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Sample records for hyperglycemia promotes atherosclerosis

  1. Abdominal adiposity largely explains associations between insulin resistance, hyperglycemia and subclinical atherosclerosis: the NEO study

    NARCIS (Netherlands)

    Gast, Karin B.; Smit, Johannes W. A.; den Heijer, Martin; Middeldorp, Saskia; Rippe, Ralph C. A.; le Cessie, Saskia; de Koning, Eelco J. P.; Jukema, J. W.; Rabelink, Ton J.; de Roos, Albert; Rosendaal, Frits R.; de Mutsert, Renée; Rosendaal, F. R.; de Mutsert, R.; Rabelink, T. J.; Smit, J. W. A.; Romijn, J. A.; Rabe, K. F.; de Roos, A.; le Cessie, S.; Hiemstra, P. S.; Kloppenburg, M.; Huizinga, T. W. J.; Pijl, H.; Tamsma, J. T.; de Koning, E. J. P.; Assendelft, W. J. J.; Reitsma, P. H.; van Dijk, K. Willems; de Vries, A. P. J.; Lamb, H. J.; Jazet, I. M.; Dekkers, O. M.; Biermasz, N. R.; Cobbaert, C. M.; Heijer, M. den; Dekker, J. M.; Penninx, B. W.

    2013-01-01

    The relative importance of insulin resistance and hyperglycemia to the development of atherosclerosis remains unclear. Furthermore, adiposity may be responsible for observed associations. Our aim was to study the relative contributions of adiposity, insulin resistance and hyperglycemia to

  2. Abdominal adiposity largely explains associations between insulin resistance, hyperglycemia and subclinical atherosclerosis: the NEO study

    NARCIS (Netherlands)

    Gast, K.B.; Smit, J.W.A.; Heijer, M. den; Middeldorp, S.; Rippe, R.C.; Cessie, S. le; Koning, E.J. de; Jukema, J.W.; Rabelink, T.J.; Roos, A. de; Rosendaal, F.R.; Mutsert, R. de; Assendelft, P.; et al.,

    2013-01-01

    OBJECTIVE: The relative importance of insulin resistance and hyperglycemia to the development of atherosclerosis remains unclear. Furthermore, adiposity may be responsible for observed associations. Our aim was to study the relative contributions of adiposity, insulin resistance and hyperglycemia to

  3. Subclinical coronary atherosclerosis by multi-scan axial tomography and its association with hyperglycemia

    International Nuclear Information System (INIS)

    Buchaca Faxas, Emilio F; Bencomo Rodriguez, Llimia; Bermudez Rojas, Sergio

    2010-01-01

    A study was conducted to assess the usefulness of multi-scan axial tomography techniques to detect, in a subclinical stage, the coronary damage in patients presenting with diabetes mellitus (DM) to describe the frequency of asymptomatic atherosclerotic affection and its potential association with the fasting and postprandial hyperglycemia. In study were included 59 patients with type 2 diabetes to compare the results of coronary calcium determination with the findings of angiography by multi-scan axial computed tomography (CAT-M). There was a concordance of a 44.1% between both studies, as well as a predominance of soft plaques in the 55.9 % of patients. The 42.4 % showed a narrowing of arterial lumen, which was significant in the 16.5 % of total. A high figure of patients with hyperglycemia had coronary damage compared to those ills with a good glycemia control (p = 0.024). This relation was more evident with the postprandial hyperglycemia (= 0.016). Hyperglycemia had a high opportunity (5.99 times) to detect coronary lesions by TAC-C compared to other major atherosclerosis risk factors like the high blood pressure, smoking, dyslipemias expressed in a significant way (p 0.045). We conclude that Angio TAC-C and Calcio Score techniques are useful to detect lesions of coronary arteries in patients with type 2 diabetes mellitus without symptoms of myocardial ischemia, which was associated to presence of a hyperglycemia, fundamentally postprandial

  4. Examining the effects of hyperglycemia on pancreatic endocrine function in humans

    DEFF Research Database (Denmark)

    Solomon, Thomas P J; Knudsen, Sine H; Karstoft, Kristian

    2012-01-01

    Investigating the impact of hyperglycemia on pancreatic endocrine function promotes our understanding of the pathophysiology of hyperglycemia-related disease.......Investigating the impact of hyperglycemia on pancreatic endocrine function promotes our understanding of the pathophysiology of hyperglycemia-related disease....

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  6. Insulin resistance and atherosclerosis : the role of visceral fat

    NARCIS (Netherlands)

    Gast, K.B.

    2016-01-01

    The main objective of this thesis was to unravel relationships between obesity, insulin resistance, hyperglycemia, and atherosclerosis. It is well-established that patients with type 2 diabetes have a 2- to 3-fold increased risk of cardiovascular disease. We investigated whether insulin resistance

  7. Hypoxia-Inducible Factor-1α Expression in Macrophages Promotes Development of Atherosclerosis

    DEFF Research Database (Denmark)

    Pedersen, Annemarie Aarup; Pedersen, Tanja X; Junker, Nanna

    2016-01-01

    transplanted with bone marrow from mice with HIF-1α deficiency in the myeloid cells or control bone marrow. The HIF-1α deficiency in myeloid cells reduced atherosclerosis in aorta of the Ldlr(-/-) recipient mice by ≈72% (P=0.006).In vitro, HIF-1α-deficient macrophages displayed decreased differentiation...... to proinflammatory M1 macrophages and reduced expression of inflammatory genes. HIF-1α deficiency also affected glucose uptake, apoptosis, and migratory abilities of the macrophages. CONCLUSIONS: HIF-1α expression in macrophages affects their intrinsic inflammatory profile and promotes development of atherosclerosis....

  8. Follicular B Cells Promote Atherosclerosis via T Cell-Mediated Differentiation Into Plasma Cells and Secreting Pathogenic Immunoglobulin G.

    Science.gov (United States)

    Tay, Christopher; Liu, Yu-Han; Kanellakis, Peter; Kallies, Axel; Li, Yi; Cao, Anh; Hosseini, Hamid; Tipping, Peter; Toh, Ban-Hock; Bobik, Alex; Kyaw, Tin

    2018-05-01

    B cells promote or protect development of atherosclerosis. In this study, we examined the role of MHCII (major histocompatibility II), CD40 (cluster of differentiation 40), and Blimp-1 (B-lymphocyte-induced maturation protein) expression by follicular B (FO B) cells in development of atherosclerosis together with the effects of IgG purified from atherosclerotic mice. Using mixed chimeric Ldlr -/- mice whose B cells are deficient in MHCII or CD40, we demonstrate that these molecules are critical for the proatherogenic actions of FO B cells. During development of atherosclerosis, these deficiencies affected T-B cell interactions, germinal center B cells, plasma cells, and IgG. As FO B cells differentiating into plasma cells require Blimp-1, we also assessed its role in the development of atherosclerosis. Blimp-1-deficient B cells greatly attenuated atherosclerosis and immunoglobulin-including IgG production, preventing IgG accumulation in atherosclerotic lesions; Blimp-1 deletion also attenuated lesion proinflammatory cytokines, apoptotic cell numbers, and necrotic core. To determine the importance of IgG for atherosclerosis, we purified IgG from atherosclerotic mice. Their transfer but not IgG from nonatherosclerotic mice into Ldlr -/- mice whose B cells are Blimp-1-deficient increased atherosclerosis; transfer was associated with IgG accumulating in atherosclerotic lesions, increased lesion inflammatory cytokines, apoptotic cell numbers, and necrotic core size. The mechanism by which FO B cells promote atherosclerosis is highly dependent on their expression of MHCII, CD40, and Blimp-1. FO B cell differentiation into IgG-producing plasma cells also is critical for their proatherogenic actions. Targeting B-T cell interactions and pathogenic IgG may provide novel therapeutic strategies to prevent atherosclerosis and its adverse cardiovascular complications. © 2018 American Heart Association, Inc.

  9. Melanocortin 1 Receptor Deficiency Promotes Atherosclerosis in Apolipoprotein E-/- Mice.

    Science.gov (United States)

    Rinne, Petteri; Kadiri, James J; Velasco-Delgado, Mauricio; Nuutinen, Salla; Viitala, Miro; Hollmén, Maija; Rami, Martina; Savontaus, Eriika; Steffens, Sabine

    2018-02-01

    The MC1-R (melanocortin 1 receptor) is expressed by monocytes and macrophages where it mediates anti-inflammatory actions. MC1-R also protects against macrophage foam cell formation primarily by promoting cholesterol efflux through the ABCA1 (ATP-binding cassette transporter subfamily A member 1) and ABCG1 (ATP-binding cassette transporter subfamily G member 1). In this study, we aimed to investigate whether global deficiency in MC1-R signaling affects the development of atherosclerosis. Apoe -/- (apolipoprotein E deficient) mice were crossed with recessive yellow (Mc1r e/e ) mice carrying dysfunctional MC1-R and fed a high-fat diet to induce atherosclerosis. Apoe -/- Mc1r e/e mice developed significantly larger atherosclerotic lesions in the aortic sinus and in the whole aorta compared with Apoe -/- controls. In terms of plaque composition, MC1-R deficiency was associated with less collagen and smooth muscle cells and increased necrotic core, indicative of more vulnerable lesions. These changes were accompanied by reduced Abca1 and Abcg1 expression in the aorta. Furthermore, Apoe -/- Mc1r e/e mice showed a defect in bile acid metabolism that aggravated high-fat diet-induced hypercholesterolemia and hepatic lipid accumulation. Flow cytometric analysis of leukocyte profile revealed that dysfunctional MC1-R enhanced arterial accumulation of classical Ly6C high monocytes and macrophages, effects that were evident in mice fed a normal chow diet but not under high-fat diet conditions. In support of enhanced arterial recruitment of Ly6C high monocytes, these cells had increased expression of L-selectin and P-selectin glycoprotein ligand 1. The present study highlights the importance of MC1-R in the development of atherosclerosis. Deficiency in MC1-R signaling exacerbates atherosclerosis by disturbing cholesterol handling and by increasing arterial monocyte accumulation. © 2017 The Authors.

  10. Acute Hyperglycemia Associated with Anti-Cancer Medication

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    Yul Hwangbo

    2017-03-01

    Full Text Available Hyperglycemia during chemotherapy occurs in approximately 10% to 30% of patients. Glucocorticoids and L-asparaginase are well known to cause acute hyperglycemia during chemotherapy. Long-term hyperglycemia is also frequently observed, especially in patients with hematologic malignancies treated with L-asparaginase-based regimens and total body irradiation. Glucocorticoid-induced hyperglycemia often develops because of increased insulin resistance, diminished insulin secretion, and exaggerated hepatic glucose output. Screening strategies for this condition include random glucose testing, hemoglobin A1c testing, oral glucose loading, and fasting plasma glucose screens. The management of hyperglycemia starts with insulin or sulfonylurea, depending on the type, dose, and delivery of the glucocorticoid formulation. Mammalian target of rapamycin (mTOR inhibitors are associated with a high incidence of hyperglycemia, ranging from 13% to 50%. Immunotherapy, such as anti-programmed death 1 (PD-1 antibody treatment, induces hyperglycemia with a prevalence of 0.1%. The proposed mechanism of immunotherapy-induced hyperglycemia is an autoimmune process (insulitis. Withdrawal of the PD-1 inhibitor is the primary treatment for severe hyperglycemia. The efficacy of glucocorticoid therapy is not fully established and the decision to resume PD-1 inhibitor therapy depends on the severity of the hyperglycemia. Diabetic patients should achieve optimized glycemic control before initiating treatment, and glucose levels should be monitored periodically in patients initiating mTOR inhibitor or PD-1 inhibitor therapy. With regard to hyperglycemia caused by anti-cancer therapy, frequent monitoring and proper management are important for promoting the efficacy of anti-cancer therapy and improving patients' quality of life.

  11. Hyperglycemia

    Science.gov (United States)

    Hyperglycemia means high blood sugar or glucose. Glucose comes from the foods you eat. Insulin is a ... glucose into your cells to give them energy. Hyperglycemia happens when your body doesn't make enough ...

  12. Curcumin analog L3 alleviates diabetic atherosclerosis by multiple effects.

    Science.gov (United States)

    Zheng, Bin; Yang, Liu; Wen, Caixia; Huang, Xiuwang; Xu, Chenxia; Lee, Kuan-Han; Xu, Jianhua

    2016-03-15

    L3, an analog of curcumin, is a compound isolated from a traditional Chinese medicine Turmeric. In this paper, we aims to explore the efficacy of L3 on diabetic atherosclerosis and the related mechanism. The effect of L3 was studied on glucose and lipid metabolism, antioxidant status, atherosclerosis-related indexes and pathological changes of main organs in the mice model of diabetes induced by streptozotocin and high-fat diet. The results showed that L3 treatment could meliorate dyslipidemia and hyperglycemia, reduce oxidative stress, enhance the activity of antioxidases, increase the nitric oxide level in plasma and aortic arch, decrease the production of reactive oxygen species in pancreas and lectin-like oxidized low-density lipoprotein receptor-1 expression in aortic arch, and meliorate the fatty and atherosclerotic degeneration in aortic arch, thereby preventing the development of diabetes and its complications. These results suggested that L3 can alleviate the diabetic atherosclerosis by multiple effects. This study provided scientific basis for the further research and clinical application of L3. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Inhibition of nuclear factor of activated T-cells (NFAT suppresses accelerated atherosclerosis in diabetic mice.

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    Anna V Zetterqvist

    Full Text Available OBJECTIVE OF THE STUDY: Diabetic patients have a much more widespread and aggressive form of atherosclerosis and therefore, higher risk for myocardial infarction, peripheral vascular disease and stroke, but the molecular mechanisms leading to accelerated damage are still unclear. Recently, we showed that hyperglycemia activates the transcription factor NFAT in the arterial wall, inducing the expression of the pro-atherosclerotic protein osteopontin. Here we investigate whether NFAT activation may be a link between diabetes and atherogenesis. METHODOLOGY AND PRINCIPAL FINDINGS: Streptozotocin (STZ-induced diabetes in apolipoprotein E(-/- mice resulted in 2.2 fold increased aortic atherosclerosis and enhanced pro-inflammatory burden, as evidenced by elevated blood monocytes, endothelial activation- and inflammatory markers in aorta, and pro-inflammatory cytokines in plasma. In vivo treatment with the NFAT blocker A-285222 for 4 weeks completely inhibited the diabetes-induced aggravation of atherosclerosis, having no effect in non-diabetic mice. STZ-treated mice exhibited hyperglycemia and higher plasma cholesterol and triglycerides, but these were unaffected by A-285222. NFAT-dependent transcriptional activity was examined in aorta, spleen, thymus, brain, heart, liver and kidney, but only augmented in the aorta of diabetic mice. A-285222 completely blocked this diabetes-driven NFAT activation, but had no impact on the other organs or on splenocyte proliferation or cytokine secretion, ruling out systemic immunosuppression as the mechanism behind reduced atherosclerosis. Instead, NFAT inhibition effectively reduced IL-6, osteopontin, monocyte chemotactic protein 1, intercellular adhesion molecule 1, CD68 and tissue factor expression in the arterial wall and lowered plasma IL-6 in diabetic mice. CONCLUSIONS: Targeting NFAT signaling may be a novel and attractive approach for the treatment of diabetic macrovascular complications.

  14. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Text Size: A A A Listen En Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical term ... body can't use insulin properly. What Causes Hyperglycemia? A number of things can cause hyperglycemia: If ...

  15. Hyperglycemia - infants

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    ... this page: //medlineplus.gov/ency/article/007228.htm Hyperglycemia - infants To use the sharing features on this page, please enable JavaScript. Hyperglycemia is abnormally high blood sugar. The medical term ...

  16. Vascular wall proteoglycan synthesis and structure as a target for the prevention of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Peter J Little

    2007-03-01

    Full Text Available Peter J Little1, 2, 3, Mandy L. Ballinger1, Narin Osman1,31Cell Biology of Diabetes Laboratory, Baker Heart Research Institute, Melbourne, Australia; Monash University, Departments of 2Medicine and 3Immunology, Central and Eastern Clinical School, Alfred Hospital, Melbourne, AustraliaAbstract: Atherosclerosis is the underlying pathology of most cardiovascular disease and it represents the major cause of premature death in modern societies. Current therapies target risk factors being hypertension, hypercholesterolemia, hypertriglyceridemia and hyperglycemia when diabetes is present however the maximum efficacy of these strategies is often 30% or less. Areas of vascular biology that may lead to the development of a complementary vascular wall directed therapy are: inflammation, oxidation, endothelial dysfunction, diabetes-specific factors —hyperglycemia and advanced glycation endproducts and lipid retention by vascular matrix specifically proteoglycans. The major structural features of proteoglycans that determine low-density lipoprotein (LDL binding are the length and sulfation pattern on the glycosaminoglycan (GAG chains. Emerging data discussed in this review indicates that these structural properties are subject to considerable regulation by vasoactive substances possibly using novel signaling pathways. For example, GAG elongation stimulated by platelet-derived growth factor is not blocked by the receptor tyrosine kinase antagonist, genistein suggesting that there may be a previously unknown signaling pathway involved in this response. Thus, modifying proteoglycan synthesis and structure may represent a prime target to prevent LDL binding and entrapment in the vessel wall and thus prevent the development and progression of atherosclerosis.Keywords: proteoglycans, signaling, lipoproteins, atherosclerosis

  17. Macrophage mitochondrial oxidative stress promotes atherosclerosis and nuclear factor-κB-mediated inflammation in macrophages.

    Science.gov (United States)

    Wang, Ying; Wang, Gary Z; Rabinovitch, Peter S; Tabas, Ira

    2014-01-31

    Mitochondrial oxidative stress (mitoOS) has been shown to correlate with the progression of human atherosclerosis. However, definitive cell type-specific causation studies in vivo are lacking, and the molecular mechanisms of potential proatherogenic effects remain to be determined. Our aims were to assess the importance of macrophage mitoOS in atherogenesis and to explore the underlying molecular mechanisms. We first validated Western diet-fed Ldlr(-/-) mice as a model of human mitoOS-atherosclerosis association by showing that non-nuclear oxidative DNA damage, a marker of mitoOS in lesional macrophages, correlates with aortic root lesion development. To investigate the importance of macrophage mitoOS, we used a genetic engineering strategy in which the OS suppressor catalase was ectopically expressed in mitochondria (mCAT) in macrophages. MitoOS in lesional macrophages was successfully suppressed in these mice, and this led to a significant reduction in aortic root lesional area. The mCAT lesions had less monocyte-derived cells, less Ly6c(hi) monocyte infiltration into lesions, and lower levels of monocyte chemotactic protein-1. The decrease in lesional monocyte chemotactic protein-1 was associated with the suppression of other markers of inflammation and with decreased phosphorylation of RelA (NF-κB p65), indicating decreased activation of the proinflammatory NF-κB pathway. Using models of mitoOS in cultured macrophages, we showed that mCAT suppressed monocyte chemotactic protein-1 expression by decreasing the activation of the IκB-kinase β-RelA NF-κB pathway. MitoOS in lesional macrophages amplifies atherosclerotic lesion development by promoting NF-κB-mediated entry of monocytes and other inflammatory processes. In view of the mitoOS-atherosclerosis link in human atheromata, these findings reveal a potentially new therapeutic target to prevent the progression of atherosclerosis.

  18. NFE2 Induces miR-423-5p to Promote Gluconeogenesis and Hyperglycemia by Repressing the Hepatic FAM3A-ATP-Akt Pathway.

    Science.gov (United States)

    Yang, Weili; Wang, Junpei; Chen, Zhenzhen; Chen, Ji; Meng, Yuhong; Chen, Liming; Chang, Yongsheng; Geng, Bin; Sun, Libo; Dou, Lin; Li, Jian; Guan, Youfei; Cui, Qinghua; Yang, Jichun

    2017-07-01

    Hepatic FAM3A expression is repressed under obese conditions, but the underlying mechanism remains unknown. This study determined the role and mechanism of miR-423-5p in hepatic glucose and lipid metabolism by repressing FAM3A expression. miR-423-5p expression was increased in the livers of obese diabetic mice and in patients with nonalcoholic fatty liver disease (NAFLD) with decreased FAM3A expression. miR-423-5p directly targeted FAM3A mRNA to repress its expression and the FAM3A-ATP-Akt pathway in cultured hepatocytes. Hepatic miR-423-5p inhibition suppressed gluconeogenesis and improved insulin resistance, hyperglycemia, and fatty liver in obese diabetic mice. In contrast, hepatic miR-423-5p overexpression promoted gluconeogenesis and hyperglycemia and increased lipid deposition in normal mice. miR-423-5p inhibition activated the FAM3A-ATP-Akt pathway and repressed gluconeogenic and lipogenic gene expression in diabetic mouse livers. The miR-423 precursor gene was further shown to be a target gene of NFE2, which induced miR-423-5p expression to repress the FAM3A-ATP-Akt pathway in cultured hepatocytes. Hepatic NFE2 overexpression upregulated miR-423-5p to repress the FAM3A-ATP-Akt pathway, promoting gluconeogenesis and lipid deposition and causing hyperglycemia in normal mice. In conclusion, under the obese condition, activation of the hepatic NFE2/miR-423-5p axis plays important roles in the progression of type 2 diabetes and NAFLD by repressing the FAM3A-ATP-Akt signaling pathway. © 2017 by the American Diabetes Association.

  19. Function and Therapeutic Potential of Mesenchymal Stem Cells in Atherosclerosis

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    Feifei Li

    2017-05-01

    Full Text Available Atherosclerosis is a complicated disorder and largely attributable to dyslipidaemia and chronic inflammation. Despite therapeutic advances over past decades, atherosclerosis remains the leading cause of mortality worldwide. Due to their capability of immunomodulation and tissue regeneration, mesenchymal stem cells (MSCs have evolved as an attractive therapeutic agent in various diseases including atherosclerosis. Accumulating evidences support the protective role of MSCs in all stages of atherosclerosis. In this review, we highlight the current understanding of MSCs including their characteristics such as molecular markers, tissue distribution, migratory property, immune-modulatory competence, etc. We also summarize MSC functions in animal models of atherosclerosis. MSC transplantation is able to modulate cytokine and chemokine secretion, reduce endothelial dysfunction, promote regulatory T cell function, decrease dyslipidemia, and stabilize vulnerable plaques during atherosclerosis development. In addition, MSCs may migrate to lesions where they develop into functional cells during atherosclerosis formation. Finally, the perspectives of MSCs in clinical atherosclerosis therapy are discussed.

  20. Racial Differences in and Prognostic Value of Biomarkers of Hyperglycemia.

    Science.gov (United States)

    Parrinello, Christina M; Sharrett, A Richey; Maruthur, Nisa M; Bergenstal, Richard M; Grams, Morgan E; Coresh, Josef; Selvin, Elizabeth

    2016-04-01

    We compared levels and associations of traditional (fasting glucose, HbA1c) and nontraditional (fructosamine, glycated albumin, and 1,5-anhydroglucitol [1,5-AG]) biomarkers of hyperglycemia with incident cardiovascular disease (CVD), incident end-stage renal disease (ESRD), and prevalent retinopathy in black and white adults. We included 10,373 participants without (8,096 white, 2,277 black) and 727 with diagnosed diabetes (425 white, 302 black) from the Atherosclerosis Risk in Communities (ARIC) Study. We used Cox proportional hazards models to compare hazards ratios of CVD and ESRD among blacks and whites from baseline (1990-1992) through 2012. We compared the odds ratios (from logistic regression) of retinopathy among blacks and whites. We tested for the interaction of each biomarker with race. Median values of biomarkers were higher among blacks versus whites (all P 0.10). The prognostic value of HbA1c, fructosamine, glycated albumin, and 1,5-AG with incident CVD, incident ESRD, and prevalent retinopathy were similar by race. Our results support similar interpretation of HbA1c and nontraditional biomarkers of hyperglycemia among black and whites with respect to long-term complications. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  1. Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1.

    Science.gov (United States)

    Sada, Kiminori; Nishikawa, Takeshi; Kukidome, Daisuke; Yoshinaga, Tomoaki; Kajihara, Nobuhiro; Sonoda, Kazuhiro; Senokuchi, Takafumi; Motoshima, Hiroyuki; Matsumura, Takeshi; Araki, Eiichi

    2016-01-01

    We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs), cellular hypoxia increased after incubation with high glucose (HG). A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD) overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1), a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner.

  2. Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1.

    Directory of Open Access Journals (Sweden)

    Kiminori Sada

    Full Text Available We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs, cellular hypoxia increased after incubation with high glucose (HG. A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1, a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner.

  3. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming

    DEFF Research Database (Denmark)

    Zimmer, Sebastian; Grebe, Alena; Bakke, Siril S

    2016-01-01

    -containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Because cholesterol accumulation and deposition of cholesterol crystals (CCs) trigger a complex inflammatory response, we tested the efficacy of the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound...... of CD as well as for augmented reverse cholesterol transport. Because CD treatment in humans is safe and CD beneficially affects key mechanisms of atherogenesis, it may therefore be used clinically to prevent or treat human atherosclerosis....

  4. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... when the body can't use insulin properly. What Causes Hyperglycemia? A number of things can cause ... 00 a.m. to 5:00 a.m.). What are the Symptoms of Hyperglycemia? The signs and ...

  5. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... help you avoid problems associated with hyperglycemia. How Do I Treat Hyperglycemia? You can often lower your ... your urine for ketones. If you have ketones, do not exercise. Exercising when ketones are present may ...

  6. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Dairy Food Tips Eating Out Quick Meal Ideas Snacks Nutrient Content Claims Understanding Carbohydrates Types of Carbohydrates ... Prevent Hyperglycemia? Your best bet is to practice good diabetes management and learn to detect hyperglycemia so ...

  7. Hyperglycemia (High Blood Glucose)

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  8. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... USB drives that can carry a person's full medical record for use in an emergency. How Can I Prevent Hyperglycemia? Your best bet is to practice good diabetes management and learn to detect hyperglycemia ...

  9. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... your blood and then treating high blood glucose early will help you avoid problems associated with hyperglycemia. ... to detect hyperglycemia so you can treat it early — before it gets worse. If you're new ...

  10. Hyperglycemia (High Blood Glucose)

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  11. Hyperglycemia (High Blood Glucose)

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  12. Hyperglycemia (High Blood Glucose)

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  13. Hyperglycemia (High Blood Glucose)

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  14. Modulation of ambient temperature promotes inflammation and initiates atherosclerosis in wild type C57BL/6 mice

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    Daniel A. Giles

    2016-11-01

    Full Text Available Objectives: Obesity and obesity-associated inflammation is central to a variety of end-organ sequelae including atherosclerosis, a leading cause of death worldwide. Although mouse models have provided important insights into the immunopathogenesis of various diseases, modeling atherosclerosis in mice has proven difficult. Specifically, wild-type (WT mice are resistant to developing atherosclerosis, while commonly used genetically modified mouse models of atherosclerosis are poor mimics of human disease. The lack of a physiologically relevant experimental model of atherosclerosis has hindered the understanding of mechanisms regulating disease development and progression as well as the development of translational therapies. Recent evidence suggests that housing mice within their thermoneutral zone profoundly alters murine physiology, including both metabolic and immune processes. We hypothesized that thermoneutral housing would allow for augmentation of atherosclerosis induction and progression in mice. Methods: ApoE−/− and WT mice were housed at either standard (TS or thermoneutral (TN temperatures and fed either a chow or obesogenic “Western” diet. Analysis included quantification of (i obesity and obesity-associated downstream sequelae, (ii the development and progression of atherosclerosis, and (iii inflammatory gene expression pathways related to atherosclerosis. Results: Housing mice at TN, in combination with an obesogenic “Western” diet, profoundly augmented obesity development, exacerbated atherosclerosis in ApoE−/− mice, and initiated atherosclerosis development in WT mice. This increased disease burden was associated with altered lipid profiles, including cholesterol levels and fractions, and increased aortic plaque size. In addition to the mild induction of atherosclerosis, we similarly observed increased levels of aortic and white adipose tissue inflammation and increased circulating immune cell expression of pathways

  15. Hyperglycemia induces memory impairment linked to increased acetylcholinesterase activity in zebrafish (Danio rerio).

    Science.gov (United States)

    Capiotti, Katiucia Marques; De Moraes, Daiani Almeida; Menezes, Fabiano Peres; Kist, Luiza Wilges; Bogo, Maurício Reis; Da Silva, Rosane Souza

    2014-11-01

    Diabetes mellitus, which causes hyperglycemia, affects the central nervous system and can impairs cognitive functions, such as memory. The aim of this study was to investigate the effects of hyperglycemia on memory as well as on the activity of acethylcholinesterase. Hyperglycemia was induced in adult zebrafish by immersion in glucose 111mM by 14 days. The animals were divided in 4 groups: control, glucose-treated, glucose-washout 7-days and glucose-washout 14-days. We evaluated the performance in inhibitory avoidance task and locomotor activity. We also determined acethylcholinesterase activity and gene expression from whole brain. In order to counteract the effect of hyperglycemia underlined by effects on acethylcholinesterase activity, we treated the animals with galantamine (0.05ng/g), an inhibitor of this enzyme. Also we evaluated the gene expression of insulin receptor and glucose transporter from zebrafish brain. The hyperglycemia promoted memory deficit in adult zebrafish, which can be explained by increased AChE activity. The ache mRNA levels from zebrafish brain were decrease in 111mM glucose group and returned to normal levels after 7 days of glucose withdrawal. Insulin receptors (insra-1, insra-2, insrb-1 and insrb-2) and glut-3 mRNA levels were not significantly changed. Our results also demonstrated that galantamine was able to reverse the memory deficit caused by hyperglycemia, demonstrating that these effects involve modulation of AChE activity. These data suggest that the memory impairment induced by hyperglycemia is underlined by the cholinergic dysfunction caused by the mechanisms involving the control of acetylcholinesterase function and gene expression. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Hyperthermia and hyperglycemia in oncology

    International Nuclear Information System (INIS)

    Zhavrid, Eh.A.; Osinskij, S.P.; Fradkin, S.Z.

    1987-01-01

    Consideration is being given to publication data and results of author's investigations into the effect of hyperthermia and hyperglycemia on physico-chemical characteristics and growth of various experimental tumors. Factors, modifying thermosensitivity, mechanisms of hyperthermia effect, various aspects of thermochimio- and thermoradiotherapy have been analyzed. Effect of artificial hyperglycemia on metabolism and kinetics of tumor and some normal cells is considered in detail. Many data, testifying to sufficient growth of efficiency of oncologic patient treatment under conditions of multimodality therapy including hyperthermia and hyperglycemia are presented

  17. Mouse models for atherosclerosis and pharmaceutical modifiers

    NARCIS (Netherlands)

    Zadelaar, A.S.M.; Kleemann, R.; Verschuren, L.; Vries-van der Weij, J. de; Hoorn, J. van der; Princen, H.M.; Kooistra, T.

    2007-01-01

    Atherosclerosis is a multifactorial highly-complex disease with numerous etiologies that work synergistically to promote lesion development. The ability to develop preventive and ameliorative treatments will depend on animal models that mimic the human subject metabolically and pathophysiologically

  18. Coronary atherosclerosis: Significance of autophagic armour.

    Science.gov (United States)

    Arora, Mansi; Kaul, Deepak

    2012-09-26

    Autophagy is a lysosomal degradation pathway of cellular components such as organelles and long-lived proteins. Though a protective role for autophagy has been established in various patho-physiologic conditions such as cancer, neurodegeneration, aging and heart failure, a growing body of evidence now reveals a protective role for autophagy in atherosclerosis, mainly by removing oxidatively damaged organelles and proteins and also by promoting cholesterol egress from the lipid-laden cells. Recent studies by Razani et al and Liao et al unravel novel pathways that might be involved in autophagic protection and in this commentary we highlight the importance of autophagy in atherosclerosis in the light of these two recent papers.

  19. Atherosclerosis induced by arsenic in drinking water in rats through altering lipid metabolism

    International Nuclear Information System (INIS)

    Cheng, Tain-Junn; Chuu, Jiunn-Jye; Chang, Chia-Yu; Tsai, Wan-Chen; Chen, Kuan-Jung; Guo, How-Ran

    2011-01-01

    Arsenic in drinking water is a global environmental health problem, and the exposure may increase cardiovascular and cerebrovascular diseases mortalities, most likely through causing atherosclerosis. However, the mechanism of atherosclerosis formation after arsenic exposure is still unclear. To study the mechanism of atherosclerosis formation after arsenic exposure and explore the role of high cholesterol diet (HCD) in this process, we fed spontaneous hypertensive rats and Wistar Kyoto rats with basal diet or HCD and provided with them drinking water containing arsenic at different ages and orders for 20 consecutive weeks. We measured high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, heat shock protein 70 (HSP 70), and high sensitive C-reactive protein (hs-CRP) at predetermined intervals and determined expressions of cholesteryl ester transfer protein-1 (CETP-1) and liver X receptor β (LXRβ) in the liver. Atherosclerosis was determined by examining the aorta with hematoxylin and eosin stain. After 20 weeks, we found arsenic, alone or combined with HCD, may promote atherosclerosis formation with transient increases in HSP 70 and hs-CRP. Early combination exposure decreased the HDL-C/LDL-C ratio without changing the levels of total cholesterol and triglyceride until 30 weeks old. Both CETP-1 and LXRβ activities were suppressed, most significantly in early combination exposure. In conclusion, arsenic exposure may induce atherosclerosis through modifying reverse cholesterol transport in cholesterol metabolism and suppressing LXRβ and CEPT-1 expressions. For decreasing atherosclerosis related mortality associated with arsenic, preventing exposure from environmental sources in early life is an important element. - Highlights: → Arsenic causes cardiovascular and cerebrovascular diseases through atherosclerosis. → Arsenic may promote atherosclerosis with transient increase in HSP 70 and hs

  20. Hyperglycemia, a Neglected Factor during Cancer Progression

    Directory of Open Access Journals (Sweden)

    Wanxing Duan

    2014-01-01

    Full Text Available Recent evidence from large cohort studies suggests that there exists a higher cancer incidence in people with type 2 diabetes (DM2. However, to date, the potential reasons for this association remain unclear. Hyperglycemia, the most important feature of diabetes, may be responsible for the excess glucose supply for these glucose-hungry cells, and it contributes to apoptosis resistance, oncogenesis, and tumor cell resistance to chemotherapy. Considering associations between diabetes and malignancies, the effect of hyperglycemia on cancer progression in cancer patients with abnormal blood glucose should not be neglected. In this paper, we describe the role that hyperglycemia plays in cancer progression and treatment and illustrate that hyperglycemia may contribute to a more malignant phenotype of cancer cells and lead to drug resistance. Therefore, controlling hyperglycemia may have important therapeutic implications in cancer patients.

  1. Medium-chain triglycerides promote macrophage reverse cholesterol transport and improve atherosclerosis in ApoE-deficient mice fed a high-fat diet.

    Science.gov (United States)

    Zhang, Xinsheng; Zhang, Yong; Liu, Yinghua; Wang, Jin; Xu, Qing; Yu, Xiaoming; Yang, Xueyan; Liu, Zhao; Xue, Changyong

    2016-09-01

    We previously observed that medium-chain triglycerides (MCTs) could reduce body fat mass and improve the metabolism of cholesterol. We hypothesized that MCTs can improve atherosclerosis by promoting the reverse cholesterol transport (RCT) process. Therefore, the objective of this study was to investigate the roles of MCTs in macrophage RCT and the progression of atherosclerosis. To test this hypothesis, 30 4-week-old ApoE-deficient (ApoE(-/-)) mice were randomly divided into 2 groups and fed a diet of 2% MCTs or long-chain triglycerides (LCTs) for 16 weeks. Ten age- and sex-matched C57BL/6J mice were fed a diet of 2% LCTs as the control. Macrophage-to-feces RCT was assessed in vivo by intraperitoneal injection of RAW 264.7 macrophages containing (3)H-labeled cholesterol, and atherosclerotic plaques were measured. The mRNA and protein expressions were determined by reverse transcriptase polymerase chain reaction and Western blot analyses, respectively. There was a greater decrease in body fat mass, atherosclerotic plaques, and an improvement in serum lipid profiles. In addition, the MCT mice group showed an increase in (3)H-tracer in the feces and a decrease in the liver. Significantly higher levels of mRNA and protein expression of hepatic ATP-binding cassette transporter A1, ATP-binding cassette transporter G5, cholesterol 7α-hydroxylase, and intestinal ATP-binding cassette transporter G8, as well as lower levels of expression of intestinal Niemann-Pick C1-like 1, were found in the MCT group. These results suggest that MCTs could obviously promote macrophage RCT and improve atherosclerosis in ApoE(-/-) mice, indicating that MCTs have the potential to prevent cardiovascular disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Ritonavir binds to and downregulates estrogen receptors: Molecular mechanism of promoting early atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Jin [Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Science, Wuhan University, Wuhan 430071 (China); Wang, Ying [Department of Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Su, Ke [Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Liu, Min [Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Science, Wuhan University, Wuhan 430071 (China); Hu, Peng-Chao [Department of Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Ma, Tian; Li, Jia-Xi [Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Science, Wuhan University, Wuhan 430071 (China); Wei, Lei [Department of Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Zheng, Zhongliang, E-mail: biochem@whu.edu.cn [State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072 (China); Yang, Fang, E-mail: fang-yang@whu.edu.cn [Department of Physiology, School of Medicine, Wuhan University, Wuhan 430071 (China)

    2014-10-01

    Estrogenic actions are closely related to cardiovascular disease. Ritonavir (RTV), a human immunodeficiency virus (HIV) protease inhibitor, induces atherosclerosis in an estrogen-related manner. However, how RTV induce pathological phenotypes through estrogen pathway remains unclear. In this study, we found that RTV increases thickness of coronary artery walls of Sprague Dawley rats and plasma free fatty acids (FFA) levels. In addition, RTV could induce foam cell formation, downregulate both estrogen receptor α (ERα) and ERβ expression, upregulate G protein-coupled estrogen receptor (GPER) expression, and all of them could be partially blocked by 17β-estradiol (E2), suggesting RTV acts as an antagonist for E2. Computational modeling shows a similar interaction with ERα between RTV and 2-aryl indoles, which are highly subtype-selective ligands for ERα. We also found that RTV directly bound to ERα and selectively inhibited the nuclear localization of ERα, and residue Leu536 in the hydrophobic core of ligand binding domain (LBD) was essential for the interaction with RTV. In addition, RTV did not change the secondary structure of ERα-LBD like E2, which explained how ERα lost the capacity of nuclear translocation under the treatment of RTV. All of the evidences suggest that ritonavir acts as an antagonist for 17β-estradiol in regulating α subtype estrogen receptor function and early events of atherosclerosis. - Graphical abstract: RTV directly binds to ERα and Leu536 in the hydrophobic core of ligand binding domain is essential for the interaction. - Highlights: • RTV increases the thickness of rat coronary artery wall and foam cell formation. • RTV downregulates the expression of ERα and ERβ. • RTV inhibits ERα promoter activity. • RTV directly binds to ERα and the key amino acid is Leu536. • RTV inhibits the nuclear translocation of ERα and GPER.

  3. Ritonavir binds to and downregulates estrogen receptors: Molecular mechanism of promoting early atherosclerosis

    International Nuclear Information System (INIS)

    Xiang, Jin; Wang, Ying; Su, Ke; Liu, Min; Hu, Peng-Chao; Ma, Tian; Li, Jia-Xi; Wei, Lei; Zheng, Zhongliang; Yang, Fang

    2014-01-01

    Estrogenic actions are closely related to cardiovascular disease. Ritonavir (RTV), a human immunodeficiency virus (HIV) protease inhibitor, induces atherosclerosis in an estrogen-related manner. However, how RTV induce pathological phenotypes through estrogen pathway remains unclear. In this study, we found that RTV increases thickness of coronary artery walls of Sprague Dawley rats and plasma free fatty acids (FFA) levels. In addition, RTV could induce foam cell formation, downregulate both estrogen receptor α (ERα) and ERβ expression, upregulate G protein-coupled estrogen receptor (GPER) expression, and all of them could be partially blocked by 17β-estradiol (E2), suggesting RTV acts as an antagonist for E2. Computational modeling shows a similar interaction with ERα between RTV and 2-aryl indoles, which are highly subtype-selective ligands for ERα. We also found that RTV directly bound to ERα and selectively inhibited the nuclear localization of ERα, and residue Leu536 in the hydrophobic core of ligand binding domain (LBD) was essential for the interaction with RTV. In addition, RTV did not change the secondary structure of ERα-LBD like E2, which explained how ERα lost the capacity of nuclear translocation under the treatment of RTV. All of the evidences suggest that ritonavir acts as an antagonist for 17β-estradiol in regulating α subtype estrogen receptor function and early events of atherosclerosis. - Graphical abstract: RTV directly binds to ERα and Leu536 in the hydrophobic core of ligand binding domain is essential for the interaction. - Highlights: • RTV increases the thickness of rat coronary artery wall and foam cell formation. • RTV downregulates the expression of ERα and ERβ. • RTV inhibits ERα promoter activity. • RTV directly binds to ERα and the key amino acid is Leu536. • RTV inhibits the nuclear translocation of ERα and GPER

  4. Autophagy in muscle of glucose-infusion hyperglycemia rats and streptozotocin-induced hyperglycemia rats via selective activation of m-TOR or FoxO3.

    Directory of Open Access Journals (Sweden)

    Pengfei Lv

    Full Text Available Autophagy is a conserved process in eukaryotes required for metabolism and is involved in diverse diseases. To investigate autophagy in skeletal muscle under hyperglycemia status, we established two hyperglycemia-rat models that differ in their circulating insulin levels, by glucose infusion and singe high-dose streptozotocin injection. We then detected expression of autophagy related genes with real-time PCR and western blot. We found that under hyperglycemia status induced by glucose-infusion, autophagy was inhibited in rat skeletal muscle, whereas under streptozotocin-induced hyperglycemia status autophagy was enhanced. Meanwhile, hyperglycemic gastrocnemius muscle was more prone to autophagy than soleus muscle. Furthermore, inhibition of autophagy in skeletal muscle in glucose-infusion hyperglycemia rats was mediated by the m-TOR pathway while m-TOR and FoxO3 both contributed to enhancement of autophagy in gastrocnemius muscle in streptozotocin-induced hyperglycemia rats. These data shows that insulin plays a relatively more important role than hyperglycemia in regulating autophagy in hyperglycemia rat muscle through selectively activating the m-TOR or FoxO3 pathway in a fiber-selective manner.

  5. Implications of alcoholic cirrhosis in atherosclerosis of autopsied patients

    Directory of Open Access Journals (Sweden)

    Luciano Alves Matias da Silveira

    Full Text Available Summary Introduction: Alcoholism is a major public health problem, which has a high social cost and affects many aspects of human activity. Liver disease is one of the first consequences of alcohol abuse, and steatosis, liver cirrhosis and hepatitis may occur. Other organs are also affected with pathological changes, such as pancreatitis, cardiomyopathies, dyslipidemias and atherosclerosis. Objective: To identify the occurrence and degree of atherosclerosis in alcohol-dependent individuals with liver cirrhosis, observing macroscopic and microscopic changes in lipid and collagen deposits and in the liver. We also aimed to verify the association of lipid and collagen fiber deposits with gender, age and body mass index, and to relate alcoholism, liver cirrhosis and atherosclerosis. Method: We performed a study based on autopsy reports of patients with alcoholic liver cirrhosis, with analysis of aorta and liver fragments to verify the occurrence and degree of atherosclerosis, as well as collagen contents. Results: Microscopic atherosclerosis was higher in young subjects (early injury and in patients with alcoholic liver cirrhosis. The macroscopic analysis of atherosclerosis in aortas showed that patients in more advanced age groups presented more severe classifications. Atherosclerosis, both micro and macroscopically, and the percentage of fibrosis in the liver and aorta were more expressive in females. Conclusion: Cirrhotic patients presented a higher percentage of fibrosis and lipidosis, and may represent a group susceptible to the accelerated progression of cardiovascular diseases. Investigative studies contribute to targeting health-promoting interventions, reducing the mortality and costs of treating cardiovascular disease.

  6. IL-1R and MyD88 signalling in CD4+ T cells promote Th17 immunity and atherosclerosis.

    Science.gov (United States)

    Engelbertsen, Daniel; Rattik, Sara; Wigren, Maria; Vallejo, Jenifer; Marinkovic, Goran; Schiopu, Alexandru; Björkbacka, Harry; Nilsson, Jan; Bengtsson, Eva

    2018-01-01

    The role of CD4+ T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper sub-sets. In this study, we tested the roles of IL-1R1 and MyD88 signalling in CD4+ T cells in atherosclerosis. We transferred apoe-/-myd88+/+ or apoe-/-myd88-/- CD4+ T cells to T- and B-cell-deficient rag1-/-apoe-/- mice fed high fat diet. Mice given apoe-/-myd88-/- CD4+ T cells exhibited reduced atherosclerosis compared with mice given apoe-/-myd88+/+ CD4+ T cells. CD4+ T cells from apoe-/-myd88-/- produced less IL-17 but similar levels of IFN-γ. Treatment of human CD4+ T cells with a MyD88 inhibitor inhibited IL-17 secretion in vitro. Transfer of il1r1-/- CD4+ T cells recapitulated the phenotype seen by transfer of myd88-/- CD4+ T cells with reduced lesion development and a reduction in Th17 and IL-17 production compared with wild type CD4+ T cell recipients. Relative collagen content of lesions was reduced in mice receiving il1r1-/- CD4+ T cells. We demonstrate that both IL1R and MyD88 signalling in CD4+ T cells promote Th17 immunity, plaque growth and may regulate plaque collagen levels. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

  7. Phytosterols and atherosclerosis

    DEFF Research Database (Denmark)

    Schrøder, Malene

    Cardiovascular disease (CVD) is the major cause of premature deaths worldwide. Coronary heart disease is the most common CVD, caused by atherosclerosis in the coronary arteries. Atherosclerosis is a multifactorial disease influenced by both genetic and environmental factors. WHO has in 2007 listed...... in its “Guidelines for assessment and management of cardiovascular risk” the following risk factors to influence progressive atherosclerosis: hypertension, abnormal blood lipids, diabetes, unhealthy diet, physical inactivity and smoking. Phytosterols (plant sterols and plant stanols) are known...... their blood cholesterol levels. The aim of this Ph.D. project was to investigate the effects of phytosterols on the development of atherosclerosis in the aorta of heterozygous Watanabe Heritable Hyperlipidemic (WHHL) rabbits. The main advantage of animal studies to human studies in atherosclerosis research...

  8. Hemichorea-hemiballismus associated with hyperglycemia: A case report

    International Nuclear Information System (INIS)

    Heo, Young Jin; Jeong, Hae Woong

    2017-01-01

    Hemichorea-hemiballism (HCHB) associated with nonketotic hyperglycemia is the most common cause of unilateral chorea in patients with type 2 diabetes mellitus. T1-weighted MRI characteristically demonstrates hyperintensity in the contralateral corpus striatum. Here we describe a case of HCHB associated with nonketotic hyperglycemia and unusual brain involvement. A 51-year-old man presented with involuntary limb movements for several months. He had a history of diabetes mellitus and poorly controlled hyperglycemia. MRI demonstrated characteristic striatal hyperintensity, with involvement of the temporal lobe and midbrain. The patient's hyperglycemia was controlled with medication. However, his involuntary movements were reduced in terms of severity, but not eliminated, by the time of discharge. HCHB associated with hyperglycemia usually resolves rapidly after correction of blood glucose levels; thus, early recognition and glycemic control are needed to prevent an irreversible outcome

  9. Hemichorea-hemiballismus associated with hyperglycemia: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Heo, Young Jin; Jeong, Hae Woong [Dept.of Radiology, Busan Paik Hospital, Inje University, Busan (Korea, Republic of)

    2017-04-15

    Hemichorea-hemiballism (HCHB) associated with nonketotic hyperglycemia is the most common cause of unilateral chorea in patients with type 2 diabetes mellitus. T1-weighted MRI characteristically demonstrates hyperintensity in the contralateral corpus striatum. Here we describe a case of HCHB associated with nonketotic hyperglycemia and unusual brain involvement. A 51-year-old man presented with involuntary limb movements for several months. He had a history of diabetes mellitus and poorly controlled hyperglycemia. MRI demonstrated characteristic striatal hyperintensity, with involvement of the temporal lobe and midbrain. The patient's hyperglycemia was controlled with medication. However, his involuntary movements were reduced in terms of severity, but not eliminated, by the time of discharge. HCHB associated with hyperglycemia usually resolves rapidly after correction of blood glucose levels; thus, early recognition and glycemic control are needed to prevent an irreversible outcome.

  10. Management of Hyperglycemia During Enteral and Parenteral Nutrition Therapy

    Science.gov (United States)

    Umpierrez, Guillermo E.

    2013-01-01

    Hyperglycemia is a frequent complication of enteral and parenteral nutrition in hospitalized patients. Extensive evidence from observational studies indicates that the development of hyperglycemia during parenteral and enteral nutrition is associated with an increased risk of death and infectious complications. There are no specific guidelines recommending glycemic targets and effective strategies for the management of hyperglycemia during specialized nutritional support. Managing hyperglycemia in these patients should include optimization of carbohydrate content and administration of intravenous or subcutaneous insulin therapy. The administration of continuous insulin infusion and insulin addition to nutrition bag are efficient approaches to control hyperglycemia during parenteral nutrition. Subcutaneous administration of long-acting insulin with scheduled or corrective doses of short-acting insulin is superior to the sliding scale insulin strategy in patients receiving enteral feedings. Randomized controlled studies are needed to evaluate safe and effective therapeutic strategies for the management of hyperglycemia in patients receiving nutritional support. PMID:23065369

  11. Frequency of Subclinical Atherosclerosis in Brazilian HIV-Infected Patients.

    Science.gov (United States)

    Salmazo, Péricles Sidnei; Bazan, Silméia Garcia Zanati; Shiraishi, Flávio Gobbis; Bazan, Rodrigo; Okoshi, Katashi; Hueb, João Carlos

    2018-04-09

    AIDS as well as atherosclerosis are important public health problems. The longer survival among HIV-infected is associated with increased number of cardiovascular events in this population, and this association is not fully understood. To identify the frequency of subclinical atherosclerosis in HIV-infected patients compared to control subjects; to analyze associations between atherosclerosis and clinical and laboratory variables, cardiovascular risk factors, and the Framingham coronary heart disease risk score (FCRS). Prospective cross-sectional case-control study assessing the presence of subclinical atherosclerosis in 264 HIV-infected patients and 279 controls. Clinical evaluation included ultrasound examination of the carotid arteries, arterial stiffness by pulse wave velocity (PWV) and augmentation index (AIx), laboratory analysis of peripheral blood, and cardiovascular risk according to FCRS criteria. The significance level adopted in the statistical analysis was p media thickness was higher in the HIV group than in controls (p media thickness, was not associated with carotid plaque frequency, and did not alter the mechanical characteristics of the arterial system (PWV and AIx). HIV-infected patients are at increased risk of atherosclerosis in association with classical cardiovascular risk factors. Treatment with protease inhibitors does not promote functional changes in the arteries, and shows no association with increased frequency of atherosclerotic plaques in carotid arteries. The FCRS may be inappropriate for this population.

  12. Risk factors for perioperative hyperglycemia in primary hip and knee replacements

    Science.gov (United States)

    Jämsen, Esa; Nevalainen, Pasi I; Eskelinen, Antti; Kalliovalkama, Jarkko; Moilanen, Teemu

    2015-01-01

    Background and purpose Background and purpose — Perioperative hyperglycemia has been associated with adverse outcomes in several fields of surgery. In this observational study, we identified factors associated with an increased risk of hyperglycemia following hip and knee replacement. Patients and methods Patients and methods — We prospectively monitored changes in glucose following primary hip and knee replacements in 191 patients with osteoarthritis. Possible associations of patient characteristics and operation-related factors with hyperglycemia (defined as glucose > 7.8 mmol/L in 2 consecutive measurements) and severe hyperglycemia (glucose > 10 mmol/L) were analyzed using binary logistic regression with adjustment for age, sex, operated joint, and anesthesiological risk score. Results Results — 76 patients (40%) developed hyperglycemia, and 48 of them (25% of the whole cohort) had severe hyperglycemia. Glycemic responses were similar following hip replacement and knee replacement. Previously diagnosed diabetes was associated with an increased risk of hyperglycemia and severe hyperglycemia, compared to patients with normal glucose metabolism, whereas newly diagnosed diabetes and milder glucose metabolism disorders had no effect. In patients without previously diagnosed diabetes, increased values of preoperative glycosylated hemoglobin (HbA1c) and fasting glucose on the day of operation were associated with hyperglycemia. Higher anesthesiological risk score—but none of the operation-related factors analyzed—was associated with an increased risk of hyperglycemia. Interpretation Interpretation — Perioperative hyperglycemia is common in primary hip and knee replacements. Previously diagnosed diabetes is the strongest risk factor for hyperglycemia. In patients with no history of diabetes, preoperative HbA1c and fasting glucose on the day of operation can be used to stratify the risk of hyperglycemia. PMID:25409255

  13. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Information Legal Assistance Success Stories Complications Hypoglycemia Hyperglycemia Skin Complications Eye Complications Neuropathy Foot Complications DKA (Ketoacidosis) & ...

  14. Is type 2 diabetes mellitus a vascular disease (atheroscleropathy with hyperglycemia a late manifestation? The role of NOS, NO, and redox stress.

    Directory of Open Access Journals (Sweden)

    Tyagi Suresh C

    2003-02-01

    Full Text Available Abstract Background Cardiovascular disease accounts for at least 85 percent of deaths for those patients with type 2 diabetes mellitus (T2DM. Additionally, 75 percent of these deaths are due to ischemic heart disease. Hypothesis Is type 2 diabetes mellitus a vascular disease (atheroscleropathy with hyperglycemia a late manifestation? The role of NOS, NO, and redox stress. Testing of the hypothesis The vulnerable three arms of the eNOS reaction responsible for the generation of eNO is discussed in relation to the hypothesis: (1. The L-arginine substrate. (2. The eNOS enzyme. (3. The BH4 cofactor. Implications of the hypothesis If we view T2DM as a vascular disease initially with a later manifestation of hyperglycemia, we may be able to better understand and modify the multiple toxicities associated with insulin resistance, metabolic syndrome, prediabetes, overt T2DM, and accelerated atherosclerosis (atheroscleropathy. The importance of endothelial nitric oxide synthase, endothelial nitric oxide, tetrahydrobiopterin (BH4, L-arginine, and redox stress are discussed in relation to endothelial cell dysfunction and the development and progression of atheroscleropathy and T2DM. In addition to the standard therapies to restore endothelial cell dysfunction and stabilization of vulnerable atherosclerotic plaques, this article will discuss the importance of folic acid (5MTHF supplementation in this complex devastating disease process. Atheroscleropathy and hyperglycemia could be early and late manifestations, respectively, in the natural progressive history of T2DM.

  15. Endothelial GPR124 Exaggerates the Pathogenesis of Atherosclerosis by Activating Inflammation

    Directory of Open Access Journals (Sweden)

    Dong-Mei Gong

    2018-01-01

    Full Text Available Background/Aims: Endothelial cell dysfunction is the principal pathological process underlying atherosclerotic cardiovascular disease. G protein-coupled receptor 124 (GPR124, an orphan receptor in the adhesion GPCR subfamily, promotes angiogenesis in the brain. In the present study, we explored the role of endothelial GPR124 in the development and progression of atherosclerosis in adult mice. Methods: Using tetracycline-inducible transgenic systems, we generated mice expressing GPR124 specifically under control of the Tie-2 promoter. The animal model of atherosclerosis was constructed by intravenously injecting AAV-PCSK9DY into tetracycline-regulated mice and feeding the mice a high-fat diet for 16 consecutive weeks. Biochemical analysis and immunohistochemistry methods were used to address the role and mechanism of GPR124 in the pathological process of atherosclerosis. Results: Higher TC (total cholesterol and LDL-C (low density lipoprotein cholesterol levels in serum and greater lipid deposition in the aortic sinus were found in atherosclerotic mice with GPR124 overexpression, coincident with the elevated proliferation of smooth muscle cells. We observed an elevation of ONOO- in the aortic sinus in this model by using immunofluorescence, and the experiments showed that the specific overexpression of GPR124 in the endothelium induced the up-regulation of CD68, NLRP3 and caspase-1 levels in the aortic sinus. Conclusion: The above results indicate that manipulating GPR124 in the endothelium may contribute to delayed pathological progression of atherosclerosis.

  16. Monitoring of Hypocalcaemia & Hyperglycemia predictive consequences of Thyroidectomy

    Science.gov (United States)

    2014-01-01

    Background Hyperglycemia and hypocalcaemia have separately been attributed to adverse outcomes in critically ill patients. The study was aim determine whether hyperglycemia and hypocalcaemia together post-operative effect of thyroidectomy and evaluate the gender & age impact on the extend of clinical condition. Methods All the patients underwent thyroidectomy in the duration of 1st Jan 2012 till 30th June, 2013 in HPP and HUSM Kelantan, Malaysia. Serum evaluation has been made on 4 consecutive reading with duration of 6 hours. The predictive trend has been established to identify the hypokalemic and hyperglycemic condition. Ethical approvals & Patients’ consent forms have been made prior to conduct this study. Results The incidence of hyperglycemia [≥ 150 mg/dl(8.3 mmol/L)] and hypocalcaemia (serum calcium effects on mortality. Conclusion As demonstrated, the prevalence of hyperglycemia and hypocalcaemia in post-thyroidectomy patients is considerable high. Also, the linear association pattern has been shown. However, considering the disease severity, the association of hyperglycemia and hypocalcaemia with surgical ward indicators of morbidity could not be verified. PMID:24684723

  17. Antenatal dexamethasone before asphyxia promotes cystic neural injury in preterm fetal sheep by inducing hyperglycemia.

    Science.gov (United States)

    Lear, Christopher A; Davidson, Joanne O; Mackay, Georgia R; Drury, Paul P; Galinsky, Robert; Quaedackers, Josine S; Gunn, Alistair J; Bennet, Laura

    2018-04-01

    Antenatal glucocorticoid therapy significantly improves the short-term systemic outcomes of prematurely born infants, but there is limited information available on their impact on neurodevelopmental outcomes in at-risk preterm babies exposed to perinatal asphyxia. Preterm fetal sheep (0.7 of gestation) were exposed to a maternal injection of 12 mg dexamethasone or saline followed 4 h later by asphyxia induced by 25 min of complete umbilical cord occlusion. In a subsequent study, fetuses received titrated glucose infusions followed 4 h later by asphyxia to examine the hypothesis that hyperglycemia mediated the effects of dexamethasone. Post-mortems were performed 7 days after asphyxia for cerebral histology. Maternal dexamethasone before asphyxia was associated with severe, cystic brain injury compared to diffuse injury after saline injection, with increased numbers of seizures, worse recovery of brain activity, and increased arterial glucose levels before, during, and after asphyxia. Glucose infusions before asphyxia replicated these adverse outcomes, with a strong correlation between greater increases in glucose before asphyxia and greater neural injury. These findings strongly suggest that dexamethasone exposure and hyperglycemia can transform diffuse injury into cystic brain injury after asphyxia in preterm fetal sheep.

  18. Chromium supplementation improved post-stroke brain infarction and hyperglycemia.

    Science.gov (United States)

    Chen, Wen-Ying; Mao, Frank Chiahung; Liu, Chia-Hsin; Kuan, Yu-Hsiang; Lai, Nai-Wei; Wu, Chih-Cheng; Chen, Chun-Jung

    2016-04-01

    Hyperglycemia is common after acute stroke and is associated with a worse outcome of stroke. Thus, a better understanding of stress hyperglycemia is helpful to the prevention and therapeutic treatment of stroke. Chromium is an essential nutrient required for optimal insulin activity and normal carbohydrate and lipid metabolism. Beyond its nutritional effects, dietary supplement of chromium causes beneficial outcomes against several diseases, in particular diabetes-associated complications. In this study, we investigated whether post-stroke hyperglycemia involved chromium dynamic mobilization in a rat model of permanent focal cerebral ischemia and whether dietary supplement of chromium improved post-stroke injury and alterations. Stroke rats developed brain infarction, hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance. Post-stroke hyperglycemia was accompanied by elevated secretion of counter-regulatory hormones including glucagon, corticosterone, and norepinephrine, decreased insulin signaling in skeletal muscles, and increased hepatic gluconeogenesis. Correlation studies revealed that counter-regulatory hormone secretion showed a positive correlation with chromium loss and blood glucose increased together with chromium loss. Daily chromium supplementation increased tissue chromium levels, attenuated brain infarction, improved hyperglycemia, and decreased plasma levels of glucagon and corticosterone in stroke rats. Our findings suggest that stroke rats show disturbance of tissue chromium homeostasis with a net loss through urinary excretion and chromium mobilization and loss might be an alternative mechanism responsible for post-stroke hyperglycemia.

  19. Inflammasomes and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    S. Vallurupalli, MD

    2016-09-01

    Full Text Available Inflammation plays an important role in atherosclerosis. Inflammasomes play a crucial role in innate immunity, which mediates the body’s response to various pathogens. Of the different types of inflammasomes, NLRP3 has been implicated in atherosclerosis through the production of proinflammatory cytokines, IL-1β and IL-18. This review describes the role of the NLRP3 inflammasome in atherosclerosis and discusses potential therapeutic targets in the inflammasome pathway.

  20. Hyperglycemia and xerostomia are key determinants of tooth decay in type 1 diabetic mice.

    Science.gov (United States)

    Yeh, Chih-Ko; Harris, Stephen E; Mohan, Sumathy; Horn, Diane; Fajardo, Roberto; Chun, Yong-Hee Patricia; Jorgensen, James; Macdougall, Mary; Abboud-Werner, Sherry

    2012-06-01

    Insulin-dependent type 1 diabetes mellitus (DM) and oral diseases are closely interrelated. Poor metabolic control in diabetics is associated with a high risk of gingivitis, periodontitis and tooth loss. Salivary flow declines in diabetics and patients suffer from xerostomia. Reduced saliva predisposes to enamel hypomineralization and caries formation; however, the mechanisms that initiate and lead to progression of tooth decay and periodontitis in type 1 DM have not been explored. To address this issue, we analyzed tooth morphology in Akita ⁻/⁻ mice that harbor a point mutation in the Ins2 insulin gene, which leads to progressive hyperglycemia. Mandibles from Akita ⁻/⁻ and wild-type littermates were analyzed by microCT, scanning EM and histology; teeth were examined for amelogenin (Amel) and ameloblastin (Ambn) expression. Mice were injected with pilocarpine to assess saliva production. As hyperglycemia may alter pulp repair, the effect of high glucose levels on the proliferation/differentiation of cultured MD10-F2 pulp cells was also analyzed. Results showed that Akita ⁻/⁻ mice at 6 weeks of age showed chalky white incisors that correlated with marked hyperglycemia and impaired saliva production. MicroCT of Akita ⁻/⁻ teeth revealed excessive enamel wearing and hypomineralization; immunostaining for Amel and Ambn was decreased. A striking feature was invasion of dentinal tubules with Streptococcus mitis and microabcesses that originated in the coronal pulp and progressed to pulp necrosis and periapical periodontitis. High levels of glucose also inhibited MD10-F2 cell proliferation and differentiation. Our findings provide the first evidence that hyperglycemia in combination with reduced saliva in a model of type1 DM leads to decreased enamel mineralization/matrix proteins and predisposes to excessive wearing and decay. Importantly, hyperglycemia adversely affects enamel matrix proteins and pulp repair. Early detection and treatment of hyperglycemia

  1. Macrophages and Their Role in Atherosclerosis: Pathophysiology and Transcriptome Analysis

    Directory of Open Access Journals (Sweden)

    Yuri V. Bobryshev

    2016-01-01

    Full Text Available Atherosclerosis can be regarded as a chronic inflammatory state, in which macrophages play different and important roles. Phagocytic proinflammatory cells populate growing atherosclerotic lesions, where they actively participate in cholesterol accumulation. Moreover, macrophages promote formation of complicated and unstable plaques by maintaining proinflammatory microenvironment. At the same time, anti-inflammatory macrophages contribute to tissue repair and remodelling and plaque stabilization. Macrophages therefore represent attractive targets for development of antiatherosclerotic therapy, which can aim to reduce monocyte recruitment to the lesion site, inhibit proinflammatory macrophages, or stimulate anti-inflammatory responses and cholesterol efflux. More studies are needed, however, to create a comprehensive classification of different macrophage phenotypes and to define their roles in the pathogenesis of atherosclerosis. In this review, we provide an overview of the current knowledge on macrophage diversity, activation, and plasticity in atherosclerosis and describe macrophage-based cellular tests for evaluation of potential antiatherosclerotic substances.

  2. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Day in the Life of Diabetes Famous People Working to Stop Diabetes Common ... to treat hyperglycemia, a condition called ketoacidosis (diabetic coma) could occur. Ketoacidosis develops ...

  3. Brain perfusion in acute and chronic hyperglycemia in rats

    International Nuclear Information System (INIS)

    Kikano, G.E.; LaManna, J.C.; Harik, S.I.

    1989-01-01

    Recent studies show that acute and chronic hyperglycemia cause a diffuse decrease in regional cerebral blood flow and that chronic hyperglycemia decreases the brain L-glucose space. Since these changes can be caused by a decreased density of perfused brain capillaries, we used 30 adult male Wistar rats to study the effect of acute and chronic hyperglycemia on (1) the brain intravascular space using radioiodinated albumin, (2) the anatomic density of brain capillaries using alkaline phosphatase histochemistry, and (3) the fraction of brain capillaries that are perfused using the fluorescein isothiocyanate-dextran method. Our results indicate that acute and chronic hyperglycemia do not affect the brain intravascular space nor the anatomic density of brain capillaries. Also, there were no differences in capillary recruitment among normoglycemic, acutely hyperglycemic, and chronically hyperglycemic rats. These results suggest that the shrinkage of the brain L-glucose space in chronic hyperglycemia is more likely due to changes in the blood-brain barrier permeability to L-glucose

  4. Type 2 diabetes: postprandial hyperglycemia and increased cardiovascular risk

    OpenAIRE

    Aryangat, Ajikumar V; Gerich, John E

    2010-01-01

    Ajikumar V Aryangat, John E GerichUniversity of Rochester, Rochester, New York, USAAbstract: Hyperglycemia is a major risk factor for both the microvascular and macrovascular complications in  patients with type 2 diabetes. This review summarizes the cardiovascular results of large outcomes trials in diabetes and presents new evidence on the role of hyperglycemia, with particular emphasis on postprandial hyperglycemia, in adverse cardiovascular outcomes in patients with type 2 diabet...

  5. Hyperglycemia Associated With Targeted Oncologic Treatment: Mechanisms and Management.

    Science.gov (United States)

    Goldman, Jonathan W; Mendenhall, Melody A; Rettinger, Sarah R

    2016-07-29

    : Molecularly targeted cancer therapy has rapidly changed the landscape of oncologic care, often improving patients' prognosis without causing as substantial a quality-of-life decrement as cytotoxic chemotherapy does. Nevertheless, targeted agents can cause side effects that may be less familiar to medical oncologists and that require the attention and expertise of subspecialists. In this review, we focus on hyperglycemia, which can occur with use of new anticancer agents that interact with cell proliferation pathways. Key mediators of these pathways include the tyrosine kinase receptors insulin growth factor receptor 1 (IGF-1R) and epidermal growth factor receptor (EGFR), as well as intracellular signaling molecules phosphatidylinositol 3-kinase (PI3K), AKT, and mammalian target of rapamycin (mTOR). We summarize available information on hyperglycemia associated with agents that inhibit these molecules within the larger context of adverse event profiles. The highest incidence of hyperglycemia is observed with inhibition of IGF-1R or mTOR, and although the incidence is lower with PI3K, AKT, and EGFR inhibitors, hyperglycemia is still a common adverse event. Given the interrelationships between the IGF-1R and cell proliferation pathways, it is important for oncologists to understand the etiology of hyperglycemia caused by anticancer agents that target those pathways. We also discuss monitoring and management approaches for treatment-related hyperglycemia for some of these agents, with a focus on our experience during the clinical development of the EGFR inhibitor rociletinib. Treatment-related hyperglycemia is associated with several anticancer agents. Many cancer patients may also have preexisting or undiagnosed diabetes or glucose intolerance. Screening can identify patients at risk for hyperglycemia before treatment with these agents. Proper monitoring and management of symptoms, including lifestyle changes and pharmacologic intervention, may allow patients to

  6. Dark adaptation during transient hyperglycemia in type 2 diabetes

    DEFF Research Database (Denmark)

    Holfort, Stig Kragelund; Jackson, Gregory R; Larsen, Michael

    2010-01-01

    It was the purpose of the present study to examine dark adaptation in subjects with type 2 diabetes during transient hyperglycemia. Twenty-four subjects with type 2 diabetes and minimal diabetic retinopathy were randomized to undergo an oral glucose tolerance test (OGTT) or to remain fasting. Dark...... glycemia increased in the 12 OGTT subjects, from 8.6±2.1 at baseline to 21.1±3.6 mM after 80 min. In the OGTT group, four out of seven subjects with delayed dark adaptation at baseline reached normal values during hyperglycemia. All examined aspects of rod adaptation were accelerated by hyperglycemia (time...... compared with healthy subjects, the delay being reversible in response to hyperglycemia....

  7. Protective effects of flavanol-rich dark chocolate on endothelial function and wave reflection during acute hyperglycemia.

