (Il-6) in rat adult aortic SMCs (RASMCs). The CYLD deficiency led to increases in the basal NF-κB transcriptional activity in RASMCs; however, did not affect the TNFα-induced NF-κB activity. Intriguingly, the TNFα-induced IκB phosphorylation was enhanced in the CYLD deficient RASMCs. While knocking down of Cyld decreased slightly the basal expression levels of IκBα and IκBβ proteins, it did not alter the kinetics of TNFα-induced IκB protein degradation in RASMCs. These results indicate that CYLD suppresses the basal NF-κB activity and TNFα-induced IκB kinase activation without affecting TNFα-induced NF-κB activity in VSMCs. In addition, knocking down of Cyld suppressed TNFα-induced activation of mitogen activated protein kinases (MAPKs) including extracellular signal-activated kinases (ERK), c-Jun N-terminal kinase (JNK), and p38 in RASMCs. TNFα-induced RASMC migration and monocyte adhesion to

Effects of the intraoperative application of dexmedetomidine on hemodynamics and cerebral oxygen metabolism of patients with cerebrovascular malformations

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Liang Feng

2017-01-01

Full Text Available Circulatory stability of patients with cerebrovascular malformations during the surgery is critical to their prognosis. Anesthesia-induced intubation, tumor separation, clamping and other operations may cause severe fluctuations in blood pressure and even result in aneurysm rupture. As a highly efficient and selective adrenergic α2 receptor agonists, dexmedetomidine hydrochloride is able to regulate the release of catecholamine by means of negative feedback so as to control blood pressure. This study aims to assess the effects of dexmedetomidine hydrochloride on hemodynamics and cerebral oxygen metabolism of intraoperative patients with cerebrovascular malformations.

Vascular care in patients with Alzheimer's disease with cerebrovascular lesions-a randomized clinical trial

NARCIS (Netherlands)

Richard, Edo; Kuiper, Roy; Dijkgraaf, Marcel G. W.; van Gool, Willem A.

2009-01-01

OBJECTIVES: To investigate whether vascular care slows dementia progression in patients with Alzheimer's disease with cerebrovascular lesions on neuroimaging. DESIGN: Multicenter randomized controlled clinical trial with 2-year follow-up. SETTING: Neurological and geriatric outpatient clinics in 10

Cerebrovascular reactivity among native-raised high altitude residents: an fMRI study

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Zhang Jiaxing

2011-09-01

Full Text Available Abstract Background The impact of long term residence on high altitude (HA on human brain has raised concern among researchers in recent years. This study investigated the cerebrovascular reactivity among native-born high altitude (HA residents as compared to native sea level (SL residents. The two groups were matched on the ancestral line, ages, gender ratios, and education levels. A visual cue guided maximum inspiration task with brief breath holding was performed by all the subjects while Blood-Oxygenation-Level-Dependent (BOLD functional Magnetic Resonance Imaging (fMRI data were acquired from them. Results Compared to SL controls, the HA group showed generally decreased cerebrovascular reactivity and longer delay in hemodynamic response. Clusters showing significant differences in the former aspect were located at the bilateral primary motor cortex, the right somatosensory association cortex, the right thalamus and the right caudate, the bilateral precuneus, the right cingulate gyrus and the right posterior cingulate cortex, as well as the left fusiform gyrus and the right lingual cortex; clusters showing significant differences in the latter aspect were located at the precuneus, the insula, the superior frontal and temporal gyrus, the somatosensory cortex (the postcentral gyrus and the cerebellar tonsil. Inspiratory reserve volume (IRV, which is an important aspect of pulmonary function, demonstrated significant correlation with the amount of BOLD signal change in multiple brain regions, particularly at the bilateral insula among the HA group. Conclusions Native-born HA residents generally showed reduced cerebrovascular reactivity as demonstrated in the hemodynamic response during a visual cue guided maximum inspiration task conducted with BOLD-fMRI. This effect was particularly manifested among brain regions that are typically involved in cerebral modulation of respiration.

Macrophage pro-inflammatory response to Francisella novicida infection is regulated by SHIP.

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Kishore V L Parsa

2006-07-01

Full Text Available Francisella tularensis, a Gram-negative facultative intracellular pathogen infecting principally macrophages and monocytes, is the etiological agent of tularemia. Macrophage responses to F. tularensis infection include the production of pro-inflammatory cytokines such as interleukin (IL-12, which is critical for immunity against infection. Molecular mechanisms regulating production of these inflammatory mediators are poorly understood. Herein we report that the SH2 domain-containing inositol phosphatase (SHIP is phosphorylated upon infection of primary murine macrophages with the genetically related F. novicida, and negatively regulates F. novicida-induced cytokine production. Analyses of the molecular details revealed that in addition to activating the MAP kinases, F. novicida infection also activated the phosphatidylinositol 3-kinase (PI3K/Akt pathway in these cells. Interestingly, SHIP-deficient macrophages displayed enhanced Akt activation upon F. novicida infection, suggesting elevated PI3K-dependent activation pathways in absence of SHIP. Inhibition of PI3K/Akt resulted in suppression of F. novicida-induced cytokine production through the inhibition of NFkappaB. Consistently, macrophages lacking SHIP displayed enhanced NFkappaB-driven gene transcription, whereas overexpression of SHIP led to decreased NFkappaB activation. Thus, we propose that SHIP negatively regulates F. novicida-induced inflammatory cytokine response by antagonizing the PI3K/Akt pathway and suppressing NFkappaB-mediated gene transcription. A detailed analysis of phosphoinositide signaling may provide valuable clues for better understanding the pathogenesis of tularemia.

Histone Deacetylase 7 Promotes Toll-like Receptor 4-dependent Proinflammatory Gene Expression in Macrophages*

Science.gov (United States)

Shakespear, Melanie R.; Hohenhaus, Daniel M.; Kelly, Greg M.; Kamal, Nabilah A.; Gupta, Praveer; Labzin, Larisa I.; Schroder, Kate; Garceau, Valerie; Barbero, Sheila; Iyer, Abishek; Hume, David A.; Reid, Robert C.; Irvine, Katharine M.; Fairlie, David P.; Sweet, Matthew J.

2013-01-01

Broad-spectrum inhibitors of histone deacetylases (HDACs) constrain Toll-like receptor (TLR)-inducible production of key proinflammatory mediators. Here we investigated HDAC-dependent inflammatory responses in mouse macrophages. Of the classical Hdacs, Hdac7 was expressed at elevated levels in inflammatory macrophages (thioglycollate-elicited peritoneal macrophages) as compared with bone marrow-derived macrophages and the RAW264 cell line. Overexpression of a specific, alternatively spliced isoform of Hdac7 lacking the N-terminal 22 amino acids (Hdac7-u), but not the Refseq Hdac7 (Hdac7-s), promoted LPS-inducible expression of Hdac-dependent genes (Edn1, Il-12p40, and Il-6) in RAW264 cells. A novel class IIa-selective HDAC inhibitor reduced recombinant human HDAC7 enzyme activity as well as TLR-induced production of inflammatory mediators in thioglycollate-elicited peritoneal macrophages. Both LPS and Hdac7-u up-regulated the activity of the Edn1 promoter in an HDAC-dependent fashion in RAW264 cells. A hypoxia-inducible factor (HIF) 1 binding site in this promoter was required for HDAC-dependent TLR-inducible promoter activity and for Hdac7- and HIF-1α-mediated trans-activation. Coimmunoprecipitation assays showed that both Hdac7-u and Hdac7-s interacted with HIF-1α, whereas only Hdac7-s interacted with the transcriptional repressor CtBP1. Thus, Hdac7-u positively regulates HIF-1α-dependent TLR signaling in macrophages, whereas an interaction with CtBP1 likely prevents Hdac7-s from exerting this effect. Hdac7 may represent a potential inflammatory disease target. PMID:23853092

Histone deacetylase 7 promotes Toll-like receptor 4-dependent proinflammatory gene expression in macrophages.

Science.gov (United States)

Shakespear, Melanie R; Hohenhaus, Daniel M; Kelly, Greg M; Kamal, Nabilah A; Gupta, Praveer; Labzin, Larisa I; Schroder, Kate; Garceau, Valerie; Barbero, Sheila; Iyer, Abishek; Hume, David A; Reid, Robert C; Irvine, Katharine M; Fairlie, David P; Sweet, Matthew J

2013-08-30

Broad-spectrum inhibitors of histone deacetylases (HDACs) constrain Toll-like receptor (TLR)-inducible production of key proinflammatory mediators. Here we investigated HDAC-dependent inflammatory responses in mouse macrophages. Of the classical Hdacs, Hdac7 was expressed at elevated levels in inflammatory macrophages (thioglycollate-elicited peritoneal macrophages) as compared with bone marrow-derived macrophages and the RAW264 cell line. Overexpression of a specific, alternatively spliced isoform of Hdac7 lacking the N-terminal 22 amino acids (Hdac7-u), but not the Refseq Hdac7 (Hdac7-s), promoted LPS-inducible expression of Hdac-dependent genes (Edn1, Il-12p40, and Il-6) in RAW264 cells. A novel class IIa-selective HDAC inhibitor reduced recombinant human HDAC7 enzyme activity as well as TLR-induced production of inflammatory mediators in thioglycollate-elicited peritoneal macrophages. Both LPS and Hdac7-u up-regulated the activity of the Edn1 promoter in an HDAC-dependent fashion in RAW264 cells. A hypoxia-inducible factor (HIF) 1 binding site in this promoter was required for HDAC-dependent TLR-inducible promoter activity and for Hdac7- and HIF-1α-mediated trans-activation. Coimmunoprecipitation assays showed that both Hdac7-u and Hdac7-s interacted with HIF-1α, whereas only Hdac7-s interacted with the transcriptional repressor CtBP1. Thus, Hdac7-u positively regulates HIF-1α-dependent TLR signaling in macrophages, whereas an interaction with CtBP1 likely prevents Hdac7-s from exerting this effect. Hdac7 may represent a potential inflammatory disease target.

Cerebrovascular accidents complicating transcatheter aortic valve implantation: frequency, timing and impact on outcomes.

Science.gov (United States)

Stortecky, Stefan; Windecker, Stephan; Pilgrim, Thomas; Heg, Dik; Buellesfeld, Lutz; Khattab, Ahmed A; Huber, Christoph; Gloekler, Steffen; Nietlispach, Fabian; Mattle, Heinrich; Jüni, Peter; Wenaweser, Peter

2012-05-15

Cerebrovascular accidents (CVA) are considered among the most serious adverse events after transcatheter aortic valve implantation (TAVI). The objective of the present study was to evaluate the frequency and timing of CVA after TAVI and to investigate the impact on clinical outcomes within 30 days of the procedure. Between August 2007 and October 2011, 389 high-risk elderly patients with symptomatic severe aortic stenosis underwent TAVI via transfemoral, transapical or subclavian access. A total of 14 patients (3.6%) experienced at least one CVA within 30 days of follow-up and most events (74%) occurred within the first day of the procedure. Patients with CVA had an increased risk of all-cause (42.3% vs. 5.1%, ORadjusted 11.7, 95% CI 3.4-40.3, pCerebrovascular accidents among patients undergoing TAVI occur predominantly during the periprocedural period, are associated with multiple implantation attempts of the bioprosthesis and significantly impair prognosis.

PREDICTORS OF CEREBROVASCULAR DISORDERS IN PATIENTS AFTER CORONARY BYPASS GRAFTING

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S. G. Sukhanov

2015-01-01

Full Text Available Background: At present, coronary bypass graft (CABG that was first introduced more than 45 years ago, is one of the most common types of surgeries in the world. Despite progress and improvements in myocardial revascularization techniques and methods aimed at higher safety of the intervention, postoperative cerebrovascular complications continue to be one of the most common problems.Aim: To identify predictors of perioperative stroke in patients undergoing CABG.Materials and methods: From January 2013 to December 2014, 2823 isolated CABG procedures have been done.Results: All-cause in-hospital mortality after isolated CABG was 1.2% (n = 36. Perioperative strokes were diagnosed in 32 (1.1% of patients. For subsequent analysis, we divided all patients into two groups. Group A included 32 patients who had a stroke in their postoperative period, group B comprised 2791 patients without severe cerebrovascular disorders. There were more female patients in group A, compared to group B (13/32 [40.6%] vs. 543/2791 [19.5%], respectively (р < 0.01, more elderly patients (21 [65.6%] vs. 1251 [44.8%] (р < 0,05 above 60 years of age, and 9 [28.1%] vs. 348 [12.5%] (р < 0.05 above 70 years, respectively. In group B, the number of patients with atrial fibrillation was 244 (8.7% vs. 7 (21.9% in group A, the difference being statistically significant at р < 0.01. Among those with stroke, diabetes was found in 12 (37.5% of patients, among those who did not have a stroke, in 212 (7.6% (p < 0.01. Significant differences were found between numbers of patients with atherosclerosis of brachyocephalic arteries (17 [53.1%] in group A vs. 624 [22.4%] in group B, p < 0.01 and atherosclerosis of lower limb arteries (16 [50%] vs. 715 [25.6%] (p < 0.01, respectively.Conclusion: The most significant prognostic factors affecting the risk of perioperative stroke are concomitant atherosclerosis of brachyocephalic arteries, of lower limb arteries, atrial fibrillation, diabetes

Vascular risk factors, cerebrovascular reactivity, and the default-mode brain network.

Science.gov (United States)

Haight, Thaddeus J; Bryan, R Nick; Erus, Guray; Davatzikos, Christos; Jacobs, David R; D'Esposito, Mark; Lewis, Cora E; Launer, Lenore J

2015-07-15

Cumulating evidence from epidemiologic studies implicates cardiovascular health and cerebrovascular function in several brain diseases in late life. We examined vascular risk factors with respect to a cerebrovascular measure of brain functioning in subjects in mid-life, which could represent a marker of brain changes in later life. Breath-hold functional MRI (fMRI) was performed in 541 women and men (mean age 50.4 years) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Cerebrovascular reactivity (CVR) was quantified as percentage change in blood-oxygen level dependent (BOLD) signal in activated voxels, which was mapped to a common brain template and log-transformed. Mean CVR was calculated for anatomic regions underlying the default-mode network (DMN) - a network implicated in AD and other brain disorders - in addition to areas considered to be relatively spared in the disease (e.g. occipital lobe), which were utilized as reference regions. Mean CVR was significantly reduced in the posterior cingulate/precuneus (β=-0.063, 95% CI: -0.106, -0.020), anterior cingulate (β=-0.055, 95% CI: -0.101, -0.010), and medial frontal lobe (β=-0.050, 95% CI: -0.092, -0.008) relative to mean CVR in the occipital lobe, after adjustment for age, sex, race, education, and smoking status, in subjects with pre-hypertension/hypertension compared to normotensive subjects. By contrast, mean CVR was lower, but not significantly, in the inferior parietal lobe (β=-0.024, 95% CI: -0.062, 0.014) and the hippocampus (β=-0.006, 95% CI: -0.062, 0.050) relative to mean CVR in the occipital lobe. Similar results were observed in subjects with diabetes and dyslipidemia compared to those without these conditions, though the differences were non-significant. Reduced CVR may represent diminished vascular functionality for the DMN for individuals with prehypertension/hypertension in mid-life, and may serve as a preclinical marker for brain dysfunction in later

Role of Nrf2 and protective effects of Metformin against tobacco smoke-induced cerebrovascular toxicity

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Shikha Prasad

2017-08-01

Full Text Available Cigarette smoking (CS is associated with vascular endothelial dysfunction in a causative way primarily related to the TS content of reactive oxygen species (ROS, nicotine, and inflammation. TS promotes glucose intolerance and increases the risk of developing type-2 diabetes mellitus (2DM with which it shares other pathogenic traits including the high risk of cerebrovascular and neurological disorders like stroke via ROS generation, inflammation, and blood-brain barrier (BBB impairment. Herein we provide evidence of the role played by nuclear factor erythroid 2-related factor (Nrf2 in CS-induced cerebrobvascular/BBB impairments and how these cerebrovascular harmful effects can be circumvented by the use of metformin (MF; a widely prescribed, firstline anti-diabetic drug treatment. Our data in fact revealed that MF activates counteractive mechanisms primarily associated with the Nrf2 pathway which drastically reduce CS toxicity at the cerebrovascular level. These include the suppression of tight junction (TJ protein downregulation and loss of BBB integrity induced by CS, reduction of inflammation and oxidative stress, renormalization of the expression levels of the major BBB glucose transporter Glut-1 and that of the anticoagulant factor thrombomodulin. Further, we provide additional insights on the controversial interplay between Nrf2 and AMPK. Keywords: Oxidative stress, Cigarette smoke, Metformin, Blood hemostasis, Blood brain barrier, Tight junctions, Nrf2, Glucose transporter

Proinflammatory cytokine levels in fibromyalgia patients are independent of body mass index

OpenAIRE

Hernandez, Maria E; Becerril, Enrique; Perez, Mayra; Leff, Philippe; Anton, Benito; Estrada, Sergio; Estrada, Iris; Sarasa, Manuel; Serrano, Enrique; Pavon, Lenin

2010-01-01

Abstract Background Fibromyalgia (FM) is characterized by chronic, widespread muscular pain and tenderness and is generally associated with other somatic and psychological symptoms. Further, circulatory levels of proinflammatory cytokines (IL-1β, TNF-α, and IL-6) may be altered in FM patients, possibly in association with their symptoms. Recently, rises in BMI have been suggested to contribute to increased circulating levels of proinflammatory cytokines in FM patients. Our aim was to measure ...

Tomografía axial computarizada en pacientes con enfermedades cerebrovasculares hemorrágicas Computerized axial tomography in patients with hemorrhagic cerebrovascular diseases

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Solángel Bolaños Vaillant

2009-10-01

Full Text Available Se efectuó un estudio descriptivo y transversal de 196 pacientes con enfermedad cerebrovascular hemorrágica, que abarcó desde enero del 2004 hasta igual mes del 2005 en el Hospital Provincial Docente “Saturnino Lora” de Santiago de Cuba, a los cuales se indicó una tomografía axial computarizada. Al relacionar las imágenes tomográficas con los síntomas y signos presentados por los enfermos, se halló lenguaje tropeloso en todos ellos; predominio de hematomas intraparenquimatosos, generalmente en ganglios basales y región temporal, así como primacía de la hipertensión arterial entre los antecedentes patológicos más importantes. Se concluyó que la tomografía axial computarizada es un medio para diagnóstico certero en las urgencias médicas por esa grave afección.A descriptive and cross sectional study of 196 patients with cerebrovascular hemorrhagic disease was carried out from January, 2004 to the same month of 2005 in "Saturnino Lora" Teaching Provincial Hospital from Santiago de Cuba, to whom a computerized axial tomography was indicated. When relating the tomographic images with the symptoms and signs which they presented, trouble speaking was detected in all of them; prevalence of intraparenchymatous hematomas, generally in basal ganglia and temporal region, as well as prevalence of hypertension among the most important pathological history. It was concluded that computarized axial tomography is a mean for precise diagnosis in medical emergencies due to that serious disorder.

Signos Vitales de los CDC–Prevención de muertes por accidentes cerebrovasculares (Preventing Stroke Deaths)

Centers for Disease Control (CDC) Podcasts

2017-09-06

Este podcast se basa en la edición de septiembre del 2017 del informe Signos Vitales de los CDC. Cada año, más de 140 000 personas mueren y muchos sobrevivientes quedan con discapacidades. El ochenta por ciento de los accidentes cerebrovasculares son prevenibles. Conozca los signos de un accidente cerebrovascular y sepa cómo prevenirlo.  Created: 9/6/2017 by Centers for Disease Control and Prevention (CDC).   Date Released: 9/6/2017.

Negative regulatory roles of ORMDL3 in the Fc epsilon RI-triggered expression of proinflammatory mediators and chemotactic response in murine mast cells

Czech Academy of Sciences Publication Activity Database

Bugajev, Viktor; Hálová, Ivana; Dráberová, Lubica; Bambousková, Monika; Potůčková, Lucie; Dráberová, Helena; Paulenda, Tomáš; Junyent, Sergi; Dráber, Petr

2016-01-01

Roč. 73, č. 6 (2016), s. 1265-1285 ISSN 1420-682X R&D Projects: GA ČR(CZ) GA14-00703S; GA ČR(CZ) GBP302/12/G101; GA ČR(CZ) GA14-09807S Institutional support: RVO:68378050 Keywords : Mast cell interference * ORMDL3 knockdown * Prostalglandin D2 * Degranulation * Chemotaxis * Proinflammatory cytokines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.788, year: 2016

Targeted adenovirus mediated inhibition of NF-kappa B-dependent inflammatory gene expression in endothelial cells in vitro and in vivo

NARCIS (Netherlands)

Kuldo, J. M.; Asgeirsdottir, S. A.; Zwiers, P. J.; Bellu, A. R.; Rots, M. G.; Schalk, J. A. C.; Ogawara, K. I.; Trautwein, C.; Banas, B.; Haisma, H. J.; Molema, G.; Kamps, J. A. A. M.

2013-01-01

In chronic inflammatory diseases the endothelium expresses mediators responsible for harmful leukocyte infiltration. We investigated whether targeted delivery of a therapeutic transgene that inhibits nuclear factor kappa B signal transduction could silence the proinflammatory activation status of

β-Catenin promotes colitis and colon cancer through imprinting of proinflammatory properties in T cells.

Science.gov (United States)

Keerthivasan, Shilpa; Aghajani, Katayoun; Dose, Marei; Molinero, Luciana; Khan, Mohammad W; Venkateswaran, Vysak; Weber, Christopher; Emmanuel, Akinola Olumide; Sun, Tianjao; Bentrem, David J; Mulcahy, Mary; Keshavarzian, Ali; Ramos, Elena M; Blatner, Nichole; Khazaie, Khashayarsha; Gounari, Fotini

2014-02-26

The density and type of lymphocytes that infiltrate colon tumors are predictive of the clinical outcome of colon cancer. High densities of T helper 17 (T(H)17) cells and inflammation predict poor outcome, whereas infiltration by T regulatory cells (Tregs) that naturally suppress inflammation is associated with longer patient survival. However, the role of Tregs in cancer remains controversial. We recently reported that Tregs in colon cancer patients can become proinflammatory and tumor-promoting. These properties were directly linked with their expression of RORγt (retinoic acid-related orphan receptor-γt), the signature transcription factor of T(H)17 cells. We report that Wnt/β-catenin signaling in T cells promotes expression of RORγt. Expression of β-catenin was elevated in T cells, including Tregs, of patients with colon cancer. Genetically engineered activation of β-catenin in mouse T cells resulted in enhanced chromatin accessibility in the proximity of T cell factor-1 (Tcf-1) binding sites genome-wide, induced expression of T(H)17 signature genes including RORγt, and promoted T(H)17-mediated inflammation. Strikingly, the mice had inflammation of small intestine and colon and developed lesions indistinguishable from colitis-induced cancer. Activation of β-catenin only in Tregs was sufficient to produce inflammation and initiate cancer. On the basis of these findings, we conclude that activation of Wnt/β-catenin signaling in effector T cells and/or Tregs is causatively linked with the imprinting of proinflammatory properties and the promotion of colon cancer.

Reduced tissue osmolarity increases TRPV4 expression and pro-inflammatory cytokines in intervertebral disc cells

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BA Walter

2016-07-01

Full Text Available The mechanical behaviour and cellular metabolism of intervertebral discs (IVDs and articular cartilage are strongly influenced by their proteoglycan content and associated osmotic properties. This osmotic environment is a biophysical signal that changes with disease and may contribute to the elevated matrix breakdown and altered biologic response to loading observed in IVD degeneration and osteoarthritis. This study tested the hypothesis that changes in osmo-sensation by the transient receptor potential vallinoid-4 (TRPV4 ion channel occur with disease and contribute to the inflammatory environment found during degeneration. Immunohistochemistry on bovine IVDs from an inflammatory organ culture model were used to investigate if TRPV4 is expressed in the IVD and how expression changes with degeneration. Western blot, live-cell calcium imaging, and qRT-PCR were used to investigate whether osmolarity changes or tumour necrosis factor α (TNFα regulate TRPV4 expression, and how altered TRPV4 expression influences calcium signalling and pro-inflammatory cytokine expression. TRPV4 expression correlated with TNFα expression, and was increased when cultured in reduced medium osmolarity and unaltered with TNFα-stimulation. Increased TRPV4 expression increased the calcium flux following TRPV4 activation and increased interleukin-1β (IL-1β and IL-6 gene expression in IVD cells. TRPV4 expression was qualitatively elevated in regions of aggrecan depletion in degenerated human IVDs. Collectively, results suggest that reduced tissue osmolarity, likely following proteoglycan degradation, can increase TRPV4 signalling and enhance pro-inflammatory cytokine production, suggesting changes in TRPV4 mediated osmo-sensation may contribute to the progressive matrix breakdown in disease.