    Science.gov (United States)

    Grassi, Davide; Desideri, Giovambattista; Necozione, Stefano; Ruggieri, Fabrizio; Blumberg, Jeffrey B; Stornello, Michele; Ferri, Claudio

    2012-09-01

    Nitric oxide plays a pivotal role in regulating vascular tone. Different studies show endothelial function is impaired during hyperglycemia. Dark chocolate increases flow-mediated dilation in healthy and hypertensive subjects with and without glucose intolerance; however, the effect of pretreatment with dark chocolate on endothelial function and other vascular responses to hyperglycemia has not been examined. Therefore, we aimed to investigate the effects of flavanol-rich dark chocolate administration on (1) flow-mediated dilation and wave reflections; (2) blood pressure, endothelin-1 and oxidative stress, before and after oral glucose tolerance test (OGTT). Twelve healthy volunteers (5 males, 28.2±2.7 years) randomly received either 100 g/d dark chocolate or flavanol-free white chocolate for 3 days. After 7 days washout period, volunteers were switched to the other treatment. Flow-mediated dilation, stiffness index, reflection index, peak-to-peak time, blood pressure, endothelin-1 and 8-iso-PGF(2α) were evaluated after each treatment phase and OGTT. Compared with white chocolate, dark chocolate ingestion improved flow-mediated dilation (P=0.03), wave reflections, endothelin-1 and 8-iso-PGF(2α) (Pwave reflections, blood pressure, and endothelin-1 and 8-iso-PGF(2α) increased after OGTT. OGTT causes acute, transient impairment of endothelial function and oxidative stress, which is attenuated by flavanol-rich dark chocolate. These results suggest cocoa flavanols may contribute to vascular health by reducing the postprandial impairment of arterial function associated with the pathogenesis of atherosclerosis.

  8. Managing Hyperglycemia (High Blood Sugar) in the Hospital: a Patient's Guide

    Science.gov (United States)

    Managing Hyperglycemia (High Blood Sugar) in the Hospital A Patient’s Guide Hyperglycemia is the medical term for blood glucose (sugar) ... org/guidelines/index.cfm). www.hormone.org Managing Hyperglycemia (High Blood Sugar) in the Hospital Patient Guide ...

  9. Leptin Is Associated With Persistence of Hyperglycemia in Acute Pancreatitis

    Science.gov (United States)

    Kennedy, James I.C.; Askelund, Kathryn J.; Premkumar, Rakesh; Phillips, Anthony R.J.; Murphy, Rinki; Windsor, John A.; Petrov, Maxim S.

    2016-01-01

    Abstract Adipokines have many homeostatic roles, including modulation of glucose metabolism, but their role in the pathophysiology of hyperglycemia associated with acute and critical illnesses in general, and acute pancreatitis (AP) in particular, is largely unknown. This study aimed to investigate the relationship between a panel of adipokines and hyperglycemia in the early course of AP, as well as the role of adipokines as predictors of AP severity. Adiponectin, leptin, omentin, resistin, and visfatin were measured on a daily basis in the first 72 hours after hospital admission. A first set of analyses was undertaken with admission glycemia stratified by severity, and a second set of analyses was undertaken based on persistence of early hyperglycemia. All of the analyses were adjusted for confounders. A total of 32 patients with AP were included in this study. None of the studied adipokines was significantly associated with glucose level on admission. Leptin was significantly (P = 0.003) increased in patients with persistent hyperglycemia. Adiponectin was significantly associated with the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in patients with persistent hyperglycemia (P = 0.015), visfatin with APACHE II score in patients with persistent hyperglycemia (P = 0.014), and omentin with APACHE II score in all of the patients regardless of the presence or absence of hyperglycemia (P = 0.021). Leptin is significantly associated with persistent hyperglycemia in the early course of AP. Omentin has a potential to become an accurate predictor of AP severity. PMID:26871770

  10. Vaccination against atherosclerosis

    NARCIS (Netherlands)

    Es, Thomas van

    2009-01-01

    Atherosclerosis, the predominantly underlying pathology of cardiovascular events, is the consequence of lipid deposition in the arterial wall, mostly as consequence of high levels of serum cholesterol. Treatment of atherosclerosis is mainly focused at the reduction of cholesterol levels by lipid

  11. Inflammatory therapeutic targets in coronary atherosclerosis – from molecular biology to clinical application

    Directory of Open Access Journals (Sweden)

    Fabian eLinden

    2014-11-01

    Full Text Available Atherosclerosis is the leading cause of death worldwide. Over the past two decades, it has been clearly recognized that atherosclerosis is an inflammatory disease of the arterial wall. Accumulating data from animal experiments have supported this hypothesis, however, clinical applications making use of this knowledge remain scarce. In spite of optimal interventional and medical therapy, the risk for recurrent myocardial infarction remains by about 20% over three years after acute coronary syndromes, novel therapies to prevent atherogenesis or treat atherosclerosis are urgently needed. This review summarizes selected potential molecu-lar inflammatory targets that may be of clinical relevance. We also review recent and ongoing clinical trails that target inflammatory processes aiming at preventing adverse cardiovascular events. Overall, it seems surprising that translation of basic science into clinical practice has not been a great success. In conclusion, we propose to focus on specific efforts that promote translational science in order to improve outcome and prognosis of patients suffering from atherosclerosis.

  12. Mitochondrial Respiration Is Reduced in Atherosclerosis, Promoting Necrotic Core Formation and Reducing Relative Fibrous Cap Thickness.

    Science.gov (United States)

    Yu, Emma P K; Reinhold, Johannes; Yu, Haixiang; Starks, Lakshi; Uryga, Anna K; Foote, Kirsty; Finigan, Alison; Figg, Nichola; Pung, Yuh-Fen; Logan, Angela; Murphy, Michael P; Bennett, Martin

    2017-12-01

    Mitochondrial DNA (mtDNA) damage is present in murine and human atherosclerotic plaques. However, whether endogenous levels of mtDNA damage are sufficient to cause mitochondrial dysfunction and whether decreasing mtDNA damage and improving mitochondrial respiration affects plaque burden or composition are unclear. We examined mitochondrial respiration in human atherosclerotic plaques and whether augmenting mitochondrial respiration affects atherogenesis. Human atherosclerotic plaques showed marked mitochondrial dysfunction, manifested as reduced mtDNA copy number and oxygen consumption rate in fibrous cap and core regions. Vascular smooth muscle cells derived from plaques showed impaired mitochondrial respiration, reduced complex I expression, and increased mitophagy, which was induced by oxidized low-density lipoprotein. Apolipoprotein E-deficient (ApoE -/- ) mice showed decreased mtDNA integrity and mitochondrial respiration, associated with increased mitochondrial reactive oxygen species. To determine whether alleviating mtDNA damage and increasing mitochondrial respiration affects atherogenesis, we studied ApoE -/- mice overexpressing the mitochondrial helicase Twinkle (Tw + /ApoE -/- ). Tw + /ApoE -/- mice showed increased mtDNA integrity, copy number, respiratory complex abundance, and respiration. Tw + /ApoE -/- mice had decreased necrotic core and increased fibrous cap areas, and Tw + /ApoE -/- bone marrow transplantation also reduced core areas. Twinkle increased vascular smooth muscle cell mtDNA integrity and respiration. Twinkle also promoted vascular smooth muscle cell proliferation and protected both vascular smooth muscle cells and macrophages from oxidative stress-induced apoptosis. Endogenous mtDNA damage in mouse and human atherosclerosis is associated with significantly reduced mitochondrial respiration. Reducing mtDNA damage and increasing mitochondrial respiration decrease necrotic core and increase fibrous cap areas independently of changes in

  13. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Your best bet is to practice good diabetes management and learn to detect hyperglycemia so you can ... about type 2 diabetes. Recipes and More: Diabetes Food Hub - recipes-and-more-1.html Recipes and ...

  14. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Professional Books Patient Access to Research Student Resources History of Diabetes Resources for School Projects How to ... Your best bet is to practice good diabetes management and learn to detect hyperglycemia so you can ...

  15. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Student Resources History of Diabetes Resources for School Projects How to Reference Our Site Diabetes Basics Myths ... Your best bet is to practice good diabetes management and learn to detect hyperglycemia so you can ...

  16. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... for energy. When your body breaks down fats, waste products called ketones are produced. Your body cannot ... Your best bet is to practice good diabetes management and learn to detect hyperglycemia so you can ...

  17. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... breast cancer and AIDS combined. Your gift today will help us get closer to curing diabetes and ... blood and then treating high blood glucose early will help you avoid problems associated with hyperglycemia. How ...

  18. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... for use in an emergency. How Can I Prevent Hyperglycemia? Your best bet is to practice good ... Recently Diagnosed Treatment & Care Complications Health Insurance For Parents & Kids Know Your Rights We Can Help Enroll ...

  19. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... In It Together We Can Help Center for Information Legal Assistance Success Stories Complications Hypoglycemia Hyperglycemia Skin ... other emergency, the medical ID can provide critical information about the person's health status, such as the ...

  20. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Your best bet is to practice good diabetes management and learn to detect hyperglycemia so you can ... It Together celebrates the steps you take Help change the conversation about type 2 diabetes. Recipes and ...

  1. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Your best bet is to practice good diabetes management and learn to detect hyperglycemia so you can ... new world where even the most common everyday events, such as eating breakfast, take on exaggerated importance. ...

  2. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Your best bet is to practice good diabetes management and learn to detect hyperglycemia so you can ... for signing up ' + ' '); $('.survey-form').show(); }, success: function (data) { $('#survey-errors').remove(); $('.survey-form .form-group .survey- ...

  3. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Your best bet is to practice good diabetes management and learn to detect hyperglycemia so you can ... Blog Online Community Site Menu Are You at Risk? Diagnosis Lower Your Risk Risk Test Alert Day ...

  4. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Your best bet is to practice good diabetes management and learn to detect hyperglycemia so you can ... glucose) Dawn Phenomenon Checking for Ketones Tight Diabetes Control donate en -- A Future Without Diabetes - a-future- ...

  5. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... flu. You have other stress, such as family conflicts or school or dating problems. You may have ... Your best bet is to practice good diabetes management and learn to detect hyperglycemia so you can ...

  6. Stress Hyperglycemia, Insulin Treatment, and Innate Immune Cells

    Directory of Open Access Journals (Sweden)

    Fangming Xiu

    2014-01-01

    Full Text Available Hyperglycemia (HG and insulin resistance are the hallmarks of a profoundly altered metabolism in critical illness resulting from the release of cortisol, catecholamines, and cytokines, as well as glucagon and growth hormone. Recent studies have proposed a fundamental role of the immune system towards the development of insulin resistance in traumatic patients. A comprehensive review of published literatures on the effects of hyperglycemia and insulin on innate immunity in critical illness was conducted. This review explored the interaction between the innate immune system and trauma-induced hypermetabolism, while providing greater insight into unraveling the relationship between innate immune cells and hyperglycemia. Critical illness substantially disturbs glucose metabolism resulting in a state of hyperglycemia. Alterations in glucose and insulin regulation affect the immune function of cellular components comprising the innate immunity system. Innate immune system dysfunction via hyperglycemia is associated with a higher morbidity and mortality in critical illness. Along with others, we hypothesize that reduction in morbidity and mortality observed in patients receiving insulin treatment is partially due to its effect on the attenuation of the immune response. However, there still remains substantial controversy regarding moderate versus intensive insulin treatment. Future studies need to determine the integrated effects of HG and insulin on the regulation of innate immunity in order to provide more effective insulin treatment regimen for these patients.

  7. Admission Hyperglycemia and Clinical Outcome in Cerebral Venous Thrombosis

    NARCIS (Netherlands)

    Zuurbier, Susanna M.; Hiltunen, Sini; Tatlisumak, Turgut; Peters, Guusje M.; Silvis, Suzanne M.; Haapaniemi, Elena; Kruyt, Nyika D.; Putaala, Jukka; Coutinho, Jonathan M.

    2016-01-01

    Background and Purpose-Admission hyperglycemia is associated with poor clinical outcome in ischemic and hemorrhagic stroke. Admission hyperglycemia has not been investigated in patients with cerebral venous thrombosis. Methods-Consecutive adult patients with cerebral venous thrombosis were included

  8. Hyperglycemia in critical patients: Determinants of insulin dose choice

    Directory of Open Access Journals (Sweden)

    Aline Klitzke Paliosa

    Full Text Available Summary Objective: To identify factors that can determine the choice of intermittent subcutaneous regular insulin dose in critically ill patients with hyperglycemia. Method: Cross-sectional study in a general adult ICU with 26 beds, data collected between September and October 2014. The variables analyzed were: sex, age, previous diagnosis of diabetes mellitus, use of corticosteroids, use of lactulose, sepsis, fasting, enteral nutrition, use of dextrose 5% in water, NPH insulin prescription and blood glucose level. Patients with one or more episodes of hyperglycemia (blood glucose greater than 180 mg/dL were included as a convenience sample, not consecutively. Those with continuous insulin prescription were excluded from analysis. Results: We included 64 records of hyperglycemia observed in 22 patients who had at least one episode of hyperglycemia. The median administered subcutaneous regular human insulin was 6 IU and among the factors evaluated only blood glucose levels were associated with the choice of insulin dose administered. Conclusion: Clinical characteristics such as diet, medications and diagnosis of diabetes mellitus are clearly ignored in the decision-making regarding insulin dose to be administered for glucose control in critically ill patients with hyperglycemia.

  9. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... around 4:00 a.m. to 5:00 a.m.). What are the Symptoms of Hyperglycemia? The signs and symptoms include the following: High blood glucose High levels of sugar in the urine Frequent urination Increased ...

  10. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... and Care > Blood Glucose Testing Share: Print Page Text Size: A A A Listen En Español Hyperglycemia ( ... compact USB drives that can carry a person's full medical record for use in an emergency. How ...

  11. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Hygiene Women A1C Insulin Pregnancy 8 Tips for Caregivers Health Insurance Health Insurance Update The Health Insurance ... when the body can't use insulin properly. What Causes Hyperglycemia? A number of things can cause ...

  12. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... for Association Events Messaging Tools Recruiting Advocates Local Market Planning Training Webinars News & Events Advocacy News Call ... Care > Blood Glucose Testing Share: Print Page Text Size: A A A Listen En Español Hyperglycemia (High ...

  13. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Your best bet is to practice good diabetes management and learn to detect hyperglycemia so you can ... It Together celebrates the steps you take Help change the conversation about type 2 diabetes. » « Connect With ...

  14. Hyperglycemia in acute ischemic stroke: pathophysiology and clinical management

    NARCIS (Netherlands)

    Kruyt, Nyika D.; Biessels, Geert Jan; DeVries, J. Hans; Roos, Yvo B.

    2010-01-01

    Patients with acute ischemic stroke frequently test positive for hyperglycemia, which is associated with a poor clinical outcome. This association between poor glycemic control and an unfavorable prognosis is particularly evident in patients with persistent hyperglycemia, patients without a known

  15. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... exercise and changes in your diet don't work, your doctor may change the amount of your medication or insulin or possibly the timing of when you take it. What if it Goes Untreated? Hyperglycemia can be a ...

  16. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Carbohydrate Counting Make Your Carbs Count Glycemic Index Low-Calorie Sweeteners Sugar and Desserts Fitness Exercise & Type ... Checking Your Blood Glucose A1C and eAG Hypoglycemia (Low blood glucose) Hyperglycemia (High blood glucose) Dawn Phenomenon ...

  17. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... June 7, 2013 Last Edited: September 16, 2014 Articles from Diabetes Forecast® magazine: bg-and-a1c-hyperglycemia, ... today and help fund grants supporting next generation scientists. Donate Today We Can Help - we-can-help. ...

  18. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... June 7, 2013 Last Edited: September 16, 2014 Articles from Diabetes Forecast® magazine: bg-and-a1c-hyperglycemia, ... Weight Loss Fitness In My Community Calendar of Events Local Offices Volunteer Opportunities Signature Events Camps Diabetes ...

  19. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... how often you should check and what your blood glucose levels should be. Checking your blood and then treating ... I Treat Hyperglycemia? You can often lower your blood glucose level by exercising. However, if your blood glucose is ...

  20. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... June 7, 2013 Last Edited: September 16, 2014 Articles from Diabetes Forecast® magazine: bg-and-a1c-hyperglycemia, ... Online Chat Closed engagement en -- Free Type 2 Education Series - 2017-06-free-type-2-education-series. ...

  1. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Last Edited: September 16, 2014 Articles from Diabetes Forecast® magazine: bg-and-a1c-hyperglycemia,tips-and-how- ... Use and Privacy Policy « American Diabetes Association Diabetes Forecast Stop Diabetes Step Out: Walk to Stop Diabetes ...

  2. Chlorogenic acid protects against atherosclerosis in ApoE-/- mice and promotes cholesterol efflux from RAW264.7 macrophages.

    Directory of Open Access Journals (Sweden)

    Chongming Wu

    Full Text Available Chlorogenic acid (CGA is one of the most abundant polyphenols in the human diet and is suggested to be a potential antiatherosclerotic agent due to its proposed hypolipidemic, anti-inflammatory and antioxidative properties. The aim of this study was to evaluate the effect of CGA on atherosclerosis development in ApoE(-/- mice and its potential mechanism. ApoE(-/- mice were fed a cholesterol-rich diet without (control or with CGA (200 and 400 mg/kg or atorvastatin (4 mg/kg for 12 weeks. During the study plasma lipid and inflammatory parameters were determined. Treatment with CGA (400 mg/kg reduced atherosclerotic lesion area and vascular dilatation in the aortic root, comparable to atorvastatin. CGA (400 mg/kg also significantly decreased plasma levels of total cholesterol, triglycerides and low-density lipoprotein-cholesterol as well as inflammatory markers. Supplementation with CGA or CGA metabolites-containing serum suppressed oxidized low-density lipoprotein (oxLDL-induced lipid accumulation and stimulated cholesterol efflux from RAW264.7 cells. CGA significantly increased the mRNA levels of PPARγ, LXRα, ABCA1 and ABCG1 as well as the transcriptional activity of PPARγ. Cholesterol efflux assay showed that three major metabolites, caffeic, ferulic and gallic acids, significantly stimulated cholesterol efflux from RAW264.7 cells. These results suggest that CGA potently reduces atherosclerosis development in ApoE(-/- mice and promotes cholesterol efflux from RAW264.7 macrophages. Caffeic, ferulic and gallic acids may be the potential active compounds accounting for the in vivo effect of CGA.

  3. Diabetes with poor glycaemic control does not promote atherosclerosis in genetically modified hypercholesterolaemic minipigs

    DEFF Research Database (Denmark)

    Al-Mashhadi, Rozh H; Bjørklund, Martin M; Mortensen, Martin B

    2015-01-01

    atherogenesis in a novel pig model of atherosclerosis, the D374Y-PCSK9 (+) transgenic minipig. METHODS: Nineteen minipigs were fed a cholesterol-enriched, high-fat diet; ten of these pigs were injected with streptozotocin to generate a model of diabetes. Restricted feeding was implemented to control the pigs......' weight gain and cholesterol intake. After 49 weeks of high-fat feeding, the major arteries were harvested for a detailed analysis of the plaque burden and histological plaque type. RESULTS: Stable hyperglycaemia was achieved in the diabetic minipigs, while the plasma total and LDL......-cholesterol and creatinine levels were unaffected. Diabetes failed to increase atherosclerosis in any of the vessels examined. The plaque burden in the aorta and right coronary artery was comparable between the groups, and was even reduced in the left anterior descending (LAD) coronary and iliofemoral arteries...

  4. Chronic hyperglycemia is related to poor functional outcome after acute ischemic stroke

    NARCIS (Netherlands)

    Luitse, Merel Ja; Velthuis, Birgitta K; Kappelle, L Jaap; van der Graaf, Yolanda; Biessels, Geert Jan

    2017-01-01

    BACKGROUND: Acute hyperglycemia is associated with poor functional outcome after ischemic stroke, but the association between chronic antecedent hyperglycemia and outcome is unclear. AIM: We assessed the association between chronic hyperglycemia, measured by hemoglobin A1c, and functional outcome in

  5. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... About Us Online Community Meal Planning Sign In Search: Search More Sites Search ≡ Are You At Risk? Diabetes Basics Living with ... In It Together We Can Help Center for Information Legal Assistance Success Stories Complications Hypoglycemia Hyperglycemia Skin ...

  6. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy 8 Tips for Caregivers Health Insurance ... 2014 Articles from Diabetes Forecast® magazine: bg-and-a1c-hyperglycemia,tips-and-how-tos, . In this section ...

  7. Low-Dose Radiation Exposure and Atherosclerosis in ApoE(-/-) Mice

    NARCIS (Netherlands)

    Mitchel, R. E. J.; Hasu, M.; Bugden, M.; Wyatt, H.; Little, M. P.; Gola, A.; Hildebrandt, G.; Priest, N. D.; Whitman, S. C.

    The hypothesis that single low-dose exposures (0.025-0.5 Gy) to low-LET radiation given at either high (about 150 mGy/min) or low (1 mGy/min) dose rate would promote aortic atherosclerosis was tested in female C57BL/6J mice genetically predisposed to this disease (ApoE(-/-)). Mice were exposed

  8. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Complications Neuropathy Foot Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & ... Non-starchy Vegetables Grains and Starchy ... has too little insulin or when the body can't use insulin properly. What Causes Hyperglycemia? A number of ...

  9. Improved animal models for testing gene therapy for atherosclerosis.

    Science.gov (United States)

    Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A

    2014-04-01

    Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long

  10. [Prediabetes as a riskmarker for stress-induced hyperglycemia in critically ill adults].

    Science.gov (United States)

    García-Gallegos, Diego Jesús; Luis-López, Eliseo

    2017-01-01

    It is not known if patients with prediabetes, a subgroup of non-diabetic patients that usually present hyperinsulinemia, have higher risk to present stress-induced hyperglycemia. The objective was to determine if prediabetes is a risk marker to present stress-induced hyperglycemia. Analytic, observational, prospective cohort study of non-diabetic critically ill patients of a third level hospital. We determined plasmatic glucose and glycated hemoglobin (HbA1c) at admission to diagnose stress-induced hyperglycemia (glucose ≥ 140 mg/dL) and prediabetes (HbA1c between 5.7 and 6.4%), respectively. We examined the proportion of non-prediabetic and prediabetic patients that developed stress hyperglycemia with contingence tables and Fisher's exact test for nominal scales. Of 73 patients studied, we found a proportion of stress-induced hyperglycemia in 6.6% in those without prediabetes and 61.1% in those with prediabetes. The Fisher's exact test value was 22.46 (p Prediabetes is a risk marker for stress-induced hyperglycemia in critically ill adults.

  11. Thyrotropin-releasing hormone (TRH) reverses hyperglycemia in rat

    International Nuclear Information System (INIS)

    Luo Luguang; Luo, John Z.Q.; Jackson, Ivor M.D.

    2008-01-01

    Hyperglycemia in thyrotropin-releasing hormone (TRH) null mice indicates that TRH is involved in the regulation of glucose homeostasis. Further, TRH levels in the pancreas peak during the stages of late embryonic and early neonatal β cell development. These observations are consistent in linking TRH to islet cell proliferation and differentiation. In this study, we examined the effect of TRH administration in damaged pancreatic rat (streptozotocin, STZ) to determine whether TRH could improve damaged pancreatic β cells function. We hypothesize that TRH is able to reverse STZ-induced hyperglycemia by increasing pancreatic islet insulin content, preventing apoptosis, and potentially induce islet regeneration. It was found that following intra-peritoneal (ip) injection, TRH (10 μg/kg body weight (bwt)) reverses STZ (65 mg/kg bwt)-induced hyperglycemia (TRH given 3 days after STZ injection). Increased circulating insulin levels and insulin content in extracted pancreas suggests that TRH reversed STZ-induced hyperglycemia through improving pancreatic islet β cell function. Further studies show a significantly lower level of apoptosis in islets treated with TRH as well as the presence of proliferation marker nestin and Brdu, suggesting that the TRH has the potential to prevent apoptosis and stimulate islet proliferation

  12. Hyperglycemia induced by pasireotide in patients with Cushing's disease or acromegaly.

    Science.gov (United States)

    Silverstein, Julie M

    2016-10-01

    Cushing's disease (CD) and acromegaly are characterized by excessive hormone secretion resulting in comorbidities such as impaired glucose metabolism, diabetes and hypertension. Pasireotide is a new-generation, multireceptor-targeted somatostatin receptor ligand approved for CD (subcutaneous [SC] injection formulation) and acromegaly (long-acting release [LAR] formulation). In clinical studies of pasireotide, hyperglycemia-related adverse events (AEs) were frequently observed. This review highlights differences in reported rates of hyperglycemia in pasireotide trials and discusses risk factors for and management of pasireotide-associated hyperglycemia. Clinical trials evaluating pasireotide in patients with CD or acromegaly were reviewed. The frequency of hyperglycemia-related AEs was lower in patients with acromegaly treated with pasireotide LAR (57.3-67.0 %) than in patients with CD treated with pasireotide SC (68.4-73.0 %). Fewer patients with acromegaly treated with pasireotide LAR discontinued therapy because of hyperglycemia-related AEs (Colao et al. in J Clin Endocrinol Metab 99(3):791-799, 2014, 3.4 %; Gadelha et al. in Lancet Diabetes Endocrinol 2(11):875-884, 2014, 4.0 %) than did patients with CD treated with pasireotide SC (Boscaro et al. in Pituitary 17(4):320-326, 2014, 5.3 %; Colao et al. in N Engl J Med 366(10):914-924, 2012, 6.0 %). Hyperglycemia-related AEs occurred in 40.0 % of patients with acromegaly treated with pasireotide SC, and 10.0 % discontinued treatment because of hyperglycemia. Ongoing studies evaluating pasireotide LAR in patients with CD and management of pasireotide-induced hyperglycemia in patients with CD or acromegaly (ClinicalTrials.gov identifiers NCT01374906 and NCT02060383, respectively) will address these key safety issues. Disease pathophysiology, drug formulation, and physician experience potentially influence the differences in reported rates of pasireotide-induced hyperglycemia in CD and acromegaly

  13. Alcohol and atherosclerosis

    Directory of Open Access Journals (Sweden)

    DA LUZ PROTASIO L.

    2001-01-01

    Full Text Available Atherosclerosis is manifested as coronary artery disease (CAD, ischemic stroke and peripheral vascular disease. Moderate alcohol consumption has been associated with reduction of CAD complications. Apparently, red wine offers more benefits than any other kind of drinks, probably due to flavonoids. Alcohol alters lipoproteins and the coagulation system. The flavonoids induce vascular relaxation by mechanisms that are both dependent and independent of nitric oxide, inhibits many of the cellular reactions associated with atherosclerosis and inflammation, such as endothelial expression of vascular adhesion molecules and release of cytokines from polymorphonuclear leukocytes. Hypertension is also influenced by the alcohol intake. Thus, heavy alcohol intake is almost always associated with systemic hypertension, and hence shall be avoided. In individuals that ingest excess alcohol, there is higher risk of coronary occlusion, arrhythmias, hepatic cirrhosis, upper gastrointestinal cancers, fetal alcohol syndrome, murders, sex crimes, traffic and industrial accidents, robberies, and psychosis. Alcohol is no treatment for atherosclerosis; but it doesn't need to be prohibited for everyone. Thus moderate amounts of alcohol (1-2 drinks/day, especially red wine, may be allowed for those at risk for atherosclerosis complications.

  14. Atorvastatin Improves Inflammatory Response in Atherosclerosis by Upregulating the Expression of GARP

    Science.gov (United States)

    Zhao, Xiaoqi; Liu, Yuzhou; Zhong, Yucheng; Liu, Bo; Yu, Kunwu; Shi, Huairui; Zhu, Ruirui; Meng, Kai; Zhang, Wei; Wu, Bangwei

    2015-01-01

    Regulatory T cells play an important role in the progression of atherosclerosis. GARP is a newly biological membrane molecule existed on activated Tregs, which is related to the release of TGF-β. The antiatherosclerosis effects of statins partly depend on their multiple immune modulatory potencies. In this paper, we present that atorvastatin could upregulate the expression of GARP and TGF-β in CD4+ T cells and increase the numbers of CD4+LAP+ and CD4+Foxp3+ regulatory T cells in ApoE−/− mice. Also, we indicate that atorvastatin promotes the aggregation of GARP+ and Foxp3+ cells and secretory of the TGF-β1 in atherosclerotic plaques. Furthermore, we prove that atorvastatin could delay the procession of atherosclerosis and improve the stability of atherosclerotic plaques. Interestingly, we report that inhibition of GARP distinctly inhibits the anti-inflammatory effects of atorvastatin. We conclude that atorvastatin improves the inflammatory response in atherosclerosis partly by upregulating the expression of GARP on regulatory T cells. PMID:26063978

  15. Characterization of Remitting and Relapsing Hyperglycemia in Post-Renal-Transplant Recipients.

    Directory of Open Access Journals (Sweden)

    Alireza Boloori

    Full Text Available Hyperglycemia following solid organ transplant is common among patients without pre-existing diabetes mellitus (DM. Post-transplant hyperglycemia can occur once or multiple times, which if continued, causes new-onset diabetes after transplantation (NODAT.To study if the first and recurrent incidence of hyperglycemia are affected differently by immunosuppressive regimens, demographic and medical-related risk factors, and inpatient hyperglycemic conditions (i.e., an emphasis on the time course of post-transplant complications.We conducted a retrospective analysis of 407 patients who underwent kidney transplantation at Mayo Clinic Arizona. Among these, there were 292 patients with no signs of DM prior to transplant. For this category of patients, we evaluated the impact of (1 immunosuppressive drugs (e.g., tacrolimus, sirolimus, and steroid, (2 demographic and medical-related risk factors, and (3 inpatient hyperglycemic conditions on the first and recurrent incidence of hyperglycemia in one year post-transplant. We employed two versions of Cox regression analyses: (1 a time-dependent model to analyze the recurrent cases of hyperglycemia and (2 a time-independent model to analyze the first incidence of hyperglycemia.Age (P = 0.018, HDL cholesterol (P = 0.010, and the average trough level of tacrolimus (P<0.0001 are significant risk factors associated with the first incidence of hyperglycemia, while age (P<0.0001, non-White race (P = 0.002, BMI (P = 0.002, HDL cholesterol (P = 0.003, uric acid (P = 0.012, and using steroid (P = 0.007 are the significant risk factors for the recurrent cases of hyperglycemia.This study draws attention to the importance of analyzing the risk factors associated with a disease (specially a chronic one with respect to both its first and recurrent incidence, as well as carefully differentiating these two perspectives: a fact that is currently overlooked in the literature.

  16. Frequency and mortality associated with hyperglycemia in critically III children

    International Nuclear Information System (INIS)

    Khan, S.A.; Haq, A.U.

    2015-01-01

    Objective: To determine the frequency of hyperglycemia in critically ill children admitted in PICU of a tertiary care hospital of Karachi and to compare the mortality of critically ill children with and without hyperglycemia. Study Design: Cross-sectional study. Place and Duration of Study: Paediatrics Intensive Care Unit (PICU) of National Institute of Child Health (NICH), Karachi, from November 2011 to April 2012. Methodology: One hundred fifty critically ill children admitted to PICU were included. Patients who had fasting blood sugar levels more than 126 mg/dl within 48 hours of admission were included in the hyperglycemic group. The normoglycemic and hyperglycemic groups were followed till 10 days to determine the mortality associated with hyperglycemia. Results: Out of 150 patients, 82 (54.7%) had hyperglycemia. Mortality rate was 48.7% (n=73/150). However, mortality rate was significantly high 57.3% (n=47) in hyperglycemic patients than non-hyperglycemic patients (p=0.019). Conclusion: The presence of stress-induced hyperglycemia in critically ill patients is a well established marker of poor outcome, and a very high mortality rate. Normoglycemia was associated with favorable outcomes in terms of hospital stay and mortality. (author)

  17. Neonatal Hyperglycemia due to Transient Neonatal Diabetes Mellitus in Puerto Rico

    Directory of Open Access Journals (Sweden)

    N. Fargas-Berríos

    2015-01-01

    Full Text Available Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM and transient neonatal diabetes mellitus (TNDM. We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor feeding tolerance and vomiting associated with hyperglycemia (385 mg/dL, glycosuria, and metabolic acidosis within the first 12 hours of life. The neonate was treated with intravenous insulin, obtaining a slight control of hyperglycemia. An adequate glycemia was achieved at 5 weeks of life. The molecular studies showed complete loss of maternal methylation at the TND differentially methylated region on chromosome 6q24. The etiology of this neonate’s hyperglycemia was a hypomethylation of the maternal TND locus. A rare cause of neonatal diabetes mellitus must be considered if a neonate presents refractory hyperglycemia. To our knowledge, this is the first case reported in Puerto Rico of transient neonatal mellitus due to the uncommon mechanism of maternal hypomethylation of the TND locus. Its prevalence in Puerto Rico is unknown.

  18. Neonatal Hyperglycemia due to Transient Neonatal Diabetes Mellitus in Puerto Rico.

    Science.gov (United States)

    Fargas-Berríos, N; García-Fragoso, L; García-García, I; Valcárcel, M

    2015-01-01

    Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM) is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor feeding tolerance and vomiting associated with hyperglycemia (385 mg/dL), glycosuria, and metabolic acidosis within the first 12 hours of life. The neonate was treated with intravenous insulin, obtaining a slight control of hyperglycemia. An adequate glycemia was achieved at 5 weeks of life. The molecular studies showed complete loss of maternal methylation at the TND differentially methylated region on chromosome 6q24. The etiology of this neonate's hyperglycemia was a hypomethylation of the maternal TND locus. A rare cause of neonatal diabetes mellitus must be considered if a neonate presents refractory hyperglycemia. To our knowledge, this is the first case reported in Puerto Rico of transient neonatal mellitus due to the uncommon mechanism of maternal hypomethylation of the TND locus. Its prevalence in Puerto Rico is unknown.

  19. Admission Hyperglycemia in Critically Ill Sepsis Patients: Association With Outcome and Host Response

    NARCIS (Netherlands)

    van Vught, Lonneke A.; Wiewel, Maryse A.; Klein Klouwenberg, Peter M. C.; Hoogendijk, Arie J.; Scicluna, Brendon P.; Ong, David S. Y.; Cremer, Olaf L.; Horn, Janneke; Bonten, Marc M. J.; Schultz, Marcus J.; van der Poll, Tom; de Beer, FrisoM; Bos, LieuweD J.; Frencken, JosF; Glas, GerieJ; van Hooijdonk, RoosmarijnT M.; Huson, Michaë laA M.; Schouten, LauraR A.; Straat, Marleen; Witteveen, Esther; Wieske, Luuk

    2016-01-01

    To investigate whether admission hyperglycemia is associated with the presentation and/or outcome of sepsis, what the influence of hyperglycemia is on key host responses to sepsis, and whether hyperglycemia differentially affects patients with diabetes mellitus. A substudy of a prospective

  20. Immune Response to Lipoproteins in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Sonia Samson

    2012-01-01

    Full Text Available Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation result in changes in their function and activate both innate and adaptive immune system. Oxidized low-density lipoprotein (LDL has been identified as one of the most important autoantigens in atherosclerosis. This escape from self-tolerance is dependent on the formation of oxidized phospholipids. The emerging understanding of the importance of immune responses against oxidized LDL in atherosclerosis has focused attention on the possibility of development of novel therapy for atherosclerosis. This review provides an overview of immune response to lipoproteins and the fascinating possibility of developing an immunomodulatory therapy for atherosclerosis.

  1. Atherosclerosis: Hypotheses and theories

    Directory of Open Access Journals (Sweden)

    E. A. Yuryeva

    2014-01-01

    Full Text Available The article gives basic theories of the pathogenesis of atherosclerosis, including inflammatory, cholesterol, lipid, lipoprotein, iron ones, as a result of metabolic syndrome, oxidative stress. In spite of carefully and deeply developed and ongoing elaborated pathogenesis theories, the etiological factors of atherosclerosis remain unknown so far. The age-related aspect of the disease is discussed; atherosclerosis is considered to be a childhood-onset disease that manifests itself at a later age. The authors propose an experimental and clinical evidence-based concept of the common etiology of syndromes of atherosclerosis, namely: the body's endogenous intoxication that is permanent or periodically progressive may be a primary cause of altered conformation of different protein molecules with their higher ability to adsorb the trace elements consolidating the structural changes. This change of proteins diminishes their functions and determines their antigenic properties, which is attended by the development of different pathogenic components in relation to the body's individual features.

  2. Hyperglycemia and acute kidney injury in critically ill children

    Directory of Open Access Journals (Sweden)

    Gordillo R

    2016-08-01

    Full Text Available Roberto Gordillo,1 Tania Ahluwalia,2 Robert Woroniecki3 1Department of Pediatrics, Division of Nephrology, 2Department of Pediatrics, University of Illinois College of Medicine, Peoria, IL, USA; 3Division of Pediatric Nephrology and Hypertension, Stony Brook Children’s Hospital, Stony Brook, NY, USA Background: Hyperglycemia and acute kidney injury (AKI are common in critically ill children and have been associated with higher morbidity and mortality. The incidence of AKI in children is difficult to estimate because of the lack of a standard definition for AKI. The pediatric RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria can be used to define AKI in children. Various biomarkers in urine and blood have been studied to detect AKI in critically ill children. However, it is not clear whether hyperglycemia is associated with AKI. Our objective was to evaluate the effect of hyperglycemia on kidney function and its effect on neutrophil gelatinase-associated lipocalin (NGAL in children. Methods: We studied retrospective and prospective cohorts of pediatric critically ill subjects admitted to the pediatric intensive care unit (PICU. We analyzed data from admission that included estimated glomerular filtration rate, plasma and urine NGAL, serum glucose and peak glycemia (highest glycemia during PICU admission, and length of hospital and PICU stay from two different institutions. Results: We found that the prevalence of hyperglycemia was 89% in the retrospective cohort and 86% in the prospective cohort, P=0.99. AKI was associated with peak glycemia, P=0.03. There was a statistically significant correlation between peak glycemia and hospital and PICU stays, P=<0.001 and P<0.001, respectively. Urine NGAL and plasma NGAL were not statistically different in subjects with and without hyperglycemia, P=0.99 and P=0.85, respectively. Subjects on vasopressors had lower estimated glomerular filtration rate and higher

  3. Diabetes, hyperglycemia, and the burden of functional disability among older adults in a community-based study.

    Science.gov (United States)

    Godino, Job G; Appel, Lawrence J; Gross, Alden L; Schrack, Jennifer A; Parrinello, Christina M; Kalyani, Rita R; Windham, Beverly Gwen; Pankow, James S; Kritchevsky, Stephen B; Bandeen-Roche, Karen; Selvin, Elizabeth

    2017-01-01

    There is a need for continued surveillance of diabetes-related functional disability. In the present study, we examined associations between diabetes, hyperglycemia, and the burden of functional disability in a community-based population. A cross-sectional analysis was conducted of 5035 participants who attended Visit 5 (2011-13) of the Atherosclerosis Risk in Communities study. Functional disability was dichotomously defined by any self-reported difficulty performing 12 tasks essential to independent living grouped into four functional domains. Associations of diagnosed diabetes (via self-report) and undiagnosed diabetes and prediabetes (via HbA1c) with functional disability were evaluated using Poisson regression. Participants had a mean age of 75 years, 42 % were male, 22 % were Black, and 31 % had diagnosed diabetes. Those with diagnosed diabetes had a significantly greater burden of functional disability than those without diabetes, even after adjustment for demographics, health behaviors, and comorbidities: prevalence ratios (95 % confidence intervals) were 1.24 (1.15, 1.34) for lower extremity mobility, 1.14 (1.07, 1.21) for general physical activities, 1.33 (1.16, 1.52) for instrumental activities of daily living (ADL), and 1.46 (1.24, 1.73) for ADL (all P  0.05). Among older adults, the burden of functional disability associated with diabetes was not entirely explained by known risk factors, including comorbidities. Hyperglycemia below the threshold for the diagnosis of diabetes was not associated with disability. Research into effective strategies for the prevention of functional disability among older adults with diabetes is needed. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  4. Constitutive GITR Activation Reduces Atherosclerosis by Promoting Regulatory CD4+ T-Cell Responses-Brief Report

    NARCIS (Netherlands)

    Meiler, Svenja; Smeets, Esther; Winkels, Holger; Shami, Annelie; Pascutti, Maria Fernanda; Nolte, Martijn A.; Beckers, Linda; Weber, Christian; Gerdes, Norbert; Lutgens, Esther

    2016-01-01

    Glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) is expressed on CD4(+) effector memory T cells and regulatory T cells; however, its role on these functionally opposing cell types in atherosclerosis is not fully understood. Low-density lipoprotein

  5. Atherosclerosis in Watanabe heritable hyperlipidaemic rabbits. Evaluation by macroscopic, microscopic and biochemical methods and comparison of atherosclerosis variables

    DEFF Research Database (Denmark)

    Hansen, B F; Mortensen, A; Hansen, J F

    1994-01-01

    estimation of aortic atherosclerosis extent and by biochemical analysis of aortic cholesterol content. No noteworthy atherosclerosis was demonstrated within 19 months in heterozygous rabbits. In homozygous rabbits, atherosclerotic lesions were seen from the age of 4 months and progressed with age. All 19......-month-old rabbits had severe atherosclerotic disease. As much as 64% of the variation in atherosclerosis extent/severity could be explained by serum cholesterol and age. A highly significant correlation between the various methods for quantitation of atherosclerosis extent and/or severity...... was demonstrated, suggesting that quantitative microscopy, macroscopic morphometry and determination of aortic cholesterol content may be equally valid as a measure of atherosclerosis in WHHL rabbits and are therefore interchangeable....

  6. Chronic Intermittent Hypoxia Induces Atherosclerosis

    OpenAIRE

    Savransky, Vladimir; Nanayakkara, Ashika; Li, Jianguo; Bevans, Shannon; Smith, Philip L.; Rodriguez, Annabelle; Polotsky, Vsevolod Y.

    2007-01-01

    Rationale: Obstructive sleep apnea, a condition leading to chronic intermittent hypoxia (CIH), is associated with hyperlipidemia, atherosclerosis, and a high cardiovascular risk. A causal link between obstructive sleep apnea and atherosclerosis has not been established.

  7. A Rabbit Model for Testing Helper-Dependent Adenovirus-Mediated Gene Therapy for Vein Graft Atherosclerosis.

    Science.gov (United States)

    Bi, Lianxiang; Wacker, Bradley K; Bueren, Emma; Ham, Ervin; Dronadula, Nagadhara; Dichek, David A

    2017-12-15

    Coronary artery bypass vein grafts are a mainstay of therapy for human atherosclerosis. Unfortunately, the long-term patency of vein grafts is limited by accelerated atherosclerosis. Gene therapy, directed at the vein graft wall, is a promising approach for preventing vein graft atherosclerosis. Because helper-dependent adenovirus (HDAd) efficiently transduces grafted veins and confers long-term transgene expression, HDAd is an excellent candidate for delivery of vein graft-targeted gene therapy. We developed a model of vein graft atherosclerosis in fat-fed rabbits and demonstrated long-term (≥20 weeks) persistence of HDAd genomes after graft transduction. This model enables quantitation of vein graft hemodynamics, wall structure, lipid accumulation, cellularity, vector persistence, and inflammatory markers on a single graft. Time-course experiments identified 12 weeks after transduction as an optimal time to measure efficacy of gene therapy on the critical variables of lipid and macrophage accumulation. We also used chow-fed rabbits to test whether HDAd infusion in vein grafts promotes intimal growth and inflammation. HDAd did not increase intimal growth, but had moderate-yet significant-pro-inflammatory effects. The vein graft atherosclerosis model will be useful for testing HDAd-mediated gene therapy; however, pro-inflammatory effects of HdAd remain a concern in developing HDAd as a therapy for vein graft disease.

  8. Diabetes and mitochondrial function: Role of hyperglycemia and oxidative stress

    International Nuclear Information System (INIS)

    Rolo, Anabela P.; Palmeira, Carlos M.

    2006-01-01

    Hyperglycemia resulting from uncontrolled glucose regulation is widely recognized as the causal link between diabetes and diabetic complications. Four major molecular mechanisms have been implicated in hyperglycemia-induced tissue damage: activation of protein kinase C (PKC) isoforms via de novo synthesis of the lipid second messenger diacylglycerol (DAG), increased hexosamine pathway flux, increased advanced glycation end product (AGE) formation, and increased polyol pathway flux. Hyperglycemia-induced overproduction of superoxide is the causal link between high glucose and the pathways responsible for hyperglycemic damage. In fact, diabetes is typically accompanied by increased production of free radicals and/or impaired antioxidant defense capabilities, indicating a central contribution for reactive oxygen species (ROS) in the onset, progression, and pathological consequences of diabetes. Besides oxidative stress, a growing body of evidence has demonstrated a link between various disturbances in mitochondrial functioning and type 2 diabetes. Mutations in mitochondrial DNA (mtDNA) and decreases in mtDNA copy number have been linked to the pathogenesis of type 2 diabetes. The study of the relationship of mtDNA to type 2 diabetes has revealed the influence of the mitochondria on nuclear-encoded glucose transporters, glucose-stimulated insulin secretion, and nuclear-encoded uncoupling proteins (UCPs) in β-cell glucose toxicity. This review focuses on a range of mitochondrial factors important in the pathogenesis of diabetes. We review the published literature regarding the direct effects of hyperglycemia on mitochondrial function and suggest the possibility of regulation of mitochondrial function at a transcriptional level in response to hyperglycemia. The main goal of this review is to include a fresh consideration of pathways involved in hyperglycemia-induced diabetic complications

  9. Hyperglycemia and Clinical Outcome in Aneurysmal Subarachnoid Hemorrhage A Meta-Analysis

    NARCIS (Netherlands)

    Kruyt, Nyika D.; Biessels, Geert Jan; de Haan, Rob J.; Vermeulen, Marinus; Rinkel, Gabriel J. E.; Coert, Bert; Roos, Yvo B. W. E. M.

    2009-01-01

    Background and Purpose-Hyperglycemia may worsen outcome after aneurysmal subarachnoid hemorrhage. We performed a systematic review to investigate the relation between admission hyperglycemia and outcome after aneurysmal subarachnoid hemorrhage. Methods-We included cohort studies or clinical trials

  10. Increased plasma dipeptidyl peptidase-4 activities are associated with high prevalence of subclinical atherosclerosis in Chinese patients with newly diagnosed type 2 diabetes: a cross-sectional study.

    Science.gov (United States)

    Zheng, T P; Liu, Y H; Yang, L X; Qin, S H; Liu, H B

    2015-10-01

    Hyperglycemia, insulin resistance, dislipidemia, oxidative stress and inflammation are well-documented risk factors for subclinical atherosclerosis. Dipeptidyl peptidase-4(DPP4) is a newly identified adipokine related to these risk factors. Hence, we aimed to investigate the association between plasma DPP4 activities and subclinical atherosclerosis in type 2 diabetes. A total of 985 newly diagnosed type 2 diabetic subjects were studied. Plasma DPP4 activity, mannose 6-phosphate receptor (M6P-R), oxidative stress parameters, inflammatory markers and common carotid artery Intima-Media Thickness (c-IMT) were measured in all participants. Participants in the highest quartile of DPP4 activity had higher HbA1c, homeostatic model assessment of insulin resistance(HOMA-IR), triglyceride, low-density lipoprotein cholesterol(LDL-C), oxidized LDL, nitrotyrosine, 8-iso-PGF2a, interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), M6P-R, c-IMT compared with participants in the lowest quartile (all P dislipidemia, oxidative stress and inflammation were higher with increasing DPP4 quartiles (P < 0.001 for trend). In the highest DPP4 quartile, subclinical atherosclerosis risk was significantly higher (OR 4.97; 95% CI 3.03-8.17) than in the lowest quartile. This association remained strong (2.17; 1.21-3.89) after further controlling for HbA1c, HOMA-IR, triglyceride, oxidized LDL, nitrotyrosine, and IL-6. This study shows that increased DPP4 activities are positively and independently associated with subclinical atherosclerosis in type 2 diabetes. Our findings suggest of potential role of DPP4 in the pathogenesis of subclinical atherosclerosis and in the prevention and management of this disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Diabetes-induced hyperglycemia impairs male reproductive function: a systematic review.

    Science.gov (United States)

    Maresch, Constanze C; Stute, Dina C; Alves, Marco G; Oliveira, Pedro F; de Kretser, David M; Linn, Thomas

    2018-01-01

    Hyperglycemia can result from a loss of pancreatic beta-cells or a decline in their function leading to decreased insulin secretion or may arise from insulin resistance and variable degrees of inadequate insulin secretion resulting in diabetes and related comorbidities. To date several reviews have addressed the issue of diabetes-related male infertility but most have focused on how metabolic syndrome causes the decline in male fertility. However, a comprehensive overview as to how diabetes-induced hyperglycemia impairs male fertility is missing. Impaired regulation of glucose and the resultant hyperglycemia are major threats to the health of individuals in modern societies especially given the rapidly rising prevalence affecting an increasing number of men in their reproductive years. Consequently, diabetes-induced hyperglycemia is likely to contribute to a decline in global birth rates especially in those societies with a high diabetic prevalence. This systematic review addresses and summarizes the impact of hyperglycemia on male reproductive health with a particular emphasis on the molecular mechanisms that influence the testis and other parts of the male reproductive tract. A systematic search of the literature published in the MEDLINE-Pubmed database (http://www.ncbi.nlm.nih.gov/pubmed) and Cochrane Library (http://www.cochranelibrary.com) was performed, as well as hand searching reference lists, from the earliest available online indexing year until May 2017, using diabetes- and male fertility-related keywords in combination with other search phrases relevant to the topic of hyperglycemia. Inclusion criteria were: clinical studies on type 1 diabetic (T1D) men and studies on T1D animal models with a focus on reproductive parameters. Case reports/series, observational studies and clinical trials were included. Studies on patients with type 2 diabetes (T2D) or animal models of T2D were excluded to distinguish hyperglycemia from other metabolic effects. A total

  12. Factors of health in the protection against death and cardiovascular disease among adults with subclinical atherosclerosis

    Science.gov (United States)

    While cardiovascular disease (CVD) prevention traditionally emphasizes risk-factor control, recent evidence also supports the promotion of "health-factors" associated with cardiovascular wellness. However, whether such health-factors exist among adults with advanced subclinical atherosclerosis is un...

  13. Anti-inflammatory and organ protective effect of insulin in scalded MODS rats without controlling hyperglycemia.

    Science.gov (United States)

    Zhu, Zhongzhen; Hu, Tian; Wang, Zhanke; Wang, Jin; Liu, Rui; Yang, Qianyong; Zhang, Xiaoyun; Xiong, Yuanyuan

    2018-02-01

    Insulin, as an anti-inflammatory drug, could not be freely used in patients who experienced trauma according to the degree of inflammation, because of the side effect of hypoglycemia. In vivo experimental evidence is lacking concerning whether the effect is dosage dependent and whether it relies on controlling hyperglycemia. By adjusting the dosage ratio of glucose and insulin, different dosages of insulin were used to treat severely scalded MODS rats to achieve uncontrolled or controlled hyperglycemia. One hundred forty rats with severe scalded were randomly divided into a hyperglycemia-controlled group, hyperglycemia-uncontrolled group, and control group. The levels of inflammation response indexes and major organ dysfunction indexes were measured and compared between groups. The blood indexes of inflammatory response and major organ dysfunction did not show statistical difference between hyperglycemia-controlled groups (A) and uncontrolled groups (B) in the same dosage of insulin (all P>0.05). The blood indexes of inflammatory response and major organ dysfunction demonstrated statistical difference in different dosages of insulin with hyperglycemia-controlled groups (A1-A3 groups) and hyperglycemia-uncontrolled groups (B1-B3 groups) (all Pcontrolling hyperglycemia. The effect of anti-inflammation and organ protection of insulin is dosage dependent in vivo; it does not rely on controlling hyperglycemia. Temporary traumatic hyperglycemia itself might not be detrimental to the body. Adjusting the ratio of insulin and glucose could provide a novel train of thought for freely treating patients with severe traumatic injury with different dosages of insulin according to the degree of inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Cyanotic congenital heart disease and atherosclerosis.

    Science.gov (United States)

    Tarp, Julie Bjerre; Jensen, Annette Schophuus; Engstrøm, Thomas; Holstein-Rathlou, Niels-Henrik; Søndergaard, Lars

    2017-06-01

    Improved treatment options in paediatric cardiology and congenital heart surgery have resulted in an ageing population of patients with cyanotic congenital heart disease (CCHD). The risk of acquired heart disease such as atherosclerosis increases with age.Previous studies have speculated whether patients with CCHD are protected against atherosclerosis. Results have shown that the coronary arteries of patients with CCHD are free from plaques and stenosis. Decreased carotid intima-media thickness and low total plasma cholesterol may indicate a reduced risk of later development of atherosclerosis. However, the evidence is still sparse and questionable, and a reasonable explanation for the decreased risk of developing atherosclerosis in patients with CCHD is still missing.This review provides an overview of what is known about the prevalence and potential causes of the reduced risk of atherosclerosis in patients with CCHD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Oral microbiota in patients with atherosclerosis.

    Science.gov (United States)

    Fåk, Frida; Tremaroli, Valentina; Bergström, Göran; Bäckhed, Fredrik

    2015-12-01

    Recent evidence suggests that the microbiota may be considered as an environmental factor that contributes to the development of atherosclerosis. Periodontal disease has been associated with cardio- and cerebrovascular events, and inflammation in the periodontium is suggested to increase the systemic inflammatory level of the host, which may in turn influence plaque composition and rupture. We previously showed that bacteria from the oral cavity and the gut could be found in atherosclerotic plaques. To elucidate whether the oral microbiota composition differed between patients with asymptomatic and symptomatic atherosclerosis we performed pyrosequencing of the oral microbiota of 92 individuals including patients with asymptomatic and symptomatic atherosclerosis and control individuals without carotid plaques or previous stroke or myocardial infarction. The overall microbial structure was similar in controls and atherosclerosis patients, but patients with symptomatic atherosclerosis had higher relative abundance of Anaeroglobus (mean 0.040% (SD 0.049)) than the control group (0.010% (SD 0.028)) (P = 0.03). Using linear regression analysis, we found that Parvimonas associated positively with uCRP and Capnocytophaga, Catonella and Lactobacillus associated with blood lipid markers. In conclusion, abundance of Anaeroglobus in the oral cavity could be associated with symptomatic atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. A Rabbit Model for Testing Helper-Dependent Adenovirus-Mediated Gene Therapy for Vein Graft Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Lianxiang Bi

    2017-12-01

    Full Text Available Coronary artery bypass vein grafts are a mainstay of therapy for human atherosclerosis. Unfortunately, the long-term patency of vein grafts is limited by accelerated atherosclerosis. Gene therapy, directed at the vein graft wall, is a promising approach for preventing vein graft atherosclerosis. Because helper-dependent adenovirus (HDAd efficiently transduces grafted veins and confers long-term transgene expression, HDAd is an excellent candidate for delivery of vein graft-targeted gene therapy. We developed a model of vein graft atherosclerosis in fat-fed rabbits and demonstrated long-term (≥20 weeks persistence of HDAd genomes after graft transduction. This model enables quantitation of vein graft hemodynamics, wall structure, lipid accumulation, cellularity, vector persistence, and inflammatory markers on a single graft. Time-course experiments identified 12 weeks after transduction as an optimal time to measure efficacy of gene therapy on the critical variables of lipid and macrophage accumulation. We also used chow-fed rabbits to test whether HDAd infusion in vein grafts promotes intimal growth and inflammation. HDAd did not increase intimal growth, but had moderate—yet significant—pro-inflammatory effects. The vein graft atherosclerosis model will be useful for testing HDAd-mediated gene therapy; however, pro-inflammatory effects of HdAd remain a concern in developing HDAd as a therapy for vein graft disease.

  17. [Transdisciplinary Approach for Sarcopenia. Sarcopenia and atherosclerosis].

    Science.gov (United States)

    Kohara, Katsuhiko

    2014-10-01

    Risk factors for sarcopenia, including aging, inflammation, oxidative stress, and sedentary life style, are also known as risks for atherosclerosis. Sarcopenia and atherosclerosis relate each other. We found that sarcopenia, especially sarcopenic visceral obesity in male subjects, was associated with higher arterial stiffness and central blood pressure. We also observed that leptin resistance may underlie the link between sarcopenia, sarcopenic obesity and atherosclerosis. In epidemiological studies, it has been demonstrated sarcopenic indices were associated with cardiovascular death. These findings indicate that sarcopenia could be regarded as risk factor for atherosclerosis and cardiovascular events.

  18. Steroid-induced hyperglycemia: An underdiagnosed problem or clinical inertia? A narrative review.

    Science.gov (United States)

    Bonaventura, Aldo; Montecucco, Fabrizio

    2018-05-01

    Corticosteroids are widely diffused drugs. An important side effect is the impairment of glycemic control both in patients with known diabetes and in normoglycemic ones potentially leading to steroid-induced diabetes mellitus (SIDM). In this review based on papers released on PubMed, MEDLINE, and EMBASE from January 2015 to October 2017, we summarized and discussed main updates about the definition, the diagnosis, and the pathophysiology of steroid-induced hyperglycemia (SIH), with a look to new therapies. Main alterations responsible for the diabetogenic effect of corticosteroids are a negative impact on insulin sensitivity along with a derangement on insulin secretion, explaining the typical post-prandial hyperglycemia linked to the promotion of gluconeogenesis. An early and precise diagnosis of SIH and/or SIDM is necessary, but current criteria do not seem sensible enough. As an afterthought, the treatment should be reasoned and tailored according to proposed glycemic thresholds and patient comorbidities, choosing between antidiabetic oral drugs and insulin, the latter being preferable among hospitalized patients. SIDM and SIH are frequent problems, but often underdiagnosed due to old diagnostic criteria. Dedicated guidelines universally shared are mandatory in order to harmonize the treatment of these conditions, thus overtaking single therapeutic strategies mostly arising from literature. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Valsartan Promoting Atherosclerotic Plaque Stabilization by Upregulating Renalase: A Potential-Related Gene of Atherosclerosis.

    Science.gov (United States)

    Zhou, Mingxue; Ma, Chao; Liu, Weihong; Liu, Hongxu; Wang, Ning; Kang, Qunfu; Li, Ping

    2015-09-01

    Renalase is a protein that can regulate sympathetic nerve activity by metabolizing catecholamines, while redundant catecholamines are thought to contribute to atherosclerosis (As). Catecholamine release can be facilitated by angiotensin (Ang) II by binding to Ang II type 1 (AT1) receptors. Valsartan, a special AT1 antagonist, can dilate blood vessels and reduce blood pressure, but it remained unclear whether valsartan can promote the stability of atherosclerotic plaque by affecting renalase. This study examined the tissue distribution of renalase in ApoE(-/-) mice fed with a high-fat diet and the effect of valsartan on expression of renalase. ApoE(-/-) mice were fed with a high-fat diet for 13 or 26 weeks. As a control, 10 C57BL mice were fed with a standard chow diet. After 13 weeks on the high-fat diet, the ApoE(-/-) mice were randomized (10 mice/group) and treated with valsartan, simvastatin, or distilled water (control group) for an additional 13 weeks accompanied by a high-fat diet. Knockout of ApoE caused a dramatic increase in expression of renalase in mice adipose tissue. With the disturbance of lipid metabolism induced by a high-fat diet, renalase expression decreased in the liver. Renalase can be expressed in smooth muscle cells and M2 macrophages in atherosclerotic plaque, and its expression gradually decreases in the fibrous cap during the transition from stable to vulnerable atherosclerotic plaque. Valsartan, an AT1 receptor antagonist, promotes the stabilization of atherosclerotic plaque by increasing the levels of renalase in serum and the expression of renalase in the fibrous cap of atherosclerotic plaque. It also reduces triglyceride levels in serum and increases the expression of renalase in the liver. Renalase may be a potential-related gene of lipid metabolism and As, and it may be the possible molecular target of valsartan to help stabilize atherosclerotic plaque. © The Author(s) 2015.

  20. Dark adaptation during transient hyperglycemia in type 2 diabetes

    DEFF Research Database (Denmark)

    Holfort, Stig Kraglund; Jackson, Gregory R; Larsen, Michael

    2010-01-01

    adaptometry was measured in one eye, chosen at random, using a computer-controlled dark adaptometer. Dark adaptation and capillary blood glucose were measured at baseline and 80 minutes into the OGTT/fasting test. Blood glucose remained stable throughout the examination in the 12 fasting subjects, whereas......It was the purpose of the present study to examine dark adaptation in subjects with type 2 diabetes during transient hyperglycemia. Twenty-four subjects with type 2 diabetes and minimal diabetic retinopathy were randomized to undergo an oral glucose tolerance test (OGTT) or to remain fasting. Dark...... glycemia increased in the 12 OGTT subjects, from 8.6±2.1 at baseline to 21.1±3.6 mM after 80 min. In the OGTT group, four out of seven subjects with delayed dark adaptation at baseline reached normal values during hyperglycemia. All examined aspects of rod adaptation were accelerated by hyperglycemia (time...

  1. Hyperglycemia induces a dynamic cooperativity of histone methylase and demethylase enzymes associated with gene-activating epigenetic marks that coexist on the lysine tail.

    Science.gov (United States)

    Brasacchio, Daniella; Okabe, Jun; Tikellis, Christos; Balcerczyk, Aneta; George, Prince; Baker, Emma K; Calkin, Anna C; Brownlee, Michael; Cooper, Mark E; El-Osta, Assam

    2009-05-01

    Results from the Diabetes Control Complications Trial (DCCT) and the subsequent Epidemiology of Diabetes Interventions and Complications (EDIC) Study and more recently from the U.K. Prospective Diabetes Study (UKPDS) have revealed that the deleterious end-organ effects that occurred in both conventional and more aggressively treated subjects continued to operate >5 years after the patients had returned to usual glycemic control and is interpreted as a legacy of past glycemia known as "hyperglycemic memory." We have hypothesized that transient hyperglycemia mediates persistent gene-activating events attributed to changes in epigenetic information. Models of transient hyperglycemia were used to link NFkappaB-p65 gene expression with H3K4 and H3K9 modifications mediated by the histone methyltransferases (Set7 and SuV39h1) and the lysine-specific demethylase (LSD1) by the immunopurification of soluble NFkappaB-p65 chromatin. The sustained upregulation of the NFkappaB-p65 gene as a result of ambient or prior hyperglycemia was associated with increased H3K4m1 but not H3K4m2 or H3K4m3. Furthermore, glucose was shown to have other epigenetic effects, including the suppression of H3K9m2 and H3K9m3 methylation on the p65 promoter. Finally, there was increased recruitment of the recently identified histone demethylase LSD1 to the p65 promoter as a result of prior hyperglycemia. These studies indicate that the active transcriptional state of the NFkappaB-p65 gene is linked with persisting epigenetic marks such as enhanced H3K4 and reduced H3K9 methylation, which appear to occur as a result of effects of the methyl-writing and methyl-erasing histone enzymes.

  2. Hyperglycemia and mortality in critically ill patients

    International Nuclear Information System (INIS)

    Rezvanfar, M.R.; Dalvandy, M.; Emami, A.R.; Rafiee, M.; Eshratee, B.

    2009-01-01

    To analyze the relation between serum glucose concentration and hospital outcome across the critically ill patients. A single-centre, retrospective study was performed at surgical and medical intensive care unit. Admission glucose, mean morning glucose, mean glucose, maximal glucose and time-averaged glucose levels were calculated for each patient. The time-averaged hyperglycemia was defined as the area under the curve above the upper limit of normal, divided by the total length of stay. Of 300 patients with a median stay of 16 days, the mortality rate was 32%. Mean fasting glucose was 121 mg/dl in survivors versus 160 mg/dl in non survivors (P=0.001). Mean admission glucose was 127 mg/dl in survivors versus 142 mg/dl in non survivors (0.03). Median time-averaged hyperglycemia was 4 mg/dl in survivors versus 17.5 mg/dl in non survivors (P < 0.006). The area under the receiver operator characteristic (ROC) curve was 0.59 for time-averaged glucose and 0.73 for mean fasting glucose. Whereas time-averaged hyperglycemia is a useful assessment for glucose control in critically ill patients, it has no priority to admission glucose and mean fasting glucose for outcome prediction. (author)

  3. Hyperglycemia and ultrasound in radiotherapy of experimental tumors (a preliminary paper)

    International Nuclear Information System (INIS)

    Muratkhodzhaev, N.K.; Prus, E.S.; Zakirkhodzhaev, U.D.; Kutlimuratov, A.B.

    1984-01-01

    Experimental studies have shown that all the types of effects, as compared with the control, result in inhibition of the tumor growth; X-ray therapy decelerates the tumor growth, but its combination with hyperglycemia produced a more vivid effect. Inhibition of the tumor growth, as compared with that in the control group, was observed under a combined effect of hyperglycemia with ultrasound, though it was noticeably weaker than under other effects. Application of a complex effect including hyperglycemia, ultrasound, X-ray therapy turned to be most effective, the succession of their application playing an important role for the antitumoral effect of the used factors

  4. Ketotic hyperglycemia with movement disorder

    Directory of Open Access Journals (Sweden)

    Disha Awasthi

    2012-01-01

    Full Text Available Chorea, hemichorea-hemiballismus and severe partial seizures may be the presenting features of nonketotic hyperglycemia in older adults with type 2 diabetes, but cases in young adults with type 1 diabetes are rare. We hereby report a very rare case of diabetic ketosis with movement disorder in a young patient.

  5. Coxsackievirus-mediated hyperglycemia is enhanced by reinfection and this occurs independent of T cells

    International Nuclear Information System (INIS)

    Horwitz, Marc S.; Ilic, Alex; Fine, Cody; Rodriguez, Enrique; Sarvetnick, Nora

    2003-01-01

    The induction of autoimmunity by viruses has been hypothesized to occur by a number of mechanisms. Coxsackievirus B4 (CB4) induces hyperglycemia in SJL mice resembling diabetes in humans. While virus is effectively cleared within 2 weeks, hyperglycemia does not appear until about 8-12 weeks postinfection at a time when replicative virus is no longer detectable. In SJL mice, reinfection with CB4 enhanced the development of hyperglycemia. As predicted, the immune system responded more rapidly to the second infection and virus was cleared more swiftly. However, while infiltrating T cells were found within the pancreas, depletion of the CD4 T cell population prior to secondary infection or use of CD8 knock-out mice had no effect on the development of virus-mediated hyperglycemia. In conclusion, enhanced hyperglycemia induced by CB4 occurs independent of the T cell response

  6. Fetal hyperglycemia changes human preadipocyte function in adult life

    DEFF Research Database (Denmark)

    Hansen, Ninna Schiøler; Strasko, Klaudia Stanislawa; Hjort, Line

    2017-01-01

    Context: Offspring of women with gestational diabetes (O-GDM) or type 1 diabetes mellitus (O-T1DM) have been exposed to hyperglycemia in utero and have an increased risk of developing metabolic disease in adulthood. Design: In total, we recruited 206 adult offspring comprising the two fetal...... acid supply. Conclusions: Taken together, these findings show that intrinsic epigenetic and functional changes exist in preadipocyte cultures from individuals exposed to fetal hyperglycemia who are at increased risk of developing metabolic disease....