Cerebrovascular accident and abnormal focus of hyperactivity revealed by dynamic study in scintiangioencephalography

International Nuclear Information System (INIS)

Planchon, C.A.; Perez, R.; Lebourges, J.

1980-01-01

A 75-year-old female was admitted to the hospital for suspicion of a cerebrovascular accident. An important focus of hyperactivity was noted during a dynamic study by scintiangioencephalography, consistent with a highly vascular tumor, but corresponding in fact to a focal transitory hyperfusion with accompanying intense neuronal activity. (orig.)

Benzo[a]pyrene and tumor necrosis factor-alpha coordinately increase genotoxic damage and the production of proinflammatory mediators in alveolar epithelial type II cells

Czech Academy of Sciences Publication Activity Database

Umannová, Lenka; Machala, M.; Topinka, Jan; Schmuczerová, Jana; Krčmář, P.; Neča, J.; Šujanová, Klára; Kozubík, Alois; Vondráček, Jan

2011-01-01

Roč. 206, č. 2 (2011), s. 121-129 ISSN 0378-4274 R&D Projects: GA ČR(CZ) GAP503/11/1227 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702; CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : DNA adducts * proinflammatory cytokines * COX -2 Subject RIV: BO - Biophysics Impact factor: 3.230, year: 2011

Major Vault Protein Regulates Class A Scavenger Receptor-mediated Tumor Necrosis Factor-α Synthesis and Apoptosis in Macrophages*

Science.gov (United States)

Ben, Jingjing; Zhang, Yan; Zhou, Rongmei; Zhang, Haiyang; Zhu, Xudong; Li, Xiaoyu; Zhang, Hanwen; Li, Nan; Zhou, Xiaodan; Bai, Hui; Yang, Qing; Li, Donghai; Xu, Yong; Chen, Qi

2013-01-01

Atherosclerosis is considered a disease of chronic inflammation largely initiated and perpetuated by macrophage-dependent synthesis and release of pro-inflammatory mediators. Class A scavenger receptor (SR-A) expressed on macrophages plays a key role in this process. However, how SR-A-mediated pro-inflammatory response is modulated in macrophages remains ill defined. Here through immunoprecipitation coupled with mass spectrometry, we reported major vault protein (MVP) as a novel binding partner for SR-A. The interaction between SR-A and MVP was confirmed by immunofluorescence staining and chemical cross-linking assay. Treatment of macrophages with fucoidan, a SR-A ligand, led to a marked increase in TNF-α production, which was attenuated by MVP depletion. Further analysis revealed that SR-A stimulated TNF-α synthesis in macrophages via the caveolin- instead of clathrin-mediated endocytic pathway linked to p38 and JNK, but not ERK, signaling pathways. Importantly, fucoidan invoked an enrichment of MVP in lipid raft, a caveolin-reliant membrane structure, and enhanced the interaction among SR-A, caveolin, and MVP. Finally, we demonstrated that MVP elimination ameliorated SR-A-mediated apoptosis in macrophages. As such, MVP may fine-tune SR-A activity in macrophages which contributes to the development of atherosclerosis. PMID:23703615

Suppression of pro-inflammatory and pro-survival biomarkers in oral cancer patients consuming a black raspberry phytochemical-rich troche

Science.gov (United States)

Knobloch, Thomas J.; Uhrig, Lana K.; Pearl, Dennis K.; Casto, Bruce C.; Warner, Blake M.; Clinton, Steven K.; Sardo-Molmenti, Christine L.; Ferguson, Jeanette M.; Daly, Brett T.; Riedl, Kenneth; Schwartz, Steven J.; Vodovotz, Yael; Buchta, Anthony J.; Schuller, David E.; Ozer, Enver; Agrawal, Amit; Weghorst, Christopher M.

2016-01-01

Black raspberries (BRBs) demonstrate potent inhibition of aerodigestive tract carcinogenesis in animal models. However, translational clinical trials evaluating the ability of BRB phytochemicals to impact molecular biomarkers in the oral mucosa remain limited. The present phase 0 study addresses a fundamental question for oral cancer food-based prevention: Do BRB phytochemicals successfully reach the targeted oral tissues and reduce pro-inflammatory and anti-apoptotic gene expression profiles? Patients with biopsy-confirmed oral squamous cell carcinomas (OSCCs) administered oral troches containing freeze-dried BRB powder from the time of enrollment to the date of curative intent surgery (13.9 ± 1.27 days). Transcriptional biomarkers were evaluated in patient-matched OSCCs and non-involved high at-risk mucosa (HARM) for BRB-associated changes. Significant expression differences between baseline OSCC and HARM tissues were confirmed using a panel of genes commonly deregulated during oral carcinogenesis. Following BRB troche administration, the expression of pro-survival genes (AURKA, BIRC5, EGFR) and pro-inflammatory genes (NFKB1, PTGS2) were significantly reduced. There were no BRB-associated Grade 3–4 toxicities or adverse events and 79.2% (N = 30) of patients successfully completed the study with high levels of compliance (97.2%). The BRB phytochemicals cyanidin-3-rutinoside and cyanidin-3-xylosylrutinoside were detected in all OSCC tissues analyzed, demonstrating that bioactive components were successfully reaching targeted OSCC tissues. We confirmed that hallmark anti-apoptotic and pro-inflammatory molecular biomarkers were over-expressed in OSCCs and that their gene expression was significantly reduced following BRB troche administration. Since these molecular biomarkers are fundamental to oral carcinogenesis and are modifiable, they may represent emerging biomarkers of molecular efficacy for BRB-mediated oral cancer chemoprevention. PMID:26701664

Motor function declines over time in human immunodeficiency virus and is associated with cerebrovascular disease, while HIV-associated neurocognitive disorder remains stable.

Science.gov (United States)

M Elicer, Isabel; Byrd, Desiree; Clark, Uraina S; Morgello, Susan; Robinson-Papp, Jessica

2018-04-25

HIV-associated neurocognitive disorders (HAND) remain prevalent in the combined antiretroviral therapy (CART) era, especially the milder forms. Despite these milder phenotypes, we have shown that motor abnormalities persist and have quantified them with the HIV Dementia Motor Scale (HDMS). Our objectives were to replicate, in an independent sample, our prior findings that the HDMS is associated with cognitive impairment in HIV, while adding consideration of age-associated comorbidities such as cerebrovascular disease, and to examine the longitudinal trajectories of cognitive and motor dysfunction. We included all participants enrolled in the Manhattan HIV Brain Bank (MHBB) from January 2007 to May 2017 who had complete baseline data (N = 164). MHBB participants undergo standardized longitudinal assessments including documentation of comorbidities and medications, blood work, the HDMS, and neurocognitive testing. We found that motor dysfunction, cognitive impairment, and cerebrovascular disease were significantly associated with each other at baseline. Cerebrovascular disease independently predicted cognitive impairment in a multivariable model. Longitudinal analysis in a subset of 78 participants with ≥ 4 years of follow-up showed a stable cognition but declining motor function. We conclude that the HDMS is a valid measurement of motor dysfunction in HIV-infected patients and is associated with cognitive impairment and the presence of cerebrovascular disease. Cognitive impairment is mild and stable in CART-treated HIV; however, motor function declines over time, which may be related to the accrual of comorbidities such as cerebrovascular disease. Further research should examine the mechanisms underlying motor dysfunction in HIV and its clinical impact.

Cerebrovascular risk factors for patients with cerebral watershed infarction: A case-control study based on computed tomography angiography in a population from Southwest China.

Science.gov (United States)

Dong, Mei-Xue; Hu, Ling; Huang, Yuan-Jun; Xu, Xiao-Min; Liu, Yang; Wei, You-Dong

2017-07-01

To determine cerebrovascular risk factors for patients with cerebral watershed infarction (CWI) from Southwest China.Patients suffering from acute ischemic stroke were categorized into internal CWI (I-CWI), external CWI (E-CWI), or non-CWI (patients without CWI) groups. Clinical data were collected and degrees of steno-occlusion of all cerebral arteries were scored. Arteries associated with the circle of Willis were also assessed. Data were compared using Pearson chi-squared tests for categorical data and 1-way analysis of variance with Bonferroni post hoc tests for continuous data, as appropriate. Multivariate binary logistic regression analysis was performed to determine independent cerebrovascular risk factors for CWI.Compared with non-CWI, I-CWI had higher degrees of steno-occlusion of the ipsilateral middle cerebral artery, ipsilateral carotid artery, and contralateral middle cerebral artery. E-CWI showed no significant differences. All the 3 arteries were independent cerebrovascular risk factors for I-CWI confirmed by multivariate binary logistic regression analysis. I-CWI had higher degrees of steno-occlusion of the ipsilateral middle cerebral artery compared with E-CWI. No significant differences were found among arteries associated with the circle of Willis.The ipsilateral middle cerebral artery, carotid artery, and contralateral middle cerebral artery were independent cerebrovascular risk factors for I-CWI. No cerebrovascular risk factor was identified for E-CWI.

Postmenopausal hormone therapy and subclinical cerebrovascular disease

Science.gov (United States)

Coker, L H.; Hogan, P E.; Bryan, N R.; Kuller, L H.; Margolis, K L.; Bettermann, K; Wallace, R B.; Lao, Z; Freeman, R; Stefanick, M L.; Shumaker, S A.

2009-01-01

Objective: The Women's Health Initiative Memory Study (WHIMS) hormone therapy (HT) trials reported that conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA) increases risk for all-cause dementia and global cognitive decline. WHIMS MRI measured subclinical cerebrovascular disease as a possible mechanism to explain cognitive decline reported in WHIMS. Methods: We contacted 2,345 women at 14 WHIMS sites; scans were completed on 1,424 (61%) and 1,403 were accepted for analysis. The primary outcome measure was total ischemic lesion volume on brain MRI. Mean duration of on-trial HT or placebo was 4 (CEE+MPA) or 5.6 years (CEE-Alone) and scans were conducted an average of 3 (CEE+MPA) or 1.4 years (CEE-Alone) post-trial termination. Cross-sectional analysis of MRI lesions was conducted; general linear models were fitted to assess treatment group differences using analysis of covariance. A (two-tailed) critical value of α = 0.05 was used. Results: In women evenly matched within trials at baseline, increased lesion volumes were significantly related to age, smoking, history of cardiovascular disease, hypertension, lower post-trial global cognition scores, and increased incident cases of on- or post-trial mild cognitive impairment or probable dementia. Mean ischemic lesion volumes were slightly larger for the CEE+MPA group vs placebo, except for the basal ganglia, but the differences were not significant. Women assigned to CEE-Alone had similar mean ischemic lesion volumes compared to placebo. Conclusions: Conjugated equine estrogen–based hormone therapy was not associated with a significant increase in ischemic brain lesion volume relative to placebo. This finding was consistent within each trial and in pooled analyses across trials. GLOSSARY 3MSE = modified Mini-Mental State Examination; BMI = body mass index; CEE = conjugated equine estrogen; CVD = cerebrovascular disease; HT = hormone therapy; MCI = mild cognitive impairment; MPA

Regulation of Viral Replication, Apoptosis and Pro-Inflammatory Responses by 17-AAG during Chikungunya Virus Infection in Macrophages

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Tapas K. Nayak

2017-01-01

Full Text Available Chikungunya virus (CHIKV infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively. Moreover, host immune modulation and apoptosis were studied through flow cytometry, Western blot and ELISA. Our current findings suggest that expression of CHIKV proteins were maximum at 8 hpi and the release of new viral progenies were remarkably increased around 12 hpi. The induction of Annexin V binding, cleaved caspase-3, cleaved caspase-9 and cleaved caspase-8 in CHIKV infected macrophages suggests activation of apoptosis through both intrinsic and extrinsic pathways. The pro-inflammatory mediators (TNF and IL-6 MHC-I/II and B7.2 (CD86 were also up-regulated during infection over time. Further, 17-AAG, a potential HSP90 inhibitor, was found to regulate CHIKV infection, apoptosis and pro-inflammatory cytokine/chemokine productions of host macrophages significantly. Hence, the present findings might bring new insight into the therapeutic implication in CHIKV disease biology.

Regulation of Viral Replication, Apoptosis and Pro-Inflammatory Responses by 17-AAG during Chikungunya Virus Infection in Macrophages.

Science.gov (United States)

Nayak, Tapas K; Mamidi, Prabhudutta; Kumar, Abhishek; Singh, Laishram Pradeep K; Sahoo, Subhransu S; Chattopadhyay, Soma; Chattopadhyay, Subhasis

2017-01-06

Chikungunya virus (CHIKV) infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively. Moreover, host immune modulation and apoptosis were studied through flow cytometry, Western blot and ELISA. Our current findings suggest that expression of CHIKV proteins were maximum at 8 hpi and the release of new viral progenies were remarkably increased around 12 hpi. The induction of Annexin V binding, cleaved caspase-3, cleaved caspase-9 and cleaved caspase-8 in CHIKV infected macrophages suggests activation of apoptosis through both intrinsic and extrinsic pathways. The pro-inflammatory mediators (TNF and IL-6) MHC-I/II and B7.2 (CD86) were also up-regulated during infection over time. Further, 17-AAG, a potential HSP90 inhibitor, was found to regulate CHIKV infection, apoptosis and pro-inflammatory cytokine/chemokine productions of host macrophages significantly. Hence, the present findings might bring new insight into the therapeutic implication in CHIKV disease biology.

Effect of Cocoa Polyphenolic Extract on Macrophage Polarization from Proinflammatory M1 to Anti-Inflammatory M2 State

Directory of Open Access Journals (Sweden)

Laura Dugo

2017-01-01

Full Text Available Polyphenols-rich cocoa has many beneficial effects on human health, such as anti-inflammatory effects. Macrophages function as control switches of the immune system, maintaining the balance between pro- and anti-inflammatory activities. We investigated the hypothesis that cocoa polyphenol extract may affect macrophage proinflammatory phenotype M1 by favoring an alternative M2 anti-inflammatory state on macrophages deriving from THP-1 cells. Chemical composition, total phenolic content, and antioxidant capacity of cocoa polyphenols extracted from roasted cocoa beans were determined. THP-1 cells were activated with both lipopolysaccharides and interferon-γ for M1 or with IL-4 for M2 switch, and specific cytokines were quantified. Cellular metabolism, through mitochondrial oxygen consumption, and ATP levels were evaluated. Here, we will show that cocoa polyphenolic extract attenuated in vitro inflammation decreasing M1 macrophage response as demonstrated by a significantly lowered secretion of proinflammatory cytokines. Moreover, treatment of M1 macrophages with cocoa polyphenols influences macrophage metabolism by promoting oxidative pathways, thus leading to a significant increase in O2 consumption by mitochondrial complexes as well as a higher production of ATP through oxidative phosphorylation. In conclusion, cocoa polyphenolic extract suppresses inflammation mediated by M1 phenotype and influences macrophage metabolism by promoting oxidative pathways and M2 polarization of active macrophages.

High-intensity interval exercise and cerebrovascular health: curiosity, cause, and consequence.

Science.gov (United States)

Lucas, Samuel J E; Cotter, James D; Brassard, Patrice; Bailey, Damian M

2015-06-01

Exercise is a uniquely effective and pluripotent medicine against several noncommunicable diseases of westernised lifestyles, including protection against neurodegenerative disorders. High-intensity interval exercise training (HIT) is emerging as an effective alternative to current health-related exercise guidelines. Compared with traditional moderate-intensity continuous exercise training, HIT confers equivalent if not indeed superior metabolic, cardiac, and systemic vascular adaptation. Consequently, HIT is being promoted as a more time-efficient and practical approach to optimize health thereby reducing the burden of disease associated with physical inactivity. However, no studies to date have examined the impact of HIT on the cerebrovasculature and corresponding implications for cognitive function. This review critiques the implications of HIT for cerebrovascular function, with a focus on the mechanisms and translational impact for patient health and well-being. It also introduces similarly novel interventions currently under investigation as alternative means of accelerating exercise-induced cerebrovascular adaptation. We highlight a need for studies of the mechanisms and thereby also the optimal dose-response strategies to guide exercise prescription, and for studies to explore alternative approaches to optimize exercise outcomes in brain-related health and disease prevention. From a clinical perspective, interventions that selectively target the aging brain have the potential to prevent stroke and associated neurovascular diseases.

Diabetes mellitus: long-term prognostic value of whole-body MR imaging for the occurrence of cardiac and cerebrovascular events.

Science.gov (United States)

Bamberg, Fabian; Parhofer, Klaus G; Lochner, Elena; Marcus, Roy P; Theisen, Daniel; Findeisen, Hannes M; Hoffmann, Udo; Schönberg, Stefan O; Schlett, Christopher L; Reiser, Maximilian F; Weckbach, Sabine

2013-12-01

To study the predictive value of whole-body magnetic resonance (MR) imaging for the occurrence of cardiac and cerebrovascular events in a cohort of patients with diabetes mellitus (DM). This HIPAA-compliant study was approved by the institutional review board. Informed consent was obtained from all patients before enrollment into the study. The authors followed up 65 patients with DM (types 1 and 2) who underwent a comprehensive, contrast material-enhanced whole-body MR imaging protocol, including brain, cardiac, and vascular sequences at baseline. Follow-up was performed by phone interview. The primary endpoint was a major adverse cardiac and cerebrovascular event (MACCE), which was defined as composite cardiac-cerebrovascular death, myocardial infarction, cerebrovascular event, or revascularization. MR images were assessed for the presence of systemic atherosclerotic vessel changes, white matter lesions, and myocardial changes. Kaplan-Meier survival and Cox regression analyses were performed to determine associations. Follow-up was completed in 61 patients (94%; median age, 67.5 years; 30 women [49%]; median follow-up, 70 months); 14 of the 61 patients (23%) experienced MACCE. Although normal whole-body MR imaging excluded MACCE during the follow-up period (0%; 95% confidence interval [CI]: 0%, 17%), any detectable ischemic and/or atherosclerotic changes at whole-body MR imaging (prevalence, 66%) conferred a cumulative event rate of 20% at 3 years and 35% at 6 years. Whole-body MR imaging summary estimate of disease was strongly predictive for MACCE (one increment of vessel score and each territory with atherosclerotic changes: hazard ratio, 13.2 [95% CI: 4.5, 40.1] and 3.9 [95% CI: 2.2, 7.5], respectively), also beyond clinical characteristics as well as individual cardiac or cerebrovascular MR findings. These initial data indicate that disease burden as assessed with whole-body MR imaging confers strong prognostic information in patients with DM. Online

Association between Smokefree Legislation and Hospitalizations for Cardiac, Cerebrovascular and Respiratory Diseases: A Meta-Analysis

Science.gov (United States)

Tan, Crystal E.; Glantz, Stanton A.

2012-01-01

Background Secondhand smoke causes cardiovascular and respiratory disease. Smokefree legislation is associated with a lower risk of hospitalization and death from these diseases. Methods and Results Random effects meta-analysis was conducted by law comprehensiveness to determine the relationship between smokefree legislation and hospital admission or death from cardiac, cerebrovascular, and respiratory diseases. Studies were identified using a systematic search for studies published before November 30, 2011 using Science Citation Index, Google Scholar, PubMed, and Embase and references in identified papers. Change in hospital admissions (or deaths) in the presence of a smokefree law, duration of follow-up, and law comprehensiveness (workplaces only; workplaces and restaurants; or workplaces, restaurants, and bars) were recorded. Forty-five studies of 33 smokefree laws with median follow-up of 24 months (range 2–57 months) were included. Comprehensive smokefree legislation was associated with significantly lower rates of hospital admissions (or deaths) for all 4 diagnostic groups: coronary events (RR .848, 95% CI .816–.881), other heart disease (RR .610, 95% CI .440–.847), cerebrovascular accidents (RR .840, 95% CI .753–.936), and respiratory disease (RR .760, 95% CI .682–.846). The difference in risk following comprehensive smokefree laws does not change with longer follow-up. More comprehensive laws were associated with larger changes in risk. Conclusions Smokefree legislation was associated with a lower risk of smoking-related cardiac, cerebrovascular, and respiratory diseases, with more comprehensive laws associated with greater changes in risk. PMID:23109514

The diagnostic value of 13N-ammonia PET in ischemic cerebrovascular disorders

International Nuclear Information System (INIS)

Qiao Shuixian; Tang Anwu; Wang Lijuan; Liu Xintong; Yuan Yanbo; Chen Liguang; Luo Yaowu; Zhang Xiangsong; Wang Shuxia; Liu Bin; Xu Weiping

2002-01-01

Objective: To evaluate the feasibility of 13 N-ammonia PET in diagnosing ischemic cerebrovascular disorders. Methods: A total of 25 subjects were investigated. Five healthy volunteers served as normal control. Twenty patients included 13 with transient ischemic attack (TIA), 6 with brain infarction and 1 with moyamoya disease. 740-925 MBq of 13 N-ammonia was injected intravenously, 3-5 min later, PET imaging was performed with T + E 2D acquisition with Siemens ECAT EXACT HR + PET scanner. Image analysis was done by visual and semiquantitative estimating. Standardized uptake value (SUV) was measured in mirror regions of cerebrum with autocopy methods. Nine patients underwent drug stress with oral acetazolamide (ACZ). Images were compared before and after oral ACZ intervention. Results: Physiological brain uptake with SUV ratio of 0.99 +- 0.15 (n=5, left/right) was observed in healthy volunteers. L/N 13 N-ammonia as radioactive tracer was a safe and noninvasive, sensitive and accurate functional imaging modality for brain perfusion. The oral ACZ stress is a safe, simple and reliable diagnostic method for ischemic cerebrovascular disorders. It is of important uses in detecting the potential reserve of cerebral blood flow

Cerebrovascular Accident Incidence in the NASA Astronaut Population

Science.gov (United States)

LaPelusa, Michael B.; Charvat, Jacqueline M.; Lee, Lesley R.; Wear, Mary L.; Van Baalen, Mary

2016-01-01

The development of atherosclerosis is strongly associated with an increased risk for cerebrovascular accidents (CVA), including stroke and transient ischemic attacks (TIA). Certain unique occupational exposures that individuals in the NASA astronaut corps face, specifically high-performance aircraft training, SCUBA training, and spaceflight, are hypothesized to cause changes to the cardiovascular system. These changes, which include (but are not limited to) oxidative damage as a result of radiation exposure and circadian rhythm disturbance, increased arterial stiffness, and increased carotid-intima-media thickness (CIMT), may contribute to the development of atherosclerosis and subsequent CVA. The purpose of this study was to review cases of CVA in the NASA astronaut corps and describe the comorbidities and occupational exposures associated with CVA.

Cerebrovascular reactivity changes in asymptomatic female athletes attributable to high school soccer participation.

Science.gov (United States)

Svaldi, Diana O; McCuen, Emily C; Joshi, Chetas; Robinson, Meghan E; Nho, Yeseul; Hannemann, Robert; Nauman, Eric A; Leverenz, Larry J; Talavage, Thomas M

2017-02-01

As participation in women's soccer continues to grow and the longevity of female athletes' careers continues to increase, prevention and care for mTBI in women's soccer has become a major concern for female athletes since the long-term risks associated with a history of mTBI are well documented. Among women's sports, soccer exhibits among the highest concussion rates, on par with those of men's football at the collegiate level. Head impact monitoring technology has revealed that "concussive hits" occurring directly before symptomatic injury are not predictive of mTBI, suggesting that the cumulative effect of repetitive head impacts experienced by collision sport athletes should be assessed. Neuroimaging biomarkers have proven to be valuable in detecting brain changes that occur before neurocognitive symptoms in collision sport athletes. Quantifying the relationship between changes in these biomarkers and head impacts experienced by female soccer athletes may prove valuable to developing preventative measures for mTBI. This study paired functional magnetic resonance imaging with head impact monitoring to track cerebrovascular reactivity changes throughout a season and to test whether the observed changes could be attributed to mechanical loading experienced by female athletes participating in high school soccer. Marked cerebrovascular reactivity changes were observed in female soccer athletes, relative both to non-collision sport control measures and pre-season measures and were localized to fronto-temporal aspects of the brain. These changes persisted 4-5 months after the season ended and recovered by 8 months after the season. Segregation of the total soccer cohort into cumulative loading groups revealed that population-level changes were driven by athletes experiencing high cumulative loads, although athletes experiencing lower cumulative loads still contributed to group changes. The results of this study imply a non-linear relationship between cumulative

The Vulnerability of Vessels Involved in the Role of Embolism and Hypoperfusion in the Mechanisms of Ischemic Cerebrovascular Diseases

Directory of Open Access Journals (Sweden)

Yong Peng Yu

2016-01-01

Full Text Available Accurate definition and better understanding of the mechanisms of stroke are crucial as this will guide the effective care and therapy. In this paper, we review the previous basic and clinical researches on the causes or mechanisms of ischemic cerebrovascular diseases (ICVD and interpret the correlation between embolism and hypoperfusion based on vascular stenosis and arterial intimal lesions. It was suggested that if there is no embolus (dynamic or in situ emboli, there might be no cerebral infarction. Three kinds of different clinical outcomes of TIA were theoretically interpreted based on its mechanisms. We suppose that there is a correlation between embolism and hypoperfusion, and which mechanisms (hypoperfusion or hypoperfusion induced microemboli playing the dominant role in each type of ICVD depends on the unique background of arterial intimal lesions (the vulnerability of vessels. That is to say, the vulnerability of vessels is involved in the role of embolism and hypoperfusion in the mechanisms of ischemic cerebrovascular diseases. This inference might enrich and provide better understandings for the underlying etiologies of ischemic cerebrovascular events.

Cornuside inhibits mast cell-mediated allergic response by down-regulating MAPK and NF-κB signaling pathways

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Li, Liangchang [Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Yanbian University, Yanji, 133002 (China); Jin, Guangyu [Yanbian University Hospital, Medicine College, Yanbian University, Yanji, 133000 (China); Jiang, Jingzhi [Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Yanbian University, Yanji, 133002 (China); Zheng, Mingyu; Jin, Yan [College of Pharmacy, Yanbian University, Yanji, 133002 (China); Lin, Zhenhua [Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji, 133002 (China); Li, Guangzhao [Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Yanbian University, Yanji, 133002 (China); Choi, Yunho, E-mail: why76@jbnu.ac.kr [Department of Anatomy, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju, 561-756 (Korea, Republic of); Yan, Guanghai, E-mail: ghyan2015@sina.com [Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Yanbian University, Yanji, 133002 (China)

2016-04-29

Aims: The present study is to investigate the effect of cornuside on mast cell-mediated allergic response, as well as its possible mechanisms of action. Methods: To test the anti-allergic effects of cornuside in vivo, local extravasation was induced by local injection of anti-dinitrophenyl immunoglobulin E (IgE) followed by intravenous antigenic challenge in passive cutaneous anaphylaxis model rats. Mast cell viability was determined using MTT assay. Histamine content from rat peritoneal mast cells was measured by the radioenzymatic method. To investigate the mechanisms by which cornuside affects the reduction of histamine release, the levels of calcium uptake were measured. To examine whether cornuside affects the expression of pro-inflammatory cytokines, Western blotting and ELISA were carried out. Results: Oral administration of cornuside inhibited passive cutaneous anaphylaxis in rats. Presence of cornuside attenuated IgE-induced histamine release from rat peritoneal mast cells. The inhibitory effect of cornuside on histamine release was mediated by the modulation of intracellular calcium. In addition, cornuside decreased phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated production and secretion of pro-inflammatory cytokines such as TNF-α and IL-6 in human mast cells. The inhibitory effect of cornuside on pro-inflammatory cytokines was dependent on nuclear factor-κB and p38 mitogen-activated protein kinase. Conclusions: The present study provides evidence that cornuside inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression. Furthermore, in vivo and in vitro anti-allergic effects of cornuside suggest a possible therapeutic application of this agent in inflammatory allergic diseases.

Cornuside inhibits mast cell-mediated allergic response by down-regulating MAPK and NF-κB signaling pathways

International Nuclear Information System (INIS)

Li, Liangchang; Jin, Guangyu; Jiang, Jingzhi; Zheng, Mingyu; Jin, Yan; Lin, Zhenhua; Li, Guangzhao; Choi, Yunho; Yan, Guanghai

2016-01-01

Aims: The present study is to investigate the effect of cornuside on mast cell-mediated allergic response, as well as its possible mechanisms of action. Methods: To test the anti-allergic effects of cornuside in vivo, local extravasation was induced by local injection of anti-dinitrophenyl immunoglobulin E (IgE) followed by intravenous antigenic challenge in passive cutaneous anaphylaxis model rats. Mast cell viability was determined using MTT assay. Histamine content from rat peritoneal mast cells was measured by the radioenzymatic method. To investigate the mechanisms by which cornuside affects the reduction of histamine release, the levels of calcium uptake were measured. To examine whether cornuside affects the expression of pro-inflammatory cytokines, Western blotting and ELISA were carried out. Results: Oral administration of cornuside inhibited passive cutaneous anaphylaxis in rats. Presence of cornuside attenuated IgE-induced histamine release from rat peritoneal mast cells. The inhibitory effect of cornuside on histamine release was mediated by the modulation of intracellular calcium. In addition, cornuside decreased phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated production and secretion of pro-inflammatory cytokines such as TNF-α and IL-6 in human mast cells. The inhibitory effect of cornuside on pro-inflammatory cytokines was dependent on nuclear factor-κB and p38 mitogen-activated protein kinase. Conclusions: The present study provides evidence that cornuside inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression. Furthermore, in vivo and in vitro anti-allergic effects of cornuside suggest a possible therapeutic application of this agent in inflammatory allergic diseases.

Study on the relationship between serum leptin level and ischemic cerebrovascular disease (ICVD)

International Nuclear Information System (INIS)

Luo Nanping; Hu Chengjing; Wang Ruishan; Yin Qiuxia; Niu Aijun; Xue Lian; Xue Shenwu; Chen Qing

2004-01-01

Objective: To investigate the inter-relationship among serum leptin insulin resistance and blood lipids, and to explore the role of leptin in the pathogenesis of ischemic cerebrovascular diseases (ICVD). Methods: Levels of serum leptin, insulin and blood lipids were determined with RIA in 131 patients with different types of ICVD and 36 controls. Results: The levels of serum leptin in ICVD patients were significantly higher than those in the controls (P<0.01). Changes of blood lipids and insulin paralleled those of leptin (cxcept with HDL-C). The serum leptin were positively correlated to cholesterol, TG and insulin levels (r=0.45, P<0.05; r=0.31, P<0.05, r=0.55, P<0.01), but negatively correlated to HDL-C (r=-0.88, P<0.05). Conclusion: The high expression of leptin in ICVD patients is associated with high lipid and insulin levels. The close relationship among them indicates that high leptin levels play an important role in the pathogenesis of metabolic syndrome as well as atheromatous cerebrovascular diseases. (authors)

Neuro-ophthalmic manifestations of cerebrovascular accidents.

Science.gov (United States)

Ghannam, Alaa S Bou; Subramanian, Prem S

2017-11-01

Ocular functions can be affected in almost any type of cerebrovascular accident (CVA) creating a burden on the patient and family and limiting functionality. The present review summarizes the different ocular outcomes after stroke, divided into three categories: vision, ocular motility, and visual perception. We also discuss interventions that have been proposed to help restore vision and perception after CVA. Interventions that might help expand or compensate for visual field loss and visuospatial neglect include explorative saccade training, prisms, visual restoration therapy (VRT), and transcranial direct current stimulation (tDCS). VRT makes use of neuroplasticity, which has shown efficacy in animal models but remains controversial in human studies. CVAs can lead to decreased visual acuity, visual field loss, ocular motility abnormalities, and visuospatial perception deficits. Although ocular motility problems can be corrected with surgery, vision, and perception deficits are more difficult to overcome. Interventions to restore or compensate for visual field deficits are controversial despite theoretical underpinnings, animal model evidence, and case reports of their efficacies.

MSCs ameliorates DPN induced cellular pathology via [Ca2+ ]i homeostasis and scavenging the pro-inflammatory cytokines.

Science.gov (United States)

Chandramoorthy, Harish C; Bin-Jaliah, Ismaeel; Karari, Hussian; Rajagopalan, Prasanna; Ahmed Shariff, Mohammed Eajaz; Al-Hakami, Ahmed; Al-Humayad, Suliman M; Baptain, Fawzi A; Ahmed, Humeda Suekit; Yassin, Hanaa Z; Haidara, Mohamed A

2018-02-01

The MSCs of various origins are known to ameliorate or modulate cell survival strategies. We investigated, whether UCB MSCs could improve the survival of the human neuronal cells and/or fibroblast assaulted with DPN sera. The results showed, the co-culture of UCB MSCs with human neuronal cells and/or fibroblasts could effectively scavenge the pro-inflammatory cytokines TNF-α, IL-1β, IFN-ɤ and IL - 12 and control the pro-apoptotic expression of p53/Bax. Further co-culture of UCB MSCs have shown to induce anti-inflammatory cytokines like IL-4, IL-10 and TGF-β and anti-apoptotic Bclxl/Bcl2 expression in the DPN sera stressed cells. Amelioration of elevated [Ca 2+ ] i and cROS, the portent behind the NFκB/Caspase-3 mediated inflammation in DPN rescued the cells from apoptosis. The results of systemic administration of BM MSCs improved DPN pathology in rat as extrapolated from human cell model. The BM MSCs ameliorated prolonged distal motor latency (control: 0.70 ± 0.06, DPN: 1.29 ± 0.13 m/s DPN + BM MSCs: 0.89 ± 0.02 m/s, p glucose levels. Together, all these results showed that administration of BM or UCB MSCs improved the DPN via ameliorating pro-inflammatory cytokine signaling and [Ca 2+ ] i homeostasis. © 2017 Wiley Periodicals, Inc.

Effects of transcutaneous electrical nerve stimulation (TENS) on proinflammatory cytokines: protocol for systematic review.

Science.gov (United States)

Almeida, Tábata Cristina do Carmo; Figueiredo, Francisco Winter Dos Santos; Barbosa Filho, Valter Cordeiro; de Abreu, Luiz Carlos; Fonseca, Fernando Luiz Affonso; Adami, Fernando

2017-07-11

Pain reduction can be achieved by lowering proinflammatory cytokine levels in the blood. Transcutaneous electrical nerve stimulation (TENS) is a non-invasive physiotherapeutic resource for pain management, but evidence on the effectiveness of this device at reducing proinflammatory cytokines in the blood is unclear. This study systematically reviews the literature on the effect of TENS on proinflammatory cytokines. A systematic review protocol was developed based on searches of articles in six electronic databases and references of retrieved articles, contact with authors, and repositories of clinical trials. Eligibility criteria: publication in peer-reviewed journals, randomized clinical trials, use of TENS in the experimental group, and pre- and post-measurements of proinflammatory cytokines in the blood. Selection of the studies and extraction of the data will be carried out by two reviewers independently. Characteristics of the study, participants, interventions and outcomes were extracted and described. Assessments were performed on the risk of bias, level of evidence and the size of the intervention effect in the studies, according to GRADE guidelines and the Cochrane Handbook for Systematic Reviews. Clinical and statistical assessments compared the effects of the interventions (meta-analysis), taking into consideration any influencing characteristics of the studies (e.g., methods and application sites). We anticipate that this review will strengthen evidence-based knowledge of the effect of TENS on proinflammatory cytokines and, as a result, direct new studies to benefit patients with specific pathologies. PROSPERO, CRD42017060379 .

Acetazolamide as a vasodilatory stimulus in cerebrovascular diseases and in conditions affecting the cerebral vasculature

NARCIS (Netherlands)

Settakis, G.; Molnár, C.; Kerényi, L.; Kollár, J.; Legemate, D.; Csiba, L.; Fülesdi, B.

2003-01-01

Pathologic processes affecting the brain vessels may damage cerebral vasodilatory capacity. Early detection of cerebral dysfunction plays an important role in the prevention of cerebrovascular diseases. In recent decades acetazolamide (AZ) has frequently been used for this purpose. In the present

Evaluation of high-pitch dual-source CT angiography for evaluation of coronary and carotid-cerebrovascular arteries

Energy Technology Data Exchange (ETDEWEB)

Sun, Kai [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Li, Kuncheng, E-mail: cjr.likuncheng@vip.163.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Han, Ruijuan [Department of Cardiology, Chaoyang Hospital, Capital Medical University, Beijing 100020 (China); Li, Wenhuan; Chen, Nan; Yang, Qi; Du, Xiangying; Wang, Chen [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Liu, Guorong; Li, Yuechun [Department of Neurology Baotou Central Hospital, Inner Mongolia, Baotou 014040 (China); Zhou, Maorong [Department of Radiology, Baotou Central Hospital, Inner Mongolia, Baotou 014040 (China); Li, Ligang; Heidrun, Endt [CT BM Clinic Marketing, Siemens Healthcare, Beijing 100102 (China)

2015-03-15

Objectives: To explore the feasibility and diagnostic accuracy of a combined one-step high-pitch dual-source computed tomography angiography (CTA) technique for evaluation of coronary and carotid-cerebrovascular arteries. Materials and methods: 85 symptomatic patients suspected of coronary artery and cerebrovascular disease referred for simultaneous coronary and carotid-cerebrovascular CTA were included. Additional invasive angiography of the coronary and cerebral arteries was performed within 30 days in 23 and 13 patients, respectively. The objective parameters of image quality, the mean CT attenuations, image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were evaluated. The subjective image quality of vessels was also assessed by 2 independent radiologists blinded to the patients’ medical history and scan protocols. The diagnostic performance of CTA including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the detection or exclusion of significant artery stenosis was calculated using the chi-squared test of contingency and correlated with the results of invasive angiography representing the standard of reference. Results: Image quality was rated excellent (score 1) in 95.3% (1074/1127), good (score 2) in 3.3% (37/1127), adequate (score 3) in 1.0% (11/1127), and non-diagnostic (score 4) in 0.4% (5/1127) of coronary segments. Image quality of carotid and cerebral vessels was rated mostly excellent (score 1, 95.12% [78/82]; score 2, 3.66% [3/82]; score 3, 1.22% [1/82]). The sensitivity, specificity, PPV and NPV for the detection of coronary stenosis were 92.2% (81.1–97.7%), 95.2% (91.7–97.5%), 79.6% (67.1–89.1%) and 98.3% (95.8–99.5%), respectively. For the detection of carotid and cerebral artery stenosis, CTA demonstrated a sensitivity of 92.8% (80.5–98.4%), a specificity of 93.5% (88.3–96.8%), a PPV of 79.6% (65.6–89.7%) and a NPV of 97.9% (94.1–99.5%). The effective

The effects of 'Oren-gedoku-to' and quantitative evaluation of cerebral blood flow for cerebrovascular diseases

International Nuclear Information System (INIS)

Ushikubo, Yukio; Sakurai, Takatoshi; Yokouchi, Tetuya

1998-01-01

Fifty-seven patients with sequela of cerebrovascular diseases were treated with 'Oren-gedoku-to' for 8 weeks to examine the possibilities of improvements in subjective symptom, motive deterioration, mental disorder, unusual behaviors and intellectual malfunction. These symptoms showed improvement of 41.6%, 54.2%, 75.0%, 63.0%, 21.3%, respectively. For 21 patients, amount of regional cerebral blood flow were measured with SPECT. Results showed an increase of 1.7ml/100g/min. at average. However, there was no statistical difference observed among 'improved' cases, 'slightly improved' cases and 'no change or deteriorated' cases. 'Oren-gedoku-to' worked effectively for cerebrovascular diseases with the exception of intellectual malfunction. Results of the SPECT suggest though, it is uncertain whether these improvements were brought about by the increase of cerebral blood flow. (author)

Identification of informative features for predicting proinflammatory potentials of engine exhausts.

Science.gov (United States)

Wang, Chia-Chi; Lin, Ying-Chi; Lin, Yuan-Chung; Jhang, Syu-Ruei; Tung, Chun-Wei

2017-08-18

The immunotoxicity of engine exhausts is of high concern to human health due to the increasing prevalence of immune-related diseases. However, the evaluation of immunotoxicity of engine exhausts is currently based on expensive and time-consuming experiments. It is desirable to develop efficient methods for immunotoxicity assessment. To accelerate the development of safe alternative fuels, this study proposed a computational method for identifying informative features for predicting proinflammatory potentials of engine exhausts. A principal component regression (PCR) algorithm was applied to develop prediction models. The informative features were identified by a sequential backward feature elimination (SBFE) algorithm. A total of 19 informative chemical and biological features were successfully identified by SBFE algorithm. The informative features were utilized to develop a computational method named FS-CBM for predicting proinflammatory potentials of engine exhausts. FS-CBM model achieved a high performance with correlation coefficient values of 0.997 and 0.943 obtained from training and independent test sets, respectively. The FS-CBM model was developed for predicting proinflammatory potentials of engine exhausts with a large improvement on prediction performance compared with our previous CBM model. The proposed method could be further applied to construct models for bioactivities of mixtures.

Proinflammatory Soluble Interleukin-15 Receptor Alpha Is Increased in Rheumatoid Arthritis

Directory of Open Access Journals (Sweden)

Ana Cecilia Machado Diaz

2012-01-01

Full Text Available Rheumatoid arthritis (RA is an autoimmune and inflammatory disease in which many cytokines have been implicated. In particular, IL-15 is a cytokine involved in the inflammatory processes and bone loss. The aim of this study was to investigate the existence in synovial fluid of soluble IL-15Rα, a private receptor subunit for IL-15 which may act as an enhancer of IL-15-induced proinflammatory cytokines. Soluble IL-15Rα was quantified by a newly developed enzyme-linked immunosorbent assay (ELISA in samples of synovial fluid from patients with RA and osteoarthritis (OA. The levels of IL-15Rα were significantly increased in RA patients compared to OA patients. Also, we studied the presence of membrane-bound IL-15 in cells from synovial fluids, another element necessary to induce pro-inflammatory cytokines through reverse signaling. Interestingly, we found high levels of IL-6 related to high levels of IL-15Rα in RA but not in OA. Thus, our results evidenced presence of IL-15Rα in synovial fluids and suggested that its pro-inflammatory effect could be related to induction of IL-6.

Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment

Science.gov (United States)

Markworth, James F.; Vella, Luke; Lingard, Benjamin S.; Tull, Dedreia L.; Rupasinghe, Thusitha W.; Sinclair, Andrew J.; Maddipati, Krishna Rao

2013-01-01

Classical proinflammatory eicosanoids, and more recently discovered lipid mediators with anti-inflammatory and proresolving bioactivity, exert a complex role in the initiation, control, and resolution of inflammation. Using a targeted lipidomics approach, we investigated circulating lipid mediator responses to resistance exercise and treatment with the NSAID ibuprofen. Human subjects undertook a single bout of unaccustomed resistance exercise (80% of one repetition maximum) following oral ingestion of ibuprofen (400 mg) or placebo control. Venous blood was collected during early recovery (0–3 h and 24 h postexercise), and serum lipid mediator composition was analyzed by LC-MS-based targeted lipidomics. Postexercise recovery was characterized by elevated levels of cyclooxygenase (COX)-1 and 2-derived prostanoids (TXB2, PGE2, PGD2, PGF2α, and PGI2), lipooxygenase (5-LOX, 12-LOX, and 15-LOX)-derived hydroxyeicosatetraenoic acids (HETEs), and leukotrienes (e.g., LTB4), and epoxygenase (CYP)-derived epoxy/dihydroxy eicosatrienoic acids (EpETrEs/DiHETrEs). Additionally, we detected elevated levels of bioactive lipid mediators with anti-inflammatory and proresolving properties, including arachidonic acid-derived lipoxins (LXA4 and LXB4), and the EPA (E-series) and DHA (D-series)-derived resolvins (RvD1 and RvE1), and protectins (PD1 isomer 10S, 17S-diHDoHE). Ibuprofen treatment blocked exercise-induced increases in COX-1 and COX-2-derived prostanoids but also resulted in off-target reductions in leukotriene biosynthesis, and a diminished proresolving lipid mediator response. CYP pathway product metabolism was also altered by ibuprofen treatment, as indicated by elevated postexercise serum 5,6-DiHETrE and 8,9-DiHETrE only in those receiving ibuprofen. These findings characterize the blood inflammatory lipid mediator response to unaccustomed resistance exercise in humans and show that acute proinflammatory signals are mechanistically linked to the induction of a

Nuclear medicine imaging in cerebrovascular disorders; Nuklearmedizinische Bildgebung bei zerebrovaskulaeren Erkrankungen

Energy Technology Data Exchange (ETDEWEB)

Barthel, H. [Universitaetsklinikum Leipzig A.oe.R. (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Leipzig Univ. (Germany). Translationszentrum fuer Regenerative Medizin; Hesse, S.; Sabri, O. [Universitaetsklinikum Leipzig A.oe.R. (Germany). Klinik und Poliklinik fuer Nuklearmedizin

2007-09-15

For diagnosing cerebrovascular disorders, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) employing blood flow and oxygen consumption markers is applied. Currently, competing imaging techniques which do not rely on radiotracers are more dominant in clinical routine. However, brain SPECT and PET substantially contribute towards diagnosis and therapy monitoring in acute and chronic cerebral ischemia. Furthermore, cerebral vasculitis, vasospasm after subarachnoid hemorrhage, brain tolerance during balloon occlusion tests and brain death can be accurately diagnosed. (orig.)

A pro-inflammatory role of deubiquitinating enzyme cylindromatosis (CYLD) in vascular smooth muscle cells

Energy Technology Data Exchange (ETDEWEB)

Liu, Shuai [Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012 (China); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States); Lv, Jiaju [Department of Urology, Shandong Provincial Hospital, Shandong University, Jinan 250021 (China); Han, Liping; Ichikawa, Tomonaga; Wang, Wenjuan; Li, Siying [Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States); Wang, Xing Li [Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012 (China); Tang, Dongqi, E-mail: tangdq@pathology.ufl.edu [Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610-0275 (United States); Cui, Taixing, E-mail: taixing.cui@uscmed.sc.edu [Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States)

2012-03-30

Highlights: Black-Right-Pointing-Pointer Cyld deficiency suppresses pro-inflammatory phenotypic switch of VSMCs. Black-Right-Pointing-Pointer Cyld deficiency inhibits MAPK rather than NF-kB activity in inflamed VSMCs. Black-Right-Pointing-Pointer CYLD is up-regulated in the coronary artery with neointimal hyperplasia. -- Abstract: CYLD, a deubiquitinating enzyme (DUB), is a critical regulator of diverse cellular processes, ranging from proliferation and differentiation to inflammatory responses, via regulating multiple key signaling cascades such as nuclear factor kappa B (NF-{kappa}B) pathway. CYLD has been shown to inhibit vascular lesion formation presumably through suppressing NF-{kappa}B activity in vascular cells. However, herein we report a novel role of CYLD in mediating pro-inflammatory responses in vascular smooth muscle cells (VSMCs) via a mechanism independent of NF-{kappa}B activity. Adenoviral knockdown of Cyld inhibited basal and the tumor necrosis factor alpha (TNF{alpha})-induced mRNA expression of pro-inflammatory cytokines including monocyte chemotactic protein-1 (Mcp-1), intercellular adhesion molecule (Icam-1) and interleukin-6 (Il-6) in rat adult aortic SMCs (RASMCs). The CYLD deficiency led to increases in the basal NF-{kappa}B transcriptional activity in RASMCs; however, did not affect the TNF{alpha}-induced NF-{kappa}B activity. Intriguingly, the TNF{alpha}-induced I{kappa}B phosphorylation was enhanced in the CYLD deficient RASMCs. While knocking down of Cyld decreased slightly the basal expression levels of I{kappa}B{alpha} and I{kappa}B{beta} proteins, it did not alter the kinetics of TNF{alpha}-induced I{kappa}B protein degradation in RASMCs. These results indicate that CYLD suppresses the basal NF-{kappa}B activity and TNF{alpha}-induced I{kappa}B kinase activation without affecting TNF{alpha}-induced NF-{kappa}B activity in VSMCs. In addition, knocking down of Cyld suppressed TNF{alpha}-induced activation of mitogen activated protein

Prevalência e padrão de distribuição das doenças cerebrovasculares em 242 idosos, procedentes de um hospital geral, necropsiados em Belo Horizonte, Minas Gerais, no período de 1976 a 1997 Prevalence and types of cerebrovascular diseases in 242 hospitalized elderly patients, autopsied in Belo Horizonte, Minas Gerais, Brazil, from 1976 to 1997

Directory of Open Access Journals (Sweden)

José Eymard H. Pittella

2002-03-01

Full Text Available OBJETIVO: Descrever a prevalência e os tipos das doenças cerebrovasculares (DCVs em indivíduos idosos necropsiados. MÉTODO: Foram consultados os laudos neuropatológicos de 242 pacientes com idade igual ou superior a 61 anos, procedentes em sua maioria do Hospital das Clínicas da Universidade Federal de Minas Gerais, em Belo Horizonte, Minas Gerais, e necropsiados consecutivamente no período 1976 a 1997. RESULTADO: Os principais grupos de doenças do sistema nervoso central (SNC foram representados por DCVs (71,9%, infecções (12,4%, neoplasias (7,1%, traumatismos crânio-encefálicos (3,7%, doenças nutricionais (2,5% e doenças degenerativas (1,7%. As DCVs mais frequentes foram: aterosclerose (61,2%, doença cerebrovascular hipertensiva (25,6% e infarto cerebral (14,9%. Observou-se aumento da frequência e da gravidade da aterosclerose e da frequência da doença cerebrovascular hipertensiva com o avançar da idade. Houve associação significativa entre doença cerebrovascular hipertensiva e aterosclerose. As DCVs foram clinicamente sintomáticas e as responsáveis diretas pelo óbito em 42,7% e 17,3% dos pacientes, respectivamente. CONCLUSÃO: As DCVs constituíram o principal grupo de doenças do SNC no idoso. A aterosclerose e a doença cerebrovascular hipertensiva foram as principais doenças deste grupo, notando-se aumento de sua frequência com o avançar da idade e associação significativa entre ambas.OBJECTIVE: To describe the prevalence and the types of cerebrovascular diseases (CVDs in autopsied elderly individuals. METHOD: Consecutive clinical charts and neuropathological reports of 242 patients aged 61 years or older were reviewed. The patients died in Hospital das Clínicas, Federal University of Minas Gerais, in Belo Horizonte, Minas Gerais, Brazil, from 1976 to 1997. RESULTS: The prevalent diseases of the central nervous system (CNS found in decreasing order were: CVDs (71.9%, infections (12.4%, neoplasms (7.1%, head

TLR-mediated inflammatory responses to Streptococcus pneumoniae are highly dependent on surface expression of bacterial lipoproteins.