  7. Probiotics and atherosclerosis – a new challenge?

    Directory of Open Access Journals (Sweden)

    Chan Yee Kwan

    2012-06-01

    Full Text Available Background Atherosclerosis is the major cause of cardiovascular disease and stroke, which are among the top 10 leading causes of death worldwide. Pathogen-associated molecular patterns (PAMPs can activate toll-like receptors (TLRs and activate nuclear factor kappa B (NFκB signaling, a central pathway in inflammation, which regulates genes that encode proinflammatory molecules essential in atherogenesis. Lipopolysaccharides (LPS, which is unique to gram negative bacteria, as well as peptidoglycan (PGN, which is found in gram positive bacteria are PAMPS and ligands of TLR4 and TLR2, respectively, both of which are essential in plaque progression in atherosclerosis. Gastrointestinal tract is suggested to be the major site for absorption and translocation of TLR2 and TLR4 stimulants. Inflammation can result in a ‘leaky gut’ that leads to higher bacterial translocation, eventually the accumulation of LPS and PGN would activate TLRs and trigger inflammation through NFκB and promote further systemic complication like atherosclerosis. Probiotics, can protect the intestinal barrier to reduce bacterial translocation and have potential systemic anti-inflammatory properties.To evaluate whether probiotics can help reduce atherosclerotic development using in vivo study.Apolipoprotein E knockout (ApoE−/ −  mice were fed on high fat diet alone, with telmisartan (Tel (1 or 5 mg/kg/day, positive controls or with probiotics (VSL#3/LGG with or without Tel (1 mg/kg/day for 12 weeks.Probiotics, Tel, or a combination of both reduced lesion size at the aortic root significantly; VSL#3 reduced serum inflammatory adhesion molecules soluble E- (sE-selectin, soluble intercellular adhesion molecule 1 (sICAM-1, soluble vascular cell adhesion molecule 1 (sVCAM-1, and plaque disrupting factor matrix metalloproteinase (MMP-9 significantly; probiotics and Tel at 5 mg/kg/day could induce changes in gut microbiota population; the efficiency of lesion reduction seemed

  8. Subclinical coronary atherosclerosis and neighbourhood deprivation in an urban region

    International Nuclear Information System (INIS)

    Dragano, Nico; Hoffmann, Barbara; Stang, Andreas; Moebus, Susanne; Verde, Pablo E.; Weyers, Simone; Moehlenkamp, Stefan; Schmermund, Axel; Mann, Klaus; Joeckel, Karl-Heinz; Erbel, Raimund; Siegrist, Johannes

    2009-01-01

    Inhabitants of deprived neighbourhoods are at higher risk of coronary heart disease. In this study we investigate the hypothesis that social inequalities at neighbourhood level become already manifest in subclinical coronary atherosclerosis, as defined by electron-beam computed tomography derived measures. Coronary artery calcification was assessed as a marker of atherosclerosis in a population based sample of 4301 men and women (45-75 years) without a history of coronary heart disease. Participants lived in three adjacent cities in Germany and were examined between 2000 and 2003 as part of the Heinz Nixdorf Recall Study. Individual level data was combined with neighbourhood level information about unemployment, welfare and living space per inhabitant. This dataset was analysed with descriptive and multilevel regression methods. An association between neighbourhood deprivation and subclinical coronary calcification was observed. After adjustment for age and individual socioeconomic status male inhabitants of high unemployment neighbourhoods had an odds ratio of 1.45 (1.11, 1.96) of exhibiting a high calcification score (>75th percentile) compared to men living in low unemployment areas. The respective odds for women was 1.29 (0.97, 1.70). Additional explorative analyses suggest that clustering of unhealthy lifestyles in deprived neighbourhoods contributes to the observed association. In conclusion, findings suggest that certain neighbourhood characteristics promote the emergence of coronary atherosclerosis. This might point to a pathway from neighbourhood deprivation to manifest coronary heart disease

  9. Telomerase Activation in Atherosclerosis and Induction of Telomerase Reverse Transcriptase Expression by Inflammatory Stimuli in Macrophages

    Science.gov (United States)

    Gizard, Florence; Heywood, Elizabeth B.; Findeisen, Hannes M.; Zhao, Yue; Jones, Karrie L.; Cudejko, Cèline; Post, Ginell R.; Staels, Bart; Bruemmer, Dennis

    2010-01-01

    Objective Telomerase serves as a critical regulator of tissue renewal. Although telomerase activity is inducible in response to various environmental cues, it remains unknown whether telomerase is activated during the inflammatory remodeling underlying atherosclerosis formation. To address this question, we investigated in the present study the regulation of telomerase in macrophages and during atherosclerosis development in LDL-receptor-deficient mice. Methods and Results We demonstrate that inflammatory stimuli activate telomerase in macrophages by inducing the expression of the catalytic subunit telomerase reverse transcriptase (TERT). Reporter and chromatin immunoprecipitation assays identified a previously unrecognized NF-κB response element in the TERT promoter, to which NF-κB is recruited during inflammation. Inhibition of NF-κB signaling completely abolished the induction of TERT expression, characterizing TERT as a bona fide NF-κB target gene. Furthermore, functional experiments revealed that TERT-deficiency results in a senescent cell phenotype. Finally, we demonstrate high levels of TERT expression in macrophages of human atherosclerotic lesions and establish that telomerase is activated during atherosclerosis development in LDL-receptor-deficient mice. Conclusion These results characterize TERT as a previously unrecognized NF-κB target gene in macrophages and demonstrate that telomerase is activated during atherosclerosis. This induction of TERT expression prevents macrophage senescence and may have important implications for the development of atherosclerosis. PMID:21106948

  10. Connective tissue diseases and noninvasive evaluation of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Ardita G

    2014-06-01

    Full Text Available Giorgio Ardita, Giacomo Failla, Paolo Maria Finocchiaro, Francesco Mugno, Luigi Attanasio, Salvatore Timineri, Michelangelo Maria Di SalvoCardiovascular Department, Angiology Unit, Ferrarotto Hospital, Catania, ItalyAbstract: Connective tissue diseases (CTDs are associated with increased risk of cardiovascular disease due to accelerated atherosclerosis. In patients with autoimmune disorders, in addition to traditional risk factors, an immune-mediated inflammatory process of the vasculature seems to contribute to atherogenesis. Several pathogenetic mechanisms have been proposed, including chronic inflammation and immunologic abnormalities, both able to produce vascular damage. Macrovascular atherosclerosis can be noninvasively evaluated by ultrasound measurement of carotid or femoral plaque. Subclinical atherosclerosis can be evaluated by well-established noninvasive techniques which rely on ultrasound detection of carotid intima-media thickness. Flow-mediated vasodilatation and arterial stiffness are considered markers of endothelial dysfunction and subclinical atherosclerosis, respectively, and have been recently found to be impaired early in a wide spectrum of autoimmune diseases. Carotid intima-media thickness turns out to be a leading marker of subclinical atherosclerosis, and many studies recognize its role as a predictor of future vascular events, both in non-CTD individuals and in CTD patients. In rheumatic diseases, flow-mediated dilatation and arterial stiffness prove to be strongly correlated with inflammation, disease damage index, and with subclinical atherosclerosis, although their prognostic role has not yet been conclusively shown. Systemic lupus erythematosus, rheumatoid arthritis, and likely antiphospholipid syndrome are better associated with premature and accelerated atherosclerosis. Inconclusive results were reported in systemic sclerosis.Keywords: rheumatic disease, subclinical atherosclerosis, arterial stiffness

  11. Nuclear medicine and atherosclerosis

    International Nuclear Information System (INIS)

    Sinzinger, H.; Virgolini, I.

    1990-01-01

    Although the pathomechanisms of atherosclerosis are well known, their radioisotopic monitoring is still in its early childhood. The current radioisotope techniques are of only limited value for contributing to the clinical diagnosis of atherosclerosis. The limited reaction time of cellular blood constituents (platelets, monocytes) with the vascular surface at the injury site makes it very difficult to catch the point of injury. Lipoproteins excellently allow receptor imaging, while vascular monitoring is only of scientific interest at present. Labelling and subsequent imaging of components of the coagulation cascade have not succeeded so far, nor have attempts using unspecific labels such as porphyrin, polyclonal IgG and Fc fragments, for example. Preliminary evidence indicates that radioisotopic techniques may be of great benefit in the future in elucidating functional aspects of the disease, while they do not contribute to examining the stage and extent of atherosclerosis. (orig.)

  12. Effect of induced hyperglycemia on metastatic spreading in Lewis lung carcinoma

    International Nuclear Information System (INIS)

    Shmakova, N.L.; Fomenkova, T.E.; Fadeeva, T.A.

    1991-01-01

    The effect of induced hyperglycemia on the intensity of metastatic dissemination of Lewis lung carcinoma was investigated in experiments on mice. Neither long-, nor short-term hyperglycemia, induced at different phases of dissemination, influenced the intensity of metastatic spreading, primary tumor growth, the time of appearance of metastases, and the average life duration of tumor-bearing animals

  13. Effect of short-term hyperglycemia on cerebral function in neurooncological patients

    International Nuclear Information System (INIS)

    Loginov, V.M.; Gnezditskij, V.V.; Emulyushina, O.N.; Mukhamedzhanov, N.Z.

    1991-01-01

    The paper is concerned with the results of investigation of the effect of short-term hyperglycemia on main cerebral functions in 13 neurooncological patients. Taking into account good tolerance of short-term hyperglycemia and the results of its effective use in general oncology, one can recommend it as a modifier in radiation therapy of brain gliomas

  14. Cytokines in atherosclerosis: an intricate balance

    NARCIS (Netherlands)

    Boshuizen, M.C.S.

    2016-01-01

    Atherosclerosis is the underlying pathology in the majority of clinical manifestations of cardiovascular diseases, which are nowadays the main global cause of mortality. Atherosclerosis is a lipid-driven chronic inflammatory disease of the arterial wall. This inflammatory response, with cytokines as

  15. In-Vivo Assessment of Coronary Atherosclerosis

    NARCIS (Netherlands)

    G.A. Rodriguez-Granillo

    2006-01-01

    textabstractIntravascular ultrasound (IVUS) has emerged as a highly accurate tool for the serial assessment of the natural history of coronary atherosclerosis and to evaluate the effect of different conventional and emerging drug therapies on the progression of atherosclerosis. The

  16. Early bone anchorage to micro- and nano-topographically complex implant surfaces in hyperglycemia.

    Science.gov (United States)

    Ajami, Elnaz; Bell, Spencer; Liddell, Robert S; Davies, John E

    2016-07-15

    The aim of this work was to investigate the effect of implant surface design on early bone anchorage in the presence of hyperglycemia. 108 Wistar rats were separated into euglycemic (EG) controls and STZ-treated hyperglycemic (HG) groups, and received bilateral femoral custom rectangular implants of two surface topographies: grit blasted (GB) and grit-blast with a superimposed calcium phosphate nanotopography (GB-DCD). The peri-implant bone was subjected to a tensile disruption test 5, 7, and 9days post-operatively (n=28/time point); the force was measured; and the residual peri-implant bone was observed by scanning electron microscopy (SEM). Disruption forces at 5days were not significantly different from zero for the GB implants (p=0.24) in either metabolic group; but were for GB+DCD implants in both metabolic groups (pmicro-surfaced implants showed significantly different disruption forces at all time points (e.g. >15N and implants, as all values were very low (implant bone showed compromised intra-fibrillar collagen mineralization in hyperglycemia, while inter-fibrillar and cement line mineralization remained unaffected. Enhanced bone anchorage to the implant surfaces was observed on the nanotopographically complex surface independent of metabolic group. The compromised intra-fibrillar mineralization observed provides a mechanism by which early bone mineralization is affected in hyperglycemia. It is generally accepted that the hyperglycemia associated with diabetes mellitus compromises bone quality, although the mechanism by which this occurs is unknown. Uncontrolled hyperglycemia is therefore a contra-indication for bone implant placement. It is also known that nano-topographically complex implant surfaces accelerate early peri-implant healing. In this report we show that, in our experimental model, nano-topographically complex surfaces can mitigate the compromised bone healing seen in hyperglycemia. Importantly, we also provide a mechanistic explanation for

  17. Neuropeptide Y gene polymorphisms confer risk of early-onset atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Svati H Shah

    2009-01-01

    Full Text Available Neuropeptide Y (NPY is a strong candidate gene for coronary artery disease (CAD. We have previously identified genetic linkage to familial CAD in the genomic region of NPY. We performed follow-up genetic, biostatistical, and functional analysis of NPY in early-onset CAD. In familial CAD (GENECARD, N = 420 families, we found increased microsatellite linkage to chromosome 7p14 (OSA LOD = 4.2, p = 0.004 in 97 earliest age-of-onset families. Tagged NPY SNPs demonstrated linkage to CAD of a 6-SNP block (LOD = 1.58-2.72, family-based association of this block with CAD (p = 0.02, and stronger linkage to CAD in the earliest age-of-onset families. Association of this 6-SNP block with CAD was validated in: (a 556 non-familial early-onset CAD cases and 256 controls (OR 1.46-1.65, p = 0.01-0.05, showing stronger association in youngest cases (OR 1.84-2.20, p = 0.0004-0.09; and (b GENECARD probands versus non-familial controls (OR 1.79-2.06, p = 0.003-0.02. A promoter SNP (rs16147 within this 6-SNP block was associated with higher plasma NPY levels (p = 0.04. To assess a causal role of NPY in atherosclerosis, we applied the NPY1-receptor-antagonist BIBP-3226 adventitially to endothelium-denuded carotid arteries of apolipoprotein E-deficient mice; treatment reduced atherosclerotic neointimal area by 50% (p = 0.03. Thus, NPY variants associate with atherosclerosis in two independent datasets (with strong age-of-onset effects and show allele-specific expression with NPY levels, while NPY receptor antagonism reduces atherosclerosis in mice. We conclude that NPY contributes to atherosclerosis pathogenesis.

  18. Survival of lung cancer patients after combined therapy with hyperglycemia

    International Nuclear Information System (INIS)

    Zharkov, V.V.; Demidchik, Yu.E.; Khodina, T.V.

    1991-01-01

    The results of a randomized study of combined therapy of lung cancer patients including large field radiotherapy (total irradiation of 20 Gy, daily fractionation of 4 Gy) and induced hyperglycemia (22-23 mmol/1) are presented. The use of new variants of combined therapy was shown to increase significantly the survival of patients, however therapeutic efficacy was different depending on the time of hyperglycemia: wheter it was used before radiotherapy sessions of after their discontinuation

  19. Atherosclerosis VII

    International Nuclear Information System (INIS)

    Fidge, N.H.; Nestel, P.J.; Flinders Univ., Adelaide

    1986-01-01

    In these proceedings the major themes of the conference have been preserved and comprise epidemiology, lipoproteins, pathogenesis, and clinical, therapeutic and nutritional aspects. The diet-lipidcoronary artery disease hypothesis has been strengthened significantly. Several long-awaited trials, reviewed here, have provided very strong support for the rationale for treating hyperlipidemia. A strategy for the prevention of atherosclerosis was defined at the conference. The genesis of atherosclerosis was shown to be more firmly grounded in the influx of lipoprotein into the arterial wall. The regulation of these processes and the rapid advances made possible by new technology were detailed in several sessions. Important new developments in the clinical area and in pharmacology give promise of greatly improved management of established disease. However, the possibility of mounting large-scale preventive measures in the near future, was given credence in the epidemiology and nutrition workshops. (Auth.)

  20. [Psychosocial factors as predictors of atherosclerosis and cardiovascular events: contribution from animal models].

    Science.gov (United States)

    Alboni, Paolo; Alboni, Marco

    2006-11-01

    Conventional risk factors (abnormal lipids, hypertension, etc.) are independent predictors of atherosclerosis and cardiovascular events; however, these factors are not specific since about half patients with acute myocardial infarction paradoxically result at low cardiovascular risk. Recent prospective studies provide convincing evidence that some psychosocial factors are independent predictors of atherosclerosis and cardiovascular events, as well. Psychosocial factors that promote atherosclerosis can be divided into two general categories: chronic stressors, including social isolation/low social support and work stress (subordination without job control) and emotional factors, including affective disorders such as depression, severe anxiety and hostility/anger. The emotional factors, such as the chronic stressors, activate the biological mechanisms of chronic stress: increased activity of the hypothalamic-pituitary-adrenal axis, sympathetic system and inflammation processes, which have atherogenic effects, and an increase in blood coagulation. In spite of the amount of published data, psychosocial factors receive little attention in the medical setting. About 30 years ago, Kuller defined the criteria for a causal relation between a risk factor and atherosclerosis and cardiac events. The first of these criteria states that experimental research should demonstrate that any new factor would increase the extent of atherosclerosis or its complications in suitable animal models. We carried out a bibliographic research in order to investigate whether the results of the studies dealing with animal examination and experimentation support the psychosocial factors as predictors of atherosclerosis. Contributions related to some of the psychosocial factors such as social isolation, subordination and hostility/anger have been found. In these studies atherosclerotic extension has been evaluated at necroscopy; however, the incidence of cardiovascular events has not been

  1. Animal models of surgically manipulated flow velocities to study shear stress-induced atherosclerosis.

    Science.gov (United States)

    Winkel, Leah C; Hoogendoorn, Ayla; Xing, Ruoyu; Wentzel, Jolanda J; Van der Heiden, Kim

    2015-07-01

    Atherosclerosis is a chronic inflammatory disease of the arterial tree that develops at predisposed sites, coinciding with locations that are exposed to low or oscillating shear stress. Manipulating flow velocity, and concomitantly shear stress, has proven adequate to promote endothelial activation and subsequent plaque formation in animals. In this article, we will give an overview of the animal models that have been designed to study the causal relationship between shear stress and atherosclerosis by surgically manipulating blood flow velocity profiles. These surgically manipulated models include arteriovenous fistulas, vascular grafts, arterial ligation, and perivascular devices. We review these models of manipulated blood flow velocity from an engineering and biological perspective, focusing on the shear stress profiles they induce and the vascular pathology that is observed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Selective potentiation of the antitumor radiation effect by means of short-term hyperglycemia

    International Nuclear Information System (INIS)

    Yarmonenko, S.P.; Shapot, V.S.; Voloshina, E.A.; Gorozhanskaya, Eh.G.; Dyuskaliev, Zh.D.; Krimker, V.M.

    1981-01-01

    Experiments on mice have shown that short-term induced hyperglycemia caused by 5-fold intraperitoneal administration of glucose at a dose of 2.6 and 1.3 g/kg increases notably the radiation injury to a solid type of Ehrlich carcinoma. Short-term induced hyperglycemia is mostly effective after irradiation. During irradiation together with its antitumor effect enhanced in the presence of short-term induced hyperglycemia there is observed selective protection of the normal tissues resulting from a decrease of oxygen pressure in them

  3. HYPERGLYCEMIA IN GRADE III AND GRADE IV MALNUTRITION WITH DEHYDRATING GASTROENTERITIS

    Directory of Open Access Journals (Sweden)

    Mallesh

    2015-07-01

    Full Text Available OBJECTIVE OF THE STUDY: To study the incidence of hyperglycemia in grade III AND IV malnutrition with no signs and some signs of dehydration. SETTING: Tertiary care center located in north Karnataka. DESIGN: Prospective observational study involving 21 children. METHODS: All the children with grade III and grade IV malnutrition presenting with diarrhea of less than 14 days duration, having no signs to some signs of dehydration. RESULTS: Hyperglycemia was observed in three of 21 children hypoglycemia was observed in six children. CONCLUSION: Although hypoglycemia is common finding in moderate and severely malnourished children with dehydrating gastroenteritis, hyperglycemia should also be suspected and treated. Long term follow up of these children is needed involving larger number of people in multicenter studies.

  4. Association between hyperglycemia and retinopathy of prematurity: a systemic review and meta-analysis

    Science.gov (United States)

    Au, Sunny C. L.; Tang, Shu-Min; Rong, Shi-Song; Chen, Li-Jia; Yam, Jason C. S.

    2015-01-01

    As the role of hyperglycemia in the development of retinopathy of prematurity (ROP) has not been well established, a meta-analysis of the association between hyperglycemia and ROP was conducted. Studies were identified through literature search in MEDLINE and EMBASE up to June 20, 2014 with keywords related to “hyperglycaemia” and “ROP”. Nine eligible studies involving 1939 neonates with 509 cases of ROP were included. Unadjusted analyses showed that hyperglycemia was significantly associated with ROP (Odds ratio [OR] = 4.16, Phyperglycemia (Standardized mean difference [SMD] = 1.21, Phyperglycemia with ROP (adjusted OR 1.08, P = 0.03); and no significant association on mean glucose level with ROP (adjusted OR = 1.08, P = 0.15). Hence, hyperglycemia cannot be definitely considered as a risk factor for ROP, and further studies should adjust for potential confounding factors to clarify this association. PMID:25766465

  5. Scotopic electrophysiology of the retina during transient hyperglycemia in type 2 diabetes

    DEFF Research Database (Denmark)

    Holfort, Stig Kraglund; Klemp, Kristian; Kofoed, Peter Kristian

    2010-01-01

    PURPOSE: To examine dark-adapted retinal function in subjects with type 2 diabetes during transient hyperglycemia. METHODS: Twenty-four subjects with type 2 diabetes and minimal diabetic retinopathy were randomized to an oral glucose tolerance test (OGTT) or a fasting regimen. One study eye...... by hyperglycemia. The scotopic ffERG amplitudes rose and fell in phase with the glycemia. Implicit times did not change with the rise and fall in glycemia. CONCLUSIONS: The change in scotopic signaling amplitude in the outer and middle layers of retina in subjects with diabetes was proportional to the change...... in capillary glucose. Cone amplitude was not influenced by hyperglycemia in this study....

  6. Application of hyperglycemia induction in combination with radiotherapy for rectal cancer treatment

    International Nuclear Information System (INIS)

    Krimker, V.M.; Goldobenko, G.V.; Ozhiganov, E.L.; Ajtakova, T.I.; Dyuskaliev, Zh.D.

    1986-01-01

    A treatment modality employing radiotherapy wih subsequent hyperglycemia induction was evolved in experiments on mice and then clinically tested in 32 cases of inoperable locally - extensive primary and recurrent cancer of the rectum. A 50% regression of tumor was registered in 14 (43.0%) out of 32 patients treated with radiotherapy in combination with hyperglycemia. Similar degree of regression was observed only in 6 (15.0%) out of 40 patientswo received who received the same radiation treatment unaccompanied by hyperglycemia. The difference was statistically significant. No untoward side-effects developed. The results are encouraging and seem to open up new vistas of clinical research

  7. Correlation between Mitochondrial Reactive Oxygen and Severity of Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Gabriel G. Dorighello

    2016-01-01

    Full Text Available Atherosclerosis has been associated with mitochondria dysfunction and damage. Our group demonstrated previously that hypercholesterolemic mice present increased mitochondrial reactive oxygen (mtROS generation in several tissues and low NADPH/NADP+ ratio. Here, we investigated whether spontaneous atherosclerosis in these mice could be modulated by treatments that replenish or spare mitochondrial NADPH, named citrate supplementation, cholesterol synthesis inhibition, or both treatments simultaneously. Robust statistical analyses in pooled group data were performed in order to explain the variation of atherosclerosis lesion areas as related to the classic atherosclerosis risk factors such as plasma lipids, obesity, and oxidative stress, including liver mtROS. Using three distinct statistical tools (univariate correlation, adjusted correlation, and multiple regression with increasing levels of stringency, we identified a novel significant association and a model that reliably predicts the extent of atherosclerosis due to variations in mtROS. Thus, results show that atherosclerosis lesion area is positively and independently correlated with liver mtROS production rates. Based on these findings, we propose that modulation of mitochondrial redox state influences the atherosclerosis extent.

  8. CT and MRI findings of chorea associated with nonketotic hyperglycemia

    International Nuclear Information System (INIS)

    Hu Dongjin; Zhang Weidong; Wu Dingquan; Meng Lishi; Chen Jian

    2008-01-01

    Objective: To explore the imaging diagnosis of chorea associated with nonketotic hyperglycemia by describing its CT and MR findings and correlating those findings with the clinical manifestations. Methods: The imaging findings and clinical data from 6 patients with chorea associated with nonketotic hyperglycemia were retrospectively analyzed. All 6 patients had unenhanced CT scans, 1 also had MR imaging examination. Three of 6 patients had follow-up CT scans and 1 of 3 patients had follow-up MR imaging studies. Results: CT studies of all 6 patients showed unilateral or bilateral hyperdense striatum. The putamen was involved in all 6 patients, the caudate nucleus or lateral portion of the globus pallidus were involved in 5 of all 6 patients. All 3 follow-up CT studies depicted a decreased or resolved hyperdensity of the abnormal striatum. T 1 -weighted MR images in 1 patient showed the hyperintense lesions of bilateral lentiform nuclei, T 2 -weighted MR images of the patient showed the hypointense lesions of the corresponding lentiform nuclei, and its follow-up MR images depicted invariable signal intensity of T 1 -weighted and T 2 -weighted images. In all patients, the chorea resolved within 2 to 6 days after treatment of the hyperglycemia. Conclusion: The characteristic imaging findings of chorea associated with nonketotic hyperglycemia can suggest an accurate diagnosis. (authors)

  9. Brain Cell Swelling During Hypocapnia Increases with Hyperglycemia or Ketosis

    Science.gov (United States)

    Glaser, Nicole; Bundros, Angeliki; Anderson, Steve; Tancredi, Daniel; Lo, Weei; Orgain, Myra; O'Donnell, Martha

    2014-01-01

    Severe hypocapnia increases the risk of DKA-related cerebral injury in children, but the reason for this association is unclear. To determine whether the effects of hypocapnia on the brain are altered during hyperglycemia or ketosis, we induced hypocapnia (pCO2 20 ± 3 mmHg) via mechanical ventilation in three groups of juvenile rats: 25 controls, 22 hyperglycemic rats (serum glucose 451± 78 mg/dL) and 15 ketotic rats (beta-hydroxy butyrate 3.0 ± 1.0 mmol/L). We used magnetic resonance imaging to measure cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) values in these groups and in 17 ventilated rats with normal pCO2 (40±3 mmHg). In a subset (n=35), after 2 hrs of hypocapnia, pCO2 levels were normalized (40±3 mmHg) and ADC and CBF measurements repeated. Declines in CBF with hypocapnia occurred in all groups. Normalization of pCO2 after hypocapnia resulted in striatal hyperemia. These effects were not substantially altered by hyperglycemia or ketosis, however, declines in ADC during hypocapnia were greater during both hyperglycemia and ketosis. We conclude that brain cell swelling associated with hypocapnia is increased by both hyperglycemia and ketosis, suggesting that these metabolic conditions may make the brain more vulnerable to injury during hypocapnia. PMID:24443981

  10. [Association between IGF system and PAPP-A in coronary atherosclerosis].

    Science.gov (United States)

    Fierro-Macías, Alfonso Eduardo; Floriano-Sánchez, Esaú; Mena-Burciaga, Victoria Michelle; Gutiérrez-Leonard, Hugo; Lara-Padilla, Eleazar; Abarca-Rojano, Edgar; Fierro-Almanzán, Alfonso Edmundo

    2016-01-01

    Atherosclerosis is a condition that involves multiple pathophysiological mechanisms and whose knowledge has not been fully elucidated. Often, scientific advances on the atherogenic pathophysiology generate that molecules not previously considered in the scene of this disease, were attributed actions on the onset or progression of it. A representative example is the study of a new mechanism involved in the atherogenic process, consisting of the association between the insulin-like growth factor (IGF) system and pregnancy-associated plasma protein-A (PAPP-A). Insulin-like growth factor system is a family of peptides that include 3 peptide hormones, 4 transmembrane receptors and 6 binding proteins. Insulin-like growth factor-1 (IGF-1) is the main ligand of the IGF system involved in coronary atherosclerosis. IGF-1 exerts its effects via activation of the IGF-1R receptor on vascular smooth muscle cells or macrophages. In vascular smooth muscle cells promotes migration and prevents apoptosis which increases plaque stability while in macrophages reduces reverse cholesterol transport leading to the formation of foam cells. Regulation of IGF-1 endothelial bioavailability is carried out by IGFBP proteases, mainly by PAPP-A. In this review, we address the mechanisms between IGF system and PAPP-A in atherosclerosis with emphasis on molecular effects on vascular smooth muscle cells and macrophages. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  11. Atherosclerosis-Driven Treg Plasticity Results in Formation of a Dysfunctional Subset of Plastic IFNγ+ Th1/Tregs.

    Science.gov (United States)

    Butcher, Matthew J; Filipowicz, Adam R; Waseem, Tayab C; McGary, Christopher M; Crow, Kevin J; Magilnick, Nathaniel; Boldin, Mark; Lundberg, Patric S; Galkina, Elena V

    2016-11-11

    Forkhead box P3 + T regulatory cells (Tregs) are key players in maintaining immune homeostasis. Evidence suggests that Tregs respond to environmental cues to permit or suppress inflammation. In atherosclerosis, Th1-driven inflammation affects Treg homeostasis, but the mechanisms governing this phenomenon are unclear. Here, we address whether atherosclerosis impacts Treg plasticity and functionality in Apoe - /- mice, and what effect Treg plasticity might have on the pathology of atherosclerosis. We demonstrate that atherosclerosis promotes Treg plasticity, resulting in the reduction of CXCR3 + Tregs and the accumulation of an intermediate Th1-like interferon (IFN)-γ + CCR5 + Treg subset (Th1/Tregs) within the aorta. Importantly, Th1/Tregs arise in atherosclerosis from bona fide Tregs, rather than from T-effector cells. We show that Th1/Tregs recovered from atherosclerotic mice are dysfunctional in suppression assays. Using an adoptive transfer system and plasticity-prone Mir146a -/- Tregs, we demonstrate that elevated IFNγ + Mir146a -/- Th1/Tregs are unable to adequately reduce atherosclerosis, arterial Th1, or macrophage content within Apoe -/- mice, in comparison to Mir146a +/+ Tregs. Finally, via single-cell RNA-sequencing and real-time -polymerase chain reaction, we show that Th1/Tregs possess a unique transcriptional phenotype characterized by coexpression of Treg and Th1 lineage genes and a downregulation of Treg-related genes, including Ikzf2, Ikzf4, Tigit, Lilrb4, and Il10. In addition, an ingenuity pathway analysis further implicates IFNγ, IFNα, interleukin-2, interleukin-7, CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), T-cell receptor, and Csnk2b-related pathways in regulating Treg plasticity. Atherosclerosis drives Treg plasticity, resulting in the accumulation of dysfunctional IFNγ + Th1/Tregs that may permit further arterial inflammation and atherogenesis. © 2016 American Heart Association, Inc.

  12. Stent-assisted angioplasty for intracranial atherosclerosis

    International Nuclear Information System (INIS)

    Nakahara, Toshinori; Sakamoto, Shigeyuki; Hamasaki, Osamu; Sakoda, Katsuaki

    2002-01-01

    We report on two patients with intracranial atherosclerosis of the carotid artery or vertebral artery treated with stent-assisted angioplasty. Both patients have severe intracranial atherosclerosis (>70%) with refractory symptoms despite optimal medical treatment. In both patients, a coronary balloon-expandable stent was successfully placed using a protective balloon technique without procedural complications. The patients were asymptomatic and neurologically intact at a mean clinical follow-up of 13 months. Follow-up angiograms did not show restenosis 3 or 4 months after procedure, respectively. Stent-assisted angioplasty for intracranial atherosclerosis in the elective patient has proven effective, with an acceptable low rate of morbidity and mortality. (orig.)

  13. The Progression and Early detection of Subclinical Atherosclerosis (PESA) study

    DEFF Research Database (Denmark)

    Fernández-Ortiz, Antonio; Jiménez-Borreguero, L Jesús; Peñalvo, José L

    2013-01-01

    The presence of subclinical atherosclerosis is a likely predictor of cardiovascular events; however, factors associated with the early stages and progression of atherosclerosis are poorly defined.......The presence of subclinical atherosclerosis is a likely predictor of cardiovascular events; however, factors associated with the early stages and progression of atherosclerosis are poorly defined....

  14. Neonatal hyperglycemia inhibits angiogenesis and induces inflammation and neuronal degeneration in the retina.

    Directory of Open Access Journals (Sweden)

    Elsa Kermorvant-Duchemin

    Full Text Available Recent evidence suggests that transient hyperglycemia in extremely low birth weight infants is strongly associated with the occurrence of retinopathy of prematurity (ROP. We propose a new model of Neonatal Hyperglycemia-induced Retinopathy (NHIR that mimics many aspects of retinopathy of prematurity. Hyperglycemia was induced in newborn rat pups by injection of streptozocine (STZ at post natal day one (P1. At various time points, animals were assessed for vascular abnormalities, neuronal cell death and accumulation and activation of microglial cells. We here report that streptozotocin induced a rapid and sustained increase of glycemia from P2/3 to P6 without affecting rat pups gain weight or necessitating insulin treatment. Retinal vascular area was significantly reduced in P6 hyperglycemic animals compared to control animals. Hyperglycemia was associated with (i CCL2 chemokine induction at P6, (ii a significant recruitment of inflammatory macrophages and an increase in total number of Iba+ macrophages/microglia cells in the inner nuclear layer (INL, and (iii excessive apoptosis in the INL. NHIR thereby reproduces several aspects of ischemic retinopathies, including ROP and diabetic retinopathies, and might be a useful model to decipher hyperglycemia-induced cellular and molecular mechanisms in the small rodent.

  15. (-)-anipamil retards atherosclerosis in Watanabe heritable hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Hansen, B F; Mortensen, A; Hansen, J F

    1995-01-01

    Calcium antagonists have been reported to limit atherosclerosis in cholesterol fed rabbits. The purpose of this study was to examine the effect of the calcium antagonist (-)-anipamil on the spontaneous development of atherosclerosis in homozygote WHHL rabbits. From the age of 7 weeks, three groups...... differences were found in serum lipids (i.e., VLDL, IDL, LDL, HDL) in the study period among the three groups. Plasma anipamil at the end of the study was 0.23 +/- 6, and 202 +/- 19 ng/ml, respectively, in the three treatment groups. The degree of atherosclerosis in the abdominal aorta was significantly lower...... (p atherosclerosis in the abdominal aorta in WHHL rabbits....

  16. Management of dexamethasone-induced hyperglycemia in patients undergoing chemotherapy in an outpatient setting: a best practice implementation project.

    Science.gov (United States)

    Sinaga, Gery; de Koeijer, Elizabeth

    2018-04-01

    The objective of this project was to implement best practice in an outpatient clinical setting in order to increase both nursing staff and patients' knowledge and awareness on the importance of blood sugar management during chemotherapy and to show that through compliance with best practice, the incidence of dexamethasone-induced hyperglycemia during chemotherapy can be minimized. Steroid-induced hyperglycemia is a commonly neglected symptom in cancer treatment, contributing to poor patient prognosis and extended hospital stay. Evidence shows that controlled blood sugar during chemotherapy is associated with improved patient outcomes and better tolerance to cancer treatment. For the purpose of this paper steroid-induced hyperglycemia will be referred to as dexamethasone-induced hyperglycemia. This project utilized the Joanna Briggs Institute Practical Application of Clinical Evidence System (JBI-PACES) and Getting Research into Practice (GRiP) audit tools to promote compliance in the clinical setting. Thirty patients participated in the audit, which was executed by nursing staff in the Medical Oncology Outpatient Unit at the Cancer Ambulatory and Community Health Support Department at the Canberra Hospital. The baseline audit revealed large gaps between best practice and current practice. This underlined the need for more education for both nursing staff and patients. Other barriers such as the absence of assessment and documentation by the clinicians and the minimum number of potential referrals to the diabetes educator were addressed by encouraging patients to speak about their diabetes, and also in the development of a simplified referral process in order to have patients reviewed by the Diabetes Educator in a timely manner. There were significant improvements after more information sessions were held and more resources made available to both nursing staff and patients, but there were also minimal to zero compliance drop on parts of the follow-up audit. In an

  17. Changes in the TNF-alpha/IL-10 ratio in hyperglycemia-associated pregnancies.

    Science.gov (United States)

    Moreli, Jusciele B; Corrêa-Silva, Simone; Damasceno, Débora C; Sinzato, Yuri K; Lorenzon-Ojea, Aline R; Borbely, Alexandre U; Rudge, Marilza V C; Bevilacqua, Estela; Calderon, Iracema M P

    2015-03-01

    TNF-α is a diabetogenic cytokine associated with adverse outcomes during pregnancy that can be counterbalanced by IL-10. We have investigated IL-10 and TNF-α balance at maternal and placental levels in hyperglycemia-associated pregnancies. One hundred and ninety-two pregnant women participated, which included normoglycemic women (ND) and women with mild gestational hyperglycemia (MGH), gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (DM2). Maternal plasma and placental tissue IL-10 and TNF-α levels were measured by ELISA and placental TNF-α was also immunolocalized. Maternal plasma TNF-α levels were highest in GDM (p=0.0190), whereas TNF-α levels were highest in placental tissues in DM2 (p=0.0095). Immunohistochemistry also showed strong reactivity with anti-TNF-α antibody in the villous structures in the DM2 group. Conversely, IL-10 levels were lowest in maternal plasma of the DM2 group (p=0.0228). The TNF-α/IL-10 ratio in maternal plasma progressively increased with the severity of hyperglycemia (pDM2 group (p=0.0150). In both, plasma and placenta, TNF-α/IL-10 ratio were correlated with mean maternal glycemia and HbA1c levels. Alterations of placenta and serum TNF-α/IL-10 balance with predominance of TNF-α were correlated with the severity of hyperglycemia during gestation. This association may offer insight into the pathogenesis of gestational hyperglycemia and associated pregnancy outcomes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Peculiarities of tumor blood supply and their role in radiotherapy, hyperthermia and hyperglycemia

    International Nuclear Information System (INIS)

    Kozin, S.V.; Furmanchuk, A.V.

    1986-01-01

    Development regularities and functional peculiarities of tumor microcirculatory channel (MCC) are considered. The role of microcirculation changes under radiotherapy and it's combinations with hyperthermia and hyperglycemia is estimated. The conclusion is drawn, that MCC reactions play a substantial role in realization of hyperthermia and hyperglycemia radiomodifying action

  19. Hawthorn (Crataegus pinnatifida Bunge) leave flavonoids attenuate atherosclerosis development in apoE knock-out mice.

    Science.gov (United States)

    Dong, Pengzhi; Pan, Lanlan; Zhang, Xiting; Zhang, Wenwen; Wang, Xue; Jiang, Meixiu; Chen, Yuanli; Duan, Yajun; Wu, Honghua; Xu, Yantong; Zhang, Peng; Zhu, Yan

    2017-02-23

    Hawthorn (Crataegus pinnatifida Bunge) leave have been used to treat cardiovascular diseases in China and Europe. Hawthorn leave flavonoids (HLF) are the main part of extraction. Whether hawthorn leave flavonoids could attenuate the development of atherosclerosis and the possible mechanism remain unknown. High-fat diet (HFD) mixed with HLF at concentrations of 5mg/kg and 20mg/kg were administered to apolipoprotein E (apoE) knock out mice. 16 weeks later, mouse serum was collected to determine the lipid profile while the mouse aorta dissected was prepared to measure the lesion area. Hepatic mRNA of genes involved in lipid metabolism were determined. Peritoneal macrophages were collected to study the impact of HLF on cholesterol efflux, formation of foam cell and the expression of ATP binding cassette transporter A1 (ABCA1). Besides, in vivo reverse cholesterol transport (RCT) was conducted. HLF attenuated the development of atherosclerosis that the mean atherosclerotic lesion area in en face aortas was reduced by 23.1% (Pflavonoids can slow down the development of atherosclerosis in apoE knockout mice via induced expression of genes involved in antioxidant activities, inhibition of the foam cell formation and promotion of RCT in vivo, which implies the potential use in the prevention of atherosclerosis. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  20. Vinpocetine attenuates lipid accumulation and atherosclerosis formation

    International Nuclear Information System (INIS)

    Cai, Yujun; Li, Jian-Dong; Yan, Chen

    2013-01-01

    Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis

  1. Vinpocetine attenuates lipid accumulation and atherosclerosis formation

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Yujun [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States); Li, Jian-Dong [Center for Inflammation, Immunity and Infection, and Department of Biology, Georgia State University, Atlanta, GA 30303 (United States); Yan, Chen, E-mail: Chen_Yan@urmc.rochester.edu [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States)

    2013-05-10

    Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis.

  2. Postprandial hyperglycemia corrected by IGF-I (Increlex®) in Laron syndrome.

    Science.gov (United States)

    Latrech, Hanane; Simon, Albane; Beltrand, Jacques; Souberbielle, Jean-Claude; Belmejdoub, Ghizlane; Polak, Michel

    2012-01-01

    Laron syndrome is caused by a mutation in the growth hormone (GH) receptor and manifests as insulin-like growth factor-I (IGF-I) deficiency, severe short stature, and early hypoglycemia. We report a case with postprandial hyperglycemia, an abnormality not reported previously. Postprandial hyperglycemia was due to chronic IGF-I deficiency, and was reversed by IGF-I replacement therapy. A Moroccan girl referred for short stature at 7 years and 8 months of age had dwarfism [height, 78 cm (-9 SDs); weight, 10 kg (-4 SDs)], hypoglycemia, and truncal obesity. Her serum IGF-I level was very low, and her baseline serum GH level was elevated to 47 mIU/l. Molecular analysis showed a homozygous mutation in the GH receptor gene. Continuous glucose monitoring before treatment showed asymptomatic hypoglycemia with postprandial hyperglycemia (2.5 g/l, 13.75 mmol/l). Treatment with recombinant human IGF-I (mecasermin, Increlex®) was started. The blood glucose profile improved with 0.04 µg/kg/day and returned to normal with 0.12 µg/kg/day. Postprandial hyperglycemia is a metabolic consequence of chronic IGF-I deficiency. The beneficial effect of IGF-I replacement therapy may be ascribable to improved postprandial transfer of glucose. Copyright © 2012 S. Karger AG, Basel.

  3. Osteoprotegerin as a marker of atherosclerosis

    DEFF Research Database (Denmark)

    Hosbond, Susanne Elisabeth; Poulsen, Tina Svenstrup; Diederichsen, Axel Cosmus Pyndt

    2012-01-01

    Abstract Objective: Osteoprotegerin (OPG) may be involved in development of atherosclerosis. To evaluate plasma concentrations of OPG in individuals with stable coronary artery disease (CAD), acute coronary syndrome (ACS), peripheral artery disease (PAD) and cerebrovascular disease (CBVD) a syste......Abstract Objective: Osteoprotegerin (OPG) may be involved in development of atherosclerosis. To evaluate plasma concentrations of OPG in individuals with stable coronary artery disease (CAD), acute coronary syndrome (ACS), peripheral artery disease (PAD) and cerebrovascular disease (CBVD...... with clearly defined cohorts qualified for this review. Results: In 11 studies OPG concentrations were elevated. Severity of atherosclerosis was significantly associated with higher OPG concentrations compared to healthy controls. No association between PAD and OPG concentrations was observed. Conclusion: OPG...

  4. A CD1d-dependent lipid antagonist to NKT cells ameliorates atherosclerosis in ApoE-/- mice by reducing lesion necrosis and inflammation.

    Science.gov (United States)

    Li, Yi; Kanellakis, Peter; Hosseini, Hamid; Cao, Anh; Deswaerte, Virginie; Tipping, Peter; Toh, Ban-Hock; Bobik, Alex; Kyaw, Tin

    2016-02-01

    Atherosclerosis-related deaths from heart attacks and strokes remain leading causes of global mortality, despite the use of lipid-lowering statins. Thus, there is an urgent need to develop additional therapies. Reports that NKT cells promote atherosclerosis and an NKT cell CD1d-dependent lipid antagonist (DPPE-PEG350, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N[methoxy(polyethyleneglycol)-350]) reduces allergen-induced inflammation led us to investigate its therapeutic potential in preventing the development and progression of experimental atherosclerosis. DPPE-PEG350 was administered to hyperlipidaemic ApoE(-/-) mice with/without established atherosclerosis. Atherosclerosis and immune cells were assessed in the aortic sinus lesions. Lesion expression of monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion protein-1 (VCAM-1) responsible for inflammatory immune cell recruitment as well as mRNA expression of IFNγ and its plasma levels were investigated. Necrotic cores and lesion smooth muscle and collagen contents important in plaque stability were determined as were plasma lipid levels. DPPE-PEG350 reduced atherosclerosis development and delayed progression of established atherosclerosis without affecting plasma lipids. CD4 and CD8 T cells and B cells in atherosclerotic lesions were decreased in DPPE-PEG350-treated mice. Lesion MCP-1 and VCAM-1 protein expression and necrotic core size were reduced without affecting lesion smooth muscle and collagen content. IFNγ and lymphocytes were unaffected by the treatment. The attenuation of progression of established atherosclerosis together with reduced development of atherosclerosis in hyperlipidaemic mice by the NKT antagonist, without affecting NKT cell or other lymphocyte numbers, suggests that targeting lesion inflammation via CD1d-dependent activation of NKT cells using DPPE-PEG350 has a therapeutic potential in treating atherosclerosis. Published on behalf of the European Society of

  5. Neonatal Hyperglycemia due to Transient Neonatal Diabetes Mellitus in Puerto Rico

    OpenAIRE

    Fargas-Berríos, N.; García-Fragoso, L.; García-García, I.; Valcárcel, M.

    2015-01-01

    Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM) is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor ...

  6. Sphingosine 1-Phosphate and Atherosclerosis

    Science.gov (United States)

    Yatomi, Yutaka

    2018-01-01

    Sphingosine 1-phosphate (S1P) is a potent lipid mediator that works on five kinds of S1P receptors located on the cell membrane. In the circulation, S1P is distributed to HDL, followed by albumin. Since S1P and HDL share several bioactivities, S1P is believed to be responsible for the pleiotropic effects of HDL. Plasma S1P levels are reportedly lower in subjects with coronary artery disease, suggesting that S1P might be deeply involved in the pathogenesis of atherosclerosis. In basic experiments, however, S1P appears to possess both pro-atherosclerotic and anti-atherosclerotic properties; for example, S1P possesses anti-apoptosis, anti-inflammation, and vaso-relaxation properties and maintains the barrier function of endothelial cells, while S1P also promotes the egress and activation of lymphocytes and exhibits pro-thrombotic properties. Recently, the mechanism for the biased distribution of S1P on HDL has been elucidated; apolipoprotein M (apoM) carries S1P on HDL. ApoM is also a modulator of S1P, and the metabolism of apoM-containing lipoproteins largely affects the plasma S1P level. Moreover, apoM modulates the biological properties of S1P. S1P bound to albumin exerts both beneficial and harmful effects in the pathogenesis of atherosclerosis, while S1P bound to apoM strengthens anti-atherosclerotic properties and might weaken the pro-atherosclerotic properties of S1P. Although the detailed mechanisms remain to be elucidated, apoM and S1P might be novel targets for the alleviation of atherosclerotic diseases in the future. PMID:28724841

  7. Effects of High Fat Feeding and Diabetes on Regression of Atherosclerosis Induced by Low-Density Lipoprotein Receptor Gene Therapy in LDL Receptor-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Florian Willecke

    Full Text Available We tested whether a high fat diet (HFD containing the inflammatory dietary fatty acid palmitate or insulin deficient diabetes altered the remodeling of atherosclerotic plaques in LDL receptor knockout (Ldlr-/- mice. Cholesterol reduction was achieved by using a helper-dependent adenovirus (HDAd carrying the gene for the low-density lipoprotein receptor (Ldlr; HDAd-LDLR. After injection of the HDAd-LDLR, mice consuming either HFD, which led to insulin resistance but not hyperglycemia, or low fat diet (LFD, showed regression compared to baseline. However there was no difference between the two groups in terms of atherosclerotic lesion size, or CD68+ cell and lipid content. Because of the lack of effects of these two diets, we then tested whether viral-mediated cholesterol reduction would lead to defective regression in mice with greater hyperglycemia. In both normoglycemic and streptozotocin (STZ-treated hyperglycemic mice, HDAd-LDLR significantly reduced plasma cholesterol levels, decreased atherosclerotic lesion size, reduced macrophage area and lipid content, and increased collagen content of plaque in the aortic sinus. However, reductions in anti-inflammatory and ER stress-related genes were less pronounced in STZ-diabetic mice compared to non-diabetic mice. In conclusion, HDAd-mediated Ldlr gene therapy is an effective and simple method to induce atherosclerosis regression in Ldlr-/- mice in different metabolic states.

  8. [The receptor theory of atherosclerosis].

    Science.gov (United States)

    Likhoded, V G; Bondarenko, V M; Gintsburg, A L

    2010-01-01

    Lipopolysaccharides of Gram-negative bacteria can interact with Toll-like receptor 4 (TLR4) and induce atheroma formation. The risk of atherosclerosis is decreased in case of TLR4 mutation. Other bacterial ligands and endogenous ligands of TLRs can also be involved in induction of atherogenesis. The general concept of atherosclerosis pathogentsis is presented. According to this concept atherogenesis can be initiated by some reactions resulting from interaction of exogenous and endogenous microbial ligands with Toll-like receptors.

  9. Hyperglycemia raises the threshold of levosimendan- but not milrinone-induced postconditioning in rat hearts.

    Science.gov (United States)

    Matsumoto, Shuhei; Cho, Sungsam; Tosaka, Shinya; Higashijima, Ushio; Maekawa, Takuji; Hara, Tetsuya; Sumikawa, Koji

    2012-01-12

    The authors examined whether milrinone and levosimendan could exert cardiac postconditioning effects in rats under normoglycemia and hyperglycemia, and whether the effects could be mediated by mitochondrial permeability transition pore (mPTP). Wistar rats underwent 30-min coronary artery occlusion followed by 2-h reperfusion. The rats received milrinone or levosimendan just before reperfusion under normoglycemic or hyperglycemic conditions with or without atractyloside, an mPTP opener. Under normoglycemia, both 30 μg/kg milrinone (29 ± 12%) and 10 μg/kg levosimendan (33 ± 13%) reduced infarct size compared with that in the control (58 ± 7%). Under hyperglycemia, milrinone (34 ± 13%) reduced infarct size at the same dose as under normoglycemia. In contrast, neither 10 nor 30 μg/kg levosimendan protected hyperglycemic hearts, and only 100 μg/kg levosimendan (32 ± 9%) reduced infarct size compared with that in the hyperglycemic control (58 ± 13%). All of these cardioprotective effects under normoglycemia and hyperglycemia are abolished by atractyloside. Milrinone and levosimendan exert postconditioning effects via inhibition of mPTP opening. Hyperglycemia raises the threshold of levosimendan-induced postconditioning, while milrinone-induced postconditioning is not influenced by hyperglycemia.

  10. Effect of stress hyperglycemia and intensive rehabilitation therapy in non-diabetic hemorrhagic stroke: Korean Stroke Cohort for Functioning and Rehabilitation.

    Science.gov (United States)

    Yoon, J A; Kim, D Y; Sohn, M K; Lee, J; Lee, S-G; Lee, Y-S; Han, E Y; Joo, M C; Oh, G-J; Han, J; Lee, S W; Park, M; Chang, W H; Shin, Y-I; Kim, Y-H

    2016-11-01

    We investigated the effect of stress hyperglycemia on the functional outcomes of non-diabetic hemorrhagic stroke. In addition, we investigated the usefulness of intensive rehabilitation for improving functional outcomes in patients with stress hyperglycemia. Non-diabetic hemorrhagic stroke patients were recruited and divided into two groups: intracerebral hemorrhage (ICH) (n = 165) and subarachnoid hemorrhage (SAH) (n = 156). Each group was divided into non-diabetics with or without stress hyperglycemia. Functional assessments were performed at 7 days and 3, 6 and 12 months after stroke onset. The non-diabetic with stress hyperglycemia groups were again divided into two groups who either received or did not receive intensive rehabilitation treatment. Serial functional outcome was compared between groups. For the ICH group, patients with stress hyperglycemia had worse modified Rankin Scale, National Institutes of Health Stroke Scale, Functional Ambulatory Category and Korean Mini-Mental State Examination scores than patients without stress hyperglycemia. For the SAH group, patients with stress hyperglycemia had worse scores on all functional assessments than patients without stress hyperglycemia at all time-points. After intensive rehabilitation treatment of patients with stress hyperglycemia, the ICH group had better scores on Functional Ambulatory Category and the SAH group had better scores on all functional assessments than patients without intensive rehabilitation treatment. Stress hyperglycemia affects the long-term prognosis of non-diabetic hemorrhagic stroke patients. Among stress hyperglycemia patients, intensive rehabilitation can enhance functional improvement after stroke. © 2016 EAN.

  11. ATHEROSCLEROSIS DISEASE: A MULTI-FACTORIAL PATHOLOGY

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    Marcieli da Luz Giroldo1; Arienne Serrano Alves1; Francielle Baptista1

    2007-06-01

    Full Text Available Atherosclerosis or arterial stiffening is a gradual disease that restricts the normal blood flow in different areas of body and maylead to secondary illnesses as myocardial infarction and cerebral stroke. Innumerable factors are related to the development ofatherosclerosis, among them are the dyslipidemia; genetic factors; arterial hypertension; diabetes mellitus; obesity; smoking;lack of exercise; pulmonary infection by Chlamydia and stress. Due to multi-factorial atherosclerosis characteristics,innumerable drugs, with differentiated mechanisms of action, are being elaborated to be used in prevention and control of thisdisease. However, beyond the pharmacological therapy, a balanced diet, physical activity and elimination of risk habits, assmoking, also are need for controlling atherosclerosis progression, as well as for the increase of expectative and quality of life

  12. Role of gut microbiota in atherosclerosis

    DEFF Research Database (Denmark)

    Jonsson, Annika Lindskog; Bäckhed, Gert Fredrik

    2017-01-01

    describe three pathways by which microbiota might affect atherogenesis. First, local or distant infections might cause a harmful inflammatory response that aggravates plaque development or triggers plaque rupture. Second, metabolism of cholesterol and lipids by gut microbiota can affect the development...... of atherosclerotic plaques. Third, diet and specific components that are metabolized by gut microbiota can have various effects on atherosclerosis; for example, dietary fibre is beneficial, whereas the bacterial metabolite trimethylamine-N-oxide is considered harmful. Although specific bacterial taxa have been...... associated with atherosclerosis, which is supported by increasing mechanistic evidence, several questions remain to be answered to understand fully how the microbiota contributes to atherosclerosis and cardiovascular disease. Such knowledge might pave the way for novel diagnostics and therapeutics based...

  13. Oral microbiota in patients with atherosclerosis

    DEFF Research Database (Denmark)

    Fåk, Frida; Tremaroli, Valentina; Bergström, Göran

    2015-01-01

    BACKGROUND AND AIMS: Recent evidence suggests that the microbiota may be considered as an environmental factor that contributes to the development of atherosclerosis. Periodontal disease has been associated with cardio- and cerebrovascular events, and inflammation in the periodontium is suggested...... to increase the systemic inflammatory level of the host, which may in turn influence plaque composition and rupture. We previously showed that bacteria from the oral cavity and the gut could be found in atherosclerotic plaques. METHODS: To elucidate whether the oral microbiota composition differed between...... patients with asymptomatic and symptomatic atherosclerosis we performed pyrosequencing of the oral microbiota of 92 individuals including patients with asymptomatic and symptomatic atherosclerosis and control individuals without carotid plaques or previous stroke or myocardial infarction. RESULTS...

  14. Influence of Erythrocyte Membrane Stability in Atherosclerosis.

    Science.gov (United States)

    da Silva Garrote-Filho, Mario; Bernardino-Neto, Morun; Penha-Silva, Nilson

    2017-04-01

    The purpose of this study is to show how an excess of cholesterol in the erythrocyte membrane contributes stochastically to the progression of atherosclerosis, leading to damage in blood rheology and O 2 transport, deposition of cholesterol (from trapped erythrocytes) in an area of intraplaque hemorrhage, and local exacerbation of oxidative stress. Cholesterol contained in the membrane of erythrocytes trapped in an intraplaque hemorrhage contributes to the growth of the necrotic nucleus. There is even a relationship between the amount of cholesterol in the erythrocyte membrane and the severity of atherosclerosis. In addition, the volume variability among erythrocytes, measured by RDW, is predictive of a worsening of this disease. Erythrocytes contribute to the development of atherosclerosis in several ways, especially when trapped in intraplate hemorrhage. These erythrocytes are oxidized and phagocytosed by macrophages. The cholesterol present in the membrane of these erythrocytes subsequently contributes to the growth of the atheroma plaque. In addition, when they rupture, erythrocytes release hemoglobin, which leads to the generation of free radicals. Finally, increased RDW may predict the worsening of atherosclerosis, due to the effects of inflammation and oxidative stress on erythropoiesis and erythrocyte volume. A better understanding of erythrocyte participation in atherosclerosis may contribute to the improvement of the prevention and treatment strategies of this disease.

  15. Function of CD147 in atherosclerosis and atherothrombosis

    Science.gov (United States)

    Wang, Cuiping; Jin, Rong; Zhu, Xiaolei; Yan, Jinchuan; Guohong, Li

    2015-01-01

    CD147, a member of the immunoglobulin super family, is a well-known potent inducer of extracellular matrix metalloproteinases. Studies show that CD147 is upregulated in inflammatory diseases. Atherosclerosis is a chronic inflammatory disease of the artery wall. Further understanding of the functions of CD147 in atherosclerosis and atherothrombosis may provide a new strategy for preventing and treating cardiovascular disease. In this review, we discuss how CD147 contributes to atherosclerosis and atherothrombosis. PMID:25604960

  16. Inflammation and immune system interactions in atherosclerosis

    NARCIS (Netherlands)

    Legein, Bart; Temmerman, Lieve; Biessen, Erik A. L.; Lutgens, Esther

    2013-01-01

    Cardiovascular disease (CVD) is the leading cause of mortality worldwide, accounting for 16.7 million deaths each year. The underlying cause of the majority of CVD is atherosclerosis. In the past, atherosclerosis was considered to be the result of passive lipid accumulation in the vessel wall.

  17. Deficiency of ATP-Binding Cassette Transporters A1 and G1 in Macrophages Increases Inflammation and Accelerates Atherosclerosis in Mice

    NARCIS (Netherlands)

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

    2013-01-01

    Rationale: Plasma high-density lipoprotein levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is attributable to the ability of high-density lipoprotein to promote cholesterol efflux from macrophage foam cells, direct experimental support for this

  18. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Lingjun, E-mail: menglingjun@nibs.ac.cn [College of Biological Sciences, China Agricultural University, Beijing 100094 (China); National Institute of Biological Sciences, Beijing 102206 (China); Jin, Wei [Institute for Immunology, Tsinghua University, Beijing 100084 (China); Wang, Yuhui [Institute of Cardiovascular Sciences, Health Science Center, Peking University, Beijing 100191 (China); Huang, Huanwei; Li, Jia; Zhang, Cai [National Institute of Biological Sciences, Beijing 102206 (China)

    2016-04-29

    Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

  19. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

    International Nuclear Information System (INIS)

    Meng, Lingjun; Jin, Wei; Wang, Yuhui; Huang, Huanwei; Li, Jia; Zhang, Cai

    2016-01-01

    Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

  20. Effect of atorvastatin on hyperglycemia-induced brain oxidative stress and neuropathy induced by diabetes

    Directory of Open Access Journals (Sweden)

    Nastaran Faghihi

    2015-04-01

    Conclusion: The findings of the present study reveal that atorvastatin is able to prevent hyperglycemia-induced diabetic neuropathy and inhibit brain oxidative stress during diabetes. It is probable that reduction of urea is one of the reasons for atorvastatin prevention of hyperglycemia-induced neuropathy.

  1. Hyperglycemia raises the threshold of levosimendan- but not milrinone-induced postconditioning in rat hearts

    Directory of Open Access Journals (Sweden)

    Matsumoto Shuhei

    2012-01-01

    Full Text Available Abstract Background The authors examined whether milrinone and levosimendan could exert cardiac postconditioning effects in rats under normoglycemia and hyperglycemia, and whether the effects could be mediated by mitochondrial permeability transition pore (mPTP. Methods Wistar rats underwent 30-min coronary artery occlusion followed by 2-h reperfusion. The rats received milrinone or levosimendan just before reperfusion under normoglycemic or hyperglycemic conditions with or without atractyloside, an mPTP opener. Results Under normoglycemia, both 30 μg/kg milrinone (29 ± 12% and 10 μg/kg levosimendan (33 ± 13% reduced infarct size compared with that in the control (58 ± 7%. Under hyperglycemia, milrinone (34 ± 13% reduced infarct size at the same dose as under normoglycemia. In contrast, neither 10 nor 30 μg/kg levosimendan protected hyperglycemic hearts, and only 100 μg/kg levosimendan (32 ± 9% reduced infarct size compared with that in the hyperglycemic control (58 ± 13%. All of these cardioprotective effects under normoglycemia and hyperglycemia are abolished by atractyloside. Conclusion Milrinone and levosimendan exert postconditioning effects via inhibition of mPTP opening. Hyperglycemia raises the threshold of levosimendan-induced postconditioning, while milrinone-induced postconditioning is not influenced by hyperglycemia.

  2. Cell cycle and apoptosis genes in atherosclerosis

    NARCIS (Netherlands)

    Boesten, Lianne Simone Mirjam

    2006-01-01

    The work described in this thesis was aimed at identifying the role of cell cycle and apoptosis genes in atherosclerosis. Atherosclerosis is the primary cause of cardiovascular disease, a disorder occurring in the large and medium-sized arteries of the body. Although in the beginning 90s promising

  3. Regulation of T cell responses in atherosclerosis

    NARCIS (Netherlands)

    Puijvelde, Gijsbrecht Henricus Maria van

    2007-01-01

    One of the most important characteristics of atherosclerosis is the chronic inflammatory response in which T cells and NKT cells are very important. In this thesis several methods to modulate the activity of these T and NKT cells in atherosclerosis are described. The induction of regulatory T cells

  4. Hyperglycemia, hypernatremia, and hyperosmolarity in 6 neonatal llamas and alpacas.

    Science.gov (United States)

    Cebra, C K

    2000-12-01

    Neonatal camelids can develop hyperglycemia, hypernatremia, and hyperosmolarity in response to a combination of stress and inadequate water intake. Clinical signs of this syndrome include a fine head tremor, ataxia, and a base-wide stance of the hind limbs, but biochemical analyses are necessary to confirm the diagnosis. Camelids appear to be susceptible to this syndrome because of a poor insulin response to hyperglycemia; hypernatremia results from free water loss associated with glucose diuresis. Water loss associated with glucose diuresis may necessitate a higher rate of fluid administration in camelids with this syndrome than is typically used for treatment of hypernatremia in calves.

  5. Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle.

    Science.gov (United States)

    Lee, Yang; Fluckey, James D; Chakraborty, Sanjukta; Muthuchamy, Mariappan

    2017-07-01

    Insulin resistance is a well-known risk factor for obesity, metabolic syndrome (MetSyn) and associated cardiovascular diseases, but its mechanisms are undefined in the lymphatics. Mesenteric lymphatic vessels from MetSyn or LPS-injected rats exhibited impaired intrinsic contractile activity and associated inflammatory changes. Hence, we hypothesized that insulin resistance in lymphatic muscle cells (LMCs) affects cell bioenergetics and signaling pathways that consequently alter contractility. LMCs were treated with different concentrations of insulin or glucose or both at various time points to determine insulin resistance. Onset of insulin resistance significantly impaired glucose uptake, mitochondrial function, oxygen consumption rates, glycolysis, lactic acid, and ATP production in LMCs. Hyperglycemia and hyperinsulinemia also impaired the PI3K/Akt while enhancing the ERK/p38MAPK/JNK pathways in LMCs. Increased NF-κB nuclear translocation and macrophage chemoattractant protein-1 and VCAM-1 levels in insulin-resistant LMCs indicated activation of inflammatory mechanisms. In addition, increased phosphorylation of myosin light chain-20, a key regulator of lymphatic muscle contraction, was observed in insulin-resistant LMCs. Therefore, our data elucidate the mechanisms of insulin resistance in LMCs and provide the first evidence that hyperglycemia and hyperinsulinemia promote insulin resistance and impair lymphatic contractile status by reducing glucose uptake, altering cellular metabolic pathways, and activating inflammatory signaling cascades.-Lee, Y., Fluckey, J. D., Chakraborty, S., Muthuchamy, M. Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle. © FASEB.

  6. Carotid Atherosclerosis and Cognitive Impairment in Nonstroke Patients

    Directory of Open Access Journals (Sweden)

    Wei-Hong Chen

    2017-01-01

    Conclusions: Carotid atherosclerosis can be used to predict the risk of cognitive impairment. Furthermore, diagnosing and treating carotid atherosclerosis at early stage might help clinicians prevent and treat vascular cognitive impairment in nonstroke patients.

  7. Life stress and atherosclerosis: a pathway through unhealthy lifestyle.

    Science.gov (United States)

    Mainous, Arch G; Everett, Charles J; Diaz, Vanessa A; Player, Marty S; Gebregziabher, Mulugeta; Smith, Daniel W

    2010-01-01

    To examine the relationship between a general measure of chronic life stress and atherosclerosis among middle aged adults without clinical cardiovascular disease via pathways through unhealthy lifestyle characteristics. We conducted an analysis of The Multi-Ethnic Study of Atherosclerosis (MESA). The MESA collected in 2000 includes 5,773 participants, aged 45-84. We computed standard regression techniques to examine the relationship between life stress and atherosclerosis as well as path analysis with hypothesized paths from stress to atherosclerosis through unhealthy lifestyle. Our outcome was sub-clinical atherosclerosis measured as presence of coronary artery calcification (CAC). A logistic regression adjusted for potential confounding variables along with the unhealthy lifestyle characteristics of smoking, excessive alcohol use, high caloric intake, sedentary lifestyle, and obesity yielded no significant relationship between chronic life stress (OR 0.93, 95% CI 0.80-1.08) and CAC. However, significant indirect pathways between chronic life stress and CAC through smoking (p = .007), and sedentary lifestyle (p = .03) and caloric intake (.002) through obesity were found. These results suggest that life stress is related to atherosclerosis once paths of unhealthy coping behaviors are considered.

  8. MicroRNAs in Hyperglycemia Induced Endothelial Cell Dysfunction

    Directory of Open Access Journals (Sweden)

    Maskomani Silambarasan

    2016-04-01

    Full Text Available Hyperglycemia is closely associated with prediabetes and Type 2 Diabetes Mellitus. Hyperglycemia increases the risk of vascular complications such as diabetic retinopathy, diabetic nephropathy, peripheral vascular disease and cerebro/cardiovascular diseases. Under hyperglycemic conditions, the endothelial cells become dysfunctional. In this study, we investigated the miRNA expression changes in human umbilical vein endothelial cells exposed to different glucose concentrations (5, 10, 25 and 40 mM glucose and at various time intervals (6, 12, 24 and 48 h. miRNA microarray analyses showed that there is a correlation between hyperglycemia induced endothelial dysfunction and miRNA expression. In silico pathways analyses on the altered miRNA expression showed that the majority of the affected biological pathways appeared to be associated to endothelial cell dysfunction and apoptosis. We found the expression of ten miRNAs (miR-26a-5p, -26b-5p, 29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -140-5p, -192-5p, -221-3p and -320a to increase gradually with increasing concentration of glucose. These miRNAs were also found to be involved in endothelial dysfunction. At least seven of them, miR-29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -221-3p, -320a and -192-5p, can be correlated to endothelial cell apoptosis.

  9. Circulating Endothelial Microparticles: A Key Hallmark of Atherosclerosis Progression

    Directory of Open Access Journals (Sweden)

    Keshav Raj Paudel

    2016-01-01

    Full Text Available The levels of circulating microparticles (MPs are raised in various cardiovascular diseases. Their increased level in plasma is regarded as a biomarker of alteration in vascular function. The prominent MPs present in blood are endothelial microparticles (EMPs described as complex submicron (0.1 to 1.0 μm vesicles like structure, released in response to endothelium cell activation or apoptosis. EMPs possess both physiological and pathological effects and may promote oxidative stress and vascular inflammation. EMPs release is triggered by inducer like angiotensin II, lipopolysaccharide, and hydrogen peroxide leading to the progression of atherosclerosis. However, there are multiple physiological pathways for EMPs generation like NADPH oxidase derived endothelial ROS formation, Rho kinase pathway, and mitogen-activated protein kinases. Endothelial dysfunction is a key initiating event in atherosclerotic plaque formation. Atheroemboli, resulting from ruptured carotid plaques, is a major cause of stroke. Increasing evidence suggests that EMPs play an important role in the pathogenesis of cardiovascular disease, acting as a marker of damage, either exacerbating disease progression or triggering a repair response. In this regard, it has been suggested that EMPs have the potential to act as biomarkers of disease status. This review aims to provide updated information of EMPs in relation to atherosclerosis pathogenesis.

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

    Science.gov (United States)

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

    2013-01-01

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

  11. Concept of Atherosclerosis Velocity: Is It a Better Measure of Cardiovascular Risk?

    Directory of Open Access Journals (Sweden)

    Seyyed Mohammad Reza Kazemi-Bajestani

    2013-09-01

    Full Text Available In most cases atherosclerosis is the underlying cause of vascular diseases, including heart disease and stroke. It is believed that endothelial injury is the earliest change in the artery wall and that this precedes the formation of lesions of atherosclerosis. Recent developments in the field of atherosclerosis have led to a renewed interest in the recognition of the parameter of time in the atherosclerosis process. We believe that the factors determining the time-dependent rate of atherosclerosis progression are important, and it is in this context that we wish to propose for the first time the term “atherosclerosis velocity”. In this review article, we summarize the existing evidence regarding atherosclerosis velocity and discuss the importance of this issue.

  12. The effect of hyperglycemia with or without hyperthermia on the radiation response of a spontaneous mouse fibrosarcoma

    International Nuclear Information System (INIS)

    Urano, M.; Todoroki, T.; Kahn, J.

    1985-01-01

    Hyperglycemia facilitates glycolysis with a resultant decrease in the tissue, particularly tumor pH. Another effect of hyperglycemia is to increase osmotic pressure in the extracellular fluid. The affect of hyperglycemia on the radiation response of our spontaneous tumor, FSa-II was examined. Further experiment includes the effect of hyperglycemia given 1 hour before local hyperthermia which was given in a 43.5 0 C water bath. Animals were C/sub 3/Hf/Sed mice from our defined flora colony. Tumor cell suspension was transplanted into the animal foot and the treatment was given when tumors reached an average diameter of 7 mm. Tumors were irradiated under clamped hypoxia, in air or under HPO (30 psi). Hyperglycemia, 5 mg/g given 1 hour before radiation, increased hypoxic cell fraction of the tumor without altering the slope fo the dose response curve. Hyperthermia enhanced the tumor response and increased hypoxic cell fraction. Further increase in the hypoxic cell fraction was noted following combined hyperglycemia and hyperthermia. Hyperthermia given 24 hours before radiation with or without glucose also increased hypoxic cell fraction, but decrease chronically hypoxic cell fraction (fraction not oxygenated under HPO)

  13. Atherosclerosis profile and incidence of cardiovascular events: a population-based survey

    Directory of Open Access Journals (Sweden)

    Bullano Michael F

    2009-09-01

    Full Text Available Abstract Background Atherosclerosis is a chronic progressive disease often presenting as clinical cardiovascular disease (CVD events. This study evaluated the characteristics of individuals with a diagnosis of atherosclerosis and estimated the incidence of CVD events to assist in the early identification of high-risk individuals. Methods Respondents to the US SHIELD baseline survey were followed for 2 years to observe incident self-reported CVD. Respondents had subclinical atherosclerosis if they reported a diagnosis of narrow or blocked arteries/carotid artery disease without a past clinical CVD event (heart attack, stroke or revascularization. Characteristics of those with atherosclerosis and incident CVD were compared with those who did not report atherosclerosis at baseline but had CVD in the following 2 years using chi-square tests. Logistic regression model identified characteristics associated with atherosclerosis and incident events. Results Of 17,640 respondents, 488 (2.8% reported having subclinical atherosclerosis at baseline. Subclinical atherosclerosis was associated with age, male gender, dyslipidemia, circulation problems, hypertension, past smoker, and a cholesterol test in past year (OR = 2.2 [all p Conclusion Self-report of subclinical atherosclerosis identified an extremely high-risk group with a >25% risk of a CVD event in the next 2 years. These characteristics may be useful for identifying individuals for more aggressive diagnostic and therapeutic efforts.

  14. Effect of Mild Hyperglycemia on Autonomic Function in Obstructive Sleep Apnea

    Science.gov (United States)

    Peltier, Amanda C.; Bagai, Kanika; Artibee, Kay; Diedrich, André; Garland, Emily; Elasy, Thomas; Shi, Yaping; Wang, Lily; Feldman, Eva L.; Robertson, David; Malow, Beth A.