Science.gov (United States)

Tomlinson, Gillian; Chimalapati, Suneeta; Pollard, Tracey; Lapp, Thabo; Cohen, Jonathan; Camberlein, Emilie; Stafford, Sian; Periselneris, Jimstan; Aldridge, Christine; Vollmer, Waldemar; Picard, Capucine; Casanova, Jean-Laurent; Noursadeghi, Mahdad; Brown, Jeremy

2014-10-01

Streptococcus pneumoniae infections induce inflammatory responses that contribute toward both disease pathogenesis and immunity, but the host-pathogen interactions that mediate these effects are poorly defined. We used the surface lipoprotein-deficient ∆lgt pneumococcal mutant strain to test the hypothesis that lipoproteins are key determinants of TLR-mediated immune responses to S. pneumoniae. We show using reporter assays that TLR2 signaling is dependent on pneumococcal lipoproteins, and that macrophage NF-κB activation and TNF-α release were reduced in response to the ∆lgt strain. Differences in TNF-α responses between Δlgt and wild-type bacteria were abrogated for macrophages from TLR2- but not TLR4-deficient mice. Transcriptional profiling of human macrophages revealed attenuated TLR2-associated responses to ∆lgt S. pneumoniae, comprising many NF-κB-regulated proinflammatory cytokine and chemokine genes. Importantly, non-TLR2-associated responses were preserved. Experiments using leukocytes from IL-1R-associated kinase-4-deficient patients and a mouse pneumonia model confirmed that proinflammatory responses were lipoprotein dependent. Our data suggest that leukocyte responses to bacterial lipoproteins are required for TLR2- and IL-1R-associated kinase-4-mediated inflammatory responses to S. pneumoniae. Copyright © 2014 The Authors.

Association between ALT level and the rate of cardio/cerebrovascular events in HIV-positive individuals

DEFF Research Database (Denmark)

Sabin, Caroline A; Ryom, Lene; Kovari, Helen

2013-01-01

An inverse association between serum alanine aminotransferase (ALT) levels and the risk of myocardial infarction (MI) has been reported in the general population. We investigated associations between ALT levels and the risk of various cardiovascular and cerebrovascular outcomes in a large cohort ...

Vagal afferents modulate cytokine-mediated respiratory control at the neonatal medulla oblongata.

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Balan, Kannan V; Kc, Prabha; Hoxha, Zana; Mayer, Catherine A; Wilson, Christopher G; Martin, Richard J

2011-09-30

Perinatal sepsis and inflammation trigger lung and brain injury in preterm infants, and associated apnea of prematurity. We hypothesized that endotoxin exposure in the immature lung would upregulate proinflammatory cytokine mRNA expression in the medulla oblongata and be associated with impaired respiratory control. Lipopolysaccharide (LPS, 0.1mg/kg) or saline was administered intratracheally to rat pups and medulla oblongatas were harvested for quantifying expression of mRNA for proinflammatory cytokines. LPS-exposure significantly increased medullary mRNA for IL-1β and IL-6, and vagotomy blunted this increase in IL-1β, but not IL-6. Whole-body flow plethysmography revealed that LPS-exposed pups had an attenuated ventilatory response to hypoxia both before and after carotid sinus nerve transection. Immunochemical expression of IL-1β within the nucleus of the solitary tract and area postrema was increased after LPS-exposure. In summary, intratracheal endotoxin-exposure in rat pups is associated with upregulation of proinflammatory cytokines in the medulla oblongata that is vagally mediated for IL-1β and associated with an impaired hypoxic ventilatory response. Copyright © 2011 Elsevier B.V. All rights reserved.

Clinical evaluation of SPECT in cerebrovascular disease

International Nuclear Information System (INIS)

Oshibuchi, Masao; Satoh, Mitsutaka; Kanda, Tetsuro; Nishi, Fumiaki; Yamane, Kanji; Fujimatsu, Masahiko; Edamitsu, Satoshi; Anno, Yasuro; Ohtake, Hisashi.

1989-01-01

In 131 patients with cerebrovascular disease, regional cerebral blood flow were determined by 123 I-IMP (N-isopropyl ( 123 I)-iodoamphetamine) or 99m Tc-HM-PAO ( 99m Tc (d, 1)-hexamethyl propyleneamine oxime) SPECT and findings were compared with those of X-CT or MRI. The perfusion deficit detected by SPECT was larger than the deficit by X-CT or MRI in every case. The perfusion deficit area was more clearly demonstrated by SPECT than by X-CT or MRI in patients with acute cerebral infarction. The hypoperfusion area determined by 123 I-IMP SPECT was wider than that by 99m Tc-HM-PAO SPECT. The crossed cerebellar diaschisis was observed in 56 out of 131 cases (43%). The results of operation were quantitatively evaluated by 123 I-IMP SPECT in 25 patients. (author)

Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis

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Logan Richard M

2010-03-01

Full Text Available Abstract Background Mucositis is a toxic side effect of anti-cancer treatments and is a major focus in cancer research. Pro-inflammatory cytokines have previously been implicated in the pathophysiology of chemotherapy-induced gastrointestinal mucositis. However, whether they play a key role in the development of radiotherapy-induced gastrointestinal mucositis is still unknown. Therefore, the aim of the present study was to characterise the expression of pro-inflammatory cytokines in the gastrointestinal tract using a rat model of fractionated radiotherapy-induced toxicity. Methods Thirty six female Dark Agouti rats were randomly assigned into groups and received 2.5 Gys abdominal radiotherapy three times a week over six weeks. Real time PCR was conducted to determine the relative change in mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF in the jejunum and colon. Protein expression of IL-1β, IL-6 and TNF in the intestinal epithelium was investigated using qualitative immunohistochemistry. Results Radiotherapy-induced sub-acute damage was associated with significantly upregulated IL-1β, IL-6 and TNF mRNA levels in the jejunum and colon. The majority of pro-inflammatory cytokine protein expression in the jejunum and colon exhibited minimal change following fractionated radiotherapy. Conclusions Pro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting.

Depression, anxiety and major adverse cardiovascular and cerebrovascular events in patients following coronary artery bypass graft surgery

DEFF Research Database (Denmark)

Tully, Phillip J; Winefield, Helen R; Baker, Robert A

2015-01-01

anhedonia, anxious arousal and general distress/negative affect symptom dimensions. Incident MACCE was defined as fatal or non-fatal; myocardial infarction, unstable angina pectoris, repeat revascularization, heart failure, sustained arrhythmia, stroke or cerebrovascular accident, left ventricular failure......BACKGROUND: Although depression and anxiety have been implicated in risk for major adverse cardiovascular and cerebrovascular events (MACCE), a theoretical approach to identifying such putative links is lacking. The objective of this study was to examine the association between theoretical...... and mortality due to cardiac causes. Time-to-MACCE was determined by hazard modelling after adjustment for EuroSCORE, smoking, body mass index, hypertension, heart failure and peripheral vascular disease. RESULTS: In the total sample, there were 698 cumulative person years of survival for analysis with a median...

Regional Brain Shrinkage over Two Years: Individual Differences and Effects of Pro-Inflammatory Genetic Polymorphisms

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Persson, N.; Ghisletta, P.; Dahle, C.L.; Bender, A.R.; Yang, Y.; Yuan, P.; Daugherty, A.M.; Raz, N.

2014-01-01

We examined regional changes in brain volume in healthy adults (N = 167, age 19-79 years at baseline; N = 90 at follow-up) over approximately two years. With latent change score models, we evaluated mean change and individual differences in rates of change in 10 anatomically-defined and manually-traced regions of interest (ROIs): lateral prefrontal cortex (LPFC), orbital frontal cortex (OF), prefrontal white matter (PFw), hippocampus (HC), parahippocampal gyrus (PhG), caudate nucleus (Cd), putamen (Pt), insula (In), cerebellar hemispheres (CbH), and primary visual cortex (VC). Significant mean shrinkage was observed in the HC, CbH, In, OF, and the PhG, and individual differences in change were noted in all regions, except the OF. Pro-inflammatory genetic variants mediated shrinkage in PhG and CbH. Carriers of two T alleles of interleukin-1β (IL-1βC-511T, rs16944) and a T allele of methylenetetrahydrofolate reductase (MTHFRC677T, rs1801133) polymorphisms showed increased PhG shrinkage. No effects of a pro-inflammatory polymorphism for C-reactive protein (CRP-286C>A>T, rs3091244) or apolipoprotein (APOE) ε4 allele were noted. These results replicate the pattern of brain shrinkage observed in previous studies, with a notable exception of the LPFC thus casting doubt on the unique importance of prefrontal cortex in aging. Larger baseline volumes of CbH and In were associated with increased shrinkage, in conflict with the brain reserve hypothesis. Contrary to previous reports, we observed no significant linear effects of age and hypertension on regional brain shrinkage. Our findings warrant further investigation of the effects of neuroinflammation on structural brain change throughout the lifespan. PMID:25264227

Proinflammatory cytokines in open versus laparoscopic cholecystectomy

International Nuclear Information System (INIS)

Abu-Eshy, Saeed A.; Al-Rofaidi, Abdallah A.; Al-Faki, Ahmed S.; Ghalib, Hashim W.; Moosa, Riyadh A.; Sadik, Ali A.; Salati, Mohammad I.

2002-01-01

Laparoscopic cholecystectomy, a minimal access surgery, is fast replacing open cholecystectomy and is being associated with less trauma. The objective of this study was to compare the proinflammatory cytokine levels in both laparoscopic cholecystectomy and open cholecystectomy. This study was carried out at Aseer Central Hospital, Aseer region, Abha Private Hospital and the College of Medicine and Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia, during the time period October 1998 through to November 2000. Sixty-one patients were included in the study, 27 of them had laparoscopic cholecystectomy and 34 had open cholecystectomy. Cytokines [Interleukin-6 Interleukin-1b, Tumor necrosis factor -a and Interleukin- 8] were measured in blood samples collected from the patients before, at and 24 hours post surgery, using commercially available kits. Interleukin-6 levels were significantly increased at 24 hours post surgery in the open cholecystectomy group of patients compared to the laparoscopic cholecystectomy group (P<0.04). No differences were found in the other cytokines levels (Interleukin-1b, tumor necrosis factor -a and Interleukin-8) between the open cholecystectomy and laparoscopic cholecystectomy groups. Laparoscopic cholecystectomy, a minimal access surgery, is associated with lower levels of the proinflammatory interleukin-6 cytokine compared to open cholecystectomy. (author)

[Lipids and cerebrovascular disease - New therapeutic options in lowering LDL-cholesterol].

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Lovadi, Emese; Csécsei, Péter; Lovig, Csenge; Karádi, Zsófia; Szapáry, László

2016-12-01

Stroke is the third most common cause of death worldwide following myocardial infaction and malignancies, furthermore, its functional outcome is the worst of all conditions. Cholesterol, especially LDL-cholesterol plays a key role in the formation of atherosclerotic plaques. It has been verified recently that escalating incidence and mortality of cerebrovascular diseases are proportional to increased levels of LDL-cholesterol. Statin therapy undeniably reduces the risk of stroke, however other methods for decreasing lipid levels have not been proved significantly effective. Preventive effect of high-dose statin treatment is without doubt, although administration of such high dosage might require special precautions for patients with prior intracerebral hemorrhage and it also risks development of incident diabetes. The recently published IMPROVE-IT study is the first to prove that the addition of ezetimibe as a non-statin type drug, to statin treatment contributes to further reduction of LDL-cholesterol. The combination treatment results in additional decrease in the incidence and mortality of cerebrovascular events, without any expansion in the number or adverse effects. These results confirm the importance of any further reduction of LDL-cholesterol levels. Achieving target values with statin-ezetimibe combination allows administration of low to moderate dose of statin, which decreases risks of adverse effects related to high-dose statin therapy. Orv. Hetil., 2016, 157(52), 2059-2065.

Transferrin-derived synthetic peptide induces highly conserved pro-inflammatory responses of macrophages.

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Haddad, George; Belosevic, Miodrag

2009-02-01

We examined the induction of macrophage pro-inflammatory responses by transferrin-derived synthetic peptide originally identified following digestion of transferrin from different species (murine, bovine, human N-lobe and goldfish) using elastase. The mass spectrometry analysis of elastase-digested murine transferrin identified a 31 amino acid peptide located in the N2 sub-domain of the transferrin N-lobe, that we named TMAP. TMAP was synthetically produced and shown to induce a number of pro-inflammatory genes by quantitative PCR. TMAP induced chemotaxis, a potent nitric oxide response, and TNF-alpha secretion in different macrophage populations; P338D1 macrophage-like cells, mouse peritoneal macrophages, mouse bone marrow-derived macrophages (BMDM) and goldfish macrophages. The treatment of BMDM cultures with TMAP stimulated the production of nine cytokines and chemokines (IL-6, MCP-5, MIP-1 alpha, MIP-1 gamma, MIP-2, GCSF, KC, VEGF, and RANTES) that was measured using cytokine antibody array and confirmed by Western blot. Our results indicate that transferrin-derived peptide, TMAP, is an immunomodulating molecule capable of inducing pro-inflammatory responses in lower and higher vertebrates.

Endogenous acute phase serum amyloid A lacks pro-inflammatory activity, contrasting the two recombinant variants that activate human neutrophils through different receptors

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Karin eChristenson

2013-04-01

Full Text Available Most notable among the acute phase proteins is serum amyloid A (SAA, levels of which can increase 1000-fold during infections, aseptic inflammation, and/or trauma. Chronically elevated SAA levels are associated with a wide variety of pathological conditions, including obesity and rheumatic diseases. Using a recombinant hybrid of the two human SAA isoforms (SAA1 and 2 that does not exist in vivo, numerous in vitro studies have given rise to the notion that acute phase SAA is a pro-inflammatory molecule with cytokine-like properties. It is however unclear whether endogenous acute phase SAA per se mediates pro-inflammatory effects. We tested this in samples from patients with inflammatory arthritis and in a transgenic mouse model that expresses human SAA1. Endogenous human SAA did not drive production of pro-inflammatory IL-8/KC in either of these settings. Human neutrophils derived from arthritis patients displayed no signs of activation, despite being exposed to severely elevated SAA levels in circulation, and SAA-rich sera also failed to activate cells in vitro. In contrast, two recombinant SAA variants (the hybrid SAA and SAA1 both activated human neutrophils, inducing L-selectin shedding, production of reactive oxygen species, and production of IL-8. The hybrid SAA was approximately 100-fold more potent than recombinant SAA1. Recombinant hybrid SAA and SAA1 activated neutrophils through different receptors, with recombinant SAA1 being a ligand for formyl peptide receptor 2 (FPR2. We conclude that even though recombinant SAAs can be valuable tools for studying neutrophil activation, they do not reflect the nature of the endogenous protein.

Morphological changes of cerebral vessels and expression patterns of MMP-2 and MMP-9 on cerebrovascular wall of alcoholic rats.

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Qi, Qian; Liu, Xia; Zhang, Guozhong; He, Wenjing; Ma, Rufei; Cong, Bin; Li, Yingmin

2014-01-01

Alcohol abuse increases the incidence of cerebral accidents, which correlates with cerebrovascular structural changes. The present study was designed to observe the cerebrovascular remodeling of drinking rats with light microscopy and transmission electron microscopy (TEM). Short-term alcohol administration induced apparent amplification of perivascular spaces around small vessels in brain tissue, while long-term administration caused pathological changes of basilar arteries (BAs), including endothelial exfoliation, inner elastic lamina (IEL) fragmentation and thickening of tunica media and adventitia. In addition, the relationship between cerebrovascular remodeling and MMP-2 and MMP-9 synthesized by endothelial cells and vascular smooth muscle cells was explored by immunohistochemistry. The two protein expression in cerebral vessels changed dynamically, peaking at 1-2 weeks after treatment, and decreasing as treatment continued. These results suggest that MMP-2 and MMP-9 may play a significant role in blood-brain barrier disruption after alcohol abuse. But the chronic changes of cerebral arteries resulted from drinking are not coincident with time course of MMP-2 and MMP-9 expression in situ.

Prognosis in Acute Cerebrovascular Accidents in Relation to Respiratory Pattern and Blood—gas Tensions

Science.gov (United States)

Rout, M. W.; Lane, D. J.; Wollner, L.

1971-01-01

Respiratory pattern and arterial blood gas tensions were assessed in patients with acute cerebrovascular accidents. Hyperventilation, low Pco2, and high arterial pH were associated with a poor prognosis, whereas patients with normal respiratory pattern and blood gas tensions survived. Periodic and Cheyne-Stokes breathing carried an intermediate prognosis. PMID:5091916

Cerebrovascular diseases in a fixed population Hiroshima and Nagasaki with special reference to relationship between type and risk factors

International Nuclear Information System (INIS)

Lin, Chow-How; Shimizu, Yukiko; Kato, Hiroo; Robertson, T.L.; Furonaka, Hiroshi.

1980-10-01

A study was made of the incidence of cerebrovascular diseases, their chronological trend, and relationship between the disease types and risk factors on 16,491 subjects of Hiroshima and Nagasaki who underwent medical examination at least once between 1958 - 74, and who were free of cerebrovascular disease at the initial examination. During the 16-year period, 1,162 cases of cerebrovascular disease developed in this study population with the diagnosis definite in 621, and the annual incidence was 3.2 per 1,000 population. By type, there were 108 cases of cerebral hemorrhage, 469 cases of cerebral infarction, 33 cases of subarachnoid hemorrhage, and 11 cases of other unclassifiable types, with cerebral infarction occurring more frequently than cerebral hemorrhage at the ratio of 4.5 : 1. The incidence of cerebrovascular diseases increased with age in both types, but the proportion of younger subjects in cerebral hemorrhage was greater than that in cerebral infarction. A secular trend of declining incidence was noted for both cerebral hemorrhage and cerebral infarction. As a risk factor of cerebral hemorrhage, elevation of systolic and diastolic blood pressure was the most closely related to onset, and left ventricular hypertrophy on electrocardiogram (ECG) and proteinuria were also related. However, a tendency was seen for the risk to be somewhat higher the lower the levels of serum cholesterol. In cerebral infarction, aging, like systolic blood pressure, was a most important risk factor. Left ventricular hypertrophy on ECG, proteinuria, and diabetes could also be risk factors. However, the relation to blood pressure, especially diastolic blood pressure, was not so great as in the case of cerebral hemorrhage. (author)

Platelet-derived growth factor (PDGF-BB-mediated induction of monocyte chemoattractant protein 1 in human astrocytes: implications for HIV-associated neuroinflammation

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Bethel-Brown Crystal

2012-12-01

Full Text Available Abstract Chemokine (C-C motif ligand 2, also known as monocyte chemoattractant protein 1 (MCP-1 is an important factor for the pathogenesis of HIV-associated neurocognitive disorders (HAND. The mechanisms of MCP-1-mediated neuropathogenesis, in part, revolve around its neuroinflammatory role and the recruitment of monocytes into the central nervous system (CNS via the disrupted blood-brain barrier (BBB. We have previously demonstrated that HIV-1/HIV-1 Tat upregulate platelet-derived growth factor (PDGF-BB, a known cerebrovascular permeant; subsequently, the present study was aimed at exploring the regulation of MCP-1 by PDGF-BB in astrocytes with implications in HAND. Specifically, the data herein demonstrate that exposure of human astrocytes to HIV-1 LAI elevated PDGF-B and MCP-1 levels. Furthermore, treating astrocytes with the human recombinant PDGF-BB protein significantly increased the production and release of MCP-1 at both the RNA and protein levels. MCP-1 induction was regulated by activation of extracellular-signal-regulated kinase (ERK1/2, c-Jun N-terminal kinase (JNK and p38 mitogen-activated protein (MAP kinases and phosphatidylinositol 3-kinase (PI3K/Akt pathways and the downstream transcription factor, nuclear factor κB (NFκB. Chromatin immunoprecipitation (ChIP assays demonstrated increased binding of NFκB to the human MCP-1 promoter following PDGF-BB exposure. Conditioned media from PDGF-BB-treated astrocytes increased monocyte transmigration through human brain microvascular endothelial cells (HBMECs, an effect that was blocked by STI-571, a tyrosine kinase inhibitor (PDGF receptor (PDGF-R blocker. PDGF-BB-mediated release of MCP-1 was critical for increased permeability in an in vitro BBB model as evidenced by blocking antibody assays. Since MCP-1 is linked to disease severity, understanding its modulation by PDGF-BB could aid in understanding the proinflammatory responses in HAND. These results suggest that astrocyte

[Systolic blood pressure and functional outcome in patients with acute stroke: a Mexican registry of acute cerebrovascular disease (RENAMEVASC)].

Science.gov (United States)

Baños-González, Manuel; Cantú-Brito, Carlos; Chiquete, Erwin; Arauz, Antonio; Ruiz-Sandoval, José Luís; Villarreal-Careaga, Jorge; Barinagarrementeria, Fernando; Lozano, José Juan

2011-01-01

To analyze the association between the admission systolic blood pressure (SBP) and 30-day outcome in patients with acute cerebrovascular disease. The REgistro NAcional Mexicano de Enfermedad VAScular Cerebral (RENAMEVASC) is a hospital-based multicenter registry performed between November 2002 and October 2004. A total of 2000 patients with clinical syndromes of acute cerebrovascular disease confirmed by neuroimaging were registered. The modified Rankin scale was used for outcome stratification. We analyzed 1721 patients who had registered their SBP: 78 (4.5%) had transient ischemic attack, 894 (51.9%) brain infarction, 534 (30.9%) intracerebral hemorrhage, 165 (9.6%) subarachnoid hemorrhage and 50 (2.9%) cerebral venous thrombosis. Among 1036 (60.2%) patients with the antecedent of hypertension, only 32.4% had regular treatment. The 30-day case fatality rate presented a J pattern with respect to SBP, so that the risk of death was highest in 65 years (RR: 2.16, IC 95%: 1.74 - 2.67). Both hypotension and significant arterial hypertension at hospital admission are associated with an adverse outcome after acute cerebrovascular disease. Nevertheless, a good functional outcome can be attained in a wide range of SBP.

Iodinated contrast media alter immune responses in pro-inflammatory states.

LENUS (Irish Health Repository)

O'Donnell, David H

2010-07-01

Hypertonic saline causes a transient elevation of blood osmolality and has been shown to alter cellular inflammatory responses in pro-inflammatory states. Intravascular administration of iodine contrast media also causes a transient elevation of blood osmolarity.

Pycnogenol Attenuates the Release of Proinflammatory Cytokines and Expression of Perilipin 2 in Lipopolysaccharide-Stimulated Microglia in Part via Inhibition of NF-κB and AP-1 Activation.

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Bin Fan

Full Text Available Over activation of microglia results in the production of proinflammatory agents that have been implicated in various brain diseases. Pycnogenol is a patented extract from French maritime pine bark (Pinus pinaster Aiton with strong antioxidant and anti-inflammatory potency. The present study investigated whether pycnogenol may be associated with the production of proinflammatory mediators in lipopolysaccharide-stimulated BV2 (mouse-derived microglia. It was found that pycnogenol treatment was dose-dependently associated with significantly less release of nitricoxide (NO, TNF-α, IL-6 and IL-1β, and lower levels of intercellular adhesion molecule1 (ICAM-1 and perilipin 2 (PLIN2. Furthermore, this effect was replicated in primary brain microglia. Levels of inducible NO synthase mRNA and protein were attenuated, whereas there was no change in the production of the anti-inflammatory cytokine IL-10. Further evidence indicated that pycnogenol treatment led to the suppression of NF-κB activation through inhibition of p65 translocation into the nucleus and inhibited DNA binding of AP-1, suggesting that these proinflammatory factors are associated with NF-κB and AP-1. We conclude that pycnogenol exerts anti-inflammatory effects through inhibition of the NF-κB and AP-1pathway, and may be useful as a therapeutic agent in the prevention of diseases caused by over activation of microglia.

Targeted overexpression of endothelial nitric oxide synthase in endothelial cells improves cerebrovascular reactivity in Ins2Akita-type-1 diabetic mice.

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Chandra, Saurav B; Mohan, Sumathy; Ford, Bridget M; Huang, Lei; Janardhanan, Preethi; Deo, Kaiwalya S; Cong, Linlin; Muir, Eric R; Duong, Timothy Q

2016-06-01

Reduced bioavailability of nitric oxide due to impaired endothelial nitric oxide synthase (eNOS) activity is a leading cause of endothelial dysfunction in diabetes. Enhancing eNOS activity in diabetes is a potential therapeutic target. This study investigated basal cerebral blood flow and cerebrovascular reactivity in wild-type mice, diabetic mice (Ins2(Akita+/-)), nondiabetic eNOS-overexpressing mice (TgeNOS), and the cross of two transgenic mice (TgeNOS-Ins2(Akita+/-)) at six months of age. The cross was aimed at improving eNOS expression in diabetic mice. The major findings were: (i) Body weights of Ins2(Akita+/-) and TgeNOS-Ins2(Akita+/-) were significantly different from wild-type and TgeNOS mice. Blood pressure of TgeNOS mice was lower than wild-type. (ii) Basal cerebral blood flow of the TgeNOS group was significantly higher than cerebral blood flow of the other three groups. (iii) The cerebrovascular reactivity in the Ins2(Akita+/-) mice was significantly lower compared with wild-type, whereas that in the TgeNOS-Ins2(Akita+/-) was significantly higher compared with the Ins2(Akita+/-) and TgeNOS groups. Overexpression of eNOS rescued cerebrovascular dysfunction in diabetic animals, resulting in improved cerebrovascular reactivity. These results underscore the possible role of eNOS in vascular dysfunction in the brain of diabetic mice and support the notion that enhancing eNOS activity in diabetes is a potential therapeutic target. © The Author(s) 2015.

Prevalence and Incidence of Myocardial Infarction and Cerebrovascular Accident in Ageing Persons with Intellectual Disability

Science.gov (United States)

Jansen, J.; Rozeboom, W.; Penning, C.; Evenhuis, H. M.

2013-01-01

Background: Epidemiological information on age-related cardiovascular disease in people with intellectual disability (ID) is scarce and inconclusive. We compared prevalence and incidence of cerebrovascular accident and myocardial infarction over age 50 in a residential population with ID to that in a general practice population. Method: Lifetime…

Intraplaque stretch in carotid atherosclerotic plaque--an effective biomechanical predictor for subsequent cerebrovascular ischemic events.

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Zhongzhao Teng

Full Text Available BACKGROUND: Stretch is a mechanical parameter, which has been proposed previously to affect the biological activities in different tissues. This study explored its utility in determining plaque vulnerability. METHODS: One hundred and six patients with mild to moderate carotid stenosis were recruited in this study (53 symptomatic and 53 asymptomatic. High resolution, multi-sequence magnetic resonance (MR imaging was performed to delineate various plaque components. Finite element method was used to predict high stretch concentration within the plaque. RESULTS: During a two-year follow-up, 11 patients in symptomatic group and 3 in asymptomatic group experienced recurrent cerebrovascular events. Plaque stretch at systole and stretch variation during one cardiac cycle was greater in symptomatic group than those in the asymptomatic. Within the symptomatic group, a similar trend was observed in patients with recurrent events compared to those without. CONCLUSION: Plaques with high stretch concentration and large stretch variation are associated with increased risk of future cerebrovascular events.

Trends in Mortality from Cerebrovascular and Hypertensive Diseases in Brazil Between 1980 and 2012

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Paolo Blanco Villela

2016-01-01

Full Text Available Abstract Background: Cerebrovascular and hypertensive diseases are among the main causes of death worldwide. However, there are limited data about the trends of these diseases over the years. Objective: To evaluate the temporal trends in mortality rates and proportional mortality from cerebrovascular and hypertensive diseases according to sex and age in Brazil between 1980 and 2012. Methods: We evaluated the underlying causes of death between 1980 and 2012 in both sexes and by age groups for circulatory diseases (CD, cerebrovascular diseases (CBVD, and hypertensive diseases (HD. We also evaluated death due to all causes (AC, external causes (EC, and ill-defined causes of death (IDCD. Data on deaths and population were obtained from the Department of Information Technology of the Unified Health System (Departamento de Informática do Sistema Único de Saúde, DATASUS/MS. We estimated crude and standardized annual mortality rates per 100,000 inhabitants and percentages of proportional mortality rates. Results: With the exception of EC, the mortality rates per 100,000 inhabitants of all other diseases increased with age. The proportional mortality of CD, CBVD, and HD increased up to the age range of 60-69 years in men and 70-79 years in women, and reached a plateau in both sexes after that. The standardized rates of CD and CBVD declined in both sexes. However, the HD rates showed the opposite trend and increased mildly during the study period. Conclusion: Despite the decline in standardized mortality rates due to CD and CBVD, there was an increase in deaths due to HD, which could be related to factors associated with the completion of the death certificates, decline in IDCD rates, and increase in the prevalence of hypertension.

Cerebral hyperperfusion and decreased cerebrovascular reactivity correlate with neurologic disease severity in MELAS.

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Rodan, L H; Poublanc, J; Fisher, J A; Sobczyk, O; Wong, T; Hlasny, E; Mikulis, D; Tein, I

2015-05-01

To study the mechanisms underlying stroke-like episodes (SLEs) in MELAS syndrome. We performed a case control study in 3 siblings with MELAS syndrome (m.3243A>G tRNA(Leu(UUR))) with variable % mutant mtDNA in blood (35 to 59%) to evaluate regional cerebral blood flow (CBF) and arterial cerebrovascular reactivity (CVR) compared to age- and sex-matched healthy study controls and a healthy control population. Subjects were studied at 3T MRI using arterial spin labeling (ASL) to measure CBF; CVR was measured as a change in % Blood Oxygen Level Dependent signal (as a surrogate of CBF) to repeated 10 mmHg step increase in arterial partial pressure of CO2 (PaCO2). MELAS siblings had decreased CVR (p ≤ 0.002) and increased CBF (p MELAS disease severity and mutation load were inversely correlated with Interictal CVR and directly correlated with frontal CBF. These metrics offer further insight into the cerebrovascular hemodynamics in MELAS syndrome and may serve as noninvasive prognostic markers to stratify risk for SLEs. Class III. Copyright © 2015 © Elsevier B.V. and Mitochondria Research Society. Published by Elsevier B.V. All rights reserved.

[TCD functional test for vertigo induced by ischemic cerebrovascular disorders].

Science.gov (United States)

Li, Q; Zhong, N; Xue, X

1999-04-01

To diagnose differentially the vetigo induced by some ischemic cerebrovascular disorder. Patients with vertebrobasilar artery transient ischemic vertigo (group A), migraine (group B), hyperventilation syndrome (group C), hypertension (group D) are measured by using TCD functional examination which included blood peak velocity of systolic (Vs) and diastolic (Vd) end-period of vertibrobasilar artery of routine TCD (TCD-R), one minute hyperventilation TCD (TCD-HV) and one minute voluntary apnea TCD (TCD-B) respectively. It showed that the Vs, Vd are decreased under the three conditions in A, B and D groups. The most apparent decrease are obversed in D group. The values of the decrease are similar between group A and B. No changes are found in C group. The abnormal Vs incidences of TCD-B measurement in group A are higher than those in group B and C, but significant lower than those in group D; and in TCD-HV test lower than group D and C, higher than group B; in TCD-R test, lower than group D, and no difference with group B and C. The abnormal incidences of Vd in group A are lower than group D and higher than group B in TCD-B test. In TCD-HV test, the group A abnormol incidences are lower than group D but higher than group B and C. In TCD-R test, the abnormal incidences are lower than group D and no difference between group B and C. The TCD measuremen is useful for differential diagnosis of vertigo induced by ischemic cerebrovascular disorders.

The accuracy of prehospital diagnosis of acute cerebrovascular accidents: an observational study

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Karli?ski, Micha?; Gluszkiewicz, Marcin; Cz?onkowska, Anna

2015-01-01

Introduction Time to treatment is the key factor in stroke care. Although the initial medical assessment is usually made by a non-neurologist or a paramedic, it should ensure correct identification of all acute cerebrovascular accidents (CVAs). Our aim was to evaluate the accuracy of the physician-made prehospital diagnosis of acute CVA in patients referred directly to the neurological emergency department (ED), and to identify conditions mimicking CVAs. Material and methods This observationa...

Biodiesel exhaust-induced cytotoxicity and proinflammatory mediator production in human airway epithelial cells.

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Mullins, Benjamin J; Kicic, Anthony; Ling, Kak-Ming; Mead-Hunter, Ryan; Larcombe, Alexander N

2016-01-01

Increasing use of biodiesel has prompted research into the potential health effects of biodiesel exhaust exposure. Few studies directly compare the health consequences of mineral diesel, biodiesel, or blend exhaust exposures. Here, we exposed human epithelial cell cultures to diluted exhaust generated by the combustion of Australian ultralow-sulfur-diesel (ULSD), unprocessed canola oil, 100% canola biodiesel (B100), and a blend of 20% canola biodiesel mixed with 80% ULSD. The physicochemical characteristics of the exhaust were assessed and we compared cellular viability, apoptosis, and levels of interleukin (IL)-6, IL-8, and Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) in exposed cultured cells. Different fuel types produced significantly different amounts of exhaust gases and different particle characteristics. All exposures resulted in significant apoptosis and loss of viability when compared with control, with an increasing proportion of biodiesel being correlated with a decrease in viability. In most cases, exposure to exhaust resulted in an increase in mediator production, with the greatest increases most often in response to B100. Exposure to pure canola oil (PCO) exhaust did not increase mediator production, but resulted in a significant decrease in IL-8 and RANTES in some cases. Our results show that canola biodiesel exhaust exposure elicits inflammation and reduces viability of human epithelial cell cultures in vitro when compared with ULSD exhaust exposure. This may be related to an increase in particle surface area and number in B100 exhaust when compared with ULSD exhaust. Exposure to PCO exhaust elicited the greatest loss of cellular viability, but virtually no inflammatory response, likely due to an overall increase in average particle size. © 2014 Wiley Periodicals, Inc.

Clinical study on magnetic resonance imaging of lacunar infarcts and cerebrovascular high-risk group

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Hironaka, Masatoshi (Hiroshima Univ. (Japan). School of Medicine)

1990-04-01

Magnetic resonance imaging (MRI) study was performed in 32 patients with recent lacunar stroke. T2-weighted images showed ischemic lesions more clearly than T1-weighted images. Sixty-six percent of 32 patients had periventricular lesions. Eighty-four percent had subcortical white matter lesions. Sixty-nine percent had lesions in basal ganglia. Twenty-eight percent had lesions in brainstem. Periventricular lesions were revealed symmetrically. On the other hand, lesions in other areas were not detected symmetrically. Severe periventricular lesions on MRI were similar to those of Binswanger's disease. Patients with severe periventricular lesions had often hypertension. Moreover, two of them had dementia. Twenty-three patients with transient ischemic attack had less remarkable lesions than patients with lacunar stroke. Thirty-seven patients with a history of cerebrovascular risk factors (hypertension, diabetes mellitus) had severer lesions compared with normal controls. Sixty-one percent of controls, who had no cerebrovascular symptoms and signs, had MRI lesions. These results suggest that MRI is useful for detection of cerebral ischemic lesions with no associated clinical symptoms or signs. (author).

Incidência de acidente cerebro-vascular embólico na cardiopatia chagásica crônica

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A. Spina-França

1974-09-01

Full Text Available A incidência de acidente vascular cerebral embólico na cardiopatia chagásica crônica foi avaliada a partir de duas séries consecutivas de casos: a primeira compreendendo 63 pacientes com cardiopatia chagásica crônica e, a segunda, 84 pacientes com acidentes cerebrovasculares, 59 dos quais de tipo não hemorrágico. Em relação aos casos de cardiopatia chagásica crônica a incidência de acidente vascular cerebral embólico mostrou-se da ordem de 3,17%; em relação aos acidentes cerebrovasculares, da ordem de 4,76% e quando considerados apenas aqueles de tipo não hemorrágico, da ordem de 6,78%.

The cerebrovascular structure and brain tissue volume: a comparative study between beagle dogs and mongrel dogs

International Nuclear Information System (INIS)

Liu Sheng; Shi Haibin; Hu Weixing; Zu Qingquan; Lu Shanshan; Xu Xiaoquan; Sun Lei; Li Linsun

2011-01-01

Objective: To compare the differences of cerebrovascular structure and brain tissue volume between beagle and mongrel dogs by using angiography and MR scanning. Methods: A total of 40 dogs, including 20 beagle dogs (beagle group) and 20 mongrel dogs (mongrel group), were enrolled in this study. Under general anesthesia, all dogs were examined with cerebral angiography and MR scanning. The cerebrovascular structure was evaluated with angiography via selective catheterization of aortic arch, bilateral external cerebral arteries (ECA), maxillary arteries, internal cerebral arteries (ICA) and vertebral arteries separately. The diameters of the ICA, middle cerebral artery (MCA), rostral cerebral artery (RCA), the anastomosis channel ICA and ECA, and basilar artery (BA) were measured at the similar point of each dog. Meanwhile the volumes of the brain tissue were calculated in coronal T2 view of MR scanning. The statistical analysis was performed among the weight of dogs, the diameter of arteries and the volume of brain tissue. The differences in the diameters and brain tissue volume were compared between the two groups. Results: No obvious variations in the cerebrovascular structure and brain tissue volume were found in these dogs. One mongrel dog was excluded from this study because of the severe stenosis of ICA. The mean weight of 20 beagle dogs and 19 mongrel dogs was (12.81±1.29) kg and (12.85±1.12) kg, respectively. The diameters of the ICA, MCA, RCA, the anastomosis channel between ICA and ECA and BA in beagle group were (1.26±0.07) mm, (0.90±0.05) mm, (0.58±0.07) mm, (0.55±0.07) mm and (0.95±0.06) mm, respectively. These parameters in mongrel group were (1.27±0.07) mm, (0.92±0.05) mm, (0.59±0.06) mm, (0.67±0.07) mm and (0.94±0.05) mm, respectively. The volume of brain in two groups was (76232.33±5018.51) mm 3 and (71863.96±4626.87) mm 3 , respectively. There were no obvious correlation among the body weight, the cerebrovascular diameters and brain

Epidermal Growth Factor Receptor Signaling Enhances the Proinflammatory Effects of Staphylococcus aureus Gamma-Toxin on the Mucosa.

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Gillman, Aaron N; Breshears, Laura M; Kistler, Charles K; Finnegan, Patrick M; Torres, Victor J; Schlievert, Patrick M; Peterson, Marnie L

2017-06-28

Staphylococcus aureus ( S. aureus ) produces many different exotoxins including the gamma-toxins, HlgAB and HlgCB. Gamma-toxins form pores in both leukocyte and erythrocyte membranes, resulting in cell lysis. The genes encoding gamma-toxins are present in most strains of S. aureus, and are commonly expressed in clinical isolates recovered from menstrual Toxic Shock Syndrome (mTSS) patients. This study set out to investigate the cytotoxic and proinflammatory effects of gamma-toxins on vaginal epithelial surfaces. We found that both HlgAB and HlgCB were cytotoxic to cultured human vaginal epithelial cells (HVECs) and induced cytokine production at sub-cytotoxic doses. Cytokine production induced by gamma-toxin treatment of HVECs was found to involve epidermal growth factor receptor (EGFR) signaling and mediated by shedding of EGFR ligands from the cell surface. The gamma-toxin subunits displayed differential binding to HVECs (HlgA 93%, HlgB 97% and HlgC 28%) with both components (HlgAB or HlgCB) required for maximum detectable binding and significant stimulation of cytokine production. In studies using full thickness ex vivo porcine vaginal mucosa, HlgAB or HlgCB stimulated a dose-dependent cytokine response, which was reduced significantly by inhibition of EGFR signaling. The effects of gamma-toxins on porcine vaginal tissue and cultured HVECs were validated using ex vivo human ectocervical tissue. Collectively, these studies have identified the EGFR-signaling pathway as a key component in gamma-toxin-induced proinflammatory changes at epithelial surfaces and highlight a potential therapeutic target to diminish toxigenic effects of S. aureus infections.

Crossed cerebellar atrophy in cases with cerebrovascular disease

International Nuclear Information System (INIS)

Yagishita, Toshiyuki; Kojima, Shigeyuki; Hirayama, Keizo; Iwabuchi, Sadamu.

1989-01-01

Crossed cerebellar atrophy (CCA) was investigated by X-ray CT to establish the incidence, mechanism, and the relation to cerebral lesions in 130 cases of unilateral supratentorial cerebrovascular diseases. The 130 cases consisted of 83 males and 47 females with cerebral infarction (65 cases) and cerebral hemorrhage (65 cases). The patients' average age was 57.6 years. Crossed cerebellar atrophy was demonstrated in 8 cases (6.2%), 6 of whom had massive cerebral infarction in the middle cerebral artery area (9.2% of the 65 cases of cerebral infarction. The six cases of CCA caused by cerebral infarction had lesions in the frontal and temporal lobes. Two had a cerebral hemorrhage in the putamen and in the thalamus, respectively, accounting for 3.1% of the 65 cases of cerebral hemorrhage. Of the 2 cases, one had putaminal hemorrhage, and the other had thalamic hemorrhage. Cerebrovascular stroke had occured in these patients with CCA more than 2 months previously. In 5 of the 8 cases of CCA, atrophy was present in the basis pedunculi and the basis pontis on the side of the cerebral lesion. However, neither dilation nor deformity of the fourth ventricle was present in any of the patients, suggesting that none of the CCA patients had atrophy of the dentate nucleus. The CCA patients had massive cerebral lesion in the frontal and temporal lobes or atrophy of the basis pedunculi and basis pontis, suggesting the presence of the transsynaptic degeneration of the cortico-ponto-cerebellar pathway. In the case of the thalamic hemorrhage, who had not hemorrhagic lesion in the frontal and temporal lobes, atrophy of the basis peduncli and basis pontis was not observed. Though dilation or deformity of the fourth ventricle is not observed in this case, presence of the degeneration of the dentate-rubro-thalamic pathway cannot be denied. CCA seems to be caused by both the transsynaptic degeneration of the cortico-ponto-cerebellar pathway and the dentate-rubro-thalamic pathway. (J.P.N.)

P2Y6 receptor potentiates pro-inflammatory responses in macrophages and exhibits differential roles in atherosclerotic lesion development.

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Ricardo A Garcia

Full Text Available BACKGROUND: P2Y(6, a purinergic receptor for UDP, is enriched in atherosclerotic lesions and is implicated in pro-inflammatory responses of key vascular cell types and macrophages. Evidence for its involvement in atherogenesis, however, has been lacking. Here we use cell-based studies and three murine models of atherogenesis to evaluate the impact of P2Y(6 deficiency on atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: Cell-based studies in 1321N1 astrocytoma cells, which lack functional P2Y(6 receptors, showed that exogenous expression of P2Y(6 induces a robust, receptor- and agonist-dependent secretion of inflammatory mediators IL-8, IL-6, MCP-1 and GRO1. P2Y(6-mediated inflammatory responses were also observed, albeit to a lesser extent, in macrophages endogenously expressing P2Y(6 and in acute peritonitis models of inflammation. To evaluate the role of P2Y(6 in atherosclerotic lesion development, we used P2Y(6-deficient mice in three mouse models of atherosclerosis. A 43% reduction in aortic arch plaque was observed in high fat-fed LDLR knockout mice lacking P2Y(6 receptors in bone marrow-derived cells. In contrast, no effect on lesion development was observed in fat-fed whole body P2Y(6xLDLR double knockout mice. Interestingly, in a model of enhanced vascular inflammation using angiotensin II, P2Y(6 deficiency enhanced formation of aneurysms and exhibited a trend towards increased atherosclerosis in the aorta of LDLR knockout mice. CONCLUSIONS: P2Y(6 receptor augments pro-inflammatory responses in macrophages and exhibits a pro-atherogenic role in hematopoietic cells. However, the overall impact of whole body P2Y(6 deficiency on atherosclerosis appears to be modest and could reflect additional roles of P2Y(6 in vascular disease pathophysiologies, such as aneurysm formation.

The role of Ca(2+) mediated signaling pathways on the effect of taurine against Streptococcus uberis infection.

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Dai, Bin; Zhang, Jinqiu; Liu, Ming; Lu, Jinye; Zhang, Yuanshu; Xu, Yuanyuan; Miao, Jinfeng; Yin, Yulong

2016-08-30

To provide insight into the mechanisms of taurine attenuation of pro-inflammatory response in mouse mammary epithelial cell line (EpH4-Ev, purchased by ATCC, USA) after Streptococcus uberis (S. uberis, 0140J) challenge, we infected MECs with S. uberis (2.5×10(7)cfumL(-1), MOI=10) for 3h and quantified changes in TLR-2 and calcium (Ca(2+)) mediated signaling pathways. The results indicate that S. uberis infection significantly increases the expression of TLR-2, intracellular Ca(2+) levels, PLC-γ1 and PKC-α, the activities of transcription factors NF-κB and NFAT, and related cytokines (TNF-α, IL-1β, IL-6, G-CSF, IL-2, KC, IL-15, FasL, MCP-1, and LIX) in culture supernatants. Taurine administration downregulated all these indices, the activities of NF-κB and NFAT. Cytokine secretions were similar using special PKC inhibitor Go 6983 and NFAT inhibitor VIVIT. Our data indicate that S. uberis infection induces pro-inflammatory response of MECs through a TLR-2 mediated signaling pathway. In addition, taurine can prevent MEC damage by affecting both PLC-γ1-Ca(2+)-PKC-α-NF-κB and PLC-γ1-Ca(2+)-NFATs signaling pathways. This is the first report to demonstrate the mechanisms of taurine attenuated pro-inflammatory response in MECs after S. uberis challenge. Copyright © 2016 Elsevier B.V. All rights reserved.

Chitosan drives anti-inflammatory macrophage polarisation and pro-inflammatory dendritic cell stimulation

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MI Oliveira

2012-07-01

Full Text Available Macrophages and dendritic cells (DC share the same precursor and play key roles in immunity. Modulation of their behaviour to achieve an optimal host response towards an implanted device is still a challenge. Here we compare the differentiation process and polarisation of these related cell populations and show that they exhibit different responses to chitosan (Ch, with human monocyte-derived macrophages polarising towards an anti-inflammatory phenotype while their DC counterparts display pro-inflammatory features. Macrophages and DC, whose interactions with biomaterials are frequently analysed using fully differentiated cells, were cultured directly on Ch films, rather than exposed to the polymer after complete differentiation. Ch was the sole stimulating factor and activated both macrophages and DC, without leading to significant T cell proliferation. After 10 d on Ch, macrophages significantly down-regulated expression of pro-inflammatory markers, CD86 and MHCII. Production of pro-inflammatory cytokines, particularly TNF-α, decreased with time for cells cultured on Ch, while anti-inflammatory IL-10 and TGF-β1, significantly increased. Altogether, these results suggest an M2c polarisation. Also, macrophage matrix metalloproteinase activity was augmented and cell motility was stimulated by Ch. Conversely, DC significantly enhanced CD86 expression, reduced IL-10 secretion and increased TNF-α and IL-1β levels. Our findings indicate that cells with a common precursor may display different responses, when challenged by the same biomaterial. Moreover, they help to further comprehend macrophage/DC interactions with Ch and the balance between pro- and anti-inflammatory signals associated with implant biomaterials. We propose that an overall pro-inflammatory reaction may hide the expression of anti-inflammatory cytokines, likely relevant for tissue repair/regeneration.