    2014-01-01

    Obstructive sleep apnea (OSA) has been hypothesized to cause a hypersympathetic state, which may be the mechanism for the increased incidence of cardiovascular disease in OSA. However, there is a high prevalence of hyperglycemia in OSA patients which may also contribute to autonomic dysfunction. Thirty-five patients with OSA and eleven controls with average body-mass index (BMI) of 32.0 ± 4.6 underwent polysomnography, glucose tolerance testing, autonomic function tests, lying and standing catecholamines, overnight urine collection, and baseline ECG and continuous blood pressure measurements for spectral analysis. A linear regression model adjusting for age and BMI was used to analyze spectral data, other outcome measures were analyzed with Kruskal-Wallis test. Twenty-three OSA patients and two control patients had hyperglycemia (based on 2001 American Diabetes Association criteria). AHI correlated with total power and low frequency (LF) power (r=0.138, 0.177, p=0.031; and r= 0.013) but not with the LF/high frequency (HF) ratio (p=0.589). Glucose negatively correlated with LF systolic power (r=-0.171, p=0.038) but not AHI (p=0.586) and was marginally associated with pnn50, total power, LF, and HF power (p ranged from 0.07 to 0.08). These data suggest that patients with OSA and mild hyperglycemia have a trend towards lower heart rate variability and sympathetic tone. Hyperglycemia is an important confounder and should be evaluated in studies of OSA and autonomic function. PMID:21796355

  15. Prevalence and intensity of hyperglycemia in non-diabetic patients undergoing coronary artery bypass graft surgery with and without cardiopulmonary bypass

    International Nuclear Information System (INIS)

    Azarfarin, R.; Asl, Azin A.

    2008-01-01

    Objective was to study the prevalence and severity of hyperglycemia in nondiabetic patients undergoing cardiac operation. In an observational prospective study, 282 non-diabetic patients underwent elective off-pump (n=101) or non on-pump (n=181) coronary artery bypass grafting (CABG) surgery from March 2006 to July 2007 in Madani Heart Hospital, Tabriz, Iran. Blood glucose (BG) levels were measured during and 24 hours after operation. Frequencies of hyperglycemia (BG>-126 mg/dl) and severe hyperglycemia (BG>-180 mg/dl) and postoperative complications were compared in the 2 study groups. Prevalence of at least one episode of severe hyperglycemia was 54.6% (154/282) in our patients during and 24 hours after operation. Intra-operative hyperglycemia was slightly higher in on-pumping group. Frequency of post-operative hyperglycemia was higher, although not significantly different between the two groups. The 2 study groups were not significantly different in frequency of severe hyperglycemia during operation, although were different within 24 hours postoperative period. Prevalence of hyperglycemia especially severe hyperglycemia was high during, and after operation in both off-pump and on-pump CABG in non-diabetic patients. There was a borderline difference in blood glucose level between on-pump and off-pump CABG patients. It may be prudent to consider glycemic control protocols in these patients especially in early post-operative period. (author)

  16. Hyperglycemia Alters the Schwann Cell Mitochondrial Proteome and Decreases Coupled Respiration in the Absence of Superoxide Production

    OpenAIRE

    Zhang, Liang; Yu, Cuijuan; Vasquez, Francisco E.; Galeva, Nadya; Onyango, Isaac; Swerdlow, Russell H.; Dobrowsky, Rick T.

    2010-01-01

    Hyperglycemia-induced mitochondrial dysfunction contributes to sensory neuron pathology in diabetic neuropathy. Although Schwann cells (SCs) also undergo substantial degeneration in diabetic neuropathy, the effect of hyperglycemia on SC mitochondrial proteome and mitochondrial function has not been examined. Stable isotope labeling with amino acids in cell culture (SILAC) was used to quantify the temporal effect of hyperglycemia on the mitochondrial proteome of primary SCs isolated from neona...

  17. Atherosclerosis in Juvenile Idiopathic Arthritis

    Directory of Open Access Journals (Sweden)

    Ewa Jednacz

    2012-01-01

    Full Text Available Atherosclerosis is a chronic inflammatory disease of the arteries. Clinical consequences of the atherosclerotic process occur in the adult population, however atherosclerotic process begins in childhood. The classic risk factors for atherosclerosis include obesity, dyslipidaemia, age, gender or family history. In recent years, attention has been drawn to the similarity between atherosclerotic inflammatory processes and inflammatory changes in the course of systemic connective tissue disease, in particular systemic lupus etythematosus (SLE or rheumatoid arthritis (RA. There is also observed the similarity of the pathogenetic background of development of atherosclerosis and juvenile idiopathic arthritis (JIA. Elevated levels of pro-inflammatory cytokines are observed in the course of juvenile idiopathic arthritis. Also homocysteine concentrations, which may play a significant role in the development of atherosclerotic lesions, are observed higher in patients with JIA. Some studies revealed higher carotid intima-media thickness (IMT index values in children with JIA. In view of the fact that atherosclerotic process begins as early as in childhood, the introduction of appropriate preventive measures in children is a matter of utmost importance.

  18. Insulin Therapy for the Management of Hyperglycemia in Hospitalized Patients

    Science.gov (United States)

    McDonnell, Marie E.; Umpierrez, Guillermo E.

    2013-01-01

    It has long been established that hyperglycemia with or without a prior diagnosis of diabetes increases both mortality and disease-specific morbidity in hospitalized patients1–4 and that goal-directed insulin therapy can improve outcomes.5–9 During the past decade, since the widespread institutional adoption of intensified insulin protocols after the publication of a landmark trial,5,10 the pendulum in the inpatient diabetes literature has swung away from achieving intensive glucose control and toward more moderate and individualized glycemic targets.11,12 This change in clinical practice is the result of several factors, including challenges faced by hospitals to coordinate glycemic control across all levels of care,13,14 publication of negative prospective trials,15,16 revised recommendations from professional organizations,17,18 and increasing evidence on the deleterious effect of hypoglycemia.19–22 This article reviews the pathophysiology of hyperglycemia during illness, the mechanisms for increased complications and mortality due to hyperglycemia and hypoglycemia, beneficial mechanistic effects of insulin therapy and provides updated recommendations for the inpatient management of diabetes in the critical care setting and in the general medicine and surgical settings.23,24 PMID:22575413

  19. Diabetic Hyperglycemia: Link to Impaired Glucose Transport in Pancreatic β Cells

    Science.gov (United States)

    Unger, Roger H.

    1991-03-01

    Glucose uptake into pancreatic β cells by means of the glucose transporter GLUT-2, which has a high Michaelis constant, is essential for the normal insulin secretory response to hyperglycemia. In both autoimmune and nonautoimmune diabetes, this glucose transport is reduced as a consequence of down-regulation of the normal β-cell transporter. In autoimmune diabetes, circulating immunoglobulins can further impair this glucose transport by inhibiting functionally intact transporters. Insights into mechanisms of the unresponsiveness of β cells to hyperglycemia may improve the management and prevention of diabetes.

  20. Clinical and epidemiological study of stress hyperglycemia among medical intensive care unit patients in Central India

    Directory of Open Access Journals (Sweden)

    Jitendra Sharma

    2017-01-01

    Full Text Available Background: Stress hyperglycemia is common in patients presenting at the emergency medical ward and is associated with poor prognosis and increased risk of mortality. Aims and Objective: To study and determine the prevalence and factors associated with stress hyperglycemia. Materials and Methods: A cross-sectional observational study was performed on 536 nondiabetic patients presented to the Intensive Care Unit (ICU at Gandhi Medical College and allied Hamidia Hospital, Bhopal, between March 31, 2015, and May 28, 2015. A detailed history including demographic profile, presence of chronic disease, history of hospitalization and ICU admission, surgical status, and major reason for ICU admission (i.e., predominant diagnostic category was collected. Hematological and other parameters based on profile of study population were also analyzed. Results: Out of 536 patients, 109 (20.33% had stress hyperglycemia. Out of 109 patients with stress hyperglycemia, 87 (16.23% patients had glycated hemoglobin (HbA1c <5.7% and 22 (4.10% patients had HbA1c between 5.7% and 6.4%. Mean age of the study population was 40.27 ± 1.44 years, with male dominance. Mean random blood glucose level was 181.46 ± 3.80 mg/dl. Frequency of stress hyperglycemia was 24.13% in stroke, 19.54% in multiple organ dysfunction syndrome (MODS, 17.24% in chronic kidney disease (CKD, 12.64% in central nervous system (CNS infection, 8.05% in chronic liver disease (CLD, and 8.05% in seizure patients. Association between stroke and stress hyperglycemia was significant (P = 0.036. Association between hospital stay more than 7 days and stress hyperglycemia was significant in stroke patients (P = 0.0029, CKD patients (P = 0.0036, CLD (P = 0.0099, and MODS patients (P = 0.0328. Conclusions: The factors associated with stress hyperglycemia were stroke, MODS, CKD, CNS infection, CLD, seizure patients, with prolonged hospital stay and expected proportion.

  1. Decreased naive and increased memory CD4(+ T cells are associated with subclinical atherosclerosis: the multi-ethnic study of atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Nels C Olson

    Full Text Available Adaptive immunity has been implicated in atherosclerosis in animal models and small clinical studies. Whether chronic immune activation is associated with atherosclerosis in otherwise healthy individuals remains underexplored. We hypothesized that activation of adaptive immune responses, as reflected by higher proportions of circulating CD4(+ memory cells and lower proportions of naive cells, would be associated with subclinical atherosclerosis.We examined cross-sectional relationships of circulating CD4(+ naive and memory T cells with biomarkers of inflammation, serologies, and subclinical atherosclerosis in 912 participants of the Multi-Ethnic Study of Atherosclerosis (MESA. Circulating CD4(+ naive cells were higher in women than men and decreased with age (all p-values <0.0001. European-Americans had higher levels of naive cells and lower levels of memory cells compared with African-Americans and Hispanic-Americans (all p-values ≤0.0005. Lower naive/higher memory cells were associated with interleukin-6 levels. In multivariate models, cytomegalovirus (CMV and H. Pylori titers were strongly associated with higher memory and lower naive cells (all p-values <0.05. Higher memory cells were associated with coronary artery calcification (CAC level in the overall population [β-Coefficient (95% confidence interval (CI  = 0.20 (0.03, 0.37]. Memory and naive (inversely cells were associated with common carotid artery intimal media thickness (CC IMT in European-Americans [memory: β =  0.02 (0.006, 0.04; naive: β = -0.02 (-0.004, -0.03].These results demonstrate that the degree of chronic adaptive immune activation is associated with both CAC and CC IMT in otherwise healthy individuals, consistent with the known role of CD4(+ T cells, and with innate immunity (inflammation, in atherosclerosis. These data are also consistent with the hypothesis that immunosenescence accelerates chronic diseases by putting a greater burden on the innate

  2. The Biochemistry of atherosclerosis

    National Research Council Canada - National Science Library

    Scanu, Angelo M; Getz, Godfrey S; Wissler, Robert W

    1979-01-01

    In this first full-length review of the biochemical parameters and their part in the pathogenesis of atherosclerosis, the reader will discover a range of coverage concerning basic etiological factors...

  3. Atherosclerosis: the interplay between lipids and immune cells

    NARCIS (Netherlands)

    Schaftenaar, Frank; Frodermann, Vanessa; Kuiper, Johan; Lutgens, Esther

    2016-01-01

    Cardiovascular disease is the leading cause of mortality worldwide. The underlying cause of the majority of cardiovascular disease is atherosclerosis. In the past, atherosclerosis was considered to be the result of passive lipid accumulation in the vessel wall. However, today's picture of the

  4. Imaging Macrophage and Hematopoietic Progenitor Proliferation in Atherosclerosis

    DEFF Research Database (Denmark)

    Ye, Yu-Xiang; Calcagno, Claudia; Binderup, Tina

    2015-01-01

    tomography-computed tomography imaging of cell proliferation in atherosclerosis. METHODS AND RESULTS: (18)F-FLT positron emission tomography-computed tomography was performed in mice, rabbits, and humans with atherosclerosis. In apolipoprotein E knock out mice, increased (18)F-FLT signal was observed...

  5. Hepatic JAK2 protects against atherosclerosis through circulating IGF-1.

    Science.gov (United States)

    Sivasubramaniyam, Tharini; Schroer, Stephanie A; Li, Angela; Luk, Cynthia T; Shi, Sally Yu; Besla, Rickvinder; Dodington, David W; Metherel, Adam H; Kitson, Alex P; Brunt, Jara J; Lopes, Joshua; Wagner, Kay-Uwe; Bazinet, Richard P; Bendeck, Michelle P; Robbins, Clinton S; Woo, Minna

    2017-07-20

    Atherosclerosis is considered both a metabolic and inflammatory disease; however, the specific tissue and signaling molecules that instigate and propagate this disease remain unclear. The liver is a central site of inflammation and lipid metabolism that is critical for atherosclerosis, and JAK2 is a key mediator of inflammation and, more recently, of hepatic lipid metabolism. However, precise effects of hepatic Jak2 on atherosclerosis remain unknown. We show here that hepatic Jak2 deficiency in atherosclerosis-prone mouse models exhibited accelerated atherosclerosis with increased plaque macrophages and decreased plaque smooth muscle cell content. JAK2's essential role in growth hormone signalling in liver that resulted in reduced IGF-1 with hepatic Jak2 deficiency played a causal role in exacerbating atherosclerosis. As such, restoring IGF-1 either pharmacologically or genetically attenuated atherosclerotic burden. Together, our data show hepatic Jak2 to play a protective role in atherogenesis through actions mediated by circulating IGF-1 and, to our knowledge, provide a novel liver-centric mechanism in atheroprotection.

  6. Local Bone Marrow Renin-Angiotensin System and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Yavuz Beyazit

    2011-01-01

    Full Text Available Local hematopoietic bone marrow (BM renin-angiotensin system (RAS affects the growth, production, proliferation differentiation, and function of hematopoietic cells. Angiotensin II (Ang II, the dominant effector peptide of the RAS, regulates cellular growth in a wide variety of tissues in pathobiological states. RAS, especially Ang II and Ang II type 1 receptor (AT1R, has considerable proinflammatory and proatherogenic effects on the vessel wall, causing progression of atherosclerosis. Recent investigations, by analyzing several BM chimeric mice whose BM cells were positive or negative for AT1R, disclosed that AT1R in BM cells participates in the pathogenesis of atherosclerosis. Therefore, AT1R blocking not only in vascular cells but also in the BM could be an important therapeutic approach to prevent atherosclerosis. The aim of this paper is to review the function of local BM RAS in the pathogenesis of atherosclerosis.

  7. Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen.

    Directory of Open Access Journals (Sweden)

    Ashkan Javid

    Full Text Available Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted.

  8. Hyperinsulinemia and hyperglycemia: risk factors for recurrence of benign paroxysmal positional vertigo

    Directory of Open Access Journals (Sweden)

    Guilherme Webster

    2015-08-01

    Full Text Available INTRODUCTION: Changes in carbohydrate metabolism may lead to recurrence of benign paroxysmal positional vertigo.OBJECTIVE: To evaluate the influence of the disturbance of carbohydrate metabolism in the recurrence of idiopathic BPPV.METHODS: A longitudinal prospective study of a cohort, with 41 months follow-up. We analyzed the results of 72 glucose-insulin curves in patients with recurrence of BPPV. The curves were classified into intolerance, hyperinsulinemia, hyperglycemia and normal.RESULTS: The RR for hyperinsulinism was 4.66 and p = 0.0015. Existing hyperglycemia showed an RR = 2.47, with p = 0.0123. Glucose intolerance had a RR of 0.63, with p = 0.096. When the examination was within normal limits, the result was RR = 0.2225 and p = 0.030.DISCUSSION: Metabolic changes can cause dizziness and vertigo and are very common in people who have cochleovestibular disorders. However, few studies discuss the relationship between idiopathic BPPV and alterations in carbohydrate metabolism. In the present study, we found that both hyperglycemia and hyperinsulinemia are risk factors for the recurrence of BPPV, whereas a normal test was considered a protective factor; all these were statistically significant. Glucose intolerance that was already present was not statistically significant in the group evaluated.CONCLUSION: Hyperinsulinemia and hyperglycemia are risk factors for the recurrence of idiopathic BPPV and a normal exam is considered a protective factor.

  9. Is there an association between coronary atherosclerosis and ...

    African Journals Online (AJOL)

    Background: Atherosclerotic disease is the most common cause of death in the United States and prostate cancer has the highest incidence among males in the United States. Reports have indicated that atherosclerosis and cancers my share common pathoetiologic and pathogenetic cascades. If atherosclerosis and ...

  10. Application of induced short-term hyperglycemia in comprehensive treatment of locally disseminated cancer of mammary gland

    International Nuclear Information System (INIS)

    Letyagin, V.P.; Poddubnyj, I.K.; Sokolova, I.G.; Ermilova, V.D.; Ajtakova, T.I.

    1984-01-01

    The paper deals with an analysis of the results of treatment of 12 patients with mammary gland cancer receiving preoperative radiation and chemotherapy and in whom short-term hyperglycemia was simultaneously induced. The peculiarities of the said modality and advantages offered by its application are discussed. The cases given the same treatment unaccompanied by hyperglycemia were in control. Since short-term hyperglycemia as a component of comprehensive treatment of mammary gland cancer resulted in a higher effectiveness of the latter, it merits attention and further studies

  11. Suppression of atherosclerosis by synthetic REV-ERB agonist

    Energy Technology Data Exchange (ETDEWEB)

    Sitaula, Sadichha [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Billon, Cyrielle [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States); Kamenecka, Theodore M.; Solt, Laura A. [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Burris, Thomas P., E-mail: burristp@slu.edu [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States)

    2015-05-08

    The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.

  12. Thymic Stromal Lymphopoietin Attenuates the Development of Atherosclerosis in ApoE−/− Mice

    Science.gov (United States)

    Yu, Kunwu; Zhu, Pengfei; Dong, Qian; Zhong, Yucheng; Zhu, Zhengfeng; Lin, Yingzhong; Huang, Ying; Meng, Kai; Ji, Qingwei; Yi, Guiwen; Zhang, Wei; Wu, Bangwei; Mao, Yi; Cheng, Peng; Zhao, Xiaoqi; Mao, Xiaobo; Zeng, Qiutang

    2013-01-01

    Background Thymic stromal lymphopoietin (TSLP) is a cytokine with multiple effects on the body. For one thing, TSLP induces Th2 immunoreaction and facilitates allergic reaction; for another, it promotes the differentiation of naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTregs) and maintains immune tolerance. However, the exact role of TSLP in atherosclerosis remains unknown. Methods and Results In vitro, we examined the phenotype of TSLP‐conditioned bone marrow dendritic cells (TSLP‐DCs) of apolipoprotein E–deficient (ApoE−/−) mice and their capacity to induce the differentiation of Tregs. Our results indicated that TSLP‐DCs obtained the characteristics of tolerogenic dendritic cells and increased a generation of CD4+ latency‐associated peptide (LAP)+ Tregs and nTregs when cocultured with naive T cells. In addition, the functional relevance of TSLP and TSLP‐DCs in the development of atherosclerosis was also determined. Interestingly, we found that TSLP was almost absent in cardiovascular tissue of ApoE−/− mice, and TSLP administration increased the levels of antioxidized low‐density lipoprotein IgM and IgG1, but decreased the levels of IgG2a in plasma. Furthermore, mice treated with TSLP and TSLP‐DCs developed significantly fewer (32.6% and 28.2%, respectively) atherosclerotic plaques in the aortic root compared with controls, along with increased numbers of CD4+LAP+ Tregs and nTregs in the spleen and decreased inflammation in the aorta, which could be abrogated by anti‐TGF‐β antibody. Conclusions Our results revealed a protective role for TSLP in atherosclerosis that is possibly mediated by reestablishing a tolerogenic immune response, which may represent a novel possibility for treatment or prevention of atherosclerosis. PMID:23985377

  13. Polymodification. Short-term hyperglycemia and local hyperthermia in hypoxiradiotherapy of transplantable solid tumors

    International Nuclear Information System (INIS)

    Kozin, S.V.; Krimker, V.M.; Yarmonenko, S.P.

    1984-01-01

    Application possibilities of hyperglycemia and local hyperthermia in combination with hypoxiradiotherapy of solid tumors, have been evaluated. The experiments conducted have shown the great possibilities of combined use of radiation, hyperglycemia, hyperthermia, for selective affection of tumours, and application of gaseous hypoxia during irradiation - for simultaneous principal protection of normal tissues. Interaction of all the agents will undoubtedly require a versatile study to develop the optimum regimes of action

  14. Diet and Atherosclerosis | Grande | South African Medical Journal

    African Journals Online (AJOL)

    Among the various factors affecting the development of atherosclerosis and its complications, the diet emerges as an important influence. This article reviews the evidence linking diet and atherosclerosis; the relation between serum cholesterol concentration and incidence of coronary heart disease, and the effect of various ...

  15. What Is Atherosclerosis?

    Science.gov (United States)

    ... builds up in the renal arteries. These arteries supply oxygen-rich blood to your kidneys. Over time, chronic kidney disease causes a slow loss of kidney function. The main function of the kidneys is to remove waste and extra water from the body. Overview The cause of atherosclerosis ...

  16. In vivo MR monitoring of pH and blood flow during hyperglycemia in a brain tumor model

    International Nuclear Information System (INIS)

    Mitchell, S.L.; Ross, B.D.; Merkle, H.; Garwood, M.

    1988-01-01

    Previous investigations have shown that tumors exhibit an acidotic pH shift following hyperglycemia, which may aid in hyperthermic treatments. P-31 and H-1 magnetic resonance spectroscopy were used to monitor hyperglycemia-induced pH and blood flow changes, respectively, in subcutaneous and intracerebral C6 gliomas in rats. Subcutaneous tumors had a 78.2% +- 8.03% (standard error of the mean) decrease in blood flow and a concomitant pH decrease of 0.76 units +- 0.08. However, intracerebral tumors displayed an average blood flow reduction of only 20.9% +- 6.1%, with no significant pH change following hyperglycemia. These results indicate that the tissue harboring the tumor may have an important role in the overall tumor response to hyperglycemia

  17. Enhanced effect of ionizing radiation in transplantable cerebral gliomas by means of a short-term hyperglycemia

    International Nuclear Information System (INIS)

    Loginov, V.M.; Krimker, V.M.; Akademiya Meditsinskikh Nauk SSSR, Moscow. Onkologicheskij Nauchnyj Tsentr)

    1985-01-01

    Experiments were staged on rats with transplantable anaplastic cerebral right hemisphere astrocytomas. Hyperglycemia was induced by means of intraperitoneal fractional administration of 40% glucose solution. Single local X-ray tumor irradiation followed on the 4-5th, 7-8th and 10-12th days after strain transplantation at the doses of 30 and 40 Gy without hyperglycemia and in combination with it. The irradiation effect was assessed by the mean survival time of the animals. Hyperglycemia was shown to increase significantly radiation injury of highly resistant experimental malignant cerebral glial tumors

  18. Analysis of epigenetic factors in mouse embryonic neural stem cells exposed to hyperglycemia.

    Directory of Open Access Journals (Sweden)

    Sukanya Shyamasundar

    Full Text Available BACKGROUND: Maternal diabetes alters gene expression leading to neural tube defects (NTDs in the developing brain. The mechanistic pathways that deregulate the gene expression remain unknown. It is hypothesized that exposure of neural stem cells (NSCs to high glucose/hyperglycemia results in activation of epigenetic mechanisms which alter gene expression and cell fate during brain development. METHODS AND FINDINGS: NSCs were isolated from normal pregnancy and streptozotocin induced-diabetic pregnancy and cultured in physiological glucose. In order to examine hyperglycemia induced epigenetic changes in NSCs, chromatin reorganization, global histone status at lysine 9 residue of histone H3 (acetylation and trimethylation and global DNA methylation were examined and found to be altered by hyperglycemia. In NSCs, hyperglycemia increased the expression of Dcx (Doublecortin and Pafah1b1 (Platelet activating factor acetyl hydrolase, isoform 1b, subunit 1 proteins concomitant with decreased expression of four microRNAs (mmu-miR-200a, mmu-miR-200b, mmu-miR-466a-3p and mmu-miR-466 d-3p predicted to target these genes. Knockdown of specific microRNAs in NSCs resulted in increased expression of Dcx and Pafah1b1 proteins confirming target prediction and altered NSC fate by increasing the expression of neuronal and glial lineage markers. CONCLUSION/INTERPRETATION: This study revealed that hyperglycemia alters the epigenetic mechanisms in NSCs, resulting in altered expression of some development control genes which may form the basis for the NTDs. Since epigenetic changes are reversible, they may be valuable therapeutic targets in order to improve fetal outcomes in diabetic pregnancy.

  19. Predictive value of serum soluble corin in the risk of hyperglycemia: A population-based prospective cohort study in China.

    Science.gov (United States)

    Zhu, Zhengbao; Zhang, Qiu; Peng, Hao; Zhong, Chongke; Guo, Daoxia; Huangfu, Xinfeng; Chao, Xiangqin; Wang, Aili; Jin, Jianhua; Zhang, Yonghong

    2018-04-01

    Serum soluble corin has been suggested to be associated with hyperglycemia by cross-sectional study. However, the prospective relationship between them remains unclear, and whether lipid component influences the relationship between them has not yet been studied. A total of 1961 participants who were free from hyperglycemia were enrolled at baseline in 2010. The serum soluble corin concentrations were measured at baseline and all participants were followed up for hyperglycemia in 2014. The association between serum soluble corin and hyperglycemia incidence was appreciably modified by high density lipoprotein cholesterol (HDL-C) (P interaction  = 0.04). Elevated serum soluble corin was associated with the risk of hyperglycemia only in the HDL-C ≥1.04 mmol/l subgroup rather than all participants. In participants with HDL-C ≥1.04 mmol/l, the adjusted odds ratio (95% CU) of hyperglycemia associated with the fourth quartiles of corin was 1.78 (1.08-2.94) compared with the lowest quartile of serum soluble corin, and there was a positive linear dose-response relationship between them (P for linearity <0.01). The ordinal analysis showed an association between serum soluble corin and hyperglycemia severity (adjusted OR, 1.81; 95% CI, 1.10-2.99; P trend  = 0.02, when 2 extreme quartiles were compared). The addition of serum soluble corin to conventional risk factors improved risk prediction for hyperglycemia (net reclassification index: 0.16; integrated discrimination improvement: 0.01) in participants with HDL-C ≥1.04 mmol/l. Serum soluble corin might be a valuable biomarker in prediction of future hyperglycemia in population with HDL-C ≥1.04 mmol/l, suggesting that corin might play a potential role in glucose metabolism. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Hyperglycemia-induced metabolic compensation inhibits metformin sensitivity in ovarian cancer

    Science.gov (United States)

    Litchfield, Lacey M.; Mukherjee, Abir; Eckert, Mark A.; Johnson, Alyssa; Mills, Kathryn A.; Pan, Shawn; Shridhar, Viji; Lengyel, Ernst; Romero, Iris L.

    2015-01-01

    Increasing interest in repurposing the diabetic medication metformin for cancer treatment has raised important questions about the translation of promising preclinical findings to therapeutic efficacy, especially in non-diabetic patients. A significant limitation of the findings to date is the use of supraphysiologic metformin doses and hyperglycemic conditions in vitro. Our goals were to determine the impact of hyperglycemia on metformin response and to address the applicability of metformin as a cancer therapeutic in non-diabetic patients. In normoglycemic conditions, lower concentrations of metformin were required to inhibit cell viability, while metformin treatment in hyperglycemic conditions resulted in increased glucose uptake and glycolytic flux, contributing to cell survival. Mechanistically, maintenance of c-Myc expression under conditions of hyperglycemia or via gene amplification facilitated metabolic escape from the effects of metformin. In vivo, treatment of an ovarian cancer mouse model with metformin resulted in greater tumor weight reduction in normoglycemic vs. hyperglycemic mice, with increased c-Myc expression observed in metformin-treated hyperglycemic mice. These findings indicate that hyperglycemia inhibits the anti-cancer effects of metformin in vitro and in vivo. Furthermore, our results suggest that metformin may elicit stronger responses in normoglycemic vs. hyperglycemic patients, highlighting the need for prospective clinical testing in patients without diabetes. PMID:26172303

  1. Metastatic spreading and growth of rhabdomyosarcoma in exposure to hyperglycemia, hyperthermia and ionizing radiation

    International Nuclear Information System (INIS)

    Ul'yanenko, S.E.; Salamatina, N.A.; Dedenkov, A.N.

    1985-01-01

    Under the effect of local UHF-hyperthermia, short-term hyperglycemia and ionizing radiation on metastasing strain of rhabdomysarcoma an increase in metastatic spreading or stimulated growth of primary tumor are not noticed. Otherwise, it is stated that hyperglycemia and hyperthermia thrice-used prevent from metastatic spreading of the tumor. Ionizing radiation decelerates both tumor growth and to a least extent its metastatic spreading

  2. 2013 Russell Ross memorial lecture in vascular biology: cellular and molecular mechanisms of diabetes mellitus-accelerated atherosclerosis.

    Science.gov (United States)

    Bornfeldt, Karin E

    2014-04-01

    Adults with diabetes mellitus are much more likely to have cardiovascular disease than those without diabetes mellitus. Genetically engineered mouse models have started to provide important insight into the mechanisms whereby diabetes mellitus promotes atherosclerosis. Such models have demonstrated that diabetes mellitus promotes formation of atherosclerotic lesions, progression of lesions into advanced hemorrhaged lesions, and that it prevents lesion regression. The proatherosclerotic effects of diabetes mellitus are driven in part by the altered function of myeloid cells. The protein S100A9 and the receptor for advanced glycation end-products are important modulators of the effect of diabetes mellitus on myelopoiesis, which might promote monocyte accumulation in lesions. Furthermore, myeloid cell expression of the enzyme acyl-CoA synthetase 1 (ACSL1), which converts long-chain fatty acids into their acyl-CoA derivatives, has emerged as causal to diabetes mellitus-induced lesion initiation. The protective effects of myeloid ACSL1-deficiency in diabetic mice, but not in nondiabetic mice, indicate that myeloid cells are activated by diabetes mellitus through mechanisms that play minor roles in the absence of diabetes mellitus. The roles of reactive oxygen species and insulin resistance in diabetes mellitus-accelerated atherosclerosis are also discussed, primarily in relation to endothelial cells. Translational studies addressing whether the mechanisms identified in mouse models are equally important in humans with diabetes mellitus will be paramount.

  3. Intranasal immunization with chitosan/pCETP nanoparticles inhibits atherosclerosis in a rabbit model of atherosclerosis.

    Science.gov (United States)

    Yuan, Xiying; Yang, Xiaorong; Cai, Danning; Mao, Dan; Wu, Jie; Zong, Li; Liu, Jingjing

    2008-07-04

    In search of a convenient and pain-free route of administration of DNA vaccine against atherosclerosis, the plasmid pCR-X8-HBc-CETP (pCETP) encoding B-cell epitope of cholesteryl ester transfer protein C-terminal fragment displayed by Hepatitis B virus core particle was condensed with chitosan to form chitosan/pCETP nanoparticles. Cholesterol-fed rabbits were then intranasally immunized with the chitosan/pCETP nanoparticles to evaluate antiatherogenic effects. The results showed that significant serum antibodies against CETP were detected by enzyme-linked immunosorbent analysis and verified by Western blot analysis. The significant anti-CETP IgG lasted for 21 weeks in the rabbits immunized intranasally. Moreover, the atherogenic index was significantly lower compared with the saline control (5.95 versus 2.39, pnanoparticles was 59.2% less than those treated with saline (29.0+/-10.9% versus 71.0+/-14.4%, pintramuscularly injected with pCETP solution (29.0+/-10.9% versus 21.2+/-14.2%, p>0.05). Thus, chitosan/pCETP nanoparticles could significantly attenuate the progression of atherosclerosis by intranasal immunization. The results suggested that intranasal administration could be potentially developed as a vaccination route against atherosclerosis.

  4. Hyperinsulinemia and hyperglycemia: risk factors for recurrence of benign paroxysmal positional vertigo.

    Science.gov (United States)

    Webster, Guilherme; Sens, Patrícia Maria; Salmito, Márcio Cavalcante; Cavalcante, José Diogo Rijo; Santos, Paula Regina Bonifácio dos; Silva, Ana Lívia Muniz da; Souza, Érica Carla Figueiredo de

    2015-01-01

    Changes in carbohydrate metabolism may lead to recurrence of benign paroxysmal positional vertigo. To evaluate the influence of the disturbance of carbohydrate metabolism in the recurrence of idiopathic BPPV. A longitudinal prospective study of a cohort, with 41 months follow-up. We analyzed the results of 72 glucose-insulin curves in patients with recurrence of BPPV. The curves were classified into intolerance, hyperinsulinemia, hyperglycemia and normal. The RR for hyperinsulinism was 4.66 and p=0.0015. Existing hyperglycemia showed an RR=2.47, with p=0.0123. Glucose intolerance had a RR of 0.63, with p=0.096. When the examination was within normal limits, the result was RR=0.2225 and p=0.030. Metabolic changes can cause dizziness and vertigo and are very common in people who have cochleovestibular disorders. However, few studies discuss the relationship between idiopathic BPPV and alterations in carbohydrate metabolism. In the present study, we found that both hyperglycemia and hyperinsulinemia are risk factors for the recurrence of BPPV, whereas a normal test was considered a protective factor; all these were statistically significant. Glucose intolerance that was already present was not statistically significant in the group evaluated. Hyperinsulinemia and hyperglycemia are risk factors for the recurrence of idiopathic BPPV and a normal exam is considered a protective factor. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  5. C-reactive protein in relation to early atherosclerosis and periodontitis.

    Science.gov (United States)

    Yakob, Maha; Meurman, Jukka H; Jogestrand, Tomas; Nowak, Jacek; Söder, Per-Östen; Söder, Birgitta

    2012-02-01

    Periodontitis may affect atherosclerosis via the chronic inflammation. We investigated high-sensitivity C-reactive protein (hsCRP) in relation to early vascular atherosclerotic changes in non-symptomatic subjects with and without long-term periodontitis. Carotid ultrasonography with calculation of common carotid artery intima-media area (cIMA) was performed, and hsCRP and atherosclerosis risk factors were analysed in randomly chosen 93 patients with periodontitis and 41 controls. The relationship between hsCRP, cIMA and atherosclerosis risk factors was evaluated with multiple logistic regression analysis. Women displayed lower hsCRP (p periodontitis, cIMA values were higher than in controls. Periodontitis appeared to be a major predictor for increased cIMA (odds ratio, 3.82; 95% confidence interval, 1.19-12.26). Neither of these factors was significantly associated with hsCRP which thus appeared not sensitive enough to be a marker for periodontitis or atherosclerosis. Hence, irrespective of low hsCRP levels, periodontitis appeared to increase the risk for atherosclerosis.

  6. Artery Tertiary Lymphoid Organs Control Aorta Immunity and Protect against Atherosclerosis via Vascular Smooth Muscle Cell Lymphotoxin β Receptors

    Science.gov (United States)

    Hu, Desheng; Mohanta, Sarajo K.; Yin, Changjun; Peng, Li; Ma, Zhe; Srikakulapu, Prasad; Grassia, Gianluca; MacRitchie, Neil; Dever, Gary; Gordon, Peter; Burton, Francis L.; Ialenti, Armando; Sabir, Suleman R.; McInnes, Iain B.; Brewer, James M.; Garside, Paul; Weber, Christian; Lehmann, Thomas; Teupser, Daniel; Habenicht, Livia; Beer, Michael; Grabner, Rolf; Maffia, Pasquale; Weih, Falk; Habenicht, Andreas J.R.

    2015-01-01

    Summary Tertiary lymphoid organs (TLOs) emerge during nonresolving peripheral inflammation, but their impact on disease progression remains unknown. We have found in aged Apoe−/− mice that artery TLOs (ATLOs) controlled highly territorialized aorta T cell responses. ATLOs promoted T cell recruitment, primed CD4+ T cells, generated CD4+, CD8+, T regulatory (Treg) effector and central memory cells, converted naive CD4+ T cells into induced Treg cells, and presented antigen by an unusual set of dendritic cells and B cells. Meanwhile, vascular smooth muscle cell lymphotoxin β receptors (VSMC-LTβRs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though VSMC-LTβRs did not affect secondary lymphoid organs: Atherosclerosis was markedly exacerbated in Apoe−/−Ltbr−/− and to a similar extent in aged Apoe−/−Ltbrfl/flTagln-cre mice. These data support the conclusion that the immune system employs ATLOs to organize aorta T cell homeostasis during aging and that VSMC-LTβRs participate in atherosclerosis protection via ATLOs. PMID:26084025

  7. Gene activation regresses atherosclerosis, promotes health, and enhances longevity

    Directory of Open Access Journals (Sweden)

    Luoma Pauli V

    2010-07-01

    Full Text Available Abstract Background Lifestyle factors and pharmacological compounds activate genetic mechanisms that influence the development of atherosclerotic and other diseases. This article reviews studies on natural and pharmacological gene activation that promotes health and enhances longevity. Results Living habits including healthy diet and regular physical activity, and pharmacotherapy, upregulate genes encoding enzymes and apolipoprotein and ATP-binding cassette transporters, acting in metabolic processes that promote health and increase survival. Cytochrome P450-enzymes, physiological factors in maintaining cholesterol homeostasis, generate oxysterols for the elimination of surplus cholesterol. Hepatic CTP:phosphocholine cytidylyltransferase-α is an important regulator of plasma HDL-C level. Gene-activators produce plasma lipoprotein profile, high HDL-C, HDL2-C and HDL-C/cholesterol ratio, which is typical of low risk of atherosclerotic disease, and also of exceptional longevity together with reduced prevalence of cardiovascular, metabolic and other diseases. High HDL contributes to protection against inflammation, oxidation and thrombosis, and associates with good cognitive function in very old people. Avoiding unhealthy stress and managing it properly promotes health and increases life expectancy. Conclusions Healthy living habits and gene-activating xenobiotics upregulate mechanisms that produce lipoprotein pattern typical of very old people and enhance longevity. Lipoprotein metabolism and large HDL2 associate with the process of living a very long life. Major future goals for health promotion are the improving of commitment to both wise lifestyle choices and drug therapy, and further the developing of new and more effective and well tolerated drugs and treatments.

  8. High-Intensity Interval Training for Improving Postprandial Hyperglycemia

    Science.gov (United States)

    Little, Jonathan P.; Francois, Monique E.

    2014-01-01

    High-intensity interval training (HIIT) has garnered attention in recent years as a time-efficient exercise option for improving cardiovascular and metabolic health. New research demonstrates that HIIT may be particularly effective for improving postprandial hyperglycemia in individuals with, or at risk for, type 2 diabetes (T2D). These findings…

  9. [Prenatal control related to the number of consultations as hyperglycemia diagnostic method].

    Science.gov (United States)

    Hernández-Valencia, Marcelino; Carrillo Pacheco, Adia

    2002-12-01

    The impaired in the metabolism of the carbohydrates in a previously healthy woman who develops hyperglycemia during the pregnancy is know as gestational diabetes, the maternal-fetal mortality and morbility is almost the same one that a pregnant normal woman, if the metabolic dysfunction is appropriately controlled, the complications can be treated with success if the pregnant one attends prenatal control. The aim of this study was to know the relationship between number of consultations and the hyperglycemia frequency to settle down. 304 pregnant patients were studied that who request childbirth attention at emergency room of the gynecology and obstetrics service were studied; two groups were formed. The first group, 176 patients with term pregnancy in inadequate control with four or less prenatal consultations. The second group, 128 patients with five or more prenatal consultations. All had a fast of at least 4 hours, to take them a sample of blood and to determine the glucose during their entrance with initial childbirth labor. There was difference in the number of consultations that received each group with 1.4 +/- 1.0 consultations for the irregular group and 6.5 +/- 1.1 for the group with regular control. The pregnant ones with no prenatal consultation presented the biggest hyperglycemia percentage, but this percentage diminished as the pregnant ones attended to a bigger number of consultations, since they were detected the dysfunction of glucose on time and they could be treated appropriately. The glycemia was normal in all the patients that had more than 6 prenatal consultations because hyperglycemia was detected in 55 (31.2%) patients of the group with irregular prenatal control, in comparison with 4 (3.1%) of those with appropriate control (p control with a smaller number of prenatal consultations, they have the biggest hyperglycemia percentage, because it was not possible to detect this dysfunction in an opportune way, this situation demonstrates the

  10. Coronary atherosclerosis in medico-legal autopsy cases

    Directory of Open Access Journals (Sweden)

    VN Prasad

    2014-09-01

    Full Text Available Background: Coronary atherosclerosis is the major cause of death worldwide. Lifestyle and habits are the major contributory factor in the development of coronary atherosclerosis. Materials and Methods: This is an autopsy-based study in which 45 autopsy cases were randomly selected for study. Proximal one third of all three epicardial coronary arteries (LAD, LCX and RCA were dissected out for study and serial sections were made and stained with H&E method and under the light microscope. Atherosclerosis was graded according to American heart association classification. The risk factors (cigarette smoking, hypertension, diabetes, alcohol consumption, age, sex were also correlated with the grade of atherosclerosis. Results: Seventy-Eight percent of American Heart Association classification grade V lesions were seen in > 70 yrs of age. Almost all cases of > 70 yrs of age had American Heart Association classification grade > IV lesions. Out of all grade IV lesions, 88.9% was seen in male while only 11.1% in female. Similarly out of all grade V lesions, 77.8% was seen in male while 22.2% in female. LAD showed maximum involvement by higher grade lesion, followed by LCX and RCA. American Heart Association classification grade > IV in LAD, LCX and RCA was seen in 25(55.6%, 5(11.1%, and 3(6.7% cases respectively. Conclusion: Higher grade lesion occurs in advancing age. Various cardiovascular risk factors were significantly associated with higher grade of lesions. The multiple risk factors had a synergistic effect on the progression of coronary atherosclerosis. DOI: http://dx.doi.org/10.3126/jpn.v4i8.11492 Journal of Pathology of Nepal; Vol.4,No8(2014 607-611

  11. Beneficial effect of 17β-estradiol on hyperglycemia and islet β-cell functions in a streptozotocin-induced diabetic rat model

    International Nuclear Information System (INIS)

    Yamabe, Noriko; Kang, Ki Sung; Zhu Baoting

    2010-01-01

    The modulating effect of estrogen on glucose homeostasis remains a controversial issue at present. In this study, we sought to determine the beneficial effect of 17β-estradiol (E 2 ) on hyperglycemia and islet β-cell functions in streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were injected i.p. with STZ to induce a relatively mild diabetic condition. The rats were then treated with E 2 orally at 500 μg/kg body weight/day for 15 days to evaluate the modulating effect on hyperglycemia, insulin secretion, and islet β-cell proliferation. E 2 administration for 10 days significantly lowered plasma glucose levels, increased plasma insulin levels, and improved glucose tolerance by attenuating insulin response to oral glucose loading. These beneficial effects of E 2 were accompanied by increases in islet number and volume, rate of islet cell proliferation, and the amount of insulin secreted. The growth-stimulatory effect of E 2 on islet cells was linked to the functions of the estrogen receptor α. Notably, these protective effects of E 2 on diabetic conditions were basically not observed when the STZ-treated rats had a more severe degree of islet damage and hyperglycemia. Taken together, we conclude that E 2 can promote the regeneration of damaged pancreatic islets by stimulating β-cell proliferation in diabetic rats, and this effect is accompanied by improvements in glucose tolerance and a decrease in plasma glucose levels. These findings suggest that oral administration of E 2 may be beneficial in diabetic patients with an accelerated loss of islet β-cells.

  12. Impact of hyperglycemia on ischemic stroke mortality in diabetic and non-diabetic patients

    International Nuclear Information System (INIS)

    Kes, V.B.; Solter, V.V.; Supanc, V.; Demarin, V.

    2007-01-01

    Previous studies suggest that infarct expansion may be responsible for increased mortality after stroke onset in patients with prolonged stress hyperglycemia on stroke mortality in patients with and without diabetes. For 630 stroke patients admitted to the neurological intensive care department within 24 hours of stroke onset, we correlated mean blood glucose levels (MBGL) at admission and 72 hours after admission in diabetic and non-diabetic patients with final outcome. Blood glucose levels higher then 6.1 mmol/L (121mg/dL) was treated as hyperglycemia. Of 630 patients (mean age 71+-6), 410 were non-diabetic (mortality, 25%) and 220 patients were diabetic (mortality, 20%). All patients who died within 28 days of hospitalization had prolonged hyperglycemia at admission and after 72 hours, despite insulin therapy). The unadjusted relative risk of in-hospital mortality within 28 days of all stroke patients was 0.68 (95% CI, 0.14-1.9) for non-diabetic patients and 0.39 (95% CI, 0.27-1.56) for diabetic patients. The unadjusted relative risk of in-hospital mortality within 28 days in ischemic stroke in patients with MBGL> 6.1-8.0 mmol/L (121-144 mg/dL) at admission after 72 hours was 1.83 (95% CI, 0.41-5.5) for non-diabetic patients and 1.13 (95% CI, 0.78-4.5) for diabetic patients and 1.13 (95%, 0.78-4.5) for diabetic patients. Non-diabetic patients with hyperglycemia had a 1.7 times higher relative risk of in-hospital 28-day mortality than patients with diabetes. Prolonged stress hyperglycemia in ischemic stroke patients increases the risk of in-hospital 28-day mortality, especially in non-diabetic patients. (author)

  13. microRNAs in the regulation of dendritic cell functions in inflammation and atherosclerosis.

    Science.gov (United States)

    Busch, Martin; Zernecke, Alma

    2012-08-01

    Atherosclerosis has been established as a chronic inflammatory disease of the vessel wall. Among the mononuclear cell types recruited to the lesions, specialized dendritic cells (DCs) have gained increasing attention, and their secretory products and interactions shape the progression of atherosclerotic plaques. The regulation of DC functions by microRNAs (miRNAs) may thus be of primary importance in disease. We here systematically summarize the biogenesis and functions of miRNAs and provide an overview of miRNAs in DCs, their targets, and potential implications for atherosclerosis, with a particular focus on the best characterized miRNAs in DCs, namely, miR-155 and miR-146. MiRNA functions in DCs range from regulation of lipid uptake to cytokine production and T cell responses with a complex picture emerging, in which miRNAs cooperate or antagonize DC behavior, thereby promoting or counterbalancing inflammatory responses. As miRNAs regulate key functions of DCs known to control atherosclerotic vascular disease, their potential as a therapeutic target holds promise and should be attended to in future research.

  14. Targeting the adaptive immune system: new strategies in the treatment of atherosclerosis

    NARCIS (Netherlands)

    Zarzycka, Barbara; Nicolaes, Gerry A. F.; Lutgens, Esther

    2015-01-01

    Atherosclerosis is a lipid-driven chronic inflammatory disease of the arterial wall. Current treatment of atherosclerosis is focused on limiting its risk factors, such as hyperlipidemia or hypertension. However, treatments that target the inflammatory nature of atherosclerosis are still under

  15. Periodontal disease and carotid atherosclerosis: A meta-analysis of 17,330 participants.

    Science.gov (United States)

    Zeng, Xian-Tao; Leng, Wei-Dong; Lam, Yat-Yin; Yan, Bryan P; Wei, Xue-Mei; Weng, Hong; Kwong, Joey S W

    2016-01-15

    The association between periodontal disease and carotid atherosclerosis has been evaluated primarily in single-center studies, and whether periodontal disease is an independent risk factor of carotid atherosclerosis remains uncertain. This meta-analysis aimed to evaluate the association between periodontal disease and carotid atherosclerosis. We searched PubMed and Embase for relevant observational studies up to February 20, 2015. Two authors independently extracted data from included studies, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for overall and subgroup meta-analyses. Statistical heterogeneity was assessed by the chi-squared test (Pperiodontal disease was associated with carotid atherosclerosis (OR: 1.27, 95% CI: 1.14-1.41; Pperiodontal disease was associated with carotid atherosclerosis; however, further large-scale, well-conducted clinical studies are needed to explore the precise risk of developing carotid atherosclerosis in patients with periodontal disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Local hyperthermia and artificial hyperglycemia in combined treatment of patients with rectum cancer

    International Nuclear Information System (INIS)

    Bezmen, V.A.; Illarionov, A.A.; Novokhrost, V.I.; Shilov, N.I.; Ospishchev, A.A.; Kejs, G.D.

    1990-01-01

    To study prospects of application of local hyperthermia, artificial hyperglycemia and radiotherapy in a preoperative period, 31 patients with rectum cancer were studied. The treatment included 3-hour artificial hyperglycemia first, then local SHF hyperthermia and telegamma irradiation using large-fractioned doses (ROD is 5 Gy, COD is 20 Gy). No serious side-effects were observed during the preoperative treatment period. The immediate and early results of combined treatment promise to improve the effectiveness of treatment of patients with rectum cancer. 3 refs

  17. Macrophage Phenotype and Function in Different Stages of Atherosclerosis

    Science.gov (United States)

    Tabas, Ira; Bornfeldt, Karin E.

    2016-01-01

    The remarkable plasticity and plethora of biological functions performed by macrophages have enticed scientists to study these cells in relation to atherosclerosis for more than 50 years, and major discoveries continue to be made today. It is now understood that macrophages play important roles in all stages of atherosclerosis, from initiation of lesions and lesion expansion, to necrosis leading to rupture and the clinical manifestations of atherosclerosis, to resolution and regression of atherosclerotic lesions. Lesional macrophages are derived primarily from blood monocytes, although recent research has shown that lesional macrophage-like cells can also be derived from smooth muscle cells. Lesional macrophages take on different phenotypes depending on their environment and which intracellular signaling pathways are activated. Rather than a few distinct populations of macrophages, the phenotype of the lesional macrophage is more complex and likely changes during the different phases of atherosclerosis and with the extent of lipid and cholesterol loading, activation by a plethora of receptors, and metabolic state of the cells. These different phenotypes allow the macrophage to engulf lipids, dead cells, and other substances perceived as danger signals; efflux cholesterol to HDL; proliferate and migrate; undergo apoptosis and death; and secrete a large number of inflammatory and pro-resolving molecules. This review article, part of the Compendium on Atherosclerosis, discusses recent advances in our understanding of lesional macrophage phenotype and function in different stages of atherosclerosis. With the increasing understanding of the roles of lesional macrophages, new research areas and treatment strategies are beginning to emerge. PMID:26892964

  18. Go-6976 Reverses Hyperglycemia-Induced Insulin Resistance Independently of cPKC Inhibition in Adipocytes

    Science.gov (United States)

    Robinson, Katherine A.; Hegyi, Krisztina; Hannun, Yusuf A.; Buse, Maria G.; Sethi, Jaswinder K.

    2014-01-01

    Chronic hyperglycemia induces insulin resistance by mechanisms that are incompletely understood. One model of hyperglycemia-induced insulin resistance involves chronic preincubation of adipocytes in the presence of high glucose and low insulin concentrations. We have previously shown that the mTOR complex 1 (mTORC1) plays a partial role in the development of insulin resistance in this model. Here, we demonstrate that treatment with Go-6976, a widely used “specific” inhibitor of cPKCs, alleviates hyperglycemia-induced insulin resistance. However, the effects of mTOR inhibitor, rapamycin and Go-6976 were not additive and only rapamycin restored impaired insulin-stimulated AKT activation. Although, PKCα, (but not –β) was abundantly expressed in these adipocytes, our studies indicate cPKCs do not play a major role in causing insulin-resistance in this model. There was no evidence of changes in the expression or phosphorylation of PKCα, and PKCα knock-down did not prevent the reduction of insulin-stimulated glucose transport. This was also consistent with lack of IRS-1 phosphorylation on Ser-24 in hyperglycemia-induced insulin-resistant adipocytes. Treatment with Go-6976 did inhibit a component of the mTORC1 pathway, as evidenced by decreased phosphorylation of S6 ribosomal protein. Raptor knock-down enhanced the effect of insulin on glucose transport in insulin resistant adipocytes. Go-6976 had the same effect in control cells, but was ineffective in cells with Raptor knock-down. Taken together these findings suggest that Go-6976 exerts its effect in alleviating hyperglycemia-induced insulin-resistance independently of cPKC inhibition and may target components of the mTORC1 signaling pathway. PMID:25330241

  19. Apolipoprotein E and carotid artery atherosclerosis - The Rotterdam study

    NARCIS (Netherlands)

    Slooter, AJC; Bots, ML; Havekes, LM; del Sol, AI; Cruts, M; Grobbee, DE; Hofman, A; Van Broeckhoven, C; Witteman, JCM; van Duijn, CM

    Background and Purpose-Carotid artery atherosclerosis is a strong predictor for future stroke. It is yet unclear whether the apolipoprotein E polymorphism (APOE) is related to atherosclerosis in the carotid arteries. The aim of the present study was to investigate the role of APOE in carotid artery

  20. Stress Induced Hyperglycemia and the Subsequent Risk of Type 2 Diabetes in Survivors of Critical Illness

    Science.gov (United States)

    Plummer, Mark P.; Finnis, Mark E.; Phillips, Liza K.; Kar, Palash; Bihari, Shailesh; Biradar, Vishwanath; Moodie, Stewart; Horowitz, Michael; Shaw, Jonathan E.; Deane, Adam M.

    2016-01-01

    Objective Stress induced hyperglycemia occurs in critically ill patients who have normal glucose tolerance following resolution of their acute illness. The objective was to evaluate the association between stress induced hyperglycemia and incident diabetes in survivors of critical illness. Design Retrospective cohort study. Setting All adult patients surviving admission to a public hospital intensive care unit (ICU) in South Australia between 2004 and 2011. Patients Stress induced hyperglycemia was defined as a blood glucose ≥ 11.1 mmol/L (200 mg/dL) within 24 hours of ICU admission. Prevalent diabetes was identified through ICD-10 coding or prior registration with the Australian National Diabetes Service Scheme (NDSS). Incident diabetes was identified as NDSS registration beyond 30 days after hospital discharge until July 2015. The predicted risk of developing diabetes was described as sub-hazard ratios using competing risk regression. Survival was assessed using Cox proportional hazards regression. Main Results Stress induced hyperglycemia was identified in 2,883 (17%) of 17,074 patients without diabetes. The incidence of type 2 diabetes following critical illness was 4.8% (821 of 17,074). The risk of diabetes in patients with stress induced hyperglycemia was approximately double that of those without (HR 1.91 (95% CI 1.62, 2.26), phyperglycemia identifies patients at subsequent risk of incident diabetes. PMID:27824898

  1. Polymorphonuclear leucocyte dysfunction during short term metabolic changes from normo- to hyperglycemia in type 1 (insulin dependent) diabetic patients

    DEFF Research Database (Denmark)

    Kjersem, H; Hilsted, J; Madsbad, S

    1988-01-01

    Polymorphonuclear leucocyte (PMN) ingestion of particles coated with lipopolysaccharide (LPS) from Escherichia coli was compared to other PMN functions in seven patients with insulin dependent diabetes mellitus (IDDM) during short-term controlled metabolic changes from normo- to hyperglycemia...... without ketoacidosis. Factors known to interfere with PMN functions were excluded. PMN ingestion of particles coated with both LPS and bovine serum albumin became reduced from normo- to hyperglycemia. PMN motility was impaired in IDDM, but did not seem to be affected by short-term changes in metabolic...... control. PMN metabolism did not change from normo-to hyperglycemia. Particle-uptake by diabetic PMN is impaired after short term hyperglycemia in the range normally occurring in diabetics in every-day life....

  2. Remission of active diabetic hepatitis after correction of hyperglycemia

    NARCIS (Netherlands)

    Tak, P. P.; ten Kate, F. J.

    1993-01-01

    A 60-year-old obese woman with type II diabetes mellitus and hepatomegaly exhibited progression of steatosis to hepatitis and cirrhosis. The patient was treated with large amounts of insulin combined with sulfonylurea, resulting in correction of the hyperglycemia. In the subsequent 9 months, weight

  3. Antihyperglycemic and Antihyperlipidemic Activity of Hydroponic Stevia rebaudiana Aqueous Extract in Hyperglycemia Induced by Immobilization Stress in Rabbits

    Directory of Open Access Journals (Sweden)

    Anush Aghajanyan

    2017-01-01

    Full Text Available Diabetes mellitus (DM is a serious worldwide problem related to human hyperglycemia. Thus, herbal preparations with antihyperglycemic properties especially leaf extracts of hydroponic Stevia rebaudiana (SR would be useful in hyperglycemia treatment. The antihyperglycemic potential of this medicinal plant grown using hydroponics methods has been evaluated. Significant reduction of some biochemical characteristics for sugars and fatty acids in blood, liver, and muscle especially fasting glucose levels, serum triglycerides, LDL-cholesterol, total cholesterol levels, and increased HDL-cholesterol ones was shown with SR aqueous extract treatment. Therefore, the aqueous extract of SR is suggested to have antihyperglycemic and antihyperlipidemic activity and to restore liver and muscle glycogen levels (hepatoprotective effects in hyperglycemia induced by immobilization stress in rabbits and might be recommended for treatment of DM (hyperglycemia.

  4. Antihyperglycemic and Antihyperlipidemic Activity of Hydroponic Stevia rebaudiana Aqueous Extract in Hyperglycemia Induced by Immobilization Stress in Rabbits

    Science.gov (United States)

    Aghajanyan, Anush; Movsisyan, Zaruhi

    2017-01-01

    Diabetes mellitus (DM) is a serious worldwide problem related to human hyperglycemia. Thus, herbal preparations with antihyperglycemic properties especially leaf extracts of hydroponic Stevia rebaudiana (SR) would be useful in hyperglycemia treatment. The antihyperglycemic potential of this medicinal plant grown using hydroponics methods has been evaluated. Significant reduction of some biochemical characteristics for sugars and fatty acids in blood, liver, and muscle especially fasting glucose levels, serum triglycerides, LDL-cholesterol, total cholesterol levels, and increased HDL-cholesterol ones was shown with SR aqueous extract treatment. Therefore, the aqueous extract of SR is suggested to have antihyperglycemic and antihyperlipidemic activity and to restore liver and muscle glycogen levels (hepatoprotective effects) in hyperglycemia induced by immobilization stress in rabbits and might be recommended for treatment of DM (hyperglycemia). PMID:28758125

  5. Extracranial cerebral arterial atherosclerosis in Iranian patients suffering ischemic strokes

    Directory of Open Access Journals (Sweden)

    Sayed Ali Mousavi

    2006-12-01

    Full Text Available BACKGROUND: To determine the distribution and severity of extracranial carotid arterial atherosclerosis in Iranian patients with ischemic stroke. METHODS: 328 patients with ischemic stroke were included in this study. Doppler ultrasound was used for evaluation of atherosclerosis in extracranial carotid arteries. The NASCET criteria were used to measure carotid stenosis. RESULTS: Ninety of 328 patients (27.4% were found to have atherosclerotic plaques; 40 of these patients were women and 50 were men. Sixty-eight patients (20.7% had artery stenosis <50%, 13 patients (3.95% had 50-70 % artery stenosis and 6 (1.8% had >70% artery stenosis. CONCLUSIONS: Extracranial atherosclerosis is not rare in Iranian patients with ischemic stroke, but most carotid artery lesions were plaques with <50% stenosis. KEY WORDS: Atherosclerosis, ischemic stroke, carotid stenosis.

  6. Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis.

    Science.gov (United States)

    Gössl, Mario; Mödder, Ulrike I; Atkinson, Elizabeth J; Lerman, Amir; Khosla, Sundeep

    2008-10-14

    This study was designed to test whether patients with coronary atherosclerosis have increases in circulating endothelial progenitor cells (EPCs) expressing an osteogenic phenotype. Increasing evidence indicates a link between bone and the vasculature, and bone marrow and circulating osteogenic cells have been identified by staining for the osteoblastic marker, osteocalcin (OCN). Endothelial progenitor cells contribute to vascular repair, but repair of vascular injury may result in calcification. Using cell surface markers (CD34, CD133, kinase insert domain receptor [KDR]) to identify EPCs, we examined whether patients with coronary atherosclerosis had increases in the percentage of EPCs expressing OCN. We studied 72 patients undergoing invasive coronary assessment: control patients (normal coronary arteries and no endothelial dysfunction, n = 21) versus 2 groups with coronary atherosclerosis-early coronary atherosclerosis (normal coronary arteries but with endothelial dysfunction, n = 22) and late coronary atherosclerosis (severe, multivessel coronary artery disease, n = 29). Peripheral blood mononuclear cells were analyzed using flow cytometry. Compared with control patients, patients with early or late coronary atherosclerosis had significant increases (approximately 2-fold) in the percentage of CD34+/KDR+ and CD34+/CD133+/KDR+ cells costaining for OCN. Even larger increases were noted in the early and late coronary atherosclerosis patients in the percentage of CD34+/CD133-/KDR+ cells costaining for OCN (5- and 2-fold, p < 0.001 and 0.05, respectively). A higher percentage of EPCs express OCN in patients with coronary atherosclerosis compared with subjects with normal endothelial function and no structural coronary artery disease. These findings have potential implications for the mechanisms of vascular calcification and for the development of novel markers for coronary atherosclerosis.

  7. Cellular and Molecular Mechanisms of Diabetic Atherosclerosis: Herbal Medicines as a Potential Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Jinfan Tian

    2017-01-01

    Full Text Available An increasing number of patients diagnosed with diabetes mellitus eventually develop severe coronary atherosclerosis disease. Both type 1 and type 2 diabetes mellitus increase the risk of cardiovascular disease associated with atherosclerosis. The cellular and molecular mechanisms affecting the incidence of diabetic atherosclerosis are still unclear, as are appropriate strategies for the prevention and treatment of diabetic atherosclerosis. In this review, we discuss progress in the study of herbs as potential therapeutic agents for diabetic atherosclerosis.

  8. Upregulation of cytosolic NADP+-dependent isocitrate dehydrogenase by hyperglycemia protects renal cells against oxidative stress.

    Science.gov (United States)

    Lee, Soh-Hyun; Ha, Sun-Ok; Koh, Ho-Jin; Kim, KilSoo; Jeon, Seon-Min; Choi, Myung-Sook; Kwon, Oh-Shin; Huh, Tae-Lin

    2010-02-28

    Hyperglycemia-induced oxidative stress is widely recognized as a key mediator in the pathogenesis of diabetic nephropathy, a complication of diabetes. We found that both expression and enzymatic activity of cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) were upregulated in the renal cortexes of diabetic rats and mice. Similarly, IDPc was induced in murine renal proximal tubular OK cells by high hyperglycemia, while it was abrogated by co-treatment with the antioxidant N-Acetyl-Cysteine (NAC). In OK cells, increased expression of IDPc by stable transfection prevented hyperglycemia-mediated reactive oxygen species (ROS) production, subsequent cellular oxidative stress and extracellular matrix accumulation, whereas these processes were all stimulated by decreased IDPc expression. In addition, production of NADPH and GSH in the cytosol was positively correlated with the expression level of IDPc in OK cells. These results together indicate that upregulation of IDPc in response to hyperglycemia might play an essential role in preventing the progression of diabetic nephropathy, which is accompanied by ROS-induced cellular damage and fibrosis, by providing NADPH, the reducing equivalent needed for recycling reduced glutathione and low molecular weight antioxidant thiol proteins.

  9. Hypertension, Hyperglycemia, and Hyperlipemia among Adolescents with Intellectual Disabilities

    Science.gov (United States)

    Lin, Pei-Ying; Lin, Lan-Ping; Lin, Jin-Ding

    2010-01-01

    The present paper aims to assess the hypertension, hyperglycemia and hyperlipidemia prevalence of adolescents with intellectual disabilities, and to recognize the health disparities between the study participants and the general population. This study conducted a cross-sectional medical chart analysis of 856 students who participated in school…

  10. Citrus Flavonoids as Regulators of Lipoprotein Metabolism and Atherosclerosis.

    Science.gov (United States)

    Mulvihill, Erin E; Burke, Amy C; Huff, Murray W

    2016-07-17

    Citrus flavonoids are polyphenolic compounds with significant biological properties. This review summarizes recent advances in understanding the ability of citrus flavonoids to modulate lipid metabolism, other metabolic parameters related to the metabolic syndrome, and atherosclerosis. Citrus flavonoids, including naringenin, hesperitin, nobiletin, and tangeretin, have emerged as potential therapeutics for the treatment of metabolic dysregulation. Epidemiological studies reveal an association between the intake of citrus flavonoid-containing foods and a decreased incidence of cardiovascular disease. Studies in cell culture and animal models, as well as a limited number of clinical studies, reveal the lipid-lowering, insulin-sensitizing, antihypertensive, and anti-inflammatory properties of citrus flavonoids. In animal models, supplementation of rodent diets with citrus flavonoids prevents hepatic steatosis, dyslipidemia, and insulin resistance primarily through inhibition of hepatic fatty acid synthesis and increased fatty acid oxidation. Citrus flavonoids blunt the inflammatory response in metabolically important tissues including liver, adipose, kidney, and the aorta. The mechanisms underlying flavonoid-induced metabolic regulation have not been completely established, although several potential targets have been identified. In mouse models, citrus flavonoids show marked suppression of atherogenesis through improved metabolic parameters as well as through direct impact on the vessel wall. Recent studies support a role for citrus flavonoids in the treatment of dyslipidemia, insulin resistance, hepatic steatosis, obesity, and atherosclerosis. Larger human studies examining dose, bioavailability, efficacy, and safety are required to promote the development of these promising therapeutic agents.

  11. Acute Phase Hyperglycemia among Patients Hospitalized with Acute Coronary Syndrome: Prevalence and Prognostic Significance

    Directory of Open Access Journals (Sweden)

    Hameed Laftah Wanoose

    2011-03-01

    Full Text Available AbstractObjectives: Regardless of diabetes status, hyperglycemia on arrival for patients presenting with acute coronary syndrome, has been associated with adverse outcomes including death. The aim of this study is to look at the frequency and prognostic significance of acute phase hyperglycemia among patients attending the coronary care unit with acute coronary syndrome over the in-hospital admission days.Methods: The study included 287 consecutive patients in the Al- Faiha Hospital in Basrah (Southern Iraq during a one year period from December 2007 to November 2008. Patients were divided into two groups with respect to admission plasma glucose level regardless of their diabetes status (those with admission plasma glucose of <140 mg/dl (7.8 mmol/L and those equal to or more than that. Acute phase hyperglycemia was defined as a non-fasting glucose level equal to or above 140 mg/dl (7.8 mmol/L regardless of past history of diabetes.Results: Sixty one point seven percent (177 of patients were admitted with plasma glucose of ≥140 mg/dl (7.8 mmol/L. There were no differences were found between both groups regarding the mean age, qualification, and smoking status, but males were predominant in both groups. A family history of diabetes, and hypertension, were more frequent in patients with plasma glucose of ≥140 mg/dl (7.8 mmol/L. There were no differences between the two groups regarding past history of ischemic heart disease, stroke, lipid profile, troponin-I levels or type of acute coronary syndrome. Again heart failure was more common in the admission acute phase hyperglycemia group, but there was no difference regarding arrhythmia, stroke, or death. Using logistic regression with heart failure as the dependent variable we found that only the admission acute phase hyperglycemia (OR=2.1344, 95�0CI=1.0282-4.4307; p=0.0419 was independently associated with heart failure. While male gender, family history of diabetes mellitus, hypertension and

  12. Effect of acid-sensing ion channel 1a on the process of liver fibrosis under hyperglycemia

    International Nuclear Information System (INIS)

    Wang, Huan; Wang, Ying-hong; Yang, Feng; Li, Xiao-feng; Tian, Yuan-yao; Ni, Ming-ming; Zuo, Long-quan; Meng, Xiao-Ming; Huang, Yan

    2015-01-01

    Metabolic syndrome characterized by hyperglycemia contributes to nonalcoholic steatohepatitis-associated liver fibrosis. This study was to investigate the effects of Acid-sensing ion Channel 1a (ASIC1a) on the process of liver fibrosis under hyperglycemia. Results showed that high glucose significantly worsen the pathology of liver fibrosis in vivo. In vitro, high glucose stimulated proliferation, activation and extracellular matrix (ECM) production in HSCs, and enhanced the effect of PDGF-BB on the activation and proliferation of HSCs. These effects could be attenuated by ASIC1a specific inhibitor Psalmotoxin-1(PcTx1) or specific ShRNA for ASIC1a through Notch1/Hes-1 pathways. These data indicate that ASIC1a plays an important role in diabetes complication liver fibrosis. - Highlights: • Hyperglycemia is a risk factor for the process of liver fibrosis. • ASIC1a may be a key factor linking between high glucose and liver fibrosis. • Notch1/Hes-1 may involve to the process of liver fibrosis under hyperglycemia.

  13. Effect of acid-sensing ion channel 1a on the process of liver fibrosis under hyperglycemia

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Huan, E-mail: wanghuan7@126.com [School of Pharmacy, Anhui Medical University, Hefei, 230032 (China); Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei, 230032 (China); Wang, Ying-hong; Yang, Feng; Li, Xiao-feng; Tian, Yuan-yao; Ni, Ming-ming; Zuo, Long-quan; Meng, Xiao-Ming [School of Pharmacy, Anhui Medical University, Hefei, 230032 (China); Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei, 230032 (China); Huang, Yan, E-mail: aydhy@126.com [School of Pharmacy, Anhui Medical University, Hefei, 230032 (China); Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei, 230032 (China)

    2015-12-25

    Metabolic syndrome characterized by hyperglycemia contributes to nonalcoholic steatohepatitis-associated liver fibrosis. This study was to investigate the effects of Acid-sensing ion Channel 1a (ASIC1a) on the process of liver fibrosis under hyperglycemia. Results showed that high glucose significantly worsen the pathology of liver fibrosis in vivo. In vitro, high glucose stimulated proliferation, activation and extracellular matrix (ECM) production in HSCs, and enhanced the effect of PDGF-BB on the activation and proliferation of HSCs. These effects could be attenuated by ASIC1a specific inhibitor Psalmotoxin-1(PcTx1) or specific ShRNA for ASIC1a through Notch1/Hes-1 pathways. These data indicate that ASIC1a plays an important role in diabetes complication liver fibrosis. - Highlights: • Hyperglycemia is a risk factor for the process of liver fibrosis. • ASIC1a may be a key factor linking between high glucose and liver fibrosis. • Notch1/Hes-1 may involve to the process of liver fibrosis under hyperglycemia.

  14. Differential Changes of Aorta and Carotid Vasodilation in Type 2 Diabetic GK and OLETF Rats: Paradoxical Roles of Hyperglycemia and Insulin

    Directory of Open Access Journals (Sweden)

    Mei-Fang Zhong

    2012-01-01

    Full Text Available We investigated large vessel function in lean Goto-Kakizaki diabetic rats (GK and Otsuka Long-Evans Tokushima Fatty diabetic rats (OLETF with possible roles of hyperglycemia/hyperosmolarity and insulin. Both young and old GK showed marked hyperglycemia with normal insulin level and well-preserved endothelium-dependent and endothelium-independent vasodilation in aorta and carotid artery. There were significant elevations in endothelial/inducible nitric oxide synthase (eNOS/iNOS and inducible/constitutive heme oxygenase (HO-1/HO-2 in GK. The endothelium-dependent vasodilation in GK was inhibited partly by NOS blockade and completely by simultaneous blocking of HO and NOS. In contrast, OLETF showed hyperinsulinemia and mild hyperglycemia but significant endothelium dysfunction beginning at early ages with concomitantly reduced eNOS. Insulin injection corrected hyperglycemia in GK but induced endothelium dysfunction and intima hyperplasia. Hyperglycemia/hyperosmolarity in vitro enhanced vessel eNOS/HO. We suggest that hyperinsulinemia plays a role in endothelium dysfunction in obese diabetic OLETF, while hyperglycemia/hyperosmolarity-induced eNOS/HO upregulation participates in the adaptation of endothelium function in lean diabetic GK.

  15. Intracranial atherosclerosis: current concepts.

    Science.gov (United States)

    Arenillas, Juan F

    2011-01-01

    The most relevant ideas discussed in this article are described here. Intracranial atherosclerotic disease (ICAD) represents the most common cause of ischemic stroke worldwide. Its importance in whites may have been underestimated. New technical developments, such as high-resolution MRI, allow direct assessment of the intracranial atherosclerotic plaque, which may have a profound impact on ICAD diagnosis and therapy in the near future. Early detection of ICAD may allow therapeutic intervention while the disease is still asymptomatic. The Barcelonès Nord and Maresme Asymptomatic Intracranial Atherosclerosis Study is presented here. The main prognostic factors that characterize the patients who are at a higher risk for ICAD recurrence are classified and discussed. The best treatment for ICAD remains to be established. The Stenting Versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Study is currently ongoing to address this crucial issue. These and other topics will be discussed at the Fifth International Intracranial Atherosclerosis Conference (Valladolid, Spain, autumn 2011).

  16. Gender-Related Differences in Atherosclerosis

    Czech Academy of Sciences Publication Activity Database

    Mathur, P.; Ošťádal, Bohuslav; Romeo, F.; Mehta, J. L.

    2015-01-01

    Roč. 29, č. 4 (2015), s. 319-327 ISSN 0920-3206 Institutional support: RVO:67985823 Keywords : atherosclerosis * gender Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.189, year: 2015

  17. Pathophysiological effects of radiation on atherosclerosis development and progression, and the incidence of cardiovascular complications

    International Nuclear Information System (INIS)

    Basavaraju, Sekhara Rao; Easterly, Clay E.

    2002-01-01

    Radiation therapy while important in the management of several diseases, is implicated in the causation of atherosclerosis and other cardiovascular complications. Cancer and atherosclerosis go through the same stages of initiation, promotion, and complication, beginning with a mutation in a single cell. Clinical observations before the 1960s lead to the belief that the heart is relatively resistant to the doses of radiation used in radiotherapy. Subsequently, it was discovered that the heart is sensitive to radiation and many cardiac structures may be damaged by radiation exposure. A significantly higher risk of death due to ischemic heart disease has been reported for patients treated with radiation for Hodgkin's disease and breast cancer. Certain cytokines and growth factors, such as TGF-β1 and IL-1 β, may stimulate radiation-induced endothelial proliferation, fibroblast proliferation, collagen deposition, and fibrosis leading to advanced lesions of atherosclerosis. The treatment for radiation-induced ischemic heart disease includes conventional pharmacological therapy, balloon angioplasty, and bypass surgery. Endovascular irradiation has been shown to be effective in reducing restenosis-like response to balloon-catheter injury in animal models. Caution must be exercised when radiation therapy is combined with doxorubicin because there appears to be a synergistic toxic effect on the myocardium. Damage to endothelial cells is a central event in the pathogenesis of damage to the coronary arteries. Certain growth factors that interfere with the apoptotic pathway may provide new therapeutic strategies for reducing the risk of radiation-induced damage to the heart. Exposure to low level occupational or environmental radiation appears to pose no undue risk of atherosclerosis development or cardiovascular mortality. But, other radiation-induced processes such as the bystander effects, abscopal effects, hormesis, and individual variations in radiosensitivity may be

  18. MicroRNA-181b Controls Atherosclerosis and Aneurysms Through Regulation of TIMP-3 and Elastin.

    Science.gov (United States)

    Di Gregoli, Karina; Mohamad Anuar, Nur Najmi; Bianco, Rosaria; White, Stephen J; Newby, Andrew C; George, Sarah J; Johnson, Jason L

    2017-01-06

    Atherosclerosis and aneurysms are leading causes of mortality worldwide. MicroRNAs (miRs) are key determinants of gene and protein expression, and atypical miR expression has been associated with many cardiovascular diseases; although their contributory role to atherosclerotic plaque and abdominal aortic aneurysm stability are poorly understood. To investigate whether miR-181b regulates tissue inhibitor of metalloproteinase-3 expression and affects atherosclerosis and aneurysms. Here, we demonstrate that miR-181b was overexpressed in symptomatic human atherosclerotic plaques and abdominal aortic aneurysms and correlated with decreased expression of predicted miR-181b targets, tissue inhibitor of metalloproteinase-3, and elastin. Using the well-characterized mouse atherosclerosis models of Apoe - /- and Ldlr -/- , we observed that in vivo administration of locked nucleic acid anti-miR-181b retarded both the development and the progression of atherosclerotic plaques. Systemic delivery of anti-miR-181b in angiotensin II-infused Apoe -/- and Ldlr -/- mice attenuated aneurysm formation and progression within the ascending, thoracic, and abdominal aorta. Moreover, miR-181b inhibition greatly increased elastin and collagen expression, promoting a fibrotic response and subsequent stabilization of existing plaques and aneurysms. We determined that miR-181b negatively regulates macrophage tissue inhibitor of metalloproteinase-3 expression and vascular smooth muscle cell elastin production, both important factors in maintaining atherosclerotic plaque and aneurysm stability. Validation studies in Timp3 -/- mice confirmed that the beneficial effects afforded by miR-181b inhibition are largely tissue inhibitor of metalloproteinase-3 dependent, while also revealing an additional protective effect through elevating elastin synthesis. Our findings suggest that the management of miR-181b and its target genes provides therapeutic potential for limiting the progression of

  19. Familial mild hyperglycemia associated with a novel ABCC8-V84I mutation within three generations

    DEFF Research Database (Denmark)

    Gonsorcikova, Lucie; Vaxillaire, Martine; Pruhova, Stepanka

    2011-01-01

    We present a unique case of a 19-year-old man with a positive family history of persistent mild hyperglycemia and a novel V84I mutation in ABCC8. The proband was initially detected to have fasting hyperglycemia (ranging 6.1-6.4 mmol/L) at the age of 12 years. Increased fasting blood glucose was a...

  20. Basic mechanisms in intracranial large-artery atherosclerosis: advances and challenges.

    Science.gov (United States)

    Arenillas, Juan F; Alvarez-Sabín, José

    2005-01-01

    Intracranial large-artery atherosclerosis is a major cause of ischemic stroke worldwide. Patients affected by this disease are at a high risk of suffering recurrent ischemic events despite antithrombotic therapy. Progression and a greater extent of intracranial atherosclerosis imply a higher risk for recurrence. Studies performed by our group in patients with symptomatic intracranial large-artery atherosclerosis have shown that: (1) C-reactive protein predicts its progression and recurrence, suggesting that inflammation may play a deleterious role in this condition; (2) a high level of the anti-angiogenic endostatin is also associated with a progressive and recurrent intracranial atherosclerosis, which might support a beneficial role for angiogenesis in this group of patients; and (3) elevated lipoprotein(a) concentration and diabetes mellitus characterize those patients with a higher number of intracranial stenoses. 2005 S. Karger AG, Basel

  1. A STUDY TO ESTABLISH ASSOCIAT ION OF HYPERGLYCEMIA AND INPATIENT MORTALITY IN PATIENTS WITH UNDIAGNOSED DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    Mohd

    2015-06-01

    Full Text Available The aim of this study was to establish the prevalence, survival, and outcome of patients presented with in - hospital hyperglycemia in which there is prior history of diabetes and without a history of diabetes. We reviewed the medical records of 2000 consecu tive adult patients admitted to MNR Medical College, a teaching hospital in Telangana; from Jan 2014 to Nov 2014 and 1886 patients were studied 144 were excluded as glycemic records were not available. New hyperglycemia was defined as fasting glucose level of 126 mg/dl on admission or in - hospital or random blood glucose of more than 200 mg/dl or more on 2 or more determinations. Hyperglycemia was present in 38% of patients admitted to the hospital, of whom 26% had a known history of diabetes, and 11.96% had no history of diabetes before the admission. It was observed that there was higher in - hospital mortality rate (16.21% in newly diagnosed hyperglycemia when compared to known diabetic patients (3.31% and subjects with normoglycemia (1.56%; both P < 0.01. In addition, new hyperglycemic patients had a prolonged hospital stay, a higher admission rate to an intensive care unit, and were less likely to be discharged to home, frequently requiring transfer to a transitional care unit or nursing home facility. Ou r results indicate that in - hospital hyperglycemia is a common finding and represents an important marker of poor clinical outcome and mortality in patients with and without a history of diabetes. Patients with newly diagnosed hyperglycemia had a significan tly higher mortality rate and a lower functional outcome than patients with a known history of diabetes or normoglycemia.

  2. The Influence of Acute Hyperglycemia in an Animal Model of Lacunar Stroke That Is Induced by Artificial Particle Embolization

    Science.gov (United States)

    Tsai, Ming-Jun; Lin, Ming-Wei; Huang, Yaw-Bin; Kuo, Yu-Min; Tsai, Yi-Hung

    2016-01-01

    Animal and clinical studies have revealed that hyperglycemia during ischemic stroke increases the stroke's severity and the infarct size in clinical and animal studies. However, no conclusive evidence demonstrates that acute hyperglycemia worsens post-stroke outcomes and increases infarct size in lacunar stroke. In this study, we developed a rat model of lacunar stroke that was induced via the injection of artificial embolic particles during full consciousness. We then used this model to compare the acute influence of hyperglycemia in lacunar stroke and diffuse infarction, by evaluating neurologic behavior and the rate, size, and location of the infarction. The time course of the neurologic deficits was clearly recorded from immediately after induction to 24 h post-stroke in both types of stroke. We found that acute hyperglycemia aggravated the neurologic deficit in diffuse infarction at 24 h after stroke, and also aggravated the cerebral infarct. Furthermore, the infarct volumes of the basal ganglion, thalamus, hippocampus, and cerebellum but not the cortex were positively correlated with serum glucose levels. In contrast, acute hyperglycemia reduced the infarct volume and neurologic symptoms in lacunar stroke within 4 min after stroke induction, and this effect persisted for up to 24 h post-stroke. In conclusion, acute hyperglycemia aggravated the neurologic outcomes in diffuse infarction, although it significantly reduced the size of the cerebral infarct and improved the neurologic deficits in lacunar stroke. PMID:27226775

  3. Emerging Roles of Tumor Necrosis Factor-Stimulated Gene-6 in the Pathophysiology and Treatment of Atherosclerosis

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    Rena Watanabe

    2018-02-01

    Full Text Available Tumor necrosis factor-stimulated gene-6 (TSG-6 is a 35-kDa glycoprotein that has been shown to exert anti-inflammatory effects in experimental models of arthritis, acute myocardial infarction, and acute cerebral infarction. Several lines of evidence have shed light on the pathophysiological roles of TSG-6 in atherosclerosis. TSG-6 suppresses inflammatory responses of endothelial cells, neutrophils, and macrophages as well as macrophage foam cell formation and vascular smooth muscle cell (VSMC migration and proliferation. Exogenous TSG-6 infusion and endogenous TSG-6 attenuation with a neutralizing antibody for four weeks retards and accelerates, respectively, the development of aortic atherosclerotic lesions in ApoE-deficient mice. TSG-6 also decreases the macrophage/VSMC ratio (a marker of plaque instability and promotes collagen fibers in atheromatous plaques. In patients with coronary artery disease (CAD, plasma TSG-6 levels are increased and TSG-6 is abundantly expressed in the fibrous cap within coronary atheromatous plaques, indicating that TSG-6 increases to counteract the progression of atherosclerosis and stabilize the plaque. These findings indicate that endogenous TSG-6 enhancement and exogenous TSG-6 replacement treatments are expected to emerge as new lines of therapy against atherosclerosis and related CAD. Therefore, this review provides support for the clinical utility of TSG-6 in the diagnosis and treatment of atherosclerotic cardiovascular diseases.

  4. Hyperglycemia stimulates coagulation, whereas hyperinsulinemia impairs fibrinolysis in healthy humans

    NARCIS (Netherlands)

    Stegenga, Michiel E.; van der Crabben, Saskia N.; Levi, Marcel; de Vos, Alex F.; Tanck, Michael W.; Sauerwein, Hans P.; van der Poll, Tom

    2006-01-01

    Type 2 diabetes and insulin resistance syndromes are associated with an increased risk for cardiovascular and thrombotic complications. A disturbed balance between coagulation and fibrinolysis has been implicated in the pathogenesis hereof. To determine the selective effects of hyperglycemia and

  5. Deficiency of ATP-binding cassette transporters A1 and G1 in macrophages increases inflammation and accelerates atherosclerosis in mice.

    Science.gov (United States)

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

    2013-05-24

    Plasma high-density lipoprotein levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is attributable to the ability of high-density lipoprotein to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking. To assess the role of macrophage cholesterol efflux pathways in atherogenesis. We developed mice with efficient deletion of the ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1) in macrophages (MAC-ABC(DKO) mice) but not in hematopoietic stem or progenitor populations. MAC-ABC(DKO) bone marrow (BM) was transplanted into Ldlr(-/-) recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared with controls. On the Western-type diet, MAC-ABC(DKO) BM-transplanted Ldlr(-/-) mice had disproportionate atherosclerosis, considering they also had lower very low-density lipoprotein/low-density lipoprotein cholesterol levels than controls. ABCA1/G1-deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, Western-type diet-fed MAC-ABC(DKO) BM-transplanted Ldlr(-/-) mice displayed monocytosis and neutrophilia in the absence of hematopoietic stem and multipotential progenitor cells proliferation. Mechanistic studies revealed increased expressions of machrophage colony stimulating factor and granulocyte colony stimulating factor in splenic macrophage foam cells, driving BM monocyte and neutrophil production. These studies show that macrophage deficiency of ABCA1/G1 is proatherogenic likely by promoting plaque inflammation and uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways.

  6. A review of plant-based compounds and medicinal plants effective on atherosclerosis

    Directory of Open Access Journals (Sweden)

    Mehrnoosh Sedighi

    2017-01-01

    Full Text Available Atherosclerosis is one of the most important cardiovascular diseases that involve vessels through the development of fatty streaks and plaques. Plant-based compounds can help treat or prevent atherosclerosis through affecting the involved factors. The main purpose of this review article is to investigate and introduce medicinal plants and their potential activities regarding antioxidant properties, effective on lipids level and development of plaque, atherosclerosis, and progression of atherosclerosis as well as the development of cardiovascular disease and ischemia. To search for the relevant articles indexed in Information Sciences Institute, PubMed, Scientific Information Database, IranMedex, and Scopus between 1980 and 2013, with further emphasis on those indexed from 2004 to 2015, we used these search terms: atherosclerosis, antioxidant, cholesterol, inflammation, and the medicinal plants below. Then, the articles with inclusion criteria were used in the final analysis of the findings. Plant-based active compounds, including phenols, flavonoids, and antioxidants, can be effective on atherosclerosis predisposing factors and hence in preventing this disease and associated harmful complications, especially through reducing cholesterol, preventing increase in free radicals, and ultimately decreasing vascular plaque and vascular resistance. Hence, medicinal plants can contribute to treating atherosclerosis and preventing its progression through reducing cholesterolemia, free radicals, inflammation, vascular resistance, and certain enzymes. They, alone or in combination with hypocholesterolemic drugs, can therefore be useful for patients with hyperlipidemia and its complications.

  7. Arterial scleroproteins in atherosclerosis and hypertension (Experimental studies)

    International Nuclear Information System (INIS)

    Yurukova, Ts.; Georgiev, P.

    1979-01-01

    The authors studied the neosynthesis of fiber protein (scleroproteins) in the aorta of rats with genetic hypertension and with experimental atherosclerosis following application of 3 H-proline and 3 H-lysine and subsequent determination of radioactivity of the collagen and elastic fractions of the aortic wall. There was a great increase in incorporation of labelled collagen and elastin precursors in the aorta of hypertensive and atherosclerotic animals, in comparison with the control rats - a manifestation of incresed ''de novo'' synthesis of fiber proteins in rats with these arterial diseases. Furthermore, the increased collagenosis dominated over that of elastogenesis. The irregular activation of the biosynthesis of both scleroproteins in hypertensive rats and in rats with atherosclerosis caused remodelling of the macromolecular structure of the arterial wall with predominance of collagen over the remaining hypertension components and progression of atherosclerosis. (author) (author)

  8. Roles and Mechanisms of Obstructive Sleep Apnea-Hypopnea Syndrome and Chronic Intermittent Hypoxia in Atherosclerosis: Evidence and Prospective

    OpenAIRE

    Ma, Linqin; Zhang, Jingchun; Liu, Yue

    2016-01-01

    The morbidity and mortality of obstructive sleep apnea-hypopnea syndrome (OSAHS) are regarded as consequences of its adverse effects on the cardiovascular system. Chronic intermittent hypoxia (CIH) induced by OSAHS can result in vascular endothelial injury, thus promoting development of atherosclerosis (AS). Studies have shown that CIH is an independent risk factor for the occurrence and development of AS, but the underlying mechanism remains unclear. Here, we review clinical and fundamental ...

  9. Glycemic control in type 2 diabetes mellitus prevents coronary arterial wall infection

    Directory of Open Access Journals (Sweden)

    Morteza Izadi

    2014-05-01

    Full Text Available BACKGROUND: Diabetes mellitus (DM is a very well-known risk factor for development of atherosclerosis, and it has been hypothesized that poor glycemic control and hyperglycemia plays a major role in this process. In the current study, we aimed to evaluate the associates of poor glycemic control in Iranian patients who have already undergone coronary artery bypass grafting (CABG, with especial focus on the inhabitation of infectious agents within the coronary arterial wall. METHODS: In January 2010, 52 consecutive patients with type 2 DM who undergone CABG at the Department of Cardiovascular Surgery of Baqiyatallah University of Medical Sciences (Tehran, Iran were included into this cross-sectional study and biopsy specimens from their coronary plaques were taken and analyzed by polymerase chain reaction (PCR methods for detecting Helicobacter species, cytomegalovirus (CMV and Chlamydia pneumoniae, and their potential relation to the glycemic control status in these patients. RESULTS: Compared to that in diabetic patients with mean fasting blood sugar (FBS levels FBS < 126, atherosclerotic lesions in type 2 diabetic patients with poor glycemic control (FBS > 126 were significantly more likely to be positive for CMV PCR test (41% vs. 9%, respectively; P = 0.05. In laboratorial test results, mean triglyceride level was significantly higher among patients of poor glycemic control (168 ± 89 vs. 222 ± 125 mg/dl, respectively; P = 0.033. Hypertension was also significantly more prevalent in this population (73% vs. 36%, respectively; P = 0.034. CONCLUSION: Type 2 diabetic patients with poor glycemic control can be at higher risk for developing CMV infection in their coronary arterial wall, which can promote atherosclerosis formation process in this patient population. According to the findings of this study, we recommend better control of serum glucose levels in type 2 diabetic patients to prevent formation/progression of atherosclerosis.   Keywords

  10. The prevalence of new onset diabetes mellitus after renal transplantation in patients with immediate posttransplant hyperglycemia in a tertiary care centre

    Directory of Open Access Journals (Sweden)

    Saba Samad Memon

    2017-01-01

    Full Text Available Objectives: This study aimed to determine the prevalence of immediate posttransplant hyperglycemia and new onset diabetes after renal transplantation (NODAT. It also aims at answering whether posttransplant hyperglycemia per se is a risk factor for future development of NODAT. Methods: A retrospective study was conducted among patients undergoing kidney transplantation under a single surgical unit in a tertiary care hospital in the past 5 years. All known patients with diabetes were excluded from the study. Immediate postoperative hyperglycemia was defined as random blood sugar (RBS ≥200 mg/dl or requirement of insulin. NODAT was defined as fasting plasma glucose ≥126 mg/dl or RBS ≥200 mg/dl or if the patient is receiving therapy for glycemic control at 6 weeks or 3 months posttransplantation. Results: The study population included 191 patients. The overall prevalence of posttransplant hyperglycemia and NODAT was 31.4% and 26.7%, respectively. NODAT developed in 28 patients (46.7% of those who had posttransplant hyperglycemia. Thus, posttransplant hyperglycemia was associated with a fourfold increased risk of NODAT (P = 0.000. Posttransplant hyperglycemia was associated with increased infections (P = 0.04 and prolonged hospital stay (P = 0.0001. Increased age was a significant risk factor for NODAT (P = 0.000, whereas gender, acute rejection episodes, cadaveric transplant, hepatitis C virus status, human leukocyte antigen mismatch, and high calcineurin levels were not significantly associated with the future development of NODAT. Conclusion: The significant risk of NODAT posed by posttransplant hyperglycemia makes it prudent to follow up these patients more diligently in a resource-limited setting wherein routine monitoring in all patients is cumbersome.

  11. Stress-Induced Hyperglycemia, but Not Diabetic Hyperglycemia, Is Associated with Higher Mortality in Patients with Isolated Moderate and Severe Traumatic Brain Injury: Analysis of a Propensity Score-Matched Population.

    Science.gov (United States)

    Rau, Cheng-Shyuan; Wu, Shao-Chun; Chen, Yi-Chun; Chien, Peng-Chen; Hsieh, Hsiao-Yun; Kuo, Pao-Jen; Hsieh, Ching-Hua

    2017-11-03

    Background : Admission hyperglycemia is associated with higher morbidity and mortality in patients with traumatic brain injury (TBI). Stress-induced hyperglycemia (SIH), a form of hyperglycemia induced by the stress response, is associated with increased patient mortality following TBI. However, admission hyperglycemia occurs not only in SIH but also in patients with diabetic hyperglycemia (DH). Current information regarding whether trauma patients with SIH represent a distinct group with differential outcomes compared to those with DH remains limited. Methods : Serum glucose concentration ≥200 mg/dL upon arrival at the emergency department was defined as hyperglycemia. Presence of diabetes mellitus (DM) was determined by patient history and/or admission glycated hemoglobin (HbA1c) level ≥6.5%. In the present study, the patient cohort included those with moderate and severe TBI, as defined by an Abbreviated Injury Scale (AIS) score ≥3 points in the head, and excluded those who had additional AIS scores ≥3 points in any other region of the body. A total of 1798 adult patients with isolated moderate to severe TBI were allocated into four groups: SIH ( n = 140), DH ( n = 187), diabetic normoglycemia (DN, n = 186), and non-diabetic normoglycemia (NDN, n = 1285). Detailed patient information was retrieved from the Trauma Registry System at a level I trauma center between 1 January 2009, and 31 December 2015. Unpaired Student's t - and Mann-Whitney U -tests were used to analyze normally and non-normally distributed continuous data, respectively. Categorical data were compared using the Pearson chi-square or two-sided Fisher's exact tests. Matched patient populations were allocated in a 1:1 ratio according to propensity scores calculated by NCSS software. Logistic regression was used to evaluate the effect of SIH and DH on the adjusted mortality outcome. Results : In patients with isolated moderate to severe TBI, the presence of SIH and DH led to 9.1-fold and 2

  12. Atherosclerosis-Associated Endothelial Cell Apoptosis by MiR-429-Mediated Down Regulation of Bcl-2

    Directory of Open Access Journals (Sweden)

    Tao Zhang

    2015-10-01

    Full Text Available Background/Aims: Endothelial cell injury and subsequent apoptosis play a key role in the development and pathogenesis of atherosclerosis, which is hallmarked by dysregulated lipid homeostasis, aberrant immunity and inflammation, and plaque-instability-associated coronary occlusion. Nevertheless, our understanding of the mechanisms underlying endothelial cell apoptosis is still limited. MicroRNA-429 (miR-29 is a known cancer suppressor that promotes cancer cell apoptosis. However, it is unknown whether miR-429 may be involved in the development of atherosclerosis through similar mechanisms. We addressed these questions in the current study. Methods: We examined the levels of endothelial cell apoptosis in ApoE (-/- mice suppled with high-fat diet (HFD, a mouse model for atherosclerosis (simplified as HFD mice. We analyzed the levels of anti-apoptotic protein Bcl-2 and the levels of miR-429 in the purified CD31+ endothelial cells from mouse aorta. Prediction of the binding between miR-429 and 3'-UTR of Bcl-2 mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. The effects of miR-429 were further analyzed in an in vitro model using oxidized low-density lipoprotein (ox-LDL-treated human aortic endothelial cells (HAECs. Results: HFD mice developed atherosclerosis in 12 weeks, while the control ApoE (-/- mice that had received normal diet (simplified as NOR mice did not. HFD mice had significantly lower percentage of endothelial cells and significantly higher percentage of mesenchymal cells in the aorta than NOR mice. Significantly higher levels of endothelial cell apoptosis were detected in HFD mice, resulting from decreases in Bcl-2 protein, but not mRNA. The decreases in Bcl-2 in endothelial cells were due to increased levels of miR-429, which suppressed the translation of Bcl-2 mRNA via 3'-UTR binding. These in vivo findings were reproduced in vitro on ox-LDL-treated HAECs. Conclusion: Atherosclerosis

  13. The biology of atherosclerosis: general paradigms and distinct pathogenic mechanisms among HIV-infected patients.

    Science.gov (United States)

    Lo, Janet; Plutzky, Jorge

    2012-06-01

    Complications of atherosclerosis, including myocardial infarction and stroke, are the leading cause of death and disability worldwide. Recent data strongly implicate cardiovascular death as a contributor to mortality among patients with human immunodeficiency virus (HIV) infection, with evidence suggesting increased incidence of atherosclerosis among these patients. Therefore, greater understanding of atherosclerotic mechanisms and how these responses may be similar or distinct in HIV-infected patients is needed. Key concepts in atherosclerosis are reviewed, including the evidence that inflammation and abnormal metabolism are major drivers of atherosclerosis, and connected to the current literature regarding atherosclerosis in the context of HIV.

  14. Liraglutide Reduces Both Atherosclerosis and Kidney Inflammation in Moderately Uremic LDLr-/- Mice.

    Directory of Open Access Journals (Sweden)

    Line S Bisgaard

    Full Text Available Chronic kidney disease (CKD leads to uremia. CKD is characterized by a gradual increase in kidney fibrosis and loss of kidney function, which is associated with a progressive increase in risk of atherosclerosis and cardiovascular death. To prevent progression of both kidney fibrosis and atherosclerosis in uremic settings, insight into new treatment options with effects on both parameters is warranted. The GLP-1 analogue liraglutide improves glucose homeostasis, and is approved for treatment of type 2 diabetes. Animal studies suggest that GLP-1 also dampens inflammation and atherosclerosis. Our aim was to examine effects of liraglutide on kidney fibrosis and atherosclerosis in a mouse model of moderate uremia (5/6 nephrectomy (NX. Uremic (n = 29 and sham-operated (n = 14 atherosclerosis-prone low density lipoprotein receptor knockout mice were treated with liraglutide (1000 μg/kg, s.c. once daily or vehicle for 13 weeks. As expected, uremia increased aortic atherosclerosis. In the remnant kidneys from NX mice, flow cytometry revealed an increase in the number of monocyte-like cells (CD68+F4/80-, CD4+, and CD8+ T-cells, suggesting that moderate uremia induced kidney inflammation. Furthermore, markers of fibrosis (i.e. Col1a1 and Col3a1 were upregulated, and histological examinations showed increased glomerular diameter in NX mice. Importantly, liraglutide treatment attenuated atherosclerosis (~40%, p < 0.05 and reduced kidney inflammation in NX mice. There was no effect of liraglutide on expression of fibrosis markers and/or kidney histology. This study suggests that liraglutide has beneficial effects in a mouse model of moderate uremia by reducing atherosclerosis and attenuating kidney inflammation.

  15. Radiomodifying effect of hyperglycemia: correlation between a glucose dose and a tumor size

    International Nuclear Information System (INIS)

    Ul'yanenko, S.E.; Polityukova, N.A.

    1991-01-01

    Experiments were made on rats with trasplantable sarcoma-45 and sarcoma M-1. Dose correlation was established during a study of hyperglycemic radiomodifying action. Glucose injection at a dose of 6-17.5 g/kg was shown to enhance irradiation action. Glucose injection below or above these doses might cause worse radiotherapy results or even the death of animals. The best effect was obtained with small-size tumors. Large tumors(over 2 cm 3 ) were less sensitive to hyperglycemia combined with irradiation. Skin radioprotective action of hyperglycemia before irradiation increased with an increase in a dose

  16. Low-grade inflammation in young adults exposed to intrauterine hyperglycemia

    DEFF Research Database (Denmark)

    Kelstrup, Louise; Clausen, Tine Dalsgaard; Mathiesen, Elisabeth R

    2012-01-01

    AIM: To investigate associations between fetal exposure to intrauterine hyperglycemia and plasma concentrations of interleukin-6 (IL-6) and high sensitivity C-reactive protein (hs-CRP) in adult offspring. METHOD: We studied 597 offspring, aged 18-27years, from four different groups concerning...

  17. Hyperglycemia and subsequent torsades de pointes with marked QT prolongation during refeeding.

    Science.gov (United States)

    Nakashima, Takashi; Kubota, Tomoki; Takasugi, Nobuhiro; Kitagawa, Yuichiro; Yoshida, Takahiro; Ushikoshi, Hiroaki; Kawasaki, Masanori; Nishigaki, Kazuhiko; Ogura, Shinji; Minatoguchi, Shinya

    2017-01-01

    A fatal cardiac complication can occasionally present in malnourished patients during refeeding; this is known as refeeding syndrome. However, to our knowledge, hyperglycemia preceding torsades de pointes with QT prolongation during refeeding has not been reported. In the present study, we present a case in which hyperglycemia preceded torsades de pointes with QT prolongation during refeeding. The aim of this study was to determine the possible mechanism underlying QT prolongation during refeeding and indicate how to prevent it. A 32-y-old severely malnourished woman (body mass index 14.57 kg/m 2 ) was admitted to the intensive care unit of our institution after resuscitation from cardiopulmonary arrest due to ventricular fibrillation. She was diagnosed with anorexia nervosa. Although no obvious electrolyte abnormalities were observed, her blood glucose level was 11 mg/dL. A 12-lead electrocardiogram at admission showed sinus rhythm with normal QT interval (QTc 0.448). Forty mL of 50% glucose (containing 20 g of glucose) was intravenously injected, followed by a drip infusion of glucose to maintain blood glucose level within normal range. After 9 h, the patient's blood glucose level increased to 569 mg/dL. However, after 38 h, an episode of marked QT prolongation (QTc 0.931) followed by torsades de pointes developed. Hyperglycemia during refeeding can present with QT prolongation; consequently, monitoring blood glucose levels may be useful in avoiding hyperglycemia, which can result in QT prolongation. Furthermore, additional monitoring of QT intervals using a 12-lead electrocardiogram should allow the early detection of QT prolongation when glucose solution is administered to a malnourished patient with (severe) hypoglycemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. MicroRNA-30c Mimic Mitigates Hypercholesterolemia and Atherosclerosis in Mice*

    Science.gov (United States)

    Irani, Sara; Pan, Xiaoyue; Peck, Bailey C. E.; Iqbal, Jahangir; Sethupathy, Praveen; Hussain, M. Mahmood

    2016-01-01

    High plasma cholesterol levels are a major risk factor for atherosclerosis. Plasma cholesterol can be reduced by inhibiting lipoprotein production; however, this is associated with steatosis. Previously we showed that lentivirally mediated hepatic expression of microRNA-30c (miR-30c) reduced hyperlipidemia and atherosclerosis in mice without causing hepatosteatosis. Because viral therapy would be formidable, we examined whether a miR-30c mimic can be used to mitigate hyperlipidemia and atherosclerosis without inducing steatosis. Delivery of a miR-30c mimic to the liver diminished diet-induced hypercholesterolemia in C57BL/6J mice. Reductions in plasma cholesterol levels were significantly correlated with increases in hepatic miR-30c levels. Long term dose escalation studies showed that miR-30c mimic caused sustained reductions in plasma cholesterol with no obvious side effects. Furthermore, miR-30c mimic significantly reduced hypercholesterolemia and atherosclerosis in Apoe−/− mice. Mechanistic studies showed that miR-30c mimic had no effect on LDL clearance but reduced lipoprotein production by down-regulating microsomal triglyceride transfer protein expression. MiR-30c had no effect on fatty acid oxidation but reduced lipid synthesis. Additionally, whole transcriptome analysis revealed that miR-30c mimic significantly down-regulated hepatic lipid synthesis pathways. Therefore, miR-30c lowers plasma cholesterol and mitigates atherosclerosis by reducing microsomal triglyceride transfer protein expression and lipoprotein production and avoids steatosis by diminishing lipid syntheses. It mitigates atherosclerosis most likely by reducing lipoprotein production and plasma cholesterol. These findings establish that increasing hepatic miR-30c levels is a viable treatment option for reducing hypercholesterolemia and atherosclerosis. PMID:27365390

  19. Identifying novel genes for atherosclerosis through mouse-human comparative genetics

    NARCIS (Netherlands)

    Wang, XS; Ishimori, N; Korstanje, R; Rollins, J; Paigen, B

    Susceptibility to atherosclerosis is determined by both environmental and genetic factors. Its genetic determinants have been studied by use of quantitative- trait - locus ( QTL) analysis. So far, 21 atherosclerosis QTLs have been identified in the mouse: 7 in a high- fat - diet model only, 9 in a

  20. Prevalence and correlates of hyperglycemia in a rural population, Vietnam: implications from a cross–sectional study

    Directory of Open Access Journals (Sweden)

    Quang Binh Tran

    2012-11-01

    Full Text Available Abstract Background Despite the increasing prevalence of type 2 diabetes in urban areas, relatively little has been known about its actual prevalence and its associations in rural areas, Vietnam. The purpose of this study was to evaluate the prevalence of impaired fasting glucose (IFG, impaired glucose tolerance (IGT, diabetes and their risk factors in a rural province, Vietnam. Methods A cross–sectional study with a representative sample was designed to estimate the hyperglycemia prevalence, using 75–g oral glucose tolerance test. Potential risk factors for hyperglycemia were analyzed using multinomial logistic regression, taken into account influences of socio–economic status, anthropometric measures, and lifestyle–related factors. Results The age and sex–adjusted prevalence rates (95% CI of isolated IFG, isolated IGT, combined IFG–IGT, and diabetes were 8.7 (7.0–10.5, 4.3 (3.2−5.4, 1.6 (0.9−2.3, and 3.7% (2.7–4.7%, respectively. There were still 73% of diabetic subjects without knowing the condition. Blood pressure, family history of diabetes, obesity–related measures (waist circumference, waist–hip ratio, body fat percentage, and abdominal obesity were the independent risk factors for hyperglycemia (IFG, IGT, and diabetes. Conclusions The prevalence of hyperglycemia in rural areas has not been as sharply increased as that reported in urban cities, Vietnam. Blood pressure and obesity–related measures were the most significant predictors for hyperglycemia level and they can be taken into account in building prognosis models to early detection of diabetes in rural Vietnamese populations.

  1. A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo

    Directory of Open Access Journals (Sweden)

    Shi-Jie Zhang

    2016-02-01

    Full Text Available Gestational diabetes mellitus (GDM is one of the leading causes of fetal malformations. However, few models have been developed to study the underlying mechanisms of GDM-induced fetal eye malformation. In this study, a high concentration of glucose (0.2 mmol per egg was injected into the air sac of chick embryos on embryo development day (EDD 1 to develop a hyperglycemia model. Results showed that 47.3% of embryonic eye malformation happened on EDD 5. In this model, the key genes regulating eye development, Pax6, Six3 and Otx2, were downregulated by hyperglycemia. Among these genes, the expression of Pax6 was the most vulnerable to hyperglycemia, being suppressed by 70%. A reduction in Pax6 gene expression induced eye malformation in chick embryos. However, increased expression of Pax6 in chick embryos could rescue hyperglycemia-induced eye malformation. Hyperglycemia stimulated O-linked N-acetylglucosaminylation, which caused oxidative stress in chick embryos. Pax6 was found to be vulnerable to free radicals, but the antioxidant edaravone could restore Pax6 expression and reverse eye malformation. These results illustrated a successful establishment of a new chick embryo model to study the molecular mechanism of hyperglycemia-induced eye malformation. The suppression of the Pax6 gene is probably mediated by oxidative stress and could be a crucial target for the therapy of GDM-induced embryonic eye malformation.

  2. A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo.

    Science.gov (United States)

    Zhang, Shi-Jie; Li, Yi-Fang; Tan, Rui-Rong; Tsoi, Bun; Huang, Wen-Shan; Huang, Yi-Hua; Tang, Xiao-Long; Hu, Dan; Yao, Nan; Yang, Xuesong; Kurihara, Hiroshi; Wang, Qi; He, Rong-Rong

    2016-02-01

    Gestational diabetes mellitus (GDM) is one of the leading causes of fetal malformations. However, few models have been developed to study the underlying mechanisms of GDM-induced fetal eye malformation. In this study, a high concentration of glucose (0.2 mmol per egg) was injected into the air sac of chick embryos on embryo development day (EDD) 1 to develop a hyperglycemia model. Results showed that 47.3% of embryonic eye malformation happened on EDD 5. In this model, the key genes regulating eye development, Pax6, Six3 and Otx2, were downregulated by hyperglycemia. Among these genes, the expression of Pax6 was the most vulnerable to hyperglycemia, being suppressed by 70%. A reduction in Pax6 gene expression induced eye malformation in chick embryos. However, increased expression of Pax6 in chick embryos could rescue hyperglycemia-induced eye malformation. Hyperglycemia stimulated O-linked N-acetylglucosaminylation, which caused oxidative stress in chick embryos. Pax6 was found to be vulnerable to free radicals, but the antioxidant edaravone could restore Pax6 expression and reverse eye malformation. These results illustrated a successful establishment of a new chick embryo model to study the molecular mechanism of hyperglycemia-induced eye malformation. The suppression of the Pax6 gene is probably mediated by oxidative stress and could be a crucial target for the therapy of GDM-induced embryonic eye malformation. © 2016. Published by The Company of Biologists Ltd.

  3. Hyperglycemia decreases mitochondrial function: The regulatory role of mitochondrial biogenesis

    International Nuclear Information System (INIS)

    Palmeira, Carlos M.; Rolo, Anabela P.; Berthiaume, Jessica; Bjork, James A.; Wallace, Kendall B.

    2007-01-01

    Increased generation of reactive oxygen species (ROS) is implicated in 'glucose toxicity' in diabetes. However, little is known about the action of glucose on the expression of transcription factors in hepatocytes, especially those involved in mitochondrial DNA (mtDNA) replication and transcription. Since mitochondrial functional capacity is dynamically regulated, we hypothesized that stressful conditions of hyperglycemia induce adaptations in the transcriptional control of cellular energy metabolism, including inhibition of mitochondrial biogenesis and oxidative metabolism. Cell viability, mitochondrial respiration, ROS generation and oxidized proteins were determined in HepG2 cells cultured in the presence of either 5.5 mM (control) or 30 mM glucose (high glucose) for 48 h, 96 h and 7 days. Additionally, mtDNA abundance, plasminogen activator inhibitor-1 (PAI-1), mitochondrial transcription factor A (TFAM) and nuclear respiratory factor-1 (NRF-1) transcripts were evaluated by real time PCR. High glucose induced a progressive increase in ROS generation and accumulation of oxidized proteins, with no changes in cell viability. Increased expression of PAI-1 was observed as early as 96 h of exposure to high glucose. After 7 days in hyperglycemia, HepG2 cells exhibited inhibited uncoupled respiration and decreased MitoTracker Red fluorescence associated with a 25% decrease in mtDNA and 16% decrease in TFAM transcripts. These results indicate that glucose may regulate mtDNA copy number by modulating the transcriptional activity of TFAM in response to hyperglycemia-induced ROS production. The decrease of mtDNA content and inhibition of mitochondrial function may be pathogenic hallmarks in the altered metabolic status associated with diabetes

  4. Insulin decreases atherosclerosis by inducing endothelin receptor B expression

    DEFF Research Database (Denmark)

    Park, Kyoungmin; Mima, Akira; Li, Qian

    2016-01-01

    Endothelial cell (EC) insulin resistance and dysfunction, caused by diabetes, accelerates atherosclerosis. It is unknown whether specifically enhancing EC-targeted insulin action can decrease atherosclerosis in diabetes. Accordingly, overexpressing insulin receptor substrate-1 (IRS1...... induction of NO action, which increases endothelin receptor B (EDNRB) expression and intracellular [Ca(2+)]. Using the mice with knockin mutation of eNOS, which had Ser1176 mutated to alanine (AKI), deleting the only known mechanism for insulin to activate eNOS/NO pathway, we observed that IRS1...... overexpression in the endothelia of Aki/ApoE(-/-) mice significantly decreased atherosclerosis. Interestingly, endothelial EDNRB expression was selectively reduced in intima of arteries from diabetic patients and rodents. However, endothelial EDNRB expression was upregulated by insulin via P13K/Akt pathway...

  5. Atherosclerosis in familial lines of pigeons fed exogenous cholesterol.

    Science.gov (United States)

    Patton, N M; Brown, R V; Middleton, C C

    1975-01-01

    Exogenous cholesterol was fed to F1 pigeons of high and low serum cholesterol differentiated lines of White Carneau and Racing Homer pigeons that had previously been developed by selection and positive assortive mating. The serum cholesterol response of the various high and low lines was dependent upon the breed and the amount of cholesterol in the diet. Racing Homer pigeons were found to be more resistant to aortic atherosclerosis and more susceptible to coronary atherosclerosis than White Carneau pigeons. Data from necropsy examinations showed significant differences in both aortic and coronary atherosclerosis between lines within the White Carneau breed, but no differences between lines of the Racing Homer breed. Mean organ weights for the 4 lines of pigeons were reported.

  6. Nanomedicine for the prevention, treatment and imaging of atherosclerosis.

    Science.gov (United States)

    Psarros, Costas; Lee, Regent; Margaritis, Marios; Antoniades, Charalambos

    2012-09-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in developed countries, with an increasing prevalence due to an aging population. The pathology underpinning CVD is atherosclerosis, a chronic inflammatory state involving the arterial wall. Accumulation of low density lipoprotein (LDL) laden macrophages in the arterial wall and their subsequent transformation into foam cells lead to atherosclerotic plaque formation. Progression of atherosclerotic lesions may gradually lead to plaque related complications and clinically manifest as acute vascular syndromes including acute myocardial or cerebral ischemia. Nanotechnology offers emerging therapeutic strategies, which may have advantage overclassical treatments for atherosclerosis. In this review, we present the potential applications of nanotechnology toward prevention, identification and treatment of atherosclerosis. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. The Interaction Between IGF-1, Atherosclerosis and Vascular Aging

    Science.gov (United States)

    Higashi, Yusuke; Quevedo, Henry C.; Tiwari, Summit; Sukhanov, Sergiy; Shai, Shaw-Yung; Anwar, Asif; Delafontaine, Patrice

    2014-01-01

    The process of vascular aging encompasses alterations in the function of endothelial (EC) and vascular smooth muscle cells (VSMCs) via oxidation, inflammation, cell senescence and epigenetic modifications, increasing the probability of atherosclerosis. Aged vessels exhibit decreased endothelial antithrombogenic properties, increased reactive oxygen species (ROS) generation and inflammatory signaling, increased migration of VSMCs to the subintimal space, impaired angiogenesis and increased elastin degradation. The key initiating step in atherogenesis is subendothelial accumulation of apolipoprotein-B containing low density lipoproteins resulting in activation of endothelial cells and recruitment of monocytes. Activated endothelial cells secrete “chemokines” that interact with cognate chemokine receptors on monocytes and promote directional migration. Recruitment of immune cells establishes a pro-inflammatory status, further causing elevated oxidative stress, which in turn triggers a series of events including apoptotic or necrotic death of vascular and non-vascular cells. Increased oxidative stress is also considered to be a key factor in mechanisms of aging-associated changes in tissue integrity and function. Experimental evidence indicates that insulin-like growth factor-1 (IGF-1) exerts anti-oxidant, anti-inflammatory and pro-survival effects on the vasculature, reducing atherosclerotic plaque burden and promoting features of atherosclerotic plaque stability. PMID:24943302

  8. [Homocystein serum levels and lipid parameters in children with atherosclerosis risk factors].

    Science.gov (United States)

    Sierakowska-Fijałek, Anna; Kaczmarek, Piotr; Pokoca, Lech; Smorag, Ireneusz; Wosik-Erenbek, Marzenna; Baj, Zbigniew

    2007-02-01

    Atherosclerosis is a disease of adult patients, however, it begins in childhood and progresses from fatty streaks to raised lesions in arteries in adolescence and young adults. Clinical manifestation of atherosclerosis in adulthood depends on the risk factors such as: lipid disorders, obesity, hypertension, smoking habits and family history of CHD. High serum homocysteine concentration is increasingly recognised as a new risk factor for atherosclerosis and other vascular diseases. Atherogenic effect of homocystein is related to cytotoxin action on the endothelial cells and their function. The aim of this study was to estimate relations between the homocysteine serum concentration and the lipid levels in children with atherosclerosis risk factors. The study was carried out on 48 children with atherosclerosis risk factors. The control group consisted of 25 healthy childrens. Total cholesterol (TC), Triglycerides (TG), HDL-C, LDL-C were determined by enzymatic method. Concentration of homocysteine was estimated by immunoenzymatic method (ELISA). Obesity, lipid disorders, and hypertension were the most frequent risk factors in the investigated children. Statistically significant higher concentration of TC, LDL-C, TG and lower HDL-C were observed in children with atherosclerosis risk factors. No significant differences in homocystein concentration were observed in the investigated groups, but homocystein concentration was significantly higher in group of children with atherosclerosis risk factors. We observed that increased number of the risk factors is followed by high homocystein concentration in the serum.

  9. Results of using artificial hyperglycemia in chemoradiation treatment of patients with local spread cancer of oral cavity mucous membranes

    International Nuclear Information System (INIS)

    Puchinina, E.A.

    1990-01-01

    The comparative estimation of the recent results of chemoradiation therapy using artificial hyperglycemia of 115 patients with local spread cancer of the 3rd and 4th stages of body of the tongue and oral cavity mucous membranes is given. Optimal combinations of irradiation and hyperglycemia are determined. It is shown that the application of artificial hyperglycemia in chemoradiation treatment of cancer of oral cavity mucous membranes is reasonable and it provides an opportunity to improve the results, especially at the 3rd stage of cancer. 15 refs

  10. Contrast-induced nephrotoxicity: possible synergistic effect of stress hyperglycemia.

    LENUS (Irish Health Repository)

    O'Donnell, David H

    2010-07-01

    Oxidative stress on the renal tubules has been implicated as a mechanism of injury in both stress hyperglycemia and contrast-induced nephrotoxicity. The purpose of this study was to determine whether the combination of these effects has a synergistic effect on accentuating renal tubular apoptosis and therefore increasing the risk of contrast-induced nephrotoxicity.

  11. Retardation of fetal dendritic development induced by gestational hyperglycemia is associated with brain insulin/IGF-I signals.

    Science.gov (United States)

    Jing, Yu-Hong; Song, Yan-Feng; Yao, Ya-Ming; Yin, Jie; Wang, De-Gui; Gao, Li-Ping

    2014-10-01

    Hyperglycemia is an essential risk factor for mothers and fetuses in gestational diabetes. Clinical observation has indicated that the offspring of mothers with diabetes shows impaired somatosensory function and IQ. However, only a few studies have explored the effects of hyperglycemia on fetal brain development. Neurodevelopment is susceptible to environmental conditions. Thus, this study aims to investigate the effects of maternal hyperglycemia on fetal brain development and to evaluate insulin and insulin-like growth factor-I (IGF-I) signals in fetal brain under hyperglycemia or controlled hyperglycemia. At day 1 of pregnancy, gestational rats were intraperitoneally injected with streptozocin (60 mg/kg). Some of the hyperglycemic gestational rats were injected with insulin (20 IU, two times a day) to control hyperglycemia; the others were injected with saline of equal volume. The gestational rats were sacrificed at days 14, 16, and 18 of embryo development. The dendritic spines of subplate cortex neurons in the fetal brain were detected by Golgi-Cox staining. The mRNA levels of insulin receptors (IRs) and IGF-IR in the fetal brain were measured using qRT-PCR. The protein levels of synaptophysin, IR, and IGF-IR in the fetal brain were detected by western blot. No significant difference in fetal brain formation was observed between the maternal hyperglycemic group and insulin-treated group. By contrast, obvious retardation of dendritic development in the fetus was observed in the maternal hyperglycemic group. Similarly, synaptophysin expression was lower in the fetus of the maternal hyperglycemic group than in that of the insulin-treated group. The mRNA and protein expression levels of IRs in the fetal brain were higher in the hyperglycemic group than in the insulin-treated group. By contrast, the levels of IGF-IR in the brain were lower in the fetus of the maternal hyperglycemic group than in that of the insulin-treated group. These results suggested that

  12. Perspectives on diagnostic strategies for hyperglycemia in pregnancy - dealing with the barriers and challenges in China.

    Science.gov (United States)

    Wei, Yumei; Yang, Huixia

    2018-04-18

    Hyperglycemia is one of the most common medical conditions women encounter during pregnancy. Hyperglycemia in pregnancy (HIP) is an issue of increasing concern to both obstetricians and administrators and it brings health issues for both mothers and offspring, not only early complications, but also long-term effects. HIP may either have been pre-gestational diabetes mellitus (pGDM), or gestational diabetes mellitus (GDM). After two-child policy fully carried out in China, the incidence of HIP would be increased further. There are many important issues such as the high prevalence of DM misdiagnosis, the diagnostic criteria of GDM, the strategies of GDM management in China need to deal with. We would focus on the barriers and challenges of diagnostic strategies for hyperglycemia in pregnancy in China. Copyright © 2018. Published by Elsevier B.V.

  13. Endothelial activation, endothelial dysfunction and premature atherosclerosis in systemic autoimmune diseases

    NARCIS (Netherlands)

    Bijl, M

    Atherosclerosis may be considered an inflammatory disease characterised by the development of atherosclerotic plaques and ischaemic cardiovascular events. Increased prevalence of cardiovascular morbidity and mortality due to (premature) atherosclerosis has been observed in patients with autoimmune

  14. A quantitative approach of abdominal aortic atherosclerosis with x-ray computed tomography

    International Nuclear Information System (INIS)

    Watanabe, Hiromi; Kubota, Kazuo; Ito, Kengo; Ono, Shuichi; Matsuzawa, Taiju

    1983-01-01

    Currently epidemiologic studies of aortic atherosclerosis are most commonly done by the conventional roentgenological or pathological methods before and after death respectively. Pathological method is difficult and only possible after death. Roentgenological method is simple and useful before death, but its inability to evaluate atherosclerosis in a constant manner is serious drawback. A simple and quantitative method for epidemiological and clinical study of atherosclerosis has been needed. It this study, we examined the usefulness of Calcification Index (C.I.) caliculated from CT films for the evaluation of abdominal aortic atherosclerosis. We analysed 42 patients (32 males, 10 females). They recieved abdominal CT examination and died within a year. First, we got C.I. from their CT films. Then we got Surface Involved (S.I.) of atherosclerotic lesion from their autopsied abdominal aorta with pathological observation. The correlation coefficient between C.I. and S.I. was 0.83 (p<0.001). So we may use C.I. for the evaluation of abdominal aortic atherosclerosis. (author)

  15. Hematocrit is associated with carotid atherosclerosis in men but not in women.

    Science.gov (United States)

    Irace, Concetta; Ciamei, Monica; Crivaro, Andrea; Fiaschi, Elio; Madia, Angela; Cortese, Claudio; Gnasso, Agostino

    2003-06-01

    It is known that blood and plasma viscosities are associated with clinical manifestations of atherosclerosis, though evidence is not conclusive particularly in women. To verify whether hematocrit and blood and plasma viscosities are independently associated with carotid atherosclerosis and whether their measurement can improve the definition of the global coronary heart disease (CHD) risk. Eight hundred and ninety-two participants in a cardiovascular disease prevention campaign were examined with regard to conventional CHD risk factors (age, blood pressure, lipids, glucose, body mass index, waist/hip ratio, cigarette smoking and diabetes), hematocrit and blood and plasma viscosities. According to the degree of carotid atherosclerosis, investigated by echo-Doppler, participants were divided in three groups: those without atherosclerosis, those with a low degree of atherosclerosis and those with a high degree of atherosclerosis. In men, age, blood pressure, intima-media thickness (IMT), hematocrit (47.4+/-3.7%, 47.8+/-3.7%, 48.4+/-3.7%, Pviscosity (4.69+/-0.51 cP, 4.77+/-0.55 cP, 4.82+/-0.51 cP, P=0.05) increased with increasing degree of carotid atherosclerosis. In women, age, blood pressure, total cholesterol and low-density lipoprotein-cholesterol, IMT and plasma viscosity (1.42+/-0.12 cP, 1.44+/-0.11 cP, 1.46+/-0.13 cP, Pviscosity was no longer different in the three groups. In discriminant analysis, hematocrit, among the hemorheological variables investigated, was independently associated with carotid score in men (F=3.66, Pviscosities were significantly associated with carotid score in women. These findings suggest that in men, both hematocrit and blood viscosity are related to carotid atherosclerosis but hematocrit would appear to have an independent effect over and above that mediated by viscosity.

  16. MicroRNA-30c Mimic Mitigates Hypercholesterolemia and Atherosclerosis in Mice.

    Science.gov (United States)

    Irani, Sara; Pan, Xiaoyue; Peck, Bailey C E; Iqbal, Jahangir; Sethupathy, Praveen; Hussain, M Mahmood

    2016-08-26

    High plasma cholesterol levels are a major risk factor for atherosclerosis. Plasma cholesterol can be reduced by inhibiting lipoprotein production; however, this is associated with steatosis. Previously we showed that lentivirally mediated hepatic expression of microRNA-30c (miR-30c) reduced hyperlipidemia and atherosclerosis in mice without causing hepatosteatosis. Because viral therapy would be formidable, we examined whether a miR-30c mimic can be used to mitigate hyperlipidemia and atherosclerosis without inducing steatosis. Delivery of a miR-30c mimic to the liver diminished diet-induced hypercholesterolemia in C57BL/6J mice. Reductions in plasma cholesterol levels were significantly correlated with increases in hepatic miR-30c levels. Long term dose escalation studies showed that miR-30c mimic caused sustained reductions in plasma cholesterol with no obvious side effects. Furthermore, miR-30c mimic significantly reduced hypercholesterolemia and atherosclerosis in Apoe(-/-) mice. Mechanistic studies showed that miR-30c mimic had no effect on LDL clearance but reduced lipoprotein production by down-regulating microsomal triglyceride transfer protein expression. MiR-30c had no effect on fatty acid oxidation but reduced lipid synthesis. Additionally, whole transcriptome analysis revealed that miR-30c mimic significantly down-regulated hepatic lipid synthesis pathways. Therefore, miR-30c lowers plasma cholesterol and mitigates atherosclerosis by reducing microsomal triglyceride transfer protein expression and lipoprotein production and avoids steatosis by diminishing lipid syntheses. It mitigates atherosclerosis most likely by reducing lipoprotein production and plasma cholesterol. These findings establish that increasing hepatic miR-30c levels is a viable treatment option for reducing hypercholesterolemia and atherosclerosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Effects of dietary calcium on atherosclerosis, aortic calcification, and icterus in rabbits fed a supplemental cholesterol diet

    Directory of Open Access Journals (Sweden)

    Culley Nathan C

    2006-06-01

    Full Text Available Abstract Background Vascular calcification is implicated in myocardial infarction, instability and rigidity of the aortic wall, and bioprosthetic failures. Although an increase in the calcium (Ca content in atherogenic diets has been shown to decrease atherosclerosis in rabbits, whether Ca supplementation and deficiency can affect atherosclerosis-related aortic calcification remains unknown. Results New Zealand White male rabbit littermates were fed an atherogenic diet containing 0.5% cholesterol and 2% peanut oil. The Ca content of the diet, which normally contains 1%, was adjusted to 0.5 or 3%. Segments of thoracic aortas were dissected from rabbits for histological evaluations and Ca and Pi determinations. Rabbits with calcium supplementation were maintained for 4 months, whereas those with calcium deficiency were maintained for 2 1/2 months due to severe icterus beyond this stage. The ratios of intimal to medial areas and calcified to intimal areas were used to semi-quantify lesion accumulation and calcification, respectively. Icterus was estimated from the extent of yellowing of the skin, sclera, and mucous membranes along with gross evidence of hepatic lipidosis and/or biliary obstructions. Statistical analysis of 16 matched littermates shows that Ca supplementation significantly decreased the lesions by 41% (p Conclusion Ca supplementation to an atherogenic diet inhibits atherosclerosis, aortic calcification, and icterus, whereas a Ca deficient-diet promotes them.

  18. Protective Effects of Hydroxychloroquine against Accelerated Atherosclerosis in Systemic Lupus Erythematosus

    Science.gov (United States)

    Cauli, Alberto

    2018-01-01

    Cardiovascular (CV) morbidity and mortality are a challenge in management of patients with systemic lupus erythematosus (SLE). Higher risk of CV disease in SLE patients is mostly related to accelerated atherosclerosis. Nevertheless, high prevalence of traditional cardiovascular risk factors in SLE patients does not fully explain the increased CV risk. Despite the pathological bases of accelerated atherosclerosis are not fully understood, it is thought that this process is driven by the complex interplay between SLE and atherosclerosis pathogenesis. Hydroxychloroquine (HCQ) is a cornerstone in treatment of SLE patients and has been thought to exert a broad spectrum of beneficial effects on disease activity, prevention of damage accrual, and mortality. Furthermore, HCQ is thought to protect against accelerated atherosclerosis targeting toll-like receptor signaling, cytokine production, T-cell and monocyte activation, oxidative stress, and endothelial dysfunction. HCQ was also described to have beneficial effects on traditional CV risk factors, such as dyslipidemia and diabetes. In conclusion, despite lacking randomized controlled trials unambiguously proving the protection of HCQ against accelerated atherosclerosis and incidence of CV events in SLE patients, evidence analyzed in this review is in favor of its beneficial effect. PMID:29670462

  19. The Prebiotic Inulin Aggravates Accelerated Atherosclerosis in Hypercholesterolemic APOE*3-Leiden Mice.

    Science.gov (United States)

    Hoving, Lisa R; de Vries, Margreet R; de Jong, Rob C M; Katiraei, Saeed; Pronk, Amanda; Quax, Paul H A; van Harmelen, Vanessa; Willems van Dijk, Ko

    2018-02-03

    The prebiotic inulin has proven effective at lowering inflammation and plasma lipid levels. As atherosclerosis is provoked by both inflammation and hyperlipidemia, we aimed to determine the effect of inulin supplementation on atherosclerosis development in hypercholesterolemic APOE*3-Leiden ( E3L ) mice. Male E3L mice were fed a high-cholesterol (1%) diet, supplemented with or without 10% inulin for 5 weeks. At week 3, a non-constrictive cuff was placed around the right femoral artery to induce accelerated atherosclerosis. At week 5, vascular pathology was determined by lesion thickness, vascular remodeling, and lesion composition. Throughout the study, plasma lipids were measured and in week 5, blood monocyte subtypes were determined using flow cytometry analysis. In contrast to our hypothesis, inulin exacerbated atherosclerosis development, characterized by increased lesion formation and outward vascular remodeling. The lesions showed increased number of macrophages, smooth muscle cells, and collagen content. No effects on blood monocyte composition were found. Inulin significantly increased plasma total cholesterol levels and total cholesterol exposure. In conclusion, inulin aggravated accelerated atherosclerosis development in hypercholesterolemic E3L mice, accompanied by adverse lesion composition and outward remodeling. This process was not accompanied by differences in blood monocyte composition, suggesting that the aggravated atherosclerosis development was driven by increased plasma cholesterol.

  20. The Prebiotic Inulin Aggravates Accelerated Atherosclerosis in Hypercholesterolemic APOE*3-Leiden Mice

    Directory of Open Access Journals (Sweden)

    Lisa R. Hoving

    2018-02-01

    Full Text Available The prebiotic inulin has proven effective at lowering inflammation and plasma lipid levels. As atherosclerosis is provoked by both inflammation and hyperlipidemia, we aimed to determine the effect of inulin supplementation on atherosclerosis development in hypercholesterolemic APOE*3-Leiden (E3L mice. Male E3L mice were fed a high-cholesterol (1% diet, supplemented with or without 10% inulin for 5 weeks. At week 3, a non-constrictive cuff was placed around the right femoral artery to induce accelerated atherosclerosis. At week 5, vascular pathology was determined by lesion thickness, vascular remodeling, and lesion composition. Throughout the study, plasma lipids were measured and in week 5, blood monocyte subtypes were determined using flow cytometry analysis. In contrast to our hypothesis, inulin exacerbated atherosclerosis development, characterized by increased lesion formation and outward vascular remodeling. The lesions showed increased number of macrophages, smooth muscle cells, and collagen content. No effects on blood monocyte composition were found. Inulin significantly increased plasma total cholesterol levels and total cholesterol exposure. In conclusion, inulin aggravated accelerated atherosclerosis development in hypercholesterolemic E3L mice, accompanied by adverse lesion composition and outward remodeling. This process was not accompanied by differences in blood monocyte composition, suggesting that the aggravated atherosclerosis development was driven by increased plasma cholesterol.

  1. Proliferating macrophages prevail in atherosclerosis.

    Science.gov (United States)

    Randolph, Gwendalyn J

    2013-09-01

    Macrophages accumulate in atherosclerotic lesions during the inflammation that is part of atherosclerosis development and progression. A new study in mice indicates that the accumulation of macrophages in atherosclerotic plaques depends on local macrophage proliferation rather than the recruitment of circulating monocytes.

  2. Effect of uremia on HDL composition, vascular inflammation, and atherosclerosis in wild-type mice

    DEFF Research Database (Denmark)

    Bang, Christian A; Bro, Susanne; Bartels, Emil D

    2007-01-01

    Wild-type mice normally do not develop atherosclerosis, unless fed cholic acid. Uremia is proinflammatory and increases atherosclerosis 6- to 10-fold in apolipoprotein E-deficient mice. This study examined the effect of uremia on lipoproteins, vascular inflammation, and atherosclerosis in wild...... in cholic acid-fed sham mice. The results suggest that moderate uremia neither induces aortic inflammation nor atherosclerosis in C57BL/6J mice despite increased LDL/HDL cholesterol ratio and altered HDL composition....

  3. Dietary hyperglycemia, glycemic index and age-related metabolic retinal diseases

    Science.gov (United States)

    The glycemic index (GI) indicates how fast blood glucose is raised after consuming a carbohydrate-containing food. Human metabolic studies indicate that GI is related to patho-physiological responses after meals. Compared with a low-GI meal, a high-GI meal is characterized with hyperglycemia during ...

  4. Short-term hyperglycemia increases endothelial glycocalyx permeability and acutely decreases lineal density of capillaries with flowing red blood cells

    NARCIS (Netherlands)

    Zuurbier, Coert J.; Demirci, Cihan; Koeman, Anneke; Vink, Hans; Ince, Can

    2005-01-01

    Hyperglycemia is becoming recognized as an important risk factor for microvascular dysfunction. We hypothesized that short-term hyperglycemia, either on the scale of hours or weeks, alters the barrier function and the volume of the endothelial glycocalyx and decreases functional capillary density

  5. Innate lymphoid cells in atherosclerosis.

    Science.gov (United States)

    Engelbertsen, Daniel; Lichtman, Andrew H

    2017-12-05

    The family of innate lymphoid cells (ILCs) consisting of NK cells, lymphoid tissue inducer cells and the 'helper'-like ILC subsets ILC1, ILC2 and ILC3 have been shown to have important roles in protection against microbes, regulation of inflammatory diseases and involved in allergic reactions. ILC1s produce IFN-γ upon stimulation with IL-12 and IL-18, ILC2s produce IL-5 and IL-13 responding to IL-33 and IL-25 while ILC3s produce IL-17 and IL-22 after stimulation with IL-23 or IL-1. Although few studies have directly investigated the role for ILCs in atherosclerosis, several studies have investigated transcription factors and cytokines shared by ILCs and T helper cells. In this review we summarize our current understanding of the role of ILC in atherosclerosis and discuss future directions. Copyright © 2017. Published by Elsevier B.V.

  6. A pilot study into measurements of markers of atherosclerosis in periodontitis

    NARCIS (Netherlands)

    Leivadaros, E; van der Velden, U; Bizzarro, S; ten Heggeler, JMAG; Gerdes, VEA; Hoek, FJ; Nagy, TOM; Scholma, J; Bakker, SJL; Gans, ROB; ten Cate, H; Loos, BG

    Background: Periodontitis may be a possible risk factor for atherosclerosis. The current pilot study explored arterial wall thickness and other variables associated with atherosclerosis in healthy subjects with and without periodontitis. Methods: Patients with moderate (N = 34) and severe

  7. Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease

    Science.gov (United States)

    Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

    2016-01-01

    Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI. PMID:27034930

  8. Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Sheila Marques Fernandes

    2016-01-01

    Full Text Available Iodinated contrast (IC is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI. Chronic kidney disease (CKD and chronic hyperglycemia (CH are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH; Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI.

  9. Redox balance and blood elemental levels in atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Napoleao, P. [Centro de Biologia Ambiental and Departamento de Biologia Animal, Faculdade de Ciencias de Lisboa, C2, Campo Grande, 1749-016 Lisbon (Portugal) and Laboratorio de Feixes de Ioes, Instituto Tecnologico e Nuclear, E.N. no 10, 2685-953 Sacavem (Portugal)]. E-mail: pnapoleao@itn.pt; Lopes, P.A. [Centro de Biologia Ambiental and Departamento de Biologia Animal, Faculdade de Ciencias de Lisboa, C2, Campo Grande, 1749-016 Lisbon (Portugal); Santos, M. [Centro de Quimica e Bioquimica and Departamento de Quimica e Bioquimica, Faculdade de Ciencias de Lisboa, 1749-016 Lisbon (Portugal); Steghens, J.-P. [Federation de Biochimie, Hopital Edouard Herriot, 3 Place d' Arsonval, 69437 03 Lyon (France); Viegas-Crespo, A.M. [Centro de Biologia Ambiental and Departamento de Biologia Animal, Faculdade de Ciencias de Lisboa, C2, Campo Grande, 1749-016 Lisbon (Portugal); Pinheiro, T. [Laboratorio de Feixes de Ioes, Instituto Tecnologico e Nuclear, E.N. no 10, 2685-953 Sacavem (Portugal); Centro de Fisica Nuclear, Universidade de Lisboa, Av. Prof. Egas Moniz, 1700 Lisbon (Portugal)

    2006-08-15

    Oxidation of lipids and proteins represents a causative event for atherogenesis, which can be opposed by antioxidant activity. Elements, such as, Fe, Cu, Zn and Se can be involved in both mechanisms. Thus, evaluation of blood elemental levels, easily detected by PIXE, and of redox parameters may be useful in assessing the risk of atherosclerosis. A group of stable patients suffering from atherosclerosis, was matched with a cohort of normo-tensive and -lipidemic volunteers. Although no major discrepancies were observed for trace elemental levels in blood, increased concentrations of K and Ca were found in atherosclerotic group. Patients presented enhance levels of antioxidant ({alpha}-tocopherol) and decreased of protein oxidation (protein carbonyls), while for the lipid oxidation marker (malondialdehyde) no variation was observed. This study contributes to a better understanding of atherosclerosis development and its relationship with blood elemental levels, and set basis for further clinical trials with pathological groups in acute phase.

  10. Circumflex coronary artery with aberrant origin and atherosclerosis

    International Nuclear Information System (INIS)

    Ozcan, E.; Bozlar, U.; Celik, T.; Tasar, M.

    2012-01-01

    Full text: Introduction: Circumflex (Cx) coronary artery congenital anomaly is reported to be less than 1% incidence. Coronary arteries with aberrant origin are more likely to have atherosclerosis according to some published literatures. Objectives and tasks: In this study we aim to present computed tomography (CT) angiography findings of a patient, who has Cx artery with aberrant origin and atherosclerotic. Materials and methods: 57-year-old woman without any symptoms who has risk factors to atherosclerosis was referred to our clinic for coronary CT angiography. Results: In CT angiography; we detected Cx coronary artery with aberrant origin (right sinus of valsalva) and retroaortic course. Also we saw intimal irregularities and calcified plaque causing severe narrowing in the proximal segment of artery. Right coronary and left anterior descendant arteries had mild atherosclerosis. Conclusion: Coroner CT angiography, which allows multiplanar imaging with high resolution, is an effective diagnostic tool for coronary artery disease, like not only congenital anomalies but also acquired atherosclerotic disease

  11. A pilot study into measurements of markers of atherosclerosis in periodontitis

    NARCIS (Netherlands)

    Leivadaros, Efstratios; van der Velden, Ubele; Bizzarro, Sergio; ten Heggeler, Johanna M. A. G.; Gerdes, Victor E. A.; Hoek, Frans J.; Nagy, Thomas O. M.; Scholma, Jose; Bakker, Stephan J. L.; Gans, Rijk O. B.; ten Cate, Hugo; Loos, Bruno G.