Subjective and objective knowledge and decisional role preferences in cerebrovascular patients compared to controls

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Riechel C

2016-08-01

Full Text Available Christina Riechel,1,* Anna Christina Alegiani,1,* Sascha Köpke,2 Jürgen Kasper,3,4 Michael Rosenkranz,1,5 Götz Thomalla,1 Christoph Heesen1,4 1Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 2Nursing Research Unit, Institute of Social Medicine and Epidemiology, University of Lübeck, Lübeck, Germany; 3Department of Health and Caring Sciences, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway; 4Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 5Department of Neurology, Albertinen-Krankenhaus, Hamburg, Germany *These authors contributed equally to this work Background: Risk knowledge and active role preferences are important for patient involvement in treatment decision-making and adherence. Although knowledge about stroke warning signs and risk factors has received considerable attention, objective knowledge on secondary prevention and further self-esteem subjective knowledge have rarely been studied. The aim of our study was to investigate knowledge and treatment decisional role preferences in cerebrovascular patients compared to controls. Methods: We performed a survey on subjective and objective stroke risk knowledge and autonomy preferences in cerebrovascular patients from our stroke outpatient clinic (n=262 and from pedestrians on the street taken as controls during a “World Stroke Day” (n=274. The questionnaire includes measures for knowledge and decisional role preferences from previously published questionnaires and newly developed measures, for example, subjective knowledge, revealed on a visual analog scale. Results: The overall stroke knowledge was low to moderate, with no differences between patients and controls. Knowledge about secondary prevention was particularly low. Only 10%–15% of participants correctly estimated the stroke absolute risk reduction potential of aspirin. The medical data

Brachial and Cerebrovascular Functions Are Enhanced in Postmenopausal Women after Ingestion of Chocolate with a High Concentration of Cocoa.

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Marsh, Channa E; Carter, Howard H; Guelfi, Kym J; Smith, Kurt J; Pike, Kerryn E; Naylor, Louise H; Green, Daniel J

2017-09-01

Background: Cocoa contains polyphenols that are thought to be beneficial for vascular health. Objective: We assessed the impact of chocolate containing distinct concentrations of cocoa on cerebrovascular function and cognition. Methods: Using a counterbalanced within-subject design, we compared the acute impact of consumption of energy-matched chocolate containing 80%, 35%, and 0% single-origin cacao on vascular endothelial function, cognition, and cerebrovascular function in 12 healthy postmenopausal women (mean ± SD age: 57.3 ± 5.3 y). Participants attended a familiarization session, followed by 3 experimental trials, each separated by 1 wk. Outcome measures included cerebral blood flow velocity (CBF v ) responses, recorded before and during completion of a computerized cognitive assessment battery (CogState); brachial artery flow-mediated dilation (FMD); and hemodynamic responses (heart rate and blood pressure). Results: When CBF v data before and after chocolate intake were compared between conditions through the use of 2-factor ANOVA, an interaction effect ( P = 0.003) and main effects for chocolate ( P = 0.043) and time ( P = 0.001) were evident. Post hoc analysis revealed that both milk chocolate (MC; 35% cocoa; P = 0.02) and dark chocolate (DC; 80% cocoa; P = 0.003) induced significantly lower cerebral blood flow responses during the cognitive tasks, after normalizing for changes in arterial pressure. DC consumption also increased brachial FMD compared with the baseline value before chocolate consumption ( P = 0.002), whereas MC and white chocolate (0% cocoa) caused no change ( P- interaction between conditions = 0.034). Conclusions: Consumption of chocolate containing high concentrations of cocoa enhanced vascular endothelial function, which was reflected by improvements in FMD. Cognitive function outcomes did not differ between conditions; however, cerebral blood flow responses during these cognitive tasks were lower in those consuming MC and DC. These

Apoptotic effects of antilymphocyte globulins on human pro-inflammatory CD4+CD28- T-cells.

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Christina Duftner

Full Text Available BACKGROUND: Pro-inflammatory, cytotoxic CD4(+CD28(- T-cells with known defects in apoptosis have been investigated as markers of premature immuno-senescence in various immune-mediated diseases. In this study we evaluated the influence of polyclonal antilymphocyte globulins (ATG-Fresenius, ATG-F on CD4(+CD28(- T-cells in vivo and in vitro. PRINCIPAL FINDINGS: Surface and intracellular three colour fluorescence activated cell sorting analyses of peripheral blood mononuclear cells from 16 consecutive transplant recipients and short-term cell lines were performed. In vivo, peripheral levels of CD3(+CD4(+CD28(- T-cells decreased from 3.7 ± 7.1% before to 0 ± 0% six hours after ATG-F application (P = 0.043 in 5 ATG-F treated but not in 11 control patients (2.9 ± 2.9% vs. 3.9 ± 3.0%. In vitro, ATG-F induced apoptosis even in CD4(+CD28(- T-cells, which was 4.3-times higher than in CD4(+CD28(+ T-cells. ATG-F evoked apoptosis was partially reversed by the broad-spectrum caspase inhibitor benzyloxycarbonyl (Cbz-Val-Ala-Asp(OMe-fluoromethylketone (zVAD-fmk and prednisolon-21-hydrogensuccinate. ATG-F triggered CD25 expression and production of pro-inflammatory cytokines, and induced down-regulation of the type 1 chemokine receptors CXCR-3, CCR-5, CX3CR-1 and the central memory adhesion molecule CD62L predominately in CD4(+CD28(- T-cells. CONCLUSION: In summary, in vivo depletion of peripheral CD3(+CD4(+CD28(- T-cells by ATG-F in transplant recipients was paralleled in vitro by ATG-F induced apoptosis. CD25 expression and chemokine receptor down-regulation in CD4(+CD28(- T-cells only partly explain the underlying mechanism.

Impact of vessel wall lesions and vascular stenoses on cerebrovascular reactivity in patients with intracranial stenotic disease

NARCIS (Netherlands)

Cogswell, Petrice M; Davis, Taylor L; Strother, Megan K; Faraco, Carlos C; Scott, Allison O; Jordan, Lori C; Fusco, Matthew R; Frederick, Blaise deB; Hendrikse, Jeroen; Donahue, Manus J

2017-01-01

PURPOSE: To compare cerebrovascular reactivity (CVR) and CVR lagtimes in flow territories perfused by vessels with vs. without proximal arterial wall disease and/or stenosis, separately in patients with atherosclerotic and nonatherosclerotic (moyamoya) intracranial stenosis. MATERIALS AND METHODS:

Targeting Cellular Calcium Homeostasis to Prevent Cytokine-Mediated Beta Cell Death.

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Clark, Amy L; Kanekura, Kohsuke; Lavagnino, Zeno; Spears, Larry D; Abreu, Damien; Mahadevan, Jana; Yagi, Takuya; Semenkovich, Clay F; Piston, David W; Urano, Fumihiko

2017-07-17

Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets. These agents are also able to restore cytokine-mediated suppression of functional ER calcium release. In addition, sitagliptin preserves function of the ER calcium pump, sarco-endoplasmic reticulum Ca 2+ -ATPase (SERCA), and decreases levels of the pro-apoptotic protein thioredoxin-interacting protein (TXNIP). Supporting the role of TXNIP in cytokine-mediated cell death, knock down of TXNIP in INS1-E cells prevents cytokine-mediated beta cell death. Our findings demonstrate that modulation of dynamic cellular calcium homeostasis and TXNIP suppression present viable pharmacologic targets to prevent cytokine-mediated beta cell loss in diabetes.

Herpesviruses viral loads and levels of proinflammatory cytokines in apical periodontitis.

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Jakovljevic, A; Knezevic, A; Nikolic, N; Soldatovic, I; Jovanovic, T; Milasin, J; Andric, M

2018-07-01

This study aimed to analyse Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) viral loads in symptomatic and asymptomatic apical periodontitis lesions, to determine levels of TNF-α, IL-1β and IL-6 in these lesions and to investigate a possible correlation between herpesviral copy numbers and levels of proinflammatory cytokines. A total of 100 samples of apical periodontitis were subjected to HCMV and EBV copy numbers analysis by nested polymerase chain reaction (PCR) and TaqMan real-time PCR. The concentrations of TNF-α, IL-1β and IL-6 were determined by ELISA method. SPSS software was used for statistical analysis. There were no significant differences in the occurrence of EBV and HCMV between symptomatic and asymptomatic periapical lesions (p = .686, p = .879, respectively). Only 12 of 74 EBV (16.2%) and four of 54 HCMV (13.5%) nested PCR-positive samples showed increased viral copy numbers above the limit of 125 copies/ml. There was no significant correlation between the levels of analysed proinflammatory cytokines and herpesviral copy numbers in our sample. The observed low viral loads point to a relatively rare occurrence of active EBV and HCMV infection in our sample. Latent herpesviral infection does not enhance the production of investigated proinflammatory cytokines. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

Changes in proinflammatory cytokines and white matter in chronically stressed rats

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Yang P

2015-03-01

Full Text Available Ping Yang,1 Zhenyong Gao,1 Handi Zhang,1 Zeman Fang,1 Cairu Wu,1 Haiyun Xu,1,2 Qing-Jun Huang1 1Mental Health Center, 2Department of Anatomy, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China Abstract: Although the pathogenesis of depression, an incapacitating psychiatric ailment, remains largely unknown, previous human and animal studies have suggested that both proinflammatory cytokines and altered oligodendrocytes play important roles in the condition. This study examined these two factors in the brains of rats following unpredictable chronic mild stress for 4 weeks, with the hypothesis that chronic stress may affect oligodendrocytes and elevate proinflammatory cytokines in the brain. After suffering unpredictable stressors for 4 weeks, the rats showed depression-like behaviors, including decreased locomotion in the open field, increased immobility time in the forced swim test, and decreased sucrose consumption and less sucrose preference when compared with controls. Immunohistochemical staining of brain sections showed higher immunoreactivity of proinflammatory cytokines in certain brain regions of stressed rats compared with controls; lower immunoreactivity of myelin basic protein and fewer mature oligodendrocytes were seen in the prefrontal cortex, but no demyelination was detected. These results are interpreted and discussed in the context of recent findings from human and animal studies. Keywords: cytokines, depression, myelination, oligodendrocytes, stress 

Adherent Human Alveolar Macrophages Exhibit a Transient Pro-Inflammatory Profile That Confounds Responses to Innate Immune Stimulation

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Tomlinson, Gillian S.; Booth, Helen; Petit, Sarah J.; Potton, Elspeth; Towers, Greg J.; Miller, Robert F.; Chain, Benjamin M.; Noursadeghi, Mahdad

2012-01-01

Alveolar macrophages (AM) are thought to have a key role in the immunopathogenesis of respiratory diseases. We sought to test the hypothesis that human AM exhibit an anti-inflammatory bias by making genome-wide comparisons with monocyte derived macrophages (MDM). Adherent AM obtained by bronchoalveolar lavage of patients under investigation for haemoptysis, but found to have no respiratory pathology, were compared to MDM from healthy volunteers by whole genome transcriptional profiling before and after innate immune stimulation. We found that freshly isolated AM exhibited a marked pro-inflammatory transcriptional signature. High levels of basal pro-inflammatory gene expression gave the impression of attenuated responses to lipopolysaccharide (LPS) and the RNA analogue, poly IC, but in rested cells pro-inflammatory gene expression declined and transcriptional responsiveness to these stimuli was restored. In comparison to MDM, both freshly isolated and rested AM showed upregulation of MHC class II molecules. In most experimental paradigms ex vivo adherent AM are used immediately after isolation. Therefore, the confounding effects of their pro-inflammatory profile at baseline need careful consideration. Moreover, despite the prevailing view that AM have an anti-inflammatory bias, our data clearly show that they can adopt a striking pro-inflammatory phenotype, and may have greater capacity for presentation of exogenous antigens than MDM. PMID:22768282

Listeria monocytogenes alters mast cell phenotype, mediator and osteopontin secretion in a listeriolysin-dependent manner.

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Catherine E Jobbings

Full Text Available Whilst mast cells participate in the immune defence against the intracellular bacterium Listeria monocytogenes, there is conflicting evidence regarding the ability of L. monocytogenes to infect mast cells. It is known that the pore-forming toxin listeriolysin (LLO is important for mast cell activation, degranulation and the release of pro-inflammatory cytokines. Mast cells, however, are a potential source of a wide range of cytokines, chemokines and other mediators including osteopontin, which contributes to the clearing of L. monocytogenes infections in vivo, although its source is unknown. We therefore aimed to resolve the controversy of mast cell infection by L. monocytogenes and investigated the extent of mediator release in response to the bacterium. In this paper we show that the infection of bone marrow-derived mast cells by L. monocytogenes is inefficient and LLO-independent. LLO, however, is required for calcium-independent mast cell degranulation as well as for the transient and selective downregulation of cell surface CD117 (c-kit on mast cells. We demonstrate that in addition to the key pro-inflammatory cytokines TNF-α and IL-6, mast cells release a wide range of other mediators in response to L. monocytogenes. Osteopontin, IL-2, IL-4, IL-13 and granulocyte macrophage colony-stimulating factor (GM-CSF, and chemokines including CCL2, CCL3, CCL4 and CCL5 are released in a MyD88-dependent manner. The wide range of mediators released by mast cells in response to L. monocytogenes may play an important role in the recruitment and activation of a variety of immune cells in vivo. The cocktail of mediators, however, is unlikely to skew the immune response to a particular effector response. We propose that mast cells provide a hitherto unreported source of osteopontin, and may provide an important role in co-ordinating the immune response during Listeria infection.

Significant Improvement Selected Mediators of Inflammation in Phenotypes of Women with PCOS after Reduction and Low GI Diet

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Małgorzata Szczuko

2017-01-01

Full Text Available Many researchers suggest an increased risk of atherosclerosis in women with polycystic ovary syndrome. In the available literature, there are no studies on the mediators of inflammation in women with PCOS, especially after dietary intervention. Eicosanoids (HETE and HODE were compared between the biochemical phenotypes of women with PCOS (normal and high androgens and after the 3-month reduction diet. Eicosanoid profiles (9(S-HODE, 13(S-HODE, 5(S-HETE, 12(S-HETE, 15(S-HETE, 5(S-oxoETE, 16(R-HETE, 16(S-HETE and 5(S, 6(R-lipoxin A4, 5(S, 6(R, 15(R-lipoxin A4 were extracted from 0.5 ml of plasma using solid-phase extraction RP-18 SPE columns. The HPLC separations were performed on a 1260 liquid chromatograph. No significant differences were found in the concentration of analysed eicosanoids in phenotypes of women with PCOS. These women, however, have significantly lower concentration of inflammatory mediators than potentially healthy women from the control group. Dietary intervention leads to a significant (p<0.01 increase in the synthesis of proinflammatory mediators, reaching similar levels as in the control group. The development of inflammatory reaction in both phenotypes of women with PCOS is similar. The pathways for synthesis of proinflammatory mediators in women with PCOS are dormant, but can be stimulated through a reduction diet. Three-month period of lifestyle change may be too short to stimulate the pathways inhibiting inflammatory process.

Metabolic Syndrome and Cardio-Cerebrovascular Risk Disparities Between Pilots and Aircraft Mechanics.

Science.gov (United States)

Kim, Myeong-Bo; Kim, Hyun-Jin; Kim, Soo-Hyeon; Lee, Suk-Ho; Lee, Se-Ho; Park, Won-Ju

2017-09-01

In the Republic of Korea Air Force, the health of pilots is strictly supervised, but there is comparatively not enough interest in aircraft mechanics' health. Among mechanics, who are heavily involved in military aircraft maintenance, the occurrence of sudden cardio-cerebrovascular diseases (CCVDs) is a possible risk factor during the maintenance process, which should be performed perfectly. We performed health examinations on 2123 male aircraft pilots and 1271 aircraft mechanics over 30 yr of age and determined the prevalence of metabolic syndrome (MetS), an important risk factor for CCVDs. The prevalence of MetS in the aircraft mechanics (21.3%) was significantly higher than in the pilots (12.6%), and the gap in prevalence tended to grow as age increased. Among aircraft mechanics in their 30s and 40s, the prevalence of MetS was lower than in the general population. However, the prevalence of MetS among aircraft mechanics in their 50s (36.0%) was similar to that in the general population (35.7%). Systematic health management is needed for aircraft mechanics for aviation safety and for the maintenance of military strength via the prevention of CCVDs.Kim M-B, Kim H-J, Kim S-H, Lee S-H, Lee S-H, Park W-J. Metabolic syndrome and cardio-cerebrovascular risk disparities between pilots and aircraft mechanics. Aerosp Med Hum Perform. 2017; 88(9):866-870.

Risk of cerebrovascular events in persons with and without HIV: A Danish nationwide population-based cohort study

DEFF Research Database (Denmark)

Rasmussen, Line D; Engsig, Frederik Neess; Christensen, Hanne

2011-01-01

OBJECTIVE:: To assess the risk of cerebrovascular events (CVE) in HIV-infected individuals and evaluate the impact of proven risk factors, injection drug abuse (IDU), immunodeficiency, highly active antiretroviral therapy (HAART) and family-related risk factors. DESIGN:: Nationwide, population...

The relationship between cerebrovascular complications and previously established use of antiplatelet therapy in left-sided infective endocarditis

DEFF Research Database (Denmark)

Snygg-Martin, Ulrika; Rasmussen, Rasmus Vedby; Hassager, Christian

2011-01-01

Cerebrovascular complications (CVC) in infective endocarditis (IE) are common. The only established treatments to reduce the incidence of CVC in IE are antibiotics and in selected cases early cardiac surgery. Potential effects of previously established antiplatelet therapy are under debate....

Comparison of carotid and cerebrovascular disease between diabetic and non-diabetic patients using dual-source CT

International Nuclear Information System (INIS)

He Ci; Yang Zhigang; Chu Zhigang; Dong Zhihui; Li Yunming; Shao Heng; Deng Wen

2011-01-01

Purpose: To clarify the differences of the carotid and cerebrovascular disease between patients with and without type 2 diabetes using dual-source CT angiography. Materials and methods: Dual-source CT angiography of the carotid and cerebrovascular arteries was performed in 79 type 2 diabetic patients and 207 non-diabetic patients. The type, extent and distribution of plaques, and luminal stenosis were compared. Results: Compared with non-diabetic patients, diabetic patients had a higher overall incidence of plaque (p 0.05), as well as for the number of diseased segments and the distribution of plaques; both mainly involved the bilateral cavernous segment of the internal carotid artery. As for the stenosis, non-obstructive lesions were more common in diabetic patients (p 0.05). Conclusion: Diabetes is associated with a higher incidence of plaque and non-obstructive stenosis. However, no significant differences were observed in the type, extent and distribution of involved plaques between diabetic and non-diabetic patients.

Autoantibodies Targeting AT1 Receptor from Patients with Acute Coronary Syndrome Upregulate Proinflammatory Cytokines Expression in Endothelial Cells Involving NF-κB Pathway

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Weijuan Li

2014-01-01

Full Text Available Our study intended to prove whether agonistic autoantibodies to angiotensin II type 1 receptor (AT1-AAs exist in patients with coronary heart disease (CHD and affect the human endothelial cell (HEC by upregulating proinflammatory cytokines expression involved in NF-κB pathway. Antibodies were determined by chronotropic responses of cultured neonatal rat cardiomyocytes coupled with receptor-specific antagonists (valsartan and AT1-EC2 as described previously. Interleukin-6 (IL-6, vascular cell adhesion molecule-1 (VCAM-1, and monocyte chemotactic protein-1 (MCP-1 expression were improved at both mRNA and protein levels in HEC, while NF-κB in the DNA level was improved detected by electrophoretic mobility shift assays (EMSA. These improvements could be inhibited by specific AT1 receptor blocker valsartan, NF-κB blocker pyrrolidine dithiocarbamate (PDTC, and specific short peptides from the second extracellular loop of AT1 receptor. These results suggested that AT1-AAs, via the AT1 receptor, induce expression of proinflammatory cytokines involved in the activation of NF-κB. AT1-AAs may play a great role in the pathogenesis of the acute coronary syndrome by mediating vascular inflammatory effects involved in the NF-κB pathway.

[Cerebrovascular mortality in Portugal: are we overemphasizing hypertension and neglecting atrial fibrillation?].

Science.gov (United States)

Providência, Rui; Gonçalves, Lino; Ferreira, Maria João

2013-11-01

Cerebrovascular disease has long been the leading cause of death in Portugal. Despite improvements in the treatment of hypertension and the resulting decrease in associated mortality, the progressive aging of the population and increased prevalence of atrial fibrillation have prevented the incidence of stroke from falling as much as desired. The authors review the evidence on the situation in Portugal and propose an intervention plan. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Methylenetetrahydrofolate reductase gene polymorphism is not related to the risk of ischemic cerebrovascular disease in a Brazilian population Polimorfismo no gene de metilenetetrahidrofolato redutase não está relacionado com o risco de doença cerebrovascular isquêmica em uma população brasileira

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Samuel Katsuyuki Shinjo

2007-01-01

Full Text Available PURPOSE: Data are conflicting concerning the risk for ischemic stroke associated with a common polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase C677T, which predisposes carriers to hyperhomocysteinemia. A meta-analysis study suggested that the 5,10-methylenetetrahydrofolate reductase 677TT genotype might have a small influence in determining susceptibility to ischemic stroke. METHODS: We analyzed the 5,10-methylenetetrahydrofolate reductase 677TT genotype polymorphism in Brazilian subjects with ischemic stroke, using a case-control design. RESULTS: We compared 5,10-methylenetetrahydrofolate reductase genotypes in groups of subjects presenting ischemic stroke (n = 127 and normal control (n = 126 and found an odds ratio of 1.97 (95% CI, 0.84-4.64 in a multivariate analysis in which results were adjusted to baseline clinical characteristics of study participants. CONCLUSION: We found that the homozygous 5,10-methylenetetrahydrofolate reductase C677T genotype was not a risk factor for ischemic stroke in these Brazilian subjects.OBJETIVO: Os dados são conflitantes em relação a risco de acidente cerebrovascular associado a polimorfismo do gene 5,10-metilenetetrahidrofolato redutase C677T, o qual predispõe a hiperhomocisteinemia. Um estudo de meta-análise sugere que o genotipo 5,10-metilenetetrahidrofolato redutase 677TT poderia ter uma pequena influência em determinar susceptibilidade a acidente cerebrovascular. MÉTODOS: Analisamos este polimorfismo em indivíduos brasileiros com acidente cerebrovascular isquêmico, baseando-se em um estudo de caso-controle. RESULTADOS: Comparamos os genótipos 5,10-metilenetetrahidrofolato redutase em grupos de indivíduos com acidente cerebrovascular isquêmico (n=127 e controle normal (n=126, e encontramos Odds Ratio de 1,97 (IC 95% 0,84 - 4,64 em uma análise multivariada, na qual os resultados foram ajustados a características clínicas basais dos indivíduos estudados. DISCUSS�

Importance of variants in cerebrovascular anatomy for potential retrograde embolization in cryptogenic stroke

International Nuclear Information System (INIS)

Markl, Michael; Semaan, Edouard; Carr, James; Collins, Jeremy; Stromberg, LeRoy; Prabhakaran, Shyam

2017-01-01

To test the hypothesis that variants in cerebrovascular anatomy will affect the number of patients demonstrating a plausible retrograde embolization mechanism from plaques in the descending aorta (DAo). Thirty-five patients (aged 63 ± 17 years) with cryptogenic stroke underwent 4D flow MRI for the assessment of aortic 3D blood flow and MR angiography for the evaluation of circle of Willis, posterior circulation, and aortic arch architecture. In patients with proven DAo plaque, retrograde embolization was considered a potential mechanism if retrograde flow extended from the DAo to a supra-aortic vessel supplying the cerebral infarct territory. Retrograde embolization with matching cerebral infarct territory was detected in six (17%) patients. Circle of Willis and aortic arch variant anatomy was found in 60% of patients, leading to reclassification of retrograde embolization risk as present in three (9%) additional patients, for a total 26% of cryptogenic stroke patients. 4D flow MRI demonstrated 26% concordance with infarct location on imaging with retrograde diastolic flow into the feeding vessels of the affected cerebral area, identifying a potential etiology for cryptogenic stroke. Our findings further demonstrate the importance of cerebrovascular anatomy when determining concordance of retrograde flow pathways with vascular stroke territory from DAo plaques. (orig.)