    2005-01-01

    Periodontitis may be a possible risk factor for atherosclerosis. The current pilot study explored arterial wall thickness and other variables associated with atherosclerosis in healthy subjects with and without periodontitis. Patients with moderate (N = 34) and severe periodontitis (N = 15) and

  12. Hyperglycemia acutely lowers the postprandial excursions of glucagon-like Peptide-1 and gastric inhibitory polypeptide in humans

    DEFF Research Database (Denmark)

    Vollmer, Kirsten; Gardiwal, Husai; Menge, Bjoern A

    2009-01-01

    INTRODUCTION: Impaired secretion of glucagon-like peptide 1 (GLP-1) has been suggested to contribute to the deficient incretin effect in patients with type 2 diabetes. It is unclear whether this is a primary defect or a consequence of the hyperglycemia in type 2 diabetes. We examined whether acute...... hyperglycemia reduces the postprandial excursions of gastric inhibitory polypeptide (GIP) and GLP-1, and if so, whether this can be attributed to changes in gastric emptying. PATIENTS AND METHODS: Fifteen nondiabetic individuals participated in a euglycemic clamp and a hyperglycemic clamp experiment, carried...... the hyperglycemic clamp experiments and 83 +/- 3 mg/dl during the euglycemia (P hyperglycemia, but meal ingestion led to a decline in glucose requirements in both experiments (P

  13. Even a Chronic Mild Hyperglycemia Affects Membrane Fluidity and Lipoperoxidation in Placental Mitochondria in Wistar Rats

    Science.gov (United States)

    Figueroa-García, María del Consuelo; Espinosa-García, María Teresa; Martinez-Montes, Federico; Palomar-Morales, Martín; Mejía-Zepeda, Ricardo

    2015-01-01

    It is known the deleterious effects of diabetes on embryos, but the effects of diabetes on placenta and its mitochondria are still not well known. In this work we generated a mild hyperglycemia model in female wistar rats by intraperitoneal injection of streptozotocin in 48 hours-old rats. The sexual maturity onset of the female rats was delayed around 6–7 weeks and at 16 weeks-old they were mated, and sacrificed at day 19th of pregnancy. In placental total tissue and isolated mitochondria, the fatty acids composition was analyzed by gas chromatography, and lipoperoxidation was measured by thiobarbituric acid reactive substances. Membrane fluidity in mitochondria was measured with the excimer forming probe dipyrenylpropane and mitochondrial function was measured with a Clark-type electrode. The results show that even a chronic mild hyperglycemia increases lipoperoxidation and decreases mitochondrial function in placenta. Simultaneously, placental fatty acids metabolism in total tissue is modified but in a different way than in placental mitochondria. Whereas the chronic mild hyperglycemia induced a decrease in unsaturated to saturated fatty acids ratio (U/S) in placental total tissue, the ratio increased in placental mitochondria. The measurements of membrane fluidity showed that fluidity of placenta mitochondrial membranes increased with hyperglycemia, showing consistency with the fatty acids composition through the U/S index. The thermotropic characteristics of mitochondrial membranes were changed, showing lower transition temperature and activation energies. All of these data together demonstrate that even a chronic mild hyperglycemia during pregnancy of early reproductive Wistar rats, generates an increment of lipoperoxidation, an increase of placental mitochondrial membrane fluidity apparently derived from changes in fatty acids composition and consequently, mitochondrial malfunction. PMID:26630275

  14. Obesity and Hyperglycemia in Korean Men with Klinefelter Syndrome: The Korean Endocrine Society Registry

    Directory of Open Access Journals (Sweden)

    Seung Jin Han

    2016-12-01

    Full Text Available BackgroundThe aim of this study was to investigate the prevalence of obesity in Korean men with Klinefelter syndrome (KS and the associated risk factors for obesity and hyperglycemia.MethodsData were collected retrospectively from medical records from 11 university hospitals in Korea between 1994 and 2014. Subjects aged ≥18 years with newly diagnosed KS were enrolled. The following parameters were recorded at baseline before treatment: chief complaint, height, weight, fasting glucose level, lipid panel, blood pressure, testosterone, luteinizing hormone, follicle-stimulating hormone, karyotyping patterns, and history of hypertension, diabetes, and dyslipidemia.ResultsData were analyzed from 376 of 544 initially enrolled patients. The rate of the 47 XXY chromosomal pattern was 94.1%. The prevalence of obesity (body mass index ≥25 kg/m2 in Korean men with KS was 42.6%. The testosterone level was an independent risk factor for obesity and hyperglycemia.ConclusionObesity is common in Korean men with KS. Hypogonadism in patients with KS was associated with obesity and hyperglycemia.

  15. Recent advances in lipoprotein and atherosclerosis: A nutrigenomic approach

    OpenAIRE

    López, Sergio; Ortega, Almudena; Varela, Lourdes; Bermúdez, Beatriz; Muriana, Francisco JG; Abia, Rocío

    2009-01-01

    Atherosclerosis is a disease in which multiple factors contribute to the degeneration of the vascular wall. Many risk factors have been identified as having influence on the progression of atherosclerosis among them, the type of diet. Multifactorial interaction among lipoproteins, vascular wall cells, and inflammatory mediators has been recognised as the basis of atherogenesis. Dietary intake affects lipoprotein concentration and composition providing risk or protection at several stages of a...

  16. Implications of alcoholic cirrhosis in atherosclerosis of autopsied patients

    OpenAIRE

    Silveira, Luciano Alves Matias da; Torquato, Bianca Gonçalves Silva; Oliveira, Mariana Silva; Juliano, Guilherme Ribeiro; Oliveira, Lívia Ferreira; Cavellani, Camila Lourencini; Ramalho, Luciana Santos; Espindula, Ana Paula; Teixeira, Vicente de Paula Antunes; Ferraz, Mara Lúcia Fonseca

    2017-01-01

    Summary Introduction: Alcoholism is a major public health problem, which has a high social cost and affects many aspects of human activity. Liver disease is one of the first consequences of alcohol abuse, and steatosis, liver cirrhosis and hepatitis may occur. Other organs are also affected with pathological changes, such as pancreatitis, cardiomyopathies, dyslipidemias and atherosclerosis. Objective: To identify the occurrence and degree of atherosclerosis in alcohol-dependent individuals ...

  17. [¹⁸F]-fluorodeoxyglucose PET imaging of atherosclerosis

    DEFF Research Database (Denmark)

    Blomberg, Björn Alexander; Høilund-Carlsen, Poul Flemming

    2015-01-01

    [(18)F]-fluorodeoxyglucose PET ((18)FDG PET) imaging has emerged as a promising tool for assessment of atherosclerosis. By targeting atherosclerotic plaque glycolysis, a marker for plaque inflammation and hypoxia, (18)FDG PET can assess plaque vulnerability and potentially predict risk...... of atherosclerosis-related disease, such as stroke and myocardial infarction. With excellent reproducibility, (18)FDG PET can be a surrogate end point in clinical drug trials, improving trial efficiency. This article summarizes key findings in the literature, discusses limitations of (18)FDG PET imaging...

  18. Reduction of mouse atherosclerosis by urokinase inhibition or with a limited-spectrum matrix metalloproteinase inhibitor

    DEFF Research Database (Denmark)

    Hu, Jie Hong; Touch, Phanith; Zhang, Jingwan

    2015-01-01

    -accelerated atherosclerosis) to investigate whether systemic inhibition of proteolytic activity of uPA or a subset of MMPs can reduce protease-induced atherosclerosis and aortic dilation. METHODS AND RESULTS: SR-uPA mice were fed a high-fat diet for 10 weeks and treated either with an antibody inhibiting mouse uPA (mU1...... surface lesion coverage. Several lines of evidence identified MMP-13 as a mediator of uPA-induced aortic MMP activity. CONCLUSIONS: Pharmacological inhibition of either uPA or selected MMPs decreased atherosclerosis in SR-uPA mice. uPA inhibition decreased aortic dilation. Differential effects of both...... agents on aortic root vs. distal aortic atherosclerosis suggest prevention of atherosclerosis progression vs. initiation. Systemic inhibition of uPA or a subset of MMPs shows promise for treating atherosclerosis....

  19. β3-Adrenoceptor activation relieves oxidative inhibition of the cardiac Na+-K+ pump in hyperglycemia induced by insulin receptor blockade.

    Science.gov (United States)

    Karimi Galougahi, Keyvan; Liu, Chia-Chi; Garcia, Alvaro; Fry, Natasha A; Hamilton, Elisha J; Figtree, Gemma A; Rasmussen, Helge H

    2015-09-01

    Dysregulated nitric oxide (NO)- and superoxide (O2 (·-))-dependent signaling contributes to the pathobiology of diabetes-induced cardiovascular complications. We examined if stimulation of β3-adrenergic receptors (β3-ARs), coupled to endothelial NO synthase (eNOS) activation, relieves oxidative inhibition of eNOS and the Na(+)-K(+) pump induced by hyperglycemia. Hyperglycemia was established in male New Zealand White rabbits by infusion of the insulin receptor antagonist S961 for 7 days. Hyperglycemia increased tissue and blood indexes of oxidative stress. It induced glutathionylation of the Na(+)-K(+) pump β1-subunit in cardiac myocytes, an oxidative modification causing pump inhibition, and reduced the electrogenic pump current in voltage-clamped myocytes. Hyperglycemia also increased glutathionylation of eNOS, which causes its uncoupling, and increased coimmunoprecipitation of cytosolic p47(phox) and membranous p22(phox) NADPH oxidase subunits, consistent with NADPH oxidase activation. Blocking translocation of p47(phox) to p22(phox) with the gp91ds-tat peptide in cardiac myocytes ex vivo abolished the hyperglycemia-induced increase in glutathionylation of the Na(+)-K(+) pump β1-subunit and decrease in pump current. In vivo treatment with the β3-AR agonist CL316243 for 3 days eliminated the increase in indexes of oxidative stress, decreased coimmunoprecipitation of p22(phox) with p47(phox), abolished the hyperglycemia-induced increase in glutathionylation of eNOS and the Na(+)-K(+) pump β1-subunit, and abolished the decrease in pump current. CL316243 also increased coimmunoprecipitation of glutaredoxin-1 with the Na(+)-K(+) pump β1-subunit, which may reflect facilitation of deglutathionylation. In vivo β3-AR activation relieves oxidative inhibition of key cardiac myocyte proteins in hyperglycemia and may be effective in targeting the deleterious cardiac effects of diabetes. Copyright © 2015 the American Physiological Society.

  20. Carotid body denervation prevents fasting hyperglycemia during chronic intermittent hypoxia.

    Science.gov (United States)

    Shin, Mi-Kyung; Yao, Qiaoling; Jun, Jonathan C; Bevans-Fonti, Shannon; Yoo, Doo-Young; Han, Woobum; Mesarwi, Omar; Richardson, Ria; Fu, Ya-Yuan; Pasricha, Pankaj J; Schwartz, Alan R; Shirahata, Machiko; Polotsky, Vsevolod Y

    2014-10-01

    Obstructive sleep apnea causes chronic intermittent hypoxia (IH) and is associated with impaired glucose metabolism, but mechanisms are unknown. Carotid bodies orchestrate physiological responses to hypoxemia by activating the sympathetic nervous system. Therefore, we hypothesized that carotid body denervation would abolish glucose intolerance and insulin resistance induced by chronic IH. Male C57BL/6J mice underwent carotid sinus nerve dissection (CSND) or sham surgery and then were exposed to IH or intermittent air (IA) for 4 or 6 wk. Hypoxia was administered by decreasing a fraction of inspired oxygen from 20.9% to 6.5% once per minute, during the 12-h light phase (9 a.m.-9 p.m.). As expected, denervated mice exhibited blunted hypoxic ventilatory responses. In sham-operated mice, IH increased fasting blood glucose, baseline hepatic glucose output (HGO), and expression of a rate-liming hepatic enzyme of gluconeogenesis phosphoenolpyruvate carboxykinase (PEPCK), whereas the whole body glucose flux during hyperinsulinemic euglycemic clamp was not changed. IH did not affect glucose tolerance after adjustment for fasting hyperglycemia in the intraperitoneal glucose tolerance test. CSND prevented IH-induced fasting hyperglycemia and increases in baseline HGO and liver PEPCK expression. CSND trended to augment the insulin-stimulated glucose flux and enhanced liver Akt phosphorylation at both hypoxic and normoxic conditions. IH increased serum epinephrine levels and liver sympathetic innervation, and both increases were abolished by CSND. We conclude that chronic IH induces fasting hyperglycemia increasing baseline HGO via the CSN sympathetic output from carotid body chemoreceptors, but does not significantly impair whole body insulin sensitivity. Copyright © 2014 the American Physiological Society.

  1. Is hyperglycemia a risk factor for neonatal morbidity and mortality?

    International Nuclear Information System (INIS)

    Gul, R.; Waheed, K. A. I.; Sheikh, M.; Javaid, S.; Haroon, F.; Fatima, S. T.

    2017-01-01

    Objective: To determine the extent of morbidity and mortality in newborns with neonatal hyperglycemia where published data are limited. Study Design: Observational case control study. Place and Duration of Study: Department of Neonatology, the Children'Hospital and the Institute of Child Health Lahore, from 1st May to 31st Oct 2015. Material and Methods: A prospective, observational case control study was conducted in the Department of Neonatology, the Children'Hospital and the Institute of Child Health, Lahore, from 1st May till 31st October 2015. The sample size was 192, with 96 babies each in ‘study’ and ‘control’ groups. All neonates fulfilling the inclusion criteria were enrolled in the ‘study group’ while ‘control group’ consisted of euglycemic babies matched for age, weight, gestational age and clinical status. All babies were monitored for morbidity intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), infections and outcome (duration of hospital stay, discharged or expired). Results: The data analysis showed that 74 percent neonates, of study group, had hyperglycemia during first week of their lives. Moreover, 84.4 percent babies were less than 2.5 kg. Significant high number of babies in the study group developed complications (p<0.001). These complications included IVH (p<0.001), NEC (p=0.024) and infections (p=0.019). As regards outcome, the neonates in the study group had significantly prolonged hospital stay (p=0.028), lower discharge rate (p=0.040) and higher mortality (p=0.040). Conclusion: Hyperglycemia not only significantly increases risk of IVH, NEC and infections, but also prolongs hospital stay and contributes to mortality among newborns. (author)

  2. Effect of hyperglycemia on mortality rates in critically ill children

    Directory of Open Access Journals (Sweden)

    Seongkuk Kim

    2010-03-01

    Full Text Available Purpose : To verify the effect of hyperglycemia on mortality rates in critically ill children and to identify the blood glucose level that influences prognosis. Methods : From July 2006 to June 2008, a total of 206 patients who were admitted to the pediatric intensive care unit (PICU at Asan Medical Center and who survived for more than 7 days were retrospectively reviewed. We analyzed the maximum glucose value within 7 days in PICU, PRISM-III score and SOFA score within 24 hours, and mortality. We did not perform an adjustment analysis of drugs affecting glucose level. Results : The maximum glucose level within 7 days in PICU was higher in the nonsurvival group than in the survival group. Using 4 cutoff values (125, 150, 175, and 200 mg/dL, the mortality of patients with hyperglycemia was found to be 13.0 %, 14.4%, 19.8%, and 21.1%, respectively, and the cutoff values of 175 and 200 mg/dL revealed significant differences in mortalities between the hyperglycemic and normoglycemic groups. The PRISM-III score was not significantly different between the hyperglycemic and normoglycemic groups under a glucose cutoff value of 175 mg/dL, but the SOFA score was higher in the hyperglycemic group. Under a glucose cutoff value of 200 mg/dL, the PRISM-III score was higher in the hyperglycemic group, and the SOFA score did not differ between the 2 groups. Conclusion : Hyperglycemia with a maximal glucose value ?#241;75 mg/dL during the first 7 days after PICU admission was associated with increased mortality in critically ill children.

  3. Management of radiation-induced accelerated carotid atherosclerosis

    International Nuclear Information System (INIS)

    Loftus, C.M.; Biller, J.; Hart, M.N.; Cornell, S.H.; Hiratzka, L.F.

    1987-01-01

    Patients with long survival following cervical irradiation are at risk for accelerated carotid atherosclerosis. The neurologic presentation in these patients mimics naturally occurring atheromatous disease, but patients often present at younger ages and with less concurrent coronary or systemic vascular disease. Hypercholesterolemia also contributes to this accelerated arteriosclerosis. Angiographic findings in this disorder include disproportionate involvement of the distal common carotid artery and unusually long carotid lesions. Pathologic findings include destruction of the internal elastic lamina and replacement of the normal intima and media with fibrous tissue. This article describes two surgical patients with radiation-induced accelerated carotid atherosclerosis who typify the presentation and characteristics of this disease

  4. Reversal of islet GIP receptor down-regulation and resistance to GIP by reducing hyperglycemia in the Zucker rat

    International Nuclear Information System (INIS)

    Piteau, Shalea; Olver, Amy; Kim, Su-Jin; Winter, Kyle; Pospisilik, John Andrew; Lynn, Francis; Manhart, Susanne; Demuth, Hans-Ulrich; Speck, Madeleine; Pederson, Raymond A.; McIntosh, Christopher H.S.

    2007-01-01

    In type 2 diabetes (T2DM) β-cell responsiveness to glucose-dependent insulinotropic polypeptide (GIP) is reduced. In a model of T2DM, the VDF Zucker rat, GIP receptor mRNA and protein levels were shown to be down-regulated. Possible restoration of responsiveness to GIP in Zucker rats by reducing hyperglycemia has been examined. ZDF rats with extreme hyperglycemia demonstrated greater islet GIP receptor mRNA down-regulation (94.3 ± 3.8%) than ZF rats (48.8 ± 22.8%). GIP receptor mRNA levels in ZDF rats returned to 83.0 ± 17.9% of lean following normalization of hyperglycemia by phlorizin treatment and pancreas perfusions demonstrated markedly improved GIP responsiveness. Treatment of VDF rats with a DP IV inhibitor (P32/98) resulted in improved glucose tolerance and restored sensitivity to GIP in isolated pancreata. These findings support the proposal that GIP receptor down-regulation in rodent T2DM is secondary to chronic hyperglycemia and that normalization of glycemia can restore GIP sensitivity

  5. Genomic Analysis of Circulating Cells: A Window into Atherosclerosis

    Science.gov (United States)

    Kang, Ju-Gyeong; Patino, Willmar D.; Matoba, Satoaki; Hwang, Paul M.

    2006-01-01

    Translational studies using genomic techniques in cardiovascular diseases are still in their infancy. Access to disease-associated cardiovascular tissues from patients has been a major impediment to progress in contrast to the diagnostic advances made by oncologists using gene expression on readily available tumor samples. Nonetheless, progress is being made for atherosclerosis by carefully designed experiments using diseased tissue or surrogate specimens. This review details the rationale and findings of a study using freshly isolated blood mononuclear cells from patients undergoing carotid endarterectomy due to atherosclerotic stenosis and from matched normal subjects. Using this cardiovascular tissue surrogate, the mRNA levels of the Finkel-Biskis-Jinkins osteosarcoma (FOS) gene in circulating monocytes were found to correlate with atherosclerosis severity in patients, and with HMG CoA reductase inhibitor (statin) therapy in normal subjects. The major finding of this investigation is discussed in relation to observations from other human atherosclerosis gene expression studies. These distinct studies converge to demonstrate the unequivocal importance of inflammation in atherosclerosis. Although the clinical utility of the specific findings remains open, the identification of similar genes by different investigations serves to validate their reports. They also provide us with insights into pathogenesis that may impact future translational applications. PMID:16781950

  6. Ageing induced vascular smooth muscle cell senescence in atherosclerosis.

    Science.gov (United States)

    Uryga, Anna K; Bennett, Martin R

    2016-04-15

    Atherosclerosis is a disease of ageing in that its incidence and prevalence increase with age. However, atherosclerosis is also associated with biological ageing, manifest by a number of typical hallmarks of ageing in the atherosclerotic plaque. Thus, accelerated biological ageing may be superimposed on the effects of chronological ageing in atherosclerosis. Tissue ageing is seen in all cells that comprise the plaque, but particularly in vascular smooth muscle cells (VSMCs). Hallmarks of ageing include evidence of cell senescence, DNA damage (including telomere attrition), mitochondrial dysfunction, a pro-inflammatory secretory phenotype, defects in proteostasis, epigenetic changes, deregulated nutrient sensing, and exhaustion of progenitor cells. In this model, initial damage to DNA (genomic, telomeric, mitochondrial and epigenetic changes) results in a number of cellular responses (cellular senescence, deregulated nutrient sensing and defects in proteostasis). Ultimately, ongoing damage and attempts at repair by continued proliferation overwhelm reparative capacity, causing loss of specialised cell functions, cell death and inflammation. This review summarises the evidence for accelerated biological ageing in atherosclerosis, the functional consequences of cell ageing on cells comprising the plaque, and the causal role that VSMC senescence plays in atherogenesis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  7. The effect of cigarette smoking on endothelial damage and atherosclerosis development – modeled and analyzed using Petri nets

    Directory of Open Access Journals (Sweden)

    Chmielewska Kaja

    2017-06-01

    Full Text Available Atherosclerosis as one of the crucial causes of cardiovascular diseases (CVD is the leading reason of death worldwide. One of the contributing factors to this phenomenon is endothelial dysfunction, which is associated with the impact of various agents and their interactions. Tobacco smoke is one of the well known factors here. For better understanding of its significance a model of its impact on atherosclerotic plaque formation has been proposed. The model contains selected aspects of the influence of tobacco smoke, dual function of nitric oxide (NO (influence of various mechanisms on NO bioavailability, oxidative stress which promotes low density lipoproteins oxidation, macrophages significance and other mechanisms leading to an aggravation of the endothelial disturbances. The model has been built using Petri nets theory and the analysis has been based on t-invariants. This approach allowed to confirm the important role of inflammation and oxidative stress in atherosclerosis development and moreover it has shown the considerable influence of the cigarette smoke.

  8. Formation of 3D cholesterol crystals from 2D nucleation sites in lipid bilayer membranes: implications for atherosclerosis.

    Science.gov (United States)

    Varsano, Neta; Fargion, Iael; Wolf, Sharon G; Leiserowitz, Leslie; Addadi, Lia

    2015-02-04

    Atherosclerosis is the major precursor of cardiovascular disease. The formation of cholesterol crystals in atherosclerotic plaques is associated with the onset of acute pathology. The cholesterol crystals induce physical injury in the plaque core, promoting cell apoptosis and triggering an increased inflammatory response. Herein we address the question of how cholesterol crystal formation occurs in atherosclerosis. We demonstrate that three-dimensional (3D) cholesterol crystals can undergo directed nucleation from bilayer membranes containing two-dimensional (2D) cholesterol crystalline domains. We studied crystal formation on supported lipid bilayers loaded with exogenous cholesterol and labeled using a monoclonal antibody that specifically recognizes ordered cholesterol arrays. Our findings show that 3D crystals are formed exclusively on the bilayer regions where there are segregated 2D cholesterol crystalline domains and that they form on the domains. This study has potentially significant implications for our understanding of the crucial step in the mechanism by which atherosclerotic lesions form.

  9. Non-Cholesterol Sterol Levels Predict Hyperglycemia and Conversion to Type 2 Diabetes in Finnish Men

    Science.gov (United States)

    Cederberg, Henna; Gylling, Helena; Miettinen, Tatu A.; Paananen, Jussi; Vangipurapu, Jagadish; Pihlajamäki, Jussi; Kuulasmaa, Teemu; Stančáková, Alena; Smith, Ulf; Kuusisto, Johanna; Laakso, Markku

    2013-01-01

    We investigated the levels of non-cholesterol sterols as predictors for the development of hyperglycemia (an increase in the glucose area under the curve in an oral glucose tolerance test) and incident type 2 diabetes in a 5-year follow-up study of a population-based cohort of Finnish men (METSIM Study, N = 1,050) having non-cholesterol sterols measured at baseline. Additionally we determined the association of 538,265 single nucleotide polymorphisms (SNP) with non-cholesterol sterol levels in a cross-sectional cohort of non-diabetic offspring of type 2 diabetes (the Kuopio cohort of the EUGENE2 Study, N = 273). We found that in a cross-sectional METSIM Study the levels of sterols indicating cholesterol absorption were reduced as a function of increasing fasting glucose levels, whereas the levels of sterols indicating cholesterol synthesis were increased as a function of increasing 2-hour glucose levels. A cholesterol synthesis marker desmosterol significantly predicted an increase, and two absorption markers (campesterol and avenasterol) a decrease in the risk of hyperglycemia and incident type 2 diabetes in a 5-year follow-up of the METSIM cohort, mainly attributable to insulin sensitivity. A SNP of ABCG8 was associated with fasting plasma glucose levels in a cross-sectional study but did not predict hyperglycemia or incident type 2 diabetes. In conclusion, the levels of some, but not all non-cholesterol sterols are markers of the worsening of hyperglycemia and type 2 diabetes. PMID:23840693

  10. Fatal Metformin Overdose Presenting with Progressive Hyperglycemia

    Directory of Open Access Journals (Sweden)

    Suchard, Jeffrey R

    2008-08-01

    Full Text Available A 29-year-old man with no history of diabetes ingested over 60 grams of metformin in a suicide attempt. He presented to the emergency department with acute renal insufficiency, severe lactic acidosis, and rapidly-progressive hyperglycemia. The patient’s peak serum glucose level of 707 mg/dL is the highest yet reported in a case of metformin toxicity. Treatment included sodium bicarbonate infusion and hemodialysis, but the patient suffered several cardiac arrests with pulseless electrical activity and ultimately expired 25 hours after the ingestion.

  11. Occipital seizures and subcortical T2 hypointensity in the setting of hyperglycemia

    Directory of Open Access Journals (Sweden)

    Swapna L. Putta

    2014-01-01

    Conclusion: Hyperglycemia should be considered in the etiology of differential diagnosis of patients with visual abnormalities suspicious for seizures, especially when the MRI shows focal subcortical T2 hypointensity with or without leptomeningeal enhancement.

  12. Polyradiomodification. Evaluation of the efficacy of the utilization of hyperglycemia in experimental hypoxiradiotherapy of tumors

    International Nuclear Information System (INIS)

    Kozin, S.V.; Dyuskaliev, Zh.D.; Yarmonenko, S.P.

    1984-01-01

    An experimental evaluation of the appropriateness of the use of short-term hyperglycemia combined with hypoxiradiotherapy of solid tumors is given. In comparing the response of tumors and overlying skin a conclusion has been made that gaseous hypoxia and the use of hyperglycemia separately yield in a considerable therapeutic benefit, and the use of the combination of these agents in some cases produces a greater therapeutic interval between tumor destruction and normal tissues. The mechanisms of the modification of radiation injuries of tumors and skin under the influence of the above two factors are discussed

  13. Oxyradical Stress, Endocannabinoids, and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Anberitha T. Matthews

    2015-12-01

    Full Text Available Atherosclerosis is responsible for most cardiovascular disease (CVD and is caused by several factors including hypertension, hypercholesterolemia, and chronic inflammation. Oxidants and electrophiles have roles in the pathophysiology of atherosclerosis and the concentrations of these reactive molecules are an important factor in disease initiation and progression. Overactive NADPH oxidase (Nox produces excess superoxide resulting in oxidized macromolecules, which is an important factor in atherogenesis. Although superoxide and reactive oxygen species (ROS have obvious toxic properties, they also have fundamental roles in signaling pathways that enable cells to adapt to stress. In addition to inflammation and ROS, the endocannabinoid system (eCB is also important in atherogenesis. Linkages have been postulated between the eCB system, Nox, oxidative stress, and atherosclerosis. For instance, CB2 receptor-evoked signaling has been shown to upregulate anti-inflammatory and anti-oxidative pathways, whereas CB1 signaling appears to induce opposite effects. The second messenger lipid molecule diacylglycerol is implicated in the regulation of Nox activity and diacylglycerol lipase β (DAGLβ is a key biosynthetic enzyme in the biosynthesis eCB ligand 2-arachidonylglycerol (2-AG. Furthermore, Nrf2 is a vital transcription factor that protects against the cytotoxic effects of both oxidant and electrophile stress. This review will highlight the role of reactive oxygen species (ROS in intracellular signaling and the impact of deregulated ROS-mediated signaling in atherogenesis. In addition, there is also emerging knowledge that the eCB system has an important role in atherogenesis. We will attempt to integrate oxidative stress and the eCB system into a conceptual framework that provides insights into this pathology.

  14. Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

    International Nuclear Information System (INIS)

    Hsieh, Yi-Chen; Lien, Li-Ming; Chung, Wen-Ting; Hsieh, Fang-I; Hsieh, Pei-Fan; Wu, Meei-Maan; Tseng, Hung-Pin; Chiou, Hung-Yi; Chen, Chien-Jen

    2011-01-01

    Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 μg/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 μg/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 μg/l). - Highlights: →Arsenic metabolic genes might be associated with carotid atherosclerosis. → A case

  15. Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Yi-Chen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Lien, Li-Ming [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan (China); Chung, Wen-Ting [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsieh, Fang-I; Hsieh, Pei-Fan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Tseng, Hung-Pin [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China); Chiou, Hung-Yi, E-mail: hychiou@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)

    2011-08-15

    Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields

  16. RENAL INVOLVEMENT IN SUBJECTS WITH PERIPHERAL ATHEROSCLEROSIS

    International Nuclear Information System (INIS)

    FAWZY, A.; IBRAHIM, S.

    2008-01-01

    Ischemic nephropathy is an important cause of renal failure.Sub-clinical renal function abnormalities may exist in patients with extra renal atherosclerosis and may precede the onset of overt ischemic nephropathy. To assess the impact of extrarenal atherosclerosis on the kidney, the study evaluated renal function in 50 subjects with differing degrees of peripheral atherosclerosis without manifest clinical or laboratory signs of ischemic nephropathy and renovascular hypertension.All laboratory testing including total LDL and HDL-cholesterol, triglycerides, ultrasonography with Doppler analysis for the localization of peripheral vascular disease (carotid and lower limb arteries), and non-invasive evaluation of renal function by radionuclide studies of renal plasma flow (MAG3 clearance) and glomerular filtration (DTPA clearance) were determined as well as smoking habit was recorded. By combining sonographic data on arterial tree stenosis (ATS), the subjects were grouped according to the atherosclerotic vascular damage (ATS involvement). The results showed no change in plasma creatinine while DTPA clearance was increased from 91.58±26.53 to 93.47±24.82 ml/min/1.73 m. MAG3 clearance was progressively declined with the severity of vascular damage from 244.86 ± 60.60 to 173.59±58.74 ml/min/1.73 m.Stepwise, multiple regression analysis indicated that MAG3 clearance was best explained by ATS involvement (standardized B coefficient -0.40; P< 0.001), smoking habit (-0.34;P=0.004) and serum LDL-cholesterol (-0.24; P<0.035).It could be concluded that the renal hemodynamic profile in atherosclerotic patients might constitute functional evidence of the silent phase of ischemic renal disease. The findings suggest that renal function should be carefully assessed in patients with extrarenal atherosclerosis, particularly in those with classic cardiovascular risk factors

  17. Ethylene Glycol Poisoning; an Unusual Cause of Hyperglycemia: A Case Report

    Directory of Open Access Journals (Sweden)

    Abdul Raoof Kunnummal Madathodi

    2015-03-01

    Full Text Available Background:Poisoning with ethylene glycol (EG can be fatal even if appropriate treatments are delivered. EG poisoning usually causes central nervous system depression, cardiovascular dysfunction, metabolic acidosis and acute renal failure (ARF. Case Report:A 33-year-old man was referred to the emergency department with reduced consciousness and dyspnea of four-hour duration due to unknown reason. The patient had no history of diabetes, hypertension, cardiac disease or asthma. He was tachycardic, tachypneic and hypertensive. Laboratory investigations revealed hyperglycemia, high serum creatinine, hyponatremia, hyperkalemia, leukocytosis and high anion gap metabolic acidosis (HAGMA. He was initially managed as diabetic ketoacidosis (DKA. Alternative diagnoses of toxic alcohols poisoning was considered as there was no improvement. EG ingestion was confirmed when the relatives found an empty bottle of automotive brake oil, a poly glycol-based product, in the patient’s room. Although he was treated with ethanol and hemodialysis, renal failure worsened and finally he succumbed to death due to severe sepsis on the seventh day of EG ingestion. Discussion: This case illustrates the difficulties posed by high toxicity as well as unraveled and delayed diagnosis of EG poisoning. High anion gap and high osmolal gap are characteristics of EG poisoning. Transient pancreatitis caused by EG and insulin resistance due to ARF are the possible explanations for hyperglycemia secondary to EG poisoning. Conclusion:EG poisoning may manifest with hyperglycemia and HAGMA resembling DKA. It is important for the clinician to have high degree of suspicion for EG poisoning in case of HAGMA and ARF refractory to common treatments.

  18. Associations between vitamin D status and atherosclerosis among Inuit in Greenland

    DEFF Research Database (Denmark)

    Gjødesen, Camilla U; Jørgensen, Marit E; Bjerregaard, Peter

    2018-01-01

    BACKGROUND AND AIMS: Low levels of vitamin D are suspected to be a risk factor for cardiovascular disease and atherosclerosis. The aim of this study was to assess the prevalence of subclinical atherosclerosis among Inuit in Greenland, and to evaluate the association with vitamin D status. We hypo...

  19. Personalized Management of Hyperglycemia in Type 2 Diabetes

    OpenAIRE

    Raz, Itamar; Riddle, Matthew C.; Rosenstock, Julio; Buse, John B.; Inzucchi, Silvio E.; Home, Philip D.; Del Prato, Stefano; Ferrannini, Ele; Chan, Juliana C.N.; Leiter, Lawrence A.; LeRoith, Derek; DeFronzo, Ralph; Cefalu, William T.

    2013-01-01

    In June 2012, 13 thought leaders convened in a Diabetes Care Editors’ Expert Forum to discuss the concept of personalized medicine in the wake of a recently published American Diabetes Association/European Association for the Study of Diabetes position statement calling for a patient-centered approach to hyperglycemia management in type 2 diabetes. This article, an outgrowth of that forum, offers a clinical translation of the underlying issues that need to be considered for effectively person...

  20. Visualization of atherosclerosis as detected by coronary artery calcium and carotid intima-media thickness reveals significant atherosclerosis in a cross-sectional study of psoriasis patients in a tertiary care center.

    Science.gov (United States)

    Santilli, S; Kast, D R; Grozdev, I; Cao, L; Feig, R L; Golden, J B; Debanne, S M; Gilkeson, R C; Orringer, C E; McCormick, T S; Ward, N L; Cooper, K D; Korman, N J

    2016-07-22

    Psoriasis is a chronic inflammatory disease of the skin and joints that may also have systemic inflammatory effects, including the development of cardiovascular disease (CVD). Multiple epidemiologic studies have demonstrated increased rates of CVD in psoriasis patients, although a causal link has not been established. A growing body of evidence suggests that sub-clinical systemic inflammation may develop in psoriasis patients, even from a young age. We aimed to evaluate the prevalence of atherosclerosis and identify specific clinical risk factors associated with early vascular inflammation. We conducted a cross-sectional study of a tertiary care cohort of psoriasis patients using coronary artery calcium (CAC) score and carotid intima-media thickness (CIMT) to detect atherosclerosis, along with high sensitivity C-reactive protein (hsCRP) to measure inflammation. Psoriasis patients and controls were recruited from our tertiary care dermatology clinic. Presence of atherosclerosis was defined using validated numeric values within CAC and CIMT imaging. Descriptive data comparing groups was analyzed using Welch's t test and Pearson Chi square tests. Logistic regression was used to analyze clinical factors associated with atherosclerosis, and linear regression to evaluate the relationship between psoriasis and hsCRP. 296 patients were enrolled, with 283 (207 psoriatic and 76 controls) having all data for the hsCRP and atherosclerosis analysis. Atherosclerosis was found in 67.6 % of psoriasis subjects versus 52.6 % of controls; Psoriasis patients were found to have a 2.67-fold higher odds of having atherosclerosis compared to controls [95 % CI (1.2, 5.92); p = 0.016], after adjusting for age, gender, race, BMI, smoking, HDL and hsCRP. In addition, a non-significant trend was found between HsCRP and psoriasis severity, as measured by PASI, PGA, or BSA, again after adjusting for confounders. A tertiary care cohort of psoriasis patients have a high prevalence of early

  1. Recurrent hypoinsulinemic hyperglycemia in neonatal rats increases PARP-1 and NF-κB expression and leads to microglial activation in the cerebral cortex.

    Science.gov (United States)

    Gisslen, Tate; Ennis, Kathleen; Bhandari, Vineet; Rao, Raghavendra

    2015-11-01

    Hyperglycemia is a common metabolic problem in extremely low-birth-weight preterm infants. Neonatal hyperglycemia is associated with increased mortality and brain injury. Glucose-mediated oxidative injury may be responsible. Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme involved in DNA repair and cell survival. However, PARP-1 overactivation leads to cell death. NF-κB is coactivated with PARP-1 and regulates microglial activation. The effects of recurrent hyperglycemia on PARP-1/NF-κB expression and microglial activation are not well understood. Rat pups were subjected to recurrent hypoinsulinemic hyperglycemia of 2 h duration twice daily from postnatal (P) day 3-P12 and killed on P13. mRNA and protein expression of PARP-1/NF-κB and their downstream effectors were determined in the cerebral cortex. Microgliosis was determined using CD11 immunohistochemistry. Recurrent hyperglycemia increased PARP-1 expression confined to the nucleus and without causing PARP-1 overactivation and cell death. NF-κB mRNA expression was increased, while IκB mRNA expression was decreased. inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) mRNA expressions were decreased. Hyperglycemia significantly increased the number of microglia. Recurrent hyperglycemia in neonatal rats is associated with upregulation of PARP-1 and NF-κB expression and subsequent microgliosis but not neuronal cell death in the cerebral cortex.

  2. Macrophage deficiency of miR-21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesis.

    Science.gov (United States)

    Canfrán-Duque, Alberto; Rotllan, Noemi; Zhang, Xinbo; Fernández-Fuertes, Marta; Ramírez-Hidalgo, Cristina; Araldi, Elisa; Daimiel, Lidia; Busto, Rebeca; Fernández-Hernando, Carlos; Suárez, Yajaira

    2017-09-01

    Atherosclerosis, the major cause of cardiovascular disease, is a chronic inflammatory disease characterized by the accumulation of lipids and inflammatory cells in the artery wall. Aberrant expression of microRNAs has been implicated in the pathophysiological processes underlying the progression of atherosclerosis. Here, we define the contribution of miR-21 in hematopoietic cells during atherogenesis. Interestingly, we found that miR-21 is the most abundant miRNA in macrophages and its absence results in accelerated atherosclerosis, plaque necrosis, and vascular inflammation. miR-21 expression influences foam cell formation, sensitivity to ER-stress-induced apoptosis, and phagocytic clearance capacity. Mechanistically, we discovered that the absence of miR-21 in macrophages increases the expression of the miR-21 target gene, MKK3, promoting the induction of p38-CHOP and JNK signaling. Both pathways enhance macrophage apoptosis and promote the post-translational degradation of ABCG1, a transporter that regulates cholesterol efflux in macrophages. Altogether, these findings reveal a major role for hematopoietic miR-21 in atherogenesis. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  3. Influence of mild hyperglycemia on cerebral FDG distribution patterns calculated by statistical parametric mapping

    International Nuclear Information System (INIS)

    Kawasaki, Keiichi; Ishii, Kenji; Saito, Yoko; Oda, Keiichi; Kimura, Yuichi; Ishiwata, Kiichi

    2008-01-01

    In clinical cerebral 2-[ 18 F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) studies, we sometimes encounter hyperglycemic patients with diabetes mellitus or patients who have not adhered to the fasting requirement. The objective of this study was to investigate the influence of mild hyperglycemia (plasma glucose range 110-160 mg/dl) on the cerebral FDG distribution patterns calculated by statistical parametric mapping (SPM). We studied 19 healthy subjects (mean age 66.2 years). First, all the subjects underwent FDG-PET scans in the fasting condition. Then, 9 of the 19 subjects (mean age 64.3 years) underwent the second FDG-PET scans in the mild hyperglycemic condition. The alterations in the FDG-PET scans were investigated using SPM- and region of interest (ROI)-based analyses. We used three reference regions: SPM global brain (SPMgb) used for SPM global mean calculation, the gray and white matter region computed from magnetic resonance image (MRIgw), and the cerebellar cortex (Cbll). The FDG uptake calculated as the standardized uptake value (average) in SPMgb, MRIgw, and Cbll regions in the mild hyperglycemic condition was 42.7%, 41.3%, and 40.0%, respectively, of that observed in the fasting condition. In SPM analysis, the mild hyperglycemia was found to affect the cerebral distribution patterns of FDG. The FDG uptake was relatively decreased in the gray matter, mainly in the frontal, temporal, and parietal association cortices, posterior cingulate, and precuneus in both SPMgb- and MRIgw-reference-based analyses. When Cbll was adopted as the reference region, those decrease patterns disappeared. The FDG uptake was relatively increased in the white matter, mainly in the centrum semiovale in all the reference-based analyses. It is noteworthy that the FDG distribution patterns were altered under mild hyperglycemia in SPM analysis. The decreased uptake patterns in SPMgb- (SPM default) and MRIgw-reference-based analyses resembled those observed in

  4. Atherosclerosis and Nanotechnology: Diagnostic and Therapeutic Applications.

    Science.gov (United States)

    Kratz, Jeremy D; Chaddha, Ashish; Bhattacharjee, Somnath; Goonewardena, Sascha N

    2016-02-01

    Over the past several decades, tremendous advances have been made in the understanding, diagnosis, and treatment of coronary artery disease (CAD). However, with shifting demographics and evolving risk factors we now face new challenges that must be met in order to further advance are management of patients with CAD. In parallel with advances in our mechanistic appreciation of CAD and atherosclerosis, nanotechnology approaches have greatly expanded, offering the potential for significant improvements in our diagnostic and therapeutic management of CAD. To realize this potential we must go beyond to recognize new frontiers including knowledge gaps between understanding atherosclerosis to the translation of targeted molecular tools. This review highlights nanotechnology applications for imaging and therapeutic advancements in CAD.

  5. The population-based Barcelona-Asymptomatic Intracranial Atherosclerosis Study (ASIA: rationale and design

    Directory of Open Access Journals (Sweden)

    Pera Guillem

    2011-02-01

    Full Text Available Abstract Background Large-artery intracranial atherosclerosis may be the most frequent cause of ischemic stroke worldwide. Traditional approaches have attempted to target the disease when it is already symptomatic. However, early detection of intracranial atherosclerosis may allow therapeutic intervention while the disease is still asymptomatic. The prevalence and natural history of asymptomatic intracranial atherosclerosis in Caucasians remain unclear. The aims of the Barcelona-ASymptomatic Intracranial Atherosclerosis (ASIA study are (1 to determine the prevalence of ASIA in a moderate-high vascular risk population, (2 to study its prognostic impact on the risk of suffering future major ischemic events, and (3 to identify predictors of the development, progression and clinical expression of this condition. Methods/Design Cross-over and cohort, population-based study. A randomly selected representative sample of 1,503 subjects with a mild-moderate-high vascular risk (as defined by a REGICOR score ≥ 5% and with neither a history of cerebrovascular nor ischemic heart disease will be studied. At baseline, all individuals will undergo extracranial and transcranial Color-Coded Duplex (TCCD ultrasound examinations to detect presence and severity of extra and intracranial atherosclerosis. Intracranial stenoses will be assessed by magnetic resonance angiography (MRA. Clinical and demographic variables will be recorded and blood samples will be drawn to investigate clinical, biological and genetic factors associated with the presence of ASIA. A long-term clinical and sonographic follow-up will be conducted thereafter to identify predictors of disease progression and of incident vascular events. Discussion The Barcelona-ASIA is a population-based study aiming to evaluate the prevalence and clinical importance of asymptomatic intracranial large-artery atherosclerosis in Caucasians. The ASIA project may provide a unique scientific resource to better

  6. The population-based Barcelona-Asymptomatic Intracranial Atherosclerosis Study (ASIA): rationale and design.

    Science.gov (United States)

    López-Cancio, Elena; Dorado, Laura; Millán, Mónica; Reverté, Silvia; Suñol, Anna; Massuet, Anna; Mataró, María; Galán, Amparo; Alzamora, Maite; Pera, Guillem; Torán, Pere; Dávalos, Antoni; Arenillas, Juan F

    2011-02-17

    Large-artery intracranial atherosclerosis may be the most frequent cause of ischemic stroke worldwide. Traditional approaches have attempted to target the disease when it is already symptomatic. However, early detection of intracranial atherosclerosis may allow therapeutic intervention while the disease is still asymptomatic. The prevalence and natural history of asymptomatic intracranial atherosclerosis in Caucasians remain unclear. The aims of the Barcelona-ASymptomatic Intracranial Atherosclerosis (ASIA) study are (1) to determine the prevalence of ASIA in a moderate-high vascular risk population, (2) to study its prognostic impact on the risk of suffering future major ischemic events, and (3) to identify predictors of the development, progression and clinical expression of this condition. Cross-over and cohort, population-based study. A randomly selected representative sample of 1,503 subjects with a mild-moderate-high vascular risk (as defined by a REGICOR score ≥ 5%) and with neither a history of cerebrovascular nor ischemic heart disease will be studied. At baseline, all individuals will undergo extracranial and transcranial Color-Coded Duplex (TCCD) ultrasound examinations to detect presence and severity of extra and intracranial atherosclerosis. Intracranial stenoses will be assessed by magnetic resonance angiography (MRA). Clinical and demographic variables will be recorded and blood samples will be drawn to investigate clinical, biological and genetic factors associated with the presence of ASIA. A long-term clinical and sonographic follow-up will be conducted thereafter to identify predictors of disease progression and of incident vascular events. The Barcelona-ASIA is a population-based study aiming to evaluate the prevalence and clinical importance of asymptomatic intracranial large-artery atherosclerosis in Caucasians. The ASIA project may provide a unique scientific resource to better understand the dynamics of intracranial atherosclerosis from

  7. Liraglutide Reduces Both Atherosclerosis and Kidney Inflammation in Moderately Uremic LDLr-/- Mice

    DEFF Research Database (Denmark)

    Bisgaard, Line S; Bosteen, Markus H; Fink, Lisbeth N

    2016-01-01

    Chronic kidney disease (CKD) leads to uremia. CKD is characterized by a gradual increase in kidney fibrosis and loss of kidney function, which is associated with a progressive increase in risk of atherosclerosis and cardiovascular death. To prevent progression of both kidney fibrosis and atherosc......Chronic kidney disease (CKD) leads to uremia. CKD is characterized by a gradual increase in kidney fibrosis and loss of kidney function, which is associated with a progressive increase in risk of atherosclerosis and cardiovascular death. To prevent progression of both kidney fibrosis...... aim was to examine effects of liraglutide on kidney fibrosis and atherosclerosis in a mouse model of moderate uremia (5/6 nephrectomy (NX)). Uremic (n = 29) and sham-operated (n = 14) atherosclerosis-prone low density lipoprotein receptor knockout mice were treated with liraglutide (1000 μg/kg, s.......c. once daily) or vehicle for 13 weeks. As expected, uremia increased aortic atherosclerosis. In the remnant kidneys from NX mice, flow cytometry revealed an increase in the number of monocyte-like cells (CD68+F4/80-), CD4+, and CD8+ T-cells, suggesting that moderate uremia induced kidney inflammation...

  8. Incretin hormones as immunomodulators of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Nuria eAlonso

    2012-09-01

    Full Text Available Atherosclerosis results from endothelial cell dysfunction and inflammatory processes affecting both macro-and microvasculature which are involved in vascular diabetic complications. Glucagon-like peptide 1 (GLP-1 is an incretin hormone responsible for amplification of insulin secretion when nutrients are given orally as opposed to intravenously and it retains its insulinotropic activity in patients with type 2 diabetes mellitus (T2D. GLP-1 based therapies, such as GLP-1 receptor (R agonists and inhibitors of dipeptidyl peptidase 4 (DPP-4, an enzyme that degrades endogenous GLP-1 are routinely used to treat patients with T2D. Recent experimental model studies have established that GLP-1R mRNA is widely expressed in several immune cells. Moreover, its activation contributes to the regulation of both thymocyte and peripheral T cells proliferation and is involved in the maintenance of peripheral regulatory T cells. GLP-1 R is also expressed in endothelial and smooth muscle cells. The effect of incretin hormones on atherosclerogenesis have recently been studied in animal models of apolipoprotein E-deficient mice (apo E-/-. These studies have demonstrated that treatment with incretin hormones or related compounds suppresses the progression of atherosclerosis and macrophage infiltration in the arterial wall as well as a marked anti-oxidative and anti-inflammatory effect on endothelial cells. This effect may have a major impact on the attenuation of atherosclerosis and may help in the design of new therapies for cardiovascular disease in patients with type 2 diabetes.

  9. Overview of Atherosclerosis and Chemical Stressors

    Science.gov (United States)

    Dr. Cascio’s presentation at the workshop titled, “titled “Understanding the Combined Effects of Environmental Chemical and Non-Chemical Stressors: Atherosclerosis as a Model” will highlight atherosclerosis’s rapidly growing role as a cause of increa...

  10. Atherosclerosis in epilepsy: its causes and implications.

    Science.gov (United States)

    Hamed, Sherifa A

    2014-12-01

    Evidence from epidemiological, longitudinal, prospective, double-blinded clinical trials as well as case reports documents age-accelerated atherosclerosis with increased carotid artery intima media thickness (CA-IMT) in patients with epilepsy. These findings raise concern regarding their implications for age-accelerated cognitive and behavioral changes in midlife and risk of later age-related cognitive disorders including neurodegenerative processes such as Alzheimer's disease (AD). Chronic epilepsy, cerebral atherosclerosis, and age-related cognitive disorders including AD share many clinical manifestations (e.g. characteristic cognitive deficits), risk factors, and structural and pathological brain abnormalities. These shared risk factors include increased CA-IMT, hyperhomocysteinemia (HHcy), lipid abnormalities, weight gain and obesity, insulin resistance (IR), and high levels of inflammatory and oxidative stresses. The resulting brain structural and pathological abnormalities include decreased volume of the hippocampus, increased cortical thinning of the frontal lobe, ventricular expansion and increased white matter ischemic disease, total brain atrophy, and β-amyloid protein deposition in the brain. The knowledge that age-accelerated atherosclerosis may contribute to age-accelerated cognitive and behavioral abnormalities and structural brain pathologies in patients with chronic epilepsy represents an important research path to pursue future clinical and management considerations. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Protracted Administration of L-Asparaginase in Maintenance Phase Is the Risk Factor for Hyperglycemia in Older Patients with Pediatric Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Yoshida, Hideki; Imamura, Toshihiko; Saito, Akiko M.; Takahashi, Yoshihiro; Suenobu, So-ichi; Hasegawa, Daiichiro; Deguchi, Takao; Hashii, Yoshiko; Kawasaki, Hirohide; Endo, Mikiya; Hori, Hiroki; Suzuki, Nobuhiro; Kosaka, Yoshiyuki; Kato, Koji; Yumura-Yagi, Keiko; Hara, Junichi; Oda, Megumi; Sato, Atsushi; Horibe, Keizo

    2015-01-01

    Although L-asparaginase related hyperglycemia is well known adverse event, it is not studied whether the profile of this adverse event is affected by intensification of L-asparaginase administration. Here, we analyzed the profile of L-asparaginase related hyperglycemia in a 1,176 patients with pediatric acute lymphoblastic leukemia treated according to the Japan Association of Childhood Leukemia Study ALL-02 protocol using protracted L-asparaginase administration in maintenance phase. We determined that a total of 75 L-asparaginase related hyperglycemia events occurred in 69 patients. Although 17 events (17/1176, 1.4%) developed in induction phase, which was lower incidence than those (10–15%) in previous reports, 45 events developed during the maintenance phase with protracted L-asparaginase administration. Multivariate analysis showed that older age at onset (≥10 years) was a sole independent risk factor for L-asparaginase-related hyperglycemia (Phyperglycemia. These findings suggest that protracted administration of L-asparaginase is the risk factor for hyperglycemia when treating adolescent and young adult acute lymphoblastic leukemia patients. PMID:26317422

  12. Experimental assessment of the role of the blood flow inhibition in hyperglycemia-enhanced radiation injury to tumor

    International Nuclear Information System (INIS)

    Kozin, S.V.; Sevast'yanov, A.I.; Yarmonenko, S.P.

    1986-01-01

    Experimental assessment of the role of the blood flow inhibition in enhancement of radiation injury to tumors using short-term hyperglycemia was provided. Experiments on mice with Ehrlich solid carcinoma showed the dependence of a rise of the antitumor effect of preceding radiation induced by glucose and glucose combined with mexamin on a degree of the blood flow inhibition under the influence of these modifying agents. It was established that a considerable enhancement of radiation injury occured but in such tumors where short-term hyperglycemia and mexamin decreased the blood flow level not less than 5-10 fold as estimated by 133 Xe clearance. The results of the above experiments showed that the noticeable inhibition of the blood flow in tumors was a necessary tough, probably, not the only condition for a high efficacy of short-term hyperglycemia used an ajuvant to radiotherapy

  13. Transcriptional profiling uncovers a network of cholesterol-responsive atherosclerosis target genes.

    Directory of Open Access Journals (Sweden)

    Josefin Skogsberg

    2008-03-01

    Full Text Available Despite the well-documented effects of plasma lipid lowering regimes halting atherosclerosis lesion development and reducing morbidity and mortality of coronary artery disease and stroke, the transcriptional response in the atherosclerotic lesion mediating these beneficial effects has not yet been carefully investigated. We performed transcriptional profiling at 10-week intervals in atherosclerosis-prone mice with human-like hypercholesterolemia and a genetic switch to lower plasma lipoproteins (Ldlr(-/-Apo(100/100Mttp(flox/flox Mx1-Cre. Atherosclerotic lesions progressed slowly at first, then expanded rapidly, and plateaued after advanced lesions formed. Analysis of lesion expression profiles indicated that accumulation of lipid-poor macrophages reached a point that led to the rapid expansion phase with accelerated foam-cell formation and inflammation, an interpretation supported by lesion histology. Genetic lowering of plasma cholesterol (e.g., lipoproteins at this point all together prevented the formation of advanced plaques and parallel transcriptional profiling of the atherosclerotic arterial wall identified 37 cholesterol-responsive genes mediating this effect. Validation by siRNA-inhibition in macrophages incubated with acetylated-LDL revealed a network of eight cholesterol-responsive atherosclerosis genes regulating cholesterol-ester accumulation. Taken together, we have identified a network of atherosclerosis genes that in response to plasma cholesterol-lowering prevents the formation of advanced plaques. This network should be of interest for the development of novel atherosclerosis therapies.

  14. The Multifaceted Uses and Therapeutic Advantages of Nanoparticles for Atherosclerosis Research.

    Science.gov (United States)

    DiStasio, Nicholas; Lehoux, Stephanie; Khademhosseini, Ali; Tabrizian, Maryam

    2018-05-08

    Nanoparticles are uniquely suited for the study and development of potential therapies against atherosclerosis by virtue of their size, fine-tunable properties, and ability to incorporate therapies and/or imaging modalities. Furthermore, nanoparticles can be specifically targeted to the atherosclerotic plaque, evading off-target effects and/or associated cytotoxicity. There has been a wealth of knowledge available concerning the use of nanotechnologies in cardiovascular disease and atherosclerosis, in particular in animal models, but with a major focus on imaging agents. In fact, roughly 60% of articles from an initial search for this review included examples of imaging applications of nanoparticles. Thus, this review focuses on experimental therapy interventions applied to and observed in animal models. Particular emphasis is placed on how nanoparticle materials and properties allow researchers to learn a great deal about atherosclerosis. The objective of this review was to provide an update for nanoparticle use in imaging and drug delivery studies and to illustrate how nanoparticles can be used for sensing and modelling, for studying fundamental biological mechanisms, and for the delivery of biotherapeutics such as proteins, peptides, nucleic acids, and even cells all with the goal of attenuating atherosclerosis. Furthermore, the various atherosclerosis processes targeted mainly for imaging studies have been summarized in the hopes of inspiring new and exciting targeted therapeutic and/or imaging strategies.

  15. Hyperglycemia and Oxidative Stress Strengthen the Association Between Myeloperoxidase and Blood Pressure

    NARCIS (Netherlands)

    van der Zwan, L.P.; Scheffer, P.G.; Dekker, J.M.; Stehouwer, C.D.A.; Heine, R.J.; Teerlink, T.

    2010-01-01

    Scavenging of the vasodilator nitric oxide by myeloperoxidase activity in the vasculature may contribute to hypertension. Because hydrogen peroxide is a cosubstrate of myeloperoxidase, hyperglycemia-induced oxidative stress may strengthen the relationship between myeloperoxidase and blood pressure.

  16. Models and Analysis of Atherosclerosis, Restenosis, and Aneurysm Formation in the Mouse

    NARCIS (Netherlands)

    de Waard, Vivian; Gijbels, Marion J. J.; Lutgens, Esther; de Winther, Menno P. J.; de Vries, Carlie J. M.

    2012-01-01

    Atherosclerosis is considered a chronic inflammatory condition of the vessel wall and involves a high chronic concentration of low-density lipoprotein (LDL) in blood. In humans, restenosis develops after intravascular interventions such as angioplasty and stent placement to treat atherosclerosis,

  17. Endogenous hydrogen sulfide is involved in the pathogenesis of atherosclerosis

    International Nuclear Information System (INIS)

    Qiao, Wang; Chaoshu, Tang; Hongfang, Jin; Junbao, Du

    2010-01-01

    Atherosclerosis is a chronic, complex, and progressive pathological process in large and medium sized arteries. The exact mechanism of this process remains unclear. Hydrogen sulfide (H 2 S), a novel gasotransmitter, was confirmed as playing a major role in the pathogenesis of many cardiovascular diseases. It plays a role in vascular smooth muscle cell (VSMC) proliferation and apoptosis, participates in the progress of hyperhomocysteinemia (HHCY), inhibits atherogenic modification of LDL, interferes with vascular calcification, intervenes with platelet function, and there are interactions between H 2 S and inflammatory processes. The role of H 2 S in atherosclerotic pathogenesis highlights the mysteries of atherosclerosis and inspires the search for innovative therapeutic strategies. Here, we review the studies to date that have considered the role of H 2 S in atherosclerosis.

  18. Occipital lobe seizures and subcortical T2 and T2* hypointensity associated with nonketotic hyperglycemia: a case report.

    Science.gov (United States)

    Sasaki, Fuyuko; Kawajiri, Sumihiro; Nakajima, Sho; Yamaguchi, Ai; Tomizawa, Yuji; Noda, Kazuyuki; Hattori, Nobutaka; Okuma, Yasuyuki

    2016-08-12

    Nonketotic hyperglycemia often causes seizures. Recently, seizures associated with nonketotic hyperglycemia have been found to be associated with subcortical T2 hypointensity on magnetic resonance imaging, especially in the occipital lobes. However, the mechanism remains unclear, although iron accumulation is suggested. We present a case of occipital lobe seizures associated with nonketotic hyperglycemia supporting the hypothesis that the mechanism of subcortical T2 hypointensity is iron accumulation using gradient-echo T2*-weighted magnetic resonance imaging. A 65-year-old Japanese man complained of intermittent pastel-colored flashing lights. On neurological examination, he also had lower right-side quadrant hemianopia. No other abnormal neurological findings were found. On laboratory analysis, his blood glucose level was 370 mg/dL, HbA1c was 11.4 %, and serum osmolarity was 326 mOsm/L. No ketones were detected in urine. A magnetic resonance imaging scan of his head showed subcortical T2 and T2* hypointensity in his left occipital lobe. Single-photon emission computed tomography with I123-N-isopropyl-iodoamphetamine revealed hyperperfusion in the left dominant occipital lobe. These magnetic resonance imaging abnormalities resolved during clinical recovery and treatment to control his blood sugar level. Therefore, a diagnosis of occipital lobe seizures associated with nonketotic hyperglycemia was made. To the best of our knowledge, this is the first case of occipital lobe seizures associated with nonketotic hyperglycemia supporting the role of iron accumulation as a mechanism for subcortical T2 hypointensity using T2*-magnetic resonance imaging.

  19. Hyperglycemia associated dissociative fugue (organic dissociative disorder) in an elderly.

    Science.gov (United States)

    Ram, Dushad; Ashoka, H G; Gowdappa, Basavnna

    2015-01-01

    Inadequate glycemic control in patients with diabetes is known to be associated with psychiatric disorders such as depression, anxiety disorder, and cognitive impairment. However, dissociative syndrome has not been reported so far. Here we are reporting a case of repeated dissociative fugue associated with hyperglycemia, in an elderly with type II diabetes. Possible neurobiological mechanism has been discussed.

  20. Hyperglycemia associated dissociative fugue (organic dissociative disorder) in an elderly

    OpenAIRE

    Ram, Dushad; Ashoka, H. G; Gowdappa, Basavnna

    2015-01-01

    Inadequate glycemic control in patients with diabetes is known to be associated with psychiatric disorders such as depression, anxiety disorder, and cognitive impairment. However, dissociative syndrome has not been reported so far. Here we are reporting a case of repeated dissociative fugue associated with hyperglycemia, in an elderly with type II diabetes. Possible neurobiological mechanism has been discussed.

  1. Edaravone, a free radical scavenger, attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia.

    Science.gov (United States)

    Okamura, Koichi; Tsubokawa, Tamiji; Johshita, Hiroo; Miyazaki, Hiroshi; Shiokawa, Yoshiaki

    2014-01-01

    Thrombolysis due to acute ischemic stroke is associated with the risk of hemorrhagic infarction, especially after reperfusion. Recent experimental studies suggest that the main mechanism contributing to hemorrhagic infarction is oxidative stress caused by disruption of the blood-brain barrier. Edaravone, a free radical scavenger, decreases oxidative stress, thereby preventing hemorrhagic infarction during ischemia and reperfusion. In this study, we investigated the effects of edaravone on hemorrhagic infarction in a rat model of hemorrhagic transformation. We used a previously established hemorrhagic transformation model of rats with hyperglycemia. Hyperglycemia was induced by intraperitoneal injection of glucose to all rats (n  =  20). The rats with hyperglycemia showed a high incidence of hemorrhagic infarction. Middle cerebral artery occlusion (MCAO) for 1.5 hours followed by reperfusion for 24 hours was performed in edaravone-treated rats (n  =  10) and control rats (n  =  10). Upon completion of reperfusion, both groups were evaluated for infarct size and hemorrhage volume and the results obtained were compared. Edaravone significantly decreased infarct volume, with the average infarct volume in the edaravone-treated rats (227.6 mm(3)) being significantly lower than that in the control rats (264.0 mm(3)). Edaravone treatment also decreased the postischemic hemorrhage volumes (53.4 mm(3) in edaravone-treated rats vs 176.4 mm(3) in controls). In addition, the ratio of hemorrhage volume to infarct volume was lower in the edaravone-treated rats (23.5%) than in the untreated rats (63.2%). Edaravone attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia.

  2. Cyanotic congenital heart disease and atherosclerosis

    DEFF Research Database (Denmark)

    Tarp, Julie Bjerre; Jensen, Annette Schophuus; Engstrøm, Thomas

    2017-01-01

    Improved treatment options in paediatric cardiology and congenital heart surgery have resulted in an ageing population of patients with cyanotic congenital heart disease (CCHD). The risk of acquired heart disease such as atherosclerosis increases with age.Previous studies have speculated whether...

  3. Risk factors for atherosclerosis - can they be used to identify the ...

    African Journals Online (AJOL)

    Risk factors are often used in preventive care programmes to identify the patient at particular risk for developing atherosclerosis. Risk factors for atherosclerosis have also been shown to be linked to the presence of the disease at a given time, a fact that may be helpful when screening for additional atherosclerotic disease in ...

  4. Effect of Diets Containing Sucrose vs. D-tagatose in Hypercholesterolemic Mice

    Energy Technology Data Exchange (ETDEWEB)

    Police, S.; Harris, J; Lodder, R; Cassis, L

    2008-01-01

    Effects of functional sweeteners on the development of the metabolic syndrome and atherosclerosis are unknown. The objective was to compare the effect of dietary carbohydrate in the form of sucrose (SUCR) to D-tagatose (TAG; an isomer of fructose currently used as a low-calorie sweetener) on body weight, blood cholesterol concentrations, hyperglycemia, and atherosclerosis in low-density lipoprotein receptor deficient (LDLr-/-) mice. LDLr-/- male and female mice were fed either standard murine diet or a diet enriched with TAG or SUCR as carbohydrate sources for 16 weeks. TAG and SUCR diets contained equivalent amounts (g/kg) of protein, fat, and carbohydrate. We measured food intake, body weight, adipocyte diameter, serum cholesterol and lipoprotein concentrations, and aortic atherosclerosis. Macrophage immunostaining and collagen content were examined in aortic root lesions. CONTROL and TAG-fed mice exhibited similar energy intake, body weights and blood glucose and insulin concentrations, but SUCR-fed mice exhibited increased energy intake and became obese and hyperglycemic. Adipocyte diameter increased in female SUCR-fed mice compared to TAG and CONTROL. Male and female SUCR-fed mice had increased serum cholesterol and triglyceride concentrations compared to TAG and CONTROL. Atherosclerosis was increased in SUCR-fed mice of both genders compared to TAG and CONTROL. Lesions from SUCR-fed mice exhibited pronounced macrophage immunostaining and reductions in collagen content compared to TAG and CONTROL mice. These results demonstrate that in comparison to sucrose, equivalent substitution of TAG as dietary carbohydrate does not result in the same extent of obesity, hyperglycemia, hyperlipidemia, and atherosclerosis.

  5. Effect of diets containing sucrose vs. D-tagatose in hypercholesterolemic mice.

    Science.gov (United States)

    Police, Sara B; Harris, J Clay; Lodder, Robert A; Cassis, Lisa A

    2009-02-01

    Effects of functional sweeteners on the development of the metabolic syndrome and atherosclerosis are unknown. The objective was to compare the effect of dietary carbohydrate in the form of sucrose (SUCR) to D-tagatose (TAG; an isomer of fructose currently used as a low-calorie sweetener) on body weight, blood cholesterol concentrations, hyperglycemia, and atherosclerosis in low-density lipoprotein receptor deficient (LDLr(-/-)) mice. LDLr(-/-) male and female mice were fed either standard murine diet or a diet enriched with TAG or SUCR as carbohydrate sources for 16 weeks. TAG and SUCR diets contained equivalent amounts (g/kg) of protein, fat, and carbohydrate. We measured food intake, body weight, adipocyte diameter, serum cholesterol and lipoprotein concentrations, and aortic atherosclerosis. Macrophage immunostaining and collagen content were examined in aortic root lesions. CONTROL and TAG-fed mice exhibited similar energy intake, body weights and blood glucose and insulin concentrations, but SUCR-fed mice exhibited increased energy intake and became obese and hyperglycemic. Adipocyte diameter increased in female SUCR-fed mice compared to TAG and CONTROL. Male and female SUCR-fed mice had increased serum cholesterol and triglyceride concentrations compared to TAG and CONTROL. Atherosclerosis was increased in SUCR-fed mice of both genders compared to TAG and CONTROL. Lesions from SUCR-fed mice exhibited pronounced macrophage immunostaining and reductions in collagen content compared to TAG and CONTROL mice. These results demonstrate that in comparison to sucrose, equivalent substitution of TAG as dietary carbohydrate does not result in the same extent of obesity, hyperglycemia, hyperlipidemia, and atherosclerosis.

  6. ECG changes after a session of regional intraarterial hyperglycemia

    International Nuclear Information System (INIS)

    Korobchenko, Z.A.; Livshits, L.I.

    1988-01-01

    ECG changes after a session of regional intraarterial hyperglycemia (RIH) in 13 patients (the mean age of 49 years) with locally advanced cancer of the tongue, oral mucosa and oropharynx were presented. Taking into account the mean age of patients and the negative ECG time course after a RIH session, the necessity of patients' examination (including ECG after a RIH session and, when indicated, a consultation by a cardiologist) was emphasized

  7. Melatonin prevents hyperglycemia in a model of sleep apnea

    OpenAIRE

    Kaminski,Renata Schenkel Rivera; Martinez,Denis; Fagundes,Micheli; Martins,Emerson Ferreira; Montanari,Carolina Caruccio; Rosa,Darlan Pase; Fiori,Cintia Zappe; Marroni,Norma Possa

    2015-01-01

    Objective Obstructive sleep apnea is a common disorder associated with aging and obesity. Apneas cause repeated arousals, intermittent hypoxia, and oxidative stress. Changes in glucolipidic profile occur in apnea patients, independently of obesity. Animal models of sleep apnea induce hyperglycemia. This study aims to evaluate the effect of the antioxidants melatonin and N-acetylcysteine on glucose, triglyceride, and cholesterol levels in animals exposed to intermittent hypoxia. Materials and ...

  8. High Glucose Promotes Aβ Production by Inhibiting APP Degradation

    Science.gov (United States)

    Zhang, Shuting; Song, Weihong

    2013-01-01

    Abnormal deposition of neuriticplaques is the uniqueneuropathological hallmark of Alzheimer’s disease (AD).Amyloid β protein (Aβ), the major component of plaques, is generated from sequential cleavage of amyloidβ precursor protein (APP) by β-secretase and γ-secretase complex. Patients with diabetes mellitus (DM), characterized by chronic hyperglycemia,have increased risk of AD development.However, the role of high blood glucose in APP processing and Aβ generation remains elusive. In this study, we investigated the effect of high glucose on APP metabolism and Aβ generation in cultured human cells. We found that high glucose treatment significantly increased APP protein level in both neuronal-like and non-neuronal cells, and promoted Aβ generation. Furthermore, we found that high glucose-induced increase of APP level was not due to enhancement of APP gene transcription but resulted from inhibition of APP protein degradation. Taken together, our data indicated that hyperglycemia could promote AD pathogenesis by inhibiting APP degradation and enhancing Aβ production. More importantly, the elevation of APP level and Aβ generation by high glucose was caused by reduction of APP turnover rate.Thus,our study provides a molecular mechanism of increased risk of developing AD in patients withDMand suggests thatglycemic control might be potentially beneficial for reducing the incidence of AD in diabetic patients and delaying the AD progression. PMID:23894546

  9. [Screening for atherosclerosis to prevent cardiovascular risk : a pro-contra debate].

    Science.gov (United States)

    Nanchen, David; Genest, Jacques

    2018-02-28

    Detecting atherosclerosis using imaging techniques is the subject of intense debate in the scientific community. Among the arguments in favor of screening, a better identification or better stratification of cardiovascular risk is mentioned, compared to cardiovascular risk scores based solely on traditional risk factors, such as blood pressure or cholesterol levels. Imaging techniques are also used to monitor the progression of atherosclerosis among patients using lipid-lowering or antihypertensive drugs in primary prevention. However, several experts in recent years have challenged the clinical utility of these imaging techniques in asymptomatic adults. This article proposes a debate « for or against » to describe the main arguments for or against the use of imaging for screening for atherosclerosis.

  10. Coronary, Carotid, and Lower-extremity Atherosclerosis and Their Interrelationship in Danish Patients with Systemic Lupus Erythematosus

    DEFF Research Database (Denmark)

    Kay, Susan Due; Poulsen, Mikael Kjaer; Diederichsen, Axel Cosmus Pyndt

    2015-01-01

    OBJECTIVE: Atherosclerosis is highly prevalent among patients with systemic lupus erythematosus (SLE), but has been demonstrated predominantly in non-European SLE cohorts and few investigations have included more than 1 imaging modality. We aimed to investigate the prevalence of atherosclerosis...... regression model, age (p Systemic Lupus International Collaborating Clinics (SLICC; p = 0.008) were significant independent risk factors for atherosclerosis at any vascular territory. CONCLUSION: Atherosclerosis is highly prevalent among Danish patients with SLE...

  11. Leukocyte Overexpression of Intracellular NAMPT Attenuates Atherosclerosis by Regulating PPARγ-Dependent Monocyte Differentiation and Function.

    Science.gov (United States)

    Bermudez, Beatriz; Dahl, Tuva Borresdatter; Medina, Indira; Groeneweg, Mathijs; Holm, Sverre; Montserrat-de la Paz, Sergio; Rousch, Mat; Otten, Jeroen; Herias, Veronica; Varela, Lourdes M; Ranheim, Trine; Yndestad, Arne; Ortega-Gomez, Almudena; Abia, Rocio; Nagy, Laszlo; Aukrust, Pal; Muriana, Francisco J G; Halvorsen, Bente; Biessen, Erik Anna Leonardus

    2017-06-01

    Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) mediates inflammatory and potentially proatherogenic effects, whereas the role of intracellular NAMPT (iNAMPT), the rate limiting enzyme in the salvage pathway of nicotinamide adenine dinucleotide (NAD) + generation, in atherogenesis is largely unknown. Here we investigated the effects of iNAMPT overexpression in leukocytes on inflammation and atherosclerosis. Low-density lipoprotein receptor-deficient mice with hematopoietic overexpression of human iNAMPT (iNAMPT hi ), on a western type diet, showed attenuated plaque burden with features of lesion stabilization. This anti-atherogenic effect was caused by improved resistance of macrophages to apoptosis by attenuated chemokine (C-C motif) receptor 2-dependent monocyte chemotaxis and by skewing macrophage polarization toward an anti-inflammatory M2 phenotype. The iNAMPT hi phenotype was almost fully reversed by treatment with the NAMPT inhibitor FK866, indicating that iNAMPT catalytic activity is instrumental in the atheroprotection. Importantly, iNAMPT overexpression did not induce any increase in eNAMPT, and eNAMPT had no effect on chemokine (C-C motif) receptor 2 expression and promoted an inflammatory M1 phenotype in macrophages. The iNAMPT-mediated effects at least partly involved sirtuin 1-dependent molecular crosstalk of NAMPT and peroxisome proliferator-activated receptor γ. Finally, iNAMPT and peroxisome proliferator-activated receptor γ showed a strong correlation in human atherosclerotic, but not healthy arteries, hinting to a relevance of iNAMPT/peroxisome proliferator-activated receptor γ pathway also in human carotid atherosclerosis. This study highlights the functional dichotomy of intracellular versus extracellular NAMPT, and unveils a critical role for the iNAMPT-peroxisome proliferator-activated receptor γ axis in atherosclerosis. © 2017 American Heart Association, Inc.

  12. The role of shear stress and arteriogenesis in maintaining vascular homeostasis and preventing cerebral atherosclerosis

    Directory of Open Access Journals (Sweden)

    David Della-Morte

    2015-01-01

    Full Text Available Shear stress (SS is a biomechanical force that is determined by blood flow, vessel geometry, and fluid viscosity. Although a wide range of known vascular risk factors promote development of atherosclerosis, atherosclerotic changes occur predominately at specific sites within the arterial tree, suggesting a critical role for local factors within the vasculature. Atherosclerotic lesions develop predominantly at branches, bends, and bifurcations in the arterial tree because these sites are exposed to low or disturbed blood flow and low SS. Low SS predisposes arteries to atherosclerosis by causing endothelial dysfunction. A natural system of preexisting cerebral collateral arteries protects against ischemia by bypassing sites of arterial occlusion through a mechanism of arteriogenesis. The main trigger for arteriogenesis is impaired vascular homeostasis (VH in response to local changes in SS induced by ischemia. VH is a critical process for maintaining the physiological function of cerebral circulation. It is regulated through a complex biological system of blood flow hemodynamic and physiological responses to flow changes. Restoration of VH by increasing arteriogenesis and SS may provide a novel therapeutic target for stroke, especially in the elderly, who are more prone to VH impairment. In this review article, we discuss the mechanisms and structures necessary to maintain VH in brain circulation, the role of SS, and risk factors leading to atherosclerosis, including the effects of aging. We also discuss arteriogenesis as an adaptive and protective process in response to ischemic injury, the imaging techniques currently available to evaluate arterogenesis such as magnetic resonance imaging/positron emission tomography (MRI/PET, and the potential therapeutic approaches against ischemic injury that target arteriogenesis.

  13. Predictors of endothelial dysfunction and atherosclerosis in rheumatoid arthritis in Indian population

    Directory of Open Access Journals (Sweden)

    Inderjeet Verma

    2017-03-01

    Conclusions: In the present study, FMD and CIMT were impaired in RA, indicating endothelial dysfunction and accelerated atherosclerosis respectively. CRP, TNF-α, serum nitrite, DAS-28 and depleted EPC population predicted endothelial dysfunction. Age, IL-6, HDL, LDL and depleted EPC population predicted accelerated atherosclerosis.

  14. Neutrophils in atherosclerosis. A brief overview

    NARCIS (Netherlands)

    Hartwig, H.; Silvestre Roig, C.; Daemen, M.; Lutgens, E.; Soehnlein, O.

    2015-01-01

    Atherosclerosis is a chronic inflammation of the arterial wall and the continuous infiltration of leukocytes into the plaque enhances the progression of the lesion. Because of the scarce detection of neutrophils in atherosclerotic plaques compared to other immune cells, their contribution was

  15. Aqueous Extract of Nypa fruticans Wurmb. Vinegar Alleviates Postprandial Hyperglycemia in Normoglycemic Rats

    Directory of Open Access Journals (Sweden)

    Nor Adlin Yusoff

    2015-08-01

    Full Text Available Nypa fruticans Wurmb. vinegar, commonly known as nipa palm vinegar (NPV has been used as a folklore medicine among the Malay community to treat diabetes. Early work has shown that aqueous extract (AE of NPV exerts a potent antihyperglycemic effect. Thus, this study is conducted to evaluate the effect of AE on postprandial hyperglycemia in an attempt to understand its mechanism of antidiabetic action. AE were tested via in vitro intestinal glucose absorption, in vivo carbohydrate tolerance tests and spectrophotometric enzyme inhibition assays. One mg/mL of AE showed a comparable outcome to the use of phloridzin (1 mM in vitro as it delayed glucose absorption through isolated rat jejunum more effectively than acarbose (1 mg/mL. Further in vivo confirmatory tests showed AE (500 mg/kg to cause a significant suppression in postprandial hyperglycemia 30 min following respective glucose (2 g/kg, sucrose (4 g/kg and starch (3 g/kg loadings in normal rats, compared to the control group. Conversely, in spectrophotometric enzymatic assays, AE showed rather a weak inhibitory activity against both α-glucosidase and α-amylase when compared with acarbose. The findings suggested that NPV exerts its anti-diabetic effect by delaying carbohydrate absorption from the small intestine through selective inhibition of intestinal glucose transporters, therefore suppressing postprandial hyperglycemia.

  16. Association between the surfactant protein D (SFTPD) gene and subclinical carotid artery atherosclerosis

    DEFF Research Database (Denmark)

    Sorensen, Grith L; Bladbjerg, Else Marie; Steffensen, Rudi

    2016-01-01

    OBJECTIVE: Surfactant protein D (SP-D) is a defense collectin with inflammation-modulating properties. SP-D deficiency inhibits atherosclerosis in vivo, and the circulatory SP-D levels have been previously associated with cardiovascular disease mortality. We hypothesized that plasma SP-D (p......SP-D) and SP-D gene (SFTPD) single nucleotide polymorphisms (SNPs) are risk factors for atherosclerosis. METHODS: We evaluated individuals who were all 60 years old and participated in The Glostrup Population Study. Subclinical atherosclerosis was diagnosed based on the ultrasonographic measurement of intima......: The results do not support that pSP-D levels influence the development of subclinical atherosclerosis. However, the SFTPD SNP data support previous observations from animal studies that SP-D plays a role in the etiology of atherosclerotic disease development. The nominal significant effects are likely...

  17. Crossroads between peripheral atherosclerosis, western-type diet and skeletal muscle pathophysiology: emphasis on apolipoprotein E deficiency and peripheral arterial disease.

    Science.gov (United States)

    Sfyri, Peggy; Matsakas, Antonios

    2017-07-08

    Atherosclerosis is a chronic inflammatory process that, in the presence of hyperlipidaemia, promotes the formation of atheromatous plaques in large vessels of the cardiovascular system. It also affects peripheral arteries with major implications for a number of other non-vascular tissues such as the skeletal muscle, the liver and the kidney. The aim of this review is to critically discuss and assimilate current knowledge on the impact of peripheral atherosclerosis and its implications on skeletal muscle homeostasis. Accumulating data suggests that manifestations of peripheral atherosclerosis in skeletal muscle originates in a combination of increased i)-oxidative stress, ii)-inflammation, iii)-mitochondrial deficits, iv)-altered myofibre morphology and fibrosis, v)-chronic ischemia followed by impaired oxygen supply, vi)-reduced capillary density, vii)- proteolysis and viii)-apoptosis. These structural, biochemical and pathophysiological alterations impact on skeletal muscle metabolic and physiologic homeostasis and its capacity to generate force, which further affects the individual's quality of life. Particular emphasis is given on two major areas representing basic and applied science respectively: a)-the abundant evidence from a well-recognised atherogenic model; the Apolipoprotein E deficient mouse and the role of a western-type diet and b)-on skeletal myopathy and oxidative stress-induced myofibre damage from human studies on peripheral arterial disease. A significant source of reactive oxygen species production and oxidative stress in cardiovascular disease is the family of NADPH oxidases that contribute to several pathologies. Finally, strategies targeting NADPH oxidases in skeletal muscle in an attempt to attenuate cellular oxidative stress are highlighted, providing a better understanding of the crossroads between peripheral atherosclerosis and skeletal muscle pathophysiology.

  18. Food and nutrition in the prevention of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Izabela Kamila Wojarska

    2018-05-01

    Full Text Available Cardiovascular disease is the most frequent cause of hospitalization (15% and death (46% in Poland, as well as worldwide (31%, by reason of strenuous activity in the field of preventative healthcare in all age groups has to be taken. Preventative nutrition of atherosclerosis predicts mostly intake restriction of food containing: fatty acids, cholesterol, salt, monosaccharides and animal protein, while increasing intake of vitamins, minerals, fiber and antioxidant substances. Eating habits and nutritional status of women who are planning pregnancy have a crucial impact on its course, development of the fetus and children’s health in later years of their life. For all of cardiac patients well balanced diet is advised. In preventative care of Cardiovascular Disease it is advised to apply the diet given by a certified dietician and adjusted to fit patient’s needs. It is to remember, that besides a good diet, an important therapeutic factor of the patients with atherosclerosis is physical activity. Cardiovascular disease is a serious concern in Poland, as well as worldwide. Eating habits are playing a big role in pathogenesis and prevention of atherosclerosis.

  19. Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations.

    Science.gov (United States)

    Thompson, Randall C; Allam, Adel H; Lombardi, Guido P; Wann, L Samuel; Sutherland, M Linda; Sutherland, James D; Soliman, Muhammad Al-Tohamy; Frohlich, Bruno; Mininberg, David T; Monge, Janet M; Vallodolid, Clide M; Cox, Samantha L; Abd el-Maksoud, Gomaa; Badr, Ibrahim; Miyamoto, Michael I; el-Halim Nur el-Din, Abd; Narula, Jagat; Finch, Caleb E; Thomas, Gregory S

    2013-04-06

    Atherosclerosis is thought to be a disease of modern human beings and related to contemporary lifestyles. However, its prevalence before the modern era is unknown. We aimed to evaluate preindustrial populations for atherosclerosis. We obtained whole body CT scans of 137 mummies from four different geographical regions or populations spanning more than 4000 years. Individuals from ancient Egypt, ancient Peru, the Ancestral Puebloans of southwest America, and the Unangan of the Aleutian Islands were imaged. Atherosclerosis was regarded as definite if a calcified plaque was seen in the wall of an artery and probable if calcifications were seen along the expected course of an artery. Probable or definite atherosclerosis was noted in 47 (34%) of 137 mummies and in all four geographical populations: 29 (38%) of 76 ancient Egyptians, 13 (25%) of 51 ancient Peruvians, two (40%) of five Ancestral Puebloans, and three (60%) of five Unangan hunter gatherers (p=NS). Atherosclerosis was present in the aorta in 28 (20%) mummies, iliac or femoral arteries in 25 (18%), popliteal or tibial arteries in 25 (18%), carotid arteries in 17 (12%), and coronary arteries in six (4%). Of the five vascular beds examined, atherosclerosis was present in one to two beds in 34 (25%) mummies, in three to four beds in 11 (8%), and in all five vascular beds in two (1%). Age at time of death was positively correlated with atherosclerosis (mean age at death was 43 [SD 10] years for mummies with atherosclerosis vs 32 [15] years for those without; phuman beings raises the possibility of a more basic predisposition to the disease. National Endowment for the Humanities, Paleocardiology Foundation, The National Bank of Egypt, Siemens, and St Luke's Hospital Foundation of Kansas City. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Effects of catechins and caffeine on the development of atherosclerosis in mice.

    Science.gov (United States)

    Liu, Litong; Nagai, Izumi; Gao, Ying; Matsushima, Yoshibumi; Kawai, Yoshichika; Sayama, Kazutoshi

    2017-10-01

    Atherosclerosis is one of the diseases related to metabolic syndrome which is caused by obesity. Previous reports have shown that green tea and its components have anti-obesity effect. We examined whether catechins and caffeine can prevent the development of atherosclerosis by oral administration, singly or in combination to the atherosclerosis model mice. Results demonstrated that the number of atherosclerotic regions in the aorta was significantly reduced by the combined treatment, and the atherosclerotic area was also improved. Serum HDL-C increased by caffeine single treatment, but no effect on the TG and TC by any treatments. Moreover, ECG illuviated to atheromatous lesions in aorta and the illuviation was enhanced by caffeine. The mRNA expression levels of LOX-1 and TNF-α showed a tendency to suppress by the combined treatment. These results indicated that the combined administration of catechins and caffeine has the inhibitory effect on the development of atherosclerosis in mice.

  1. Murine Norovirus 4 (MNV-4 Infections Trigger Various Effects on Atherosclerosis Development

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    Rafeezul Mohamed

    2018-05-01

    Full Text Available Murine norovirus (MNV infection can cause morbidity and mortality to immune compromised mice, especially colonies in research laboratory. MNV also can infect and propagates in macrophages and dendritic cells which trigger atherosclerosis development through the accumulation of these cells followed by the formation of foam cells. Recently, MNV-4 infection was associated with an increase in aortic sinus lesion size in LDLR (low-density lipoprotein receptor and ApoE (Apolipoprotein E deficient mice, both are well established mouse models for atherosclerosis research. Therefore, this review is intended to summarize the impacts of MNV infection in these two mouse models of atherosclerosis. The findings from all the related studies are important in understanding the fundamental effect of MNV infection on atherosclerosis development. In addition, this information could provide insight to researchers on the evaluation to eliminate MNV infection in research facility to avoid any unintended effect in their research, particularly in-vivo studies involving mice.

  2. Risk of Hyperglycemia and Diabetes after Early-Life Famine Exposure: A Cross-Sectional Survey in Northeastern China

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    Yangyu Zhang

    2018-05-01

    Full Text Available Previous studies suggested that malnutrition during early life may play an essential role in later outcomes and disease risk in adulthood. We aimed to investigate the risks of hyperglycemia and diabetes 50 years after early-life famine exposure in a Northeastern Chinese population. We used the data from 5690 adults born between 1956 and 1965 in selected communities from a 2012 cross-sectional study. The early-childhood exposure cohort showed an increased risk of hyperglycemia compared with the unexposed cohort in the female population (odds ratio (OR 1.46; 95% confidence interval (CI 1.04, 2.06. The increased risk of diabetes in the early-childhood and fetal exposure cohorts was 37.0% (95% CI 1.05–1.79 and 50% (95% CI 1.15–1.96, respectively. For women, the risk of diabetes was more pronounced in the fetal-exposed cohort (OR 1.82; 95% CI 1.26–2.63 than in the early-childhood cohort (OR 1.57; 95% CI 1.08–2.26. Early-life exposure to famine increased the risk of diabetes. Furthermore, early-childhood exposure to famine might increase the risk of hyperglycemia in women. A policy for preventing early life malnutrition should be drafted by the government to prevent hyperglycemia and diabetes in adulthood.

  3. Hyperglycemia associated dissociative fugue (organic dissociative disorder in an elderly

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    Dushad Ram

    2015-01-01

    Full Text Available Inadequate glycemic control in patients with diabetes is known to be associated with psychiatric disorders such as depression, anxiety disorder, and cognitive impairment. However, dissociative syndrome has not been reported so far. Here we are reporting a case of repeated dissociative fugue associated with hyperglycemia, in an elderly with type II diabetes. Possible neurobiological mechanism has been discussed.

  4. Biological signatures of asymptomatic extra- and intracranial atherosclerosis: the Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) study.

    Science.gov (United States)

    López-Cancio, Elena; Galán, Amparo; Dorado, Laura; Jiménez, Marta; Hernández, María; Millán, Mónica; Reverté, Silvia; Suñol, Anna; Barallat, Jaume; Massuet, Anna; Alzamora, Maria Teresa; Dávalos, Antonio; Arenillas, Juan Francisco

    2012-10-01

    Intracranial atherosclerotic disease (ICAD) remains a challenge for stroke primary and secondary prevention. Molecular pathways involved in the development of ICAD from its asymptomatic stages are largely unknown. In our population-based study, we aimed to compare the risk factor and biomarker profiles associated with intracranial and extracranial asymptomatic cerebral atherosclerosis. The Asymptomatic Intracranial Atherosclerosis (AsIA) study cohort includes a random sample population of 933 white subjects >50 years with a moderate to high vascular risk (based on REGICOR score) and without a history of stroke (64% males; mean age, 66 years). Carotid and intracranial atherosclerosis were screened by cervical and transcranial color-coded Duplex ultrasound, being moderate to severe stenoses confirmed by MR angiography. We registered clinical and anthropometric data and created a biobank with blood samples at baseline. A panel of biomarkers involved in atherothrombogenesis was determined: C-reactive protein, asymmetric-dimethylarginine, resistin, and plasminogen activator inhibitor-1. Insulin resistance was quantified by Homeostasis Model Assessment index. After multinomial regression analyses, male sex, hypertension, smoking, and alcoholic habits were independent risk factors of isolated extracranial atherosclerotic disease. Diabetes and metabolic syndrome conferred a higher risk for ICAD than for extracranial atherosclerotic disease. Moreover, metabolic syndrome and insulin resistance were independent risk factors of moderate to severe ICAD but were not risk factors of moderate to severe extracranial atherosclerotic disease. Regarding biomarkers, asymmetric-dimethylarginine was independently associated with isolated ICAD and resistin with combined ICAD-extracranial atherosclerotic disease. Our findings show distinct clinical and biological profiles in subclinical ICAD and extracranial atherosclerotic disease. Insulin resistance emerged as an important molecular

  5. Toll-Like Receptor-2 Mediates Diet and/or Pathogen Associated Atherosclerosis: Proteomic Findings

    OpenAIRE

    Madan, Monika; Amar, Salomon

    2008-01-01

    Accumulating evidence implicates a fundamental link between the immune system and atherosclerosis. Toll-like receptors are principal sensors of the innate immune system. Here we report an assessment of the role of the TLR2 pathway in atherosclerosis associated with a high-fat diet and/or bacteria in ApoE(+/-) mice.To explore the role of TLR2 in inflammation- and infection-associated atherosclerosis, 10 week-old ApoE(+/-)-TLR2(+/+), ApoE(+/-)-TLR2(+/-) and ApoE(+/-)-TLR2(-/-) mice were fed eit...

  6. Molecular Imaging of Inflammation in Atherosclerosis

    Science.gov (United States)

    Wildgruber, Moritz; Swirski, Filip K.; Zernecke, Alma

    2013-01-01

    Acute rupture of vulnerable plaques frequently leads to myocardial infarction and stroke. Within the last decades, several cellular and molecular players have been identified that promote atherosclerotic lesion formation, maturation and plaque rupture. It is now widely recognized that inflammation of the vessel wall and distinct leukocyte subsets are involved throughout all phases of atherosclerotic lesion development. The mechanisms that render a stable plaque unstable and prone to rupture, however, remain unknown and the identification of the vulnerable plaque remains a major challenge in cardiovascular medicine. Imaging technologies used in the clinic offer minimal information about the underlying biology and potential risk for rupture. New imaging technologies are therefore being developed, and in the preclinical setting have enabled new and dynamic insights into the vessel wall for a better understanding of this complex disease. Molecular imaging has the potential to track biological processes, such as the activity of cellular and molecular biomarkers in vivo and over time. Similarly, novel imaging technologies specifically detect effects of therapies that aim to stabilize vulnerable plaques and silence vascular inflammation. Here we will review the potential of established and new molecular imaging technologies in the setting of atherosclerosis, and discuss the cumbersome steps required for translating molecular imaging approaches into the clinic. PMID:24312156

  7. [25 year experience with using surgical correction of dislipidemia in treatment of patients with atherosclerosis].

    Science.gov (United States)

    Sedov, V M; Mirchuk, K K; Sedletskiĭ, Iu I

    2011-01-01

    An analysis of results of using partial ileoshunting for the treatment of dislipidemia in 159 patients with atherosclerosis has shown that operation of partial ileoshunting has an obligatory, pronounced and lifelong lipidcorrecting effect. An antiatherogenic effect of the operation of partial ileoshunting is manifested as the improvement of the clinical course of the disease caused by atherosclerosis, by less number of thrombotic complications of atherosclerosis and less lethality from cardio-vascular diseases. At a longer follow-up period, the efficiency of partial ileoshunting as a means of secondary prophylactics of atherosclerosis is confirmed but in case of liquidation after operation of dislipoproteidemia.

  8. Post-challenge hyperglycemia is a significant risk factor for the development of hepatocellular carcinoma in patients with chronic hepatitis C

    International Nuclear Information System (INIS)

    Takahashi, Hirokazu; Mizuta, Toshihiko; Eguchi, Yuichiro

    2011-01-01

    Several epidemiological studies have reported that diabetes mellitus is a risk factor for hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-positive patients. However, it is unclear whether or not post-challenge hyperglycemia is a risk factor. The purpose of this study was to determine the association between post-challenge hyperglycemia and hepatocarcinogenesis in HCV-positive patients. A total of 203 HCV-RNA-positive subjects (108 males, mean age 54.3±10.8 years; 95 females, mean age 56.6±10.3 years; genotype 1b/2a/2b/3a: 152/38/12/1) who underwent liver biopsy and a 75-g oral glucose tolerance test, and who were treated with interferon (IFN) were enrolled in this study. None of the subjects had been treated with antidiabetic drugs. The subjects underwent ultrasonography and/or computed tomography every 6 months after the end of the IFN therapy. Thirteen patients, including one patient who achieved a sustained viral response (SVR) with IFN, developed HCC. On multivariate analysis, male sex, age >65 years, excessive alcohol consumption, non-SVR, liver steatosis area >5% in liver specimens, and 120-min post-challenge hyperglycemia were risk factors for the development of HCC. After matching subjects for sex, age, alcohol intake, and response to the IFN therapy, advanced fibrosis stages [hazard ratio (HR) 2.8], liver steatosis (HR 5.4), and 120-min post-challenge hyperglycemia (HR 4.9) were significant risk factors for the development of HCC. Furthermore, after matching for the fibrosis stage, liver steatosis (HR 5.7) and 120-min post-challenge hyperglycemia (HR 6.9) remained as significant factors for HCC development. Post-challenge hyperglycemia is an independent risk factor for HCC in HCV-positive patients. (author)

  9. Glucagon-like peptide-1 decreases intracerebral glucose content by activating hexokinase and changing glucose clearance during hyperglycemia

    DEFF Research Database (Denmark)

    Gejl, Michael; Egefjord, Lærke; Lerche, Susanne

    2012-01-01

    Type 2 diabetes and hyperglycemia with the resulting increase of glucose concentrations in the brain impair the outcome of ischemic stroke, and may increase the risk of developing Alzheimer's disease (AD). Reports indicate that glucagon-like peptide-1 (GLP-1) may be neuroprotective in models of AD...... in the actions of GLUT1 and glucose metabolism: GLP-1 ensures less fluctuation of brain glucose levels in response to alterations in plasma glucose, which may prove to be neuroprotective during hyperglycemia....

  10. Gender-Specific Association of Desacylated Ghrelin with Subclinical Atherosclerosis in the Metabolic Syndrome.

    Science.gov (United States)

    Zanetti, Michela; Gortan Cappellari, Gianluca; Semolic, Annamaria; Burekovic, Ismet; Fonda, Maurizio; Cattin, Luigi; Barazzoni, Rocco

    2017-07-01

    Ghrelin, a gastric hormone with pleiotropic effects modulates vascular function and may influence atherosclerosis. Plasma ghrelin is reduced in the metabolic syndrome (MS), which is also characterized by early atherosclerosis. Ghrelin circulates in acylated (AG) and desacylated (DAG) forms. Their relative impact and that of gender on subclinical atherosclerosis in MS is unknown. To investigate potential associations of total, AG and DAG with carotid atherosclerosis and with gender in the MS. Plasma total ghrelin, AG, DAG and carotid artery IMT (cIMT) were measured in 46 MS patients (NCEP-ATP III criteria, 22M/24F). Compared with males, females had higher (p ghrelin nor AG and DAG were associated with cIMT in all MS patients nor in the male subgroup. In females, a negative (p ghrelin and AG. In multivariate modeling, DAG remained negatively (p <0.05) associated with cIMT after adjusting for plasma glucose and cardiovascular risk factors. These data indicate a negative independent association between DAG and cIMT in middle-aged women with the MS and suggest a gender-specific modulatory function of DAG in the development of atherosclerosis. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

  11. Self-monitoring of blood glucose is associated with problem-solving skills in hyperglycemia and hypoglycemia.

    Science.gov (United States)

    Wang, Jing; Zgibor, Janice; Matthews, Judith T; Charron-Prochownik, Denise; Sereika, Susan M; Siminerio, Linda

    2012-01-01

    The purpose of this study was to examine the association between self-monitoring of blood glucose (SMBG) and problem-solving skills in response to detected hyperglycemia and hypoglycemia among patients with type 2 diabetes. Data were obtained from the American Association of Diabetes Educators Outcome System, implemented in 8 diabetes self-management education programs in western Pennsylvania. SMBG was measured by asking patients how often they checked, missed checking, or checked blood glucose later than planned. Problem-solving skill was measured by asking how often they modified their behaviors after detecting high or low blood glucose. Most patients checked their blood glucose at least once per day. However, when blood glucose was high or low, many of them reported doing nothing, and only some of them resolved the problem. There were significant associations between self-monitoring of blood glucose and problem-solving skills for hyperglycemia and hypoglycemia, after controlling for age, gender, ethnicity, education, and time since diagnosis. Patients reported poor problem-solving skills when detecting hyperglycemia and hypoglycemia via SMBG. Patients need to learn problem-solving skills along with SMBG training to achieve glycemic control.

  12. Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus.

    Science.gov (United States)

    Yahagi, Kazuyuki; Kolodgie, Frank D; Lutter, Christoph; Mori, Hiroyoshi; Romero, Maria E; Finn, Aloke V; Virmani, Renu

    2017-02-01

    The continuing increase in the prevalence of diabetes mellitus in the general population is predicted to result in a higher incidence of cardiovascular disease. Although the mechanisms of diabetes mellitus-associated progression of atherosclerosis are not fully understood, at clinical and pathological levels, there is an appreciation of increased disease burden and higher levels of arterial calcification in these subjects. Plaques within the coronary arteries of patients with diabetes mellitus generally exhibit larger necrotic cores and significantly greater inflammation consisting mainly of macrophages and T lymphocytes relative to patients without diabetes mellitus. Moreover, there is a higher incidence of healed plaque ruptures and positive remodeling in hearts from subjects with type 1 diabetes mellitus and type 2 diabetes mellitus, suggesting a more active atherogenic process. Lesion calcification in the coronary, carotid, and other arterial beds is also more extensive. Although the role of coronary artery calcification in identifying cardiovascular disease and predicting its outcome is undeniable, our understanding of how key hormonal and physiological alterations associated with diabetes mellitus such as insulin resistance and hyperglycemia influence the process of vascular calcification continues to grow. Important drivers of atherosclerotic calcification in diabetes mellitus include oxidative stress, endothelial dysfunction, alterations in mineral metabolism, increased inflammatory cytokine production, and release of osteoprogenitor cells from the marrow into the circulation. Our review will focus on the pathophysiology of type 1 diabetes mellitus- and type 2 diabetes mellitus-associated vascular disease with particular focus on coronary and carotid atherosclerotic calcification. © 2016 American Heart Association, Inc.

  13. Parameters of platelet activity in patients with thyrotoxicosis in the presence of chronic hyperglycemia and atrial fibrillation

    Directory of Open Access Journals (Sweden)

    G G Petrik

    2011-06-01

    Full Text Available Object. The study of platelet hemostasis in patients with thyrotoxicosis in the presence of chronic hyperglycemia and atrial fibrillation to prevent coagulation disorders. Material and methods. A comprehensive analysis of the parameters of platelet and coagulation hemostasis in 91 patients (67 women and 24 men with uncomplicated thyrotoxicosis, as well as with the atrial fibrillation or a combination of hyperthyroidism with diabetes has been completed. Results. The aggregation activity of platelets in uncomplicated thyrotoxicosis comparable with that of healthy people. atrial fibrillation, as well as chronic hyperglycemia, modify platelet activity by increasing the average volume of platelets, their ability to aggregate intensification of the release reaction and along with the decrease of disaggregation properties. Regardless of the presence of diabetes or atrial fibrillation, hyperthyroidism is accompanied by the activation of coagulation. Conclusion. The presence of transforming effects of chronic hyperglycemia and atrial fibrillation on the platelet activity determines the feasibility of differentiated approach to the prevent of coagulation disorders in patients with thyrotoxicosis.

  14. Therapeutic implications of chemokine-mediated pathways in atherosclerosis: realistic perspectives and utopias.

    Science.gov (United States)

    Apostolakis, Stavros; Amanatidou, Virginia; Spandidos, Demetrios A

    2010-09-01

    Current perspectives on the pathogenesis of atherosclerosis strongly support the involvement of inflammatory mediators in the establishment and progression of atherosclerostic lesions. Chemokine-mediated mechanisms are potent regulators of such processes by orchestrating the interactions of inflammatory cellular components of the peripheral blood with cellular components of the arterial wall. The increasing evidence supporting the role of chemokine pathways in atherosclerosis renders chemokine ligands and their receptors potential therapeutic targets. In the following review, we aim to highlight the special structural and functional features of chemokines and their receptors in respect to their roles in atherosclerosis, and examine to what extent available data can be applied in disease management practices.

  15. Inpatient hyperglycemia management: the opportunities of a new basal insulin

    Directory of Open Access Journals (Sweden)

    Natalino Simioni

    2016-06-01

    Full Text Available The management of hospitalized diabetic patients for any cause is often difficult and affected not only by the comorbidities of the patient but also by the hospital setting. It is well known that at the admission the antidiabetic drugs should be discontinued on behalf of insulin therapy with insulin analogues, as a function of a basal-bolus insulin approach according to the phenotype of the patient, type of nutrition (enteral or parenteral rather than oral, or concomitant hyperglycemic therapy (e.g., steroid. The average stay of diabetic patients hospitalized for any cause is significantly correlated with both the number of hypoglycemia and hyperglycemia. Compared to patients treated with sliding scale patients using a custom algorithm show a significant reduction in the number of hypoglycemia and hyperglycemia episodes and in the length of stay. We analyze the clinical profile of a novel basal insulin, degludec, and explore the potential clinical benefit for diabetic inpatient. The continuation of insulin therapy at home in the immediate post-hospitalization (if necessary, also correlates with a reduction in the rate of re-hospitalization, which combined with close follow-up diabetes can result in a reduction of chronic complications.

  16. ß-Cell Specific Overexpression of GPR39 Protects against Streptozotocin-Induced Hyperglycemia

    DEFF Research Database (Denmark)

    Egerod, Kristoffer Lihme; Jin, Chunyu; Petersen, Pia Steen

    2011-01-01

    and OGTT. Although the overexpression of the constitutively active GPR39 receptor in animals not treated with streptozotocin appeared by itself to impair the glucose tolerance slightly and to decrease the ß-cell mass, it nevertheless totally protected against the gradual hyperglycemia in the steptozotocin...

  17. α-Defensins Induce a Post-translational Modification of Low Density Lipoprotein (LDL) That Promotes Atherosclerosis at Normal Levels of Plasma Cholesterol.

    Science.gov (United States)

    Abu-Fanne, Rami; Maraga, Emad; Abd-Elrahman, Ihab; Hankin, Aviel; Blum, Galia; Abdeen, Suhair; Hijazi, Nuha; Cines, Douglas B; Higazi, Abd Al-Roof

    2016-02-05

    Approximately one-half of the patients who develop clinical atherosclerosis have normal or only modest elevations in plasma lipids, indicating that additional mechanisms contribute to pathogenesis. In view of increasing evidence that inflammation contributes to atherogenesis, we studied the effect of human neutrophil α-defensins on low density lipoprotein (LDL) trafficking, metabolism, vascular deposition, and atherogenesis using transgenic mice expressing human α-defensins in their polymorphonuclear leukocytes (Def(+/+)). Accelerated Def(+/+) mice developed α-defensin·LDL complexes that accelerate the clearance of LDL from the circulation accompanied by enhanced vascular deposition and retention of LDL, induction of endothelial cathepsins, increased endothelial permeability to LDL, and the development of lipid streaks in the aortic roots when fed a regular diet and at normal plasma levels of LDL. Transplantation of bone marrow from Def(+/+) to WT mice increased LDL clearance, increased vascular permeability, and increased vascular deposition of LDL, whereas transplantation of WT bone marrow to Def(+/+) mice prevented these outcomes. The same outcome was obtained by treating Def(+/+) mice with colchicine to inhibit the release of α-defensins. These studies identify a potential new link between inflammation and the development of atherosclerosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Biomarkers of Subclinical Atherosclerosis in Patients with Autoimmune Disorders

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    Elisabetta Profumo

    2012-01-01

    Full Text Available Atherosclerosis is accelerated in rheumatoid arthritis (RA and psoriatic arthritis (PsA. We investigated a possible association of oxidized low-density lipoproteins (ox-LDLs, nitric oxide (NO, 3-nitrotyrosine, vitamin A, vitamin E, and β-carotene serum levels with subclinical atherosclerosis in RA and PsA. By the use of ELISA, we observed higher ox-LDL levels in patients with intima-media thickness (IMT > 1 than in patients with IMT ≤ 1 and a negative correlation between NO levels and IMT values. By the use of high-performance liquid chromatography, we determined higher levels of vitamin A in patients with PsA and IMT ≤ 1 than in controls and lower levels of β-carotene in patients with RA and PsA than in controls. β-carotene concentrations were negatively correlated to the duration of disease in RA. Our study confirms that ox-LDLs and NO may be markers of accelerated atherosclerosis in RA and PsA whereas vitamins seem to be associated only to the presence of the autoimmune disorders.

  19. Correlation between Stress Hyperglycemia and Short-Term Prognosis in non Diabetic Patients with Acute Myocardial Infarction

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    Rafighdoust Amirhossein

    2009-03-01

    Full Text Available Background: Abnormal hyperglycemia is a common finding in early phase of acute myocardial infarction that is named as stress hyperglycemia. In this study we have evaluated primary blood sugar of non-diabetic patients with acute myocardial infarction at the time of admission to compare the early complications between patients with high or normal blood sugar. We aimed to find any relation between primary blood sugar and post MI complication rate. Materials and Methods: One hundred non-diabetic patients with acute myocardial infarction who were referred to heart emergency ward of Imam Reza Hospital (Mashhad, Iran were included in this study. According to primary blood glucose level, 50 patients with blood glucose > 126 mg/dl were compared with 50 patients with normal blood glucose level. All patients were evaluated during hospitalization and daily clinical examinations laboratory tests, and routine non-invasive assessments were done. The results were analyzed by SPSS software and the level of signification difference was described as p<0.05.Results: Sinus tachycardia, atrial fibrillation, bundle branch block, ventricular extrasystole, prolonged PR-interval and heart failure according to Klip classification and also according to echocardiographic index (EF<50 were statistically significant and more common in hyperglycemic patients (P<0.05. Thromboembolic and mechanical complications (papillary muscle dysfunction, pericarditis, phlebitis and angina were also more common in hyperglycemic group although the differences were not significant statistically. Conclusion: It seems that high rate of early complications in non-diabetic patients with acute myocardial infarction is directly related to primary hyperglycemia (stress hyperglycemia.

  20. Hyperglycemia induced damage to mitochondrial respiration in renal mesangial and tubular cells: Implications for diabetic nephropathy

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    Anna Czajka

    2016-12-01

    Full Text Available Damage to renal tubular and mesangial cells is central to the development of diabetic nephropathy (DN, a complication of diabetes which can lead to renal failure. Mitochondria are the site of cellular respiration and produce energy in the form of ATP via oxidative phosphorylation, and mitochondrial dysfunction has been implicated in DN. Since the kidney is an organ with high bioenergetic needs, we postulated that hyperglycemia causes damage to renal mitochondria resulting in bioenergetic deficit. The bioenergetic profiles and the effect of hyperglycemia on cellular respiration of human primary mesangial (HMCs and proximal tubular cells (HK-2 were compared in normoglycemic and hyperglycemic conditions using the seahorse bio-analyzer. In normoglycemia, HK-2 had significantly lower basal, ATP-linked and maximal respiration rates, and lower reserve capacity compared to HMCs. Hyperglycemia caused a down-regulation of all respiratory parameters within 4 days in HK-2 but not in HMCs. After 8 days of hyperglycemia, down-regulation of respiratory parameters persisted in tubular cells with compensatory up-regulated glycolysis. HMCs had reduced maximal respiration and reserve capacity at 8 days, and by 12 days had compromised mitochondrial respiration despite which they did not enhance glycolysis. These data suggest that diabetes is likely to lead to a cellular deficit in ATP production in both cell types, although with different sensitivities, and this mechanism could significantly contribute to the cellular damage seen in the diabetic kidney. Prevention of diabetes induced damage to renal mitochondrial respiration may be a novel therapeutic approach for the prevention/treatment of DN.

  1. Association of hypomagnesemia with hyperglycemia and its renal complication in outpatients

    International Nuclear Information System (INIS)

    Ain, Q.U.; Ijaz, A.; Asif, N.; Rafi, T.; Ansari, U.; Tariq, A.

    2017-01-01

    Objective: To evaluate the association of hypomagnesemia with hyperglycemia and its renal complication in outpatients. Study Design: Case control study. Place and Duration of Study: Department of chemical pathology and endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from October 2014 to July 2015. Material and Methods: Adults of either gender aged 20 years and above comprising 63 subjects with hyperglycemia and 63 controls with normoglycemia were consecutively inducted in the study. Patients with malabsorption, thyroid dysfunction or adrenal dysfunction, renal impairment, taking mineral supplement, pregnancy, lactation and any acute illness were excluded from the study. Fasting plasma glucose (FPG) and serum magnesium (Mg) level were measured on ADVIA 1800 siemens clinical chemistry auto-analyzer with hexokinase and xylidyl blue methods, respectively. Urine albumin was analyzed by Immunoturbidimetric method and urine creatinine was measured by the Jaffe kinetic assay on same analyzer. Albumin/creatinine ratio (ACR) was calculated. Pearson correlation coefficient 'r' was calculated for serum Mg with FPG and ACR. Mean serum Mg levels in hyperglycemic and normoglycemic groups were compared using in dependent sample 't' test. Frequency of hypomagnesemia (serum magnesium ≤ 0.66 mmol/L) was also calculated in hyperglycemic subjects with type 2 diabetes mellitus (T2DM). A p-value <0.05 was considered statistically significant. Results: Serum Mg has significant inverse correlation with FPG (r=-0.543, p=0.001) and ACR (r=-0.474; p=0.001).Mean serum Mg was 0.78 mmol/l in hyperglycemics and 0.88 mmol/l in normoglycemics (p=0.001). The frequency of hypomagnesemia in subjects with type 2 Diabetes Mellitus (T2DM) was found to be 18.8 percent while no subject with pre-diabetes and normoglycemia had hypomagnesemia. Conclusion: Subjects with hyperglycemia had significantly lower mean serum Mg levels compared with healthy counterparts. Hypomagnesemia was also

  2. Increased LDL susceptibility to oxidation accelerates future carotid artery atherosclerosis

    Directory of Open Access Journals (Sweden)

    Aoki Toshinari

    2012-01-01

    Full Text Available Abstract Background We analyzed the causal relationship between LDL susceptibility to oxidation and the development of new carotid artery atherosclerosis over a period of 5 years. We previously described the determinants related to a risk of cardiovascular changes determined in a Japanese population participating in the Niigata Study, which is an ongoing epidemiological investigation of the prevention of cardiovascular diseases. Methods We selected 394 individuals (169 males and 225 females who underwent a second carotid artery ultrasonographic examination in 2001 - 2002 for the present study. The susceptibility of LDL to oxidation was determined as the photometric absorbance and electrophoretic mobility of samples that had been collected in 1996 - 1997. The measurements were compared with ultrasonographic findings obtained in 2001 - 2002. Results The multivariate-adjusted model showed that age (odds ratio (OR, 1.034; 95% confidence interval (95%CI, 1.010 - 1.059, HbA1c (OR, 1.477; 95%CI, 0.980 - 2.225, and photometric O/N (OR, 2.012; 95%CI, 1.000 - 4.051 were significant variables that could independently predict the risk of new carotid artery atherosclerosis. Conclusion The susceptibility of LDL to oxidation was a significant parameter that could predict new carotid artery atherosclerosis over a 5-year period, and higher susceptibility was associated with a higher incidence of new carotid artery atherosclerosis.

  3. [The frequency of risk factors for atherosclerosis in youth aged 16 and 18 years--students of upper-secondary schools in Poland].

    Science.gov (United States)

    Jodkowska, Maria; Oblacińska, Anna; Mikiel-Kostyra, Krystyna; Tabak, Izabela

    2012-01-01

    1. To examine the prevalence of selected risk factors for atherosclerosis: overweight, tobacco smoking, low physical activity, psychological distress and type A personality (characterized by tenseness, impatience, competitiveness, and aggressiveness) in adolescents and to assess the frequency the coexistence of risk factors (≥3) in relation to gender, age and school type. A cross-sectional study was carried out in a representative sample of youth aged 16 and 18 years (N=2983) in 8 voivodeships in Poland. The frequency of five atherosclerosis risk factors and their coexistence (≥3) was examined using self-reported questionnaires, in relation to gender, age and school type. Logistic regression analyses were used to assess the influence of the variables (gender, age and school type) on odds ratios of risk factor coexistence. Low physical activity was the most common risk factor, statistically more frequent in students from Basic Vocational Schools than in other school types (pSchools there was also the highest percentage of cigarette smokers (pSchools. The highest risk factor accumulation (≥3) was observed among students from Basic Vocational Schools (40%), significantly more frequent in girls than boys (47.5% and 37.5% respectively). Multivariable analyses show that students from Basic Vocational Schools had twice the odds (OR=2.25, pcoexistence of risk factors for atherosclerosis as compared with students from General Upper Secondary Schools, girls had almost twice as many occurrences (OR=1.83, pschool types requires precise definition of priority health promotion activities depending on school type. 2. Students from Basic Vocational Schools should be the target group for intervention aimed at reducing atherosclerosis risk factors.

  4. Regulation of the renin–angiotensin system in coronary atherosclerosis: A review of the literature

    Directory of Open Access Journals (Sweden)

    Ramadan A Hammoud

    2008-01-01

    Full Text Available Ramadan A Hammoud, Christopher S Vaccari, Sameer H Nagamia, Bobby V KhanEmory University School of Medicine, Division of Cardiology, Grady Memorial Hospital Vascular Research Laboratory, Atlanta, Georgia, USAAbstract: Activation of the renin–angiotensin system (RAS is significant in the pathogenesis of cardiovascular disease and specifically coronary atherosclerosis. There is strong evidence that the RAS has effects on the mechanisms of action of atherosclerosis, including fibrinolytic balance, endothelial function, and plaque stability. Pharmacological inhibition of the renin angiotensin system includes angiotensin converting enzyme (ACE inhibitors, angiotensin receptor blockers (ARBs, and renin inhibitors. These agents have clinical benefits in reducing morbidity and mortality in the management of hypertension. In addition, ACE inhibitors and ARBs have shown to be effective in the management of congestive heart failure and acute myocardial infarction. This review article discusses the biochemical and molecular mechanisms involving the RAS in coronary atherosclerosis as well as the effects of RAS inhibition in clinical studies involving coronary atherosclerosis.Keywords: angiotensin II, atherosclerosis, endothelium, inflammation, vasculature

  5. Particulate matter and atherosclerosis: a bibliometric analysis of original research articles published in 1973–2014

    Directory of Open Access Journals (Sweden)

    Feifei Wang

    2016-04-01

    Full Text Available Abstract Background Epidemiological and experimental studies have suggested that exposure to particulate air pollution may promote progression of atherosclerosis. Methods In the present study, the characteristics and trends of the research field of particulate matter (PM and atherosclerosis were analyzed using bibliometric indicators. Bibliometric analysis was based on original papers obtained from PubMed/MEDLINE search results (from 1973 to 2014 using Medical Subject Headings (MeSH terms. A fully-detailed search strategy was employed, and articles were imported into the Thomson Data Analyzer (TDA software. Results The visualizing network of the collaborative researchers was analyzed by Ucinet 6 software. Main research topics and future focuses were explored by co-word and cluster analysis. The characteristics of these research articles were summarized. The number of published articles has increased from five for the period 1973–1978 to 89 for the period 2009–2014. Tobacco smoke pollution, smoke and air PM were the most studied targets in this research field. Coronary disease was the top health outcome posed by PM exposure. The aorta and endothelium vascular were the principal locations of atherosclerotic lesions, which were enhanced by PM exposure. Oxidative stress and inflammation were of special concern in the current mechanistic research system. The top high-frequency MeSH terms were clustered, and four popular topics were further presented. Conclusion Based on the quantitative analysis of bibliographic information and MeSH terms, we were able to define the study characteristics and popular topics in the field of PM and atherosclerosis. Our analysis would provide a comprehensive background reference for researchers in this field of study.

  6. Heat Shock Proteins: Pathogenic Role in Atherosclerosis and Potential Therapeutic Implications

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    Arman Kilic

    2012-01-01

    Full Text Available Heat shock proteins (HSPs are a highly conserved group of proteins that are constitutively expressed and function as molecular chaperones, aiding in protein folding and preventing the accumulation of misfolded proteins. In the arterial wall, HSPs have a protective role under normal physiologic conditions. In disease states, however, HSPs expressed on the vascular endothelial cell surface can act as targets for detrimental autoimmunity due to their highly conserved sequences. Developing therapeutic strategies for atherosclerosis based on HSPs is challenged by the need to balance such physiologic and pathologic roles of these proteins. This paper summarizes the role of HSPs in normal vascular wall processes as well as in the development and progression of atherosclerosis. The potential implications of HSPs in clinical therapies for atherosclerosis are also discussed.

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

    Science.gov (United States)

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

    2017-02-01

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

  8. Impact of hyperglycemia on morbidity and mortality, length of hospitalization and rates of re-hospitalization in a general hospital setting in Brazil

    Directory of Open Access Journals (Sweden)

    Leite Silmara AO

    2010-07-01

    Full Text Available Abstract Background Hyperglycemia in hospitalized patients is known to be related to a higher incidence of clinical and surgical complications and poorer outcomes. Adequate glycemic control and earlier diagnosis of type 2 diabetes during hospitalization are cost-effective measures. Methods This prospective cohort study was designed to determine the impact of hyperglycemia on morbidity and mortality in a general hospital setting during a 3-month period by reviewing patients' records. The primary purposes of this trial were to verify that hyperglycemia was diagnosed properly and sufficiently early and that it was managed during the hospital stay; we also aimed to evaluate the relationship between in-hospital hyperglycemia control and outcomes such as complications during the hospital stay, extent of hospitalization, frequency of re-hospitalization, death rates and number of days in the ICU (Intensive Care Unit after admission. Statistical analyses utilized the Kruskall-Wallis complemented by the "a posteriori" d.m.s. test, Spearman correlation and Chi-squared test, with a level of significance of 5% (p Results We reviewed 779 patient records that fulfilled inclusion criteria. The patients were divided into 5 groups: group (1 diabetic with normal glycemic levels according to American Diabetes Association criteria for in-hospital patients (n = 123; group (2 diabetics with hyperglycemia (n = 76; group (3 non-diabetics with hyperglycemia (n = 225; group (4diabetics and non-diabetics with persistent hyperglycemia during 3 consecutive days (n = 57 and group (5 those with normal glucose control (n = 298. Compared to patients in groups 1 and 5, patients in groups 2, 3 and 4 had significantly higher mortality rates (17.7% vs. 2.8% and Intensive Care Unit admissions with complications (23.3% vs. 4.5%. Patients in group 4 had the longest hospitalizations (mean 15.5 days, and group 5 had the lowest re-hospitalization rate (mean of 1.28 hospitalizations. Only

  9. Parental history of diabetes modifies the association between abdominal adiposity and hyperglycemia

    NARCIS (Netherlands)

    van Dam, R M; Boer, J M; Feskens, E.J.; Seidell, J C

    OBJECTIVE: To examine whether the association between abdominal obesity and hyperglycemia differs according to the presence of a parental history of diabetes. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study of 3,068 men and women, aged 20-65 years, without known diabetes who were

  10. NT-proBNP levels, atherosclerosis and vascular function in asymptomatic type 2 diabetic patients with microalbuminuria: peripheral reactive hyperaemia index but not NT-proBNP is an independent predictor of coronary atherosclerosis

    DEFF Research Database (Denmark)

    Reinhard, Henrik; Wiinberg, Niels; Hansen, Peter R

    2011-01-01

    for atherosclerosis is unclear. We examined the interrelationship between P-NT-proBNP, presence of atherosclerosis and/or vascular dysfunction in the coronary, carotid and peripheral arteries in asymptomatic type 2 diabetic patients with microalbuminuria that received intensive multifactorial treatment. METHODS...... AND RESULTS: P-NT-proBNP was measured in 200 asymptomatic type 2 patients without known cardiac disease that received intensive multifactorial treatment for CV risk reduction. Patients were examined for coronary, carotid and peripheral atherosclerosis, as defined by coronary calcium score=400, carotid intima...

  11. Increased YKL-40 expression in patients with carotid atherosclerosis

    DEFF Research Database (Denmark)

    Michelsen, Axel Gottlieb; Rathcke, C.N.; Skjelland, M.

    2010-01-01

    atherosclerosis and 20 healthy controls. Carotid expression of YKL-40 was examined by real time RT-PCR in 57 of the patients. Regulation and effect of YKL-40 were examined in THP-1 monocytes. Results: Our main findings were: (1) serum YKL-40 levels were significantly elevated in patients with carotid...... atherosclerosis, with particularly high levels in those with symptomatic disease; (2) patients with recent ischemic symptoms (within 2 months) had higher YKL-40 mRNA levels in carotid plaque than other patients; (3) in vitro, the beta-adrenergic receptor agonist isoproterenol, toll-like receptor (TLR) 2 and TLR4...

  12. Ultraviolet-Visible and Fluorescence Spectroscopy Techniques Are Important Diagnostic Tools during the Progression of Atherosclerosis: Diet Zinc Supplementation Retarded or Delayed Atherosclerosis

    Science.gov (United States)

    Abdelhalim, Mohamed Anwar K.; Moussa, Sherif A. Abdelmottaleb; AL-Mohy, Yanallah Hussain

    2013-01-01

    Background. In this study, we examined whether UV-visible and fluorescence spectroscopy techniques detect the progression of atherosclerosis in serum of rabbits fed on high-cholesterol diet (HCD) and HCD supplemented with zinc (HCD + Zn) compared with the control. Methods. The control rabbits group was fed on 100 g/day of normal diet. The HCD group was fed on Purina Certified Rabbit Chow supplemented with 1.0% cholesterol plus 1.0% olive oil (100 g/day) for the same period. The HCD + Zn group was fed on normal Purina Certified Rabbit Chow plus 1.0% cholesterol and 1.0% olive oil supplemented with 470 ppm Zn for the same feeding period. UV-visible and fluorescence spectroscopy and biochemistry in Rabbit's blood serum and blood hematology were measured in Rabbit's blood. Results. We found that the fluorescent peak of HCD shifted toward UV-visible wavelength compared with the control using fluorescent excitation of serum at 192 nm. In addition, they showed that supplementation of zinc (350 ppm) restored the fluorescent peak closely to the control. By using UV-visible spectroscopy approach, we found that the peak absorbance of HCD (about 280 nm) was higher than that of control and that zinc supplementation seemed to decrease the absorbance. Conclusions. This study demonstrates that ultraviolet-visible and fluorescence spectroscopy techniques can be applied as noninvasive techniques on a sample blood serum for diagnosing or detecting the progression of atherosclerosis. The Zn supplementation to rabbits fed on HCD delays or retards the progression of atherosclerosis. Inducing anemia in rabbits fed on HCD delays the progression of atherosclerosis. PMID:24350281

  13. A review of Chlamydia pneumoniae and atherosclerosis

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Fasting, H; Henneberg, E W

    1999-01-01

    Chlamydia pneumoniae is a Gram-negative obligate intracellular bacterium that causes acute upper and lower respiratory infections. Its distribution is worldwide. Seroepidemiological studies have shown an association between C. pneumoniae and atherosclerosis, and the risk of acute myocardial...

  14. Potential Mechanisms Linking Atherosclerosis and Increased Cardiovascular Risk in COPD: Focus On Sirtuins

    Science.gov (United States)

    Corbi, Graziamaria; Bianco, Andrea; Turchiarelli, Viviana; Cellurale, Michele; Fatica, Federica; Daniele, Aurora; Mazzarella, Gennaro; Ferrara, Nicola

    2013-01-01

    The development of atherosclerosis is a multi-step process, at least in part controlled by the vascular endothelium function. Observations in humans and experimental models of atherosclerosis have identified monocyte recruitment as an early event in atherogenesis. Chronic inflammation is associated with ageing and its related diseases (e.g., atherosclerosis and chronic obstructive pulmonary disease). Recently it has been discovered that Sirtuins (NAD+-dependent deacetylases) represent a pivotal regulator of longevity and health. They appear to have a prominent role in vascular biology and regulate aspects of age-dependent atherosclerosis. Many studies demonstrate that SIRT1 exhibits anti-inflammatory properties in vitro (e.g., fatty acid-induced inflammation), in vivo (e.g., atherosclerosis, sustainment of normal immune function in knock-out mice) and in clinical studies (e.g., patients with chronic obstructive pulmonary disease). Because of a significant reduction of SIRT1 in rodent lungs exposed to cigarette smoke and in lungs of patients with chronic obstructive pulmonary disease (COPD), activation of SIRT1 may be a potential target for chronic obstructive pulmonary disease therapy. We review the inflammatory mechanisms involved in COPD-CVD coexistence and the potential role of SIRT1 in the regulation of these systems. PMID:23774840

  15. Postprandial hyperglycemia in patients with noninsulin-dependent diabetes mellitus. Role of hepatic and extrahepatic tissues

    International Nuclear Information System (INIS)

    Firth, R.G.; Bell, P.M.; Marsh, H.M.; Hansen, I.; Rizza, R.A.

    1986-01-01

    Patients with noninsulin-dependent diabetes mellitus (NIDDM) have both preprandial and postprandial hyperglycemia. To determine the mechanism responsible for the postprandial hyperglycemia, insulin secretion, insulin action, and the pattern of carbohydrate metabolism after glucose ingestion were assessed in patients with NIDDM and in matched nondiabetic subjects using the dual isotope and forearm catheterization techniques. Prior to meal ingestion, hepatic glucose release was increased (P less than 0.001) in the diabetic patients measured using [2- 3 H] or [3- 3 H] glucose. After meal ingestion, patients with NIDDM had excessive rates of systemic glucose entry (1,316 +/- 56 vs. 1,018 +/- 65 mg/kg X 7 h, P less than 0.01), primarily owing to a failure to suppress adequately endogenous glucose release (680 +/- 50 vs. 470 +/- 32 mg/kg X 7 h, P less than 0.01) from its high preprandial level. Despite impaired suppression of endogenous glucose production during a hyperinsulinemic glucose clamp (P less than 0.001) and decreased postprandial C-peptide response (P less than 0.05) in NIDDM, percent suppression of hepatic glucose release after oral glucose was comparable in the diabetic and nondiabetic subjects (45 +/- 3 vs. 39 +/- 2%). Although new glucose formation from meal-derived three-carbon precursors (53 +/- 3 vs. 40 +/- 7 mg/kg X 7 h, P less than 0.05) was greater in the diabetic patients, it accounted for only a minor part of this excessive postprandial hepatic glucose release. Postprandial hyperglycemia was exacerbated by the lack of an appropriate increase in glucose uptake whether measured isotopically or by forearm glucose uptake. Thus excessive hepatic glucose release and impaired glucose uptake are involved in the pathogenesis of postprandial hyperglycemia in patients with NIDDM

  16. Small animal positron emission tomography imaging and in vivo studies of atherosclerosis

    DEFF Research Database (Denmark)

    Hag, Anne Mette Fisker; Ripa, Rasmus Sejersten; Pedersen, Sune Folke

    2013-01-01

    Atherosclerosis is a growing health challenge globally, and despite our knowledge of the disease has increased over the last couple of decades, many unanswered questions remain. As molecular imaging can be used to visualize, characterize and measure biological processes at the molecular and cellu...... knowledge obtained from in vivo positron emission tomography studies of atherosclerosis performed in small animals....

  17. Effect of Hyperglycemia on Purinergic and Nitrergic Inhibitory Neuromuscular Transmission in the Antrum of the Stomach: Implications for Fast Gastric Emptying

    Directory of Open Access Journals (Sweden)

    Xue-Dao He

    2018-01-01

    Full Text Available BackgroundHyperglycemia has been reported to enhance vagovagal reflex that causes the release of inhibitory neurotransmitter, nitric oxide (NO, at the neuromuscular junction in the antrum to relax the antrum and slow gastric emptying by stimulating glucose-sensitive afferent neurons. However, hyperglycemia has also been reported to cause fast gastric emptying that may be due to suppression of the inhibitory motor neurons.AimsThe purpose of the present study was to investigate changes in inhibitory neuromuscular transmission in the gastric antrum due to hyperglycemia.MethodsInhibitory electrical junction potentials were recorded from gastric antral muscle strips, using intracellular electrodes under non-adrenergic, non-cholinergic conditions. Studies were performed in non-hyperglycemic NOD (NH-NOD, NOD mice as they develop hyperglycemia (H-NOD and their age-matched controls. The purinergic inhibitory junction potential (pIJP and nitrergic IJP (nIJP were isolated pharmacologically.ResultsThe control pIJP was large, around −18 mV and nIJP was small, around −9 mV. In NH-NOD the IJPs were not affected, but in H-NOD pIJP was nearly abolished and nIJP was significantly reduced. In H-NOD mice, membrane hyperpolarization caused by exogenous α,β-MeATP or diethylenetriamine NO adduct was similar to that in wild-type controls (P > 0.05. H-NOD smooth muscles were significantly depolarized as compared to NH-NOD smooth muscles.ConclusionThese observations show that hyperglycemia causes suppression of purinergic and nitrergic transmission by acting on the motor neurons that form the last neuron in the vagovagal circuit. Moreover, the loss the neurotransmission is due to a defect in neurotransmitter release rather than a defect in signal transduction. Hyperglycemia also causes depolarization of smooth muscles that may increase their excitability.

  18. Increased Cardiovascular Events and Subclinical Atherosclerosis in Rheumatoid Arthritis Patients: 1 Year Prospective Single Centre Study.

    Directory of Open Access Journals (Sweden)

    Piero Ruscitti

    Full Text Available Several studies showed the close relationship between Rheumatoid Arthritis (RA and cerebro-cardiovascular events (CVEs and subclinical atherosclerosis. In this study, we investigated the occurrence of CVEs and subclinical atherosclerosis during the course of RA and we evaluated the possible role of both traditional cardiovascular (CV and disease related risk factors to predict the occurrence of new CVEs and the onset of subclinical atherosclerosis.We designed a single centre, bias-adjusted, prospective, observational study to investigate, in a homogeneous subset of RA patients, the occurrence of new onset of CVEs and subclinical atherosclerosis. Statistical analyses were performed to evaluate the role of traditional CV and disease-related risk factors to predict the occurrence of new CVEs and subclinical atherosclerosis.We enrolled 347 RA patients prospectively followed for 12 months. An increased percentage of patients experienced CVEs, developed subclinical atherosclerosis and was affected by systemic arterial hypertension (SAH, type 2 diabetes mellitus and metabolic syndrome (MS, at the end of follow up. Our analysis showed that the insurgence of both SAH and MS, during the follow up, the older age, the CVE familiarity and the lack of clinical response, were associated with a significantly increased risk to experience CVEs and to develop subclinical atherosclerosis.Our study quantifies the increased expected risk for CVEs in a cohort of RA patients prospectively followed for 1 year. The occurrence of both new CVEs and subclinical atherosclerosis in RA patients may be explained by inflammatory burden as well as traditional CV risk factors.

  19. Modulation of genes involved in inflammation and cell death in atherosclerosis-susceptible mice

    NARCIS (Netherlands)

    Zadelaar, Anna Susanne Maria

    2006-01-01

    In this thesis we focus on atherosclerosis as the main cause of cardiovascular disease. Since inflammation and cell death are important processes in the onset and progression of atherosclerosis, we investigate the role of several genes involved in inflammation and cell death in the vessel wall and

  20. The effect of local hyperglycemia on skin cells in vitro and on wound healing in euglycemic rats

    DEFF Research Database (Denmark)

    Kruse, Carla R; Singh, Mansher; Sørensen, Jens A

    2016-01-01

    BACKGROUND: Multiple previous studies have established that high systemic blood glucose concentration impairs skin wound healing. However, the effects of local hyperglycemia on wound healing are not well defined. Comprehensive animal studies and in vitro studies using both fibroblasts and keratin......BACKGROUND: Multiple previous studies have established that high systemic blood glucose concentration impairs skin wound healing. However, the effects of local hyperglycemia on wound healing are not well defined. Comprehensive animal studies and in vitro studies using both fibroblasts...

  1. Olive oil and postprandial hyperlipidemia: implications for atherosclerosis and metabolic syndrome.

    Science.gov (United States)

    Montserrat-de la Paz, Sergio; Bermudez, Beatriz; Cardelo, Magdalena P; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G

    2016-12-07

    Olive oil is the primary source of fat in the Mediterranean diet, which is associated with a significant improvement in health status, as measured by reduced mortality from several chronic diseases. The current pandemic of obesity, metabolic syndrome, and type 2 diabetes is intimately associated with an atherogenic dyslipidemic phenotype. The core components of the dyslipidemia of the metabolic syndrome, which most likely initiate atherosclerosis, are the "lipid triad" consisting of high plasma triglycerides, low levels of high-density lipoproteins, and a preponderance of small, dense low-density lipoproteins at fasting. However, postprandial (non-fasting) TGs (postprandial hyperlipidemia) are also recognized as an important component for atherosclerosis. Herein, the purpose of this review was to provide an update on the effects and mechanisms related to olive oil on postprandial hyperlipidemia and its implications for the onset and progression of atherosclerosis and metabolic syndrome.

  2. Site-Specific Antioxidative Therapy for Prevention of Atherosclerosis and Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Hajime Otani

    2013-01-01

    Full Text Available Oxidative stress has been implicated in pathophysiology of aging and age-associated disease. Antioxidative medicine has become a practice for prevention of atherosclerosis. However, limited success in preventing cardiovascular disease (CVD in individuals with atherosclerosis using general antioxidants has prompted us to develop a novel antioxidative strategy to prevent atherosclerosis. Reducing visceral adipose tissue by calorie restriction (CR and regular endurance exercise represents a causative therapy for ameliorating oxidative stress. Some of the recently emerging drugs used for the treatment of CVD may be assigned as site-specific antioxidants. CR and exercise mimetic agents are the choice for individuals who are difficult to continue CR and exercise. Better understanding of molecular and cellular biology of redox signaling will pave the way for more effective antioxidative medicine for prevention of CVD and prolongation of healthy life span.

  3. Antioxidant rich grape pomace extract suppresses postprandial hyperglycemia in diabetic mice by specifically inhibiting alpha-glucosidase

    Directory of Open Access Journals (Sweden)

    Hogan Shelly

    2010-08-01

    Full Text Available Abstract Background Postprandial hyperglycemia is an early defect of type 2 diabetes and one of primary anti-diabetic targets. Treatment of postprandial hyperglycemia can be achieved by inhibiting intestinal α-glucosidase, the key enzyme for oligosaccharide digestion and further glucose absorption. Grape pomace is winemaking byproduct rich in bioactive food compounds such as phenolic antioxidants. This study evaluated the anti-diabetic potential of two specific grape pomace extracts by determining their antioxidant and anti-postprandial hyperglycemic activities in vitro and in vivo. Methods The extracts of red wine grape pomace (Cabernet Franc and white wine grape pomace (Chardonnay were prepared in 80% ethanol. An extract of red apple pomace was included as a comparison. The radical scavenging activities and phenolic profiles of the pomace extracts were determined through the measurement of oxygen radical absorbance capacity, DPPH radical scavenging activity, total phenolic content and flavonoids. The inhibitory effects of the pomace extracts on yeast and rat intestinal α-glucosidases were determined. Male 6-week old C57BLKS/6NCr mice were treated with streptozocin to induce diabetes. The diabetic mice were then treated with vehicle or the grape pomace extract to determine whether the oral intake of the extract can suppress postprandial hyperglycemia through the inhibition of intestinal α-glucosidases. Results The red grape pomace extract contained significantly higher amounts of flavonoids and phenolic compounds and exerted stronger oxygen radical absorbance capacity than the red apple pomace extract. Both the grape pomace extracts but not the apple pomace extract exerted significant inhibition on intestinal α-glucosidases and the inhibition appears to be specific. In the animal study, the oral intake of the grape pomace extract (400 mg/kg body weight significantly suppressed the postprandial hyperglycemia by 35% in streptozocin

  4. Antioxidant rich grape pomace extract suppresses postprandial hyperglycemia in diabetic mice by specifically inhibiting alpha-glucosidase.

    Science.gov (United States)

    Hogan, Shelly; Zhang, Lei; Li, Jianrong; Sun, Shi; Canning, Corene; Zhou, Kequan

    2010-08-27

    Postprandial hyperglycemia is an early defect of type 2 diabetes and one of primary anti-diabetic targets. Treatment of postprandial hyperglycemia can be achieved by inhibiting intestinal α-glucosidase, the key enzyme for oligosaccharide digestion and further glucose absorption. Grape pomace is winemaking byproduct rich in bioactive food compounds such as phenolic antioxidants. This study evaluated the anti-diabetic potential of two specific grape pomace extracts by determining their antioxidant and anti-postprandial hyperglycemic activities in vitro and in vivo. The extracts of red wine grape pomace (Cabernet Franc) and white wine grape pomace (Chardonnay) were prepared in 80% ethanol. An extract of red apple pomace was included as a comparison. The radical scavenging activities and phenolic profiles of the pomace extracts were determined through the measurement of oxygen radical absorbance capacity, DPPH radical scavenging activity, total phenolic content and flavonoids. The inhibitory effects of the pomace extracts on yeast and rat intestinal α-glucosidases were determined. Male 6-week old C57BLKS/6NCr mice were treated with streptozocin to induce diabetes. The diabetic mice were then treated with vehicle or the grape pomace extract to determine whether the oral intake of the extract can suppress postprandial hyperglycemia through the inhibition of intestinal α-glucosidases. The red grape pomace extract contained significantly higher amounts of flavonoids and phenolic compounds and exerted stronger oxygen radical absorbance capacity than the red apple pomace extract. Both the grape pomace extracts but not the apple pomace extract exerted significant inhibition on intestinal α-glucosidases and the inhibition appears to be specific. In the animal study, the oral intake of the grape pomace extract (400 mg/kg body weight) significantly suppressed the postprandial hyperglycemia by 35% in streptozocin-induced diabetic mice following starch challenge. This is the

  5. Factors associated with accelerated subclinical atherosclerosis in patients with spondyloarthritis without overt cardiovascular disease.