Importance of variants in cerebrovascular anatomy for potential retrograde embolization in cryptogenic stroke

Energy Technology Data Exchange (ETDEWEB)

Markl, Michael [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Northwestern University, Department of Biomedical Engineering, McCormick School of Engineering, Chicago, IL (United States); Semaan, Edouard; Carr, James; Collins, Jeremy [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Stromberg, LeRoy [Northwestern University, Department of Neurology, Feinberg School of Medicine, Chicago, IL (United States); Edward Hospital, Department of Radiology, Naperville, IL (United States); Prabhakaran, Shyam [Northwestern University, Department of Neurology, Feinberg School of Medicine, Chicago, IL (United States)

2017-10-15

To test the hypothesis that variants in cerebrovascular anatomy will affect the number of patients demonstrating a plausible retrograde embolization mechanism from plaques in the descending aorta (DAo). Thirty-five patients (aged 63 ± 17 years) with cryptogenic stroke underwent 4D flow MRI for the assessment of aortic 3D blood flow and MR angiography for the evaluation of circle of Willis, posterior circulation, and aortic arch architecture. In patients with proven DAo plaque, retrograde embolization was considered a potential mechanism if retrograde flow extended from the DAo to a supra-aortic vessel supplying the cerebral infarct territory. Retrograde embolization with matching cerebral infarct territory was detected in six (17%) patients. Circle of Willis and aortic arch variant anatomy was found in 60% of patients, leading to reclassification of retrograde embolization risk as present in three (9%) additional patients, for a total 26% of cryptogenic stroke patients. 4D flow MRI demonstrated 26% concordance with infarct location on imaging with retrograde diastolic flow into the feeding vessels of the affected cerebral area, identifying a potential etiology for cryptogenic stroke. Our findings further demonstrate the importance of cerebrovascular anatomy when determining concordance of retrograde flow pathways with vascular stroke territory from DAo plaques. (orig.)

Osteoprotegerin CGA haplotype protection against cerebrovascular complications in anti-CCP negative patients with rheumatoid arthritis.

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Fernanda Genre

Full Text Available Rheumatoid arthritis is an inflammatory disease with high incidence of cardiovascular disease due to accelerated atherosclerosis. Osteoprotegerin (OPG has been associated with increased risk of atherosclerotic disease in the general population. Several polymorphisms in the OPG gene with functional effects on cardiovascular disease in non-rheumatic individuals have been described. Therefore, we aimed to analyze the effect of three of these functional OPG polymorphisms on the risk of cardiovascular disease in a large and well-characterized cohort of Spanish patients with rheumatoid arthritis.Three OPG gene variants (rs3134063, rs2073618 and rs3134069 were genotyped by TaqMan assays in 2027 Spanish patients with rheumatoid arthritis. Anti-cyclic citrullinated peptide (anti-CCP antibody testing was positive in 997 of 1714 tested. Also, 18.3% of the whole series had experienced cardiovascular events, including 5.4% with cerebrovascular accidents. The relationship between OPG variants and cardiovascular events was assessed using Cox regression.No association between OPG gene variants and cardiovascular disease was observed in the whole group of rheumatoid arthritis patients or in anti-CCP positive patients. Nevertheless, a protective effect of CGA haplotype on the risk of cardiovascular disease in general, and specifically in the risk of cerebrovascular complications after adjusting for sex, age at disease diagnosis and traditional cardiovascular risk factors was disclosed in anti-CCP negative patients (HR = 0.54; 95%CI: 0.31-0.95; p = 0.032 and HR = 0.17; 95%CI: 0.04-0.78; p = 0.022, respectively.Our results indicate a protective effect of the OPG CGA haplotype on cardiovascular risk, mainly due to a protective effect against cerebrovascular events in anti-CCP negative rheumatoid arthritis patients.

Cases similar to the cerebrovascular 'Moyamoya disease'. Investigation by angiography and computed tomography

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Tomura, Noriaki; Inugami, Atsushi; Higano, Shuichi; Fujita, Hideaki; Abe, Toushi; Shishido, Fumio; Uemura, Kazuo

1988-10-01

Findings of cerebral computed tomographies were investigated in 13 patients who did not satisfy the criteria of cerebrovascular Moyamoya disease, but showed the Moyamoya vessels (so-called pseudo-Moyamoya disease). Their ages ranged from 15 to 70 years old. Single patients were diagnosed as having pituitary adenoma after radiation therapy, head trauma, aplastic anemia, and the Rainoud phenomenon, and five as having hypertension. Angiography revealed occlusion and stenosis in the unilateral carotid forks in 7 and 5 patients, respectively. Other appearances included transdural anastomosis via the superficial temporal arteries, the anterior ethmoid arteries, and the collateral pathway from the perforating branches to the cortical branches. Low density areas were seen on CT in 10 patients, seven of whom had multiple areas. Low density areas were seen in the cerebral basal ganglia, watershed zone, and the outer side of the lateral cerebral body, in that order. Four patients had intracranial hemorrhage, subarachnoid hemorrhage, and hemorrhage infarction. Pseudo-Moyamoya disease was sometimes of the incomplete form of the cerebrovascular Moyamoya disease, and attributable to arterial stenosis or constricture due to radiation therapy. (Namekawa, K.).

Social Cognition Deficits: Current Position and Future Directions for Neuropsychological Interventions in Cerebrovascular Disease

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Progress Njomboro

2017-01-01

Full Text Available Neuropsychological assessments of cognitive dysfunction in cerebrovascular illness commonly target basic cognitive functions involving aspects of memory, attention, language, praxis, and number processing. Here, I highlight the clinical importance of often-neglected social cognition functions. These functions recruit a widely distributed neural network, making them vulnerable in most cerebrovascular diseases. Sociocognitive deficits underlie most of the problematic social conduct observed in patients and are associated with more negative clinical outcomes (compared to nonsocial cognitive deficits. In clinical settings, social cognition deficits are normally gleaned from collateral information from caregivers or from indirect inferences made from patients’ performance on standard nonsocial cognitive tests. Information from these sources is however inadequate. I discuss key social cognition functions, focusing initially on deficits in emotion perception and theory of mind, two areas that have gained sizeable attention in neuroscientific research, and then extend the discussion into relatively new, less covered but crucial functions involving empathic behaviour, social awareness, social judgements, and social decision making. These functions are frequently impaired following neurological change. At present, a wide range of psychometrically robust social cognition tests is available, and this review also makes the case for their inclusion in neuropsychological assessments.

Polyarticular gout attacks following cerebrovascular accidents: is hemiparesis in fact protective? 2 cases and a review of the literature.

Science.gov (United States)

Hsiao, Susan J; Vaynrub, Maksim; Furer, Victoria; Samuels, Jonathan

2010-09-01

Cerebrovascular disease appears to have implications on rheumatic diseases, including gout. Accumulating evidence suggests that hemiparesis exerts a protective effect against gout via the down-regulation of mechanical and neural modulators of inflammation in neurologically impaired extremities. We present 2 divergent cases of unilateral gout following cerebrovascular events. One patient with a hemorrhagic stroke developed polyarticular gout only on the ipsilateral side to his hemiparesis, while another patient with basilar artery thrombosis and locked-in syndrome suffered a polyarticular gout flare only on the side that had regained limited function. As suggested by these cases, the effect of hemiparesis on gout is complex. Further insight into the interplay between gouty flares and hemiparesis may lead to novel therapeutic strategies for gout.

Prolongation of bleeding time and inhibition of platelet aggregation by low-dose acetylsalicylic acid in patients with cerebrovascular disease

DEFF Research Database (Denmark)

Boysen, G; Boss, A H; Ødum, Niels

1984-01-01

the bleeding time averaged 11.2 minutes in contrast to 7.0 minutes in the placebo group, p less than 0.001. This study confirms our previous findings of platelet inhibition by low-dose acetylsalicylic acid in patients with cerebrovascular disease. The prolongation of the bleeding time demonstrates that we......Platelet aggregation and bleeding time was measured in 43 cerebrovascular patients participating in a controlled double-blind study of low-dose acetylsalicylic acid. In 19 patients with satisfactory inhibition of the platelet aggregation obtained by 50 to 70 mg acetylsalicylic acid per day...... are dealing not merely with an in vitro phenomenon but with a significant in vivo effect. The study provides the rationale for clinical evaluations of low-dose acetylsalicylic acid in stroke prophylaxis....

Cerebral blood flow and cerebrovascular response to acetazolamide in patients with chronic alcoholism

OpenAIRE

Oishi, M; Mochizuki, Y; Takasu, T

1997-01-01

Cerebral blood flow and cerebrovascular response to acetazolamide were studied in 12 patients with chronic alcoholism and 12 age matched healthy controls. Blood flows in the cerebral cortex, thalamus, and putamen were significantly lower in the chronic alcoholic group than in the healthy control group. The increase in blood flow caused by acetazolamide did not show any significant difference between the two groups. These findings suggest that the decreased cerebral blood flow i...

Central nervous system infections masquerading as cerebrovascular accidents: Case series and review of literature.

Science.gov (United States)

Hayes, Lisa; Malhotra, Prashant

2014-01-01

Central nervous system (CNS) infections can have various presentations including Cerebrovascular accidents (CVA) which may go unrecognized as a presentation of infection. We describe three cases of different CNS infections complicated by CVA. Case 1 describes a 27-year-old man, presenting with symptoms consistent with a transient ischemic attack found to have racemose neurocysticercosis. Case 2 describes a 55-year-old man with low grade fevers for 4 weeks accompanied by visual and gait disturbances and delayed speech diagnosed with multiple small left thalamocapsular and superior cerebellar infarcts secondary to cryptococcal meningitis. The third case describes a man with pneumococcal meningitis complicated by cerebellar infarcts. CNS vascular compromise secondary to infections may be due to vasculitis, an immune-mediated parainfectious process causing vasospasm or thrombosis, or a hypercoagulable state with endothelial dysfunction. Patients with CVAs are at risk for aspiration pneumonia, urinary tract infections (especially catheter related) and other nosocomial infections and their clinical presentation may be very similar to CNS infections. The cases described demonstrate that CNS infections need to be considered in the differential diagnosis of CVAs presenting with fevers. The signs and symptoms of non-CNS infections associated with CVAs may be clinically indistinguishable from those of CNS infections. The outcomes of untreated CNS infections are extremely poor. It is thus imperative to have a high index of suspicion for CNS infection when evaluating CVAs with fevers or other signs of infection.

Modeling Cerebrovascular Pathophysiology in Amyloid-β Metabolism using Neural-Crest-Derived Smooth Muscle Cells

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Christine Cheung

2014-10-01

Full Text Available Summary: There is growing recognition of cerebrovascular contributions to neurodegenerative diseases. In the walls of cerebral arteries, amyloid-beta (Aβ accumulation is evident in a majority of aged people and patients with cerebral amyloid angiopathy. Here, we leverage human pluripotent stem cells to generate vascular smooth muscle cells (SMCs from neural crest progenitors, recapitulating brain-vasculature-specific attributes of Aβ metabolism. We confirm that the lipoprotein receptor, LRP1, functions in our neural-crest-derived SMCs to mediate Aβ uptake and intracellular lysosomal degradation. Hypoxia significantly compromises the contribution of SMCs to Aβ clearance by suppressing LRP1 expression. This enabled us to develop an assay of Aβ uptake by using the neural crest-derived SMCs with hypoxia as a stress paradigm. We then tested several vascular protective compounds in a high-throughput format, demonstrating the value of stem-cell-based phenotypic screening for novel therapeutics and drug repurposing, aimed at alleviating amyloid burden. : The contribution of blood vessel pathologies to neurodegenerative disorders is relatively neglected, partly due to inadequate human tissues for research. By using human stem cells, Cheung et al. establish a method of generating vascular smooth muscle cells (SMCs from neural crest progenitors, the primary precursors that give rise to brain blood vessels. These stem-cell-derived SMCs display defective amyloid processing under chronic hypoxia, a phenomenon well documented in the cerebral vasculatures of aged people and patients with Alzheimer’s disease.

Proinflammatory adipokine leptin mediates disinfection byproduct bromodichloromethane-induced early steatohepatitic injury in obesity

International Nuclear Information System (INIS)

Das, Suvarthi; Kumar, Ashutosh; Seth, Ratanesh Kumar; Tokar, Erik J.; Kadiiska, Maria B.; Waalkes, Michael P.; Mason, Ronald P.; Chatterjee, Saurabh

2013-01-01

Today's developed world faces a major public health challenge in the rise in the obese population and the increased incidence in fatty liver disease. There is a strong association among diet induced obesity, fatty liver disease and development of nonalcoholic steatohepatitis but the environmental link to disease progression remains unclear. Here we demonstrate that in obesity, early steatohepatitic lesions induced by the water disinfection byproduct bromodichloromethane are mediated by increased oxidative stress and leptin which act in synchrony to potentiate disease progression. Low acute exposure to bromodichloromethane (BDCM), in diet-induced obesity produced oxidative stress as shown by increased lipid peroxidation, protein free radical and nitrotyrosine formation and elevated leptin levels. Exposed obese mice showed histopathological signs of early steatohepatitic injury and necrosis. Spontaneous knockout mice for leptin or systemic leptin receptor knockout mice had significantly decreased oxidative stress and TNF-α levels. Co-incubation of leptin and BDCM caused Kupffer cell activation as shown by increased MCP-1 release and NADPH oxidase membrane assembly, a phenomenon that was decreased in Kupffer cells isolated from leptin receptor knockout mice. In obese mice that were BDCM-exposed, livers showed a significant increase in Kupffer cell activation marker CD68 and, increased necrosis as assessed by levels of isocitrate dehydrogenase, events that were decreased in the absence of leptin or its receptor. In conclusion, our results show that exposure to the disinfection byproduct BDCM in diet-induced obesity augments steatohepatitic injury by potentiating the effects of leptin on oxidative stress, Kupffer cell activation and cell death in the liver. - Highlights: ► BDCM acute exposure sensitizes liver to increased free radical stress in obesity. ► BDCM-induced higher leptin contributes to early steatohepatitic lesions. ► Increased leptin mediates protein

Proinflammatory adipokine leptin mediates disinfection byproduct bromodichloromethane-induced early steatohepatitic injury in obesity

Energy Technology Data Exchange (ETDEWEB)

Das, Suvarthi [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States); Kumar, Ashutosh [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, Research Triangle Park, NC 27709 (United States); Seth, Ratanesh Kumar [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States); Tokar, Erik J. [Inorganic Toxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Kadiiska, Maria B. [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, Research Triangle Park, NC 27709 (United States); Waalkes, Michael P. [Inorganic Toxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Mason, Ronald P. [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, Research Triangle Park, NC 27709 (United States); Chatterjee, Saurabh, E-mail: schatt@mailbox.sc.edu [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States)

2013-06-15

Today's developed world faces a major public health challenge in the rise in the obese population and the increased incidence in fatty liver disease. There is a strong association among diet induced obesity, fatty liver disease and development of nonalcoholic steatohepatitis but the environmental link to disease progression remains unclear. Here we demonstrate that in obesity, early steatohepatitic lesions induced by the water disinfection byproduct bromodichloromethane are mediated by increased oxidative stress and leptin which act in synchrony to potentiate disease progression. Low acute exposure to bromodichloromethane (BDCM), in diet-induced obesity produced oxidative stress as shown by increased lipid peroxidation, protein free radical and nitrotyrosine formation and elevated leptin levels. Exposed obese mice showed histopathological signs of early steatohepatitic injury and necrosis. Spontaneous knockout mice for leptin or systemic leptin receptor knockout mice had significantly decreased oxidative stress and TNF-α levels. Co-incubation of leptin and BDCM caused Kupffer cell activation as shown by increased MCP-1 release and NADPH oxidase membrane assembly, a phenomenon that was decreased in Kupffer cells isolated from leptin receptor knockout mice. In obese mice that were BDCM-exposed, livers showed a significant increase in Kupffer cell activation marker CD68 and, increased necrosis as assessed by levels of isocitrate dehydrogenase, events that were decreased in the absence of leptin or its receptor. In conclusion, our results show that exposure to the disinfection byproduct BDCM in diet-induced obesity augments steatohepatitic injury by potentiating the effects of leptin on oxidative stress, Kupffer cell activation and cell death in the liver. - Highlights: ► BDCM acute exposure sensitizes liver to increased free radical stress in obesity. ► BDCM-induced higher leptin contributes to early steatohepatitic lesions. ► Increased leptin mediates

Changes in the Levels of Pro-Inflammatory Cytokines in Patients with Generalized Periodontitis and Hypertension, Depending on the Method of Treatment

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T. Vicharenko

2017-12-01

Full Text Available Inflammatory mediators have an important role in the pathogenesis of periodontal disease. One of the leading mediators of the initiation of the pathological process is interleukin-1 (IL-1 – an endogenous pyrogen, a lymphocyte-activating factor. Numerous pro-inflammatory effects of interleukin-1β (IL-1β occur in synergy with tumor necrosis factor alpha (TNF-α and interleukin-6 (IL-6, effects on hematopoiesis, participates in nonspecific anti-infective defense. The objective of the study is to determine levels of interleukin-6 and tumor necrosis factor alpha (TNF-α in patients with hypertension II stage and generalized periodontitis of the II degree depending on the treatment method. There were examined 30 patients with hypertension of the II stage and with generalized periodontitis of the II degree. Patients’ age ranged from 35 to 54 years. These patients were divided into two groups. The control group included 10 patients without general somatic pathology and with healthy periodontitis of the same age.  The result of the analysis of tumor necrosis factor alpha (TNF-α in patients in the first group before the treatment was 10.69±2.33 pg/ml. After the treatment this indicator was 6.97±1.57 pg/ml (p>0.1 in patients of the first group. In patients of the second group the tumor necrosis factor alpha (TNF-α was 9.49±2.2 pg/ml; after the treatment according to the offered scheme this figure decreased up to 2.77±0.9 pg/ml (p0.1. In the second group, before the treatment the level of  interleukin-6 was 9.65±2.41 pg/ml; after the treatment according to the offered scheme it was 2.62±0.5 pg/ml (p<0.01. In the control group the interleukin-6 level was 2.24±0.51 pg/ml. Analyzing the obtained results after the treatment in both groups we can conclude: after the treatment of generalized periodontitis of the II degree in patients with hypertension of the II stage, indices of pro-inflammatory cytokines decreased and ranged in normal limits; in

Toll-Like Receptor 2 mediates in vivo pro- and anti-inflammatory effects of Mycobacterium tuberculosis and modulates autoimmune encephalomyelitis

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Alessia ePiermattei

2016-05-01

Full Text Available Mycobacteria display pro- and anti-inflammatory effects in human and experimental pathology. We show here that both effects are mediated by Toll like receptor 2 (Tlr2, by exploiting a previously characterized Tlr2 variant (Met82Ile. Tlr2 82ile promoted self-specific pro-inflammatory polarization as well as expansion of ag-specific FoxP3+ Tregs, while Tlr2 82met impairs the expansion of Tregs and reduces the production of IFN-γ and IL-17 pro-inflammatory cytokines. Preferential dimerization with Tlr1 or Tlr6 could not explain these differences. In silico, we showed that Tlr2 variant Met82Ile modified the binding pocket for peptidoglycans and participate directly to a putative binding pocket for sugars and Cadherins. The distinct pro- and anti-inflammatory actions impacted on severity, extent of remission and distribution of the lesions within the Central Nervous System of Experimental Autoimmune Encephalomyelitis. Thus, Tlr2 has a janus function in vivo as mediator of the role of bacterial products in balancing pro- and anti-inflammatory immune responses.

Cerebrovascular disease in newborn infants: report of three cases with clinical follow-up and brain SPECT imaging

Energy Technology Data Exchange (ETDEWEB)

Moura-Ribeiro, Maria Valeriana L. de; Ciasca, Sylvia Maria; Vale-Cavalcanti, Mariza; Etchebehere, Elba C.S.C.; Camargo, Edwaldo E. [Universidade Estadual de Campinas, SP (Brazil). Faculdade de Ciencias Medicas

1999-07-01

The clinical and neurological findings of three neonates with the diagnosis of cerebrovascular disease are reported. The neuropsychological evaluation disclosed impairment of fine motor function, coordination, language, perception and behavioral disturbances. Brain SPECT imaging revealed perfusional deficits in the three cases. (author)

Cerebrovascular disease in newborn infants: report of three cases with clinical follow-up and brain SPECT imaging

International Nuclear Information System (INIS)

Moura-Ribeiro, Maria Valeriana L. de; Ciasca, Sylvia Maria; Vale-Cavalcanti, Mariza; Etchebehere, Elba C.S.C.; Camargo, Edwaldo E.

1999-01-01

The clinical and neurological findings of three neonates with the diagnosis of cerebrovascular disease are reported. The neuropsychological evaluation disclosed impairment of fine motor function, coordination, language, perception and behavioral disturbances. Brain SPECT imaging revealed perfusional deficits in the three cases. (author)

Association between smoke-free legislation and hospitalizations for cardiac, cerebrovascular, and respiratory diseases: a meta-analysis.

Science.gov (United States)

Tan, Crystal E; Glantz, Stanton A

2012-10-30

Secondhand smoke causes cardiovascular and respiratory disease. Smoke-free legislation is associated with a lower risk of hospitalization and death from these diseases. Random-effects meta-analysis was conducted by law comprehensiveness to determine the relationship between smoke-free legislation and hospital admission or death from cardiac, cerebrovascular, and respiratory diseases. Studies were identified by using a systematic search for studies published before November 30, 2011 with the use of the Science Citation Index, Google Scholar, PubMed, and Embase and references in identified articles. Change in hospital admissions (or deaths) in the presence of a smoke-free law, duration of follow-up, and law comprehensiveness (workplaces only; workplaces and restaurants; or workplaces, restaurants, and bars) were recorded. Forty-five studies of 33 smoke-free laws with median follow-up of 24 months (range, 2-57 months) were included. Comprehensive smoke-free legislation was associated with significantly lower rates of hospital admissions (or deaths) for all 4 diagnostic groups: coronary events (relative risk, 0.848; 95% confidence interval 0.816-0.881), other heart disease (relative risk, 0.610; 95% confidence interval, 0.440-0.847), cerebrovascular accidents (relative risk, 0.840; 95% confidence interval, 0.753-0.936), and respiratory disease (relative risk, 0.760; 95% confidence interval, 0.682-0.846). The difference in risk following comprehensive smoke-free laws does not change with longer follow-up. More comprehensive laws were associated with larger changes in risk. Smoke-free legislation was associated with a lower risk of smoking-related cardiac, cerebrovascular, and respiratory diseases, with more comprehensive laws associated with greater changes in risk.

Hospital registry in special department for patients with acute cerebrovascular disease

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Maslyuk О.А.

2014-12-01

Full Text Available Aim: organization and follow-up of a registry of patients with cerebrovascular disease in in special department. Materials and methods. In the period from January 2011 to December 2013 all cases of cerebrovascular disease in the special department were recorded. Each patient had an electronic case book and thematic record, developed on the basis of the materials of the National Stoke Association of "Registry of stroke." Results. 418 cases of cerebral stroke were registered. Male to female ratio was 3.7: 1. Patients with initial diagnosed cerebral stroke were 78%, secondary 22%. The average age of patients was 63. The big number of strokes was observed in men aged 56-57 years; in women aged 75-77 years. TOAST criteria for subtypes of ischemic stroke were distributed to: atherothrombotic (29,3%, cardioembolic (29,1 %, 22,4% lacunar ischemic stroke due to other established reasons (8,8%, crptogenic (10,4%. Hemorrhagic stroke was observed in 16.8% of cases. Parenchymal hemorrhage was observed in 10.7% of cases, nontraumatic subarachnoid hemorrhage (4,5%. Among the risk factors in patients with ischemic stroke identified: arterial hypertension (88,9%, coronary heart disease (43%, heart rhythm disorders (28,4%, diabetes (18,6%. The proportion of endovascular interventions performed for 3 years was 31.2%. Mortality rate was 3.74% (10 people in 2011; 4.65% (14 people in 2012; 2.48% (7 people in 2013. Conclusion. Follow up the hospital stroke registry allowed to estimate the structure andcourse of cerebral stroke, found the risk factors to identify the most important factors of death.