    Science.gov (United States)

    Giollo, Alessandro; Dalbeni, Andrea; Cioffi, Giovanni; Ognibeni, Federica; Gatti, Davide; Idolazzi, Luca; Orsolini, Giovanni; Minuz, Pietro; Rossini, Maurizio; Fava, Cristiano; Viapiana, Ombretta

    2017-11-01

    Data on the progression of atherosclerosis in spondyloarthritis (SpA) are scarce, despite a high burden of cardiovascular diseases (CVD). The aim of this study was to identify the predictors of an accelerated subclinical atherosclerosis in patients with SpA. Study participants were 66 patients free of CVD classified according to ASAS criteria. The patients were evaluated at baseline and after 13.5 ± 3.6 months. Ultrasound measurements of carotid intima-media thickness (cIMT) and distensibility coefficient (cDC) were used to assess the extent of subclinical atherosclerosis. cIMT progression rate was calculated dividing the cIMT change by the time between the scans. Accelerated atherosclerosis was defined as the top cIMT progression rate quartile. At baseline, the mean Framingham Risk Score was 14 ± 11%. At follow-up, cIMT increased in 39 patients (59%; mean difference 0.01 ± 0.10; p = 0.334). Mean cIMT progression rate was 0.01 mm/year (95% CI - 0.02 to 0.03). cDC was unchanged at follow-up. Patients with accelerated atherosclerosis (n = 16) had significantly higher serum creatinine and lower glomerular filtration rate (eGFR) at baseline. In multiple logistic regression, only eGFR and the presence of syndesmophytes were associated with an accelerated atherosclerosis, independent of traditional cardiovascular risk factors. In patients with SpA without overt CV disease, a decrease in renal function and radiographic damage are conditions associated with the development of subclinical accelerated atherosclerosis. Longitudinal assessment of cIMT could be useful to better evaluate the individual CV risk of these patients improving their prognostic stratification.

  6. Contrasting effect of fish oil supplementation on the development of atherosclerosis in murine models

    DEFF Research Database (Denmark)

    Zampolli, Antonella; Bysted, Anette; Leth, Torben

    2006-01-01

    Objective: Increased fish oil intake is associated with protection against coronary heart disease and sudden death, while effects on atherosclerosis are controversial. We explored the effects of supplementing fish oil (rich in n-3 polyunsaturated fatty acids, PUFA) or corn oil (rich in n-6 PUFA......) in two different models of atherosclerosis. Methods and Results: Sixty-three low density lipoprotein receptor-deficient (LDLR-/-) mice and sixty-nine apolipoprotein E-deficient (apoE(-/-)) mice were fed diets without supplementations or supplemented with either 1% fish oil or 1% corn oil. In apo......E(-/-) mice, neither fish oil nor corn oil had any major impact on plasma lipids or atherosclerosis. In LDLR-/- mice, conversely, the fish oil and the corn oil group had lower levels of LDL-cholesterol and triglycerides and had lesser atherosclerosis in the aortic root and in the entire aorta (P

  7. Blood-Brain Glucose Transfer: Repression in Chronic Hyperglycemia

    Science.gov (United States)

    Gjedde, Albert; Crone, Christian

    1981-10-01

    Diabetic patients with increased plasma glucose concentrations may develop cerebral symptoms of hypoglycemia when their plasma glucose is rapidly lowered to normal concentrations. The symptoms may indicate insufficient transport of glucose from blood to brain. In rats with chronic hyperglycemia the maximum glucose transport capacity of the blood-brain barrier decreased from 400 to 290 micromoles per 100 grams per minute. When plasma glucose was lowered to normal values, the glucose transport rate into brain was 20 percent below normal. This suggests that repressive changes of the glucose transport mechanism occur in brain endothelial cells in response to increased plasma glucose.

  8. Torcetrapib does not reduce atherosclerosis beyond atorvastatin and induces more proinflammatory lesions than atorvastatin

    NARCIS (Netherlands)

    Haan, W. de; Vries-van der Weij, J. de; Hoorn, J.W.A. van der; Gautier, T.; Hoogt, C.C. van der; Westerterp, M.; Romijn, J.A.; Jukema, J.W.; Havekes, L.M.; Princen, H.M.G.; Rensen, P.C.N.

    2008-01-01

    BACKGROUND - Although cholesteryl ester transfer protein (CETP) inhibition is regarded as a promising strategy to reduce atherosclerosis by increasing high-density lipoprotein cholesterol, the CETP inhibitor torcetrapib given in addition to atorvastatin had no effect on atherosclerosis and even

  9. Torcetrapib does not reduce atherosclerosis beyond atorvastatin and induces more proinflammatory lesions than atorvastatin

    NARCIS (Netherlands)

    de Haan, Willeke; de Vries-van der Weij, Jitske; van der Hoorn, Jose W. A.; Gautier, Thomas; van der Hoogt, Caroline C.; Westerterp, Marit; Romijn, Johannes A.; Jukema, J. Wouter; Havekes, Louis M.; Princen, Hans M. G.; Rensen, Patrick C. N.

    2008-01-01

    Background-Although cholesteryl ester transfer protein (CETP) inhibition is regarded as a promising strategy to reduce atherosclerosis by increasing high-density lipoprotein cholesterol, the CETP inhibitor torcetrapib given in addition to atorvastatin had no effect on atherosclerosis and even

  10. Torcetrapib does not reduce atherosclerosis beyond atorvastatin and induces more proinflammatory lesions than atorvastatin

    NARCIS (Netherlands)

    de Haan, Willeke; de Vries-van der Weij, Jitske; van der Hoorn, José W. A.; Gautier, Thomas; van der Hoogt, Caroline C.; Westerterp, Marit; Romijn, Johannes A.; Jukema, J. Wouter; Havekes, Louis M.; Princen, Hans M. G.; Rensen, Patrick C. N.

    2008-01-01

    Although cholesteryl ester transfer protein (CETP) inhibition is regarded as a promising strategy to reduce atherosclerosis by increasing high-density lipoprotein cholesterol, the CETP inhibitor torcetrapib given in addition to atorvastatin had no effect on atherosclerosis and even increased

  11. Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Liang-Jun Yan

    2014-01-01

    Full Text Available Chronic overnutrition creates chronic hyperglycemia that can gradually induce insulin resistance and insulin secretion impairment. These disorders, if not intervened, will eventually be followed by appearance of frank diabetes. The mechanisms of this chronic pathogenic process are complex but have been suggested to involve production of reactive oxygen species (ROS and oxidative stress. In this review, I highlight evidence that reductive stress imposed by overflux of NADH through the mitochondrial electron transport chain is the source of oxidative stress, which is based on establishments that more NADH recycling by mitochondrial complex I leads to more electron leakage and thus more ROS production. The elevated levels of both NADH and ROS can inhibit and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH, respectively, resulting in blockage of the glycolytic pathway and accumulation of glycerol 3-phospate and its prior metabolites along the pathway. This accumulation then initiates all those alternative glucose metabolic pathways such as the polyol pathway and the advanced glycation pathways that otherwise are minor and insignificant under euglycemic conditions. Importantly, all these alternative pathways lead to ROS production, thus aggravating cellular oxidative stress. Therefore, reductive stress followed by oxidative stress comprises a major mechanism of hyperglycemia-induced metabolic syndrome.

  12. Histone Deacetylase Inhibition Restores Retinal Pigment Epithelium Function in Hyperglycemia.

    Directory of Open Access Journals (Sweden)

    Danielle Desjardins

    Full Text Available In diabetic individuals, macular edema is a major cause of vision loss. This condition is refractory to insulin therapy and has been attributed to metabolic memory. The retinal pigment epithelium (RPE is central to maintaining fluid balance in the retina, and this function is compromised by the activation of advanced glycation end-product receptors (RAGE. Here we provide evidence that acute administration of the RAGE agonist, glycated-albumin (gAlb or vascular endothelial growth factor (VEGF, increased histone deacetylase (HDAC activity in RPE cells. The administration of the class I/II HDAC inhibitor, trichostatin-A (TSA, suppressed gAlb-induced reductions in RPE transepithelial resistance (in vitro and fluid transport (in vivo. Systemic TSA also restored normal RPE fluid transport in rats with subchronic hyperglycemia. Both gAlb and VEGF increased HDAC activity and reduced acetyl-α-tubulin levels. Tubastatin-A, a relatively specific antagonist of HDAC6, inhibited gAlb-induced changes in RPE cell resistance. These data are consistent with the idea that RPE dysfunction following exposure to gAlb, VEGF, or hyperglycemia is associated with increased HDAC6 activity and decreased acetyl-α-tubulin. Therefore, we propose inhibiting HDAC6 in the RPE as a potential therapy for preserving normal fluid homeostasis in the hyperglycemic retina.

  13. Increased Hepatic Expression of Endothelial Lipase Inhibits Cholesterol Diet-Induced Hypercholesterolemia and Atherosclerosis in Transgenic Rabbits.

    Science.gov (United States)

    Wang, Chuan; Nishijima, Kazutoshi; Kitajima, Shuji; Niimi, Manabu; Yan, Haizhao; Chen, Yajie; Ning, Bo; Matsuhisa, Fumikazu; Liu, Enqi; Zhang, Jifeng; Chen, Y Eugene; Fan, Jianglin

    2017-07-01

    Endothelial lipase (EL) is a key determinant in plasma high-density lipoprotein-cholesterol. However, functional roles of EL on the development of atherosclerosis have not been clarified. We investigated whether hepatic expression of EL affects plasma lipoprotein metabolism and cholesterol diet-induced atherosclerosis. We generated transgenic (Tg) rabbits expressing the human EL gene in the liver and then examined the effects of EL expression on plasma lipids and lipoproteins and compared the susceptibility of Tg rabbits with cholesterol diet-induced atherosclerosis with non-Tg littermates. On a chow diet, hepatic expression of human EL in Tg rabbits led to remarkable reductions in plasma levels of total cholesterol, phospholipids, and high-density lipoprotein-cholesterol compared with non-Tg controls. On a cholesterol-rich diet for 16 weeks, Tg rabbits exhibited significantly lower hypercholesterolemia and less atherosclerosis than non-Tg littermates. In Tg rabbits, gross lesion area of aortic atherosclerosis was reduced by 52%, and the lesions were characterized by fewer macrophages and smooth muscle cells compared with non-Tg littermates. Increased hepatic expression of EL attenuates cholesterol diet-induced hypercholesterolemia and protects against atherosclerosis. © 2017 American Heart Association, Inc.

  14. Progression and regression of atherosclerosis in APOE3-Leiden transgenic mice : An immunohistochemical study

    NARCIS (Netherlands)

    Gijbels, M.J.J.; Cammen, M. van der; Laan, L.J.W. van der; Emeis, J.J.; Havekes, L.M.; Hofker, M.H.; Kraal, G.

    1999-01-01

    Apolipoprotein E3-Leiden (APOE3-Leiden) transgenic mice develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. We have studied the progression and regression of atherosclerosis using immunohistochemistry. Female transgenic mice were fed a moderate fat diet to study

  15. Age, gender and hypertension as major risk factors in development of subclinical atherosclerosis

    Directory of Open Access Journals (Sweden)

    Ajla Rahimić Ćatić

    2013-04-01

    Full Text Available Introduction: Intima-media thickness (IMT measurement of the common carotid artery (CCA is considered as useful indicator of carotid atherosclerosis. Early detection of atherosclerosis and its associated risk factors is important to prevent stroke and heart diseases. The aim of the present study was to investigate which risk factors are better determinants of subclinical atherosclerosis, measured by common carotidartery intima media thickness (CCA-IMT.Methods: A total of 74 subjects were randomly selected in this cross – sectional study. Information on the patient’s medical history and laboratory fi ndings were obtained from their clinical records. Risk factors relevant to this study were age, gender, cigarette smoking status, diabetes, hypertension and dyslipidemia. Ultrasound scanning of carotid arteries was performed with a 7,5 MHz linear array transducer (GE Voluson730 pro. The highest value of six common carotid artery measurements was taken as the fi nal IMT. Increased CCA-IMT was defi ned when it was > 1 mm.Results: Our data demonstrated higher CCA-IMT values in male patients compared with female patients. Increased CCA-IMT was the most closely related to age (PConclusion: Age, gender and hypertension are the most important risk factors in development of carotid atherosclerosis. Early detection of atherosclerosis among high-risk populations is important in order to prevent stroke and heart diseases, which are leading causes of death worldwide.

  16. Polyphenols and Oxidative Stress in Atherosclerosis-Related Ischemic Heart Disease and Stroke

    Directory of Open Access Journals (Sweden)

    Yu-Chen Cheng

    2017-01-01

    Full Text Available Good nutrition could maintain health and life. Polyphenols are common nutrient mainly derived from fruits, vegetables, tea, coffee, cocoa, mushrooms, beverages, and traditional medicinal herbs. They are potential substances against oxidative-related diseases, for example, cardiovascular disease, specifically, atherosclerosis-related ischemic heart disease and stroke, which are health and economic problems recognized worldwide. In this study, we reviewed the risk factors for atherosclerosis, including hypertension, diabetes mellitus, hyperlipidemia, obesity, and cigarette smoking as well as the antioxidative activity of polyphenols, which could prevent the pathology of atherosclerosis, including endothelial dysfunction, low-density lipoprotein oxidation, vascular smooth muscle cell proliferation, inflammatory process by monocytes, macrophages or T lymphocytes, and platelet aggregation. The strong radical-scavenging properties of polyphenols would exhibit antioxidative and anti-inflammation effects. Polyphenols reduce ROS production by inhibiting oxidases, reducing the production of superoxide, inhibiting OxLDL formation, suppressing VSMC proliferation and migration, reducing platelet aggregation, and improving mitochondrial oxidative stress. Polyphenol consumption also inhibits the development of hypertension, diabetes mellitus, hyperlipidemia, and obesity. Despite the numerous in vivo and in vitro studies, more advanced clinical trials are necessary to confirm the efficacy of polyphenols in the treatment of atherosclerosis-related vascular diseases.

  17. Level of pancreatic and gastrointestinal hormones in blood of patients with stomach neoplasm in complex treatment using artificial hyperglycemia

    International Nuclear Information System (INIS)

    Zen'kovich, G.A.; Tsyrus', T.P.; Ermilova, N.I.

    1988-01-01

    It is shown that performing of hyperglycemia courses results in some breakage of tissue tolerance to glucose, decrease of active plase of secreted insulin. No other functional violations were revealed in pancreas. Insulin-producing function of pancreas is reserved. Glucagon and gastrin level considerably decreases at the end of each course of hyperglycemia. Somatostation level in the blood of the examined patients doesn't differ and was in the limits of physiological standard. 4 refs.; 1 tab

  18. Macrophage Liver Kinase B1 Inhibits Foam Cell Formation and Atherosclerosis.

    Science.gov (United States)

    Liu, Zhaoyu; Zhu, Huaiping; Dai, Xiaoyan; Wang, Cheng; Ding, Ye; Song, Ping; Zou, Ming-Hui

    2017-10-13

    LKB1 (liver kinase B1) is a serine/threonine kinase and tumor suppressor, which regulates the homeostasis of hematopoietic cells and immune responses. Macrophages transform into foam cells upon taking-in lipids. No role for LKB1 in foam cell formation has previously been reported. We sought to establish the role of LKB1 in atherosclerotic foam cell formation. LKB1 expression was examined in human carotid atherosclerotic plaques and in western diet-fed atherosclerosis-prone Ldlr -/- and ApoE -/- mice. LKB1 expression was markedly reduced in human plaques when compared with nonatherosclerotic vessels. Consistently, time-dependent reduction of LKB1 levels occurred in atherosclerotic lesions in western diet-fed Ldlr -/- and ApoE -/- mice. Exposure of macrophages to oxidized low-density lipoprotein downregulated LKB1 in vitro. Furthermore, LKB1 deficiency in macrophages significantly increased the expression of SRA (scavenger receptor A), modified low-density lipoprotein uptake and foam cell formation, all of which were abolished by blocking SRA. Further, we found LKB1 phosphorylates SRA resulting in its lysosome degradation. To further investigate the role of macrophage LKB1 in vivo, ApoE -/- LKB1 fl/fl LysM cre and ApoE -/- LKB1 fl/fl mice were fed with western diet for 16 weeks. Compared with ApoE -/- LKB1 fl/fl wild-type control, ApoE -/- LKB1 fl/fl LysM cre mice developed more atherosclerotic lesions in whole aorta and aortic root area, with markedly increased SRA expression in aortic root lesions. We conclude that macrophage LKB1 reduction caused by oxidized low-density lipoprotein promotes foam cell formation and the progression of atherosclerosis. © 2017 American Heart Association, Inc.

  19. Impact of Prediabetic Status on Coronary Atherosclerosis

    Science.gov (United States)

    Kurihara, Osamu; Takano, Masamichi; Yamamoto, Masanori; Shirakabe, Akihiro; Kimata, Nakahisa; Inami, Toru; Kobayashi, Nobuaki; Munakata, Ryo; Murakami, Daisuke; Inami, Shigenobu; Okamatsu, Kentaro; Ohba, Takayoshi; Ibuki, Chikao; Hata, Noritake; Seino, Yoshihiko; Mizuno, Kyoichi

    2013-01-01

    OBJECTIVE To determine if prediabetes is associated with atherosclerosis of coronary arteries, we evaluated the degree of coronary atherosclerosis in nondiabetic, prediabetic, and diabetic patients by using coronary angioscopy to identify plaque vulnerability based on yellow color intensity. RESEARCH DESIGN AND METHODS Sixty-seven patients with coronary artery disease (CAD) underwent angioscopic observation of multiple main-trunk coronary arteries. According to the American Diabetes Association guidelines, patients were divided into nondiabetic (n = 16), prediabetic (n = 28), and diabetic (n = 23) groups. Plaque color grade was defined as 1 (light yellow), 2 (yellow), or 3 (intense yellow) based on angioscopic findings. The number of yellow plaques (NYPs) per vessel and maximum yellow grade (MYG) were compared among the groups. RESULTS Mean NYP and MYG differed significantly between the groups (P = 0.01 and P = 0.047, respectively). These indexes were higher in prediabetic than in nondiabetic patients (P = 0.02 and P = 0.04, respectively), but similar in prediabetic and diabetic patients (P = 0.44 and P = 0.21, respectively). Diabetes and prediabetes were independent predictors of multiple yellow plaques (NYPs ≥2) in multivariate logistic regression analysis (odds ratio [OR] 10.8 [95% CI 2.09–55.6], P = 0.005; and OR 4.13 [95% CI 1.01–17.0], P = 0.049, respectively). CONCLUSIONS Coronary atherosclerosis and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable between prediabetic and diabetic patients. Slight or mild disorders in glucose metabolism, such as prediabetes, could be a risk factor for CAD, as is diabetes itself. PMID:23223344

  20. Association between diabetic retinopathy and subclinical atherosclerosis in China: Results from a community-based study.

    Science.gov (United States)

    Liu, Yu; Teng, Xiangyu; Zhang, Wei; Zhang, Ruifeng; Liu, Wei

    2015-09-01

    To evaluate the association of diabetic retinopathy with subclinical atherosclerosis in middle-aged and elderly Chinese with type 2 diabetes. A cross-sectional community-based study was performed among 1607 patients aged 40 years or older in Shanghai. Non-mydriatic digital fundus photography examination was used in diabetic retinopathy detection. Presence of elevated carotid intima-media thickness or carotid plaque was defined as subclinical atherosclerosis. The prevalence of diabetic retinopathy was 15.1% in total patients. Patients with diabetic retinopathy were more likely to have elevated carotid intima-media thickness, carotid plaque and subclinical atherosclerosis than those without diabetic retinopathy (37.9% vs 30.7%, 57.6% vs 49.6% and 64.6% vs 57.1%, respectively). The presence of diabetic retinopathy was significantly associated with increased odds of subclinical atherosclerosis (odds ratio = 1.93, 95% confidence interval = 1.03-3.60) after full adjustments. The presence of diabetic retinopathy was significantly associated with subclinical atherosclerosis in middle-aged and elderly patients with type 2 diabetics in China. © The Author(s) 2015.

  1. Early phase glucagon and insulin secretory abnormalities, but not incretin secretion, are similarly responsible for hyperglycemia after ingestion of nutrients

    DEFF Research Database (Denmark)

    Yabe, Daisuke; Kuroe, Akira; Watanabe, Koin

    2015-01-01

    AIMS: Hypersecretion of glucagon and reduced insulin secretion both contribute to hyperglycemia in type 2 diabetes (T2DM). However, the relative contributions of impaired glucagon and insulin secretions in glucose excursions at the various stages of T2DM development remain to be determined. METHODS...... secretions but not incretin secretion are involved in hyperglycemia after ingestion of nutrients in T2DM of even a short duration....

  2. Hibiscus sabdariffa calyx palliates insulin resistance, hyperglycemia, dyslipidemia and oxidative rout in fructose-induced metabolic syndrome rats.

    Science.gov (United States)

    Ajiboye, Taofeek O; Raji, Hikmat O; Adeleye, Abdulwasiu O; Adigun, Nurudeen S; Giwa, Oluwayemisi B; Ojewuyi, Oluwayemisi B; Oladiji, Adenike T

    2016-03-30

    The effect of Hibiscus sabdariffa calyx extract was evaluated in high-fructose-induced metabolic syndrome rats. Insulin resistance, hyperglycemia, dyslipidemia and oxidative rout were induced in rats using high-fructose diet. High-fructose diet-fed rats were administered 100 and 200 mg kg(-1) body weight of H. sabdariffa extract for 3 weeks, starting from week 7 of high-fructose diet treatment. High-fructose diet significantly (P Hibiscus extract. Overall, aqueous extract of H. sabdariffa palliates insulin resistance, hyperglycemia, dyslipidemia and oxidative rout in high-fructose-induced metabolic syndrome rats. © 2015 Society of Chemical Industry.

  3. Osteocalcin, Vascular Calcification, and Atherosclerosis: A Systematic Review and Meta-analysis

    Directory of Open Access Journals (Sweden)

    Sophie A. Millar

    2017-07-01

    Full Text Available BackgroundOsteocalcin (OC is an intriguing hormone, concomitantly being the most abundant non-collagenous peptide found in the mineralized matrix of bone, and expanding the endocrine function of the skeleton with far-reaching extra-osseous effects. A new line of enquiry between OC and vascular calcification has emerged in response to observations that the mechanism of vascular calcification resembles that of bone mineralisation. To date, studies have reported mixed results. This systematic review and meta-analysis aimed to identify any association between OC and vascular calcification and atherosclerosis.Methods and resultsDatabases were searched for original, peer reviewed human studies. A total of 1,453 articles were retrieved, of which 46 met the eligibility criteria. Overall 26 positive, 17 negative, and 29 neutral relationships were reported for assessments between OC (either concentration in blood, presence of OC-positive cells, or histological staining for OC and extent of calcification or atherosclerosis. Studies that measured OC-positive cells or histological staining for OC reported positive relationships (11 studies. A higher percentage of Asian studies found a negative relationship (36% in contrast to European studies (6%. Studies examining carboxylated and undercarboxylated forms of OC in the blood failed to report consistent results. The meta-analysis found no significant difference between OC concentration in the blood between patients with “atherosclerosis” and control (p = 0.13, n = 1,197.ConclusionNo definitive association was determined between OC and vascular calcification or atherosclerosis; however, the presence of OC-positive cells and histological staining had a consistent positive correlation with calcification or atherosclerosis. The review highlighted several themes, which may influence OC within differing populations leading to inconclusive results. Large, longitudinal studies are required to further

  4. Prevalence, Vascular Distribution, and Multiterritorial Extent of Subclinical Atherosclerosis in a Middle-Aged Cohort

    DEFF Research Database (Denmark)

    Fernández-Friera, Leticia; Peñalvo, José L; Fernández-Ortiz, Antonio

    2015-01-01

    age, 45.8 years; 63% male) to evaluate the systemic extent of atherosclerosis in the carotid, abdominal aortic, and iliofemoral territories by 2-/3-dimensional ultrasound and coronary artery calcification by computed tomography. The extent of subclinical atherosclerosis, defined as presence of plaque...

  5. White Matter Lesions, Carotid and Coronary Atherosclerosis in Late-Onset Depression and Healthy Controls

    DEFF Research Database (Denmark)

    Devantier, Torben Albert; Nørgaard, Bjarne Linde; Poulsen, Mikael Kjær

    2016-01-01

    BACKGROUND: Cerebral white matter lesions (WMLs) are more common in individuals with late-onset or late-life depression. It has been proposed that carotid atherosclerosis may predispose to WMLs by inducing cerebral hypoperfusion. This hemodynamic effect of carotid atherosclerosis could be importa...

  6. Inherited disorders of HDL metabolism and atherosclerosis

    NARCIS (Netherlands)

    Hovingh, G Kees; de Groot, E.P.; van der Steeg, Wim; Boekholdt, S Matthijs; Hutten, Barbara A; Kuivenhoven, J.A.; Kastelein, John J P

    PURPOSE OF REVIEW: Genetic disorders of HDL metabolism are rare and, as a result, the assessment of atherosclerosis risk in individuals suffering from these disorders has been difficult. Ultrasound imaging of carotid arteries has provided a tool to assess the risk in hereditary hypo and

  7. Inherited disorders of HDL metabolism and atherosclerosis

    NARCIS (Netherlands)

    Hovingh, G. Kees; de Groot, Eric; van der Steeg, Wim; Boekholdt, S. Matthijs; Hutten, Barbara A.; Kuivenhoven, Jan Albert; Kastelein, John J. P.

    2005-01-01

    Purpose of review Genetic disorders of HDL metabolism are rare and, as a result, the assessment of atherosclerosis risk in individuals suffering from these disorders has been difficult. Ultrasound imaging of carotid arteries has provided a tool to assess the risk in hereditary hypo and

  8. Effect of ascorbic acid on prevention of hypercholesterolemia induced atherosclerosis.

    Science.gov (United States)

    Das, S; Ray, R; Snehlata; Das, N; Srivastava, L M

    2006-04-01

    The notion that oxidation of lipids and propagation of free radicals may contribute to the pathogenesis of atherosclerosis is supported by a large body of evidence. To circumvent the damage caused by oxygen free radicals, antioxidants are needed which provide the much needed neutralization of free radical by allowing the pairing of electrons. In this study we have investigated the effect of ascorbic acid, a water soluble antioxidant on the development of hypercholesterolemia induced atherosclerosis in rabbits. Rabbits were made hypercholesterolemic and atherosclerotic by feeding 100 mg cholesterol/day. Different doses of ascorbic acid were administered to these rabbits. Low dose of ascorbic acid (0.5 mg/100 g body weight/day) did not have any significant effect on the percent of total area covered by atherosclerotic plaque. However, ascorbic acid when fed at a higher dose (15 mg/100 g body weight/day) was highly effective in reducing the atherogenecity. With this dose the percent of total surface area covered by atherosclerotic plaque was significantly less (p ascorbic acid may have great promise in the prevention of hypercholesterolemia induced atherosclerosis.

  9. A rabbit model of atherosclerosis at carotid artery: MRI visualization and histopathological characterization

    International Nuclear Information System (INIS)

    Ma, Zhan-Long; Teng, Gao-Jun; Chen, Jun; Zhang, Hong-Ying; Cao, Ai-Hong; Ni, Yicheng

    2008-01-01

    To induce a rabbit model of atherosclerosis at carotid artery, to visualize the lesion evolution with magnetic resonance imaging (MRI), and to characterize the lesion types by histopathology. Atherosclerosis at the right common carotid artery (RCCA) was induced in 23 rabbits by high-lipid diet following balloon catheter injury to the endothelium. The rabbits were examined in vivo with a 1.5-T MRI and randomly divided into three groups of 6 weeks (n=6), 12 weeks (n=8) and 15 weeks (n=9) for postmortem histopathology. The lesions on both MRI and histology were categorized according to the American Heart Association (AHA) classifications of atherosclerosis. Type I and type II of atherosclerotic changes were detected at week 6, i.e., nearly normal signal intensity (SI) of the injured RCCA wall without stenosis on MRI, but with subendothelial inflammatory infiltration and proliferation of smooth muscle cells on histopathology. At week 12, 75.0% and 62.5% of type III changes were encountered on MRI and histopathology respectively with thicker injured RCCA wall of increased SI on T 1 -weighted and proton density (PD)-weighted MRI and microscopically a higher degree of plaque formation. At week 15, carotid atherosclerosis became more advanced, i.e., type IV and type V in 55.6% and 22.2% of the lesions with MRI and 55.6% and 33.3% of the lesions with histopathology, respectively. Statistical analysis revealed a significant agreement (p<0.05) between the MRI and histological findings for lesion classification (r=0.96). A rabbit model of carotid artery atherosclerosis has been successfully induced and noninvasively visualized. The atherosclerotic plaque formation evolved from type I to type V with time, which could be monitored with 1.5-T MRI and confirmed with histomorphology. This experimental setting can be applied in preclinical research on atherosclerosis. (orig.)

  10. Functional blockage of EMMPRIN ameliorates atherosclerosis in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Liu, Hong; Yang, Li-xia; Guo, Rui-wei; Zhu, Guo-Fu; Shi, Yan-Kun; Wang, Xian-mei; Qi, Feng; Guo, Chuan-ming; Ye, Jin-shan; Yang, Zhi-hua; Liang, Xing

    2013-10-09

    Extracellular matrix metalloproteinase inducer (EMMPRIN), a 58-kDa cell surface glycoprotein, has been identified as a key receptor for transmitting cellular signals mediating metalloproteinase activities, as well as inflammation and oxidative stress. Clinical evidence has revealed that EMMPRIN is expressed in human atherosclerotic plaque; however, the relationship between EMMPRIN and atherosclerosis is unclear. To evaluate the functional role of EMMPRIN in atherosclerosis, we treated apolipoprotein E-deficient (ApoE(-/-)) mice with an EMMPRIN function-blocking antibody. EMMPRIN was found to be up-regulated in ApoE(-/-) mice fed a 12-week high-fat diet in contrast to 12 weeks of normal diet. Administration of a function-blocking EMMPRIN antibody (100 μg, twice per week for 4 weeks) to ApoE(-/-) mice, starting after 12 weeks of high-fat diet feeding caused attenuated and more stable atherosclerotic lesions, less reactive oxygen stress generation on plaque, as well as down-regulation of circulating interleukin-6 and monocyte chemotactic protein-1 in ApoE(-/-) mice. The benefit of EMMPRIN functional blockage was associated with reduced metalloproteinases proteolytic activity, which delayed the circulating monocyte transmigrating into atherosclerotic lesions. EMMPRIN antibody intervention ameliorated atherosclerosis in ApoE(-/-) mice by the down-regulation of metalloproteinase activity, suggesting that EMMPRIN may be a viable therapeutic target in atherosclerosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Nanoparticles containing a liver X receptor agonist inhibit inflammation and atherosclerosis.

    Science.gov (United States)

    Zhang, Xue-Qing; Even-Or, Orli; Xu, Xiaoyang; van Rosmalen, Mariska; Lim, Lucas; Gadde, Suresh; Farokhzad, Omid C; Fisher, Edward A

    2015-01-28

    Liver X receptor (LXR) signaling pathways regulate lipid metabolism and inflammation, which has generated widespread interest in developing synthetic LXR agonists as potential therapeutics for the management of atherosclerosis. In this study, it is demonstrated that nanoparticles (NPs) containing the synthetic LXR agonist GW3965 (NP-LXR) exert anti-inflammatory effects and inhibit the development of atherosclerosis without causing hepatic steatosis. These NPs are engineered through self-assembly of a biodegradable diblock poly(lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-b-PEG) copolymer. NP-LXR is significantly more effective than free GW3965 at inducing LXR-target gene expression and suppressing inflammatory factors in macrophages in vitro and in vivo. Additionally, the NPs elicit negligible lipogenic gene stimulation in the liver. Using the Ldlr (-/-) mouse model of atherosclerosis, abundant colocalization of fluorescently labeled NPs within plaque macrophages following systemic administration is seen. Notably, six intravenous injections of NP-LXR over 2 weeks markedly reduce the CD68-positive cell (macrophage) content of plaques (by 50%) without increasing total cholesterol or triglycerides in the liver and plasma. Together, these findings identify GW3965-encapsulated PLGA-b-PEG NPs as a promising nanotherapeutic approach to combat atherosclerosis, providing the benefits of LXR agonists without their adverse effects on hepatic and plasma lipid metabolism. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Correlation between high blood IL-6 level, hyperglycemia, and glucose control in septic patients.

    Science.gov (United States)

    Nakamura, Masataka; Oda, Shigeto; Sadahiro, Tomohito; Watanabe, Eizo; Abe, Ryuzo; Nakada, Taka-Aki; Morita, Yasumasa; Hirasawa, Hiroyuki

    2012-12-12

    The aim of the present study was to investigate the relationship between the blood IL-6 level, the blood glucose level, and glucose control in septic patients. This retrospective observational study in a general ICU of a university hospital included a total of 153 patients with sepsis, severe sepsis, or septic shock who were admitted to the ICU between 2005 and 2010, stayed in the ICU for 7 days or longer, and did not receive steroid therapy prior to or after ICU admission. The severity of stress hyperglycemia, status of glucose control, and correlation between those two factors in these patients were investigated using the blood IL-6 level as an index of hypercytokinemia. A significant positive correlation between blood IL-6 level and blood glucose level on ICU admission was observed in the overall study population (n = 153; r = 0.24, P = 0.01), and was stronger in the nondiabetic subgroup (n = 112; r = 0.42, P glucose control (blood glucose level blood IL-6 level on ICU admission (P blood IL-6 level after ICU admission remained significantly higher and the 60-day survival rate was significantly lower in the failed glucose control group than in the successful glucose control group (P blood IL-6 level was correlated with hyperglycemia and with difficulties in glucose control in septic patients. These results suggest the possibility that hypercytokinemia might be involved in the development of hyperglycemia in sepsis, and thereby might affect the success of glucose control.

  13. The role of oxidative stress and NADPH oxidase in the pathogenesis of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Dorota Bryk

    2017-01-01

    Full Text Available Reactive oxygen species (ROS play a key role in the pathogenesis of atherosclerosis. The main mechanisms which are involved are low-density lipoprotein oxidative modification, inactivation of nitric oxide and modulation of redox-sensitive signaling pathways. ROS contribute to several aspects of atherosclerosis including endothelial cell dysfunction, monocyte/macrophage recruitment and activation, stimulation of inflammation, and inducing smooth muscle cell migration and proliferation. NADPH oxidase is the main source of ROS in the vasculature. This enzyme consists of a membrane-bound heterodimer of gp91phox and p22phox, cytosolic regulatory subunits p47phox, p67phox and p40phox, and small GTP-binding proteins rac1 and rac 2. Seven distinct isoforms of this enzyme have been identified, of which four (NOX1, 2, 4 and 5 may have cardiovascular function. In this paper, we review the current state of knowledge concerning the role of oxidative stress and NOX enzymes in pathogenesis of atherosclerosis. Moreover, we analyze the experimental studies that explore the relationship between the NOX family and atherosclerosis.

  14. Oxidized low-density lipoprotein-induced apoptotic dendritic cells as a novel therapy for atherosclerosis

    NARCIS (Netherlands)

    Frodermann, Vanessa; van Puijvelde, Gijs H M; Wierts, Laura; Lagraauw, H Maxime; Foks, Amanda C; van Santbrink, Peter J; Bot, Ilze; Kuiper, Johan; de Jager, Saskia C A

    2015-01-01

    Modulation of immune responses may form a powerful approach to treat atherosclerosis. It was shown that clearance of apoptotic cells results in tolerance induction to cleared Ags by dendritic cells (DCs); however, this seems impaired in atherosclerosis because Ag-specific tolerance is lacking. This

  15. Deletion of the Men1 Gene Prevents Streptozotocin-Induced Hyperglycemia in Mice

    Directory of Open Access Journals (Sweden)

    Yuqing Yang

    2010-01-01

    Full Text Available Diabetes ultimately results from an inadequate number of functional beta cells in the islets of Langerhans. Enhancing proliferation of functional endogenous beta cells to treat diabetes remains underexplored. Here, we report that excision of the Men1 gene, whose loss-of-function mutation leads to inherited multiple endocrine neoplasia type 1 (MEN1, rendered resistant to streptozotocin-induced hyperglycemia in a tamoxifen-inducible and temporally controlled Men1 excision mouse model as well as in a tissue-specific Men1 excision mouse model. Men1 excision prevented mice from streptozotocin-induced hyperglycemia mainly through increasing the number of functional beta cells. BrdU incorporation by beta cells, islet size, and circulating insulin levels were significantly increased in Men1-excised mice. Membrane localization of glucose transporter 2 was largely preserved in Men1-excised beta cells, but not in Men1-expressing beta cells. Our findings suggest that repression of menin, a protein encoded by the Men1 gene, might be a valuable means to maintain or increase the number of functional endogenous beta cells to prevent or ameliorate diabetes.

  16. Platelets and their chemokines in atherosclerosis – clinical applications

    Directory of Open Access Journals (Sweden)

    Philipp evon Hundelshausen

    2014-08-01

    Full Text Available The concept of platelets as important players in the process of atherogenesis has become increasingly accepted due to accumulating experimental and clinical evidence. Despite the progress in understanding the molecular details of atherosclerosis, particularly by using animal models, the inflammatory and thrombotic roles of activated platelet s especially in the human system remain difficult to dissect, as often only the complications of atherosclerosis i.e. stroke and myocardial infarction are definable but not the plaque burden.Platelet indices including platelet count and mean platelet volume and soluble mediators released by activated platelets are associated with atherosclerosis. The chemokine CXCL4 has multiple atherogenic activities e.g. altering the differentiation of T cells and macrophages by inhibiting neutrophil and monocyte apoptosis and by increasing the uptake of oxLDL and synergizing with CCL5. CCL5 is released and deposited on endothelium by activated platelets thereby triggering atherogenic monocyte recruitment, which can be attenuated by blocking the corresponding chemokine receptor CCR5. Atheroprotective and plaque stabilizing properties are attributed to CXCL12, which plays an important role in regenerative processes by attracting progenitor cells. Its release from luminal attached platelets accelerates endothelial healing after injury. Platelet surface molecules GPIIb/IIIa, GP1bα, P-selectin, JAM-A and the CD40/CD40L dyade are crucially involved in the interaction with endothelial cells, leukocytes and matrix molecules affecting atherogenesis. Beyond the effects on the arterial inflammatory infiltrate, platelets affect cholesterol metabolism by binding, modifying and endocytosing LDL particles via their scavenger receptors and contribute to the formation of lipid laden macrophages. Current medical therapies for the prevention of atherosclerotic therapies enable the elucidation of mechanisms linking platelets to inflammation

  17. Qualitative analysis of subcutaneous Lispro and regular insulin injections for stress hyperglycemia: a pilot numerical study.

    Science.gov (United States)

    Strilka, Richard J; Armen, Scott B; Indeck, Matthew C

    2014-09-07

    Increased glucose variability (GV) is an independent risk factor for mortality in the critically ill; unfortunately, the optimal insulin therapy that minimizes GV is not known. We simulate the glucose-insulin feedback system to study how stress hyperglycemia (SH) states, taken to be a non-uniform group of physiologic disorders with varying insulin resistance (IR) and similar levels of hyperglycemia, respond to the type and dose of subcutaneous (SQ) insulin. Two groups of 100 virtual patients are studied: those receiving and those not receiving continuous enteral feeds. Stress hyperglycemia was facilitated by doubling the gluconeogenesis rate and IR was stepwise varied from a borderline to a high value. Lispro and regular insulin were simulated with dosages that ranged from 0 to 6 units; the resulting GV was analyzed after each insulin injection. The numerical model used consists of a set of non-linear differential equations with two time delays and five adjustable parameters. The results show that regular insulin decreased GV in both patient groups and rarely caused hypoglycemia. With continuous enteral feeds and borderline to mild IR, Lispro showed minimal effect on GV; however, rebound hyperglycemia that increased GV occurred when the IR was moderate to high. Without a nutritional source, Lispro worsened GV through frequent hypoglycemia episodes as the injection dose increased. The inferior performance of Lispro is a result of its rapid absorption profile; half of its duration of action is similar to the glucose ultradian period. Clinical trials are needed to examine whether these numerical results represent the glucose-insulin dynamics that occur in intensive care units, and if such dynamics are present, their clinical effects should be evaluated. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Physical Activity, TV Watching Time, Sleeping, and Risk of Obesity and Hyperglycemia in the Offspring of Mothers with Gestational Diabetes Mellitus

    Science.gov (United States)

    Zhang, Tao; Wang, Peng; Liu, Huikun; Wang, Leishen; Li, Weiqin; Leng, Junhong; Li, Nan; Zhang, Shuang; Qi, Lu; Tuomilehto, Jaakko; Yu, Zhijie; Yang, Xilin; Hu, Gang

    2017-01-01

    We investigated the association of physical activity, TV watching time, sleeping time with the risks of obesity and hyperglycemia among 1263 offspring aged 1-5 years of mothers with gestational diabetes (GDM) in a cross-sectional study. Logistic regression models were used to obtain the odd ratios (ORs) (95% confidence intervals [CI]) of childhood obesity and hyperglycemia associated with different levels of indoor activity, outdoor activity, TV watching, and sleeping time. The multivariable-adjusted ORs of obesity based on different levels of TV watching time (0, <1.0, and ≥1.0 hour/day) were 1.00, 1.21 (95% CI 0.72-2.05), and 2.20 (95% CI 1.33-3.63) (Ptrend = 0.003), respectively. The multivariable-adjusted ORs of hyperglycemia based on different levels of indoor activity (<5.0, 5.0-6.9, and ≥7.0 hours/day) were 1.00, 0.74 (95% CI 0.45-1.21), and 0.49 (95% CI 0.28-0.84) (Ptrend = 0.034), respectively. The multivariable-adjusted ORs of hyperglycemia associated with different levels of sleeping time (<11.0, 11.0-11.9, and ≥12.0 hours/day) were 1.00, 0.67 (95% CI 0.42-1.05), and 0.39 (95% CI 0.23-0.67) (Ptrend = 0.003), respectively. The present study indicated a positive association of TV watching with the risk of obesity, and an inverse association of either indoor activity or sleeping time with the risk of hyperglycemia among offspring born to GDM mothers in Tianjin, China.

  19. The relationship between obesity, hyperglycemia symptoms, and health-related quality of life among Hispanic and non-Hispanic white children and adolescents

    Directory of Open Access Journals (Sweden)

    Rohrer James E

    2006-01-01

    Full Text Available Abstract Background The current study was conducted to evaluate the effects of overweight, hyperglycemia symptoms, Hispanic ethnicity, and language barriers on health-related quality of life (HRQoL among children and adolescents. Methods Parents'/guardians of a population based sample of 5530 children between ages 3 and 18 were administered the parents' version of the KINDL® survey instrument to assess HRQoL in children and adolescents. Multiple linear regression analysis was used to assess relationships between HRQoL, body mass index, and hyperglycemia symptoms categories. Results The mean age of children was 10.6 (SD = 4.3. The mean KINDL® total score was 79.7 (SD = 11.6 and the mean physical functioning score was 81.9 (SD = 20.3. Male children exhibited better physical health as compared to the female children (p p = 0.008. However, the association was not significant for the four of the six subscales including the physical health domain. Children with hyperglycemia symptoms and a family history of diabetes also had significantly lower overall and physical health HRQoL (p p p = 0.001. Conclusion Results suggest that overweight may reduce overall quality of life among children, though it does not directly influence physical functioning. However, hyperglycemia symptoms may affect both overall health and physical functioning. Findings also suggest the need for developing programs directed at overcoming language barriers that may face Spanish-speaking children or their parents. Furthermore, targeting children who have hyperglycemia symptoms with public information campaigns may be more appropriate than targeting overweight children.

  20. A Role of RIP3-Mediated Macrophage Necrosis in Atherosclerosis Development

    OpenAIRE

    Lin, Juan; Li, Hanjie; Yang, Min; Ren, Junming; Huang, Zhe; Han, Felicia; Huang, Jian; Ma, Jianhui; Zhang, Duanwu; Zhang, Zhirong; Wu, Jianfeng; Huang, Deli; Qiao, Muzhen; Jin, Guanghui; Wu, Qiao

    2013-01-01

    Necrotic death of macrophages has long been known to be present in atherosclerotic lesions but has not been studied. We examined the role of receptor interacting protein (RIP) 3, a mediator of necrotic cell death, in atherosclerosis and found that RIP3−/−;Ldlr−/− mice were no different from RIP3+/+;Ldlr−/− mice in early atherosclerosis but had significant reduction in advanced atherosclerotic lesions. Similar results were observed in Apoe−/− background mice. Bone marrow transplantation reveal...

  1. Outcomes in Patients With Metastatic Renal Cell Carcinoma Who Develop Everolimus-Related Hyperglycemia and Hypercholesterolemia: Combined Subgroup Analyses of the RECORD-1 and REACT Trials.

    Science.gov (United States)

    Bono, Petri; Oudard, Stephane; Bodrogi, Istvan; Hutson, Thomas E; Escudier, Bernard; Machiels, Jean-Pascal; Thompson, John A; Figlin, Robert A; Ravaud, Alain; Basaran, Mert; Porta, Camillo; Bracarda, Sergio; Brechenmacher, Thomas; Lin, Chinjune; Voi, Maurizio; Grunwald, Viktor; Motzer, Robert J

    2016-10-01

    Hyperglycemia and hypercholesterolemia are class effects of mammalian target of rapamycin inhibitors. The purpose of this study was to characterize safety and efficacy of patients with metastatic renal cell carcinoma (mRCC) treated with everolimus in RECORD-1 (REnal Cell cancer treatment with Oral RAD001 given Daily) and REACT (RAD001 Expanded Access Clinical Trial in RCC) who developed these events. Adults with vascular endothelial growth factor-refractory mRCC received everolimus 10 mg/d in the randomized RECORD-1 (n = 277) and open-label REACT (n = 1367) studies. Outcomes included safety, treatment duration, overall response, and progression-free survival for patients who developed hypercholesterolemia or hyperglycemia. In RECORD-1, 12% (33 of 277) and 20% (55 of 277) of patients developed any grade hyperglycemia or hypercholesterolemia, respectively, with only 6% (78 of 1367) and 1% (14 of 1367) of the same events, respectively, in REACT. Median everolimus treatment duration was similar for patients with hyperglycemia or hypercholesterolemia (RECORD-1, 6.2 and 6.2 months, respectively; REACT, 4.4 and 4.5 months, respectively), but longer than the overall populations (RECORD-1, 4.6 months; REACT, 3.2 months). In RECORD-1/REACT, 82%/68% of patients with hyperglycemia and 75%/71% of patients with hypercholesterolemia achieved partial response or stable disease. The incidence of clinically notable Grade 3 or 4 adverse events, other than anemia and lymphopenia, appeared to be similar across trials and subgroups. Although there was a trend for improved progression-free survival with development of hyperglycemia or hypercholesterolemia, the association was not statistically significant. Hyperglycemia and hypercholesterolemia were observed in low numbers of patients, and although these events might be associated with improved response to everolimus, the differences were not significant. These findings should be validated with prospective biomarker studies. Copyright

  2. Individuals with Type 1 and Type 2 Diabetes Mellitus Trade Increased Hyperglycemia for Decreased Hypoglycemia When Glycemic Variability is not Improved.

    Science.gov (United States)

    Jangam, Sujit R; Hayter, Gary; Dunn, Timothy C

    2018-02-01

    Glycemic variability refers to oscillations in blood glucose within a day and differences in blood glucose at the same time on different days. Glycemic variability is linked to hypoglycemia and hyperglycemia. The relationship among these three important metrics is examined here, specifically to show how reduction in both hypo- and hyperglycemia risk is dependent on changes in variability. To understand the importance of glycemic variability in the simultaneous reduction of hypoglycemia and hyperglycemia risk, we introduce the glycemic risk plot-estimated HbA1c % (eA1c) vs. minutes below 70 mg/dl (MB70) with constant variability contours for predicting post-intervention risks in the absence of a change in glycemic variability. The glycemic risk plot illustrates that individuals who do not reduce glycemic variability improve one of the two metrics (hypoglycemia risk or hyperglycemia risk) at the cost of the other. It is important to reduce variability to improve both risks. These results were confirmed by data collected in a randomized controlled trial consisting of individuals with type 1 and type 2 diabetes on insulin therapy. For type 1, a total of 28 individuals out of 35 (80%) showed improvement in at least one of the risks (hypo and/or hyper) during the 100-day course of the study. Seven individuals (20%) showed improvement in both. Similar data were observed for type 2 where a total of 36 individuals out of 43 (84%) showed improvement in at least one risk and 8 individuals (19%) showed improvement in both. All individuals in the study who showed improvement in both hypoglycemia and hyperglycemia risk also showed a reduction in variability. Therapy changes intended to improve an individual's hypoglycemia or hyperglycemia risk often result in the reduction of one risk at the expense of another. It is important to improve glucose variability to reduce both risks or at least maintain one risk while reducing the other. Abbott Diabetes Care.

  3. Targeting annexin A7 by a small molecule suppressed the activity of phosphatidylcholine-specific phospholipase C in vascular endothelial cells and inhibited atherosclerosis in apolipoprotein E⁻/⁻mice.

    Science.gov (United States)

    Li, H; Huang, S; Wang, S; Zhao, J; Su, L; Zhao, B; Zhang, Y; Zhang, S; Miao, J

    2013-09-19

    Phosphatidylcholine-specific phospholipase C (PC-PLC) is a key factor in apoptosis and autophagy of vascular endothelial cells (VECs), and involved in atherosclerosis in apolipoprotein E⁻/⁻ (apoE⁻/⁻) mice. But the endogenous regulators of PC-PLC are not known. We recently found a small chemical molecule (6-amino-2, 3-dihydro-3-hydroxymethyl-1, 4-benzoxazine, ABO) that could inhibit oxidized low-density lipoprotein (oxLDL)-induced apoptosis and promote autophagy in VECs, and further identified ABO as an inhibitor of annexin A7 (ANXA7) GTPase. Based on these findings, we hypothesize that ANXA7 is an endogenous regulator of PC-PLC, and targeting ANXA7 by ABO may inhibit atherosclerosis in apoE⁻/⁻ mice. In this study, we tested our hypothesis. The results showed that ABO suppressed oxLDL-induced increase of PC-PLC level and activity and promoted the co-localization of ANXA7 and PC-PLC in VECs. The experiments of ANXA7 knockdown and overexpression demonstrated that the action of ABO was ANXA7-dependent in cultured VECs. To investigate the relation of ANXA7 with PC-PLC in atherosclerosis, apoE⁻/⁻ mice fed with a western diet were treated with 50 or 100 mg/kg/day ABO. The results showed that ABO decreased PC-PLC levels in the mouse aortic endothelium and PC-PLC activity in serum, and enhanced the protein levels of ANXA7 in the mouse aortic endothelium. Furthermore, both dosages of ABO significantly enhanced autophagy and reduced apoptosis in the mouse aortic endothelium. As a result, ABO significantly reduced atherosclerotic plaque area and effectively preserved a stable plaques phenotype, including reduced lipid deposition and pro-inflammatory macrophages, increased anti-inflammatory macrophages, collagen content and smooth muscle cells, and less cell death in the plaques. In conclusion, ANXA7 was an endogenous regulator of PC-PLC, and targeting ANXA7 by ABO inhibited atherosclerosis in apoE⁻/⁻ mice.

  4. (18)F-FDG PET imaging of murine atherosclerosis

    DEFF Research Database (Denmark)

    Hag, Anne Mette Fisker; Pedersen, Sune Folke; Christoffersen, Christina

    2012-01-01

    To study whether (18)F-FDG can be used for in vivo imaging of atherogenesis by examining the correlation between (18)F-FDG uptake and gene expression of key molecular markers of atherosclerosis in apoE(-/-) mice....

  5. Effects of apolipoprotein M in uremic atherosclerosis

    DEFF Research Database (Denmark)

    Bosteen, Markus Høybye; Madsen Svarrer, Eva Martha; Bisgaard, Line Stattau

    2017-01-01

    BACKGROUND AND AIMS: Chronic kidney disease is characterized by uremia and causes premature death, partly due to accelerated atherosclerosis. Apolipoprotein (apo) M is a plasma carrier protein for the lipid sphingosine-1-phosphate (S1P). The Apom-S1P complex associates with HDL, and may contribute...

  6. [The impact of electronic cigarettes usage on the endothelial function and the progression of atherosclerosis].

    Science.gov (United States)

    Knura, Miłosz; Dragon, Jonasz; Łabuzek, Krzysztof; Okopień, Bogusław

    2018-01-23

    The exponetial growth in popularity of electronic cigarettes in the world markets intensifies the debate about their health effects. The smoking of traditional tabacoo products is a factor associated with the endothelium damage and progression of atherosclerosis. The elimination of the combustion process in electronic cigarettes allows to conclude that they are less harmful to a vascular endothelium than traditional tobacco products. E-cigarette aerosol contains many compounds that have an influence on initiation and progression of atherosclerosis. Nicotine protherogenic action is not fully explained. On one hand, nicotine modifies metabolic pathways leading to atherosclerosis, whereas epidemiological studies do not show an increased risk of cardiovascular disease in the population using nicotine replacement therapy or snuff. Acrolein, formaldehyde and the ultrafine particles generated during e-liquid heating have an impact on initiation and progression of atherosclerosis, but their level is lower than that of tobacco smoke. In order to assess accurately the longterm effects of e-cigarettes, it is necessary to conduct epidemiological studies measuring the effects of using e-cigarettes. It is claimed that the use of electronic cigarettes has a potential impact on the development of atherosclerosis, but is significantly lower than that of traditional cigarettes.

  7. [Age-related macular degeneration as a local manifestation of atherosclerosis - a novel insight into pathogenesis].

    Science.gov (United States)

    Machalińska, Anna

    2013-01-01

    Age-related macular degeneration is the leading cause of irreversible visual impairment and disability among the elderly in developed countries. There is compelling evidence that atherosclerosis and age-related macular degeneration share a similar pathogenic process. The association between atherosclerosis and age-related macular degeneration has been inferred from histological, biochemical and epidemiological studies. Many published data indicate that drusen are similar in molecular composition to plaques in atherosclerosis. Furthermore, a great body of evidence has emerged over the past decade that implicates the chronic inflammatory processes in the pathogenesis and progression of both disorders. We speculate that vascular atherosclerosis and age-related macular degeneration may represent different manifestations of the same disease induced by a pathologic tissue response to the damage caused by oxidative stress and local ischemia. In this review, we characterise in detail a strong association between age-related macular degeneration and atherosclerosis development, and we postulate the hypothesis that age-related macular degeneration is a local manifestation of a systemic disease. This provides a new approach for understanding the aspects of pathogenesis and might improve the prevention and treatment of both diseases which both result from ageing of the human body.

  8. Risk factors of atherosclerosis and clinical and morphological comparisons in systemic vasculitides

    Directory of Open Access Journals (Sweden)

    Leonid Aleksandrovich Strizhakov

    2012-01-01

    Full Text Available Objective: to study the incidence rates of angina, myocardial infarction (MI, stroke, and the frequency of endovascular interventions in patients with systemic vasculitides, and the incidence rate of atherosclerosis according to autopsy data. Subjects and methods. Three hundred and twenty-one patients with systemic vasculitides: Wegener's granulomatosis (n = 138, Takayasu's arteritis (n = 79, polyarteritis nodosum (n = 55, and Churg-Strauss syndrome (n = 49 were examined; 55 autopsies were analyzed in patients with the above diseases. Results. Fifty-one (15.6% of the 321 patients were diagnosed as having cardiovascular diseases (CVD: angina pectoris (7.1% and MI (3.1% and endovascular interventions (0.9%. The risk of cardiovascular events was found to be associated with traditional risk factors, such as male gender and age. Arterial hypertension, hypercholesterolaemia, and increased serum creatinine were more frequently detected in the CVD group that showed no significant differences from the non-CVD group. According to autopsy results, atherosclerosis was identified in the patients with Wegener's granulomatosis (52%, Takayasu's arteritis (50%, polyarteritis nodosum (52.6%, and Churg-Strauss syndrome (57.1%. Conclusion. CVD and atherosclerosis are common in systemic vasculitides, which requires the traditional risk factors of atherosclerosis to be actively corrected.

  9. Effect of plasma homocysteine level and urinary monomethylarsonic acid on the risk of arsenic-associated carotid atherosclerosis

    International Nuclear Information System (INIS)

    Wu, M.-M.; Chiou, H.-Y.; Hsueh, Y.-M.; Hong, C.-T.; Su, C.-L.; Chang, S.-F.; Huang, W.-L.; Wang, H.-T.; Wang, Y.-H.; Hsieh, Y.-C.; Chen, C.-J.

    2006-01-01

    Arsenic-contaminated well water has been shown to increase the risk of atherosclerosis. Because of involving S-adenosylmethionine, homocysteine may modify the risk by interfering with the biomethylation of ingested arsenic. In this study, we assessed the effect of plasma homocysteine level and urinary monomethylarsonic acid (MMA V ) on the risk of atherosclerosis associated with arsenic. In total, 163 patients with carotid atherosclerosis and 163 controls were studied. Lifetime cumulative arsenic exposure from well water for study subjects was measured as index of arsenic exposure. Homocysteine level was determined by high-performance liquid chromatography (HPLC). Proportion of MMA V (MMA%) was calculated by dividing with total arsenic species in urine, including arsenite, arsenate, MMA V , and dimethylarsinic acid (DMA V ). Results of multiple linear regression analysis show a positive correlation of plasma homocysteine levels to the cumulative arsenic exposure after controlling for atherosclerosis status and nutritional factors (P < 0.05). This correlation, however, did not change substantially the effect of arsenic exposure on the risk of atherosclerosis as analyzed in a subsequent logistic regression model. Logistic regression analyses also show that elevated plasma homocysteine levels did not confer an independent risk for developing atherosclerosis in the study population. However, the risk of having atherosclerosis was increased to 5.4-fold (95% CI, 2.0-15.0) for the study subjects with high MMA% (≥16.5%) and high homocysteine levels (≥12.7 μmol/l) as compared to those with low MMA% (<9.9%) and low homocysteine levels (<12.7 μmol/l). Elevated homocysteinemia may exacerbate the formation of atherosclerosis related to arsenic exposure in individuals with high levels of MMA% in urine

  10. Proinflammatory Status, Genetics and Atherosclerosis

    Czech Academy of Sciences Publication Activity Database

    Poledne, R.; Lorenzová, A.; Stávek, P.; Valenta, Zdeněk; Hubáček, J.; Suchánek, R.; Piťha, J.

    2009-01-01

    Roč. 58, Suppl. 2 (2009), S111-S118 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M06014 Grant - others:GA MŠk(CZ) 1M0510 Program:1M Institutional research plan: CEZ:AV0Z10300504 Keywords : atherosclerosis * inflammation * C-reactive protein * genetics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.430, year: 2009 http://www.biomed.cas.cz/physiolres/pdf/58%20Suppl%202/58_S111.pdf

  11. [Evolution of pathogenesis of atherosclerosis in phylogenesis].

    Science.gov (United States)

    Titov, V N

    2014-01-01

    The first atherosclerosis pandemics developed in phylogenesis when animals went out of the ocean, the second coincided with mutations of proteins that transferred zero-cholesterol esters, the third (present-day pandemics) results from disturbed biological function of trophology, abnormally high content of saturated fatty acids and their trans-forms in food, and blockade of bioavailability of polyenic FA (PNFA) for cells. The blood pool of ligand-free lipoproteins, phylogenetically early macrophages are only partly utilized in intima giving rise to atheromatosis. When active absorption of w-3 and w-6 PNFA is blocked, the cells synthesize by way of compensation non-physiological w-9 eicosanoids which creates the basis of pathogenesis of atherosclerosis, pathology ofautocrine regulation, and paracrine humoral regulation of cell communities and the body. A rise in the frequency of non-infectious diseases above 5-7% is regarded as pathology of biological functions and reactions. Non-physiological environmental effects should be neutralized by normalization of tropholgy function, exotrophic biological reaction. Metabolic pandemics may have two outcomes. First: (a) effective reduction to a minimum of infavourable environmental effects, i.e. normalization of the nutritive function, (b) matching it with possibilities of lipoproteins, (c) reduction of morbidity and mortality from atherosclerosis. Second: man continues to develop as in phylogenesis and adapts himself to nonphysiological nutrition. Mortality from infarction and stroke will remain high during the next 40-50 thousand years. Increased content of w-3 PNFA in food without reduction of NAF with blockade of bioavailability will further facilitate atheromatosis. Man should rely on physiological nutrition, there is no reason to rely on hypolipidemic agents. Otherwise, the second outcome awaits the mankind. Tertium non datum.

  12. Beneficial Effect of Jojoba Seed Extracts on Hyperglycemia-Induced Oxidative Stress in RINm5f Beta Cells.

    Science.gov (United States)

    Belhadj, Sahla; Hentati, Olfa; Hamdaoui, Ghaith; Fakhreddine, Khaskhoussi; Maillard, Elisa; Dal, Stéphanie; Sigrist, Séverine

    2018-03-20

    Hyperglycemia occurs during diabetes and insulin resistance. It causes oxidative stress by increasing reactive oxygen species (ROS) levels, leading to cellular damage. Polyphenols play a central role in defense against oxidative stress. In our study, we investigated the antioxidant properties of simmondsin, a pure molecule present in jojoba seeds, and of the aqueous extract of jojoba seeds on fructose-induced oxidative stress in RINm5f beta cells. The exposure of RINm5f beta cells to fructose triggered the loss of cell viability (-48%, p jojoba seed extract makes jojoba a powerful agent to prevent the destruction of RINm5f beta cells induced by hyperglycemia.

  13. Asymmetrical distribution of atherosclerosis in the carotid artery: identical patterns across age, race, and gender

    NARCIS (Netherlands)

    Tajik, Parvin; Meijer, Rudy; Duivenvoorden, Raphaël; Peters, Sanne A. E.; Kastelein, John J.; Visseren, Frank J.; Crouse, John R.; Palmer, Mike K.; Raichlen, Joel S.; Grobbee, Diederick E.; Bots, Michiel L.

    2012-01-01

    Background: Small autopsy studies and clinical practice indicated that carotid atherosclerosis develops in an asymmetrical helical pattern coinciding with regions of low shear stress. We investigated the distribution of carotid atherosclerosis as determined by maximum carotid intima-media thickness

  14. Aterosclerose experimental em coelhos Experimental atherosclerosis in rabbits

    Directory of Open Access Journals (Sweden)

    Waleska C. Dornas

    2010-08-01

    Full Text Available Numerosas pesquisas têm sido realizadas utilizando modelos experimentais para estudar o desenvolvimento da aterosclerose com dieta induzindo hiperlipidemia. Devido ao fato de que coelhos são muito sensíveis a dietas ricas em colesterol e acumulam grandes quantidades no plasma, a utilização destes animais como modelo experimental para avaliar o desenvolvimento de aterosclerose é de grande relevância, trazendo informação sobre fatores que contribuem para progressão e regressão aplicadas a situações humanas. Sendo assim, nessa revisão a função aterogênica do colesterol é mostrada em trabalhos que incluem o coelho como modelo experimental, uma vez que este animal tornou-se o mais popular modelo experimental de aterosclerose.Many researches have been conducted in experimental models in order to study the development of atherosclerosis from hyperlipidemia-inducing diets. Since rabbits are very sensitive to cholesterol-rich diets and accumulate large amounts of cholesterol in their plasma, their use as experimental models to evaluate the development of atherosclerosis is highly relevant and brings information on factors that contribute to the progression and regression of this condition that can be applied to humans. As such, this review includes studies on the atherogenic function of cholesterol based on rabbits as the experimental model, since they have become the most largely used experimental model of atherosclerosis.

  15. Endothelium Protective Function of Statins in Men and Women with Coronary Atherosclerosis

    OpenAIRE

    M. V. Klimushina; N. G. Gumanova; A. Ju. Gorshkov; N. E. Gavrilova; V. A. Metel'skaja; S. A. Boytsov

    2016-01-01

    Aim. To study the relationship between serum endothelin levels and lipid-lowering therapy in patients with confirmed coronary atherosclerosis.Material and methods. Patients (n=447; 320 men and 127 women; mean age 62.7±8.8 years) with coronary atherosclerosis, confirmed by coronary angiography, were included into the study. Serum endothelin levels were assessed by enzyme immunoassay (ELISA).Results. Negative correlation between the statins receiving and serum endothelin level was found in men ...

  16. Sympathetic nervous dysregulation in the absence of systolic left ventricular dysfunction in a rat model of insulin resistance with hyperglycemia

    Directory of Open Access Journals (Sweden)

    Suuronen Erik J

    2011-08-01

    Full Text Available Abstract Background Diabetes mellitus is strongly associated with cardiovascular dysfunction, derived in part from impairment of sympathetic nervous system signaling. Glucose, insulin, and non-esterified fatty acids are potent stimulants of sympathetic activity and norepinephrine (NE release. We hypothesized that sustained hyperglycemia in the high fat diet-fed streptozotocin (STZ rat model of sustained hyperglycemia with insulin resistance would exhibit progressive sympathetic nervous dysfunction in parallel with deteriorating myocardial systolic and/or diastolic function. Methods Cardiac sympathetic nervous integrity was investigated in vivo via biodistribution of the positron emission tomography radiotracer and NE analogue [11C]meta-hydroxyephedrine ([11C]HED. Cardiac systolic and diastolic function was evaluated by echocardiography. Plasma and cardiac NE levels and NE reuptake transporter (NET expression were evaluated as correlative measurements. Results The animal model displays insulin resistance, sustained hyperglycemia, and progressive hypoinsulinemia. After 8 weeks of persistent hyperglycemia, there was a significant 13-25% reduction in [11C]HED retention in myocardium of STZ-treated hyperglycemic but not euglycemic rats as compared to controls. There was a parallel 17% reduction in immunoblot density for NE reuptake transporter, a 1.2 fold and 2.5 fold elevation of cardiac and plasma NE respectively, and no change in sympathetic nerve density. No change in ejection fraction or fractional area change was detected by echocardiography. Reduced heart rate, prolonged mitral valve deceleration time, and elevated transmitral early to atrial flow velocity ratio measured by pulse-wave Doppler in hyperglycemic rats suggest diastolic impairment of the left ventricle. Conclusions Taken together, these data suggest that sustained hyperglycemia is associated with elevated myocardial NE content and dysregulation of sympathetic nervous system

  17. Accelerated atherosclerosis in patients with systemic autoimmune diseases

    NARCIS (Netherlands)

    De Leeuw, K.; Kallenberg, Cees; Bijl, Marc; Shoenfeld, Y.; Gershwin, M.E.; Shoenfeld, Y; Gershwin, ME

    2005-01-01

    Systemic autoimmune diseases such as systemic lupus erythematosus and Wegener's granulomatosis are associated with a significantly increased prevalence of cardiovascular disease (CVD) compared with age- and sex-matched controls. Many risk factors are involved in the pathogenesis of atherosclerosis,

  18. Clinical evaluation of atherosclerosis and mechanical properties of the thoracic aorta

    International Nuclear Information System (INIS)

    Saiki, Atsushi

    1991-01-01

    To evaluate the aortic wall atherosclerosis, X-ray CT and ECG gated radionuclide angiography were performed in 25 subjects. They were classified into 17 normotensive group (N) and 8 hypertensive group (HT). The time-activity curve was generated using radionuclide angiography in the portion of the thoracic aorta. The aortic wall distensibility was expressed as 100ΔV/V 0 / PP, where ΔV was difference between maximum and minimum (V 0 ) counts of the aorta, and PP was pulse pressure. The degree of the aortic wall atherosclerosis was evaluated by X-ray CT. The aortic wall CT-score was calculated from the CT-scores measured whithin the region of interest of the other margin of the aorta and of the background by X-ray CT. There was a significant correlation between aortic wall CT-score and systolic blood pressure (r=0.59, p<0.01) or aortic wall distensibility (r=-0.74, p<0.01)), but no correlation existed between aortic wall CT-score and diastolic blood pressure (r=0.11, p:NS). The aortic wall distensibility was higher and the aortic wall CT-score was lower in N-group than in HT-group, whereas there was no difference of the radius of the aorta between both groups. These results suggest that the aortic wall atherosclerosis advanced progressively in hypertensive patients and systolic blood pressure was a good predictor of the degree of the aortic atherosclerosis. (author)

  19. Agent Based Modeling of Atherosclerosis: A Concrete Help in Personalized Treatments

    Science.gov (United States)

    Pappalardo, Francesco; Cincotti, Alessandro; Motta, Alfredo; Pennisi, Marzio

    Atherosclerosis, a pathology affecting arterial blood vessels, is one of most common diseases of the developed countries. We present studies on the increased atherosclerosis risk using an agent based model of atherogenesis that has been previously validated using clinical data. It is well known that the major risk in atherosclerosis is the persistent high level of low density lipoprotein (LDL) concentration. However, it is not known if short period of high LDL concentration can cause irreversible damage and if reduction of the LDL concentration (either by life style or drug) can drastically or partially reduce the already acquired risk. We simulated four different clinical situations in a large set of virtual patients (200 per clinical scenario). In the first one the patients lifestyle maintains the concentration of LDL in a no risk range. This is the control case simulation. The second case is represented by patients having high level of LDL with a delay to apply appropriate treatments; The third scenario is characterized by patients with high LDL levels treated with specific drugs like statins. Finally we simulated patients that are characterized by several oxidative events (smoke, sedentary life style, assumption of alcoholic drinks and so on so forth) that effective increase the risk of LDL oxidation. Those preliminary results obviously need to be clinically investigated. It is clear, however, that SimAthero has the power to concretely help medical doctors and clinicians in choosing personalized treatments for the prevention of the atherosclerosis damages.

  20. Prevalence and long-term clinical significance of intracranial atherosclerosis after ischaemic stroke or transient ischaemic attack

    DEFF Research Database (Denmark)

    Ovesen, Christian; Abild, Annemette; Christensen, Anders Fogh

    2013-01-01

    We investigated the prevalence and long-term risk associated with intracranial atherosclerosis identified during routine evaluation.......We investigated the prevalence and long-term risk associated with intracranial atherosclerosis identified during routine evaluation....

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