β-agonists selectively modulate proinflammatory gene expression in skeletal muscle cells via non-canonical nuclear crosstalk mechanisms.

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Krzysztof Kolmus

Full Text Available The proinflammatory cytokine Tumour Necrosis Factor (TNF-α is implicated in a variety of skeletal muscle pathologies. Here, we have investigated how in vitro cotreatment of skeletal muscle C2C12 cells with β-agonists modulates the TNF-α-induced inflammatory program. We observed that C2C12 myotubes express functional TNF receptor 1 (TNF-R1 and β2-adrenoreceptors (β2-ARs. TNF-α activated the canonical Nuclear Factor-κB (NF-κB pathway and Mitogen-Activated Protein Kinases (MAPKs, culminating in potent induction of NF-κB-dependent proinflammatory genes. Cotreatment with the β-agonist isoproterenol potentiated the expression of inflammatory mediators, including Interleukin-6 (IL-6 and several chemokines. The enhanced production of chemotactic factors upon TNF-α/isoproterenol cotreatment was also suggested by the results from migrational analysis. Whereas we could not explain our observations by cytoplasmic crosstalk, we found that TNF-R1-and β2-AR-induced signalling cascades cooperate in the nucleus. Using the IL-6 promoter as a model, we demonstrated that TNF-α/isoproterenol cotreatment provoked phosphorylation of histone H3 at serine 10, concomitant with enhanced promoter accessibility and recruitment of the NF-κB p65 subunit, cAMP-response element-binding protein (CREB, CREB-binding protein (CBP and RNA polymerase II. In summary, we show that β-agonists potentiate TNF-α action, via nuclear crosstalk, that promotes chromatin relaxation at selected gene promoters. Our data warrant further study into the mode of action of β-agonists and urge for caution in their use as therapeutic agents for muscular disorders.

Kefir-isolated bacteria and yeasts inhibit Shigella flexneri invasion and modulate pro-inflammatory response on intestinal epithelial cells.

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Bolla, P A; Abraham, A G; Pérez, P F; de Los Angeles Serradell, M

2016-02-01

The aim of this work was to evaluate the ability of a kefir-isolated microbial mixture containing three bacterial and two yeast strains (MM) to protect intestinal epithelial cells against Shigella flexneri invasion, as well as to analyse the effect on pro-inflammatory response elicited by this pathogen. A significant decrease in S. flexneri strain 72 invasion was observed on both HT-29 and Caco-2 cells pre-incubated with MM. Pre-incubation with the individual strains Saccharomyces cerevisiae CIDCA 8112 or Lactococcus lactis subsp. lactis CIDCA 8221 also reduced the internalisation of S. flexneri into HT-29 cells although in a lesser extent than MM. Interestingly, Lactobacillus plantarum CIDCA 83114 exerted a protective effect on the invasion of Caco-2 and HT-29 cells by S. flexneri. Regarding the pro-inflammatory response on HT-29 cells, S. flexneri infection induced a significant activation of the expression of interleukin 8 (IL-8), chemokine (C-C motif) ligand 20 (CCL20) and tumour necrosis factor alpha (TNF-α) encoding genes (P<0.05), whereas incubation of cells with MM did not induce the expression of any of the mediators assessed. Interestingly, pre-incubation of HT-29 monolayer with MM produced an inhibition of S. flexneri-induced IL-8, CCL20 and TNF-α mRNA expression. In order to gain insight on the effect of MM (or the individual strains) on this pro-inflammatory response, a series of experiments using a HT-29-NF-κB-hrGFP reporter system were performed. Pre-incubation of HT-29-NF-κB-hrGFP cells with MM significantly dampened Shigella-induced activation. Our results showed that the contribution of yeast strain Kluyveromyces marxianus CIDCA 8154 seems to be crucial in the observed effect. In conclusion, results presented in this study demonstrate that pre-treatment with a microbial mixture containing bacteria and yeasts isolated from kefir, resulted in inhibition of S. flexneri internalisation into human intestinal epithelial cells, along with the

Lipoxins and aspirin-triggered lipoxin alleviate bone cancer pain in association with suppressing expression of spinal proinflammatory cytokines

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Hu Shan

2012-12-01

Full Text Available Abstract Background The neuroinflammatory responses in the spinal cord following bone cancer development have been shown to play an important role in cancer-induced bone pain (CIBP. Lipoxins (LXs, endogenous lipoxygenase-derived eicosanoids, represent a unique class of lipid mediators that possess a wide spectrum of anti-inflammatory and pro-resolving actions. In this study, we investigated the effects of intrathecal injection with lipoxin and related analogues on CIBP in rats. Methods The CIBP model was induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells. Mechanical thresholds were determined by measuring the paw withdrawal threshold to probing with a series of calibrated von Frey filaments. Lipoxins and analogues were administered by intrathecal (i.t. or intravenous (i.v. injection. The protein level of LXA4 receptor (ALX was tested by western blot. The localization of lipoxin receptor in spinal cord was assessed by fluorescent immunohistochemistry. Real-time PCR was carried out for detecting the expression of pro-inflammatory cytokines. Results Our results demonstrated that: 1 i.t. injection with the same dose (0.3 nmol of lipoxin A4 (LXA4, lipoxin B4 (LXB4 or aspirin-triggered-15-epi-lipoxin A4 (ATL could alleviate the mechanical allodynia in CIBP on day 7 after surgery. ATL showed a longer effect than the others and the effect lasted for 6 hours. ATL administered through i.v. injection could also attenuate the allodynia in cancer rats. 2 The results from western blot indicate that there is no difference in the expression of ALX among the naive, sham or cancer groups. 3 Immunohistochemistry showed that the lipoxin receptor (ALX-like immunoreactive substance was distributed in the spinal cord, mainly co-localized with astrocytes, rarely co-localized with neurons, and never co-localized with microglia. 4 Real-time PCR analysis revealed that, compared with vehicle, i.t. injection with ATL could significantly

Involvement of Pro-Inflammatory Macrophages in Liver Pathology of Pirital Virus-Infected Syrian Hamsters

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Corey L. Campbell

2018-05-01

Full Text Available New World arenaviruses cause fatal hemorrhagic disease in South America. Pirital virus (PIRV, a mammarenavirus hosted by Alston’s cotton rat (Sigmodon alstoni, causes a disease in Syrian golden hamsters (Mesocricetus auratus (biosafety level-3, BSL-3 that has many pathologic similarities to the South American hemorrhagic fevers (BSL-4 and, thus, is considered among the best small-animal models for human arenavirus disease. Here, we extend in greater detail previously described clinical and pathological findings in Syrian hamsters and provide evidence for a pro-inflammatory macrophage response during PIRV infection. The liver was the principal target organ of the disease, and signs of Kupffer cell involvement were identified in mortally infected hamster histopathology data. Differential expression analysis of liver mRNA revealed signatures of the pro-inflammatory response, hematologic dysregulation, interferon pathway and other host response pathways, including 17 key transcripts that were also reported in two non-human primate (NHP arenavirus liver-infection models, representing both Old and New World mammarenavirus infections. Although antigen presentation may differ among rodent and NHP species, key hemostatic and innate immune-response components showed expression parallels. Signatures of pro-inflammatory macrophage involvement in PIRV-infected livers included enrichment of Ifng, Nfkb2, Stat1, Irf1, Klf6, Il1b, Cxcl10, and Cxcl11 transcripts. Together, these data indicate that pro-inflammatory macrophage M1 responses likely contribute to the pathogenesis of acute PIRV infection.

The truncated splice variant of peroxisome proliferator-activated receptor alpha, PPARα-tr, autonomously regulates proliferative and pro-inflammatory genes

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Thomas, Maria; Bayha, Christine; Klein, Kathrin; Müller, Simon; Weiss, Thomas S.; Schwab, Matthias; Zanger, Ulrich M.

2015-01-01

The peroxisome proliferator-activated receptor alpha (PPARα) controls lipid/energy homeostasis and inflammatory responses. The truncated splice variant PPARα-tr was suggested to exert a dominant negative function despite being unable to bind consensus PPARα DNA response elements. The distribution and variability factor of each PPARα variant were assessed in the well-characterized cohort of human liver samples (N = 150) on the mRNA and protein levels. Specific siRNA-mediated downregulation of each transcript as well as specific overexpression with subsequent qRT-PCR analysis of downstream genes was used for investigation of specific functional roles of PPARα-wt and PPARα-tr forms in primary human hepatocytes. Bioinformatic analyses of genome-wide liver expression profiling data suggested a possible role of PPARα-tr in downregulating proliferative and pro-inflammatory genes. Specific gene silencing of both forms in primary human hepatocytes showed that induction of metabolic PPARα-target genes by agonist WY14,643 was prevented by PPARα-wt knock-down but neither prevented nor augmented by PPARα-tr knock-down. WY14,643 treatment did not induce proliferative genes including MYC, CDK1, and PCNA, and knock-down of PPARα-wt had no effect, while PPARα-tr knock-down caused up to 3-fold induction of these genes. Similarly, induction of pro-inflammatory genes IL1B, PTGS2, and CCL2 by IL-6 was augmented by knock-down of PPARα-tr but not of PPARα-wt. In contrast to human proliferative genes, orthologous mouse genes were readily inducible by WY14,643 in PPARα-tr non-expressing AML12 mouse hepatocytes. Induction was augmented by overexpression of PPARα-wt and attenuated by overexpression of PPARα-tr. Pro-inflammatory genes including IL-1β, CCL2 and TNFα were induced by WY14,643 in mouse and human cells and both PPARα forms attenuated induction. As potential mechanism of PPARα-tr inhibitory action we suggest crosstalk with WNT/β-catenin pathway. Finally

The national burden of cerebrovascular diseases in Spain: a population-based study using disability-adjusted life years.

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Catalá-López, Ferrán; Fernández de Larrea-Baz, Nerea; Morant-Ginestar, Consuelo; Álvarez-Martín, Elena; Díaz-Guzmán, Jaime; Gènova-Maleras, Ricard

2015-04-20

The aim of the present study was to determine the national burden of cerebrovascular diseases in the adult population of Spain. Cross-sectional, descriptive population-based study. We calculated the disability-adjusted life years (DALY) metric using country-specific data from national statistics and epidemiological studies to obtain representative outcomes for the Spanish population. DALYs were divided into years of life lost due to premature mortality (YLLs) and years of life lived with disability (YLDs). DALYs were estimated for the year 2008 by applying demographic structure by sex and age-groups, cause-specific mortality, morbidity data and new disability weights proposed in the recent Global Burden of Disease study. In the base case, neither YLLs nor YLDs were discounted or age-weighted. Uncertainty around DALYs was tested using sensitivity analyses. In Spain, cerebrovascular diseases generated 418,052 DALYs, comprising 337,000 (80.6%) YLLs and 81,052 (19.4%) YLDs. This accounts for 1,113 DALYs per 100,000 population (men: 1,197 and women: 1,033) and 3,912 per 100,000 in those over the age of 65 years (men: 4,427 and women: 2,033). Depending on the standard life table and choice of social values used for calculation, total DALYs varied by 15.3% and 59.9% below the main estimate. Estimates provided here represent a comprehensive analysis of the burden of cerebrovascular diseases at a national level. Prevention and control programmes aimed at reducing the disease burden merit further priority in Spain. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Improvement of postoperative cognitive dysfunction and attention network function of patients with ischemic cerebrovascular disease via dexmedetomidine.

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Zhang, Jingchao; Wang, Guoliang; Zhang, Fangxiang; Zhao, Qian

2018-03-01

The protective effect of dexmedetomidine on cognitive dysfunction and decreased attention network function of patients with ischemic cerebrovascular disease after stenting was investigated. Fifty-eight patients with ischemic cerebrovascular disease undergoing stenting in Guizhou Provincial People's Hospital were selected and randomly divided into control group (n=29) and dexmedetomidine group (n=29). The dexmedetomidine group was treated with dexmedetomidine before induced anesthesia, while the control group was given the same dose of normal saline; and the normal volunteers of the same age were selected as the normal group (n=29). At 3 days after operation, the levels of serum S100B and nerve growth factor (NGF) in each group were detected using the enzyme-linked immunosorbent assay, and the level of brain-derived neurotrophic factor (BDNF) was detected via western blotting. Montreal cognitive assessment (MoCA) and attention network test (ANT) were performed. Moreover, the cognitive function and attention network function, and the effects of dexmedetomidine on cognitive function and attention network function were evaluated. The concentrations of serum S100B and NGF in dexmedetomidine group was lower than those in control group (Pfunction scores, attention scores, delayed memory scores, targeted network efficiency and executive control network efficiency in dexmedetomidine group were obviously higher than those in control group (Pcognitive function and attention network function of patients with ischemic cerebrovascular disease have a certain degree of damage, and the preoperative administration of dexmedetomidine can effectively improve the patient's cognitive dysfunction and attention network function after operation.

Fluoride exposure abates pro-inflammatory response and induces in vivo apoptosis rendering zebrafish (Danio rerio) susceptible to bacterial infections.

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Singh, Rashmi; Khatri, Preeti; Srivastava, Nidhi; Jain, Shruti; Brahmachari, Vani; Mukhopadhyay, Asish; Mazumder, Shibnath

2017-04-01

The present study describes the immunotoxic effect of chronic fluoride exposure on adult zebrafish (Danio rerio). Zebrafish were exposed to fluoride (71.12 mg/L; 1/10 LC 50 ) for 30 d and the expression of selected genes studied. We observed significant elevation in the detoxification pathway gene cyp1a suggesting chronic exposure to non-lethal concentration of fluoride is indeed toxic to fish. Fluoride mediated pro-oxidative stress is implicated with the downregulation in superoxide dismutase 1 and 2 (sod1/2) genes. Fluoride affected DNA repair machinery by abrogating the expression of the DNA repair gene rad51 and growth arrest and DNA damage inducible beta a gene gadd45ba. The upregulated expression of casp3a coupled with altered Bcl-2 associated X protein/B-cell lymphoma 2 ratio (baxa/bcl2a) clearly suggested chronic fluoride exposure induced the apoptotic cascade in zebrafish. Fluoride-exposed zebrafish when challenged with non-lethal dose of fish pathogen A. hydrophila revealed gross histopathology in spleen, bacterial persistence and significant mortality. We report that fluoride interferes with system-level output of pro-inflammatory cytokines tumour necrosis factor-α, interleukin-1β and interferon-γ, as a consequence, bacteria replicate efficiently causing significant fish mortality. We conclude, chronic fluoride exposure impairs the redox balance, affects DNA repair machinery with pro-apoptotic implications and suppresses pro-inflammatory cytokines expression abrogating host immunity to bacterial infections. Copyright © 2017 Elsevier Ltd. All rights reserved.

Terapéuticas intervencionistas para el accidente cerebrovascular isquémico

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Alejandra T. Rabadán; Luciano Sposato; Claudio Mazia

2010-01-01

En los últimos 20 años se han desarrollado nuevas opciones para el tratamiento y para la prevención del accidente cerebrovascular (ACV) isquémico, muchas de ellas de carácter intervencionista, tales como la endarterectomía carotídea y la trombolisis intravenosa con activador tisular del plasminógeno. La evidencia científica ha llevado a su difusión y utilización en países desarrollados mientras que en naciones emergentes se observa un retraso en su adopción. Otras modalidades terapéuticas que...

Sintered indium-tin oxide particles induce pro-inflammatory responses in vitro, in part through inflammasome activation.

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Melissa A Badding

Full Text Available Indium-tin oxide (ITO is used to make transparent conductive coatings for touch-screen and liquid crystal display electronics. As the demand for consumer electronics continues to increase, so does the concern for occupational exposures to particles containing these potentially toxic metal oxides. Indium-containing particles have been shown to be cytotoxic in cultured cells and pro-inflammatory in pulmonary animal models. In humans, pulmonary alveolar proteinosis and fibrotic interstitial lung disease have been observed in ITO facility workers. However, which ITO production materials may be the most toxic to workers and how they initiate pulmonary inflammation remain poorly understood. Here we examined four different particle samples collected from an ITO production facility for their ability to induce pro-inflammatory responses in vitro. Tin oxide, sintered ITO (SITO, and ventilation dust particles activated nuclear factor kappa B (NFκB within 3 h of treatment. However, only SITO induced robust cytokine production (IL-1β, IL-6, TNFα, and IL-8 within 24 h in both RAW 264.7 mouse macrophages and BEAS-2B human bronchial epithelial cells. Our lab and others have previously demonstrated SITO-induced cytotoxicity as well. These findings suggest that SITO particles activate the NLRP3 inflammasome, which has been implicated in several immune-mediated diseases via its ability to induce IL-1β release and cause subsequent cell death. Inflammasome activation by SITO was confirmed, but it required the presence of endotoxin. Further, a phagocytosis assay revealed that pre-uptake of SITO or ventilation dust impaired proper macrophage phagocytosis of E. coli. Our results suggest that adverse inflammatory responses to SITO particles by both macrophage and epithelial cells may initiate and propagate indium lung disease. These findings will provide a better understanding of the molecular mechanisms behind an emerging occupational health issue.

Elevated arterial blood pressure after superior cavo-pulmonary anastomosis is associated with elevated pulmonary artery pressure and cerebrovascular dysautoregulation.

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Cabrera, Antonio G; Kibler, Kathleen K; Blaine Easley, R; Goldsworthy, Michelle; Shekerdemian, Lara S; Andropoulos, Dean B; Heinle, Jeffrey; Gottlieb, Erin A; Vu, Eric; Brady, Ken M

2018-04-18

BackgroundElevated arterial blood pressure (ABP) is common after superior bidirectional cavopulmonary anastomosis (BCPA). The effects of elevated ABP after BCPA on cerebrovascular hemodynamics are unknown. We sought to determine the relationship between elevated ABP and cerebrovascular autoregulation after BCPA.MethodsProspective, observational study on infants with single-ventricle physiology after BCPA surgery. Continuous recordings of mean ABP, mean cavopulmonary artery pressure (PAP), near-infrared spectroscopy measures of cerebral oximetry (regional cerebral oxygen saturation (rSO 2 )), and relative cerebral blood volume index were obtained from admission to extubation. Autoregulation was measured as hemoglobin volume index (HVx). Physiologic variables, including the HVx, were tested for variance across ABP.ResultsSixteen subjects were included in the study. Elevated ABP post-BCPA was associated with both, elevated PAP (PABP and alterations in rSO 2 . Using piecewise regression, the relationship of PAP to ABP demonstrated a breakpoint at 68 mm Hg (interquartile range (IQR) 62-70 mm Hg). Curve fit of HVx as a function of ABP identified optimal ABP supporting robust autoregulation at a median ABP of 55 mm Hg (IQR 51-64 mm Hg).ConclusionsElevated ABP post-BCPA is associated with cerebrovascular dysautoregulation, and elevated PAP. The effects, of prolonged dysautoregulation within this population, require further study.Pediatric Research advance online publication, 18 April 2018; doi:10.1038/pr.2018.31.

Clinical Characteristics of Cerebrovascular Pathology with Patients Suffering from Ph-Negative Myeloproliferative Disease

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Marine M. Tanashyan

2016-09-01

Full Text Available Background: Disturbances of microcirculation play a significant role in the development and progression of both acute and chronic cerebrovascular diseases (CVD and may be associated with different hemogram abnormalities. One of the reasons of the prothrombogenic state of the endothelium is the increase in the number of blood corpuscles leading to (non-Ph myeloproliferative disorders (MPD including essential thrombocythemia (ET, polycythemia vera (PV, and primary myelofibrosis (PM. Materials and Methods: The study included 167 patients: 102 patients with Ph-MPD and the control group comprising 65 patients with CVD. According to MPD subtype, the patients were divided into three groups: patients with ET (37%, n = 38, male/female 7/31, age 52 ± 7 years, those with PV (40%, n = 41, male/female 20/21, age 50 ± 6 years and those with PM (23%, n = 23, male/female 5/18, age 54 ± 4 years. Results: In 79% (n = 81 of cases in the study group (with Ph-MPD, patients had chronic CVD, with the most frequently identified symptoms being asthenia (92% and headache (72%. Headache in Ph-MPD patients was more frequently (86% associated with PM, while in patients with PV and ET it was equally distributed (70%. Neurological symptoms in 53% of cases were associated with focal changes of the brain on MRI localized in the subcortical area of the frontal and parietal lobes. Twenty-one (21% patients suffered an acute cerebrovascular accident, 8 of them had thrombotic occlusion of one of the internal carotid arteries leading to hemispheric infarcts. Endothelial function (as measured by flow-dependent dilation of the brachial artery was severely impaired in all study groups (median 5% with normal cut-off at 10%, the lowest degree of vasodilator activity being specific for patients with a history of stroke (p = 0.011. Conclusion: Patients suffering from MPD had asymptomatic focal changes in the brain in the absence of concomitant vascular disease (hypertension

Congenital and genetic cerebrovascular anomalies as risk factors for stroke in Saudi Arabia

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Salih, Mustafa A.; Al-Jarallah, Ahmed A.; Kentab, Amal Y.; Murshid, Waleed R.; Zahraa, Jihad N.; Abdel-Gader, Abdel-Galil M.; Alorainy, Ibrahim A.; Hassan, Hamdy H.; Tjan, G. T.

2006-01-01

To explore the role of and report congenital and genetic cerebrovascular anomalies as risk factors for stroke in a prospective and retrospective cohort of Saudi children. Children with stroke were evaluated at the Division of Pediatric Neurology (Dpn), or were seen as inpatients in the Pediatric Wards at King Khalid University Hospital (KKUH), Riyadh, Kingdom of Saudi Arabia during the periods July 1992 to February 2001 (retrospective study) and February 2001 to March 2003 (prospective study). Stroke work-up for each suspected case included hemostatic assays, serological, biochemical and neurophysiological tests. Neuroimaging modalities included routine skill x-rays, CT, MRI, magnetic resonance angiography (MRA) and conventional cerebral angiography. Of 104 children with stroke, congenital and genetic cerebrovascular anomalies were the underlying risk factor in 7 (6.7%). The patients were evaluated at the DPN at a mean age of 66 months (range = 8 months to 11 years, median = 6 years); and they had stroke at a mean age of 48 months (range = 2 months to 10 years, median = 8 months). Four patients had stroke in association with neurocutaneous syndromes. Two had Sturge-Weber syndrome (SWS), one had Klippel-Trenaunay syndrome associated with SWS, and the fourth had neurofibromatosis type 1. Two patients had intracranial hemorrhage secondary to ruptured aneurysm. A girl (aged 9 years and 4 months) had left posterior cerebral artery aneurysm. She was diagnosed to have autosomal dominant polycystic kidney disease following renal ultrasonography. She died 5 months later despite surgical intervention (clipping of aneurysm). The second child was an 8-months-old boy who presented with subarachnoid and intraventricular hemorrhage (IVH) following ruptured anterior communicating artery aneurysm. He recovered with no residual symptoms following successful clipping of the aneurysm. Arteriovenous malformation (AVM) caused IVH in a 7-year-old boy who reported to hospital 5 hours

Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro

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Sárvári, Anitta K., E-mail: anittasarvari@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Veréb, Zoltán, E-mail: jzvereb@gmail.com [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Uray, Iván P., E-mail: ipuray@mdanderson.org [Clinical Cancer Prevention Department, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Fésüs, László, E-mail: fesus@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); MTA DE Apoptosis, Genomics and Stem Cell Research Group of the Hungarian Academy of Sciences (Hungary); Balajthy, Zoltán, E-mail: balajthy@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary)

2014-08-08

Highlights: • Antipsychotics modulate the expression of adipogenic genes in human adipocytes. • Secretion of proinflammatory cytokine IL8 and MCP-1 is induced by antipsychotics. • Adipocyte-dependent inflammatory abnormality could develop during chronic treatment. • Infiltrated macrophages would further enhance proinflammatory cytokine production. - Abstract: Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin

Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro

International Nuclear Information System (INIS)

Sárvári, Anitta K.; Veréb, Zoltán; Uray, Iván P.; Fésüs, László; Balajthy, Zoltán

2014-01-01

Highlights: • Antipsychotics modulate the expression of adipogenic genes in human adipocytes. • Secretion of proinflammatory cytokine IL8 and MCP-1 is induced by antipsychotics. • Adipocyte-dependent inflammatory abnormality could develop during chronic treatment. • Infiltrated macrophages would further enhance proinflammatory cytokine production. - Abstract: Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin