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Sample records for cerebrovascular proinflammatory mediators

  1. Regulation of enhanced cerebrovascular expression of proinflammatory mediators in experimental subarachnoid hemorrhage via the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway

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    Maddahi Aida

    2012-12-01

    Full Text Available Abstract Background Subarachnoid hemorrhage (SAH is associated with high morbidity and mortality. It is suggested that the associated inflammation is mediated through activation of the mitogen-activated protein kinase (MAPK pathway which plays a crucial role in the pathogenesis of delayed cerebral ischemia after SAH. The aim of this study was first to investigate the timecourse of altered expression of proinflammatory cytokines and matrix metalloproteinase in the cerebral arteries walls following SAH. Secondly, we investigated whether administration of a specific mitogen-activated protein kinase kinase (MEK1/2 inhibitor, U0126, given at 6 h after SAH prevents activation of the MEK/extracellular signal-regulated kinase 1/2 pathway and the upregulation of cerebrovascular inflammatory mediators and improves neurological function. Methods SAH was induced in rats by injection of 250 μl of autologous blood into basal cisterns. U0126 was given intracisternally using two treatment regimens: (A treatments at 6, 12, 24 and 36 h after SAH and experiments terminated at 48 h after SAH, or (B treatments at 6, 12, and 24 h after SAH and terminated at 72 h after SAH. Cerebral arteries were harvested and interleukin (IL-6, IL-1β, tumor necrosis factor α (TNFα, matrix metalloproteinase (MMP-9 and phosphorylated ERK1/2 (pERK1/2 levels investigated by immunohistochemistry. Early activation of pERK1/2 was measured by western blot. Functional neurological outcome after SAH was also analyzed. Results Expression levels of IL-1β, IL-6, MMP-9 and pERK1/2 proteins were elevated over time with an early increase at around 6 h and a late peak at 48 to 72 h post-SAH in cerebral arteries. Enhanced expression of TNFα in cerebral arteries started at 24 h and increased until 96 h. In addition, SAH induced sensorimotor and spontaneous behavior deficits in the animals. Treatment with U0126 starting at 6 h after SAH prevented activation of MEK-ERK1/2 signaling. Further, U0126

  2. Thrombin, a mediator of cerebrovascular inflammation in AD and hypoxia

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    Debjani eTripathy

    2013-05-01

    Full Text Available Considerable evidence implicates hypoxia and vascular inflammation in Alzheimer’s disease (AD. Thrombin, a multifunctional inflammatory mediator, is demonstrable in the brains of AD patients both in the vessel walls and senile plaques. Hypoxia-inducible factor 1α (HIF-1α, a key regulator of the cellular response to hypoxia, is also upregulated in the vasculature of human AD brains. The objective of this study is to investigate inflammatory protein expression in the cerebrovasculature of transgenic AD mice and to explore the role of thrombin as a mediator of cerebrovascular inflammation and oxidative stress in AD and in hypoxia-induced changes in brain endothelial cells. Immunofluorescent analysis of the cerebrovasculature in AD mice demonstrates significant (p<0.01-0.001 increases in thrombin, HIF-1α, interleukin-6 (IL-6, monocyte chemoattractant protein-1 (MCP-1, matrix metalloproteinases (MMPs, and reactive oxygen species (ROS compared to controls. Administration of the thrombin inhibitor dabigatran (100 mg/kg to AD mice for 34 wks significantly decreases expression of inflammatory proteins and ROS. Exposure of cultured brain endothelial cells to hypoxia for 6 h causes an upregulation of thrombin, HIF-1α, MCP-1, IL-6 and MMP2 and ROS. Treatment of endothelial cells with the dabigatran (1 nM reduces ROS generation and inflammatory protein expression (p<0.01-0.001. The data demonstrate that inhibition of thrombin in culture blocks the increase in inflammatory protein expression and ROS generation evoked by hypoxia. Also, administration of dabigatran to transgenic AD mice diminishes expression of inflammatory proteins and ROS in the cerebromicrovasculature. Taken together, these results suggest that inhibiting thrombin generation could have therapeutic value in AD and other disorders where hypoxia, inflammation and oxidative stress are involved.

  3. Proinflammatory mediators stimulate neutrophil-directed angiogenesis.

    LENUS (Irish Health Repository)

    McCourt, M

    2012-02-03

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

  4. ALPK1 affects testosterone mediated regulation of proinflammatory cytokines production.

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    Kuo, Tzer-Min; Yeh, Kun-Tu; Hsu, Hui-Ting; Chiang, Shang-Lun; Chang, Jan-Gowth; Huang, Chung-Ming; Tu, Hung-Pin; Liu, Chiu-Shong; Ko, Ying-Chin

    2015-11-01

    Alpha-protein kinase 1, also known as alpha-kinase 1 (ALPK1), is associated with chronic kidney disease (CKD), myocardial infarction, gout and type 2 diabetes mellitus (DM). In addition to having an inductive effect on the proinflammatory cytokines in monocytic THP1 cells, ALPK1 is expressed abundantly in the mouse testes. Low testosterone levels are commonly associated with arthritis, CKD, type 2 DM, cardiovascular disease and inflammation. The testosterone's anti-inflammatory effect has been demonstrated to reduce proinflammatory cytokines and adhesion molecules. In this study, we found that ALPK1 transgenic mice showed lower levels of testosterone in both the testes and the serum. Decreasing endogenous ALPK1 enhanced testosterone levels and transcripts of testosterone-regulated genes (P450scc, 3beta-HSD, P450C17, 17beta-HSD, StAR, and INSL3) in TM3 Leydig cells. In contrast, increasing testosterone decreased ALPK1 in both TM3 and monocytic THP1 cells. This decrease was accompanied by a reduction of the proinflammatory cytokines. Increased ALPK1 levels attenuated the testosterone effects in THP1 cells. Finally, we also found that ALPK1 increased the release of TNF-alpha and TGF-beta1 in the human embryonic kidney 293 cells, while testosterone inhibited ALPK1 in the primary kidney cells. Taken together, this data suggests that the balance between ALPK1 and testosterone plays a critical role in the testosterone-mediated inhibition of proinflammatory cytokines.

  5. Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways.

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    Huang, Shurong; Rutkowsky, Jennifer M; Snodgrass, Ryan G; Ono-Moore, Kikumi D; Schneider, Dina A; Newman, John W; Adams, Sean H; Hwang, Daniel H

    2012-09-01

    Toll-like receptor 4 (TLR4) and TLR2 were shown to be activated by saturated fatty acids (SFAs) but inhibited by docosahexaenoic acid (DHA). However, one report suggested that SFA-induced TLR activation in cell culture systems is due to contaminants in BSA used for solubilizing fatty acids. This report raised doubt about proinflammatory effects of SFAs. Our studies herein demonstrate that sodium palmitate (C16:0) or laurate (C12:0) without BSA solubilization induced phosphorylation of inhibitor of nuclear factor-κB α, c-Jun N-terminal kinase (JNK), p44/42 mitogen-activated-kinase (ERK), and nuclear factor-κB subunit p65, and TLR target gene expression in THP1 monocytes or RAW264.7 macrophages, respectively, when cultured in low FBS (0.25%) medium. C12:0 induced NFκB activation through TLR2 dimerized with TLR1 or TLR6, and through TLR4. Because BSA was not used in these experiments, contaminants in BSA have no relevance. Unlike in suspension cells (THP-1), BSA-solubilized C16:0 instead of sodium C16:0 is required to induce TLR target gene expression in adherent cells (RAW264.7). C16:0-BSA transactivated TLR2 dimerized with TLR1 or TLR6 and through TLR4 as seen with C12:0. These results and additional studies with the LPS sequester polymixin B and in MyD88(-/-) macrophages indicated that SFA-induced activation of TLR2 or TLR4 is a fatty acid-specific effect, but not due to contaminants in BSA or fatty acid preparations.

  6. Ultraviolet Radiation and the Slug Transcription Factor Induce Proinflammatory and Immunomodulatory Mediator Expression in Melanocytes

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    Stephanie H. Shirley

    2012-01-01

    Full Text Available Despite extensive investigation, the precise contribution of the ultraviolet radiation (UVR component of sunlight to melanoma etiology remains unclear. UVR induces keratinocytes to secrete proinflammatory and immunomodulatory mediators that promote inflammation and skin tumor development; expression of the slug transcription factor in keratinocytes is required for maximal production of these mediators. In the present studies we examined the possibility that UVR-exposed melanocytes also produce proinflammatory mediators and that Slug is important in this process. Microarray studies revealed that both UVR exposure and Slug overexpression altered transcription of a variety of proinflammatory mediators by normal human melanocytes; some of these mediators are also known to stimulate melanocyte growth and migration. There was little overlap in the spectra of cytokines produced by the two stimuli. However IL-20 was similarly induced by both stimuli and the NFκB pathway appeared to be important in both circumstances. Further exploration of UVR-induced and Slug-dependent pathways of cytokine induction in melanocytes may reveal novel targets for melanoma therapy.

  7. Nitric Oxide Is a Mediator of Antiproliferative Effects Induced by Proinflammatory Cytokines on Pancreatic Beta Cells

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    Quintana-Lopez, Laura; Blandino-Rosano, Manuel; Perez-Arana, Gonzalo; Lechuga-Sancho, Alfonso; Aguilar-Diosdado, Manuel

    2013-01-01

    Nitric oxide (NO) is involved in several biological processes. In type 1 diabetes mellitus (T1DM), proinflammatory cytokines activate an inducible isoform of NOS (iNOS) in β cells, thus increasing NO levels and inducing apoptosis. The aim of the current study is to determine the role of NO (1) in the antiproliferative effect of proinflammatory cytokines IL-1β, IFN-γ, and TNF-α on cultured islet β cells and (2) during the insulitis stage prior to diabetes onset using the Biobreeding (BB) rat strain as T1DM model. Our results indicate that NO donors exert an antiproliferative effect on β cell obtained from cultured pancreatic islets, similar to that induced by proinflammatory cytokines. This cytokine-induced antiproliferative effect can be reversed by L-NMMA, a general NOS inhibitor, and is independent of guanylate cyclase pathway. Assays using NOS isoform specific inhibitors suggest that the NO implicated in the antiproliferative effect of proinflammatory cytokines is produced by inducible NOS, although not in an exclusive way. In BB rats, early treatment with L-NMMA improves the initial stage of insulitis. We conclude that NO is an important mediator of antiproliferative effect induced by proinflammatory cytokines on cultured β cell and is implicated in β-cell proliferation impairment observed early from initial stage of insulitis. PMID:23840099

  8. Nitric Oxide Is a Mediator of Antiproliferative Effects Induced by Proinflammatory Cytokines on Pancreatic Beta Cells

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    Laura Quintana-Lopez

    2013-01-01

    Full Text Available Nitric oxide (NO is involved in several biological processes. In type 1 diabetes mellitus (T1DM, proinflammatory cytokines activate an inducible isoform of NOS (iNOS in β cells, thus increasing NO levels and inducing apoptosis. The aim of the current study is to determine the role of NO (1 in the antiproliferative effect of proinflammatory cytokines IL-1β, IFN-γ, and TNF-α on cultured islet β cells and (2 during the insulitis stage prior to diabetes onset using the Biobreeding (BB rat strain as T1DM model. Our results indicate that NO donors exert an antiproliferative effect on β cell obtained from cultured pancreatic islets, similar to that induced by proinflammatory cytokines. This cytokine-induced antiproliferative effect can be reversed by L-NMMA, a general NOS inhibitor, and is independent of guanylate cyclase pathway. Assays using NOS isoform specific inhibitors suggest that the NO implicated in the antiproliferative effect of proinflammatory cytokines is produced by inducible NOS, although not in an exclusive way. In BB rats, early treatment with L-NMMA improves the initial stage of insulitis. We conclude that NO is an important mediator of antiproliferative effect induced by proinflammatory cytokines on cultured β cell and is implicated in β-cell proliferation impairment observed early from initial stage of insulitis.

  9. Pro-Inflammatory Cytokine-Mediated Anemia: Regarding Molecular Mechanisms of Erythropoiesis

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    F. Morceau

    2009-01-01

    Full Text Available Anemia of cancer and chronic inflammatory diseases is a frequent complication affecting quality of life. For cancer patients it represents a particularly bad prognostic. Low level of erythropoietin is considered as one of the causes of anemia in these pathologies. The deficiency in erythropoietin production results from pro-inflammatory cytokines effect. However, few data is available concerning molecular mechanisms involved in cytokine-mediated anemia. Some recent publications have demonstrated the direct effect of pro-inflammatory cytokines on cell differentiation towards erythroid pathway, without erythropoietin defect. This suggested that pro-inflammatory cytokine-mediated signaling pathways affect erythropoietin activity. They could interfere with erythropoietin-mediated signaling pathways, inducing early apoptosis and perturbing the expression and regulation of specific transcription factors involved in the control of erythroid differentiation. In this review we summarize the effect of tumor necrosis factor (TNFα, TNF-related apoptosis-inducing ligand (TRAIL, and interferon (IFN-γ on erythropoiesis with a particular interest for molecular feature.

  10. Substrate Stiffness Regulates Proinflammatory Mediator Production through TLR4 Activity in Macrophages

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    Previtera, Michelle L.; Sengupta, Amitabha

    2015-01-01

    Clinical data show that disease adversely affects tissue elasticity or stiffness. While macrophage activity plays a critical role in driving disease pathology, there are limited data available on the effects of tissue stiffness on macrophage activity. In this study, the effects of substrate stiffness on inflammatory mediator production by macrophages were investigated. Bone marrow–derived macrophages were grown on polyacrylamide gels that mimicked the stiffness of a variety of soft biological tissues. Overall, macrophages grown on soft substrates produced less proinflammatory mediators than macrophages grown on stiff substrates when the endotoxin LPS was added to media. In addition, the pathways involved in stiffness–regulated proinflammation were investigated. The TLR4 signaling pathway was examined by evaluating TLR4, p–NF–κB p65, MyD88, and p–IκBα expression as well as p–NF–κB p65 translocation. Expression and translocation of the various signaling molecules were higher in macrophages grown on stiff substrates than on soft substrates. Furthermore, TLR4 knockout experiments showed that TLR4 activity enhanced proinflammation on stiff substrates. In conclusion, these results suggest that proinflammatory mediator production initiated by TLR4 is mechanically regulated in macrophages. PMID:26710072

  11. Subfornical organ mediates sympathetic and hemodynamic responses to blood-borne proinflammatory cytokines.

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    Wei, Shun-Guang; Zhang, Zhi-Hua; Beltz, Terry G; Yu, Yang; Johnson, Alan Kim; Felder, Robert B

    2013-07-01

    Proinflammatory cytokines play an important role in regulating autonomic and cardiovascular function in hypertension and heart failure. Peripherally administered proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), act on the brain to increase blood pressure, heart rate, and sympathetic nerve activity. These molecules are too large to penetrate the blood-brain barrier, and so the mechanisms by which they elicit these responses remain unknown. We tested the hypothesis that the subfornical organ (SFO), a forebrain circumventricular organ that lacks a blood-brain barrier, plays a major role in mediating the sympathetic and hemodynamic responses to circulating proinflammatory cytokines. Intracarotid artery injection of TNF-α (200 ng) or IL-1β (200 ng) dramatically increased mean blood pressure, heart rate, and renal sympathetic nerve activity in rats with sham lesions of the SFO (SFO-s). These excitatory responses to intracarotid artery TNF-α and IL-1β were significantly attenuated in SFO-lesioned (SFO-x) rats. Similarly, the increases in mean blood pressure, heart rate, and renal sympathetic nerve activity in response to intravenous injections of TNF-α (500 ng) or IL-1β (500 ng) in SFO-s rats were significantly reduced in the SFO-x rats. Immunofluorescent staining revealed a dense distribution of the p55 TNF-α receptor and the IL-1 receptor accessory protein, a subunit of the IL-1 receptor, in the SFO. These data suggest that SFO is a predominant site in the brain at which circulating proinflammatory cytokines act to elicit cardiovascular and sympathetic responses.

  12. Micro-RNA dysregulation in multiple sclerosis favours pro-inflammatory T-cell-mediated autoimmunity.

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    Guerau-de-Arellano, Mireia; Smith, Kristen M; Godlewski, Jakub; Liu, Yue; Winger, Ryan; Lawler, Sean E; Whitacre, Caroline C; Racke, Michael K; Lovett-Racke, Amy E

    2011-12-01

    Pro-inflammatory T cells mediate autoimmune demyelination in multiple sclerosis. However, the factors driving their development and multiple sclerosis susceptibility are incompletely understood. We investigated how micro-RNAs, newly described as post-transcriptional regulators of gene expression, contribute to pathogenic T-cell differentiation in multiple sclerosis. miR-128 and miR-27b were increased in naïve and miR-340 in memory CD4(+) T cells from patients with multiple sclerosis, inhibiting Th2 cell development and favouring pro-inflammatory Th1 responses. These effects were mediated by direct suppression of B lymphoma Mo-MLV insertion region 1 homolog (BMI1) and interleukin-4 (IL4) expression, resulting in decreased GATA3 levels, and a Th2 to Th1 cytokine shift. Gain-of-function experiments with these micro-RNAs enhanced the encephalitogenic potential of myelin-specific T cells in experimental autoimmune encephalomyelitis. In addition, treatment of multiple sclerosis patient T cells with oligonucleotide micro-RNA inhibitors led to the restoration of Th2 responses. These data illustrate the biological significance and therapeutic potential of these micro-RNAs in regulating T-cell phenotypes in multiple sclerosis.

  13. Ghrelin's Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on β-Cell Functionality

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    Diaz-Ganete, Antonia; Baena-Nieto, Gloria; Lomas-Romero, Isabel M.; Lopez-Acosta, Jose Francisco; Cozar-Castellano, Irene; Medina, Francisco; Segundo, Carmen; Lechuga-Sancho, Alfonso M.

    2015-01-01

    Ghrelin is a peptidic hormone, which stimulates cell proliferation and inhibits apoptosis in several tissues, including pancreas. In preclinical stage of type 1 diabetes, proinflammatory cytokines generate a destructive environment for β-cells known as insulitis, which results in loss of β-cell mass and impaired insulin secretion, leading to diabetes. Our aim was to demonstrate that ghrelin could preserve β-cell viability, turnover rate, and insulin secretion acting as a counter balance of cytokines. In the present work we reproduced proinflammatory milieu found in insulitis stage by treating murine cell line INS-1E and rat islets with a cytokine cocktail including IL-1β, IFNγ, and TNFα and/or ghrelin. Several proteins involved in survival pathways (ERK 1/2 and Akt/PKB) and apoptosis (caspases and Bcl-2 protein family and endoplasmic reticulum stress markers) as well as insulin secretion were analyzed. Our results show that ghrelin alone has no remarkable effects on β-cells in basal conditions, but interestingly it activates cell survival pathways, downregulates apoptotic mediators and endoplasmic reticulum stress, and restores insulin secretion in response to glucose when beta-cells are cytokine-exposed. These data suggest a potential role of ghrelin in preventing or slowing down the transition from a preclinical to clinically established diabetes by ameliorating the effects of insulitis on β-cells. PMID:26257781

  14. Inhibition of pro-inflammatory mediators: role of Bacopa monniera (L.) Wettst.

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    Viji, Vijayan; Helen, Antony

    2011-10-01

    Bacopa monniera (L.) Wettst is a renowned plant in the Ayurvedic system of medicine. The present study seeks to identify the anti-inflammatory activity of two fractions from the methanolic extract of Bacopa, viz. the triterpenoid and bacoside-enriched fractions. The ability of these two fractions to inhibit the production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 was tested using lipopolysaccharide (LPS)-activated peripheral blood mononuclear cells and peritoneal exudate cells in vitro. We found that triterpenoid and bacoside-enriched fractions significantly inhibited LPS-activated TNF-α, IL-6 and nitrite production in mononuclear cells. Significant antioxidant activity was exhibited by the bacoside enriched fraction compared to the triterpenoid fraction. Carrageenan-induced hind paw oedema assay revealed that triterpenoid and bacoside-enriched fractions exerted anti-oedematogenic effect, while in the arthritis model only the triterpenoid fraction exerted an anti-arthritic potential. The present study provides an insight into the ability of Bacopa monniera to inhibit inflammation through modulation of pro-inflammatory mediator release.

  15. Proinflammatory effects of pancreatic elastase are mediated through TLR4 and NF-kappaB.

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    Hietaranta, Antti; Mustonen, Harri; Puolakkainen, Pauli; Haapiainen, Reijo; Kemppainen, Esko

    2004-10-01

    Pancreatic elastase has been implicated in the pathophysiology of severe acute pancreatitis, characterized by systemic inflammatory response, distant organ failure, and high mortality. Here we show that pancreatic elastase activates transcription factors NF-kappaB, AP-1, and NFAT in human myeloid cells (U-937 and THP-1) in culture. Pancreatic elastase also induces TNF-alpha secretion and increased expression of CD11b in THP-1 cells which can be inhibited by neutralizing anti-Toll-like receptor 4 (TLR4) antibodies. NF-kappaB blocking agents (MG-132, PGA1) prevented elastase-induced TNF-alpha secretion from THP-1 cells. Our results suggest that pancreatic elastase-induced proinflammatory effects are mediated by TLR4 and NF-kappaB in human myeloid cells.

  16. Lower prevalence of carotid plaque hemorrhage in women, and its mediator effect on sex differences in recurrent cerebrovascular events.

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    Neghal Kandiyil

    Full Text Available Women are at lower risk of stroke, and appear to benefit less from carotid endarterectomy (CEA than men. We hypothesised that this is due to more benign carotid disease in women mediating a lower risk of recurrent cerebrovascular events. To test this, we investigated sex differences in the prevalence of MRI detectable plaque hemorrhage (MRI PH as an index of plaque instability, and secondly whether MRI PH mediates sex differences in the rate of cerebrovascular recurrence.Prevalence of PH between sexes was analysed in a single centre pooled cohort of 176 patients with recently symptomatic, significant carotid stenosis (106 severe [≥70%], 70 moderate [50-69%] who underwent prospective carotid MRI scanning for identification of MRI PH. Further, a meta-analysis of published evidence was undertaken. Recurrent events were noted during clinical follow up for survival analysis.Women with symptomatic carotid stenosis (50%≥ were less likely to have plaque hemorrhage (PH than men (46% vs. 70% with an adjusted OR of 0.23 [95% CI 0.10-0.50, P<0.0001] controlling for other known vascular risk factors. This negative association was only significant for the severe stenosis subgroup (adjusted OR 0.18, 95% CI 0.067-0.50 not the moderate degree stenosis. Female sex in this subgroup also predicted a longer time to recurrent cerebral ischemic events (HR 0.38 95% CI 0.15-0.98, P = 0.045. Further addition of MRI PH or smoking abolished the sex effects with only MRI PH exerting a direct effect. Meta-analysis confirmed a protective effect of female sex on development of PH: unadjusted OR for presence of PH = 0.54 (95% CI 0.45-0.67, p<0.00001.MRI PH is significantly less prevalent in women. Women with MRI PH and severe stenosis have a similar risk as men for recurrent cerebrovascular events. MRI PH thus allows overcoming the sex bias in selection for CEA.

  17. Eugenol suppressed the expression of lipopolysaccharide-induced proinflammatory mediators in human macrophages.

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    Lee, Ya-Yun; Hung, Shan-Ling; Pai, Sheng-Fang; Lee, Yuan-Ho; Yang, Shue-Fen

    2007-06-01

    Eugenol is commonly used as an analgesic agent during acute pulpitis and is a major component of root canal sealers. Despite the frequent applications of eugenol in the practice of dentistry, little is known about the role of eugenol under the status of inflammation. This study was aimed to investigate the influence of eugenol on human macrophages (U937) under the stimulation of lipopolysaccharide (LPS). Eugenol was shown to block the release of the bone resorbing mediators, including interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and prostaglandin E2 from LPS-stimulated macrophages. In contrast, eugenol alone did not alter the expression levels of these proinflammatory mediators in macrophages. Consistent with downregulation of bone-resorbing mediators, eugenol suppressed the messenger RNA expression of LPS-induced IL-1beta, TNF-alpha, and cyclooxygenase-2 in macrophages. The results suggest a potential anti-inflammatory effect of eugenol in the acute inflamed pulps and apical periodontitis.

  18. Influence of ulinastatin on pulmonary surfactant protein, anti-inflammatory and pro-inflammatory mediator in patients with severe pneumonia

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    Li Wang; Rui Kang; Jia-Li Xie; Ya-Ni Xue

    2016-01-01

    Objective:To observe the influence of ulinastatin on pulmonary surfactant protein and anti-inflammatory and pro-inflammatory mediator in patients with severe pneumonia. Methods:A total of 54 patients with severe pneumonia treated in our hospital from April 2014 to May 2015 were selected as the study object, and they were randomly divided into control group (conventional treatment of severe pneumonia group) and observation group (conventional treatment and ulinastatin group), with 27 cases in each group. Then the serum levels of pulmonary surfactant protein,anti-inflammatory and pro-inflammatory mediators in two groups before and after treatment at 1 day, 3 day and 5 day were compared. Results:The serum level of pulmonary surfactant protein, anti-inflammatory and pro-inflammatory mediators in two groups before treatment had no significant differences, all P>0.05, and those serum indexes in observation group after treatment at 1 day, 3 day and 5 day were all significantly better than those of the control group, all P<0.05. Conclusions:The ulinastatin can effectively improve the pulmonary surfactant protein, anti-inflammatory and pro-inflammatory mediators in patients with severe pneumonia, and its improvement role for various of severe pneumonia are obvious.

  19. The sterols isolated from Evening Primrose oil modulate the release of proinflammatory mediators.

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    Montserrat-de la Paz, Sergio; Fernández-Arche, Angeles; Angel-Martín, María; García-Giménez, María Dolores

    2012-09-15

    Evening Primrose oil is a natural product extracted by cold-pressed from Oenothera biennis L. seeds. The unsaponifiable matter of this oil is an important source of interesting minor compounds, like long-chain fatty alcohols, sterols and tocopherols. In the present study, sterols were isolated from the unsaponifiable matter of Evening Primrose oil, and the composition was identified and quantified by GC and GC-MS. The major components of sterols fraction were β-Sitosterol and campesterol. We investigated the ability of sterols from Evening Primrose oil to inhibit the release of different proinflammatory mediators in vitro by murine peritoneal macrophages stimulated with lipopolysaccharide. Sterols significantly and dose-dependently decreased nitric oxide production. Western blot analysis showed that nitric oxide reduction was a consequence of the inhibition of inducible nitric oxide synthetase expression. Sterols also reduced tumor necrosis factor-α, interleukine 1β and tromboxane B₂. However, sterols did not reduce prostaglandin E₂. The reduction of eicosanoid release was related to the inhibition of cyclooxygenase-2 expression. These results showed that sterols may have a protective effect on some mediators involved in inflammatory damage development, suggesting its potential value as a putative functional component of Evening Primrose oil.

  20. Inhibition of Pro-inflammatory mediators and cytokines by Chlorella Vulgaris extracts

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    G Sibi

    2016-01-01

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

  1. The Proinflammatory Cytokine High-Mobility Group Box-1 Mediates Retinal Neuropathy Induced by Diabetes

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    Ahmed M. Abu El-Asrar

    2014-01-01

    Full Text Available To test the hypothesis that increased expression of proinflammatory cytokine high-mobility group box-1 (HMGB1 in epiretinal membranes and vitreous fluid from patients with proliferative diabetic retinopathy and in retinas of diabetic rats plays a pathogenetic role in mediating diabetes-induced retinal neuropathy. Retinas of 1-month diabetic rats and HMGB1 intravitreally injected normal rats were studied using Western blot analysis, RT-PCR and glutamate assay. In addition, we studied the effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced biochemical changes in the retina. Diabetes and intravitreal injection of HMGB1 in normal rats induced significant upregulation of HMGB1 protein and mRNA, activated extracellular signal-regulated kinase 1 and 2 (ERK1/2, cleaved caspase-3 and glutamate; and significant downregulation of synaptophysin, tyrosine hydroxylase, glutamine synthetase, and glyoxalase 1. Constant glycyrrhizin intake from the onset of diabetes did not affect the metabolic status of the diabetic rats, but it significantly attenuated diabetes-induced upregulation of HMGB1 protein and mRNA, activated ERK1/2, cleaved caspase-3, and glutamate. In the glycyrrhizin-fed diabetic rats, the decrease in synaptophysin, tyrosine hydroxylase, and glyoxalase 1 caused by diabetes was significantly attenuated. These findings suggest that early retinal neuropathy of diabetes involves upregulated expression of HMGB1 and can be ameliorated by inhibition of HMGB1.

  2. Bioactive extract from moringa oleifera inhibits the pro-inflammatory mediators in lipopolysaccharide stimulated macrophages

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    Masoumeh Tangestani Fard

    2015-01-01

    Full Text Available Introduction: Inflammation is a well-known physiological response to protect the body against infection and restore tissue injury. Nevertheless, the chronic inflammation can trigger various inflammatory associated diseases/disorder. Moringa oleifera is a widely grown plant in most tropical countries and it has been recognized traditionally for several medicinal benefits. Objectives: The objective of this study was to investigate the anti-inflammatory properties of M. oleifera extract on lipopolysaccharide (LPS - stimulated macrophages. Materials and Methods: The anti-inflammatory effect of M. oleifera hydroethanolic bioactive leaves extracts was evaluated by assessing the inhibition of nitric oxide (NO production during Griess reaction and the expression of pro-inflammatory mediators in macrophages. Results: Interestingly, we found that M. oleifera hydroethanolic bioactive leaves extract significantly inhibited the secretion of NO production and other inflammatory markers such as prostaglandin E 2 , tumor necrosis factor alpha, interleukin (IL-6, and IL-1b. Meanwhile, the bioactive extract has induced the production of IL-10 in a dose-dependent manner. In addition, M. oleifera hydroethanolic bioactive leaves extract effectively suppressed the protein expression of inflammatory markers inducible NO synthase, cyclooxygenase-2, and nuclear factor kappa-light-chain-enhancer of activated B-cells p65 in LPS-induced RAW264.7 macrophages in a dose-dependent manner. Conclusion: These findings support the traditional use of M. oleifera plant as an effective treatment for inflammation associated diseases/disorders.

  3. Role of Calprotectin as a Modulator of the IL27-Mediated Proinflammatory Effect on Endothelial Cells

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    Ginolhac, Aurélien; Kähne, Thilo; Sauter, Thomas; Salsmann, Alexandre; Bueb, Jean-Luc

    2015-01-01

    An underlying endothelial dysfunction plays a fundamental role in the pathogenesis of cardiovascular events and is the central feature of atherosclerosis. The protein-based communication between leukocytes and inflamed endothelial cells leading to diapedesis has been largely investigated and several key players such as IL6, TNFα, or the damage associated molecular pattern molecule (DAMP) calprotectin are now well identified. However, regarding cytokine IL27, the controversial current knowledge about its inflammatory role and the involved regulatory elements requires clarification. Therefore, we examined the inflammatory impact of IL27 on primary endothelial cells and the potentially modulatory effect of calprotectin on both transcriptome and proteome levels. A qPCR-based screening demonstrated high IL27-mediated gene expression of IL7, IL15, CXCL10, and CXCL11. Calprotectin time-dependent downregulatory effects were observed on IL27-induced IL15 and CXCL10 gene expression. A mass spectrometry-based approach of IL27 ± calprotectin cell stimulation enlightened a calprotectin modulatory role in the expression of 28 proteins, mostly involved in the mechanism of leukocyte transmigration. Furthermore, we showed evidence for STAT1 involvement in this process. Our findings provide new evidence about the IL27-dependent proinflammatory signaling which may be under the control of calprotectin and highlight the need for further investigations on molecules which might have antiatherosclerotic functions. PMID:26663990

  4. A novel benzenediamine derivate rescued mice from experimental sepsis by attenuating proinflammatory mediators via IRAK4.

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    Dou, Huan; Song, Yuxian; Liu, Xianqin; Yang, Liu; Jiang, Nan; Chen, Dai; Li, Erguang; Tan, Renxiang; Hou, Yayi

    2014-08-01

    We designed and synthesized a novel benzenediamine derivate, FC-99, that was tested for its ability to protect mice from experimental sepsis. Moreover, we sought to determine whether FC-99 could control a bacterial infection and to clarify the mechanism by which FC-99 inhibited LPS-activated macrophages. The effects of FC-99 on inflammation were evaluated in two experimental sepsis models and in cultured macrophages. Microarrays and docking and molecular dynamics simulations were used to determine the target of FC-99. Surface plasmon resonance and molecular detection were performed to confirm the direct interaction of FC-99 with its target. FC-99 protected mice from experimental sepsis. The mice that received FC-99 exhibited a diminished inflammatory response, had a lower local bacterial burden, and experienced a significantly improved survival rate. Genome-wide transcriptional profiling of FC-99-treated macrophages identified IRAK4 as a drug-regulated gene involved in LPS/TLR4 signaling. A computer search and calculations indicated that IRAK4 directly interacted with FC-99. Surface plasmon resonance, IRAK4-regulated signaling pathway analysis, and gene expression profiling of proinflammatory mediators confirmed the direct interaction between FC-99 and IRAK4. FC-99 is a potential therapeutic molecule for sepsis that alleviated experimental sepsis by directly inhibiting IRAK4 activation, which represents a novel target for sepsis therapy.

  5. Role of Calprotectin as a Modulator of the IL27-Mediated Proinflammatory Effect on Endothelial Cells.

    Science.gov (United States)

    Dorosz, Susann A; Ginolhac, Aurélien; Kähne, Thilo; Naumann, Michael; Sauter, Thomas; Salsmann, Alexandre; Bueb, Jean-Luc

    2015-01-01

    An underlying endothelial dysfunction plays a fundamental role in the pathogenesis of cardiovascular events and is the central feature of atherosclerosis. The protein-based communication between leukocytes and inflamed endothelial cells leading to diapedesis has been largely investigated and several key players such as IL6, TNFα, or the damage associated molecular pattern molecule (DAMP) calprotectin are now well identified. However, regarding cytokine IL27, the controversial current knowledge about its inflammatory role and the involved regulatory elements requires clarification. Therefore, we examined the inflammatory impact of IL27 on primary endothelial cells and the potentially modulatory effect of calprotectin on both transcriptome and proteome levels. A qPCR-based screening demonstrated high IL27-mediated gene expression of IL7, IL15, CXCL10, and CXCL11. Calprotectin time-dependent downregulatory effects were observed on IL27-induced IL15 and CXCL10 gene expression. A mass spectrometry-based approach of IL27 ± calprotectin cell stimulation enlightened a calprotectin modulatory role in the expression of 28 proteins, mostly involved in the mechanism of leukocyte transmigration. Furthermore, we showed evidence for STAT1 involvement in this process. Our findings provide new evidence about the IL27-dependent proinflammatory signaling which may be under the control of calprotectin and highlight the need for further investigations on molecules which might have antiatherosclerotic functions.

  6. Role of Calprotectin as a Modulator of the IL27-Mediated Proinflammatory Effect on Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Susann A. Dorosz

    2015-01-01

    Full Text Available An underlying endothelial dysfunction plays a fundamental role in the pathogenesis of cardiovascular events and is the central feature of atherosclerosis. The protein-based communication between leukocytes and inflamed endothelial cells leading to diapedesis has been largely investigated and several key players such as IL6, TNFα, or the damage associated molecular pattern molecule (DAMP calprotectin are now well identified. However, regarding cytokine IL27, the controversial current knowledge about its inflammatory role and the involved regulatory elements requires clarification. Therefore, we examined the inflammatory impact of IL27 on primary endothelial cells and the potentially modulatory effect of calprotectin on both transcriptome and proteome levels. A qPCR-based screening demonstrated high IL27-mediated gene expression of IL7, IL15, CXCL10, and CXCL11. Calprotectin time-dependent downregulatory effects were observed on IL27-induced IL15 and CXCL10 gene expression. A mass spectrometry-based approach of IL27 ± calprotectin cell stimulation enlightened a calprotectin modulatory role in the expression of 28 proteins, mostly involved in the mechanism of leukocyte transmigration. Furthermore, we showed evidence for STAT1 involvement in this process. Our findings provide new evidence about the IL27-dependent proinflammatory signaling which may be under the control of calprotectin and highlight the need for further investigations on molecules which might have antiatherosclerotic functions.

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

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    Andressa Vilas Boas Nogueira

    2014-01-01

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

  8. Baclofen, a GABABR agonist, ameliorates immune-complex mediated acute lung injury by modulating pro-inflammatory mediators.

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    Shunying Jin

    Full Text Available Immune-complexes play an important role in the inflammatory diseases of the lung. Neutrophil activation mediates immune-complex (IC deposition-induced acute lung injury (ALI. Components of gamma amino butyric acid (GABA signaling, including GABA B receptor 2 (GABABR2, GAD65/67 and the GABA transporter, are present in the lungs and in the neutrophils. However, the role of pulmonary GABABR activation in the context of neutrophil-mediated ALI has not been determined. Thus, the objective of the current study was to determine whether administration of a GABABR agonist, baclofen would ameliorate or exacerbate ALI. We hypothesized that baclofen would regulate IC-induced ALI by preserving pulmonary GABABR expression. Rats were subjected to sham injury or IC-induced ALI and two hours later rats were treated intratracheally with saline or 1 mg/kg baclofen for 2 additional hours and sacrificed. ALI was assessed by vascular leakage, histology, TUNEL, and lung caspase-3 cleavage. ALI increased total protein, tumor necrosis factor α (TNF-α and interleukin-1 receptor associated protein (IL-1R AcP, in the bronchoalveolar lavage fluid (BALF. Moreover, ALI decreased lung GABABR2 expression, increased phospho-p38 MAPK, promoted IκB degradation and increased neutrophil influx in the lung. Administration of baclofen, after initiation of ALI, restored GABABR expression, which was inhibited in the presence of a GABABR antagonist, CGP52432. Baclofen administration activated pulmonary phospho-ERK and inhibited p38 MAPK phosphorylation and IκB degradation. Additionally, baclofen significantly inhibited pro-inflammatory TNF-α and IL-1βAcP release and promoted BAL neutrophil apoptosis. Protective effects of baclofen treatment on ALI were possibly mediated by inhibition of TNF-α- and IL-1β-mediated inflammatory signaling. Interestingly, GABABR2 expression was regulated in the type II pneumocytes in lung tissue sections from lung injured patients, further suggesting

  9. Baclofen, a GABABR agonist, ameliorates immune-complex mediated acute lung injury by modulating pro-inflammatory mediators.

    Science.gov (United States)

    Jin, Shunying; Merchant, Michael L; Ritzenthaler, Jeffrey D; McLeish, Kenneth R; Lederer, Eleanor D; Torres-Gonzalez, Edilson; Fraig, Mostafa; Barati, Michelle T; Lentsch, Alex B; Roman, Jesse; Klein, Jon B; Rane, Madhavi J

    2015-01-01

    Immune-complexes play an important role in the inflammatory diseases of the lung. Neutrophil activation mediates immune-complex (IC) deposition-induced acute lung injury (ALI). Components of gamma amino butyric acid (GABA) signaling, including GABA B receptor 2 (GABABR2), GAD65/67 and the GABA transporter, are present in the lungs and in the neutrophils. However, the role of pulmonary GABABR activation in the context of neutrophil-mediated ALI has not been determined. Thus, the objective of the current study was to determine whether administration of a GABABR agonist, baclofen would ameliorate or exacerbate ALI. We hypothesized that baclofen would regulate IC-induced ALI by preserving pulmonary GABABR expression. Rats were subjected to sham injury or IC-induced ALI and two hours later rats were treated intratracheally with saline or 1 mg/kg baclofen for 2 additional hours and sacrificed. ALI was assessed by vascular leakage, histology, TUNEL, and lung caspase-3 cleavage. ALI increased total protein, tumor necrosis factor α (TNF-α and interleukin-1 receptor associated protein (IL-1R AcP), in the bronchoalveolar lavage fluid (BALF). Moreover, ALI decreased lung GABABR2 expression, increased phospho-p38 MAPK, promoted IκB degradation and increased neutrophil influx in the lung. Administration of baclofen, after initiation of ALI, restored GABABR expression, which was inhibited in the presence of a GABABR antagonist, CGP52432. Baclofen administration activated pulmonary phospho-ERK and inhibited p38 MAPK phosphorylation and IκB degradation. Additionally, baclofen significantly inhibited pro-inflammatory TNF-α and IL-1βAcP release and promoted BAL neutrophil apoptosis. Protective effects of baclofen treatment on ALI were possibly mediated by inhibition of TNF-α- and IL-1β-mediated inflammatory signaling. Interestingly, GABABR2 expression was regulated in the type II pneumocytes in lung tissue sections from lung injured patients, further suggesting a

  10. Citral and eugenol modulate DNA damage and pro-inflammatory mediator genes in murine peritoneal macrophages.

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    Porto, Marilia de Paula; da Silva, Glenda Nicioli; Luperini, Bruno Cesar Ottoboni; Bachiega, Tatiana Fernanda; de Castro Marcondes, João Paulo; Sforcin, José Maurício; Salvadori, Daisy Maria Fávero

    2014-11-01

    Citral and eugenol have been broadly studied because of their anti-inflammatory, antioxidant and antiparasitic potentials. In this study, the effects of citral (25, 50 and 100 µg/mL) and eugenol (0.31, 0.62, 1.24 and 2.48 µg/mL) on the expression (RT-PCR) of the pro-inflammatory mediator genes NF-κB1, COX-2 and TNF-α were evaluated in mouse peritoneal macrophages with or without activation by a bacterial lipopolysaccharide (LPS). Additionally, the genotoxic potentials of two compounds and their capacities to modulate the DNA damage induced by doxorubicin (DXR) were investigated using the comet assay. The data revealed that neither citral nor eugenol changed COX-2, NF-κB1 or TNF-α expression in resting macrophages. However, in LPS-activated cells, citral induced the hypoexpression of COX-2 (100 µg/mL) and TNF-α (50 and 100 µg/mL). Hypoexpression of TNF-α was also detected after cellular exposure to eugenol at the highest concentration (2.48 µg/mL). Both compounds exhibited genotoxic potential (citral at 50 and 100 µg/mL and eugenol at all concentrations) but also showed chemopreventive effects, in various treatment protocols. Both citral and eugenol might modulate inflammatory processes and DXR-induced DNA damage, but the use of these compounds must be viewed with caution because they are also able to induce primary DNA lesions.

  11. Hyperglycemic myocardial damage is mediated by proinflammatory cytokine: macrophage migration inhibitory factor.

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    Xi-Yong Yu

    Full Text Available BACKGROUND: Diabetes has been regarded as an inflammatory condition which is associated with left ventricular diastolic dysfunction (LVDD. The purpose of this study was to examine the expression levels of macrophage migration inhibitory factor (MIF and G protein-coupled receptor kinase 2 (GRK2 in patients with early diabetic cardiomyopathy, and to investigate the mechanisms involved in MIF expression and GRK2 activation. METHODS: 83 patients in the age range of 30-64 years with type 2 diabetes and 30 matched healthy men were recruited. Left ventricular diastolic function was evaluated by cardiac Doppler echocardiography. Plasma MIF levels were determined by ELISA. To confirm the clinical observation, we also studied MIF expression in prediabetic rats with impaired glucose tolerance (IGT and relationship between MIF and GRK2 expression in H9C2 cardiomyoblasts exposed to high glucose. RESULTS: Compared with healthy subjects, patients with diabetes have significantly increased levels of plasma MIF which was further increased in diabetic patients with Left ventricular diastolic dysfunction (LVDD. The increased plasma MIF levels in diabetic patients correlated with plasma glucose, glycosylated hemoglobin and urine albumin levels. We observed a significant number of TUNEL-positive cells in the myocardium of IGT-rats but not in the control rats. Moreover, we found higher MIF expression in the heart of IGT with cardiac dysfunction compared to that of the controls. In H9C2 cardiomyoblast cells, MIF and GRK2 expression was significantly increased in a glucose concentration-dependant manner. Furthermore, GRK2 expression was abolished by siRNA knockdown of MIF and by the inhibition of CXCR4 in H9C2 cells. CONCLUSIONS: Our findings indicate that hyperglycemia is a causal factor for increased levels of pro-inflammatory cytokine MIF which plays a role in the development of cardiomyopathy occurring in patients with type 2 diabetes. The elevated levels of MIF

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

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    Yatin M. Shivkar

    2003-01-01

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

  13. Regulation by GD3 of the proinflammatory response of microglia mediated by interleukin-15.

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    Gómez-Nicola, Diego; Doncel-Pérez, Ernesto; Nieto-Sampedro, Manuel

    2006-04-01

    The interleukin (IL)-15-dependent immune responses of murine microglia were strongly affected by low concentrations of the ganglioside GD3. The ganglioside binding to IL-15 inhibited the proinflammatory effects of the cytokine, reducing IL-15-dependent T-cell proliferation as well as mRNA expression for IL-15Ralpha, p65, and NFATc2 in the N13 murine microglial cell line. Treatment of primary murine microglial cultures with GD3 abolished IL-15 production, without affecting cellular viability, but decreased the production of nitric oxide, a direct sensor of inflammation and nuclear factor-kappaB activity. We conclude that low doses of GD3 could inhibit specific proinflammatory mechanisms and modulate the inflammatory environment, leading to a less reactive scene. Microglial cells are one of the main actors in the inflammatory events that follow CNS trauma or an autoimmune disease episode, modulating the internal production of cytokines, growth factors, and other homeostatic molecules that may determine the evolution and outcome of tissue damage. Proinflammatory cytokines have a relevant role in the initial events, and modulation of their activity by gangliosides could cut down their harmful effects and interfere with invasion of the CNS by peripheral immune cells. The antiinflammatory properties of GD3 could be significant in the treatment of pain subsequent to CNS damage.

  14. Entamoeba histolytica cysteine proteinase 5 binds integrin on colonic cells and stimulates NFkappaB-mediated pro-inflammatory responses.

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    Hou, Yongzhong; Mortimer, Leanne; Chadee, Kris

    2010-11-12

    Integrins are important mammalian receptors involved in normal cellular functions and the pathogenesis of inflammation and disease. Entamoeba histolytica is a protozoan parasite that colonizes the gut, and in 10% of infected individuals, causes amebic colitis and liver abscess resulting in 10(5) deaths/year. E. histolytica-induced host inflammatory responses are critical in the pathogenesis of the disease, yet the host and parasite factors involved in disease are poorly defined. Here we show that pro-mature cysteine proteinase 5 (PCP5), a major virulent factor that is abundantly secreted and/or present on the surface of ameba, binds via its RGD motif to α(V)β(3) integrin on Caco-2 colonic cells and stimulates NFκB-mediated pro-inflammatory responses. PCP5 RGD binding to α(V)β(3) integrin triggered integrin-linked kinase(ILK)-mediated phosphorylation of Akt-473 that bound and induced the ubiquitination of NF-κB essential modulator (NEMO). As NEMO is required for activation of the IKKα-IKKβ complex and NFκB signaling, these events markedly up-regulated pro-inflammatory mediator expressions in vitro in Caco-2 cells and in vivo in colonic loop studies in wild-type and Muc2(-/-) mice lacking an intact protective mucus barrier. These results have revealed that EhPCP5 RGD motif is a ligand for α(V)β(3) integrin-mediated adhesion on colonic cells and represents a novel mechanism that E. histolytica trophozoites use to trigger an inflammatory response in the pathogenesis of intestinal amebiasis.

  15. Ratio of pro-resolving and pro-inflammatory lipid mediator precursors as potential markers for aggressive periodontitis.

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    Hager R Zein Elabdeen

    Full Text Available Aggressive periodontitis (AgP is a rapidly progressing type of periodontal disease in otherwise healthy individuals which causes destruction of the supporting tissues of the teeth. The disease is initiated by pathogenic bacteria in the dental biofilm, and the severity of inflammation and attachment loss varies with the host response. Recently, there has been an increased interest in determining the role of lipid mediators in inflammatory events and the concept of pro-inflammatory and pro-resolution lipid mediators has been brought into focus also in periodontal disease. The present study aimed to determine the profile of omega-3 or n3- as well as omega-6 or n6- polyunsaturated fatty acids (PUFAs and PUFA-metabolites of linoleic acid, arachidonic acid (AA, eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA in gingival crevicular fluid (GCF, saliva and serum in AgP patients and healthy controls. In total, 60 selected n3- and n6-PUFAs and various PUFA metabolites were measured using high performance liquid chromatography-tandem electrospray ionisation mass spectrometry (HPLC-ESI-MS-MS. Of these, 51 could be quantified in this study. The concentrations of the majority were low in saliva samples compared with serum and GCF, but were mainly higher in AgP patients compared with healthy controls in all three kinds of sample. Ratios of n3- to n6-PUFAs (DHA + EPA/AA were significantly lower in the GCF of AgP patients than in the healthy controls. Furthermore, various ratios of the direct precursors of the pro-resolution lipid mediators (precursors of resolvins and protectins were calculated against the precursors of mainly pro-inflammatory lipid mediators. These ratios were mainly lower in GCF and saliva of AgP patients, compared with healthy controls, but only reached significance in GCF (P<0.05. To conclude, the ratios of precursors of pro-resolution/pro-inflammatory lipid mediators seem to be more relevant for describing the disease status of Ag

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

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    Antonia Diaz-Ganete

    2015-01-01

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

  17. Endocannabinoids in cerebrovascular regulation.

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    Benyó, Zoltán; Ruisanchez, Éva; Leszl-Ishiguro, Miriam; Sándor, Péter; Pacher, Pál

    2016-04-01

    The cerebral blood flow is tightly regulated by myogenic, endothelial, metabolic, and neural mechanisms under physiological conditions, and a large body of recent evidence indicates that inflammatory pathways have a major influence on the cerebral blood perfusion in certain central nervous system disorders, like hemorrhagic and ischemic stroke, traumatic brain injury, and vascular dementia. All major cell types involved in cerebrovascular control pathways (i.e., smooth muscle, endothelium, neurons, astrocytes, pericytes, microglia, and leukocytes) are capable of synthesizing endocannabinoids and/or express some or several of their target proteins [i.e., the cannabinoid 1 and 2 (CB1 and CB2) receptors and the transient receptor potential vanilloid type 1 ion channel]. Therefore, the endocannabinoid system may importantly modulate the regulation of cerebral circulation under physiological and pathophysiological conditions in a very complex manner. Experimental data accumulated since the late 1990s indicate that the direct effect of cannabinoids on cerebral vessels is vasodilation mediated, at least in part, by CB1 receptors. Cannabinoid-induced cerebrovascular relaxation involves both a direct inhibition of smooth muscle contractility and a release of vasodilator mediator(s) from the endothelium. However, under stress conditions (e.g., in conscious restrained animals or during hypoxia and hypercapnia), cannabinoid receptor activation was shown to induce a reduction of the cerebral blood flow, probably via inhibition of the electrical and/or metabolic activity of neurons. Finally, in certain cerebrovascular pathologies (e.g., subarachnoid hemorrhage, as well as traumatic and ischemic brain injury), activation of CB2 (and probably yet unidentified non-CB1/non-CB2) receptors appear to improve the blood perfusion of the brain via attenuating vascular inflammation.

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

    Science.gov (United States)

    Shivkar, Yatin M; Kumar, Vijay L

    2003-01-01

    INTRODUCTiON: Calotropis procera is known to produce contact dermatitis and the latex of this plant produces intense inflammation when injected locally. However, the precise mode of its pro-inflammatory effect is not known. In present study we have pharmacologically characterized the inflammation induced by latex of C. procera in a rat paw edema model and determined the role of histamine in latex-induced inflammation. METHODS: Inflammation was induced in the hind paw of rats by injecting different doses of dried latex (DL) of C. procera. The inhibitory effect of phenylbutazone, dexamethasone, celecoxib, cyproheptadine, chlorpheniramine and compound 48/80 on edema volume was evaluated and compared with that against carrageenan. The histamine content of DL was measured fluorometrically. RESULTS: DL produced dose-dependent inflammation of the rat paw. Cyproheptadine and chlorpheniramine effectively inhibited DL-induced inflammation (90%; p phenylbutazone, dexamethasone and celecoxib were more effective against carrageenan-induced inflammation. Depletion of mast cell histamine by compound 48/80 produced a significant decrease in DL-induced inflammation as compared with carrageenan (500% versus 25%). DL was also found to contain about 6 microg/g of histamine. CONCLUSIONS: Thus, our study shows that the biogenic amines play a significant role in C. procera latex-induced inflammation and antihistaminic drugs could be effectively used to inhibit inflammatory response elicited by exposure to latex. PMID:14760937

  19. The signal transduction mediated by erythropoietin and proinflammatory cytokines in the JAK/STAT pathway in the children with cerebral palsy.

    Science.gov (United States)

    Tao, Weiyuan; Wen, Fang; Zhang, Hong; Liu, Guheng

    2009-03-01

    It is well established that erythropoietin (EPO) is a pleiotropic cytokine, which has a brain-derived neuroprotective effect in the central nervous system (CNS). Immune abnormality has a close relationship with cerebral palsy (CP), and may be even involved in the development of CP. There is evidence that the amount of EPO in CP children is lower than in normal children, but the levels of proinflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha, are higher in the CP children. The signal transduction mediated by EPO that has a neuroprotective effect and mediated by proinflammatory cytokines that lead to brain damage shares the common JAK/STAT pathway. Under acute stress, the JAK/STAT pathway is occupied by massive proinflammatory cytokines, and the negative feedback inhibition factors like suppressor of cytokine signaling (SOCS) proteins are simultaneously activated, which exist in reciprocal inhibition to EPO in the JAK/STAT pathway. As a result, the signal transduction mediated by EPO is prevented or reduced, and the neuroprotective effect of EPO is eventually weakened. In this review, a novel approach to CP treatment through neurodevelopmental treatment (NDT) is put forward by analysis of the interrelationship of signal transduction mediated by EPO and proinflammatory cytokines in the JAK/STAT pathway and their roles in the development of CP, and some reasonable ideas for CP treatment are provided.

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

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    Yu Xiao

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

  1. Cerebrovascular arteriopathy (arteriosclerosis) and ischemic childhood stroke.

    Science.gov (United States)

    Daniels, S R; Bates, S; Lukin, R R; Benton, C; Third, J; Glueck, C J

    1982-01-01

    The aim of this report is to describe the intracranial cerebrovascular abnormalities and clinical status of 8 children who had familial lipoprotein disorders and evidence of thromboembolic cerebrovascular disease. Six of the 8 children had low levels of plasma high density lipoprotein cholesterol, two had high triglyceride levels, and all came from kindreds characterized by familial lipoprotein abnormalities and premature cardio- and/or cerebrovascular atherosclerosis. Vascular occlusion, irregularities of the arterial lumen, beading, tortuosity, and evidence of collateralization were consistently noted. We speculate that cerebrovascular arteriosclerosis in pediatric ischemic stroke victims who have familial lipoprotein abnormalities may be related to lipoprotein-mediated endothelial damage and thrombosis formation, or to the failure to restore endothelial cells' integrity following damage. The apparent association of lipoproteins and strokes in children and their families merits further exploration, particularly when assessing cerebral angiograms in pediatric ischemic stroke victims. In children with unexplained ischemic cerebrovascular accidents, the diagnostic possibility of occlusive arteriosclerosis with thrombosis must be entertained.

  2. Selection for pro-inflammatory mediators produces chickens more resistant to Clostridium perfringens-induced necrotic enteritis.

    Science.gov (United States)

    Swaggerty, C L; McReynolds, J L; Byrd, J A; Pevzner, I Y; Duke, S E; Genovese, K J; He, H; Kogut, M H

    2016-02-01

    We developed a novel selection method based on an inherently high and low phenotype of pro-inflammatory mediators and produced "high" and "low" line chickens. We have shown high line birds are more resistant to Salmonella enterica serovar Enteritidis and Eimeria tenella compared to the low line. Clostridium perfringens is the fourth leading cause of bacterial-induced foodborne illness, and is also an economically important poultry pathogen and known etiologic agent of necrotic enteritis (NE). The objective of this study was to determine if high line birds were also more resistant to NE than low line birds using an established model. Birds were reared in floor pens and challenges were conducted twice (high line = 25/trial, 50 birds total; low line = 26/trial, 52 birds total). Day-old chicks were provided a 55% wheat-corn-based un-medicated starter diet. A bursal disease vaccine was administered at 10× the recommended dose via the ocular route at 14-d-of-age. Birds were challenged daily for 3 d beginning at 16-d-of-age by oral gavage (3 mL) with 10(7) colony forming units (cfu) of C. perfringens/mL then necropsied at 21-d-of-age. All birds had sections of the intestine examined and scored for lesions while the first 10 necropsied also had gut content collected for C. perfringens enumeration. Chickens from the high line were more resistant to C. perfringens-induced NE pathology compared to the low line, as indicated by reduced lesion scores. Ninety percent of the high line birds had lesions of zero or one compared to 67% of the low line birds. Wilcoxon rank sum test showed significantly higher lesion scores in the low line birds compared to the high line (P < 0.0001). There were no differences in the C. perfringens recovered (P = 0.83). These data provide additional validation and support selection based on elevated levels of pro-inflammatory mediators produces chickens with increased resistance against foodborne and poultry pathogens.

  3. Biodiesel exhaust-induced cytotoxicity and proinflammatory mediator production in human airway epithelial cells.

    Science.gov (United States)

    Mullins, Benjamin J; Kicic, Anthony; Ling, Kak-Ming; Mead-Hunter, Ryan; Larcombe, Alexander N

    2016-01-01

    Increasing use of biodiesel has prompted research into the potential health effects of biodiesel exhaust exposure. Few studies directly compare the health consequences of mineral diesel, biodiesel, or blend exhaust exposures. Here, we exposed human epithelial cell cultures to diluted exhaust generated by the combustion of Australian ultralow-sulfur-diesel (ULSD), unprocessed canola oil, 100% canola biodiesel (B100), and a blend of 20% canola biodiesel mixed with 80% ULSD. The physicochemical characteristics of the exhaust were assessed and we compared cellular viability, apoptosis, and levels of interleukin (IL)-6, IL-8, and Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) in exposed cultured cells. Different fuel types produced significantly different amounts of exhaust gases and different particle characteristics. All exposures resulted in significant apoptosis and loss of viability when compared with control, with an increasing proportion of biodiesel being correlated with a decrease in viability. In most cases, exposure to exhaust resulted in an increase in mediator production, with the greatest increases most often in response to B100. Exposure to pure canola oil (PCO) exhaust did not increase mediator production, but resulted in a significant decrease in IL-8 and RANTES in some cases. Our results show that canola biodiesel exhaust exposure elicits inflammation and reduces viability of human epithelial cell cultures in vitro when compared with ULSD exhaust exposure. This may be related to an increase in particle surface area and number in B100 exhaust when compared with ULSD exhaust. Exposure to PCO exhaust elicited the greatest loss of cellular viability, but virtually no inflammatory response, likely due to an overall increase in average particle size.

  4. Acidosis downregulates platelet haemostatic functions and promotes neutrophil proinflammatory responses mediated by platelets.

    Science.gov (United States)

    Etulain, Julia; Negrotto, Soledad; Carestia, Agostina; Pozner, Roberto Gabriel; Romaniuk, María Albertina; D'Atri, Lina Paola; Klement, Giannoula Lakka; Schattner, Mirta

    2012-01-01

    Acidosis is one of the hallmarks of tissue injury such as trauma, infection, inflammation, and tumour growth. Although platelets participate in the pathophysiology of all these processes, the impact of acidosis on platelet biology has not been studied outside of the quality control of laboratory aggregation assays or platelet transfusion optimization. Herein, we evaluate the effect of physiologically relevant changes in extracellular acidosis on the biological function of platelets, placing particular emphasis on haemostatic and secretory functions. Platelet haemostatic responses such as adhesion, spreading, activation of αIIbβ3 integrin, ATP release, aggregation, thromboxane B2 generation, clot retraction and procoagulant activity including phosphatidilserine exposure and microparticle formation, showed a statistically significant inhibition of thrombin-induced changes at pH of 7.0 and 6.5 compared to the physiological pH (7.4). The release of alpha granule content was differentially regulated by acidosis. At low pH, thrombin or collagen-induced secretion of vascular endothelial growth factor and endostatin were dramatically reduced. The release of von Willebrand factor and stromal derived factor-1α followed a similar, albeit less dramatic pattern. In contrast, the induction of CD40L was not changed by low pH, and P-selectin exposure was significantly increased. While the generation of mixed platelet-leukocyte aggregates and the increased chemotaxis of neutrophils mediated by platelets were further augmented under acidic conditions in a P-selectin dependent manner, the increased neutrophil survival was independent of P-selectin expression. In conclusion, our results indicate that extracellular acidosis downregulates most of the haemostatic platelet functions, and promotes those involved in amplifying the neutrophil-mediated inflammatory response.

  5. Proinflammatory adipokine leptin mediates disinfection byproduct bromodichloromethane-induced early steatohepatitic injury in obesity

    Energy Technology Data Exchange (ETDEWEB)

    Das, Suvarthi [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States); Kumar, Ashutosh [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, Research Triangle Park, NC 27709 (United States); Seth, Ratanesh Kumar [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States); Tokar, Erik J. [Inorganic Toxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Kadiiska, Maria B. [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, Research Triangle Park, NC 27709 (United States); Waalkes, Michael P. [Inorganic Toxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Mason, Ronald P. [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, Research Triangle Park, NC 27709 (United States); Chatterjee, Saurabh, E-mail: schatt@mailbox.sc.edu [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States)

    2013-06-15

    Today's developed world faces a major public health challenge in the rise in the obese population and the increased incidence in fatty liver disease. There is a strong association among diet induced obesity, fatty liver disease and development of nonalcoholic steatohepatitis but the environmental link to disease progression remains unclear. Here we demonstrate that in obesity, early steatohepatitic lesions induced by the water disinfection byproduct bromodichloromethane are mediated by increased oxidative stress and leptin which act in synchrony to potentiate disease progression. Low acute exposure to bromodichloromethane (BDCM), in diet-induced obesity produced oxidative stress as shown by increased lipid peroxidation, protein free radical and nitrotyrosine formation and elevated leptin levels. Exposed obese mice showed histopathological signs of early steatohepatitic injury and necrosis. Spontaneous knockout mice for leptin or systemic leptin receptor knockout mice had significantly decreased oxidative stress and TNF-α levels. Co-incubation of leptin and BDCM caused Kupffer cell activation as shown by increased MCP-1 release and NADPH oxidase membrane assembly, a phenomenon that was decreased in Kupffer cells isolated from leptin receptor knockout mice. In obese mice that were BDCM-exposed, livers showed a significant increase in Kupffer cell activation marker CD68 and, increased necrosis as assessed by levels of isocitrate dehydrogenase, events that were decreased in the absence of leptin or its receptor. In conclusion, our results show that exposure to the disinfection byproduct BDCM in diet-induced obesity augments steatohepatitic injury by potentiating the effects of leptin on oxidative stress, Kupffer cell activation and cell death in the liver. - Highlights: ► BDCM acute exposure sensitizes liver to increased free radical stress in obesity. ► BDCM-induced higher leptin contributes to early steatohepatitic lesions. ► Increased leptin mediates

  6. Andrographolide inhibits intracellular Chlamydia trachomatis multiplication and reduces secretion of proinflammatory mediators produced by human epithelial cells.

    Science.gov (United States)

    Hua, Ziyu; Frohlich, Kyla M; Zhang, Yan; Feng, Xiaogeng; Zhang, Jiaxing; Shen, Li

    2015-02-01

    Chlamydia trachomatis is the most common sexually transmitted bacterial disease worldwide. Untreated C. trachomatis infections may cause inflammation and ultimately damage tissues. Here, we evaluated the ability of Andrographolide (Andro), a natural diterpenoid lactone component of Andrographis paniculata, to inhibit C. trachomatis infection in cultured human cervical epithelial cells. We found that Andro exposure inhibited C. trachomatis growth in a dose- and time-dependent manner. The greatest inhibitory effect was observed when exponentially growing C. trachomatis was exposed to Andro. Electron micrographs demonstrated the accumulation of unusual, structurally deficient chlamydial organisms, correlated with a decrease in levels of OmcB expressed at the late stage of infection. Additionally, Andro significantly reduced the secretion of interleukin6, CXCL8 and interferon-γ-induced protein10 produced by host cells infected with C. trachomatis. These results indicate the efficacy of Andro to perturb C. trachomatis transition from the metabolically active reticulate body to the infectious elementary body and concurrently reduce the production of a proinflammatory mediator by epithelial cells in vitro. Further dissection of Andro's anti-Chlamydia action may provide identification of novel therapeutic targets.

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

    Directory of Open Access Journals (Sweden)

    Tannheimer Stacey L

    2012-03-01

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

  8. Unusual Water-mediated Antigenic Recognition of the Proinflammatory Cytokine Interleukin-18

    Energy Technology Data Exchange (ETDEWEB)

    Argiriadi, Maria A.; Xiang, Tao; Wu, Chengbin; Ghayur, Tariq; Borhani, David W.; (Abbott)

    2009-10-21

    binding may in some cases be water-mediated.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    against bacterial lipopolysaccharide (LPS) stimulation. LPS-mediated pro-inflammatory cytokine productions on mBMMCs obtained from Toll-like receptor4 (TLR4)-deficient mice, TLR2-defficient mice, and their wildtype, were specifically attenuated by the addition of either mouse MBL-A or ficolin-A in a dose...... cytokine production by LPS-mediated TLR4 in mBMMCs appears to be down-regulated, indicating that mouse MBL and ficolin may have an inhibitory function toward mouse TLR4-mediated excessive inflammation on the mast cells....

  10. Expression of pro-inflammatory mediators is inhibited by an avocado/soybean unsaponifiables and epigallocatechin gallate combination

    Science.gov (United States)

    2014-01-01

    Background Osteoarthritis (OA) is characterized by inflammation, joint immobility, and pain. Non-pharmacologic agents modulating pro-inflammatory mediator expression offer considerable promise as safe and effective treatments for OA. We previously determined the anti-inflammatory effect of an avocado/soybean unsaponifiables (ASU) and epigallocatechin gallate (EGCG) combination on prostaglandin E2 (PGE2) production and nuclear factor-kappa B (NF-κB) translocation. The aim of this study was to evaluate the effects of ASU + EGCG on pro-inflammatory gene expression. Findings Articular chondrocytes from carpal joints of mature horses were pre-incubated for 24 hours with control media alone or ASU (8.3 μg/mL) + EGCG (40 ng/mL), followed by one hour activation with interleukin-1 beta (IL-1β, 10 ng/mL) and tumor necrosis factor-alpha (TNF-α, 1 ng/mL). Total cellular RNA was isolated and real-time PCR performed to measure IL-1β, TNF-α, interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), and interleukin-8 (IL-8) gene expression. Intracellular localization of NF-κB was analyzed by immunohistochemistry and Western blot. Pre-treatment with ASU + EGCG significantly (P < 0.001) decreased gene expression of IL-1β, TNF-α, IL-6, COX-2, and IL-8 in cytokine-activated chondrocytes. Western blot and immunostaining confirmed NF-κB translocation inhibition. Conclusions We demonstrate that ASU + EGCG inhibits cytokine-induced gene expression of IL-1β, TNF-α, IL-6, COX-2, and IL-8 through modulation of NF-κB. Our results indicate that the activity of ASU + EGCG affects a wide array of inflammatory molecules in addition to decreasing PGE2 synthesis in activated chondrocytes. The responsiveness of chondrocytes to this combination supports its potential utility for the inhibition of joint inflammation. PMID:24678847

  11. Docosahexaenoic acid decreases pro-inflammatory mediators in an in vitro murine adipocyte macrophage co-culture model.

    Directory of Open Access Journals (Sweden)

    Anna A De Boer

    Full Text Available Paracrine interactions between adipocytes and macrophages contribute to chronic inflammation in obese adipose tissue. Dietary strategies to mitigate such inflammation include long-chain polyunsaturated fatty acids, docosahexaenoic (DHA and eicosapentaenoic (EPA acids, which act through PPARγ-dependent and independent pathways. We utilized an in vitro co-culture model designed to mimic the ratio of macrophages:adipocytes in obese adipose tissue, whereby murine 3T3-L1 adipocytes were cultured with RAW 264.7 macrophages in direct contact, or separated by a trans-well membrane (contact-independent mechanism, with 125 µM of albumin-complexed DHA, EPA, palmitic acid (PA, or albumin alone (control. Thus, we studied the effect of physical cell contact versus the presence of soluble factors, with or without a PPARγ antagonist (T0070907 in order to elucidate putative mechanisms. After 12 hr, DHA was the most anti-inflammatory, decreasing MCP1 and IL-6 secretion in the contact system (-57%, -63%, respectively, p ≤ 0.05 with similar effects in the trans-well system. The trans-well system allowed for isolation of cell types for inflammatory mediator analysis. DHA decreased mRNA expression (p<0.05 of Mcp1 (-7.1 fold and increased expression of the negative regulator, Mcp1-IP (+1.5 fold. In macrophages, DHA decreased mRNA expression of pro-inflammatory M1 polarization markers (p ≤ 0.05, Nos2 (iNOS; -7 fold, Tnfα (-4.2 fold and Nfκb (-2.3 fold, while increasing anti-inflammatory Tgfβ1 (+1.7 fold. Interestingly, the PPARγ antagonist co-administered with DHA or EPA in co-culture reduced (p ≤ 0.05 adiponectin cellular protein, without modulating other cytokines (protein or mRNA. Overall, our findings suggest that DHA may lessen the degree of MCP1 and IL-6 secreted from adipocytes, and may reduce the degree of M1 polarization of macrophages recruited to adipose tissue, thereby decreasing the intensity of pro-inflammatory cross-talk between adipocytes

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

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2016-12-01

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

  13. Downregulation of pro-inflammatory mediators by a water extract of Schisandra chinensis (Turcz.) Baill fruit in lipopolysaccharide-stimulated RAW 264.7 macrophage cells.

    Science.gov (United States)

    Dilshara, Matharage Gayani; Jayasooriya, Rajapaksha Gedara Prasad Tharanga; Kang, Chang-Hee; Lee, Seungheon; Park, Sang Rul; Jeong, Jin-Woo; Choi, Yung Hyun; Seo, Yong Taek; Jang, Young Pyo; Kim, Gi-Young

    2013-09-01

    Schisandra chinensis has a long-standing history of medicinal use as a tonic, a sedative, an anti-tussive, and an anti-aging drug. Nevertheless, the antagonistic effects of S. chinensis against lipopolysaccharide (LPS)-stimulated responses have not yet been studied. In this study, we investigated whether water extract of S. chinensis fruit (WESC) has the ability to attenuate the expression of pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor-α (TNF-α) in LPS-stimulated RAW 264.7 macrophage cells. WESC inhibited the expression of LPS-induced pro-inflammatory mediators, namely, NO, PGE2, and TNF-α. Furthermore, gene expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α was inhibited both at mRNA and protein synthesis levels, without any cytotoxic effect. Moreover, WESC significantly suppressed LPS-induced DNA-binding activity of NF-κB by inhibiting degradation of IκBα. It was found that pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor, downregulates the expression of these pro-inflammatory genes to be closely regulated by NF-κB activity. Furthermore, we found that WESC retains dephosphorylation of Akt in response to LPS, and consequently suppressed the DNA-binding activity of NF-κB in RAW 264.7 macrophage cells. LY294002, a specific Akt inhibitor, attenuated LPS-induced pro-inflammatory gene expression via suppression of NF-κB activity. Taken together, our results indicate that WESC downregulates the expression of pro-inflammatory genes involved in the synthesis of NO, PGE2, and TNF-α in LPS-stimulated RAW 264.7 macrophage cells by suppressing Akt-dependent NF-κB activity.

  14. Pro-inflammatory cytokines derived from West Nile virus (WNV-infected SK-N-SH cells mediate neuroinflammatory markers and neuronal death

    Directory of Open Access Journals (Sweden)

    Nerurkar Vivek R

    2010-10-01

    Full Text Available Abstract Background WNV-associated encephalitis (WNVE is characterized by increased production of pro-inflammatory mediators, glial cells activation and eventual loss of neurons. WNV infection of neurons is rapidly progressive and destructive whereas infection of non-neuronal brain cells is limited. However, the role of neurons and pathological consequences of pro-inflammatory cytokines released as a result of WNV infection is unclear. Therefore, the objective of this study was to examine the role of key cytokines secreted by WNV-infected neurons in mediating neuroinflammatory markers and neuronal death. Methods A transformed human neuroblastoma cell line, SK-N-SH, was infected with WNV at multiplicity of infection (MOI-1 and -5, and WNV replication kinetics and expression profile of key pro-inflammatory cytokines were analyzed by plaque assay, qRT-PCR, and ELISA. Cell death was measured in SK-N-SH cell line in the presence and absence of neutralizing antibodies against key pro-inflammatory cytokines using cell viability assay, TUNEL and flow cytometry. Further, naïve primary astrocytes were treated with UV-inactivated supernatant from mock- and WNV-infected SK-N-SH cell line and the activation of astrocytes was measured using flow cytometry and ELISA. Results WNV-infected SK-N-SH cells induced the expression of IL-1β, -6, -8, and TNF-α in a dose- and time-dependent manner, which coincided with increase in virus-induced cell death. Treatment of cells with anti-IL-1β or -TNF-α resulted in significant reduction of the neurotoxic effects of WNV. Furthermore treatment of naïve astrocytes with UV-inactivated supernatant from WNV-infected SK-N-SH cell line increased expression of glial fibrillary acidic protein and key inflammatory cytokines. Conclusion Our results for the first time suggest that neurons are one of the potential sources of pro-inflammatory cytokines in WNV-infected brain and these neuron-derived cytokines contribute to WNV

  15. Systemic vascular function, measured with forearm flow mediated dilatation, in acute and stable cerebrovascular disease: a case-control study

    Directory of Open Access Journals (Sweden)

    Blacker David

    2010-10-01

    Full Text Available Abstract Background Acute ischaemic stroke is associated with alteration in systemic markers of vascular function. We measured forearm vascular function (using forearm flow mediated dilatation to clarify whether recent acute ischaemic stroke/TIA is associated with impaired systemic vascular function. Methods Prospective case control study enrolling 17 patients with recent acute ischaemic stroke/TIA and 17 sex matched controls with stroke more than two years previously. Forearm vascular function was measured using flow medicated dilatation (FMD. Results Flow mediated dilatation was 6.0 ± 1.1% in acute stroke/TIA patients and 4.7 ± 1.0% among control subjects (p = 0.18. The mean paired difference in FMD between subjects with recent acute stroke and controls was 1.25% (95% CI -0.65, 3.14; p = 0.18. Endothelium independent dilatation was measured in six pairs of participants and was similar in acute stroke/TIA patients (22.6 ± 4.3% and control subjects (19.1 ± 2.6%; p = 0.43. Conclusions Despite the small size of this study, these data indicate that recent acute stroke is not necessarily associated with a clinically important reduction in FMD.

  16. The UII/UT system mediates upregulation of proinflammatory cytokines through p38 MAPK and NF-κB pathways in LPS-stimulated Kupffer cells.

    Science.gov (United States)

    Liu, Liang Ming; Liang, Dong Yu; Ye, Chang Gen; Tu, Wen Juan; Zhu, Tong

    2015-01-01

    The urotensin II (UII)/UII receptor (UT) system is closely related to immune inflammation. In acute liver failure (ALF), the UII/UT system can promote the production and release of proinflammatory cytokines, inducing an inflammatory injury response in liver tissue. However, the mechanism by which the hepatic UII/UT system promotes proinflammatory cytokine production and release is not clear. To solve this problem, we used primary Kupffer cells (KCs) as the model system in the current study. The results showed that after lipopolysaccharide (LPS) stimulation, KCs showed significantly increased expression and release of UII/UT and proinflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Pretreatment with urantide, which is a UT receptor antagonist, significantly inhibited the LPS-stimulated expression and release of UII/UT, TNF-α, and IL-1β by KCs. In addition, LPS stimulation induced nuclear p38 mitogen-activated protein kinase (MAPK) protein phosphorylation and expression of the nuclear nuclear factor κB (NF-κB) p65 subunit in KCs and enhanced the binding activity of NF-κB to DNA molecules, whereas urantide pretreatment significantly inhibited the LPS-stimulated nuclear expression and activity of these molecules in KCs. Therefore, our conclusion is that the UII/UT system mediates LPS-stimulated production and release of proinflammatory cytokine by KCs, and this mediating effect at least partially relies on the inflammatory signaling pathway molecules p38 MAPK and NF-κB.

  17. The relationship between plasminogen activation inhibitor-1 and proinflammatory and counterinflammatory mediators in children with meningococcal septic shock

    NARCIS (Netherlands)

    Kornelisse, R.F.; Hazalzet, J.A.; Savelkoul, H.F.J.; Hop, W.C.J.; Suur, M.H.; Borsboom, A.N.J.; Risseeuw-Appel, I.M.; Voort, van der E.; Neijens, H.J.; Groot, de R.

    1996-01-01

    Proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL]-6 and -8), counterinflammatory compounds (IL-10 and soluble TNF receptors p55 and p75 [sTNFR-55 and -75]), and hemostatic parameters were determined in 38 patients with meningococcal septic shock. Eleven patients (29%)

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

    Directory of Open Access Journals (Sweden)

    Steven R. H. Beach

    2015-05-01

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

  19. Anti-Inflammatory Effect of Apigenin on LPS-Induced Pro-Inflammatory Mediators and AP-1 Factors in Human Lung Epithelial Cells.

    Science.gov (United States)

    Patil, Rajeshwari H; Babu, R L; Naveen Kumar, M; Kiran Kumar, K M; Hegde, Shubha M; Nagesh, Rashmi; Ramesh, Govindarajan T; Sharma, S Chidananda

    2016-02-01

    Apigenin is one of the plant flavonoids present in fruits and vegetables, acting as an important nutraceutical component. It is recognized as a potential antioxidant, antimicrobial, and anti-inflammatory molecule. In the present study, the mechanism of anti-inflammatory action of apigenin on lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and activator protein-1 (AP-1) factors in human lung A549 cells was investigated. The anti-inflammatory activity of apigenin on LPS-induced inflammation was determined by analyzing the expression of pro-inflammatory cytokines, nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and different AP-1 factors. Apigenin significantly inhibited the LPS-induced expression of iNOS, COX-2, expression of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, and TNF-α), and AP-1 proteins (c-Jun, c-Fos, and JunB) including nitric oxide production. Study confirms the anti-inflammatory effect of apigenin by inhibiting the expression of inflammatory mediators and AP-1 factors involved in the inflammation and its importance in the treatment of lung inflammatory diseases.

  20. Propofol protects against focal cerebral ischemia via inhibition of microglia-mediated proinflammatory cytokines in a rat model of experimental stroke.

    Directory of Open Access Journals (Sweden)

    Rong Zhou

    Full Text Available Ischemic stroke induces microglial activation and release of proinflammatory cytokines, contributing to the expansion of brain injury and poor clinical outcome. Propofol has been shown to ameliorate neuronal injury in a number of experimental studies, but the precise mechanisms involved in its neuroprotective effects remain unclear. We tested the hypothesis that propofol confers neuroprotection against focal ischemia by inhibiting microglia-mediated inflammatory response in a rat model of ischemic stroke. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO for 2 h followed by 24 h of reperfusion. Propofol (50 mg/kg/h or vehicle was infused intravenously at the onset of reperfusion for 30 minutes. In vehicle-treated rats, MCAO resulted in significant cerebral infarction, higher neurological deficit scores and decreased time on the rotarod compared with sham-operated rats. Propofol treatment reduced infarct volume and improved the neurological functions. In addition, molecular studies demonstrated that mRNA expression of microglial marker Cd68 and Emr1 was significantly increased, and mRNA and protein expressions of proinflammatory cytokines tumor necrosis factor-α, interleukin-1β and interleukin-6 were augmented in the peri-infarct cortical regions of vehicle-treated rats 24 h after MCAO. Immunohistochemical study revealed that number of total microglia and proportion of activated microglia in the peri-infarct cortical regions were markedly elevated. All of these findings were ameliorated in propofol-treated rats. Furthermore, vehicle-treated rats had higher plasma levels of interleukin-6 and C-reactive protein 24 h after MCAO, which were decreased after treatment with propofol. These results suggest that propofol protects against focal cerebral ischemia via inhibition of microglia-mediated proinflammatory cytokines. Propofol may be a promising therapeutic agent for the treatment of ischemic stroke and other

  1. Impact of D-pinitol on the attenuation of proinflammatory cytokines, hyperglycemia-mediated oxidative stress and protection of kidney tissue ultrastructure in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Sivakumar, Selvaraj; Palsamy, Periyasamy; Subramanian, Sorimuthu Pillai

    2010-10-06

    Oxidative stress plays a crucial role in the progression and development of diabetes and its complications due to chronic hyperglycemia. The present study was aimed to investigate the kidney tissue protective nature of d-pinitol, a cyclitol present in soybean, by assessing the key markers of hyperglycemia-mediated oxidative stress, proinflammatory cytokines and ultrastructural alterations in streptozotocin-induced diabetic rats. Oral administration of d-pinitol (50mg/kg body weight/day) for 30 days to diabetic group of rats showed a significant elevation in the level of total protein and significant decline in the levels of blood urea, serum uric acid, creatinine and advanced glycation endproducts (AGEs) and kidney proinflammatory cytokines such as TNF-alpha, IL-1beta, IL-6, NF-kappaB p65 subunit and nitrite. Further, d-pinitol administration elicited a significant attenuation in the activities of kidney enzymatic antioxidants such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) and the levels of kidney non-enzymatic antioxidants such as vitamin E, vitamin C and reduced glutathione (GSH) in the diabetic group of rats, with a concomitant decline in the levels of kidney lipid peroxides, hydroperoxides and protein carbonyls. The histological and ultrastructural observations on the kidney tissues also confirmed the renoprotective nature of d-pinitol. Thus the present study demonstrated the renoprotective nature of d-pinitol by attenuating the hyperglycemia-mediated proinflammatory cytokines and antioxidant competence in kidney tissues of streptozotocin-induced diabetic rats.

  2. Depression in cerebrovascular diseases

    OpenAIRE

    Voskresenskaya, Tatyana

    2009-01-01

    The paper discusses the topical problem of depression in cerebrovascular diseases. It shows its possible causes, mechanisms of occurrence, clinical picture and negative impact on the course of cerebrovascular disease and recovery of neurological functions. There is a bilateral association between stroke and depression: on the one hand, stroke is a risk factor for the development of depression and, on the other, depression is a both direct and indirect risk factor for the development of stroke...

  3. Extract of buckwheat sprouts scavenges oxidation and inhibits pro-inflammatory mediators in lipopolysaccharide-stimulated macrophages (RAW264.7)

    Institute of Scientific and Technical Information of China (English)

    Rajendra Karki; Cheol-Ho Park; Dong-Wook Kim

    2013-01-01

    OBJECTIVE:Buckwheat has been considered as a potential source of nutraceutical components on the world market of probiotic foodstuffs.The purpose of this study was to evaluate the effects of tartary buckwheat (Fagopyrum tataricum) sprouts on oxidation and pro-inflammatory mediators.METHODS:The anti-oxidant effects of buckwheat extract (BWE) and rutin were evaluated by using 1,1-diphenyl-2-picrylhydrazyl (DPPH)-and nitric oxide (NO)-scavenging activities,serum peroxidation and chelating assays.Lipopolysaccharide (LPS)-stimulated RAW264.7 cells were used to evaluate anti-inflammatory activities of buckwheat and rutin.NO production in LPS-stimulated RAW264.7 cells was determined by using Griess reagent.The expressions of inducible nitric oxide synthase (iNOS),cyclooxygenase-2 (COX-2),nuclear factor-kappa B (NF-κB) p65 subunit in cytosolic and nuclear portions were determined by Western blot analysis.Also,the production of inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was determined by enzyme-linked immunosorbent assay.RESULTS:Inhibitory concentration 50 values for DPPH-and NO-scavenging activities of BWE were 24.97 and 72.54 μg/mL respectively.BWE inhibited serum oxidation and possessed chelating activity.Furthermore,BWE inhibited IL-6 and TNF-α production in LPS-stimulated RAW264.7 cells.Also,BWE inhibited iNOS and COX-2 expression and NF-κB p65 translocation.CONCLUSION:Buckwheat sprouts possessed strong antioxidant activity and inhibited production of pro-inflammatory mediators in the applied model systems.Thus,buckwheat can be suggested to be beneficial in inflammatory diseases by inhibiting the free radicals and inflammatory mediators.

  4. Genkwanin inhibits proinflammatory mediators mainly through the regulation of miR-101/MKP-1/MAPK pathway in LPS-activated macrophages.

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    Yuan Gao

    Full Text Available Genkwanin is one of the major non-glycosylated flavonoids in many herbs with anti-inflammatory activities. Although its anti-inflammatory activity in vivo has been reported, the potential molecular mechanisms remain obscure. In this study, by pharmacological and genetic approaches, we explore the anti-inflammatory effects of genkwanin in LPS-activated RAW264.7 macrophages. Genkwanin potently decreases the proinflammatory mediators, such as iNOS, TNF-α, IL-1β and IL-6, at the transcriptional and translational levels without cytotoxicity, indicating the excellent anti-inflammatory potency of genkwanin in vitro. Mechanism study shows that genkwanin significantly suppresses the p38- and JNK-mediated AP-1 signaling pathway and increases the mitogen-activated protein kinase (MAPK phosphatase 1 (MKP-1 expression at the posttranscriptional level. We also confirmed that microRNA-101 (miR-101 is a negative regulator of MKP-1 expression. Moreover, regardless of miR-101-deficient cells or miR-101-abundant cells, the suppression effects of genkwanin on supernatant proinflammatory mediators' levels are far less than that in respective negative control cells, suggesting that genkwanin exerts anti-inflammatory effect mainly through reducing miR-101 production. However, genkwanin can't affect the level of phospho-Akt (p-Akt, indicating that the phosphorylation of Akt may be not responsible for the effect of genkwanin on miR-101 production. We conclude that genkwanin exerts its anti-inflammatory effect mainly through the regulation of the miR-101/MKP-1/MAPK pathway.

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

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    Johan Øvrevik

    2015-07-01

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

  6. Gelam Honey Inhibits the Production of Proinflammatory, Mediators NO, PGE2, TNF-α, and IL-6 in Carrageenan-Induced Acute Paw Edema in Rats

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    Saba Zuhair Hussein

    2012-01-01

    Full Text Available Natural honey is well known for its therapeutic value and has been used in traditional medicine of different cultures throughout the world. The aim of this study was to investigate the anti-inflammatory effect of Malaysian Gelam honey in inflammation-induced rats. Paw edema was induced by a subplantar injection of 1% carrageenan into the rat right hind paw. Rats were treated with the nonsteroidal anti-inflammatory drug (NSAID Indomethacin (10 mg/kg, p.o. or Gelam honey at different doses (1 or 2 g/kg, p.o.. The increase in footpad thickness was considered to be edema, which was measured using a dial caliper. Plasma and paw tissue were collected to analyze the production of inflammatory mediators, such as NO, PGE2, TNF-α, and IL-6, as well as iNOS and COX-2. The results showed that Gelam honey could reduce edema in a dose-dependent fashion in inflamed rat paws, decrease the production of NO, PGE2, TNF-α, and IL-6 in plasma, and suppress the expression of iNOS, COX-2, TNF-α, and IL-6 in paw tissue. Oral pretreatment of Gelam honey at 2 g/kg of body weight at two time points (1 and 7 days showed a significantly decreased production of proinflammatory cytokines, which was similar to the effect of the anti-inflammatory drug Indomethacin (NSAID, both in plasma and tissue. Thus, our results suggest that Gelam honey has anti-inflammatory effects by reducing the rat paw edema size and inhibiting the production of proinflammatory mediators. Gelam honey is potentially useful for treating inflammatory conditions.

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

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    Ying Jie Ma

    2013-07-01

    Full Text Available It is unknown how soluble pattern-recognition receptors inblood, such as mannose-binding lectin (MBL and ficolins,modulate mast cell-mediated inflammatory responses. Weinvestigate how mouse MBL-A or ficolin-A regulate mouse bonemarrow-derived mast cells (mBMMCs-derived inflammatoryresponse against bacterial lipopolysaccharide (LPS stimulation.LPS-mediated pro-inflammatory cytokine productions onmBMMCs obtained from Toll-like receptor4 (TLR4-deficientmice, TLR2-defficient mice, and their wildtype, were specificallyattenuated by the addition of either mouse MBL-A orficolin-A in a dose-dependent manner. However, the inhibitoryeffects by mouse MBL-A or ficolin-A were restored by theaddition of mannose or N-acetylglucosamine, respectively.These results suggest that mouse MBL-A and ficolin-A bind toLPS via its carbohydrate-recognition domain and fibrinogen-likedomain, respectively, whereby cytokine production by LPSmediatedTLR4 in mBMMCs appears to be down-regulated,indicating that mouse MBL and ficolin may have an inhibitoryfunction toward mouse TLR4-mediated excessive inflammationon the mast cells. [BMB Reports 2013; 46(7: 376-381

  8. Cigarette smoke-induced damage-associated molecular pattern release from necrotic neutrophils triggers proinflammatory mediator release.

    Science.gov (United States)

    Heijink, Irene H; Pouwels, Simon D; Leijendekker, Carin; de Bruin, Harold G; Zijlstra, G Jan; van der Vaart, Hester; ten Hacken, Nick H T; van Oosterhout, Antoon J M; Nawijn, Martijn C; van der Toorn, Marco

    2015-05-01

    Cigarette smoking, the major causative factor for the development of chronic obstructive pulmonary disease, is associated with neutrophilic airway inflammation. Cigarette smoke (CS) exposure can induce a switch from apoptotic to necrotic cell death in airway epithelium. Therefore, we hypothesized that CS promotes neutrophil necrosis with subsequent release of damage-associated molecular patterns (DAMPs), including high mobility group box 1 (HMGB1), alarming the innate immune system. We studied the effect of smoking two cigarettes on sputum neutrophils in healthy individuals and of 5-day CS or air exposure on neutrophil counts, myeloperoxidase, and HMGB1 levels in bronchoalveolar lavage fluid of BALB/c mice. In human peripheral blood neutrophils, mitochondrial membrane potential, apoptosis/necrosis markers, caspase activity, and DAMP release were studied after CS exposure. Finally, we assessed the effect of neutrophil-derived supernatants on the release of chemoattractant CXCL8 in normal human bronchial epithelial cells. Cigarette smoking caused a significant decrease in sputum neutrophil numbers after 3 hours. In mice, neutrophil counts were significantly increased 16 hours after repeated CS exposure but reduced 2 hours after an additional exposure. In vitro, CS induced necrotic neutrophil cell death, as indicated by mitochondrial dysfunction, inhibition of apoptosis, and DAMP release. Supernatants from CS-treated neutrophils significantly increased the release of CXCL8 in normal human bronchial epithelial cells. Together, these observations show, for the first time, that CS exposure induces neutrophil necrosis, leading to DAMP release, which may amplify CS-induced airway inflammation by promoting airway epithelial proinflammatory responses.

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

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    Halleskog Carina

    2012-05-01

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

  10. Thrombin inhibits HMGB1-mediated proinflammatory signaling responses when endothelial protein C receptor is occupied by its natural ligand

    Directory of Open Access Journals (Sweden)

    Jong-Sup Bae

    2013-11-01

    Full Text Available High mobility group box 1 (HMGB1 is involved in thepathogenesis of vascular diseases. Unlike activated protein C(APC, the activation of PAR-1 by thrombin is known to elicitproinflammatory responses. To determine whether the occupancyof EPCR by the Gla-domain of APC is responsible for thePAR-1-dependent antiinflammatory activity of the protease, wepretreated HUVECs with the PC zymogen and then activatedPAR-1 with thrombin. It was found that thrombin downregulatesthe HMGB1-mediated induction of both TNF-α andIL-6 and inhibits the activation of both p38 MAPK and NF-κB inHUVECs pretreated with PC. Furthermore, thrombin inhibitedHMGB1-mediated hyperpermeability and leukocyte adhesion/migration by inhibiting the expression of cell adhesion moleculesin HUVECs if EPCR was occupied. Collectively, theseresults suggest the concept that thrombin can initiate proinflammatoryresponses in vascular endothelial cells through theactivation of PAR-1 may not hold true for normal vesselsexpressing EPCR under in vivo conditions. [BMB Reports 2013;46(11: 544-549

  11. Essential Oils from Ugandan Medicinal Plants: In Vitro Cytotoxicity and Effects on IL-1β-Induced Proinflammatory Mediators by Human Gingival Fibroblasts.

    Science.gov (United States)

    Ocheng, Francis; Bwanga, Freddie; Almer Boström, Elisabeth; Joloba, Moses; Borg-Karlson, Anna-Karin; Yucel-Lindberg, Tülay; Obua, Celestino; Gustafsson, Anders

    2016-01-01

    The study investigated cytotoxicity of essential oils from four medicinal plants (Bidens pilosa, Ocimum gratissimum, Cymbopogon nardus, and Zanthoxylum chalybeum) on human gingival fibroblasts and their effects on proinflammatory mediators' secretion. Cytotoxicity of essential oils was investigated using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. Effects of essential oils at subcytotoxicity concentrations on interleukin- (IL-) 6, IL-8, and prostaglandin E2 (PGE2) secretions by gingival fibroblasts treated with IL-1β (300 pg/mL) were evaluated by ELISA and EIA. IC50 values of the essential oils ranged from 26 μg/mL to 50 μg/mL. Baseline and IL-1β-induced secretion of PGE2 was inhibited by treatment with essential oil from O. gratissimum. Essential oils from B. pilosa and C. nardus had synergistic effects with IL-1β on PGE2 seceretion. In conclusion, the study suggests that essential oil from O. gratissimum decreases gingival fibroblasts secretion of PGE2, while essential oils from B. pilosa and C. nardus increase PGE2 secretion. Essential oil from Z. chalybeum was the most cytotoxic, while oil from C. nardus was the least cytotoxic. Although the clinical significance of these findings remains to be determined, it may be suggested that essential oil from O. gratissimum, applied at subcytotoxicity concentrations, could reduce the participation of gingival fibroblasts in the gingival inflammation and tissue destruction associated with periodontitis.

  12. Veronicastrum axillare Alleviates Lipopolysaccharide-Induced Acute Lung Injury via Suppression of Proinflammatory Mediators and Downregulation of the NF-κB Signaling Pathway

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    Quanxin Ma

    2016-01-01

    Full Text Available Veronicastrum axillare is a traditional medical plant in China which is widely used in folk medicine due to its versatile biological activities, especially for its anti-inflammatory effects. However, the detailed mechanism underlying this action is not clear. Here, we studied the protective effects of V. axillare against acute lung injury (ALI, and we further explored the pharmacological mechanisms of this action. We found that pretreatment with V. axillare suppressed the release of proinflammatory cytokines in the serum of ALI mice. Histological analysis of lung tissue demonstrated that V. axillare inhibited LPS-induced lung injury, improved lung morphology, and reduced the activation of nuclear factor-κB (NF-κB in the lungs. Furthermore, the anti-inflammatory actions of V. axillare were investigated in vitro. We observed that V. axillare suppressed the mRNA expression of interleukin-1β (IL-1β, IL-6, monocyte chemotactic protein-1 (MCP-1, cyclooxygenase-2 (COX-2, and tumor necrosis factor-α (TNF-α in RAW264.7 cells challenged with LPS. Furthermore, pretreatment of V. axillare in vitro reduced the phosphorylation of p65 and IκB-α which is activated by LPS. In conclusion, our data firstly demonstrated that the anti-inflammatory effects of V. axillare against ALI were achieved through downregulation of the NF-κB signaling pathway, thereby reducing the production of inflammatory mediators.

  13. Wear particle-mediated expressions of pro-inflammatory cytokines,NF-κB and RANK were impacted by lanthanum chloride in RAW264.7 cells

    Institute of Scientific and Technical Information of China (English)

    DAI Min; JIANG Chuan; LIU Xiang; LI Zhe; CHENG Xigao; ZOU Yang; NIE Tao

    2013-01-01

    To explore the impact of different concentrations of lanthanum chloride (LaCl3) on critical components of wear particle-mediated signaling pathways in inflammation and osteoclastogenesis,RAW264.7 cells were naturally divided into eight groups and analyzed by CCK-8 assay,flow cytometry,ELISA,RT-PCR and western blot after treatments.The results showed that three concentrations of LaCl3 had no influence on viability of RAW264.7 cells and down-regulated receptor activator of nuclear factor κB (RANK) instead of macrophage colony-stimulating factor receptor (M-CSFR).Additionally,2.5 and 10 μmol/L LaCl3 could signifi-cantly inhibit gene and protein levels of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-lβ,i.e.,TNF-α and IL-1β) and NF-κB/p65,but 100 μrnol/L LaCl3 did not exert an obvious inflammation-inhibiting effect,and even induced inflammation.In conclusion,these findings demonstrated that LaC13 was able to suppress wear particle-induced inflammation and activation of NF-κB in a certain range of concentrations in vitro and mainly decrease the expression of RANK,but not M-CSFR,all of which were generally recognized to play a pivotal role in osteoclastogenesis.

  14. Apigenin modulates the expression levels of pro-inflammatory mediators to reduce the human insulin amyloid-induced oxidant damages in SK-N-MC cells.

    Science.gov (United States)

    Amini, R; Yazdanparast, R; Ghaffari, S H

    2015-06-01

    Amyloid depositions of proteins play crucial roles in a wide variety of degenerative disorders called amyloidosis. Although the exact mechanisms involved in amyloid-mediated cytotoxicity remain unknown, increased formation of reactive oxygen species (ROS) and nitrogen species and overproduction of pro-inflammatory cytokines are believed to play key roles in the process. In that regard, we investigated the effect of apigenin, a common dietary flavonoid with high antioxidant and anti-inflammatory properties on potential factors involved in cytotoxicity of human insulin amyloids. Pretreatment of SK-N-MC neuroblastoma cells with apigenin increased cell viability and reduced the apoptosis induced by insulin fibrils. In addition, apigenin attenuated insulin fibril-induced ROS production and lipid peroxidation. Our result also demonstrated that pretreatment of the fibril-affected cells with apigenin caused an increase in catalase activity and the intracellular glutathione content along with reduction in nitric oxide production and nuclear factor κB, tumor necrosis factor α, and interleukin 6 gene expression based on real-time polymerase chain reaction evaluation. In accordance with these results, apigenin could be a promising candidate in the design of natural-based drugs for treatment or prevention of amyloid-related disorders.

  15. Essential Oils from Ugandan Medicinal Plants: In Vitro Cytotoxicity and Effects on IL-1β-Induced Proinflammatory Mediators by Human Gingival Fibroblasts

    Science.gov (United States)

    Bwanga, Freddie; Joloba, Moses; Borg-Karlson, Anna-Karin; Yucel-Lindberg, Tülay; Obua, Celestino

    2016-01-01

    The study investigated cytotoxicity of essential oils from four medicinal plants (Bidens pilosa, Ocimum gratissimum, Cymbopogon nardus, and Zanthoxylum chalybeum) on human gingival fibroblasts and their effects on proinflammatory mediators' secretion. Cytotoxicity of essential oils was investigated using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. Effects of essential oils at subcytotoxicity concentrations on interleukin- (IL-) 6, IL-8, and prostaglandin E2 (PGE2) secretions by gingival fibroblasts treated with IL-1β (300 pg/mL) were evaluated by ELISA and EIA. IC50 values of the essential oils ranged from 26 μg/mL to 50 μg/mL. Baseline and IL-1β-induced secretion of PGE2 was inhibited by treatment with essential oil from O. gratissimum. Essential oils from B. pilosa and C. nardus had synergistic effects with IL-1β on PGE2 seceretion. In conclusion, the study suggests that essential oil from O. gratissimum decreases gingival fibroblasts secretion of PGE2, while essential oils from B. pilosa and C. nardus increase PGE2 secretion. Essential oil from Z. chalybeum was the most cytotoxic, while oil from C. nardus was the least cytotoxic. Although the clinical significance of these findings remains to be determined, it may be suggested that essential oil from O. gratissimum, applied at subcytotoxicity concentrations, could reduce the participation of gingival fibroblasts in the gingival inflammation and tissue destruction associated with periodontitis. PMID:27807462

  16. 2-Phenylnaphthalene Derivatives Inhibit Lipopolysaccharide-Induced Pro-Inflammatory Mediators by Downregulating of MAPK/NF-κB Pathways in RAW 264.7 Macrophage Cells

    Science.gov (United States)

    Chang, Chi-Fen; Liao, Kang-Chun; Chen, Chung-Hwan

    2017-01-01

    The anti-inflammatory pharmacological effect of eight 2-phenylnaphthalenes (PNAP-1−PNAP-8) on lipopolysaccharide (LPS)-induced RAW 264.7 (a mouse cell line) was investigated. Among them, 6,7-dihydroxy-2-(4′-hydroxyphenyl)naphthalene (PNAP-6) and 2-(4′-aminophenyl)-6,7-dimethoxynaphthalene (PNAP-8) exhibited the best anti-inflammatory activity in this study. PNAP-6 and PNAP-8 not only significantly decreased the expression of inducible nitric oxide synthase and cyclooxygenase-II, but also inhibited the production of nitric oxide, interleukin-6, and tumor necrosis factor-α in LPS stimulated cells. Moreover, PNAP-6 and PNAP-8 inhibited nuclear factor (NF)-κB activation by decreasing the degradation of IκB and nuclear translocation of NF-κB subunit (p65). In addition, PNAP-6 and PNAP-8 also attenuated the phosphorylation of ERK, p38, and JNK. These results suggest that PNAP-6 and PNAP-8 exert anti-inflammatory activities by down regulating NF-κB activation and the mitogen-activated protein kinase signaling pathway in LPS-stimulated Raw 264.7 cells. This is the first study demonstrating that PNAPs can inhibit LPS-induced pro-inflammatory mediators in macrophages cells. PMID:28060845

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Chia-Yi Tseng

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

  19. Categorization of cerebrovascular intervention methods

    Institute of Scientific and Technical Information of China (English)

    Wenxin Zhao; Gelin Xu; Xinfeng Liu

    2008-01-01

    BACKGROUND: Cerebrovascular intervention is a medical strategy to diagnose and treat cerebrovascular disease by intravascular intervention techniques. With the continual developments of computer technology, imageology, and angiography, cerebrovascular intervention techniques have developed rapidly.OBJECTIVE: To summarize and to evaluate vascular imaging diagnostic techniques, vascular intra-arterial thrombolysis, vascular intra-arterial angioplasty, and vascular embolization in clinical applications.RETRIEVAL STRATEGY: An online search was conducted in PubMed for English language reports, published from January 2002 to January 2008, containing the key words: intervention therapy, cerebral vascular disease, endovascular intervention and angioplasty. A total of 57 publications were identified. Inclusion criteria: articles about cerebrovascular intervention for cerebrovascular disease; articles published either in high impact factor journals or in recent years. Exclusion criteria: duplicated articles.LITERATURE EVALUATION: 30 articles were identified concerning intravascular intervention techniques and arterial angioplasty. Of those, 7 articles were reviews and 23 were clinical or basic studies.DATA SYNTHESIS: Carotid artery and basilar artery stenosis were important etiological factors for ischemic cerebrovascular disease. The mechanism of stenosis induction included atherosclerotic plaque exfoliation and stenosis could cause hemodynamic changes to induce cerebral infarction. Therefore, the treatment of carotid artery and basilar artery stenosis played a key role in preventing ischemic cerebral infarction. The international organization for subarachnoid hemorrhage aneurysm has conclusively shown that both relative and absolute risk factors of intravascular embolotherapy were reduced compared to those of surgical occlusion, demonstrating the important role of vascular embolization for the treatment of intracranial aneurysm. Endovascular stents were placed into the

  20. CRISPR/CAS9-Mediated Genome Editing of miRNA-155 Inhibits Proinflammatory Cytokine Production by RAW264.7 Cells

    Directory of Open Access Journals (Sweden)

    Weixia Jing

    2015-01-01

    Full Text Available MicroRNA 155 (miR-155 is a key proinflammatory regulator in clinical and experimental rheumatoid arthritis (RA. Here we generated a miR-155 genome knockout (GKO RAW264.7 macrophage cell line using the clustered regulatory interspaced short palindromic repeat (CRISPR/CRISPR-associated protein 9 (CAS9 technology. While upregulating the Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1, the miR-155 GKO line is severely impaired in producing proinflammatory cytokines but slightly increased in osteoclastogenesis upon treatment with receptor activator of nuclear factor-κB ligand (RANKL. Taken together, our results suggest that genome editing of miR-155 holds the potential as a therapeutic strategy in RA.

  1. Autophagy down regulates pro-inflammatory mediators in BV2 microglial cells and rescues both LPS and alpha-synuclein induced neuronal cell death

    Science.gov (United States)

    Bussi, Claudio; Ramos, Javier Maria Peralta; Arroyo, Daniela S.; Gaviglio, Emilia A.; Gallea, Jose Ignacio; Wang, Ji Ming; Celej, Maria Soledad; Iribarren, Pablo

    2017-01-01

    Autophagy is a fundamental cellular homeostatic mechanism, whereby cells autodigest parts of their cytoplasm for removal or turnover. Neurodegenerative disorders are associated with autophagy dysregulation, and drugs modulating autophagy have been successful in several animal models. Microglial cells are phagocytes in the central nervous system (CNS) that become activated in pathological conditions and determine the fate of other neural cells. Here, we studied the effects of autophagy on the production of pro-inflammatory molecules in microglial cells and their effects on neuronal cells. We observed that both trehalose and rapamycin activate autophagy in BV2 microglial cells and down-regulate the production of pro-inflammatory cytokines and nitric oxide (NO), in response to LPS and alpha-synuclein. Autophagy also modulated the phosphorylation of p38 and ERK1/2 MAPKs in BV2 cells, which was required for NO production. These actions of autophagy modified the impact of microglial activation on neuronal cells, leading to suppression of neurotoxicity. Our results demonstrate a novel role for autophagy in the regulation of microglial cell activation and pro-inflammatory molecule secretion, which may be important for the control of inflammatory responses in the CNS and neurotoxicity. PMID:28256519

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

    Directory of Open Access Journals (Sweden)

    Sang-Rim Kang

    2011-01-01

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

  3. Cholesterol crystals enhance TLR2-and TLR4-mediated pro-inflammatory cytokine responses of monocytes to the proatherogenic oral bacterium Porphyromonas gingivalis

    DEFF Research Database (Denmark)

    Køllgaard, Tania Maria Simonsen; Enevold, Christian; Bendtzen, Klaus

    2017-01-01

    Cholesterol deposits and pro-inflammatory cytokines play an essential role in the pathogenesis of atherosclerosis, a predominant cause of cardiovascular disease (CVD). Epidemiological evidence has linked periodontal disease (PD) with atherosclerotic CVD. Accordingly, viable periodontal pathogens......, tumor necrosis factor (TNF)-α, IL-6, and IL-8. Moreover, CHCs markedly enhanced secretion of IL-1β by monocytes stimulated with the toll-like receptor (TLR) 4 agonist Escherichia coli lipopolysaccharide (LPS), and the TLR2 agonist Staphylococcus aureus lipoteichoic acid. Notably, CHCs also enhanced IL-1...

  4. Cerebrovascular manifestations following scorpion sting

    OpenAIRE

    Nataraja P; Naveen Prasad SV; Obulareddy G; Anil Ch; Naveen T; Vengamma B

    2016-01-01

    Scorpion sting is a common clinical problem in Rayalaseema area of Andhra Pradesh State in India. Clilnical presentation of scorpion envenomation can range from mild local pain to systemic manifestations involving almost all systems. Cerebrovascular manifestations of scorpion sting have been sparsely documented. We report two cases who presented with ischaemic stroke and haemorrhagic stroke following scorpion sting.

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

    Directory of Open Access Journals (Sweden)

    Coffey Matt

    2011-02-01

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

  6. Long-lasting pro-inflammatory suppression of microglia by LPS-preconditioning is mediated by RelB-dependent epigenetic silencing.

    Science.gov (United States)

    Schaafsma, W; Zhang, X; van Zomeren, K C; Jacobs, S; Georgieva, P B; Wolf, S A; Kettenmann, H; Janova, H; Saiepour, N; Hanisch, U-K; Meerlo, P; van den Elsen, P J; Brouwer, N; Boddeke, H W G M; Eggen, B J L

    2015-08-01

    Microglia, the innate immune cells of the central nervous system (CNS), react to endotoxins like bacterial lipopolysaccharides (LPS) with a pronounced inflammatory response. To avoid excess damage to the CNS, the microglia inflammatory response needs to be tightly regulated. Here we report that a single LPS challenge results in a prolonged blunted pro-inflammatory response to a subsequent LPS stimulation, both in primary microglia cultures (100 ng/ml) and in vivo after intraperitoneal (0.25 and 1mg/kg) or intracerebroventricular (5 μg) LPS administration. Chromatin immunoprecipitation (ChIP) experiments with primary microglia and microglia acutely isolated from mice showed that LPS preconditioning was accompanied by a reduction in active histone modifications AcH3 and H3K4me3 in the promoters of the IL-1β and TNF-α genes. Furthermore, LPS preconditioning resulted in an increase in the amount of repressive histone modification H3K9me2 in the IL-1β promoter. ChIP and knock-down experiments showed that NF-κB subunit RelB was bound to the IL-1β promoter in preconditioned microglia and that RelB is required for the attenuated LPS response. In addition to a suppressed pro-inflammatory response, preconditioned primary microglia displayed enhanced phagocytic activity, increased outward potassium currents and nitric oxide production in response to a second LPS challenge. In vivo, a single i.p. LPS injection resulted in reduced performance in a spatial learning task 4 weeks later, indicating that a single inflammatory episode affected memory formation in these mice. Summarizing, we show that LPS-preconditioned microglia acquire an epigenetically regulated, immune-suppressed phenotype, possibly to prevent excessive damage to the central nervous system in case of recurrent (peripheral) inflammation.

  7. Mycobacterium avium subspecies induce differential expression of pro-inflammatory mediators in a murine macrophage model: evidence for enhanced pathogenicity of Mycobacterium avium subspecies paratuberculosis.

    Science.gov (United States)

    Basler, Tina; Geffers, Robert; Weiss, Siegfried; Valentin-Weigand, Peter; Goethe, Ralph

    2008-01-01

    Mycobacterium avium subspecies (ssp.) paratuberculosis (MAP) is the etiological agent of paratuberculosis, a chronic, non-treatable granulomatous enteritis of ruminants. MAP is the only mycobacterium affecting the intestinal tract, which is of interest since it is presently the most favoured pathogen linked to Crohn's disease (CD) in humans due to its frequent detection in CD tissues. MAP is genetically closely related to other M. avium ssp. such as M. avium ssp. avium (MAA) and M. avium ssp. hominissuis (MAH) which can cause mycobacteriosis in animals and immunocompromised humans. We have recently shown that murine macrophage cell lines represent suitable systems to analyse M. avium ssp. patho-mechanisms and could show that MAP, but not MAA, specifically inhibited the antigen-specific stimulatory capacity for CD4(+) T-cells. In the present study, we compared gene expression profiles of murine RAW264.7 macrophages in response to infections with MAP or MAA using murine high-density oligonucleotide Affymetrix microarrays. A comparison of MAP and MAA infection revealed 17 differentially expressed genes. They were expressed at a much lower level in MAP-infected macrophages than in MAA-infected macrophages. Among these were the genes for IL-1beta, IL-1alpha, CXCL2, PTGS2 (COX2), lipocalin (LCN2) and TNF, which are important pro-inflammatory factors. The microarray data were confirmed for selected genes by quantitative real-time reverse transcription PCR and, by protein array analyses and ELISA. Similar to MAA, infection with MAH also showed robust induction of IL-1beta, CXCL2, COX2, LCN2 and TNF. Taken together, our results from M. avium ssp.-infected murine macrophages provide evidence that MAP in contrast to MAA and MAH specifically suppresses the pro-inflammatory defence mechanisms of infected macrophages.

  8. Movement disorders in cerebrovascular disease.

    Science.gov (United States)

    Mehanna, Raja; Jankovic, Joseph

    2013-06-01

    Movement disorders can occur as primary (idiopathic) or genetic disease, as a manifestation of an underlying neurodegenerative disorder, or secondary to a wide range of neurological or systemic diseases. Cerebrovascular diseases represent up to 22% of secondary movement disorders, and involuntary movements develop after 1-4% of strokes. Post-stroke movement disorders can manifest in parkinsonism or a wide range of hyperkinetic movement disorders including chorea, ballism, athetosis, dystonia, tremor, myoclonus, stereotypies, and akathisia. Some of these disorders occur immediately after acute stroke, whereas others can develop later, and yet others represent delayed-onset progressive movement disorders. These movement disorders have been encountered in patients with ischaemic and haemorrhagic strokes, subarachnoid haemorrhage, cerebrovascular malformations, and dural arteriovenous fistula affecting the basal ganglia, their connections, or both.

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

    Directory of Open Access Journals (Sweden)

    Ted H. Elsasser

    2013-10-01

    Full Text Available While vitamin E has been used for decades in cattle diets, the principle form used traditionally is the synthetic α-isoform acetate or succinate and largely no data exist on the biological partitioning or functionality of the major naturally occurring γ- and δ-isoforms in cattle. Using tyrosine 3’-nitrated protein (pNT as a biomarker of nitrosative cell stress, we sought to evaluate the effectiveness of short-term feeding supplementation of high content natural α-tocopherol (α-T, 96% α-isomer compared to high content γ- and δ-enriched low α-content mixed tocopherol oils (γ-T, ~70% γ-, 20% δ-, <5% α-isoform to mitigate systemic and hepatic aspects of the proinflammatory response to endotoxin (LPS. Calves fed diets supplemented with α-T, γ-T for five days or no tocopherol supplement (T0E were challenged with a low-level of LPS (0.25 μg/kg, iv, E. coli 055:B5 sufficient to effect a liver nitration response. As fed, α-T or γ-T increased plasma and liver content of the respective tocopherols reflecting their relative abundance in the respective diets. Plasma or tissue mediators and biomarkers of the proinflammatory response [plasma concentrations of tumor necrosis factor-α (TNF-α, P<0.001, nitrate+nitrite (NOx, P<0.01, and serum amyloid A (SAA, P<0.001], and general liver content of pNT (P<0.005 increased after LPS. LPS-mediated increases in TNF-α were not dif- ferent between diet treatments; both plasma NOx (P<0.05 and generalized liver pNT (P<0.03 responses were attenuated significantly in α-T and γ-T versus T0E calves. Plasma SAA was significantly decreased in γ-T calves at 24 h post-LPS relative to responses in α-T or T0E calves. The nitration of the mitochondrial proteins 24 h post-LPS was not only attenuated in α-T and γ-T vs T0E, but also the mitigating effect of γ-T on these specific nitration events was greater than that of α-T (P<0.01. Results are consistent with the concept that short-term α-T or

  10. Essential Oils from Ugandan Medicinal Plants: In Vitro Cytotoxicity and Effects on IL-1β-Induced Proinflammatory Mediators by Human Gingival Fibroblasts

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    Francis Ocheng

    2016-01-01

    Full Text Available The study investigated cytotoxicity of essential oils from four medicinal plants (Bidens pilosa, Ocimum gratissimum, Cymbopogon nardus, and Zanthoxylum chalybeum on human gingival fibroblasts and their effects on proinflammatory mediators’ secretion. Cytotoxicity of essential oils was investigated using 3-(4, 5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide assay. Effects of essential oils at subcytotoxicity concentrations on interleukin- (IL- 6, IL-8, and prostaglandin E2 (PGE2 secretions by gingival fibroblasts treated with IL-1β (300 pg/mL were evaluated by ELISA and EIA. IC50 values of the essential oils ranged from 26 μg/mL to 50 μg/mL. Baseline and IL-1β-induced secretion of PGE2 was inhibited by treatment with essential oil from O. gratissimum. Essential oils from B. pilosa and C. nardus had synergistic effects with IL-1β on PGE2 seceretion. In conclusion, the study suggests that essential oil from O. gratissimum decreases gingival fibroblasts secretion of PGE2, while essential oils from B. pilosa and C. nardus increase PGE2 secretion. Essential oil from Z. chalybeum was the most cytotoxic, while oil from C. nardus was the least cytotoxic. Although the clinical significance of these findings remains to be determined, it may be suggested that essential oil from O. gratissimum, applied at subcytotoxicity concentrations, could reduce the participation of gingival fibroblasts in the gingival inflammation and tissue destruction associated with periodontitis.

  11. Ginsenoside Rg3 Improves Recovery from Spinal Cord Injury in Rats via Suppression of Neuronal Apoptosis, Pro-Inflammatory Mediators, and Microglial Activation

    Directory of Open Access Journals (Sweden)

    Dong-Kyu Kim

    2017-01-01

    Full Text Available Spinal cord injury (SCI is one of the most devastating medical conditions; however, currently, there are no effective pharmacological interventions for SCI. Ginsenoside Rg3 (GRg3 is one of the protopanaxadiols that show anti-inflammatory, anti-oxidant, and neuroprotective effects. The present study investigated the neuroprotective effect of GRg3 following SCI in rats. SCI was induced using a static compression model at vertebral thoracic level 10 for 5 min. GRg3 was administrated orally at a dose of 10 or 30 mg/kg/day for 14 days after the SCI. GRg3 (30 mg/kg treatment markedly improved behavioral motor functions, restored lesion size, preserved motor neurons in the spinal tissue, reduced Bax expression and number of TUNEL-positive cells, and suppressed mRNA expression of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin (IL-1β, and IL-6. GRg3 also attenuated the over-production of cyclooxygenase-2 and inducible nitric oxide synthase after SCI. Moreover, GRg3 markedly suppressed microglial activation in the spinal tissue. In conclusion, GRg3 treatment led to a remarkable recovery of motor function and a reduction in spinal tissue damage by suppressing neuronal apoptosis and inflammatory responses after SCI. These results suggest that GRg3 may be a potential therapeutic agent for the treatment of SCI.

  12. Wolbachia endosymbiont of Brugia malayi elicits a T helper type 17-mediated pro-inflammatory immune response through Wolbachia surface protein.

    Science.gov (United States)

    Pathak, Manisha; Verma, Meenakshi; Srivastava, Mrigank; Misra-Bhattacharya, Shailja

    2015-02-01

    Wolbachia is an endosymbiotic bacterium of the filarial nematode Brugia malayi. The symbiotic relationship between Wolbachia and its filarial host is dependent on interactions between the proteins of both organisms. However, little is known about Wolbachia proteins that are involved in the inflammatory pathology of the host during lymphatic filariasis. In the present study, we cloned, expressed and purified Wolbachia surface protein (r-wsp) from Wolbachia and administered it to mice, either alone or in combination with infective larvae of B. malayi (Bm-L3) and monitored the developing immune response in infected animals. Our results show that spleens and mesenteric lymph nodes of mice immunized with either r-wsp or infected with Bm-L3 show increased percentages of CD4(+) T helper type 17 (Th17) cells and Th1 cytokines like interferon-γ and interleukin-2 (IL-2) along with decreased percentages of regulatory T cells, Th2 cytokines like IL-4 and IL-10 and transforming growth factor β (TGF-β) levels in culture supernatants of splenocytes. These observations were stronger in mice immunized with r-wsp alone. Interestingly, when mice were first immunized with r-wsp and subsequently infected with Bm-L3, percentages of CD4(+) Th17 cells and Th1 cytokines increased even further while that of regulatory T cells, Th2 cytokines and TGF-β levels decreased. These results for the first time show that r-wsp acts synergistically with Bm-L3 in promoting a pro-inflammatory response by increasing Th17 cells and at the same time diminishes host immunological tolerance by decreasing regulatory T cells and TGF-β secretion.

  13. The rLrp of Mycobacterium tuberculosis inhibits proinflammatory cytokine production and downregulates APC function in mouse macrophages via a TLR2-mediated PI3K/Akt pathway activation-dependent mechanism.

    Science.gov (United States)

    Liu, Yuan; Li, Jia-Yun; Chen, Su-Ting; Huang, Hai-Rong; Cai, Hong

    2016-11-01

    We demonstrate that Mycobacterium tuberculosis recombinant leucine-responsive regulatory protein (rLrp) inhibits lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α), interleukin-6, and interleukin-12 production and blocks the nuclear translocation of subunits of the nuclear-receptor transcription factor NF-κB (Nuclear factor-kappa B). Moreover, rLrp attenuated LPS-induced DNA binding and NF-κB transcriptional activity, which was accompanied by the degradation of inhibitory IκBα and a consequent decrease in the nuclear translocation of the NF-κB p65 subunit. RLrp interfered with the LPS-induced clustering of TNF receptor-associated factor 6 and with interleukin-1 receptor-associated kinase 1 binding to TAK1. Furthermore, rLrp did not attenuate proinflammatory cytokines or the expression of CD86 and major histocompatibility complex class-II induced by interferon-gamma in the macrophages of Toll-like receptor 2 deletion (TLR2(-/-)) mice and in protein kinase b (Akt)-depleted mouse cells, indicating that the inhibitory effects of rLrp were dependent on TLR2-mediated activation of the phosphatidylinositol 3-OH kinase (PI3K)/Akt pathway. RLrp could also activate the PI3K/Akt pathway by stimulating the rapid phosphorylation of PI3K, Akt, and glycogen synthase kinase 3 beta in macrophages. In addition, 19 amino acid residues in the N-terminus of rLrp were determined to be important and required for the inhibitory effects mediated by TLR2. The inhibitory function of these 19 amino acids of rLrp raises the possibility that mimetic inhibitory peptides could be used to restrict innate immune responses in situations in which prolonged TLR signaling has deleterious effects. Our study offers new insight into the inhibitory mechanisms by which the TLR2-mediated PI3K/Akt pathway ensures the transient expression of potent inflammatory mediators.

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

    Science.gov (United States)

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

    2016-07-08

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

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

    Science.gov (United States)

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

    2015-10-23

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

  16. A diarylheptanoid from lesser galangal (Alpinia officinarum) inhibits proinflammatory mediators via inhibition of mitogen-activated protein kinase, p44/42, and transcription factor nuclear factor-kappa B.

    Science.gov (United States)

    Yadav, Prem N; Liu, Zhihua; Rafi, Mohamed M

    2003-06-01

    The diarylheptanoid 7-(4'-hydroxy-3'-methoxyphenyl)-1-phenylhept-4-en-3-one (HMP) is a naturally occurring phytochemical found in lesser galangal (Alpinia officinarum). In the present study, we have demonstrated the anti-inflammatory properties of this compound on mouse macrophage cell line (RAW 264.7) and human peripheral blood mononuclear cells (PBMCs) in vitro. Treatment of RAW 264.7 cells with HMP (6.25-25 microM) significantly inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production. This compound also inhibited the release of LPS-induced proinflammatory cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) from human PB-MCs in vitro. In addition, Western blotting and reverse transcription-polymerase chain reaction analysis demonstrated that HMP decreased LPS-induced inducible nitric-oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and mRNA expression in RAW 264.7 cells. Furthermore, HMP treatment also reduced nuclear factor-kappa B (NF-kappa B) DNA binding induced by LPS in RAW 264.7 cells. To elucidate the molecular mechanism for inhibition of proinflammatory mediators by HMP (25 microM), we have studied the effect of HMP on LPS-induced p38 and p44/42 mitogen-activated protein kinase (MAPK). We observed that the phosphorylation of p44/42 MAPK in LPS-stimulated RAW 264.7 cells was markedly inhibited by HMP, whereas activation of p38 MAPK was not affected. These results suggested that HMP from lesser galangal suppressed the LPS-induced production of NO, IL-1 beta, and TNF-alpha and expression of iNOS and COX-2 gene expression by inhibiting NF-kappa B activation and phosphorylation of p44/42 MAPK.

  17. Genetic Causes of Cerebrovascular Disorders in Childhood

    NARCIS (Netherlands)

    M.E.C. Meuwissen (Marije)

    2014-01-01

    markdownabstract__Abstract__ Cerebrovascular disorders in childhood comprise ischemic stroke and hemorrhagic stroke. This thesis comprises a escription of genetic causes of childhood cerebrovascular disorders. Two examples of genetic causes of ischemic stroke, comprising a case of ACTA2 mutation an

  18. Eagle syndrome revisited: cerebrovascular complications.

    Science.gov (United States)

    Todo, Tsuyoshi; Alexander, Michael; Stokol, Colin; Lyden, Patrick; Braunstein, Glenn; Gewertz, Bruce

    2012-07-01

    Cervical pain caused by the elongation of the styloid process (Eagle syndrome) is well known to otolaryngologists but is rarely considered by vascular surgeons. We report two patients with cerebrovascular symptoms of Eagle syndrome treated in our medical center in the past year. Case 1: an 80-year-old man with acromegaly presented with dizziness and syncope with neck rotation. The patient was noted to have bilateral elongated styloid processes impinging on the internal carotid arteries. After staged resections of the styloid processes through cervical approaches, the symptoms resolved completely. Case 2: a 57-year-old man presented with acute-onset left-sided neck pain radiating to his head immediately after a vigorous neck massage. Hospital course was complicated by a 15-minute transient ischemic attack resulting in aphasia. Angiography revealed bilateral dissections of his internal carotid arteries, with a dissecting aneurysm on the right. Both injuries were immediately adjacent to the bilateral elongated styloid processes. Despite immediate anticoagulation therapy, he experienced aphasia and right hemiparesis associated with an occlusion of his left carotid artery. He underwent emergent catheter thrombectomy and carotid stent placement, with near-complete resolution of his symptoms. Elongated styloid processes characteristic of Eagle syndrome can result in both temporary impingement and permanent injury to the extracranial carotid arteries. Although rare, Eagle syndrome should be considered in the differential diagnosis in patients with cerebrovascular symptoms, especially those induced by positional change.

  19. Evaluation of inhibitory activities of plant extracts on production of LPS-stimulated pro-inflammatory mediators in J774 murine macrophages.

    Science.gov (United States)

    Verma, Nandini; Tripathi, Subhash K; Sahu, Debasis; Das, Hasi R; Das, Rakha H

    2010-03-01

    Whole plant methanolic extracts of 14 traditionally used medicinal herbs were evaluated for their anti-inflammatory activity. Extracts of Grindelia robusta, Salix nigra, Arnica montana, and Quassia amara showed up to 4.5-fold inhibition of nitric oxide (NO) production in the J774 murine macrophage cells challenged with LPS without cytotoxicity. These four selected extracts significantly reduced the protein levels of inducible NO synthase (iNOS) and the cyclooxygenase-2 (COX-2) as observed by Western blot analysis. Culture supernatants from cells treated with these extracts indicated 3-5-fold reduction of tumor necrosis factor-alpha (TNF-alpha). However, only G. robusta and Q. amara extracts significantly inhibited (by 50%) IL-1beta and IL-12 secretions. Furthermore, all these plant extracts were shown to prevent the LPS-mediated nuclear translocation of nuclear factor-kappaB (NF-kappaB). All the above observations indicate the anti-inflammatory potential of these plant extracts.

  20. Aging negatively skews macrophage TLR2- and TLR4-mediated pro-inflammatory responses without affecting the IL-2-stimulated pathway.

    Science.gov (United States)

    Boehmer, Eric D; Meehan, Michael J; Cutro, Brent T; Kovacs, Elizabeth J

    2005-12-01

    We recently reported that macrophages from aged mice produced less tumor necrosis factor (TNF)-alpha following lipopolysaccharide (LPS) stimulation than macrophages from young animals. This correlated with decreased levels of phosphorylated and total p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs). Here, we went on to determine if age affects other Toll-like (TLR) and non-TLR signaling pathways. We found that LPS- and zymosan-stimulated TNF-alpha and IL-6 production is attenuated in splenic macrophages from aged mice compared to young. Conversely, LPS-stimulated, but not zymosan-stimulated, IL-10 production from the aged group was elevated over that of the young group. In contrast, IL-2-stimulated TNF-alpha and IL-6 production was not affected by age. The age-associated changes did not correlate with alterations in the cell-surface expression of TLR2, TLR4, or IL-2Rbeta. Macrophages from aged mice demonstrated lower p38 MAPK and MAPK-activated protein kinase (APK)-2 activation. Protein expression of p38, but not MAPK-APK-2, was reduced with age. Additionally, nuclear factor (NF)-kappaB activation was significantly decreased in macrophages from aged mice after exposure to LPS, but not IL-2. These data indicate that age-associated macrophage signaling alterations are pathway-specific and suggest that TLR-mediated pathways are impaired with age at the level of MAPK expression.

  1. Artemisia asiatica Nakai Attenuates the Expression of Proinflammatory Mediators in Stimulated Macrophages Through Modulation of Nuclear Factor-κB and Mitogen-Activated Protein Kinase Pathways.

    Science.gov (United States)

    Kim, Eun-Kyung; Tang, Yujiao; Cha, Kwang-Suk; Choi, Heeri; Lee, Chun Bok; Yoon, Jin-Hwan; Kim, Sang Bae; Kim, Jong-Shik; Kim, Jong Moon; Han, Weon Cheol; Choi, Suck-Jun; Lee, Sangmin; Choi, Eun-Ju; Kim, Sang-Hyun

    2015-08-01

    The present study aimed to examine the anti-inflammatory effects and potential mechanism of action of Artemisia asiatica Nakai (A. asiatica Nakai) extract in activated murine macrophages. A. asiatica Nakai extract showed dose-dependent suppression of lipopolysaccharide (LPS)-induced nitric oxide, inducible nitric oxide synthase, and cyclooxygenase-2 activity. It also showed dose-dependent inhibition of nuclear factor-κB (NF-κB) translocation from the cytosol to the nucleus and as an inhibitor of NF-κB-alpha phosphorylation. The extract's inhibitory effects were found to be mediated through NF-κB inhibition and phosphorylation of extracellular signal-regulated kinase 1/2 and p38 in LPS-stimulated J774A.1 murine macrophages, suggesting a potential mechanism for the anti-inflammatory activity of A. asiatica Nakai. To our knowledge, this is the first report of the anti-inflammatory effects of A. asiatica Nakai on J774A.1 murine macrophages; these results may help develop functional foods possessing an anti-inflammatory activity.

  2. WIN-34B May Have Analgesic and Anti-Inflammatory Effects by Reducing the Production of Pro-Inflammatory Mediators in Cells via Inhibition of IκB Signaling Pathways

    Science.gov (United States)

    Kim, Kyoung Soo; Choi, Hyun Mi; Yang, Hyung-In; Yoo, Myung Chul

    2012-01-01

    WIN-34B showed analgesic and anti-inflammatory effects in various animal models of pain and osteoarthritis. However, the molecular mechanism by which WIN-34B inhibits pain and inflammation in vivo remains to be elucidated. We investigated the molecular mechanisms of the actions of WIN-34B using various in vitro models using fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA FLSs), RAW264.7 cells and peritoneal macrophages. WIN-34B inhibited the level of IL-6, PGE2, and MMP-13 in IL-1β-stimulated RA FLSs in a dose-dependent manner. The mRNA levels were also inhibited by WIN-34B. The level of PGE2, NO, IL-1β, and TNF-α were inhibited by WIN-34B at different concentrations in LPS-stimulated RAW264.7 cells. The production of NO and PGE2 was inhibited by WIN-34B in a dose-dependent manner in LPS-stimulated peritoneal macrophages. All of these effects were comparable to the positive control, celecoxib or indomethacin. IκB signaling pathways were inhibited by WIN-34B, and the migration of NF-κB into the nucleus was inhibited, which is consistent with the degradation of IκB-α. Taken together, the results suggest that WIN-34B has potential as a therapeutic drug to reduce pain and inflammation by inhibiting the production of pro-inflammatory mediators. PMID:24116274

  3. 5-Bromo-2-hydroxy-4-methyl-benzaldehyde inhibited LPS-induced production of pro-inflammatory mediators through the inactivation of ERK, p38, and NF-κB pathways in RAW 264.7 macrophages.

    Science.gov (United States)

    Kim, Kil-Nam; Ko, Seok-Chun; Ye, Bo-Ram; Kim, Min-Sun; Kim, Junseong; Ko, Eun-Yi; Cho, Su-Hyeon; Kim, Daekyung; Heo, Soo-Jin; Jung, Won-Kyo

    2016-10-25

    The aim of the present study was to investigate the effects of 5-bromo-2-hydroxy-4-methyl-benzaldehyde (BHMB) on inflammatory responses to lipopolysaccharide (LPS) in RAW 264.7 cells and the associated mechanism of action. BHMB concentration-dependently suppressed protein and mRNA expressions of iNOS and COX-2, thereby inhibiting the production of NO and PGE2 in LPS-stimulated RAW 264.7 cells. BHMB also reduced the mRNA expression of TNF-α, IL-6, and IL-1β in LPS-stimulated RAW 264.7 cells. To elucidate the mechanism underlying the anti-inflammatory activity of BHMB, we investigated the effects of BHMB on the mitogen-activated protein kinase and nuclear factor-kappa B (NF-κB) pathways. BHMB suppressed the phosphorylation and degradation of IκB-α and markedly inhibited the nuclear translocation of p65 and p50 in LPS-stimulated RAW 264.7 cells. The compound also inhibited the LPS-stimulated phosphorylation of ERK and p38. Taken together, these results illustrated that BHMB suppresses pro-inflammatory mediator and cytokine expression in LPS-stimulated RAW 264.7 cells by inhibiting the phosphorylation of ERK and p38 and the activation of NF-κB.

  4. The role of inflammation and interleukin-1 in acute cerebrovascular disease

    Directory of Open Access Journals (Sweden)

    Galea J

    2013-08-01

    Full Text Available James Galea,1 David Brough21Manchester Academic Health Sciences Center, Brain Injury Research Group, Clinical Sciences Building, Salford Royal Foundation Trust, Salford, UK; 2Faculty of Life Sciences, University of Manchester, AV Hill Building, Manchester, UKAbstract: Acute cerebrovascular disease can affect people at all stages of life, from neonates to the elderly, with devastating consequences. It is responsible for up to 10% of deaths worldwide, is a major cause of disability, and represents an area of real unmet clinical need. Acute cerebrovascular disease is multifactorial with many mechanisms contributing to a complex pathophysiology. One of the major processes worsening disease severity and outcome is inflammation. Pro-inflammatory cytokines of the interleukin (IL-1 family are now known to drive damaging inflammatory processes in the brain. The aim of this review is to discuss the recent literature describing the role of IL-1 in acute cerebrovascular disease and to provide an update on our current understanding of the mechanisms of IL-1 production. We also discuss the recent literature where the effects of IL-1 have been targeted in animal models, thus reviewing potential future strategies that may limit the devastating effects of acute cerebrovascular disease.Keywords: cerebral ischemia, stroke, inflammation, microglia, interleukin-1, caspase-1

  5. FastStats: Cerebrovascular Disease or Stroke

    Science.gov (United States)

    ... this? Submit Button NCHS Home Cerebrovascular Disease or Stroke Recommend on Facebook Tweet Share Compartir Data are ... Morbidity Number of adults who ever had a stroke: 6.5 million Percent of adults who ever ...

  6. Mortalidad intrahospitalaria por accidente cerebrovascular

    Directory of Open Access Journals (Sweden)

    Federico Rodríguez Lucci

    2013-08-01

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

  7. Polyclonal light chains in cerebrovascular disease

    Directory of Open Access Journals (Sweden)

    Patrizia Fiori

    2010-08-01

    Full Text Available Patrizia Fiori1, Maria Giannetti Luigi2, Linda Iurato1, Carminantonio Tammaro3, Gigliola Esposito3, Antonio Monaco11Central Operative Unit of Neurology (Dir. A Monaco, 2Infantile Neuropsychiatry and Social Service (Dir. LM Giannetti, 3Laboratory (Dir. CA Tammaro, ASL AV, Civil Hospital of Ariano Irpino, University of Naples, ItalyAbstract: Altered membrane permeability is a hallmark of inflammation and ischemia with systemic spreading. Renal dysfunction is a risk factor for cardiovascular, cerebrovascular, and metabolic diseases. The aim of the present study was to assess proteinuria and urinary polyclonal light chains in acute stroke and chronic cerebrovascular disease compared with other neurologic diseases. Our results showed significantly increased levels of urinary polyclonal light chains in cerebrovascular disease compared with other neurologic diseases. The highest values of urinary polyclonal κ chains were found in acute stroke compared with chronic cerebrovascular disease and other neurologic diseases, while the level of λ chains was mainly increased in chronic cerebrovascular diseases. The shift to chronic renal failure seems to be signaled by a decreased polyclonal light chain/creatinemia ratio. The absence of a significant correlation with blood pressure and other seric parameters suggests that polyclonal light chains are an early marker of reversible vascular impairment with renal dysfunction before progression to irreversible renal failure and need for dialysis and/or intensive care.Keywords: polyclonal light chains, cerebrovascular disease, renal failure

  8. Alcoholism: a systemic proinflammatory condition.

    Science.gov (United States)

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

    2014-10-28

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

  9. Low-level laser therapy (LLLT; 780 nm) acts differently on mRNA expression of anti- and pro-inflammatory mediators in an experimental model of collagenase-induced tendinitis in rat.

    Science.gov (United States)

    Pires, Débora; Xavier, Murilo; Araújo, Tiago; Silva, José Antônio; Aimbire, Flavio; Albertini, Regiane

    2011-01-01

    Low-level laser therapy (LLLT) has been found to produce anti-inflammatory effects in a variety of disorders. Tendinopathies are directly related to unbalance in expression of pro- and anti-inflammatory cytokines which are responsible by degeneration process of tendinocytes. In the current study, we decided to investigate if LLLT could reduce mRNA expression for TNF-α, IL-1β, IL-6, TGF-β cytokines, and COX-2 enzyme. Forty-two male Wistar rats were divided randomly in seven groups, and tendinitis was induced with a collagenase intratendinea injection. The mRNA expression was evaluated by real-time PCR in 7th and 14th days after tendinitis. LLLT irradiation with wavelength of 780 nm required for 75 s with a dose of 7.7 J/cm(2) was administered in distinct moments: 12 h and 7 days post tendinitis. At the 12 h after tendinitis, the animals were irradiated once in intercalate days until the 7th or 14th day in and them the animals were killed, respectively. In other series, 7 days after tendinitis, the animals were irradiated once in intercalated days until the 14th day and then the animals were killed. LLLT in both acute and chronic phases decreased IL-6, COX-2, and TGF-β expression after tendinitis, respectively, when compared to tendinitis groups: IL-6, COX-2, and TGF-β. The LLLT not altered IL-1β expression in any time, but reduced the TNF-α expression; however, only at chronic phase. We conclude that LLLT administered with this protocol reduces one of features of tendinopathies that is mRNA expression for pro-inflammatory mediators.

  10. Migraine, cerebrovascular disease and the metabolic syndrome

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    Alexandra J Sinclair

    2012-01-01

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

  11. Aortoiliac occlusive disease masquerading as cerebrovascular accident

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    Nandeesh B

    2007-01-01

    Full Text Available Acute aortoiliac occlusion is an unusual but potentially catastrophic condition causing acute limb ischemia and associated with early and high rates of mortality and morbidity. It is caused by either embolic occlusion of the infra renal aorta at the bifurcation or beyond or thrombosis of the abdominal aorta and its large terminal branches. Neurological symptoms are rare manifestation of acute aortoiliac occlusion and when neurological symptoms predominate, patients are mistakenly considered to have cerebrovascular event. We present a 60-year-old man with atherosclerotic thrombotic occlusion of the left common iliac artery causing acute painful monoplegia. We mistook the acute monoplegia due to acute limb ischemia for cerebrovascular accident. Pathologic examination revealed a firm thrombus occluding the origin of left common iliac artery and extending along the length of the vessel. Acute aortic iliac occlusion can masquerade as a cerebrovascular stroke and a thorough clinical evaluation and imaging studies allow early diagnosis and instituting life-saving treatment timely.

  12. [Primary antiphospholipid syndrome and cerebrovascular disturbances].

    Science.gov (United States)

    Kalashnikova, L A

    2005-01-01

    Neurological, including cecbrovascular, disorders frequently emerge in primary antiphospholipid syndrome (PAS). Clinical peculiarities of PAS were studied in 113 patients with cerebrovascular disturbances. Its had mainly ischemic patogenesis. Structure of cerebrovascular disorders was as follows: stroke (33% cases), transient ischemic lesions (10%), its combination (57%), thrombosis of brain venous sinuses (3%), vascular dementia (27%). Besides it were found epileptic seizures, peripheral neuropathy, headache, chorea and some symptoms of myasthenia, parkinsonism, multiple sclerosis and psychotic disorders. In all cases antibodies to phospholipids have been detected. Secondary prophylaxis includes regular use of anticoagulants and small doses of aspiriny.

  13. Cognitive impairments in patients with cerebrovascular steno-occlusive disease

    Institute of Scientific and Technical Information of China (English)

    石丹

    2012-01-01

    Objective To explore the relationship between cerebrovascular steno-occlusive disease and neuropsychological performance by cognitive function assessment. Methods Using a case-control study,45 patients with cerebrovascular steno-occlusive lesions (patient group) and 59 control subjects without cerebrovascular

  14. The proinflammatory cytokine response to Chlamydia trachomatis elementary bodies in human macrophages is partly mediated by a lipoprotein, the macrophage infectivity potentiator, through TLR2/TLR1/TLR6 and CD14.

    Science.gov (United States)

    Bas, Sylvette; Neff, Laurence; Vuillet, Madeleine; Spenato, Ursula; Seya, Tsukasa; Matsumoto, Misako; Gabay, Cem

    2008-01-15

    Chlamydiae components and signaling pathway(s) responsible for the production of proinflammatory cytokines by human monocytes/macrophages are not clearly identified. To this aim, Chlamydia trachomatis-inactivated elementary bodies (EB) as well as the following seven individual Ags were tested for their ability to induce the production of proinflammatory cytokines by human monocytes/macrophages and THP-1 cells: purified LPS, recombinant heat shock protein (rhsp)70, rhsp60, rhsp10, recombinant polypeptide encoded by open reading frame 3 of the plasmid (rpgp3), recombinant macrophage infectivity potentiator (rMip), and recombinant outer membrane protein 2 (rOmp2). Aside from EB, rMip displayed the highest ability to induce release of IL-1beta, TNF-alpha, IL-6, and IL-8. rMip proinflammatory activity could not be attributed to Escherichia coli LPS contamination as determined by the Limulus Amoebocyte lysate assay, insensitivity to polymyxin B (50 microg/ml), and different serum requirement. We have recently demonstrated that Mip is a "classical" bacterial lipoprotein, exposed at the surface of EB. The proinflammatory activity of EB was significantly attenuated in the presence of polyclonal Ab to rMip. Native Mip was able to induce TNF-alpha and IL-8 secretion, whereas a nonlipidated C20A rMip variant was not. Proinflammatory activity of rMip was unaffected by heat or proteinase K treatments but was greatly reduced by treatment with lipases, supporting a role of lipid modification in this process. Stimulating pathways appeared to involve TLR2/TLR1/TLR6 with the help of CD14 but not TLR4. These data support a role of Mip lipoprotein in pathogenesis of C. trachomatis-induced inflammatory responses.

  15. Effect of high-intensity training on endothelial function in patients with cardiovascular and cerebrovascular disease: A systematic review

    Directory of Open Access Journals (Sweden)

    Mia Kolmos

    2016-12-01

    Full Text Available Objectives: Exercise improves endothelial dysfunction, the key manifestation of cardiovascular and cerebrovascular disease, and is recommended in both cardiovascular and cerebrovascular rehabilitation. Disagreement remains, however, on the role of intensity of exercise. The purpose of this review was to gather current knowledge on the effects of high-intensity training versus moderate-intensity continuous exercise on endothelial function in cardiovascular and cerebrovascular patients. Methods: A systematic review was performed in PubMed database, Embase and Cochrane libraries and on PEDro using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were restricted to cardiovascular and cerebrovascular patients, and healthy subjects as general reference. Interventions comprised of high-intensity training alone, high-intensity training compared to moderate-intensity continuous exercise, or no training, with endothelial function as outcome measure. Endothelial function was measured either physiologically by flow-mediated dilatation and/or by systemic biomarkers. Data were analyzed descriptively due to non-comparability for a meta-analysis to be performed. Results: A total of 20 studies were included in the review. Although there was great heterogenecity in design, population and exercise protocols, all studies found high-intensity training to be safe. High-intensity training was equal to moderate-intensity continuous exercise through improvement in endothelial function in 15 of the 20 selected studies, as measured by flow-mediated dilatation, nitric oxide bioavailability and circulating biomarkers. Only a few studies examined high-intensity training in cerebrovascular patients, none with endothelial function as outcome. Conclusion: High-intensity training is promising as a time-efficient exercise strategy in cardiovascular rehabilitation, but data on endothelial effects in cerebrovascular rehabilitation are

  16. Association of Fibrin Monomer Polymerization Function, Cerebrovascular Risk Factors and Ischemic Cerebrovascular Disease in Old People

    Institute of Scientific and Technical Information of China (English)

    洪梅; 魏文宁; 李红戈; 杨锐; 杨焰

    2003-01-01

    Summary: In order to investigate the association of fibrin monomer polymerization function (FMPF)with traditional cerebrovascular risk factors and ischemic cerebrovascular disease in old people, 1 : 1paired case-control comparative study was performed for FMPF and traditional cerebrovascular riskfactors on 110 cases of old ischemic cerebrovascular disease and 110 controls matched on age, sex andliving condition. The results showed that cerebrovascular risk factors were more prevalent in casegroup than in control group. In the case group, FMPF was significantly higher than in controlgroup. There was a significant positive correlation between hypertension and fibrin monomer poly-merization velocity (FMPV), hypertension and fibrinogen (Fbg), alcohol consumption and Fbg, butno significant correlation between diabetic mellitus, smoking and FMPF was found. Among the pa-rameters of blood lipids, there were significant positive correlations between total cholesterol (TC)and parameters of FMPF to varying degrees, triglycerides (TG) and FMPV, TG and Fbg. Our re-sults also showed there were significant linear trends between TC and FMPV (P<0. 001), TC andFbg (P=0. 0087), TG and FMPV/Amax (maximum absorbance)(P=0. 0143) respectively. Multi-ple logistic regression analysis revealed that FMPF in case group remained significantly higher thancontrol group after adjustment of all risk factors that were significant in univariate analysis. It wasconcluded that there is a possible pathophysiological link between FMPF and cerebrovascular risk fac-tors. An elevated FMPF is associated with ischemic cerebrovascular disease and an independent riskfactor of this disease. In old people, detection of FMPF might be a useful screening to identify indi-viduals at increased cerebrothrombotic risk.

  17. Role of transcranial Doppler in cerebrovascular disease

    Directory of Open Access Journals (Sweden)

    Amit A Kulkarni

    2016-01-01

    Full Text Available Transcranial Doppler (TCD is the only noninvasive modality for the assessment of real-time cerebral blood flow. It complements various anatomic imaging modalities by providing physiological-flow related information. It is relatively cheap, easily available, and can be performed at the bedside. It has been suggested as an essential component of a comprehensive stroke centre. In addition to its importance in acute cerebrovascular ischemia, its role is expanding in the evaluation of cerebral hemodynamics in various disorders of the brain. The “established” clinical indications for the use of TCD include cerebral ischemia, sickle cell disease, detection of right-to-left shunts, subarachnoid hemorrhage, periprocedural or surgical monitoring, and brain death. We present the role of TCD in acute cerebrovascular ischemia, sonothrombolysis, and intracranial stenosis.

  18. EMPREGO DE STENTS CEREBRAIS NAS PATOLOGIAS CEREBROVASCULARES

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    Laís Rocha Lopes

    2015-06-01

    Full Text Available Objective: To understand the applicability and characteristics of the stents for the treatment of cerebrovascular pathologies in order to understand its viability for the therapy. Methods: Scientific articles were used based on electronic search as PubMed, Scientific Electronic Library Online (SciELO, Intechopen, Medscape. An international and up to date source of articles was used. Results: Cerebrovascular diseases have emerged as the second most important cause of mortality worldwide, from this principle we observe the importance of this study. Recently, as a solution form, stents have become a major treatment option for difficult and not feasible cerebral aneurysms single winding. Intracranial stents serve as a bridge to the neo-endothelialization by providing a reduction in blood flow into the aneurysm. The use of stents for treatment should be seriously analyzed according to their feasibility, the knowledge of the professional about their brands, features and deployment techniques, and theoretical part of the professional needs to have dexterity to the application of an intracranial stent. Conclusions: This review raises an awareness of this subject, starts from the concept of cerebrovascular disease and aneurysms as well as the genesis of the stents, progressing to elucidate all product brands and specific characteristics of each, ending with its applicability, as well as making clear the purpose and mechanism of stents.

  19. Auditory Dysfunction in Patients with Cerebrovascular Disease

    Directory of Open Access Journals (Sweden)

    Sadaharu Tabuchi

    2014-01-01

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

  20. Curcumin attenuates the release of pro-inflammatory cytokines in lipopolysaccharide-stimulated BV2 microglia

    Institute of Scientific and Technical Information of China (English)

    Cheng-yun JIN; Jae-dong LEE; Cheol PARK; Yung hyun CHOI; Gi-young KIM

    2007-01-01

    Aim: Pro-inflammatory mediators, such as prostaglandin E2 (PGE2) and nitric oxide(NO), and pro-inflammatory cytokines such as intedeukini(IL)- 1β, IL-6, and TNF-α, play pivotal roles in brain injuries. The anti-inflammatory properties are known to be associated with significant reductions in pro-inflammatory mediators in brain injuries. In the present study we investigate whether the effects of curcumin on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimu-lated BV2 microglia. Methods: Curcumin were administered and their effects on LPS-induced pro-inflammatory mediators were monitored by Western blotting and RT-PCR. Result: Curcumin significantly inhibited the release of NO, PGE2,and pro-inflammatory cytokines in a dose-dependent manner. Curcumin also attenuated the expressions of inducible NO synthase and cyclooxygenase-2 mRNA and protein levels. Moreover, curcumin suppressed NF-κB activation via the translocation of p65 into the nucleus. Our data also indicate that curcumin exerts anti-inflammatory properties by suppressing the transcription of proinflammatory cytokine genes through the NF-rd3 signaling pathway. Conclusion: Anti-inflam-matory properties of curcumin may be useful for treating the inflammatory and deleterious effects of microglial activation in response to LPS stimulation.

  1. Factors influencing ischemic cerebrovascular disease complicated by hyperhomocysteinemia

    Institute of Scientific and Technical Information of China (English)

    Zhongping An; Yonghong Xing; Sha Jin

    2008-01-01

    BACKGROUND: Hyperhomocysteinemia, as an important risk factor for ischemic cerebrovascular disease is receiving increasing attention.OBJECTIVE: To analyze whether differences of gender, age, cerebrovascular disease typing, and disease conditions exist when ischemic cerebrovascular disease occurs together with hyperhomocysteinemia. DESIGN: A controlled observation. SETTING: Department of Neurology, Tianjin Huanhu Hospital. PARTICIPANTS: A total of 601 acute ischemic cerebrovascular disease inpatients, comprising 386 males and 215 females, aged 33-90 years old, were admitted to the Department of Stroke, Tianjin Huanhu Hospital between August 2005 and April 2007, and were recruited for this study. All included patients consisted of 342 aged patients (≥ 60 years old) and 92 middle-aged and young patients ( 0.05). No significant difference in incidence of hyperhomocysteinemia existed between mild, moderate, and severe cerebrovascular disease patients (P > 0.05). CONCLUSION: There is a greater chance of ischemic cerebrovascular disease complicated by hyperhomocysteinemia in older, male patients.

  2. Enfermedad cerebrovascular: incidencia y tratamiento actual

    OpenAIRE

    Julio César Fernández-Travieso

    2014-01-01

    La enfermedad cerebrovascular o ictus representa la tercera causa de mortalidad de la población adulta y la primera de discapacidad result ante, por lo cual constituye un importante problema de salud a nivel mundial. El tratamiento del ictus en la fase aguda depende, además de la exitosa aplicación de la terapia adecuada, de una cadena de emergencia que permita su diagnóstico y manejo adecuad o y rápido, y aú n cuando se logre la supervivencia, muchos pacientes sobreviven con importantes limi...

  3. Nitric oxide synthase inhibition and cerebrovascular regulation

    DEFF Research Database (Denmark)

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

    1994-01-01

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

  4. Dysregulated proinflammatory and fibrogenic phenotype of fibroblasts in cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    François Huaux

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  6. Dysphagia in patients with cerebrovascular disease. Update.

    Directory of Open Access Journals (Sweden)

    Amarilis Barbié Rubiera

    2009-03-01

    Full Text Available An important number of patients with cerebrovascular disease also present dysphagia as a result of damage in cerebral hemispheres or brainstem, which contributes to negative morbility and functional rehabilitation prognosis due to the complications liked with this condition. It is a significant cause of nutritional dysfunctions, including increased in-hospital undernourishment, increased per patient expenditure and longer in-hospital stay. One of the objectives of the Nutritional Support Team of the Neuroscience and Neurology Institute is to reduce undernourishment causes in patients with neurological diseases. A wide review of the subject was performed including experts´ opinions, from the above mentioned institutions, in order to gather an updated report related with the significance of early diagnosis of dysphagia in patients with ictus and the opportune and correct use of therapeutic measures to reduce complication risk.

  7. Impact of Cerebrovascular Disease Mortality on Life Expectancy in China

    Institute of Scientific and Technical Information of China (English)

    LI Guo Qi; LI Yan; ZHAO Dong; FAN Jie; LIU Jing; WANG Wei; WANG Miao; QI Yue; XIE Wu Xiang; LIU Jun; ZHAO Fan

    2014-01-01

    Objective To evaluate the impact of cerebrovascular disease mortality on life expectancy (LE) in China in 2010 compared with 2005, and to identify the high-risk population (age, sex, and region) where cerebrovascular disease mortality has had a major impact on LE. Methods LE and cause-eliminated LE were calculated by using standard life tables which used adjusted mortality data from the Death Surveillance Data Sets in 2005 and 2010 from the National Disease Surveillance System. Decomposition was used to quantitate the impact of cerebrovascular disease in different age groups. Results LE in China was 73.24 years in 2010, which was higher in women and urban residents compared with men and rural residents. The loss of LE caused by cerebrovascular disease mortality was 2.26 years, which was higher in men and rural residents compared with women and urban residents. More than 30%of the loss of LE were attributed to premature death from cerebrovascular disease in people aged Conclusion Cerebrovascular disease mortality had a major impact on LE in China, with a significant difference between urban and rural residents. LE is likely to be further increased by reducing cerebrovascular disease mortality, and special attention should be paid to reducing premature deaths in people aged<65 years.

  8. SYSTOLIC HYPERTENSION. IMPACT ON CEREBROVASCULAR DISEASE

    Directory of Open Access Journals (Sweden)

    Juan Eloy Cruz Quesada

    2011-08-01

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

  9. Cerebrovascular diseases and depression: epidemiology, mechanisms and treatment.

    Science.gov (United States)

    Göthe, F; Enache, D; Wahlund, L O; Winblad, B; Crisby, M; Lökk, J; Aarsland, D

    2012-09-01

    Both cerebrovascular disease (CVD) and depression are common conditions in the elderly, and there is emerging evidence of a bi-directional relationship: 1) depression can cause CVD and stroke, transient ischemic attack; and 2) subcortical CVD are associated with increased risk for depression. The frequency of poststroke depression is highest during the first month after the stroke, but remains high even after several years. Depression is associated with poorer functional prognosis and higher mortality after stroke. There is good evidence that severity of functional impairment, high neuroticism, low social support as well as genetic factors are associated with an increased risk for post-stroke depression. Deep white matter lesions are the most consistent imaging correlate of depression. Potential mechanisms mediating the association between depression and CVD are neuroinflammation and HPA-axis activation, fronto-subcortical circuit lesions, and serotonergic dysfunction. Antidepressants have demonstrated effect on poststroke depression in meta-analyses, and such drugs as well as vitamin B can reduce the incidence of depression in stroke survivors. In addition, serotonergic drugs may strengthen poststroke motor and cognitive recovery, potentially through restorative mechanisms. Psychotherapeutic strategies such as problem-solving therapy seem to be effective. There is emerging evidence that treatment of cardiovascular disease and risk-factors can reduce the risk for late-life depression, but more studies are needed to test this hypothesis.

  10. Obesity Paradox in the Course of Cerebrovascular Diseases.

    Science.gov (United States)

    Brzecka, Anna; Ejma, Maria

    2015-01-01

    Obesity remains an important risk factor of cardiovascular and cerebrovascular diseases. However, it has been observed that increased body fat and body mass index predicted longer survival after the occurrence of a cardiovascular event. This observation has been named the obesity paradox. Initially, the term obesity paradox referred to the observation of the better outcome of cardiovascular diseases, such as heart failure and coronary heart disease, in obese patients as compared to underweight and normal-weight patients. Recently, similar, although fewer, observations confirm the occurrence of the obesity paradox in patients with acute cerebrovascular diseases. The underlying reasons for the protective effects of excessive body fat tissue against the consequences of acute cardiovascular and cerebrovascular diseases are poorly understood. The effect of preconditioning may be associated with the obesity paradox. The issue of the correlation between obesity and better survival of patients with cardiovascular and cerebrovascular diseases still remains largely unexplored. Debates for and against the obesity paradox continue.

  11. Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  12. Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  13. Cystatin cures visceral leishmaniasis by NF-κB-mediated proinflammatory response through co-ordination of TLR/MyD88 signaling with p105-Tpl2-ERK pathway.

    Science.gov (United States)

    Kar, Susanta; Ukil, Anindita; Das, Pijush K

    2011-01-01

    Cystatin could completely cure experimental visceral leishmaniasis by switching the differentiation of Th2 cells to Th1 type, as well as upregulating NO, and activation of NF-κB played a major role in these processes. Analysis of upstream signaling events revealed that TLR 2/4-mediated MyD88-dependent participation of IL-1R-activated kinase (IRAK)1, TNF receptor-associated factor (TRAF)6 and TGFβ-activated kinase (TAK)1 is essential to induce cystatin-mediated IκB kinase (IKK)/NF-κB activation in macrophages. Cystatin plus IFN-γ activated the IKK complex to induce phosphorylation-mediated degradation of p105, the physiological partner and inhibitor of the MEK kinase, tumor progression locus 2 (Tpl-2). Consequently, Tpl-2 was liberated from p105, thereby stimulating activation of the MEK/ERK MAPK cascade. Cystatin plus IFN-γ-induced IKK-β post-transcriptionally modified p65/RelA subunit of NF-κB by dual phosphorylation in infected phagocytic cells. IKK induced the phosphorylation of p65 directly on Ser-536 residue whereas phosphorylation on Ser 276 residue was by sequential activation of Tpl-2/MEK/ERK/MSK1. Collectively, the present study indicates that cystatin plus IFN-γ-induced MyD88 signaling may bifurcate at the level of IKK, leading to a divergent pathway regulating NF-κB activation by IκBα phosphorylation and by p65 transactivation through Tpl-2/MEK/ERK/MSK1.

  14. Current therapy for chronic cerebrovascular attack

    Directory of Open Access Journals (Sweden)

    A. A. Shmonin

    2015-01-01

    Full Text Available Chronic cerebrovascular attack (CCVA is a brain lesion caused by vascular factors. CCVA appears as cognitive impairments (CIs, affective (emotional disorders and focal syndromes. Treatment for CCVA requires a comprehensive approach. Effective combination therapy for CCVA involves secondary prevention of stroke and CIs; treatment of CIs; treatment of depression and other affective disorders; and neuroprotective therapy. Basic therapy for CCVA includes modification of risk factors, antihypertensive, hypolipidemic, and antithrombotic therapies. Central acetylcholinesterase inhibitors (galantamine, rivastigmine, donepezil and a reversible NMDA receptor blocker (memantine are symptomatically used at a stage of vascular and mixed dementia. There are no unique guidelines for the therapy of mild and moderate vascular nondementia-related CIs. Drug use, based on the neurochemical mechanisms underlying the development of vascular CIs, is substantiated. When choosing psychotropic agents, it is necessary to take into account the causes and clinical manifestations of neuromediator deficiency. Antidepressants are used as essential drugs. Neuroleptics and tranquilizers are additionally administered in complex-pattern syndromes, such as depression with marked anxiety. Prescription of neuroprotectors may be effective in treating both stroke and CCVA. These medicaments are most effective when a damaging factor acts, i.e. neuroprotectors should be given in a risk situation and to reduce damage. Citicoline is one of the most test drugs in a group of neuroprotectors. 

  15. Audiological profile in cases with cerebrovascular accidents

    Directory of Open Access Journals (Sweden)

    Matlapudi Venkata Subbarao

    2015-01-01

    Full Text Available Background: Over the past decades there has been increase demand of audiological complaints coinciding with neurological impairments due to cerebrovascular accidents (CVAs. Most of the cases represent inconsistent responses to acoustic stimuli or total lack of response to sound, documented as auditory agnosia. Aim: The present investigation aims at understanding of potential anatomical co-relates to the involvement of the cortical structure and the processing of auditory stimuli. Materials and Methods: A case series with convenient sampling method included eight cases (six male and two female with age range 45-55 years with CVA, were taken for this study. Of them two cases were found with lesion in right middle cerebral artery, four cases with left middle cerebral artery and two cases with left posterior cerebral artery lesion confirmed from magnetic resonance imaging scan. Audiological test battery including otoscopy, tuning fork test, pure tone audiometry, speech audiometry, immittance audiometry, dichotic-diotic listening test, auditory brainstem responses, otoacoustic emissions and gap detection tests were carried out including routine ENT evaluation. Results and Conclusion: Result suggests; there is a significant difference in hearing threshold and speech perception in all the eight subjects. The findings and compromised vascular anatomy in all these cases were discussed in this article.

  16. Symptomatic Epilepsies due to Cerebrovascular Diseases

    Science.gov (United States)

    Dakaj, Nazim; Shatri, Nexhat; Isaku, Enver; Zeqiraj, Kamber

    2014-01-01

    Introduction: Cerebro-vascular diseases (CVD) are the leading cause of symptomatic epilepsies. This study aims to investigate: a) Frequency of epilepsy in patients with CVD; b) Correlation of epilepsy with the type of CVD (ischemic and hemorrhage) and with age. Methodology: It is analyzed medical documentation of 816 hospitalized patients with CVD in the clinic of Neurology in University Clinical Center (UCC) during the period January - December 2010. The study included data on patients presenting with epileptic seizures after CVD, and those with previously diagnosed epilepsy, are not included in the study. The diagnosis of CVD, are established in clinical neurological examination and the brain imaging (computer tomography and magnetic resonance imaging). The diagnosis of epilepsy is established by the criteria of ILAE (International League against Epilepsy) 1983, and epileptic seizures are classified according to the ILAE classification, of 1981. Results: Out of 816 patients with CVD, 692 were with ischemic stroke and 124 with hemorrhage. From 816 patients, epileptic seizures had 81 (10%), of which 9 patients had been diagnosed with epilepsy earlier and they are not included in the study. From 72 (99%) patients with seizures after CVD 25 (33%) have been with ischemia, whereas 47 (67%) with hemorrhage. Conclusion: CVD present fairly frequent cause of symptomatic epilepsies among patients treated in the clinic of Neurology at UCC (about 10%). The biggest number of patients with epilepsy after CVD was with intracerebral hemorrhage. PMID:25685086

  17. Down-regulation of monocarboxylate transporter 1 (MCT1) gene expression in the colon of piglets is linked to bacterial protein fermentation and pro-inflammatory cytokine-mediated signalling.

    Science.gov (United States)

    Villodre Tudela, Carmen; Boudry, Christelle; Stumpff, Friederike; Aschenbach, Jörg R; Vahjen, Wilfried; Zentek, Jürgen; Pieper, Robert

    2015-02-28

    The present study investigated the influence of bacterial metabolites on monocarboxylate transporter 1 (MCT1) expression in pigs using in vivo, ex vivo and in vitro approaches. Piglets (n 24) were fed high-protein (26 %) or low-protein (18 %) diets with or without fermentable carbohydrates. Colonic digesta samples were analysed for a broad range of bacterial metabolites. The expression of MCT1, TNF-α, interferon γ (IFN-γ) and IL-8 was determined in colonic tissue. The expression of MCT1 was lower and of TNF-α and IL-8 was higher with high-protein diets (P< 0·05). MCT1 expression was positively correlated with l-lactate, whereas negatively correlated with NH₃ and putrescine (P< 0·05). The expression of IL-8 and TNF-α was negatively correlated with l-lactate and positively correlated with NH₃ and putrescine, whereas the expression of IFN-γ was positively correlated with histamine and 4-ethylphenol (P< 0·05). Subsequently, porcine colonic tissue and Caco-2 cells were incubated with Na-butyrate, NH₄Cl or TNF-α as selected bacterial metabolites or mediators of inflammation. Colonic MCT1 expression was higher after incubation with Na-butyrate (P< 0·05) and lower after incubation with NH₄Cl or TNF-α (P< 0·05). Incubation of Caco-2 cells with increasing concentrations of these metabolites confirmed the up-regulation of MCT1 expression by Na-butyrate (linear, P< 0·05) and down-regulation by TNF-α and NH₄Cl (linear, P< 0·05). The high-protein diet decreased the expression of MCT1 in the colon of pigs, which appears to be linked to NH₃- and TNF-α-mediated signalling.

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

    Directory of Open Access Journals (Sweden)

    Anne-Cécile eBoulay

    2015-02-01

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

  19. Polymorphic membrane protein (PMP) 20 and PMP 21 of Chlamydia pneumoniae induce proinflammatory mediators in human endothelial cells in vitro by activation of the nuclear factor-kappaB pathway.

    Science.gov (United States)

    Niessner, Alexander; Kaun, Christoph; Zorn, Gerlinde; Speidl, Walter; Türel, Zeynep; Christiansen, Gunna; Pedersen, Anna-Sofie; Birkelund, Svend; Simon, Susan; Georgopoulos, Apostolos; Graninger, Wolfgang; de Martin, Rainer; Lipp, Joachim; Binder, Bernd R; Maurer, Gerald; Huber, Kurt; Wojta, Johann

    2003-07-01

    We tested whether polymorphic membrane proteins (PMPs) of Chlamydia pneumoniae might play a role in triggering an inflammatory response in human endothelial cells. Of 15 purified, recombinant chlamydial PMPs tested, 2 (PMP 20 and PMP 21) dose-dependently increased the production of the inflammatory mediators interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1), in cultured human endothelial cells; production of IL-8 was also increased. When endothelial cells were infected by live C. pneumoniae, an increase in the production of IL-6, IL-8, and MCP-1 was seen. We used adenovirus-induced overexpression of IkappaBalpha-an inhibitor of nuclear factor (NF)-kappaB-to demonstrate that PMP 20 and PMP 21 increase the production of IL-6 and MCP-1 in human endothelial cells by activation of the NF-kappaB pathway, because, in cells overexpressing IkappaBalpha, treatment with the respective PMP did not result in increased production of IL-6 and MCP-1. Thus, C. pneumoniae could, by interactions of its PMPs with the endothelium, contribute to the process of vascular injury during the development and progression of atherosclerotic lesions.

  20. NIRS-based noninvasive cerebrovascular regulation assessment

    Science.gov (United States)

    Miller, S.; Richmond, I.; Borgos, J.; Mitra, K.

    2016-03-01

    Alterations to cerebral blood flow (CBF) have been implicated in diverse neurological conditions, including mild traumatic brain injury, microgravity induced intracranial pressure (ICP) increases, mild cognitive impairment, and Alzheimer's disease. Near infrared spectroscopy (NIRS)-measured regional cerebral tissue oxygen saturation (rSO2) provides an estimate of oxygenation of the interrogated cerebral volume that is useful in identifying trends and changes in oxygen supply to cerebral tissue and has been used to monitor cerebrovascular function during surgery and ventilation. In this study, CO2-inhalation-based hypercapnic breathing challenges were used as a tool to simulate CBF dysregulation, and NIRS was used to monitor the CBF autoregulatory response. A breathing circuit for the selective administration of CO2-compressed air mixtures was designed and used to assess CBF regulatory responses to hypercapnia in 26 healthy young adults using non-invasive methods and real-time sensors. After a 5 or 10 minute baseline period, 1 to 3 hypercapnic challenges of 5 or 10 minutes duration were delivered to each subject while rSO2, partial pressure of end tidal CO2 (PETCO2), and vital signs were continuously monitored. Change in rSO2 measurements from pre- to intrachallenge (ΔrSO2) detected periods of hypercapnic challenges. Subjects were grouped into three exercise factor levels (hr/wk), 1: 0, 2:>0 and 10. Exercise factor level 3 subjects showed significantly greater ΔrSO2 responses to CO2 challenges than level 2 and 1 subjects. No significant difference in ΔPETCO2 existed between these factor levels. Establishing baseline values of rSO2 in clinical practice may be useful in early detection of CBF changes.

  1. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    Energy Technology Data Exchange (ETDEWEB)

    Erez, Neta, E-mail: netaerez@post.tau.ac.il [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Glanz, Sarah [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Raz, Yael [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Obstetrics and Gynecology, LIS Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Avivi, Camilla [Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Barshack, Iris [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

    2013-08-02

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  2. Placental ischemia-induced increases in brain water content and cerebrovascular permeability: role of TNF-α.

    Science.gov (United States)

    Warrington, Junie P; Drummond, Heather A; Granger, Joey P; Ryan, Michael J

    2015-12-01

    Cerebrovascular complications and increased risk of encephalopathies are characteristic of preeclampsia and contribute to 40% of preeclampsia/eclampsia-related deaths. Circulating tumor necrosis factor-α (TNF-α) is elevated in preeclamptic women, and infusion of TNF-α into pregnant rats mimics characteristics of preeclampsia. While this suggests that TNF-α has a mechanistic role to promote preeclampsia, the impact of TNF-α on the cerebral vasculature during pregnancy remains unclear. We tested the hypothesis that TNF-α contributes to cerebrovascular abnormalities during placental ischemia by first infusing TNF-α in pregnant rats (200 ng/day ip, from gestational day 14 to 19) at levels to mimic those reported in preeclamptic women. TNF-α increased mean arterial pressure (MAP, P blood-brain barrier (BBB) permeability in the anterior cerebrum or posterior cerebrum. We then assessed the role of endogenous TNF-α in mediating these abnormalities in a model of placental ischemia induced by reducing uterine perfusion pressure followed by treatment with the soluble TNF-α receptor (etanercept, 0.8 mg/kg sc) on gestational day 18. Etanercept reduced placental ischemia-mediated increases in MAP, anterior brain water content (P permeability (202 ± 44% in placental ischemic rats to 101 ± 28% of normal pregnant rats). Our results indicate that TNF-α mechanistically contributes to cerebral edema by increasing BBB permeability and is an underlying factor in the development of cerebrovascular abnormalities associated with preeclampsia complicated by placental ischemia.

  3. Risk factors of cerebrovascular diseases and their intervention and management

    Directory of Open Access Journals (Sweden)

    En XU

    2015-01-01

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

  4. Interleukin 17 induces cartilage collagen breakdown: novel synergistic effects in combination with proinflammatory cytokines

    OpenAIRE

    Koshy, P.; Henderson, N; Logan, C.; Life, P; Cawston, T; Rowan, A

    2002-01-01

    Objective: To investigate whether interleukin 17 (IL17), derived specifically from T cells, can promote type II collagen release from cartilage. The ability of IL17 to synergise with other proinflammatory mediators to induce collagen release from cartilage, and what effect anti-inflammatory agents had on this process, was also assessed.

  5. 7-T MRI in Cerebrovascular Diseases : Challenges to Overcome and Initial Results

    NARCIS (Netherlands)

    Harteveld, Anita A; van der Kolk, Anja G; Zwanenburg, Jaco J M; Luijten, Peter R; Hendrikse, J

    2016-01-01

    Magnetic resonance imaging (MRI) plays a key role in the investigation of cerebrovascular diseases. Compared with computed tomography (CT) and digital subtraction angiography (DSA), its advantages in diagnosing cerebrovascular pathology include its superior tissue contrast, its ability to visualize

  6. A meta-analysis of cerebrovascular disease and hyperhomocysteinaemia

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  7. Effects of Dietary Nitrates on Systemic and Cerebrovascular Hemodynamics

    Directory of Open Access Journals (Sweden)

    Vernon Bond

    2013-01-01

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

  8. Cerebrovascular Reactivity in Complex Diagnostics of Vertebrobasilar Insufficiency

    Directory of Open Access Journals (Sweden)

    Goydenko V. S.

    2016-12-01

    Full Text Available The article presents the results of the assessment of cerebrovascular reactivity parameters due to transcranial Doppler sonography in 104 patients (62 women and 42 men with spondilogenic vertebrobasilar insufficiency. Mean age of patients was 42.9±12.2 years. It was found that the assessment of cerebrovascular reactivity and type of response to functional loading tests allows to confirm vertebrobasilar stage insufficiency, to determine the activity of various regulatory mechanisms of compensation of cerebral circulation and adaptation reserve of the cerebral vascular system.

  9. Role of proinflammatory cytokines on lipopolysaccharide-induced phase shifts in locomotor activity circadian rhythm.

    Science.gov (United States)

    Leone, M Juliana; Marpegan, Luciano; Duhart, José M; Golombek, Diego A

    2012-07-01

    We previously reported that early night peripheral bacterial lipopolysaccharide (LPS) injection produces phase delays in the circadian rhythm of locomotor activity in mice. We now assess the effects of proinflammatory cytokines on circadian physiology, including their role in LPS-induced phase shifts. First, we investigated whether differential systemic induction of classic proinflammatory cytokines could explain the time-specific behavioral effects of peripheral LPS. Induction levels for plasma interleukin (IL)-1α, IL-1β, IL-6, or tumor necrosis factor (TNF)-α did not differ between animals receiving a LPS challenge in the early day or early night. We next tested the in vivo effects of central proinflammatory cytokines on circadian physiology. We found that intracerebroventricular (i.c.v.) delivery of TNF-α or interleukin IL-1β induced phase delays on wheel-running activity rhythms. Furthermore, we analyzed if these cytokines mediate the LPS-induced phase shifts and found that i.c.v. administration of soluble TNF-α receptor (but not an IL-1β antagonistic) prior to LPS stimulation inhibited the phase delays. Our work suggests that the suprachiasmatic nucleus (SCN) responds to central proinflammatory cytokines in vivo, producing phase shifts in locomotor activity rhythms. Moreover, we show that the LPS-induced phase delays are mediated through the action of TNF-α at the central level, and that systemic induction of proinflammatory cytokines might be necessary, but not sufficient, for this behavioral outcome.

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

    Directory of Open Access Journals (Sweden)

    Sonia eDuchemin

    2012-08-01

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

  11. The Cerebrovascular Disease and Nutritional State. Enfermedad cerebrovascular y estado nutricional

    Directory of Open Access Journals (Sweden)

    Mayelin Blanco Suárez

    2007-05-01

    Full Text Available Background: It is recognized the importance of malnutrition as a cause of morbidity and mortality in medical and surgical affections. The nutritional assessment of the patient should be based on a correct evaluation of different aspects. Objective: To assess the nutritional state of patients affected by cerebrovascular diseases in its ischemic form and the incidence of complications and deaths. Methods: A randomized simple and open clinical trial which is also prospective and longitudinal, not controlled by placebos that included 80 patients with a tomographed-clinical diagnosis of cerebral infarction admitted at the Higher Institute of Military Medicine during 2005. Clinical and dietary record, weight, size, daily assessments of the immunological performance by means of peripheral count of lymphocytes were analyzed. Results: Out of the total, 90 per cent of the patients had a weight loss lesser than 10 % of the ideal weight and, the 10% made evident a discrete increasing of weight. Patients with complications presented higher per cent of loss of weight and higher figures of urinary nitrogen. The higher per cent of loss of weight and the lowest lymphocytes count were found in patients with septic complications. An abbaissement in adequate nutritional parameters was found in deceased patients. Significant differences in the report of the initial malnourished patient’s complication existed. Conclusions: It was evident the relationship between the evolution of the cerebrovascular disease and the nutritional state which is conditioned by the appearance of complications with emphasis on sepsis. That’s why it is necessary to pay special attention to the nutrition of patients with neuroictus.
    Fundamento: Se reconoce la trascendencia de la desnutrición como causa de morbilidad y mortalidad en afecciones médicas y quir

  12. Evento cerebrovascular isquémico en el adulto joven

    Directory of Open Access Journals (Sweden)

    Verónica Leandro-Sandí

    2013-09-01

    Full Text Available El evento cerebrovascular isquémico es un desorden multifactorial, en el que contribuyen factores genéticos y ambientales. A pesar de que se reconoce un aumento del riesgo de eventos cerebrovasculares cuando existe una historia familiar positiva (de hasta un 75% en ciertos estudios, no se conoce la contribución exacta que tiene la genética en el desarrollo de eventos cerebrales isquémicos en el paciente joven. El papel que desempeña la predisposición genética sobre la ocurrencia de estos eventos, difiere según la edad y el tipo de evento. Los factores genéticos se conjugan con los factores de riesgo convencionales, como hipertensión arterial, diabetes y niveles de homocisteína, que a su vez interactúan con el ambiente en el desarrollo de aterosclerosis. La homocisteína por sí sola, ha sido considerada un factor aterogénico en enfermedades cardiovasculares y cerebrovasculares. Se refiere el caso de un paciente de 49 años conocido sano, quien presenta un evento cerebrovascular isquémico de la circulación cerebral anterior, con un valor en la escala para derrame del Instituto Nacional de Salud de 7 puntos al ingreso y una mutación heterocigota del gen de la metiltetrahidrofolato reductasa (región de mutación C677T.

  13. NSAIDs and cardiovascular drugs in neurodegenerative and cerebrovascular diseases

    NARCIS (Netherlands)

    M.D.M. Haag (Mendel)

    2009-01-01

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

  14. Myocardial stress in patients with acute cerebrovascular events

    DEFF Research Database (Denmark)

    Jespersen, Christian M; Fischer Hansen, Jørgen

    2008-01-01

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

  15. Depression as the cause and consequence of cerebrovascular diseases

    Directory of Open Access Journals (Sweden)

    Rabi-Žikić Tamara

    2007-01-01

    Full Text Available Inbtroduction: Recent epidemiological, clinical, neuroimaging and neuropathological studies have reported substantial evidence on the complex interactive relationships between depression and cerebrovascular diseases, especially in older populations, and plausible explanations of the etiopathogenetic mechanisms in both directions have been proposed. Poststroke depression Although there is no general consensus regarding its prevalence, it is widely accepted that major depression after stroke is common and that it should be recognized as a key factor in rehabilitation and outcome following stroke. Vascular depression The "vascular depression" hypothesis presupposes that late-onset depression may often result from vascular damage to frontal-subcortical circuits implicated in mood regulation. This concept has stimulated many researches and the obtained results support the proposed hypothesis. Depression as a stroke risk factor Recent large studies have emphasized the role of depression per se in the development of subsequent stroke. Mechanisms proposed to explain the increased risk of cerebrovascular diseases in depressed patients There are a number of plausible mechanisms that could explain why depression may increase the risk of subsequent cerebrovascular disease, the most important being sympathoadrenal hyperactivity, platelet activation, an increase in inflammatory cytokines and an increased risk of arrhythmias. Conclusion: Thorough clinical examinations determining the conventional stroke risk factors in the population with depression, as well as management of depression as part of the overall measures for the reduction of cerebrovascular risk factors are of utmost importance.

  16. Cerebrovascular angiotensin AT1 receptor regulation in cerebral ischemia

    DEFF Research Database (Denmark)

    Edvinsson, L.

    2008-01-01

    The mechanism behind the positive response to the inhibition of the angiotensin II receptor AT(1) in conjunction with stroke is elusive. Here we demonstrate that cerebrovascular AT(1) receptors show increased expression (upregulation) after cerebral ischemia via enhanced translation. This enhanced...

  17. Cerebrovascular response to acute metabolic acidosis in humans.

    NARCIS (Netherlands)

    Ven, M.T.P. van de; Colier, W.N.J.M.; Kersten, B.T.P.; Oeseburg, B.; Folgering, H.T.M.

    2003-01-01

    OBJECTIVES: Evaluation of the cerebrovascular response (delta CBV/delta PaCO2) during baseline metabolic conditions and acute metabolic acidosis. METHODS: 15 healthy subjects, 5 m, 10 f, 56 +/- 10 yrs were investigated. For acidification, NH4Cl was given orally. CBV was measured using Near Infrared

  18. Cerebrovascular contributions to aging and Alzheimer's disease in Down syndrome.

    Science.gov (United States)

    Wilcock, Donna M; Schmitt, Frederick A; Head, Elizabeth

    2016-05-01

    Down syndrome (DS) is a common cause of intellectual disability and is also associated with early age of onset of Alzheimer's disease (AD). Due to an extra copy of chromosome 21, most adults over 40years old with DS have beta-amyloid plaques as a result of overexpression of the amyloid precursor protein. Cerebrovascular pathology may also be a significant contributor to neuropathology observed in the brains of adults with DS. This review describes the features of cardiovascular dysfunction and cerebrovascular pathology in DS that may be modifiable risk factors and thus targets for interventions. We will describe cerebrovascular pathology, the role of co-morbidities, imaging studies indicating vascular pathology and the possible consequences. It is clear that our understanding of aging and AD in people with DS will benefit from further studies to determine the role that cerebrovascular dysfunction contributes to cognitive health. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.

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

    Science.gov (United States)

    Bećarević, Mirjana; Ignjatović, Svetlana

    2016-10-01

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

  20. Cerebrovascular risk factors and clinical classification of strokes.

    Science.gov (United States)

    Pinto, Antonio; Tuttolomondo, Antonino; Di Raimondo, Domenico; Fernandez, Paola; Licata, Giuseppe

    2004-08-01

    Cerebrovascular risk represents a progressive and evolving concept owing to the particular distribution of risk factors in patients with ischemic stroke and in light of the newest stroke subtype classifications that account for pathophysiological, instrumental, and clinical criteria. Age represents the strongest nonmodifiable risk factor associated with ischemic stroke, while hypertension constitutes the most important modifiable cerebrovascular risk factor, confirmed by a host of epidemiological data and by more recent intervention trials of primary (HOT, Syst-Eur, LIFE) and secondary (PROGRESS) prevention of stroke in hypertensive patients. To be sure, a curious relationship exists between stroke and diabetes. Although the Framingham Study, The Honolulu Heart Program, and a series of Finnish studies reported a linear relationship between improved glucose metabolism and cerebral ischemia, the clinical and prognostic profile of diabetic patients with ischemic stroke remains to be fully understood. Our group, on the basis of TOAST classification--a diagnostic classification of ischemic stroke developed in 1993 that distinguishes five different clinical subtypes of ischemic stroke: large-artery atherosclerosis (LAAS), cardioembolic infarct (CEI), lacunar infarct (LAC), stroke of other determined origin (ODE), and stroke of undetermined origin (UDE), and now extensively used in clinical and scientific context--analysed the prevalence of cerebrovascular risk factors and the distribution of TOAST subtypes in more 300 patients with acute ischemic stroke in two consecutives studies that reported the significant association between diabetes and the lacunar subtype and a better clinical outcome for diabetic patients, most likely related to the higher prevalence of the lacunar subtype. Well-confirmed are the roles of cigarette smoking, atrial fibrillation, and asymptomatic carotid stenosis as cerebrovascular risk factors. Particularly interesting seems to be the function of

  1. [Interleukins network in rheumatoid arthritis pathophysiology: beyond proinflammatory cytokines].

    Science.gov (United States)

    Sánchez-Ramón, Silvia; López-Longo, Francisco Javier; Carreño, Luis

    2011-03-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovitis and progressive destruction of the joint cartilage and underlying bone, together with diverse extra-articular manifestations. Cytokines act as soluble effector mediators of the inflammatory process. Therapeutic neutralization with monoclonal antibodies against the pro-inflammatory cytokines TNF-alpha and interleukin 1 (IL-1) has shown a clear efficacy on inflammation and clinical manifestations of RA, although a percentage of patients do not respond. This review covers new relevant cytokines in the RA physiopathology and potential biomarkers of inflammation. The current challenge is to develop biomarkers that enable an earlier diagnosis, as well as prognostic markers and new therapeutic candidates. Combined administration of several of these cytokines could eventually address a personalized treatment approach for each patient.

  2. Resveratrol preserves cerebrovascular density and cognitive function in aging mice

    Directory of Open Access Journals (Sweden)

    Charlotte A Oomen

    2009-12-01

    Full Text Available Resveratrol, a natural polyphenol abundant in grapes and red wine, has been reported to exert numerous beneficial health effects. Among others, acute neuroprotective effects of resveratrol have been reported in several models of neurodegeneration, both in vitro and in vivo. In the present study we examined the neuroprotective effects of long term dietary supplementation with resveratrol in mice on behavioral, neurochemical and cerebrovascular level. We report a preserved cognitive function in resveratrol treated aging mice, as shown by an enhanced acquisition of a spatial Y-maze task. This was paralleled by a higher microvascular density and a lower number of microvascular abnormalities in comparison to aging non-treated control animals. We found no effects of resveratrol supplementation on cholinergic cell number or fiber density. The present findings support the hypothesis that resveratrol exerts beneficial effects on the brain by maintaining cerebrovascular health. Via this mechanism resveratrol can contribute to the preservation of cognitive function during aging.

  3. Gray Cerebrovascular Image Skeleton Extraction Algorithm Using Level Set Model

    Directory of Open Access Journals (Sweden)

    Jian Wu

    2010-06-01

    Full Text Available The ambiguity and complexity of medical cerebrovascular image makes the skeleton gained by conventional skeleton algorithm discontinuous, which is sensitive at the weak edges, with poor robustness and too many burrs. This paper proposes a cerebrovascular image skeleton extraction algorithm based on Level Set model, using Euclidean distance field and improved gradient vector flow to obtain two different energy functions. The first energy function controls the  obtain of topological nodes for the beginning of skeleton curve. The second energy function controls the extraction of skeleton surface. This algorithm avoids the locating and classifying of the skeleton connection points which guide the skeleton extraction. Because all its parameters are gotten by the analysis and reasoning, no artificial interference is needed.

  4. Etiological and clinical analysis on 220 children with cerebrovascular diseases

    Directory of Open Access Journals (Sweden)

    Zhi-hong TANG

    2014-03-01

    Full Text Available Etiological and clinical analyses of 220 children with cerebrovascular diseases were retrospectively analyzed. One hundred and forty-nine cases (67.73% were male, and 71 cases (32.27% were female. There were 186 cases (84.55% of patients to be found with clear causes, most of which were arteriovenous malformation (80/220, 36.36%, traumatic brain injury (38/220, 17.27%, intracranial infection (15/220, 6.82% , intracranial aneurysm (13/220, 5.91% , delayed vitamin K deficiency (12/220, 5.45% , congenital heart disease (9/220, 4.09% and cavernous malformation (7/220, 3.18%. The etiological and clinical features of children cerebrovascular diseases are distinct, and timely diagnosis and treatment will help to improve patients' prognosis. doi: 10.3969/j.issn.1672-6731.2014.03.017

  5. Diamox-enhanced brain SPECT in cerebrovascular diseases

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yun Young [College of Medicine, Hanyang University, Seoul (Korea, Republic of)

    2007-04-15

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

  6. Microbubbles as drug delivery systems in cerebrovascular diseases.

    Science.gov (United States)

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

    2009-11-01

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

  7. Cerebrovascular disturbances in children with Arnold-Kiary anomaly I

    Directory of Open Access Journals (Sweden)

    Kozlitina T.N.

    2012-03-01

    Full Text Available Data of diagnostics of cerebrovascular disorders in craniovertebral passage due to Arnold — Kiary anomaly I have been considered. Clinical picture of the disease in different age groups has been represented. Condition of extra- and intracranial part of vertebral arteries and venous plexuses of the cervical part of vertebral column and craniovertebral passage, pathological asymmetry of the blood flow have been estimated. Efficacy of conservative and surgical treatment has been compared.

  8. Digital subtraction angiography in pediatric cerebrovascular occlusive disease

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-08-01

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

  9. EFFECT OF ACUPUNCTURE ON THE INTELLIGENCE OF CEREBROVASCULAR DEMENTIA PATIENT

    Institute of Scientific and Technical Information of China (English)

    陈邦国

    2000-01-01

    Cerebrovascular dementia is a common disese in the old and medium-aged people. Its morbidity constitutes about 10-20% of all the dementia patients and results mainly from all-round decline of the brain function due to cerebral atheroscleorsis and cerebral infarction. The author of the present paper adopted acupuncture therapy to; treat this kind of disease and observed its effect on dementia patient's intelligence. Here is the report.

  10. HIGH SENSITIVE C-REACTIVE PROTEIN IN CEREBROVASCULAR ISCHEMIA

    OpenAIRE

    Padmalatha; Neeraja

    2016-01-01

    BACKGROUND Cerebrovascular ischemia is recognized as a major health problem, which causes significant morbidity and mortality. The main pathophysiology of ischemic stroke is atherosclerosis of cerebral vessels. Hs-CRP is a sensitive marker of inflammation tissue injury in the arterial wall, which contributes to atherosclerosis. In this study, we aim to investigate the association of hs-CRP in patients with ischemic stroke and to correlate hs-CRP levels with possible risk facto...

  11. A novel pro-inflammatory protein of Streptococcus suis 2 induces the Toll-like receptor 2-dependent expression of pro-inflammatory cytokines in RAW 264.7 macrophages via activation of ERK1/2 pathway.

    Science.gov (United States)

    Zhang, Qiang; Yang, Yujie; Yan, Shuxian; Liu, Jiantao; Xu, Zhongmin; Yu, Junping; Song, Yajing; Zhang, Anding; Jin, Meilin

    2015-01-01

    Streptococcus suis 2 is an important swine pathogen and an emergent zoonotic pathogen. Excessive inflammation caused by S. suis is responsible for the high levels of early mortality observed in septic shock-like syndrome cases. However, the mechanisms through which S. suis 2 (SS2) causes excessive inflammation remain unclear. Thus, this study aimed to identify novel pro-inflammatory mediators that play important roles in the development of therapies against SS2 infection. In this study, the novel pro-inflammatory protein HP0459, which was encoded by the SSUSC84_0459 gene, was discovered. The stimulation of RAW 264.7 macrophages with recombinant HP0459 protein induced the expression of pro-inflammatory cytokines (IL-1β, MCP-1 and TNF-α). Compared with the wild-type (WT) strain, the isogenic knockout of HP0459 in SS2 led to reduced production of pro-inflammatory cytokines in RAW264.7 macrophages and in vivo. The pro-inflammatory activity of HP0459 was significantly reduced by an antibody against Toll-like receptor 2 (TLR2) in RAW264.7 macrophages and was lower in TLR2-deficient (TLR2-/-) macrophages than in WT macrophages. Furthermore, specific inhibitors of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathways significantly decreased the HP0459-induced pro-inflammatory cytokine production, and a western blot assay showed that HP0459 stimulation induced the activation of the ERK1/2 pathway. Taken together, our data indicate that HP0459 is a novel pro-inflammatory mediator of SS2 and induces TLR2-dependent pro-inflammatory activity in RAW264.7 macrophages through the ERK1/2 pathway.

  12. Antioxidants and Dementia Risk: Consideration through a Cerebrovascular Perspective

    Directory of Open Access Journals (Sweden)

    Virginie Lam

    2016-12-01

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

  13. Cerebral blood flow in sickle cell cerebrovascular disease

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-05-01

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

  14. Autumn Weather and Winter Increase in Cerebrovascular Disease Mortality

    LENUS (Irish Health Repository)

    McDonagh, R

    2016-11-01

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

  15. Lipoprotein receptor-related protein-1 mediates amyloid-beta-mediated cell death of cerebrovascular cells.

    NARCIS (Netherlands)

    Wilhelmus, M.M.; Otte-Holler, I.; Triel, J.J. van; Veerhuis, R.; Maat-Schieman, M.L.; Bu, G.; Waal, R.M.W. de; Verbeek, M.M.

    2007-01-01

    Inefficient clearance of A beta, caused by impaired blood-brain barrier crossing into the circulation, seems to be a major cause of A beta accumulation in the brain of late-onset Alzheimer's disease patients and hereditary cerebral hemorrhage with amyloidosis Dutch type. We observed association of r

  16. Sleep duration, cardiovascular disease, and proinflammatory biomarkers

    Directory of Open Access Journals (Sweden)

    Grandner MA

    2013-07-01

    Full Text Available Michael A Grandner,1,2 Megan R Sands-Lincoln,3 Victoria M Pak,2,4 Sheila N Garland1,5 1Behavioral Sleep Medicine Program, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, PA, USA; 2Center for Sleep and Circadian Neurobiology, University of Pennsylvania, PA, USA; 3Center for Evidence Based Medicine, Elsevier Inc, Philadelphia, PA, USA; 4Division of Sleep Medicine, Perelman School of Medicine, University of Pennsylvania, PA, USA; 5Department of Family Medicine and Community Health, Perelman School of Medicine, University of Pennsylvania, PA, USA Abstract: Habitual sleep duration has been associated with cardiometabolic disease, via several mechanistic pathways, but few have been thoroughly explored. One hypothesis is that short and/or long sleep duration is associated with a proinflammatory state, which could increase risk for cardiovascular and metabolic diseases. This hypothesis has been largely explored in the context of experimental sleep deprivation studies which have attempted to demonstrate changes in proinflammatory markers following acute sleep loss in the laboratory. Despite the controlled environment available in these studies, samples tend to lack generalization to the population at large and acute sleep deprivation may not be a perfect analog for short sleep. To address these limitations, population based studies have explored associations between proinflammatory markers and habitual sleep duration. This review summarizes what is known from experimental and cross-sectional studies about the association between sleep duration, cardiovascular disease, and proinflammatory biomarkers. First, the association between sleep duration with both morbidity and mortality, with a focus on cardiovascular disease, is reviewed. Then, a brief review of the potential role of proinflammatory markers in cardiovascular disease is presented. The majority of this review details specific findings related to specific

  17. Respiratory dysfunction and proinflammatory chemokines in the pneumonia virus of mice (PVM) model of viral bronchiolitis.

    Science.gov (United States)

    Bonville, Cynthia A; Bennett, Nicholas J; Koehnlein, Melissa; Haines, Deborah M; Ellis, John A; DelVecchio, Alfred M; Rosenberg, Helene F; Domachowske, Joseph B

    2006-05-25

    We explore relationships linking clinical symptoms, respiratory dysfunction, and local production of proinflammatory chemokines in the pneumonia virus of mice (PVM) model of viral bronchiolitis. With a reduced inoculum of this natural rodent pathogen, we observe virus clearance by day 9, while clinical symptoms and respiratory dysfunction persist through days 14 and 17 postinoculation, respectively. Via microarray and ELISA, we identify expression profiles of proinflammatory mediators MIP-1alpha, MCP-1, and MIP-2 that correlate with persistent respiratory dysfunction. MIP-1alpha is localized in bronchial epithelium, which is also the major site of PVM replication. Interferon-gamma was detected in lung tissue, but at levels that do not correlate with respiratory dysfunction. Taken together, we present a modification of our pneumovirus infection model that results in improved survival and data that stand in support of a connection between local production of specific mediators and persistent respiratory dysfunction in the setting of acute viral bronchiolitis.

  18. Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer's Coordinating Centre.

    Science.gov (United States)

    Toledo, Jon B; Arnold, Steven E; Raible, Kevin; Brettschneider, Johannes; Xie, Sharon X; Grossman, Murray; Monsell, Sarah E; Kukull, Walter A; Trojanowski, John Q

    2013-09-01

    Cerebrovascular disease and vascular risk factors are associated with Alzheimer's disease, but the evidence for their association with other neurodegenerative disorders is limited. Therefore, we compared the prevalence of cerebrovascular disease, vascular pathology and vascular risk factors in a wide range of neurodegenerative diseases and correlate them with dementia severity. Presence of cerebrovascular disease, vascular pathology and vascular risk factors was studied in 5715 cases of the National Alzheimer's Coordinating Centre database with a single neurodegenerative disease diagnosis (Alzheimer's disease, frontotemporal lobar degeneration due to tau, and TAR DNA-binding protein 43 immunoreactive deposits, α-synucleinopathies, hippocampal sclerosis and prion disease) based on a neuropathological examination with or without cerebrovascular disease, defined neuropathologically. In addition, 210 'unremarkable brain' cases without cognitive impairment, and 280 cases with pure cerebrovascular disease were included for comparison. Cases with cerebrovascular disease were older than those without cerebrovascular disease in all the groups except for those with hippocampal sclerosis. After controlling for age and gender as fixed effects and centre as a random effect, we observed that α-synucleinopathies, frontotemporal lobar degeneration due to tau and TAR DNA-binding protein 43, and prion disease showed a lower prevalence of coincident cerebrovascular disease than patients with Alzheimer's disease, and this was more significant in younger subjects. When cerebrovascular disease was also present, patients with Alzheimer's disease and patients with α-synucleinopathy showed relatively lower burdens of their respective lesions than those without cerebrovascular disease in the context of comparable severity of dementia at time of death. Concurrent cerebrovascular disease is a common neuropathological finding in aged subjects with dementia, is more common in Alzheimer

  19. Complement-dependent Proinflammatory Properties of the Alzheimer's Disease β-Peptide

    OpenAIRE

    Bradt, Bonnie M.; Kolb, William P.; Cooper, Neil R.

    1998-01-01

    Large numbers of neuritic plaques (NP), largely composed of a fibrillar insoluble form of the β-amyloid peptide (Aβ), are found in the hippocampus and neocortex of Alzheimer's disease (AD) patients in association with damaged neuronal processes, increased numbers of activated astrocytes and microglia, and several proteins including the components of the proinflammatory complement system. These studies address the hypothesis that the activated complement system mediates the cellular changes th...

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

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young Sik; Baek, Seung Yon; Rhee, Chung Sik; Kim, Hee Seup [Ewha Womans University College of Medicine, Seoul (Korea, Republic of)

    1984-06-15

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

  1. Tratamiento de Terapia Ocupacional en el accidente cerebrovascular

    OpenAIRE

    Domingo García, AM

    2006-01-01

    RESUMENEntre los muchos pacientes que necesitan tratamiento rehabilitador en Terapia Ocupacional están los que en la edad adulta han sufrido un accidente cerebrovascular.Uno de los factores de riesgo asociados con más frecuencia a las alteraciones del sistema nervioso central es el progresivo envejecimiento de la población, debido a esto orientaré el siguiente artículo hacia la intervención sobre la población geriátrica.La Terapia Ocupacional ofrece un tratamiento global que abarca las áreas ...

  2. Change of scaling-induced proinflammatory cytokine on the clinical efficacy of periodontitis treatment.

    Science.gov (United States)

    Shyu, Kou-Gi; Choy, Cheuk-Sing; Wang, Daniel Chung-Lang; Huang, Wei-Chen; Chen, Shyuan-Yow; Chen, Chien-Hsun; Lin, Che-Tong; Chang, Chao-Chien; Huang, Yung-Kai

    2015-01-01

    Proinflammatory cytokines are key inflammatory mediators in periodontitis. This study aimed to investigate the relationship between proinflammatory cytokines in saliva and periodontal status. To investigate the usefulness of cytokines in the therapeutic approach for periodontal disease, the relationship between stimulated cytokine changes and the periodontitis treatment outcome was investigated in this study. Saliva was obtained from 22 patients diagnosed by dentists as having chronic periodontitis. The proinflammatory cytokine (interleukin-1α (IL-1α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor α (TNF-α), and tumor necrosis factor β (TNF-β)) levels were determined using a commercially available kit. The IL-1β and IL-6 levels increased, whereas the TNF-β levels decreased with the severity of periodontitis (4 mm pocket percentage). Poststimulation IL-1α, IL-6, and IL-8 levels were higher in patients who had an improved treatment outcome. The differences of IL-6 levels (cut point: 0.05 μg/g) yielded a sensitivity and specificity of 90.0% and 81.82%, respectively, for predicting the periodontitis treatment outcome. Among the proinflammatory cytokines, stimulated IL-6 was an excellent marker for predicting the periodontitis treatment outcome.

  3. Lipin-2 reduces proinflammatory signaling induced by saturated fatty acids in macrophages.

    Science.gov (United States)

    Valdearcos, Martín; Esquinas, Esperanza; Meana, Clara; Peña, Lucía; Gil-de-Gómez, Luis; Balsinde, Jesús; Balboa, María A

    2012-03-30

    Lipin-2 is a member of the lipin family of enzymes, which are key effectors in the biosynthesis of lipids. Mutations in the human lipin-2 gene are associated with inflammatory-based disorders; however, the role of lipin-2 in cells of the immune system remains obscure. In this study, we have investigated the role of lipin-2 in the proinflammatory action of saturated fatty acids in murine and human macrophages. Depletion of lipin-2 promotes the increased expression of the proinflammatory genes Il6, Ccl2, and Tnfα, which depends on the overstimulation of the JNK1/c-Jun pathway by saturated fatty acids. In contrast, overexpression of lipin-2 reduces the release of proinflammatory factors. Metabolically, the absence of lipin-2 reduces the cellular content of triacylglycerol in saturated fatty acid-overloaded macrophages. Collectively, these studies demonstrate a protective role for lipin-2 in proinflammatory signaling mediated by saturated fatty acids that occurs concomitant with an enhanced cellular capacity for triacylglycerol synthesis. The data provide new insights into the role of lipin-2 in human and murine macrophage biology and may open new avenues for controlling the fatty acid-related low grade inflammation that constitutes the sine qua non of obesity and associated metabolic disorders.

  4. Inhibition of lovastatin on proliferation and expression of proinflammatory cytokines in cultured human glomerular mesangial cells

    Institute of Scientific and Technical Information of China (English)

    李航; 李学旺; 段琳; 李晨红

    2003-01-01

    Objective To study the effects and mechanism of lovastatin on cell proliferation and expression of proinflammatory cytokines in cultured human glomerular mesangial cells.Methods The influence of lovastatin on HMC proliferation was evaluated with 3H-thymidine incorporation. mRNA expression of proinflammatory cytokines (IL-1β, IL-6, TNF-α, and MCP-1) and activation of NF-κB of HMC were measured using Reverse transcription-polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA) respectively.Results Lovastatin was found to have inhibitory effects on human mesangial cell (HMC) proliferation and lipopolysaccharide (LPS)-mediated human mesangine cell HMC mRNA expression of proinflammatory cytokines via activation of NF-κB. The effect of lovstatin on HMC could be prevented when the mevalonate and farnesol were added to the culture.Conclusion Lovastatin may decrease HMC proliferation and production of proinflammatory cytokines through the inhibition of NF-κB activation. This provided experimental evidence for further evaluation of the renal protective effect of HRI, suggesting that it may be a potent agent for prevention of progressive reanl diseases aside from its lipid-lowering effect.

  5. Overexpression of HDAC6 induces pro-inflammatory responses by regulating ROS-MAPK-NF-κB/AP-1 signaling pathways in macrophages.

    Science.gov (United States)

    Youn, Gi Soo; Lee, Keun Wook; Choi, Soo Young; Park, Jinseu

    2016-08-01

    Although histone deacetylase 6 (HDAC6) has been implicated in inflammatory diseases, direct involvement and its action mechanism of HDAC6 in the transcriptional regulation of pro-inflammatory genes have been unclear. In this study, we investigated the possible role of HDAC6 in the expression of pro-inflammatory mediators, indicator of macrophage activation, in RAW 264.7 cells and primary mouse macrophages. HDAC6 overexpression significantly enhanced expression of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, with concomitant reduction in acetylated α-tubulin. HDAC6 overexpression significantly induced ROS generation via upregulation of NADPH oxidase expression and activity. Inhibition of ROS generation by N-acetyl cysteine, diphenyl iodonium and apocynin suppressed HDAC6-induced pro-inflammatory cytokines. An HDAC6 enzymatic inhibitor significantly inhibited ROS generation and expression of HDAC6-induced pro-inflammatory mediators, indicating the requirement of HDAC6 enzymatic activity for induction of pro-inflammatory cytokines. In addition, HDAC6 overexpression increased activation of MAPK species including ERK, JNK, and p38. Furthermore, HDAC6 overexpression resulted in activation of the NF-κB and AP-1 signaling pathways. Overall, our results provide the first evidence that HDAC6 is capable of inducing expression of pro-inflammatory genes by regulating the ROS-MAPK-NF-κB/AP-1 pathways and serves as a molecular target for inflammation.

  6. The impact of ambient particulate matter (PM10) on the population mortality for cerebrovascular diseasesa case-crossover study

    Institute of Scientific and Technical Information of China (English)

    王旭英

    2013-01-01

    Objective To analyze the association between the concentration of ambient inhalable particulate matter(PM10) and population mortality for cerebrovascular diseases and to explore the impact of PM10 on cerebrovascular

  7. Tratamiento de la hipertensión arterial en accidente cerebrovascular

    OpenAIRE

    Luna Vela, Fredy Andrés

    2013-01-01

    Revisión sistemática de la literatura en la que se discuten las controversias del manejo de la presión arterial en las emergencias neurológicas agudas cerebrovasculares como accidente cerebrovascular isquémico, hemorrágico y hemorragia subaracnoidea.

  8. Pathobiology of human cerebrovascular malformations: basic mechanisms and clinical relevance.

    Science.gov (United States)

    Gault, Judith; Sarin, Hemant; Awadallah, Nabil A; Shenkar, Robert; Awad, Issam A

    2004-07-01

    Cerebrovascular malformations affect more than 3% of the population, exposing them to a lifetime risk of hemorrhagic stroke, seizures, and focal neurological deficits. Cerebral cavernous malformations (CCMs) exhibit an immature vessel wall, a brittle hemorrhagic tendency, and epileptogenesis, whereas arteriovenous malformations (AVMs) lack capillary beds and manifest apoplectic bleeding under high-flow conditions. There are also more benign venous anomalies, capillary malformations, and lesions with mixed and transitional features. Advances have been made toward understanding the natural history, radiological and pathological correlates, and clinical management. Yet, mechanisms of lesion genesis and clinical manifestations remain largely unknown, and the clinical behavior in individual patients is highly unpredictable. Lesion pathogenesis likely involves abnormal assembly or maintenance of blood vessels, resulting in dysmorphic vessel phenotypes. Familial CCM disease is in part caused by mutations in a cytoskeletal-related protein that is likely integral to interendothelial cell connectivity and maturation of the vascular wall. Rare familial forms of AVM disease have been correlated with two different transforming growth factor-beta receptor components, possibly causing disturbance in signaling during vascular assembly. Relevance of these mechanisms to the more common and otherwise identical sporadic CCM and AVM lesions is being explored. In this report, basic mechanisms of vasculogenesis and angiogenesis and how they possibly relate to the common cerebrovascular malformation lesions are reviewed. Novel concepts are discussed related to the cellular, molecular, and genetic substrates in CCM and AVM as well as to how this knowledge can be applied to predict, explain, and possibly modify clinical disease manifestations.

  9. Fetal cerebrovascular circulation: a review of prenatal ultrasound assessment.

    Science.gov (United States)

    Degani, S

    2008-01-01

    Antenatal intrauterine cerebrovascular events were found to play an important role in the pathogenesis of perinatal brain damage. Changes in placental vascular resistance, cardiac contractibility, vessel compliance, and blood viscosity alter the normal dynamics of fetal cerebral circulation. The circulatory mechanisms described in animal fetuses also operate in the human fetus. The isthmus of the aorta represents a watershed area reflecting the redistribution of blood during increased peripheral resistance and hypoxia. The fetal cerebrovascular system acts locally within the skull and interacts with the other components of fetal circulation to compensate by redistribution of blood in case of shortage in resources. The introduction of various sonographic techniques and the collection of data from the arterial and venous cerebral circulation have improved our understanding of the regulatory mechanisms involved in fetal cerebral hemodynamic events. Anatomical and physiological considerations of cerebral vasculature in health and disease are relevant in the research of variations in fetal brain blood perfusion. Changes in flow characteristics in fetal cerebral vasculature can be used for clinical decisions. However, caution is advised before applying research data into practice. The clinical utility is well established in situations of fetal compromise such as growth restriction and anemia.

  10. Correlation of cerebrovascular disorder and anxiety: The Kecskemet study

    Science.gov (United States)

    Sipos, Kornel; Bodo, Michael; Szalay, Piroska; Szucs, Attila

    2010-04-01

    In order to test the hypothesis that anxiety is a risk factor for cardiovascular disease, specifically stroke, we simultaneously measured anxiety and cerebral vascular alternation, using a computer-based system, "Cerberus." Sixty nine psychiatric patients (including an alcoholic subgroup) were selected as subjects for measurements conducted in Kecskemet, Hungary. The five-item short form of anxiety test (STAI) was administered twice during the same session. Between each test, brain pulse waves were recorded by rheoencephalogram (REG). A REG peak time above 180 milliseconds was considered a cerebrovascular alteration (modified after Jenkner). Data were sorted into two groups: low anxiety (N=10) and high anxiety (N=10). Significant differences were found between cardiovascular risk factors (panxiety group, and two in the low anxiety group. For the two anxiety groups, there were no significant differences in body mass index, cardiovascular sympathetic-parasympathetic balance, age and symptoms of transient ischemic attack. The correlation of REG and age was significantly different only for the alcoholic subgroup (Szalay et al, 2007). These data support the hypothesis that a correlation exists between cerebrovascular disorder and anxiety in the studied population.

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

    Directory of Open Access Journals (Sweden)

    Maddula Mohana

    2009-09-01

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

  12. ROLE OF SMOKING AND ALCOHOLISM IN CEREBROVASCULAR ACCIDENTS

    Directory of Open Access Journals (Sweden)

    Y. Indira,

    2014-06-01

    Full Text Available Though previously stroke was considered an old man disease, it is increasing among the young and middle aged people are not likely to die of stroke as they are of heart attack, but they are likely to be disabled for rest of their lives. As the cases of stroke admitted to medical wards, formed nearly 1/10th to 1/8th of total bed strength at any time, and their prolonged stay at hospital attracted our attention. To study the etiological factors for the present study we have thoroughly evaluated 50 pts, with acute cerebrovascular disease and focused more attention in the revaluation of physiological variants of clinical importance by examining the blood for complete blood picture, which may help a long way in near future to predict the risk group in developing an acute cerebrovascular stroke and to avoid risk factors and to take measures to rectify the variations so as to minimize the mortality due to stroke.

  13. Cerebrovascular Disease in Children: Recent Advances in Diagnosis and Management

    Science.gov (United States)

    Bowers, Karen J.; deVeber, Gabrielle A.; Ferriero, Donna M.; Roach, E. Steve; Vexler, Zinaida S.; Maria, Bernard L.

    2017-01-01

    Cerebrovascular disease in children manifests in many forms, all of which have devastating and long-lasting effects. Recent advances in diagnostic imaging have revealed that this condition is much more common in the pediatric population than previously believed, affecting as many as 1 in 1500 neonates and 1 in 3000 children. The underlying mechanisms that cause stroke—ischemic stroke, sinovenous thrombosis, and hemorrhagic stroke—are only beginning to be understood; however, progress has been made toward better understanding the mechanisms of disease, particularly in the fields of genetics, inflammation, and thrombus formation. Furthermore, new imaging techniques, and better understanding of how to use imaging in managing stroke, have enabled practitioners to more quickly and accurately identify cerebrovascular disease type in children, which is key to mitigation of negative outcomes. The 2010 Neurobiology of Disease in Children symposium, held in conjunction with the 39th annual meeting of the Child Neurology Society, aimed to (1) describe clinical issues surrounding childhood stroke, including diagnosis and acute care; (2) discuss recent advances in the understanding of the pathogenesis of childhood stroke; (3) review current management of and therapies for childhood stroke, including controversial therapies; and (4) establish research directions for investigators. This article summarizes the speakers’ presentations and includes an edited transcript of question-and-answer sessions. PMID:21778188

  14. Knee Joint Dysfunctions That Influence Gait in Cerebrovascular Injury

    Science.gov (United States)

    Lucareli, Paulo Roberto Garcia; Greve, Julia Maria D’Andrea

    2008-01-01

    INTRODUCTION There is still no consensus among different specialists on the subject of kinematic variation during the hemiparetic gait, including the main changes that take place during the gait cycle and whether the gait velocity changes the patterns of joint mobility. One of the most frequently discussed joints is the knee. OBJECTIVES This study aims to evaluate the variables found in the angular kinematics of knee joint, and to describe the alterations found in the hemiparetic gait resulting from cerebrovascular injury. METHODS This study included 66 adult patients of both genders with a diagnosis of either right or left hemiparesis resulting from ischemic cerebrovascular injury. All the participants underwent three-dimensional gait evaluation, an the angular kinematics of the joint knee were selected for analysis. RESULTS The results were distributed into four groups formed based on the median of the gait speed and the side of hemiparesis. CONCLUSIONS The relevant clinical characteristics included the important mechanisms of loading response in the stance, knee hyperextension in single stance, and reduction of the peak flexion and movement amplitude of the knee in the swing phase. These mechanisms should be taken into account when choosing the best treatment. We believe that the findings presented here may aid in preventing the occurrence of the problems found, and also in identifying the origin of these problems. PMID:18719753

  15. Proinflammatory cytokines oppose opioid induced acute and chronic analgesia

    OpenAIRE

    Hutchinson, Mark R.; Coats, Benjamen D; Lewis, Susannah S.; Zhang, Yingning; Sprunger, David B.; Rezvani, Niloofar; Baker, Eric M.; Jekich, Brian M.; Wieseler, Julie L.; Somogyi, Andrew A; Martin, David; Poole, Stephen; Judd, Charles M.; Steven F. Maier; Watkins, Linda R.

    2008-01-01

    Spinal proinflammatory cytokines are powerful pain-enhancing signals that contribute to pain following peripheral nerve injury (neuropathic pain). Recently, one proinflammatory cytokine, interleukin-1, was also implicated in the loss of analgesia upon repeated morphine exposure (tolerance). In contrast to prior literature, we demonstrate that the action of several spinal proinflammatory cytokines oppose systemic and intrathecal opioid analgesia, causing reduced pain suppression. In vitro morp...

  16. The collaterome: A novel conceptual framework of systems biology in cerebrovascular disorders

    Directory of Open Access Journals (Sweden)

    David S Liebeskind

    2015-01-01

    Full Text Available The collaterome is the elaborate neurovascular architecture within the brain that regulates and determines the compensatory ability, response, and outcome of cerebrovascular pathophysiology. Based on the fundamental aspects of the cerebral collateral circulation, this model provides a conceptual framework or novel approach to cerebrovascular disorders that endorses systems biology rather than traditional reductionism. The nature of this holistic approach mirrors the innate or endogenous compensatory ability of collaterals, extending this concept to reconsider current approaches to cerebrovascular disorders. The distinction of asymptomatic and symptomatic physiology, and normal brain health versus cerebrovascular disease and the management of cerebrovascular disorders from diagnosis to therapeutic strategies may be reconsidered from this conceptual framework that builds upon established knowledge in the stroke literature.

  17. Follistatin-like protein 1 suppressed pro-inflammatory cytokines expression during neuroinflammation induced by lipopolysaccharide.

    Science.gov (United States)

    Cheng, Kai-Yuan; Liu, Yi; Han, Ying-Guang; Li, Jing-Kun; Jia, Jia-Lin; Chen, Bin; Yao, Zhi-Xiao; Nie, Lin; Cheng, Lei

    2017-04-01

    Follistain-like protein 1 (FSTL1), has been recently demonstrated to be involved in the embryo development of nervous system and glioblastoma. However, the role of FSTL1 in neuroinflammation remains unexplored. In this study, the expression of FSTL1 in astrocytes was verified and its role was studied in neuroinflammation induced by in vivo intracerebroventricular (ICV) injection of lipopolysaccharide (LPS) or LPS treatment to astrocytes in vitro. FSTL1 was significantly induced after ICV LPS injection or LPS treatment. FSTL1 suppressed upregulation of pro-inflammatory cytokines in astrocytes after LPS treatment. Moreover, FSTL1 downregulated expression of pro-inflammatory cytokines through suppressing MAPK/p-ERK1/2 pathway in astrocytes. Our results suggest that FSTL1 may play an anti-inflammatory role in neuroinflammation mediated by astrocytes.

  18. PET in cerebrovascular disease; PET bei zerebrovaskulaeren Erkrankungen

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-03-01

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

  19. Allicin enhances host pro-inflammatory immune responses and protects against acute murine malaria infection

    Directory of Open Access Journals (Sweden)

    Feng Yonghui

    2012-08-01

    Full Text Available Abstract Background During malaria infection, multiple pro-inflammatory mediators including IFN-γ, TNF and nitric oxide (NO play a crucial role in the protection against the parasites. Modulation of host immunity is an important strategy to improve the outcome of malaria infection. Allicin is the major biologically active component of garlic and shows anti-microbial activity. Allicin is also active against protozoan parasites including Plasmodium, which is thought to be mediated by inhibiting cysteine proteases. In this study, the immunomodulatory activities of allicin were assessed during acute malaria infection using a rodent malaria model Plasmodium yoelii 17XL. Methods To determine whether allicin modulates host immune responses against malaria infection, mice were treated with allicin after infection with P. yoelii 17XL. Mortality was checked daily and parasitaemia was determined every other day. Pro-inflammatory mediators and IL-4 were quantified by ELISA, while NO level was determined by the Griess method. The populations of dendritic cells (DCs, macrophages, CD4+ T and regulatory T cells (Treg were assessed by FACS. Results Allicin reduced parasitaemia and prolonged survival of the host in a dose-dependent manner. This effect is at least partially due to improved host immune responses. Results showed that allicin treatment enhanced the production of pro-inflammatory mediators such as IFN-γ, TNF, IL-12p70 and NO. The absolute numbers of CD4+ T cells, DCs and macrophages were significantly higher in allicin-treated mice. In addition, allicin promoted the maturation of CD11c+ DCs, whereas it did not cause major changes in IL-4 and the level of anti-inflammatory cytokine IL-10. Conclusions Allicin could partially protect host against P. yoelii 17XL through enhancement of the host innate and adaptive immune responses.

  20. Hepatitis C virus (HCV)-induced suppressor of cytokine signaling (SOCS) 3 regulates proinflammatory TNF-α responses.

    Science.gov (United States)

    Collins, Aideen S; Ahmed, Suaad; Napoletano, Silvia; Schroeder, Martina; Johnston, James A; Hegarty, John E; O'Farrelly, Cliona; Stevenson, Nigel J

    2014-08-01

    TNF-α is a proinflammatory cytokine, dramatically elevated during pathogenic infection and often responsible for inflammation-induced disease pathology. SOCS proteins are inhibitors of cytokine signaling and regulators of inflammation. In this study, we found that both SOCS1 and SOCS3 were transiently induced by TNF-α and negatively regulate its NF-κB-mediated signal transduction. We discovered that PBMCs from HCV-infected patients have elevated endogenous SOCS3 expression but less TNF-α-mediated IκB degradation and proinflammatory cytokine production than healthy controls. HCV protein expression in Huh7 hepatocytes also induced SOCS3 and directly inhibited TNF-α-mediated IL-8 production. Furthermore, we found that SOCS3 associates with TRAF2 and inhibits TRAF2-mediated NF-κB promoter activity, suggesting a mechanism by which SOCS3 inhibits TNF-α-mediated signaling. These results demonstrate a role for SOCS3 in regulating proinflammatory TNF-α signal transduction and reveal a novel immune-modulatory mechanism by which HCV suppresses inflammatory responses in primary immune cells and hepatocytes, perhaps explaining mild pathology often associated with acute HCV infection.

  1. Proinflammatory and anti-inflammatory cytokines in meningococcal disease.

    OpenAIRE

    Riordan, F A; Marzouk, O; Thomson, A. P.; Sills, J A; Hart, C. A.

    1996-01-01

    Interleukin-10 (IL-10), an anti-inflammatory cytokine, was measured in 131 children with meningococcal disease. IL-10 concentrations were significantly higher in children who died and correlated positively with proinflammatory cytokines. Children who die from meningococcal disease have high IL-10 concentrations, which do not suppress proinflammatory cytokines.

  2. Spironolactone inhibits production of proinflammatory cytokines by human mononuclear cells

    DEFF Research Database (Denmark)

    Hansen, Peter Riis; Rieneck, Klaus; Bendtzen, Klaus

    2004-01-01

    The mineralocorticoid receptor antagonist spironolactone (SPIR) reduces the mortality and morbidity in patients with congestive heart failure (CHF). Overexpression of proinflammatory cytokines contribute to the development and progression of CHF.......The mineralocorticoid receptor antagonist spironolactone (SPIR) reduces the mortality and morbidity in patients with congestive heart failure (CHF). Overexpression of proinflammatory cytokines contribute to the development and progression of CHF....

  3. Cerebrovascular Diseases and Risk Factors: a Strategy of Primary Prevention

    Directory of Open Access Journals (Sweden)

    Miguel Angel Buergo Zuaznábar

    2007-05-01

    Full Text Available Cerebrovascular diseases constitute a health problem worldwide and have the tendency to grow up. Chronic diseases sometimes are considered transmissible diseases at a level of risk factors. The alimentary habits and the levels of physical activity at present are risk behaviors which are spread all over the world passing from one population to another as an infectious disease with incidence in the morbidity profiles worldwide. While age and sex as well as genetic vulnerability are no modifiable elements, great part of the risks associated to age and sex can be reduced. In such risks, behavior factors (alimentary habits, physical inactivity, smoking habit and alcoholism, biological factors (dyslipidemia, hypertension, overweight, and hyperinsulinemia and finally the social factors which cover a complex combination of socio-economic, cultural parameters, and other elements of the environment that interact among them. This work covers risk factors and the behavior to be followed for its modification.

  4. [PECULIARITIES OF THE CEREBROVASCULAR EFFECTS OF GLUTAMIC ACID].

    Science.gov (United States)

    Gan'shina, T S; Kurza, E V; Kurdyumov, I N; Maslennikov, D V; Mirzoyan, R S

    2016-01-01

    Experiments on nonlinear rats subjected to global transient cerebral ischemia revealed the ability of glutamic acid to improve cerebral circulation. Consequently, the excitatory amino acid can produce adverse (neurotoxic) and positive (anti-ischemic) effects in cerebral ischemia. The cerebrovascular effect of glutamic acid in cerebral ischemia is attenuated on the background action of the MNDA receptor blocker MK-801 (0.5 mg/kg intravenously) and eliminated by bicuculline. When glutamic acid is combined with the non-competitive MNDA receptor antagonist MK-801, neither one nor another drug shows its vasodilator effect. The results are indicative of the interaction between excitatory and inhibitory systems on the level of cerebral vessels and once again confirm our previous conclusion about the decisive role of GABA(A) receptors in brain vessels in the implementation of anti-ischemic activity of endogenous compounds (melatonin) and well-known pharmacological substances (mexidol, afobazole), and new chemical compounds based on GABA-containing lipid derivatives.

  5. Diagnosis and treatment of chronic cerebrovascular disease, use of pentoxifylline

    Directory of Open Access Journals (Sweden)

    V. A. Parfenov

    2016-01-01

    Full Text Available Chronic cerebrovascular disease (CCVD is one of the most common  iagnoses in Russian neurology, by which is meant vascular cognitive impairment (VCI in modern foreign literature. There are data available in the literature on the diagnosis and treatment of CCVD (VCI. Theresults of the author’s studies show that CCVD often masks other diseases (anxiety and depressive disorders, primary headache, peripheral vestibulopathy, and Alzheimer's disease that are unfortunately poorly diagnosed in our country, so patients do not receive effective treatment. To modify risk factors for stroke (smoking and alcohol cessation, sufficient exercise, to normalize blood pressure (the use of antihypertensivemedications, to reduce blood cholesterol levels (statins, to perform antithrombotic therapy (antiplatelet agents and anticoagulants, and to use cognitive enhancers are of key importance when treating patients with CCVD (VCI. There are data on the use of pentoxifylline in patients with CCVD, vascular dementia.

  6. Expressional changes in cerebrovascular receptors after experimental transient forebrain ischemia

    DEFF Research Database (Denmark)

    Johansson, Sara; Povlsen, Gro Klitgaard; Edvinsson, Lars

    2012-01-01

    of vasoconstrictive endothelin and 5-hydroxytryptamine receptors in cerebral arteries. Experimental transient forebrain ischemia of varying durations was induced in male wistar rats, followed by reperfusion for 48 hours. Neurological function was assessed daily by three different tests and cerebrovascular expression......Global ischemic stroke is one of the most prominent consequences of cardiac arrest, since the diminished blood flow to the brain results in cell damage and sometimes permanently impaired neurological function. The post-arrest period is often characterised by cerebral hypoperfusion due to subacute...... the insult, a phenomenon that leads to increased contraction of cerebral arteries, reduced perfusion of the affected area and worsened ischemic damage. Based on these findings, the aim of the present study was to investigate if transient global cerebral ischemia is associated with upregulation...

  7. Cerebrovascular reactivity in migraineurs as measured by transcranial Doppler

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, T.D.; Harpold, G.J. (Alabama Univ., Birmingham, AL (USA). School of Medicine); Troost, B.T. (Bowman Gray School of Medicine, Winston-Salem, NC (USA))

    1990-04-01

    Transcranial Doppler ultrasound is a relatively new diagnostic modality which allows the non-invasive assessment of intracranial circulation. A total of 10 migraine patients were studied and compared to healthy controls without headaches. Migraineurs during the headache-free interval demonstrated excessive cerebrovascular reactivity to CO{sub 2}, evidenced by an increase in middle cerebral artery blood flow velocity of 47% {plus minus} 15% compared to 28% {plus minus} 14% in controls. Differences between the two study groups revealed no significant decrease in middle cerebral artery blood flow velocity with hypocapnia. However, the differences between middle cerebral artery blood flow velocity during hyperventilation and CO{sub 2} inhalation were significantly different comparing migraineurs and controls. Instability of the baseline blood flow velocities was also noted in migraineurs during the interictal period. Characteristics which may allow differentiation of migraineurs from other headache populations could possibly be obtained from transcranial Doppler ultrasound flow studies. 24 refs., 2 tabs.

  8. Clinical and angiographic comparison of asymptomatic occlusive cerebrovascular disease.

    Science.gov (United States)

    Gorelick, P B; Caplan, L R; Langenberg, P; Hier, D B; Pessin, M; Patel, D; Taber, J

    1988-06-01

    We compared clinical and arteriographic features in 106 patients with symptomatic unilateral carotid territory occlusive disease to determine the frequency and distribution of occlusive arterial lesions in asymptomatic vessels. Among black patients who were predominantly from Chicago, young, and female, there were fewer transient ischemic attacks and myocardial infarcts, less claudication, and more asymptomatic lesions of the supraclinoid internal carotid artery, anterior cerebral artery stem, and the middle cerebral artery stem. Among white patients predominantly from New England, elderly, and male, there was more frequent and severe occlusive asymptomatic disease at extracranial carotid and vertebral artery sites. Knowledge of the distribution of asymptomatic lesions will help guide evaluation and treatment strategies for patients with occlusive cerebrovascular disease.

  9. /sup 111/In platelet scintigraphy in cerebrovascular disease

    Energy Technology Data Exchange (ETDEWEB)

    Powers, W.J.; Siegel, B.A.; Davis, H.H.; Mathias, C.J.; Clark, H.B.; Welch, M.J.

    1982-09-01

    We obtained scintigraphic images of the neck from 100 patients with suspected cerebrovascular disease after injecting /sup 111/In-labeled autologous platelets. One or more focuses of increased activity, implying local platelet accumulation, were seen along the course of the cervical carotid arteries in 52 patients. In 64 patients, there was a highly significant correlation between the results of scintigraphy and carotid arteriography (p . 10(6)). There was no significant correlation between the scintigraphic findings and the previous or subsequent occurrence of transient ischemic attack or cerebral infarction in the carotid circulation. These data suggest that factors other than the simple formation of platlet thrombi in the cervical carotid arteries are of primary importance in the pathogenesis of stroke.

  10. Pharmacoepidemiological Study on Cerebrovascular Accident in Tertiary Care Hospital

    Directory of Open Access Journals (Sweden)

    Prathyusha GR

    2016-08-01

    Full Text Available Stroke is the third leading cause of death in the United States (US and a leading cause of serious, long-term disability. Incidence of ischemic stroke is higher than hemorrhagic stroke. The aim is to conduct pharmacoepidemiology study on cerebrovascular accident patient by evaluating the use and the effects of drugs, and quantification of adverse drug reactions, drug utilization studies to improve the quality and use of medicines. A prospective observational study was conducted in department of general medicine and ICU at Mallareddy hospital, data was collected from 130 patients and it was proposed to be conducted for 6 months. Among 130 patients 78(60% are males and 52(40% are females. Among all age groups major number of CVA patients was seen in 60-69 years (30%. Among them 92% of strokes are Ischemic majorly seen in both males and females and8% strokes are hemorrhagic. Ischemic stroke (94.87% is majorly seen in 60-69 yr age group. Among various risk factors Hypertension (36.43% is the major risk factor found in males (60% and females (40%.Antiplatelet drugs (25.75% are the highest number of drugs given in patients 71.27% in males and 28.72% in females. Highest numbers of drugs are given in 50-59yrs age group and are antiplatelets. As a clinical pharmacist 16 adverse drug reactions and 25 drug interactions are reported. Proper patient counselling is needed to reduce hypertension and to reduce the risk for cerebrovascular accident. Among all antiplatelet drugs are majorly given in males and lipid lowering drugs in females.

  11. Dopamine does not limit fetal cerebrovascular responses to hypoxia.

    Science.gov (United States)

    Mayock, Dennis E; Bennett, Rachel; Robinson, Roderick D; Gleason, Christine A

    2007-01-01

    Dopamine is used clinically to stabilize mean arterial blood pressure (MAP) in sick infants. One goal of this therapeutic intervention is to maintain adequate cerebral blood flow (CBF) and perfusion pressure. High-dose intravenous dopamine has been previously demonstrated to increase cerebrovascular resistance (CVR) in near-term fetal sheep. We hypothesized that this vascular response might limit cerebral vasodilatation during acute isocapnic hypoxia. We studied nine near-term chronically catheterized unanesthetized fetal sheep. Using radiolabeled microspheres to measure fetal CBF, we calculated CVR at baseline, during fetal hypoxia, and then with the addition of an intravenous dopamine infusion at 2.5, 7.5, and 25 microg.kg(-1).min(-1) while hypoxia continued. During acute isocapnic fetal hypoxia, CBF increased 73.0 +/- 14.1% and CVR decreased 38.9 +/- 4.9% from baseline. Dopamine infusion at 2.5 and 7.5 microg.kg(-1).min(-1), begun during hypoxia, did not alter CVR or MAP, but MAP increased when dopamine infusion was increased to 25 microg.kg(-1).min(-1). Dopamine did not alter CBF or affect the CBF response to hypoxia at any dose. However, CVR increased at a dopamine infusion rate of 25 microg.kg(-1).min(-1). This increase in CVR at the highest dopamine infusion rate is likely an autoregulatory response to the increase in MAP, similar to our previous findings. Therefore, in chronically catheterized unanesthetized near-term fetal sheep, dopamine does not alter the expected cerebrovascular responses to hypoxia.

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

    Directory of Open Access Journals (Sweden)

    Fabricio Ferreira de Oliveira

    2015-03-01

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

  13. Cerebral Endothelial Function Determined by Cerebrovascular Reactivity to L-Arginine

    Directory of Open Access Journals (Sweden)

    Janja Pretnar-Oblak

    2014-01-01

    Full Text Available Endothelium forms the inner cellular lining of blood vessels and plays an important role in many physiological functions including the control of vasomotor tone. Cerebral endothelium is probably one of the most specific types but until recently it was impossible to determine its function. In this review, the role of cerebrovascular reactivity to L-arginine (CVR-L-Arg for assessment of cerebral endothelial function is discussed. L-Arginine induces vasodilatation through enhanced production of nitric oxide (NO in the cerebral endothelium. Transcranial Doppler sonography is used for evaluation of cerebral blood flow changes. The method is noninvasive, inexpensive, and enables reproducible measurements. CVR-L-Arg has been compared to flow-mediated dilatation as a gold standard for systemic endothelial function and intima-media thickness as a marker for morphological changes. However, it seems to show specific cerebral endothelial function. So far CVR-L-Arg has been used to study cerebral endothelial function in many pathological conditions such as stroke, migraine, etc. In addition CVR-L-Arg has also proven its usefulness in order to show potential improvement after pharmacological interventions. In conclusion CVR-L-Arg is a promising noninvasive research method that could provide means for evaluation of cerebral endothelial function in physiological and pathological conditions.

  14. Circulating vitamin D, calcium and risk of cerebrovascular disease: a systematic review and meta-analysis.

    Science.gov (United States)

    Chowdhury, Rajiv; Stevens, Sarah; Ward, Heather; Chowdhury, Susmita; Sajjad, Ayesha; Franco, Oscar H

    2012-08-01

    Available literature suggests that both vitamin D and calcium may be associated with a wide range of non-skeletal outcomes. However, epidemiological evidence supporting their individual associations with incident cerebrovascular disease is scarce. We conducted a systematic review and meta-analysis of prospective cohort studies, published before February 2012 and sought from MEDLINE, EMBASE, BIOSIS and the Science Citation Index databases, and reported cerebrovascular disease (defined as any fatal or non-fatal ischemic stroke, hemorrhagic stroke, cerebrovascular accident or transient ischemic attack) by circulating vitamin D (25-hydroxy vitamin D [25(OH)D] as active metabolite) and calcium levels. Two independent investigators abstracted information on 25(OH)D and calcium, cerebrovascular outcomes and other characteristics from selected studies. Relative risks (RRs) were pooled by both random and fixed effects meta-analyses and were further examined under different study-level characteristics. Publication bias was assessed with funnel plots and Egger's asymmetry test. From 5,778 initial references, nine unique prospective cohort studies met our inclusion criteria. Seven studies (involving 47,809 participants and 926 cerebrovascular events) focused on circulating 25(OH)D and 3 reported on circulating calcium (22,577 participants and 727 events). For 25(OH)D, in a comparison of individuals in the top third versus those in the bottom third at baseline, the combined RR for cerebrovascular disease, adjusted for several conventional risk factors, was 0.60 (95 % CI 0.48, 0.72). The corresponding RR in the prospective studies that reported on baseline circulating calcium levels for cerebrovascular disease was 1.40 (95 % CI 1.19, 1.64). There was no apparent evidence of heterogeneity or publication bias among included studies. Available data indicate that higher circulating level of vitamin D is associated with a decreased risk of cerebrovascular disease. Conversely

  15. Cisplatin cytotoxicity of auditory cells requires secretions of proinflammatory cytokines via activation of ERK and NF-kappaB.

    Science.gov (United States)

    So, Hongseob; Kim, HyungJin; Lee, Jeong-Han; Park, Channy; Kim, Yunha; Kim, Eunsook; Kim, Jin-Kyung; Yun, Ki-Jung; Lee, Kang-Min; Lee, Haa-Yung; Moon, Sung-Kyun; Lim, David J; Park, Raekil

    2007-09-01

    The ototoxicity of cisplatin, a widely used chemotherapeutic agent, involves a number of mechanisms, including perturbation of redox status, increase in lipid peroxidation, and formation of DNA adducts. In this study, we demonstrate that cisplatin increased the early immediate release and de novo synthesis of proinflammatory cytokines, including TNF-alpha, IL-1beta, and IL-6, through the activation of ERK and NF-kappaB in HEI-OC1 cells, which are conditionally immortalized cochlear cells that express hair cell markers. Both neutralization of proinflammatory cytokines and pharmacologic inhibition of ERK significantly attenuated the death of HEI-OC1 auditory cells caused by cisplatin and proinflammatory cytokines. We also observed a significant increase in the protein and mRNA levels of proinflammatory cytokines in both serum and cochleae of cisplatin-injected rats, which was suppressed by intraperitoneal injection of etanercept, an inhibitor of TNF-alpha. Immunohistochemical studies revealed that TNF-alpha expression was mainly located in the spiral ligament, spiral limbus, and the organ of Corti in the cochleae of cisplatin-injected rats. NF-kappaB protein expression, which overlapped with terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling-positive signal, was very strong in specific regions of the cochleae, including the organ of Corti, spiral ligament, and stria vascularis. These results indicate that proinflammatory cytokines, especially TNF-alpha, play a central role in the pathophysiology of sensory hair cell damage caused by cisplatin.

  16. Salvianolic acid B inhibits platelets-mediated inflammatory response in vascular endothelial cells.

    Science.gov (United States)

    Xu, Shixin; Zhong, Aiqin; Bu, Xiaokun; Ma, Huining; Li, Wei; Xu, Xiaomin; Zhang, Junping

    2015-01-01

    Salvianolic acid B (SAB) is a hydrophilic component isolated from the Chinese herb Salviae miltiorrhizae, which has been used clinically for the treatment of ischemic cardiovascular and cerebrovascular diseases. Platelets-mediated vascular inflammatory response contributes to the initiation and progression of atherosclerosis. In this paper, we focus on the modulating effects of SAB on the inflammatory reaction of endothelial cells triggered by activated platelets. Human umbilical vein endothelial cells (EA.hy926) were pretreated with SAB followed by co-culture with ADP-activated platelets. Adhesion of platelets to endothelial cells was observed by amorphological method. The activation of nuclear factor-kappa B was evaluated by NF-κB p65 nuclear translocation and the protein phosphorylation. A determination of the pro-inflammatory mediators (ICAM-1, IL-1β, IL-6, IL-8, MCP-1) mRNA and protein were also conducted. In addition, the inhibitory effects of SAB on platelets activation were also evaluated using a platelet aggregation assay and assessing the release level of soluble P-selectin. The results showed that SAB dose-dependently inhibited ADP- or α-thrombin-induced human platelets aggregation in platelet rich plasma (PRP) samples, and significantly decreased soluble P-selectin release from both agonists stimulated washed platelets. It was also found that pre-treatment with SAB reduced adhesion of ADP-activated platelets to EA.hy926 cells and inhibited NF-κB activation. In addition, SAB significantly suppressed pro-inflammatory mediators mRNA and protein in EA.hy926 cells in a dose-dependent manner. These results indicated that, in addition to its inhibitory effects on platelets activation, SAB was able to attenuate platelets-mediated inflammatory responses in endothelial cells even if the platelets had already been activated. This anti-inflammatory effect was related to the inhibition of NF-κB activation. Our findings suggest that SAB may be a potential

  17. Roles of proinflammatory cytokines and the Fas/Fas ligand interaction in the pathogenesis of inflammatory myopathies.

    Science.gov (United States)

    Kondo, Masahiro; Murakawa, Yohko; Harashima, Nanae; Kobayashi, Shotai; Yamaguchi, Shuhei; Harada, Mamoru

    2009-09-01

    Within the lesions of inflammatory myopathies, muscle fibres and invading mononuclear cells express Fas and Fas ligand (FasL), respectively. However, the roles of the Fas/FasL interaction in the pathogenesis of inflammatory myopathies are not fully understood. In the present study, we investigated the roles of proinflammatory cytokines and the Fas/FasL system in the pathogenesis of inflammatory myopathies. In vitro culturing of muscle cells with the proinflammatory cytokines interferon-gamma, tumour necrosis factor-alpha, and interleukin (IL)-1beta synergistically increased Fas expression, susceptibility to Fas-mediated apoptosis, and the expression of cytoplasmic caspases 8 and 3. In addition, culturing of muscle cells with activated CD4(+) T cells induced muscle cell apoptosis, which was partially inhibited by anti-FasL antibody. We also tested the possibility that T helper (Th) 17, which is an IL-17-producing helper T-cell subset that plays crucial roles in autoimmune and inflammatory responses, participates in the pathogenesis of inflammatory myopathies. Interestingly, in vitro culturing of dendritic cells with anti-Fas immunoglobulin M (IgM) or activated CD4(+) T cells induced the expression of mRNA for IL-23p19, but not for IL-12p35, in addition to proinflammatory cytokines. Furthermore, IL-23p19 and IL-17 mRNAs were detected in the majority of biopsy samples from patients with inflammatory myopathies. Taken together, these results suggest that proinflammatory cytokines enhance Fas-mediated apoptosis of muscle cells, and that the Fas/FasL interaction between invading dendritic cells and CD4(+) T cells induces local production of IL-23 and proinflammatory cytokines, which can promote the proliferation of Th17 cells and enhance Fas-mediated apoptosis of muscle cells, respectively.

  18. Ephedrine hydrochloride protects mice from LPS challenge by promoting IL-10 secretion and inhibiting proinflammatory cytokines.

    Science.gov (United States)

    Zheng, Yuejuan; Guo, Ziyi; He, Weigang; Yang, Yang; Li, Yuhu; Zheng, Aoxiang; Li, Ping; Zhang, Yan; Ma, Jinzhu; Wen, Mingyue; Yang, Muyi; An, Huazhang; Ji, Guang; Yu, Yizhi

    2012-05-01

    Sepsis and its derivative endotoxic shock are still serious conditions with high mortality in the intensive care unit. The mechanisms that ensure the balance of proinflammatory cytokines and anti-inflammatory cytokine production are of particular importance. As an active α- and β-adrenergic agonist, ephedrine hydrochloride (EH) is a widely used agent for cardiovascular diseases, especially boosting blood pressure. Here we demonstrate that EH increased Toll-like receptor 4 (TLR4)-mediated production of interleukin 10 (IL-10) through p38 MAPK activation. Simultaneously, EH negatively regulated the production of proinflammatory cytokines. Consistently, EH increased lipopolysaccharide (LPS)-induced serum IL-10 and inhibited tumor necrotic factor-α (TNFα) production in vivo. As a result, EH treatment protected mice from endotoxic shock by lethal LPS challenge. In brief, our data demonstrated that EH could contribute to immune homeostasis by balancing the production of proinflammatory cytokines and anti-inflammatory cytokine in TLR4 signaling. This study provides a potential usage of EH in autoimmunologic diseases or other severe inflammations.

  19. Neurotensin Decreases the Proinflammatory Status of Human Skin Fibroblasts and Increases Epidermal Growth Factor Expression

    Directory of Open Access Journals (Sweden)

    Lucília Pereira da Silva

    2014-01-01

    Full Text Available Fibroblasts colonization into injured areas during wound healing (WH is responsible for skin remodelling and is also involved in the modulation of inflammation, as fibroblasts are immunologically active. Herein, we aimed to determine neurotensin effect on the immunomodulatory profile of fibroblasts, both in homeostatic and inflammatory conditions. Neurotensin mediated responses occurred through NTR1 or NTR3 receptors, while under inflammatory conditions NTR1 expression increase seemed to modulate neurotensin responses. Among different immunomodulatory genes, CCL11, IL-8, and IL-6 were the most expressed genes, while CCL4 and EGF were the less expressed genes. After neurotensin exposure, IL-8 mRNA expression was increased while CCL11 was decreased, suggesting a proinflammatory upregulation and chemoattractant ability downregulation of fibroblasts. Under inflammatory conditions, gene expression was significantly increased. After neurotensin exposure, CCL4 and IL-6 mRNA expression were decreased while CCL11 was increased, suggesting again a decrease in the chemoattractant capacity of fibroblasts and in their proinflammatory status. Furthermore, the expression of EGF, a crucial growth factor for skin cells proliferation and WH, was increased in all conditions. Overall, neurotensin, released by nerve fibers or skin cells, may be involved in the decrease of the chemotaxis and the proinflammatory status in the proliferation and remodelling phases of WH.

  20. Normal aging and cognition: the unacknowledged contribution of cerebrovascular risk factors.

    Science.gov (United States)

    Morra, L; Zade, D; McGlinchey, R E; Milberg, W P

    2013-01-01

    Despite the widespread assumption that cognitive decline is an inherent part of the normal aging process, research suggests that part of the variance in age-related cognitive decline is attributable to modifiable factors common in geriatric populations such as cerebrovascular risk factors. We completed a literature search using Science Citation Index and evaluated the most cited articles from the last 10 years to determine the extent to which investigations of normal aging and cognition account for the influence of cerebrovascular risk factors. We found that the majority of the most frequently cited literature does not adequately account for the contribution of cerebrovascular risk factors and therefore, it is possible that many conclusions about normal aging and cognition are flawed or incomplete. Further investigation of the role of cerebrovascular risk factors in age-related cognitive decline is imperative to more accurately understand the effect of aging on cognition.

  1. A cohort study on the relationship between cerebrovascular hemodynamic changing and risk of strok

    Institute of Scientific and Technical Information of China (English)

    郭吉平

    2013-01-01

    Objective To study the role of cerebrovascular hemodynamic indexes(CVHI)changing in stroke and to provide reference for stroke prevention and risk factor study.Methods From 2003 to 2004,participants aged 40 years

  2. Clinical study of model-based blood flow quantification on cerebrovascular data

    NARCIS (Netherlands)

    Groth, A.; Wächter-Stehle, I.; Brina, O.; Perren. F.; Rüfenacht, D.; Bruijns, T.; Bertram, M.; Weese, J.

    2011-01-01

    Diagnosis and treatment decisions of cerebrovascular diseases are currently based on structural information like the endovascular lumen. In future, clinical diagnosis will increasingly be based on functional information which gives direct information about the physiological parameters and, hence, is

  3. Mapping white matter diffusion and cerebrovascular reactivity in carotid occlusive disease

    NARCIS (Netherlands)

    Conklin, J.; Fierstra, J.; Crawley, A. P.; Han, J. S.; Poublanc, J.; Silver, F. L.; Tymianski, M.; Fisher, J. A.; Mandell, D. M.; Mikulis, D. J.

    2011-01-01

    Objective: To characterize the relationship between cerebrovascular reactivity (CVR) and white matter (WM) diffusion in patients with internal carotid artery (ICA) occlusive disease. Methods: In this exploratory observational study, 41 patients with severe stenosis or occlusion of the extracranial I

  4. Central and cerebrovascular effects of leg crossing in humans with sympathetic failure

    NARCIS (Netherlands)

    M.P. Harms; W. Wieling; W.N. Colier; J.W. Lenders; N.H. Secher; J.J. van Lieshout

    2010-01-01

    Leg crossing increases arterial pressure and combats symptomatic orthostatic hypotension in patients with sympathetic failure This study compared the central and cerebrovascular effects of leg crossing in patients with sympathetic failure and healthy controls. We addressed the relationship between M

  5. Clinical Practice Guidelines for Cerebrovascular Disease Treatment Guía de práctica clínica para el tratamiento de la enfermedad cerebrovascular

    Directory of Open Access Journals (Sweden)

    Tania Pérez Ramos

    2009-03-01

    Full Text Available Clinical Practice Guidelines for Cerebrovascular Disease Treatment. Even when this term makes reference to the whole process affecting part of cerebral vessel system and cerebral tissue, this document focuses on the cerebrovascular or acute neurological event abruptly affecting the cerebral tissue and the neurological condition of the patient. This condition is usually cause by an abrupt vessel occlusion, of thrombotic or embolic origin, or by subarachnoid or intraventricular intraparenchymatous hemorrhage, of aneurism origin, related with hypertension or with a tumour or arteriovenous defects. The main concepts, classification and conduct are reviewed, stressing the cerebrovascular accident. It includes assessment guidelines focused on the most important aspects to be accomplished.Guía de práctica clínica para el tratamiento del paciente con enfermedad cerebrovascular. Aunque el término se refiere a todo el proceso que afecta a parte de la vasculatura cerebral y al tejido cerebral que irriga, el documento se centraliza en el accidente cerebrovascular o evento neurológico agudo que afecta en forma súbita al tejido cerebral y compromete el estado neurológico del paciente, causado por una oclusión súbita de un vaso, de origen trombótico o embólico (isquémico o por una hemorragia intraparenquimatosa, subaracnoidea o intraventricular, de origen aneurismático, hipertensivo o secundario a un tumor o malformación arteriovenosa (hemorrágico. Se revisan los conceptos, clasificación y conducta con énfasis en el tratamiento de accidente cerebrovascular isquémico. Concluye con su guía de evaluación, enfocada en los aspectos más importantes a cumplir.

  6. Revisión actualizada sobre enfermedad cerebrovascular: estudio de un caso

    OpenAIRE

    Bardají Fandos, Teodosia

    2003-01-01

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

  7. Clinical Observation on Acupuncture Treatment of Cerebrovascular Dementia- A Report of 32 Cases

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Cerebrovascular dementia is a common disease in the middle-aged and old people. Its incidence makes up about 10-20% of all kinds of dementia. It is mainly caused by general degeneration of the brain function resulted from cerebral arteriosclerosis and cerebral infarction. The author has treated 32 cases of cerebrovascular dementia with acupuncture in the recent years with satisfactory therapeutic results. A report follows.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-28

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

  9. PM10-biogenic fraction drives the seasonal variation of proinflammatory response in A549 cells.

    Science.gov (United States)

    Camatini, Marina; Corvaja, Viviana; Pezzolato, Eleonora; Mantecca, Paride; Gualtieri, Maurizio

    2012-02-01

    PM10 was collected in a Milan urban site, representative of the city air quality, during winter and summer 2006. Mean daily PM10 concentration was 48 μg m(-3) during summer and 148 μg m(-3) during winter. Particles collected on Teflon filters were chemically characterized and the endotoxin content determined by the LAL test. PM10-induced cell toxicity, assessed with MTT and LDH methods, and proinflammatory potential, monitored by IL-6 and IL-8 cytokines release, were investigated on the human alveolar epithelial cell line A549 exposed to increasing doses of PM. Besides untreated cells, exposure to inert carbon particles (2-12 μm) was also used as additional control. Both cell toxicity and proinflammatory potency resulted to be higher for summer PM10 with respect of winter PM10, with IL-6 showing the highest dose-dependent release. The relevance of biogenic components adsorbed onto PM10 in eliciting the proinflammatory mediators release was investigated by inhibition experiments. Polymixin B (Poly) was used to inhibit particle-bind LPS while Toll-like receptor-2 antibody (a-TLR2) to specifically block the activation of this receptor. While cell viability was not modulated in cells coexposed to PM10 and Poly or a-TLR2 or both, inflammatory response did it, with IL-6 release being the most inhibited. In conclusion, Milan PM10-induced seasonal-dependent biological effects, with summer particles showing higher cytotoxic and proinflammatory potential. Cytotoxicity seemed to be unaffected by the PM biogenic components, while inflammation was significantly reduced after the inhibition of some biogenic activated pathways. Besides, the PM-associated biogenic activity does not entirely justify the PM-induced inflammatory effects. © 2010 Wiley Periodicals, Inc. Environ Toxicol 2012.

  10. Putative Role of Serum Amyloid-A and Proinflammatory Cytokines as Biomarkers for Behcet's Disease

    Science.gov (United States)

    Lopalco, Giuseppe; Lucherini, Orso Maria; Vitale, Antonio; Talarico, Rosaria; Lopalco, Antonio; Galeazzi, Mauro; Lapadula, Giovanni; Cantarini, Luca; Iannone, Florenzo

    2015-01-01

    Abstract Behcet's disease (BD) is a multisystemic disorder of unknown etiology characterized by relapsing oral–genital ulcers, uveitis, and involvement of vascular, gastrointestinal, neurological, and musculoskeletal system. Although disease pathogenesis is still unclear, both innate and adaptive immunity have shown to play a pivotal role, and multiple proinflammatory cytokines seem to be involved in different pathogenic pathways that eventually lead to tissue damage. The aims of our study were to evaluate serum cytokines levels of IL-8, IL-18, IFN-α2a, IL-6, IFN-γ, CXCL10, CXCL11, CXCL9, and SAA levels in patients with BD, in comparison to healthy controls (HC), and to correlate their levels to disease activity. We included 78 serum samples obtained from 58 BD patients and analyzed a set of proinflammatory cytokines including IL-8, IL-18, IFN-α2a, IL-6, IFN-γ, CXCL10, CXCL11, and CXCL9 by multiplex bead analysis as well as SAA by enzyme-linked immunosorbent assay. Compared to HC, BD patients showed elevated cytokine levels of IL-8, IL-18, IFN-α2a, and IL-6, and low levels of CXCL11. BD patients with SAA serum levels >20 mg/L showed higher levels of proinflammatory markers than HC or group with SAA ≤20 mg/L. IL-18, IFN-α2a, and IL-6 were higher in BD group with SAA >20 mg/L than HC, while IL-8 and CXCL9 levels were higher than in patients with SAA ≤20 mg/L and HC. Active BD patients with SAA >20 mg/L exhibited elevated levels of inflammatory mediators, suggesting that may exist a relationship between SAA and proinflammatory cytokines in the intricate scenario of BD pathogenesis. PMID:26496336

  11. Care for patients with cerebrovascular disease in a general hospital. 2 years experience

    Directory of Open Access Journals (Sweden)

    Joan Omar Rojas Fuentes

    2010-08-01

    Full Text Available Background: The care of patients with cerebrovascular disease requires an organized system from pre-hospital care until discharge of the patient, to ensure the continuity of rehabilitation. In order to provide differentiated services to patients with this condition was created in the General Hospital Universitario "Dr. Gustavo Lima Aldereguía "a specialized room for attention to these diseases and the rehabilitation of patients. Objective: To determine the benefits obtained with differentiated services to patients with cerebrovascular disease in a general hospital. Methods: Descriptive case series that included 1038 patients admitted to the specialized chamber for cerebrovascular disease. We analyzed the following variables: stay, type of cerebrovascular disease, clinical classification, the Barthel index and discharge status. Results: 972 patients suffered from cerebrovascular disease, hospital stay was reduced by two days, the attention of specialized equipment increased from 51.75% to 79.2% patients were discharged with a mild degree of functional dependence. Conclusions: The differentiated services to cerebrovascular disease in general hospitals shows benefits for patients.

  12. Uric acid levels and their relation to incapacities in acute cerebrovascular disease

    Directory of Open Access Journals (Sweden)

    Julio López Argüelles

    2010-02-01

    Full Text Available Background: cerebrovascular disease and ischemic cardiopathy can be considered as an epidemic and constitute the first cause of incapacities in developed countries. Multiple studies have shown the association between uric acid levels and cerebrovascular diseases. Objective: To correlate the levels of serum uric acid and incapacities in the acute phase of cerebrovascular disease. Methods: A correlational study was carried out with 217 patients with acute cerebrovascular disease. The patient’s incapacity level was measured by using the Barthel Index and those results were related with the serum uric acid levels and other variables. Results: Male patients have higher levels of uric acid (p=0, 04; r=0, 13. Age and Barthel index were p < 0,001; r = -0, 30 and uric acid levels and Barthel Index were p=0, 03; r=-0, 14. The principal predicting factors of incapacity in the acute phase of cerebrovascular disease were the high levels of uric acid, age and diabetes mellitus. Conclusions: It is shown that the highest is the level of uric acid at advanced age; the greatest is the risk of suffering from incapacity in acute phases of cerebrovascular diseases.

  13. Calidad de vida de cuidadores de adultos con accidente cerebrovascular

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    INNA ELIDA FLÓREZ TORRES

    2010-10-01

    Full Text Available Objetivo: describir la calidad de vida de los cuidadores familiares de adultos con secuelas de accidente cerebrovascular, en Cartagena, Colombia. Método: estudio descriptivo cuantitativo realizado durante el segundo semestre de 2008. Muestra no probabilística por conveniencia de 97 cuidadores. Se empleó el instrumento propuesto por Ferrell et ál. Para valorar cada uno de los bienestares que integran la calidad de vida se utilizaron medidas de tendencia central y coeficiente de variación. Resultados: el grupo de cuidadores presentó en el bienestar físico un promedio de 11,1 con relación al máximo puntaje, lo que indica el peor estado de salud; los bienestares psicológico y social tuvieron promedios de 48,8 y 21,9, respectivamente, con menor afectación. El mejor estado se halló en el bienestar espiritual, con promedio de 22,6. Conclusiones: la experiencia de ser cuidador modifica de manera importante la calidad de vida de las personas; los cuidadores, como fuente importante de cuidado informal, requieren apoyo de los sistemas de salud y, como parte de este, de los profesionales de enfermería.

  14. Computed tomographic evaluation in 8 patient of cerebrovascular moyamoya disease

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    Ko, Young Tae; Lee, Jung Suk; Suh, Soo Jhi; Kim, Soon Yong [School of Medicine, Kyung-Hee University Hospital, Seoul (Korea, Republic of)

    1980-12-15

    CT findings in eight cerebrovascular moyamoya disease were compared with carotid angiographic findings and the results were as follows: 1. The patient's age was ranged from 2 to 49 years. Of eight patients, five were less than 17 years old and the rests were two 23 years and one 49 years of age. 2. Except one 6 years old boy, all of them were female patients. 3. In precontrast CT scan of 8 cases, 6 cases of cortical atrophy, 6 cases of ventricular dilatation and 5 cases of low density area were observed. In postcontrast study the children group shows abnormal contrast enhancement in 3 out of 5 patients but all adult reveal no contrast enhancement. 4. The isodense area in CT were thought to represent good collateral manifested by angiographic moyamoya vascular network and leptomeningeal anastomosis while the low density area in CT appears to poor colleaterals manifested by transdural anastomosis. 5. To evaluate the possibility of this disease, carotid angiography should be performed to the hemiplgic child who shows multiple low density area and abnormal enhancement in CT scan. 6. CT is not only reliable for evaluation of ventricular hemorrhage but also brain damage in patients with moyamoya disease.

  15. Change of blood rheology in newborn and its cerebrovascular damage

    Institute of Scientific and Technical Information of China (English)

    Guang-Ming Chen; Chun-Hua Lai; Jun-Feng Lv; Bing-Yan Yang; Li Xing-Xi

    2016-01-01

    Objective:To explore the blood rheology, changes in myocardial enzyme spectrum and brain damage in newborn whose hematocritg (HCT) are among 60%-65%.Methods:A total of 100 cases newborn whose HCT among 60%-65% with blood routine examination were set as observation group, 100 cases newborn whose HCT <60% were set as control group, compared the blood rheology, changes in myocardial enzyme spectrum and brain damage between two groups.Results:The HCT, whole blood viscosity (high), whole blood viscosity (low shear), erythrocyte aggregation index, erythrocyte rigidity index, aspertate aminotransferase, creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, Vs, Vs and the abnormal rate of aEEG examination in observation group were significantly higher than the control group, the difference had statistical significance, RI in observation group were significantly lower than the control group, the difference had statistical significance.Conclusions:newborn whose HCT among 60%-65% but not with polycythemia have appeared and cerebrovascular lesions, it should cause clinical positive value.

  16. Cerebrovascular accidents in sickle cell disease: rates and risk factors.

    Science.gov (United States)

    Ohene-Frempong, K; Weiner, S J; Sleeper, L A; Miller, S T; Embury, S; Moohr, J W; Wethers, D L; Pegelow, C H; Gill, F M

    1998-01-01

    Cerebrovascular accident (CVA) is a major complication of sickle cell disease. The incidence and mortality of and risk factors for CVA in sickle cell disease patients in the United States have been reported only in small patient samples. The Cooperative Study of Sickle Cell Disease collected clinical data on 4,082 sickle cell disease patients enrolled from 1978 to 1988. Patients were followed for an average of 5.2 +/- 2.0 years. Age-specific prevalence and incidence rates of CVA in patients with the common genotypes of sickle cell disease were determined, and the effects of hematologic and clinical events on the risk of CVA were analyzed. The highest rates of prevalence of CVA (4.01%) and incidence (0.61 per 100 patient-years) were in sickle cell anemia (SS) patients, but CVA occurred in all common genotypes. The incidence of infarctive CVA was lowest in SS patients 20 to 29 years of age and higher in children and older patients. Conversely, the incidence of hemorrhagic stroke in SS patients was highest among patients aged 20 to 29 years. Across all ages the mortality rate was 26% in the 2 weeks after hemorrhagic stroke. No deaths occurred after infarctive stroke. Risk factors for infarctive stroke included prior transient ischemic attack, low steady-state hemoglobin concentration and rate of and recent episode of acute chest syndrome, and elevated systolic blood pressure. Hemorrhagic stroke was associated with low steady-state hemoglobin and high leukocyte count.

  17. Cerebrovascular complications in children with sickle cell disease.

    Science.gov (United States)

    De Montalembert, M; Wang, W

    2013-01-01

    Cerebrovascular accidents were until recently responsible for much mortality and morbidity in children with sickle cell disease; the likelihood of a child with HbSS having a stroke was 11% before age 20 years, with a peak incidence of ischemic stroke between 2 and 5 years of age, and of hemorrhagic strokes between 20 and 29 years of age. Vessels occlusion is likely initiated by intimal proliferation and amplified by inflammation, excessive adhesion of cells to activated endothelium, hypercoagulable state, and vascular tone dysregulation. Silent infarcts may occur and are associated with decreased cognitive functions. Transcranial Doppler ultrasonography (TCD) was more recently demonstrated able to achieve early detection of the children at high risk for clinical strokes. A randomized study demonstrated that a first stroke may be prevented by monthly transfusion in children with abnormal TCD, leading to a recommendation for annual TCD screening of children aged between 2 and 16 years and monthly transfusion for those with abnormal results. In children who have had a first stroke, the risk of recurrence is more than 50% and is greatly reduced by chronic transfusion, although not completely abolished. Hematopoietic stem cell transplant is indicated in children with cerebral vasculopathy who have an HLA-identical sibling.

  18. Cerebrovascular mental stress reactivity is impaired in hypertension

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    Naqvi Tasneem Z

    2009-07-01

    Full Text Available Abstract Background Brachial artery reactivity in response to shear stress is altered in subjects with hypertension. Since endothelial dysfunction is generalized, we hypothesized that carotid artery (CA reactivity would also be altered in hypertension. Purpose To compare (CA endothelium-dependent vasodilation in response to mental stress in normal and hypertensive subjects. Methods We evaluated CA reactivity to mental stress in 10 young healthy human volunteers (aged 23 ± 4 years, 20 older healthy volunteers (aged 49 ± 11 years and in 28 patients with essential hypertension (aged 51 ± 13 years. In 10 healthy volunteers and 12 hypertensive subjects, middle cerebral artery (MCA PW transcranial Doppler was performed before and 3 minutes after mental stress. Results Mental stress by Stroop color word conflict, math or anger recall tests caused CA vasodilation in young healthy subjects (0.61 ± 0.06 to 0.65 ± 0.07 cm, p Conclusion Mental stress produces CA vasodilation and is accompanied by an increase in CA and MCA blood flow in healthy subjects. This mental stress induced CA vasodilation and flow reserve is attenuated in subjects with hypertension and may reflect cerebral vascular endothelial dysfunction. Assessment of mental stress induced CA reactivity by ultrasound is a novel method for assessing the impact of hypertension on cerebrovascular endothelial function and blood flow reserve.

  19. Magnetization transfer MR of cerebrovascular disorders using calculated images

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    Enomoto, Kyoko; Watabe, Tsuneya; Amanuma, Makoto; Heshiki, Atsuko [Saitama Medical School, Moroyama, Saitama (Japan)

    1997-06-01

    This study applied a magnetization transfer contrast method to patients with cerebrovascular disorders. A 1.5 T superconducting MR unit was used, and magnetization transfer ratio (MTR) images were calculated by evaluating two paired images before and after off-resonance gradient echo pulse sequences. The normal white matter showed the highest MTRs, CSF the lowest, and gray matter, intermediate. Cerebral ischemic patients showed two patterns according to the chronological stage of the affected area. Lesions in the acute and subacute stages revealed higher transfer rates than those in the chronic stage. Patients with cerebral hemorrhage were divided into three groups: the hyperacute group showed a low transfer pattern; the acute group presented inhomogeneous high transfer rates; and the subacute group showed remarkably low transfer rates. In the acute and subacute ischemic stages, increased macromolecules caused higher MTRs than in the chronic stage. In hemorrhagic groups, low MTRs in subacute hemorrhage reflected the transfer of methemoglobin. High MTRs in acute hemorrhage with rich deoxyhemoglobin suggested increased fibrin, plasma, and serum components of macromolecules. The MTC method provided new chronological information on cerebral hemorrhage, adding to that provided by routine MR images. (author)

  20. Relationship between retinal vascular occlusions and incident cerebrovascular diseases

    Science.gov (United States)

    Zhou, Yue; Zhu, Wengen; Wang, Changyun

    2016-01-01

    Abstract Several studies investigating the role of retinal vascular occlusions, on cerebrovascular diseases (CVD) have been reported, but the results are still inconsistent. We therefore sought to evaluate the relationship between retinal vascular occlusions and CVD. We systematically searched the Cochrane Library, PubMed, and ScienceDirect databases through January 31, 2016 for studies evaluating the effect of retinal vascular occlusions on the risk of CVD. Data were abstracted using predefined criteria, and then pooled by RevMan 5.3 software. A total of 9 retrospective studies were included in this meta-analysis. When compared with individuals without retinal vascular occlusions, both individuals with retinal artery occlusion (RAO) (odds ratio [OR] = 2.01, 95% confidence interval [CI]: 1.21–3.34; P = 0.005) and individuals with retinal vein occlusion (RVO) (OR = 1.37, 95% CI: 1.24–1.50; P < 0.00001) had higher risks of developing CVD. Additionally, both individuals with central retinal artery occlusion (CRAO) (OR = 2.00, 95% CI: 1.12–3.56; P = 0.02) and branch retinal artery occlusion (BRAO) (OR = 1.60, 95% CI: 1.03–1.48; P = 0.04) were significantly associated with increased risk of CVD. Published literatures support both RVO and RAO are associated with increased risks of CVD. Further prospective studies are needed to confirm these findings. PMID:27368050

  1. Dysphagia in patients with cerebrovascular disease. Update. Disfagia en paciente con enfermedad cerebrovascular. Actualización.

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    Yolanda Aguilera Martínez

    2009-03-01

    Full Text Available An important number of patients with cerebrovascular disease also present dysphagia as a result of damage in cerebral hemispheres or brainstem, which contributes to negative morbility and functional rehabilitation prognosis due to the complications liked with this condition. It is a significant cause of nutritional dysfunctions, including increased in-hospital undernourishment, increased per patient expenditure and longer in-hospital stay. One of the objectives of the Nutritional Support Team of the Neuroscience and Neurology Institute is to reduce undernourishment causes in patients with neurological diseases. A wide review of the subject was performed including experts´ opinions, from the above mentioned institutions, in order to gather an updated report related with the significance of early diagnosis of dysphagia in patients with ictus and the opportune and correct use of therapeutic measures to reduce complication risk.Gran número de pacientes con enfermedad cerebrovascular padecen de disfagia, por lesiones de hemisferios o del tronco cerebral, lo que, además de contribuir a un mal pronóstico en términos de morbilidad y recuperación funcional, por las complicaciones que acarrea, es causa importante de afectación del estado nutricional, con incremento de la desnutrición intrahospitalaria, de la estadía y de los costos por enfermo. Uno de los propósitos del Grupo de Apoyo Nutricional del Instituto de Neurología y Neurocirugía es minimizar las causas de desnutrición en los enfermos con trastornos neurológicos. Se realizó una amplia revisión del tema y se consultaron expertos del país, procedentes de las instituciones mencionadas antes, con el objetivo de conformar un informe actualizado relacionado con la importancia del diagnóstico precoz de la disfagia en el paciente con ictus y la aplicación oportuna y adecuada de medidas terapéuticas que disminuyan el riesgo de complicaciones.

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

    Science.gov (United States)

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

    2016-09-01

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

  3. Clinic Practical Guides for Cerebrovascular Diseases Guías de práctica clínica para las enfermedades cerebrovasculares

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    Alejandro Pando Cabrera

    Full Text Available The clinic practical guides for cerebrovascular diseases are presented. They include different aspects as its concept, classification, and epidemiological data in Cuba as well as worldwide. They also offer its diagnosis, classification, complications and treatment. The frequency of assessment of its application including the tools to measure the quality of life in patients with cerebrovascular accident and the way to proceed with them are shown
    Se presentan las guías de práctica clínica para las enfermedades cerebrovasculares. Incluye aspectos como su concepto y clasificación, datos epidemiológicos en el mundo y en Cuba, así como su diagnóstico, clasificación, complicaciones y tratamiento. Se ofrece la forma y frecuencia de la evaluación de su aplicación e incluye instrumentos para medir calidad de vida de los enfermos con accidentes cerebrovasculares.

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

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    Panayiota Papadopoulos

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

  5. Complement-dependent proinflammatory properties of the Alzheimer's disease beta-peptide.

    Science.gov (United States)

    Bradt, B M; Kolb, W P; Cooper, N R

    1998-08-03

    Large numbers of neuritic plaques (NP), largely composed of a fibrillar insoluble form of the beta-amyloid peptide (Abeta), are found in the hippocampus and neocortex of Alzheimer's disease (AD) patients in association with damaged neuronal processes, increased numbers of activated astrocytes and microglia, and several proteins including the components of the proinflammatory complement system. These studies address the hypothesis that the activated complement system mediates the cellular changes that surround fibrillar Abeta deposits in NP. We report that Abeta peptides directly and independently activate the alternative complement pathway as well as the classical complement pathway; trigger the formation of covalent, ester-linked complexes of Abeta with activation products of the third complement component (C3); generate the cytokine-like C5a complement-activation fragment; and mediate formation of the proinflammatory C5b-9 membrane attack complex, in functionally active form able to insert into and permeabilize the membrane of neuronal precursor cells. These findings provide inflammation-based mechanisms to account for the presence of complement components in NP in association with damaged neurons and increased numbers of activated glial cells, and they have potential implications for the therapy of AD.

  6. Endocannabinoids alleviate proinflammatory conditions by modulating innate immune response in muller glia during inflammation.

    Science.gov (United States)

    Krishnan, Gopinath; Chatterjee, Nivedita

    2012-11-01

    Muller cells play a prominent role in inflammatory conditions of the retina. They are part of the retinal innate immune response. The endocannabinoid system functions as an immune modulator in both the peripheral immune system as well as the central nervous system. We hypothesized that the neuroprotective ability of exogenous endocannabinoids in the retina is partially mediated through Muller glia. This study reports that exposure to endocannabinoids in activated but not resting primary human Muller glia inhibit production of several proinflammatory cytokines, while elevating anti-inflammatory mediators. Cytokine generation in activated Muller glia is regulated by endocannabinoids through the mitogen-activated protein kinase (MAPK) family at multiple signaling stages. Anandamide (AEA) acts to control MAPK phosphorylation through MKP-1. Both AEA and 2-arachidonoylglycerol (2-AG) inhibit the transcription factor NF-κB and increases the regulatory protein, IL1-R-associated kinase 1-binding protein 1. Endocannabinoids also increase expression of Tristetraprolin in activated Muller cells, which is implicated in affecting AU-rich proinflammatory cytokine mRNA. We demonstrate that exogenous application of AEA and 2-AG aid in retinal cell survival under inflammatory conditions by creating an anti-inflammatory milieu. Endocannabinoids or synthetic cannabinoid therapy may therefore orchestrate a molecular switch to bias the innate immune system suchthat the balance of pro- and anti-inflammatory cytokine generation creates a prosurvival milieu.

  7. 3D culture broadly regulates tumor cell hypoxia response and angiogenesis via pro-inflammatory pathways.

    Science.gov (United States)

    DelNero, Peter; Lane, Maureen; Verbridge, Scott S; Kwee, Brian; Kermani, Pouneh; Hempstead, Barbara; Stroock, Abraham; Fischbach, Claudia

    2015-07-01

    Oxygen status and tissue dimensionality are critical determinants of tumor angiogenesis, a hallmark of cancer and an enduring target for therapeutic intervention. However, it is unclear how these microenvironmental conditions interact to promote neovascularization, due in part to a lack of comprehensive, unbiased data sets describing tumor cell gene expression as a function of oxygen levels within three-dimensional (3D) culture. Here, we utilized alginate-based, oxygen-controlled 3D tumor models to study the interdependence of culture context and the hypoxia response. Microarray gene expression analysis of tumor cells cultured in 2D versus 3D under ambient or hypoxic conditions revealed striking interdependence between culture dimensionality and hypoxia response, which was mediated in part by pro-inflammatory signaling pathways. In particular, interleukin-8 (IL-8) emerged as a major player in the microenvironmental regulation of the hypoxia program. Notably, this interaction between dimensionality and oxygen status via IL-8 increased angiogenic sprouting in a 3D endothelial invasion assay. Taken together, our data suggest that pro-inflammatory pathways are critical regulators of tumor hypoxia response within 3D environments that ultimately impact tumor angiogenesis, potentially providing important therapeutic targets. Furthermore, these results highlight the importance of pathologically relevant tissue culture models to study the complex physical and chemical processes by which the cancer microenvironment mediates new vessel formation.

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

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    Yunfei Pu

    2013-11-01

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

  9. Changes in DNA Methylation and Chromatin Structure of Pro-inflammatory Cytokines Stimulated by LPS in Broiler Peripheral Blood Mononuclear Cells.

    Science.gov (United States)

    Shen, Jing; Liu, Yanli; Ren, Xiaochun; Gao, Kang; Li, Yulong; Li, Shizhao; Yao, Junhu; Yang, Xiaojun

    2016-07-01

    The pro-inflammatory cytokines IL-1β, IL-6, and tumor necrosis factor (TNF)-α mediate inflammation, which is a protective response by body to ensure removal of detrimental stimuli, as well as a healing process for repairing damaged tissue. The overproduction of pro-inflammatory cytokines can induce autoimmune diseases and can be fatal. The aim of this study was to investigate epigenetic mechanisms in the regulation of pro-inflammatory cytokines expression after lipopolysaccharide (LPS) stimulation of broiler peripheral blood mononuclear cells (PBMC). Gene expression, promoter DNA methylation, and chromatin accessibility of pro-inflammatory cytokines in untreated and LPS-treated PBMC were compared. The expression of epigenetic enzymes DNA methyltransferase (DNMT) 1, histone deacetylase (HDAC), and histone acetylase (HAT) were measured after LPS stimulation. The results showed the activated gene expression of pro-inflammatory cytokines in broiler PBMC stimulated 3 h by LPS. The demethylation of IL-6 gene - 302 and -264 cytosine-guanine (CpG) sites, as well as TNF-α gene -371 CpG site, occurred after LPS treatment (P pro-inflammatory cytokines.

  10. Defining the role of DAG, mitochondrial function, and lipid deposition in palmitate-induced proinflammatory signaling and its counter-modulation by palmitoleate.

    Science.gov (United States)

    Macrae, Katherine; Stretton, Clare; Lipina, Christopher; Blachnio-Zabielska, Agnieszka; Baranowski, Marcin; Gorski, Jan; Marley, Anna; Hundal, Harinder S

    2013-09-01

    Chronic exposure of skeletal muscle to saturated fatty acids, such as palmitate (C16:0), enhances proinflammatory IKK-NFκB signaling by a mechanism involving the MAP kinase (Raf-MEK-ERK) pathway. Raf activation can be induced by its dissociation from the Raf-kinase inhibitor protein (RKIP) by diacylglycerol (DAG)-sensitive protein kinase C (PKC). However, whether these molecules mediate the proinflammatory action of palmitate, an important precursor for DAG synthesis, is currently unknown. Here, involvement of DAG-sensitive PKCs, RKIP, and the structurally related monounsaturated fatty acid palmitoleate (C16:1) on proinflammatory signaling are investigated. Palmitate, but not palmitoleate, induced phosphorylation/activation of the MEK-ERK-IKK axis and proinflammatory cytokine (IL-6, CINC-1) expression. Palmitate increased intramyocellular DAG and invoked PKC-dependent RKIP(Ser153) phosphorylation, resulting in RKIP-Raf1 dissociation and MEK-ERK signaling. These responses were mimicked by PMA, a DAG mimetic and PKC activator. However, while pharmacological inhibition of PKC suppressed PMA-induced activation of MEK-ERK-IKK signaling, activation by palmitate was upheld, suggesting that DAG-sensitive PKC and RKIP were dispensable for palmitate's proinflammatory action. Strikingly, the proinflammatory effect of palmitate was potently repressed by palmitoleate. This repression was not due to reduced palmitate uptake but linked to increased neutral lipid storage and enhanced cellular oxidative capacity brought about by palmitoleate's ability to restrain palmitate-induced mitochondrial dysfunction.

  11. Tratamiento de Terapia Ocupacional en el accidente cerebrovascular

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    Domingo García, AM

    2006-02-01

    Full Text Available RESUMENEntre los muchos pacientes que necesitan tratamiento rehabilitador en Terapia Ocupacional están los que en la edad adulta han sufrido un accidente cerebrovascular.Uno de los factores de riesgo asociados con más frecuencia a las alteraciones del sistema nervioso central es el progresivo envejecimiento de la población, debido a esto orientaré el siguiente artículo hacia la intervención sobre la población geriátrica.La Terapia Ocupacional ofrece un tratamiento global que abarca las áreas funcional, motriz, sensorial, perceptivo y cognitiva. No debemos olvidar el asesoramiento realizado al paciente, a la familia y/ o cuidadores sobre el manejo de la persona que ha sufrido un ictus, la adaptación del entorno y la prescripción, uso y manejo de ayudas técnicas cuando sea necesario.Las propuestas terapéuticas que expondré a continuación, no son recetas únicas que se puedan emplear del mismo modo en todos las personas que hayan sufrido un ictus. Con cada paciente será necesario una evaluación individualizada de su situación y una adaptación de la terapia según sus déficit específicos.La meta final de la Terapia Ocupacional es la integración óptima del paciente dentro de su entorno familiar y social, con el mayor grado de autonomía posible.ABSTRACTAmong the patients who need Occupational Therapy’s rehabilitation treatment, there are those who have suffered a cerebrovascular damage when elderly.People’s gradual ageing is one of the risk factors in the nervous central system’s alterations and this is why I am going to write about intervention on geriatric population.The Occupational Therapy’s rehabilitation treatment works on the functional, motor, sensorial, perceptive and cognitive areas. Moreover, we should not forget to advise the patient and his/her family or caregivers about the way of treating ,the environment’s adaptation, the prescription and use of technical aids when needed.The following therapeutic

  12. HIGH SENSITIVE C-REACTIVE PROTEIN IN CEREBROVASCULAR ISCHEMIA

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    Padmalatha

    2016-02-01

    Full Text Available BACKGROUND Cerebrovascular ischemia is recognized as a major health problem, which causes significant morbidity and mortality. The main pathophysiology of ischemic stroke is atherosclerosis of cerebral vessels. Hs-CRP is a sensitive marker of inflammation tissue injury in the arterial wall, which contributes to atherosclerosis. In this study, we aim to investigate the association of hs-CRP in patients with ischemic stroke and to correlate hs-CRP levels with possible risk factors of ischemic stroke and to assess the prognostic value of hs-CRP in ischemic stroke. METHODS In the present case control study after meeting inclusion and exclusion criteria, 50 patients with acute ischemic stroke admitted in the medical ward, King George Hospital, during the period between April 2014 and October 2014 and 40 asymptomatic age and sex matched control subjects were included. RESULTS The mean hs-CRP value in cases is 3.78+5.28mg/dl and in controls is 0.425+0.305mg/dl. Mean hs-CRP value is higher (3.78mg/dl in cases when compared to controls (0.425mg/dl, which is statistically significant. P admitted with severe degree of weakness (0-1/5 power with mean hs-CRP value of 4.28+4.07 without significant improvement in the power at the time of discharge; 8(16%> with mean hs-CRP value of 10.43+7.74 were expired. CONCLUSION Acute ischemic patients had higher mean hs-CRP values when compared to healthy asymptomatic control subjects P0.05. Higher mean hs-CRP values were associated with poor outcome after acute ischemic stroke. P<0.001.

  13. Haemodynamic and cerebrovascular responses to glycerol infusion in dogs.

    Science.gov (United States)

    Chen, J L; Wang, Y C; Wang, J Y

    1989-11-01

    1. The response of cerebral blood vessels to hyperosmolar agents in vivo remains controversial, and little is known about the effect of glycerol on cerebral vessels. In this study we investigated the cerebrovascular response to intravenous administration of glycerol (1 g/kg, infused over 25 min) in dogs under pentobarbital anaesthesia. 2. intracranial pressure, systemic arterial pressure, mean arterial blood pressure, serum osmolarity and packed cell volume were continuously monitored, and blood gases were checked frequently. Through a parietal cranial window, pial vessel diameter was measured by means of a surgical microscope and a video image-analyser. 3. Pial vessel diameter increased gradually with a maximum at 30 min after the beginning of glycerol infusion. The maximum increase in diameter in small (less than or equal to 100 microns) vessels was 14.3%, whereas that in large (greater than 100 microns) vessels was 10.3%. There was only a slight increase (less than 4%) in pial vessel diameter in vehicle-infused animals. The intracranial pressure decreased drastically after glycerol infusion, whereas the mean arterial blood pressure remained constant. There were correlations between the rise in serum osmolarity, fall in packed cell volume and vasodilatation, indicating that glycerol caused vasodilatation accompanied by plasma volume expansion. 4. Our data suggest that glycerol produces cerebral vasodilatation, which might be beneficial in cerebral ischaemia and vasospasm, in addition to its intracranial pressure-reducing effect on normal or oedematous brain. The degree of vasodilatation was not sufficient to affect the predominant intracranial pressure drop resulting from cerebral dehydration.

  14. Imaging of cerebrovascular pathology in animal models of Alzheimer's disease

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    Klohs, Jan; Rudin, Markus; Shimshek, Derya R.; Beckmann, Nicolau

    2014-01-01

    In Alzheimer's disease (AD), vascular pathology may interact with neurodegeneration and thus aggravate cognitive decline. As the relationship between these two processes is poorly understood, research has been increasingly focused on understanding the link between cerebrovascular alterations and AD. This has at last been spurred by the engineering of transgenic animals, which display pathological features of AD and develop cerebral amyloid angiopathy to various degrees. Transgenic models are versatile for investigating the role of amyloid deposition and vascular dysfunction, and for evaluating novel therapeutic concepts. In addition, research has benefited from the development of novel imaging techniques, which are capable of characterizing vascular pathology in vivo. They provide vascular structural read-outs and have the ability to assess the functional consequences of vascular dysfunction as well as to visualize and monitor the molecular processes underlying these pathological alterations. This article focusses on recent in vivo small animal imaging studies addressing vascular aspects related to AD. With the technical advances of imaging modalities such as magnetic resonance, nuclear and microscopic imaging, molecular, functional and structural information related to vascular pathology can now be visualized in vivo in small rodents. Imaging vascular and parenchymal amyloid-β (Aβ) deposition as well as Aβ transport pathways have been shown to be useful to characterize their dynamics and to elucidate their role in the development of cerebral amyloid angiopathy and AD. Structural and functional imaging read-outs have been employed to describe the deleterious affects of Aβ on vessel morphology, hemodynamics and vascular integrity. More recent imaging studies have also addressed how inflammatory processes partake in the pathogenesis of the disease. Moreover, imaging can be pivotal in the search for novel therapies targeting the vasculature. PMID:24659966

  15. Cerebrovascular Time Constant in Patients with Head Injury.

    Science.gov (United States)

    Trofimov, Alex; Kalentiev, George; Gribkov, Alexander; Voennov, Oleg; Grigoryeva, Vera

    2016-01-01

    The cerebrovascular time constant (τ) theoretically estimates how fast the cerebral arterial bed is filled by blood volume after a sudden change in arterial blood pressure during one cardiac cycle. The aim of this study was to assess the time constant of the cerebral arterial bed in patients with traumatic brain injury (TBI) with and without intracranial hematomas (IH). We examined 116 patients with severe TBI (mean 35 ± 15 years, 61 men, 55 women). The first group included 58 patients without IH and the second group included 58 patients with epidural (7), subdural (48), and multiple (3) hematomas. Perfusion computed tomography (PCT) was performed 1-12 days after TBI in the first group and 2-8 days after surgical evacuation of the hematoma in the second group. Arteriovenous amplitude of regional cerebral blood volume oscillation was calculated as the difference between arterial and venous blood volume in the "region of interest" of 1 cm(2). Mean arterial pressure was measured and the flow rate of the middle cerebral artery was recorded with transcranial Doppler ultrasound after PCT. The time constant was calculated by the formula modified by Kasprowicz. The τ was shorter (p = 0.05) in both groups 1 and 2 in comparison with normal data. The time constant in group 2 was shorter than in group 1, both on the side of the former hematoma (р = 0.012) and on the contralateral side (р = 0.044). The results indicate failure of autoregulation of cerebral capillary blood flow in severe TBI, which increases in patients with polytrauma and traumatic IH.

  16. Combined effects of proinflammatory cytokines and intermittent cyclic mechanical strain in inhibiting osteogenicity in human periodontal ligament cells.

    Science.gov (United States)

    Sun, Chaofan; Chen, Lijiao; Shi, Xinlian; Cao, Zhensheng; Hu, Bibo; Yu, Wenbin; Ren, Manman; Hu, Rongdang; Deng, Hui

    2016-09-01

    Mechanical strain plays an important role in bone formation and resorption during orthodontic tooth movement. The mechanism has not been fully studied, and the process becomes complex with increased amounts of periodontal patients seeking orthodontic care. Our aims were to elucidate the combined effects of proinflammatory cytokines and intermittent cyclic strain (ICS) on the osteogenic capacity of human periodontal ligament cells. Cultured human periodontal ligament cells were exposed to proinflammatory cytokines (interleukin-1β 5 ng/mL and tumor necrosis factor-α 10 ng/mL) for 1 and 5 days, and ICS (0.5 Hz, 12% elongation) was applied for 4 h per day. The autocrine of inflammatory cytokines was measured by enzyme-linked immunosorbent assay. The expression of osteoblast markers runt-related transcription factor 2 and rabbit collagen type I was determined using real-time polymerase chain reaction and Western blot. The osteogenic capacity was also detected by alkaline phosphatase (ALP) staining, ALP activity, and alizarin red staining. We demonstrated that ICS impaired the osteogenic capacity of human periodontal ligament cells when incubated with proinflammatory cytokines, as evidenced by the low expression of ALP staining, low ALP activity, reduced alizarin red staining, and reduced osteoblast markers. These data, for the first time, suggest that ICS has a negative effect on the inductive inhibition of osteogenicity in human PDL cells mediated by proinflammatory cytokines.

  17. Nonlinear effects of respiration on the crosstalk between cardiovascular and cerebrovascular control systems.

    Science.gov (United States)

    Bari, Vlasta; Marchi, Andrea; De Maria, Beatrice; Rossato, Gianluca; Nollo, Giandomenico; Faes, Luca; Porta, Alberto

    2016-05-13

    Cardiovascular and cerebrovascular regulatory systems are vital control mechanisms responsible for guaranteeing homeostasis and are affected by respiration. This work proposes the investigation of cardiovascular and cerebrovascular control systems and the nonlinear influences of respiration on both regulations through joint symbolic analysis (JSA), conditioned or unconditioned on respiration. Interactions between cardiovascular and cerebrovascular regulatory systems were evaluated as well by performing correlation analysis between JSA indexes describing the two control systems. Heart period, systolic and mean arterial pressure, mean cerebral blood flow velocity and respiration were acquired on a beat-to-beat basis in 13 subjects experiencing recurrent syncope episodes (SYNC) and 13 healthy individuals (non-SYNC) in supine resting condition and during head-up tilt test at 60° (TILT). Results showed that JSA distinguished conditions and groups, whereas time domain parameters detected only the effect of TILT. Respiration affected cardiovascular and cerebrovascular regulatory systems in a nonlinear way and was able to modulate the interactions between the two control systems with different outcome in non-SYNC and SYNC groups, thus suggesting that the analysis of the impact of respiration on cardiovascular and cerebrovascular regulatory systems might improve our understanding of the mechanisms underpinning the development of postural-related syncope.

  18. Brain imaging changes associated with risk factors for cardiovascular and cerebrovascular disease in asymptomatic patients.

    Science.gov (United States)

    Friedman, Joseph I; Tang, Cheuk Y; de Haas, Hans J; Changchien, Lisa; Goliasch, Georg; Dabas, Puneet; Wang, Victoria; Fayad, Zahi A; Fuster, Valentin; Narula, Jagat

    2014-10-01

    Reviews of imaging studies assessing the brain effects of vascular risk factors typically include a substantial number of studies with subjects with a history of symptomatic cardiovascular or cerebrovascular disease and/or events, limiting our ability to disentangle the primary brain effects of vascular risk factors from those of resulting brain and cardiac damage. The objective of this study was to perform a systematic review of brain changes from imaging studies in patients with vascular risk factors but without clinically manifest cardiovascular or cerebrovascular disease or events. The 77 studies included in this review demonstrate that in persons without symptomatic cardiovascular, cerebrovascular, or peripheral vascular disease, the vascular risk factors of hypertension, diabetes mellitus, obesity, hyperlipidemia, and smoking are all independently associated with brain imaging changes before the clinical manifestation of cardiovascular or cerebrovascular disease. We conclude that the identification of brain changes associated with vascular risk factors, before the manifestation of clinically significant cerebrovascular damage, presents a window of opportunity wherein adequate treatment of these modifiable vascular risk factors may prevent the development of irreversible deleterious brain changes and potentially alter patients' clinical course.

  19. Nonlinear effects of respiration on the crosstalk between cardiovascular and cerebrovascular control systems

    Science.gov (United States)

    Bari, Vlasta; Marchi, Andrea; De Maria, Beatrice; Rossato, Gianluca; Nollo, Giandomenico; Faes, Luca; Porta, Alberto

    2016-05-01

    Cardiovascular and cerebrovascular regulatory systems are vital control mechanisms responsible for guaranteeing homeostasis and are affected by respiration. This work proposes the investigation of cardiovascular and cerebrovascular control systems and the nonlinear influences of respiration on both regulations through joint symbolic analysis (JSA), conditioned or unconditioned on respiration. Interactions between cardiovascular and cerebrovascular regulatory systems were evaluated as well by performing correlation analysis between JSA indexes describing the two control systems. Heart period, systolic and mean arterial pressure, mean cerebral blood flow velocity and respiration were acquired on a beat-to-beat basis in 13 subjects experiencing recurrent syncope episodes (SYNC) and 13 healthy individuals (non-SYNC) in supine resting condition and during head-up tilt test at 60° (TILT). Results showed that JSA distinguished conditions and groups, whereas time domain parameters detected only the effect of TILT. Respiration affected cardiovascular and cerebrovascular regulatory systems in a nonlinear way and was able to modulate the interactions between the two control systems with different outcome in non-SYNC and SYNC groups, thus suggesting that the analysis of the impact of respiration on cardiovascular and cerebrovascular regulatory systems might improve our understanding of the mechanisms underpinning the development of postural-related syncope.

  20. Cerebrovascular Acute Radiation Syndrome : Radiation Neurotoxins, Mechanisms of Toxicity, Neuroimmune Interactions.

    Science.gov (United States)

    Popov, Dmitri; Maliev, Slava

    Introduction: Cerebrovascular Acute Radiation Syndrome (CvARS) is an extremely severe in-jury of Central Nervous System (CNS) and Peripheral Nervous System (PNS). CvARS can be induced by the high doses of neutron, heavy ions, or gamma radiation. The Syndrome clinical picture depends on a type, timing, and the doses of radiation. Four grades of the CvARS were defined: mild, moderate, severe, and extremely severe. Also, four stages of CvARS were developed: prodromal, latent, manifest, outcome -death. Duration of stages depends on the types, doses, and time of radiation. The CvARS clinical symptoms are: respiratory distress, hypotension, cerebral edema, severe disorder of cerebral blood microcirculation, and acute motor weakness. The radiation toxins, Cerebro-Vascular Radiation Neurotoxins (SvARSn), determine development of the acute radiation syndrome. Mechanism of action of the toxins: Though pathogenesis of radiation injury of CNS remains unknown, our concept describes the Cv ARS as a result of Neurotoxicity and Excitotoxicity, cell death through apoptotic necrosis. Neurotoxicity occurs after the high doses radiation exposure, formation of radiation neuro-toxins, possible bioradicals, or group of specific enzymes. Intracerebral hemorrhage can be a consequence of the damage of endothelial cells caused by radiation and the radiation tox-ins. Disruption of blood-brain barrier (BBB)and blood-cerebrospinal fluid barrier (BCFB)is possibly the most significant effect of microcirculation disorder and metabolic insufficiency. NMDA-receptors excitotoxic injury mediated by cerebral ischemia and cerebral hypoxia. Dam-age of the pyramidal cells in layers 3 and 5 and Purkinje cell layer the cerebral cortex , damage of pyramidal cells in the hippocampus occur as a result of cerebral ischemia and intracerebral bleeding. Methods: Radiation Toxins of CV ARS are defined as glycoproteins with the molec-ular weight of RT toxins ranges from 200-250 kDa and with high enzymatic activity

  1. Postprandial hyperglycemia and cerebrovascular diseases%餐后高血糖与脑血管病

    Institute of Scientific and Technical Information of China (English)

    辛家厚; 周农

    2009-01-01

    Postprandial hyperglycemia is a risk factor for atherosclerosis and cerebro-vascular diseases. This article reviews the mechanisms of cerebrovascular diseases caused by postprandial hyperglycemia from aspects of postprandial hyperglycemia participating in the pathophysiological mechanisms of atherosclerosis, and the relations between postprandial hyperglycemia and cerebrovascular diseases.%餐后血糖升高是动脉粥样硬化和脑血管病的危险因素.文章分别从餐后高血糖参与动脉粥样硬化的病理生理学机制、餐后高血糖与脑血管病的关系及其病理生理学机制等方面,综述了餐后高血糖引起脑血管病的机制.

  2. Cancer as a Proinflammatory Environment: Metastasis and Cachexia

    Directory of Open Access Journals (Sweden)

    Nelson Inácio Pinto

    2015-01-01

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

  3. Pro-inflammatory responses of human bronchial epithelial cells to acute nitrogen dioxide exposure.

    Science.gov (United States)

    Ayyagari, Vijayalakshmi N; Januszkiewicz, Adolph; Nath, Jayasree

    2004-04-15

    Nitrogen dioxide (NO2) is an environmental oxidant, known to be associated with lung epithelial injury. In the present study, cellular pro-inflammatory responses following exposure to a brief high concentration of NO2 (45 ppm) were assessed, using normal human bronchial epithelial (NHBE) cells as an in vitro model of inhalation injury. Generation and release of pro-inflammatory mediators such as nitric oxide (NO), IL-8, TNF-alpha, IFN-gamma and IL-1beta were assessed at different time intervals following NO2 exposure. Effects of a pre-existing inflammatory condition was tested by treating the NHBE cells with different inflammatory cytokines such as IFN-gamma, IL-8, TNF-alpha, IL-1beta, either alone or in combination, before exposing them to NO2. Immunofluorescence studies confirmed oxidant-induced formation of 3-nitrotyrosine in the NO2-exposed cells. A marked increase in the levels of nitrite (as an index of NO) and IL-8 were observed in the NO2-exposed cells, which were further enhanced in the presence of the cytokines. Effects of various NO inhibitors combined, with immunofluorescence and Western blotting data, indicated partial contribution of the nitric oxide synthases (NOSs) toward the observed increase in nitrite levels. Furthermore, a significant increase in IL-1beta and TNF-alpha generation was observed in the NO2-exposed cells. Although NO2 exposure alone did induce slight cytotoxicity (<12%), but presence of inflammatory cytokines such as TNF-alpha and IFN-gamma resulted in an increased cell death (28-36%). These results suggest a synergistic role of inflammatory mediators, particularly of NO and IL-8, in NO2-mediated early cellular changes. Our results also demonstrate an increased sensitivity of the cytokine-treated NHBE cells toward NO2, which may have significant functional implications in vivo.

  4. Interleukin-32 production associated with biliary innate immunity and proinflammatory cytokines contributes to the pathogenesis of cholangitis in biliary atresia.

    Science.gov (United States)

    Okamura, A; Harada, K; Nio, M; Nakanuma, Y

    2013-08-01

    Biliary atresia (BA) is thought to be associated with infections by viruses such as Reoviridae and is characterized histologically by fibrosclerosing cholangitis with proinflammatory cytokine-mediated inflammation. Interleukin (IL)-32 affects the continuous inflammation by increasing the production of proinflammatory cytokines. In this study, the role of IL-32 in the cholangitis of BA was examined. Immunohistochemistry for IL-32 and caspase 1 was performed using 21 samples of extrahepatic bile ducts resected from BA patients. Moreover, using cultured human biliary epithelial cells (BECs), the expression of IL-32 and its induction on stimulation with a Toll-like receptor [(TLR)-3 ligand (poly(I:C)] and proinflammatory cytokines was examined. BECs composing extrahepatic bile ducts showing cholangitis expressed IL-32 in BA, but not in controls. Caspase 1 was expressed constantly on BECs of both BA and control subjects. Furthermore, poly(I:C) and proinflammatory cytokines [(IL-1β, interferon (IFN)-γ and tumour necrosis factor (TNF)-α] induced IL-32 expression strongly in cultured BECs, accompanying the constant expression of TLR-3 and caspase 1. Our results imply that the expression of IL-32 in BECs was found in the damaged bile ducts of BA and induced by biliary innate immunity via TLR-3 and proinflammatory cytokines. These findings suggest that IL-32 is involved initially in the pathogenic mechanisms of cholangitis in BA and also plays an important role in the amplification and continuance of periductal inflammatory reactions. It is therefore tempting to speculate that inhibitors of IL-32 could be useful for attenuating cholangitis in BA.

  5. Cerebral blood flow, oxidative metabolism and cerebrovascular carbon dioxide reactivity in patients with acute bacterial meningitis

    DEFF Research Database (Denmark)

    Møller, Kirsten; Strauss, Gitte Irene; Thomsen, Gerda;

    2002-01-01

    BACKGROUND: The optimal arterial carbon dioxide tension (P(a)CO(2)) in patients with acute bacterial meningitis (ABM) is unknown and controversial. The objective of this study was to measure global cerebral blood flow (CBF), cerebrovascular CO(2) reactivity (CO(2)R), and cerebral metabolic rates...... to baseline ventilation, whereas CMR(glu) increased. CONCLUSION: In patients with acute bacterial meningitis, we found variable levels of CBF and cerebrovascular CO(2) reactivity, a low a-v DO(2), low cerebral metabolic rates of oxygen and glucose, and a cerebral lactate efflux. In these patients...

  6. Different cerebrovascular effects of medroxyprogesterone acetate and norethisterone acetate in the New Zealand White rabbit

    DEFF Research Database (Denmark)

    Pedersen, S H; Pedersen, N G; Dalsgaard, T;

    2004-01-01

    of different progestins on cerebrovascular reactivity in an animal model. METHODS: Fifty-six ovariectomized New Zealand White rabbits were randomized into seven groups receiving hormone treatment for 4 weeks: medroxyprogesterone acetate (MPA) (10 mg/day); norethisterone acetate (NETA) (3 mg/day); conjugated....... No overall differences were seen between CEE and E2. CONCLUSIONS: In rabbit cerebral arteries, MPA treatment causes a higher development in arterial tension compared with NETA, indicating that different progestins may display different cerebrovascular effects. However, when accompanied by estrogens...

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

    Directory of Open Access Journals (Sweden)

    Victoria Florea

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

  8. Ex vivo and in vitro production of pro-inflammatory cytokines in Blau syndrome

    Directory of Open Access Journals (Sweden)

    P. Galozzi

    2015-03-01

    Full Text Available The objective was to study both ex vivo and in vitro secretion of pro-inflammatory cytokines in patients affected by Blau syndrome (BS and carrying p.E383K mutation in the CARD15/NOD2 gene associated with the disease. For ex vivo studies, peripheral blood mononuclear cells (PBMCs, serum from three patients and healthy controls have been collected. PBMCs have been cultured in the presence or absence of inflammatory enhancers, such as lipopolysaccharide (LPS and muramyl dipeptide (MDP. The levels of interleukin (IL-1β, IL-6, IL-8, tumor necrosis factor (TNF-α and interferon (IFN-γ were assayed by either immunoassay or array-based system. For in vitro studies, different constructs were created cloning human wild-type and p.E383K-mutated NOD2 cDNA into the expression vector pCMV-Tag2c. HEK293 cell lines were stably transfected, cultured with or without MDP and IL-8 level was assayed in their surnatants. Statistical analysis in both studies was performed using non-parametric tests. Both ex vivo and in vitro studies have not identified a significant increase in secretion of the analyzed proinflammatory cytokines. p.E383K-mutated NOD2 transfected cells express low level of IL-8. The ex vivo basal level results from both serum and PBMCs surnatants present similar levels of IL-1β, IL-6, TNF-α and IFN-γ in patients and controls. The presence of the stimulant agents (LPS and MDP, either individual or paired, does not lead to significant increases in all cytokines concentrations in patients compared to controls. Taken together, the ex vivo and in vitro data suggest that there is not a primary mediation of IL-1β and other pro-inflammatory cytokines in BS patients carrying p.E383K.

  9. [Elevation of proinflammatory cytokines level at early age as the risk factor of neurological and mental pathology development].

    Science.gov (United States)

    Zubarev, O E; Klimenko, V M

    2011-10-01

    Proinflammatory cytokines Interleukin-1, Interleukin-6 (IL-1, IL-6) and tumour necrosis factor alpha (TNFalpha), the key mediators of neuroimmune interactions, are the common pathogenic part of various kinds of the perinatal pathology leading to severe neurological and mental diseases. In the review, features of expression of the proinflammatory cytokines and their receptors in the brain at early age under normal and pathological conditions, their influence on processes of maturing of the CNS cells are described, the data of experimental and clinical researches of disturbances of the mental functions arising in adults owing to elevation of the IL-1, IL-6 levels and TNFalpha in early ontogenesis are cited. The role of the cytokines in pathogenesis of schizophrenia, a syndrome of attention deficiency, autism and a Parkinsonism is discussed.

  10. Myeloperoxidase modulates lung epithelial responses to pro-inflammatory agents

    NARCIS (Netherlands)

    Haegens, A.; Vernooy, J. H. J.; Heeringa, P.; Mossman, B. T.; Wouters, E. F. M.

    2008-01-01

    During extensive inflammation, neutrophils undergo secondary necrosis causing myeloperoxidase (MPO) release that may damage resident lung cells. Recent observations suggest that MPO has pro-inflammatory properties, independent of its enzymatic activity. The aims of the present study were to characte

  11. Interleukin 10 inhibits pro-inflammatory cytokine responses and killing of Burkholderia pseudomallei

    Science.gov (United States)

    Kessler, Bianca; Rinchai, Darawan; Kewcharoenwong, Chidchamai; Nithichanon, Arnone; Biggart, Rachael; Hawrylowicz, Catherine M.; Bancroft, Gregory J.; Lertmemongkolchai, Ganjana

    2017-01-01

    Melioidosis, caused by Burkholderia pseudomallei, is endemic in northeastern Thailand and Northern Australia. Severe septicemic melioidosis is associated with high levels of pro-inflammatory cytokines and is correlated with poor clinical outcomes. IL-10 is an immunoregulatory cytokine, which in other infections can control the expression of pro-inflammatory cytokines, but its role in melioidosis has not been addressed. Here, whole blood of healthy seropositive individuals (n = 75), living in N. E. Thailand was co-cultured with B. pseudomallei and production of IL-10 and IFN-γ detected and the cellular sources identified. CD3− CD14+ monocytes were the main source of IL-10. Neutralization of IL-10 increased IFN-γ, IL-6 and TNF-α production and improved bacteria killing. IFN-γ production and microbicidal activity were impaired in individuals with diabetes mellitus (DM). In contrast, IL-10 production was unimpaired in individuals with DM, resulting in an IL-10 dominant cytokine balance. Neutralization of IL-10 restored the IFN-γ response of individuals with DM to similar levels observed in healthy individuals and improved killing of B. pseudomallei in vitro. These results demonstrate that monocyte derived IL-10 acts to inhibit potentially protective cell mediated immune responses against B. pseudomallei, but may also moderate the pathological effects of excessive cytokine production during sepsis. PMID:28216665

  12. Rationale and Means to Target Pro-Inflammatory Interleukin-8 (CXCL8 Signaling in Cancer

    Directory of Open Access Journals (Sweden)

    Laura M. Campbell

    2013-08-01

    Full Text Available It is well established that chronic inflammation underpins the development of a number of human cancers, with pro-inflammatory signaling within the tumor microenvironment contributing to tumor progression and metastasis. CXCL8 is an ELR+ pro-inflammatory CXC-chemokine which mediates its effects via signaling through two G protein-coupled receptors, CXCR1 and CXCR2. Elevated CXCL8-CXCR1/2 signaling within the tumor microenvironment of numerous cancers is known to enhance tumor progression via activation of signaling pathways promoting proliferation, angiogenesis, migration, invasion and cell survival. This review provides an overview of established roles of CXCL8-CXCR1/2 signaling in cancer and subsequently, discusses the possible strategies of targeting CXCL8-CXCR1/2 signaling in cancer, covering indirect strategies (e.g., anti-inflammatories, NFκB inhibitors and direct CXCL8 or CXCR1/2 inhibition (e.g., neutralizing antibodies, small molecule receptor antagonists, pepducin inhibitors and siRNA strategies. Reports of pre-clinical cancer studies and clinical trials using CXCL8-CXCR1/2-targeting strategies for the treatment of inflammatory diseases will be discussed. The future translational opportunities for use of such agents in oncology will be discussed, with emphasis on exploitation in stratified populations.

  13. Neutralization Versus Reinforcement of Proinflammatory Cytokines to Arrest Autoimmunity in Type 1 Diabetes.

    Science.gov (United States)

    Kaminitz, Ayelet; Ash, Shifra; Askenasy, Nadir

    2016-09-27

    As physiological pathways of intercellular communication produced by all cells, cytokines are involved in the pathogenesis of inflammatory insulitis as well as pivotal mediators of immune homeostasis. Proinflammatory cytokines including interleukins, interferons, transforming growth factor-β, tumor necrosis factor-α, and nitric oxide promote destructive insulitis in type 1 diabetes through amplification of the autoimmune reaction, direct toxicity to β-cells, and sensitization of islets to apoptosis. The concept that neutralization of cytokines may be of therapeutic benefit has been tested in few clinical studies, which fell short of inducing sustained remission or achieving disease arrest. Therapeutic failure is explained by the redundant activities of individual cytokines and their combinations, which are rather dispensable in the process of destructive insulitis because other cytolytic pathways efficiently compensate their deficiency. Proinflammatory cytokines are less redundant in regulation of the inflammatory reaction, displaying protective effects through restriction of effector cell activity, reinforcement of suppressor cell function, and participation in islet recovery from injury. Our analysis suggests that the role of cytokines in immune homeostasis overrides their contribution to β-cell death and may be used as potent immunomodulatory agents for therapeutic purposes rather than neutralized.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  15. Preserved metabolic coupling and cerebrovascular reactivity during mild hypothermia after cardiac arrest.

    NARCIS (Netherlands)

    Bisschops, L.L.A.; Hoedemaekers, C.W.E.; Simons, K.S.; Hoeven, J.G. van der

    2010-01-01

    OBJECTIVE: Although mild hypothermia improves outcome in patients after out-of-hospital cardiac arrest, the cardiodepressive effects of hypothermia may lead to secondary brain damage. This study was performed to assess the cerebral blood flow, cerebral oxygen extraction, and cerebrovascular reactivi

  16. A novel distinctive cerebrovascular phenotype is associated with heterozygous Arg179 ACTA2 mutations

    NARCIS (Netherlands)

    Munot, Pinki; Saunders, Dawn E.; Milewicz, Dianna M.; Regalado, Ellen S.; Ostergaard, John R.; Braun, Kees P.; Kerr, Timothy; Lichtenbelt, Klaske D.; Philip, Sunny; Rittey, Christopher; Jacques, Thomas S.; Cox, Timothy C.; Ganesan, Vijeya

    2012-01-01

    Mutations in the ACTA2 gene lead to diffuse and diverse vascular diseases; the Arg179His mutation is associated with an early onset severe phenotype due to global smooth muscle dysfunction. Cerebrovascular disease associated with ACTA2 mutations has been likened to moyamoya disease, but appears to h

  17. Cerebrovascular risk factors and subsequent depression in older general practice patients

    NARCIS (Netherlands)

    Nuyen, Jasper; Spreeuwenberg, Peter M.; Beekman, Aartjan T.F.; Groenewegen, Peter P.; Bos, Geertrudis A.M. van den; Schellevis, Francois G.

    2007-01-01

    Background: This general practice-based case-control study tested the association between cerebrovascular risk factors (CVRFs) and the development of later-life depression by focusing on the impact of exposure duration to CVRFs and the modifying influence of age at depression onset. Methods: Cases w

  18. Rare cerebrovascular anomalies in a patient with Cornelia De Lange Syndrome

    Directory of Open Access Journals (Sweden)

    Jesse Jones

    2015-01-01

    Conclusion: Advance knowledge of cerebrovascular variants associated with CDL may help interventionalists prepare to approach such cases. Additionally, further inquiry into the function of proteins encoded by genes associated with CDL could better our understanding of vascular development in the brain.

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  20. Cerebrovascular risk factors and subsequent depression in older general practice patients.

    NARCIS (Netherlands)

    Nuyen, J.; Spreeuwenberg, P.M.; Beekman, A.T.F.; Groenewegen, P.P.; Bos, G.A.M. van den; Schellevis, F.G.

    2007-01-01

    Background: This general practice-based case-control study tested the association between cerebrovascular risk factors (CVRFs) and the development of later-life depression by focusing on the impact of exposure duration to CVRFs and the modifying influence of age at depression onset. Methods: Cases w

  1. Clinical and anatomical consequences of impaired cerebrovascular reserve as detectable by quantitative functional MR imaging

    NARCIS (Netherlands)

    Fierstra, J.

    2012-01-01

    Brain areas exhibiting impaired cerebrovascular reserve are believed to be at higher risk of ischemic tissue injury under circumstances in which cerebral blood flow is insufficient to meet metabolic demand. Other than for acute ischemia, which results in apparent (irreversible) loss of brain tissue

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    to radiation and is capable of inducing atherosclerosis. The objective of the study was to elucidate whether ionizing radiation from radioiodine might contribute to cerebrovascular morbidity. METHODS: In a retrospective register cohort study, 4000 hyperthyroid and 1022 euthyroid goitre patients treated...

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

    Science.gov (United States)

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

    2016-03-01

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

  4. Neckties and Cerebrovascular Reactivity in Young Healthy Males: A Pilot Randomised Crossover Trial

    Directory of Open Access Journals (Sweden)

    Mark Rafferty

    2011-01-01

    Full Text Available Background. A necktie may elevate intracranial pressure through compression of venous return. We hypothesised that a tight necktie would deleteriously alter cerebrovascular reactivity. Materials and Methods. A necktie was simulated using bespoke apparatus comprising pneumatic inner-tube with aneroid pressure-gauge. Using a randomised crossover design, cerebrovascular reactivity was measured with the “pseudo-tie” worn inflated or deflated for 5 minutes (simulating tight/loose necktie resp.. Reactivity was calculated using breath hold index (BHI and paired “t” testing used for comparative analysis. Results. We enrolled 40 healthy male volunteers. There was a reduction in cerebrovascular reactivity of 0.23 units with “tight” pseudotie (BHI loose 1.44 (SD 0.48; BHI tight 1.21 (SD 0.38 P<.001. Conclusion. Impairment in cerebrovascular reactivity was found with inflated pseudo-tie. However, mean BHI is still within a range of considered normal. The situation may differ in patients with vascular risk factors, and confirmatory work is recommended.

  5. Reduction of the cerebrovascular volume in a transgenic mouse model of Alzheimer's disease.

    Science.gov (United States)

    Bourasset, Fanchon; Ouellet, Mélissa; Tremblay, Cyntia; Julien, Carl; Do, Tuan Minh; Oddo, Salvatore; LaFerla, Frank; Calon, Frédéric

    2009-03-01

    Combined evidence from neuroimaging and neuropathological studies shows that signs of vascular pathology and brain hypoperfusion develop early in Alzheimer's disease (AD). To investigate the functional implication of these abnormalities, we have studied the cerebrovascular volume and selected markers of blood-brain barrier (BBB) integrity in 11-month-old 3 x Tg-AD mice, using the in situ brain perfusion technique. The cerebrovascular volume of distribution of two vascular space markers, [3H]-inulin and [14C]-sucrose, was significantly lower (-26% and -27%, respectively; p diazepam was similar between 3xTg-AD mice and controls, suggesting no difference in the functional integrity of the BBB. We also report a 32% increase (p < 0.001) in the thickness of basement membranes surrounding cortical microvessels along with a 20% increase (p < 0.05) of brain collagen content in 3xTg-AD mice compared to controls. The present data indicate that the cerebrovascular space is reduced in a mouse model of Abeta and tau accumulation, an observation consistent with the presence of cerebrovascular pathology in AD.

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

    Directory of Open Access Journals (Sweden)

    Samaneh Yekta

    2014-01-01

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

  7. Prevalence and Incidence of Myocardial Infarction and Cerebrovascular Accident in Ageing Persons with Intellectual Disability

    Science.gov (United States)

    Jansen, J.; Rozeboom, W.; Penning, C.; Evenhuis, H. M.

    2013-01-01

    Background: Epidemiological information on age-related cardiovascular disease in people with intellectual disability (ID) is scarce and inconclusive. We compared prevalence and incidence of cerebrovascular accident and myocardial infarction over age 50 in a residential population with ID to that in a general practice population. Method: Lifetime…

  8. Recurrence of cerebrovascular events in young adults with a secundum atrial septal defect

    NARCIS (Netherlands)

    Winkens, Bjorn; Dimopoulos, Konstantinos; Fernandes, Susan M.; Gatzoulis, Michael A.; Landzberg, Michael J.; Mulder, Barbara J. M.

    2010-01-01

    Background: The recurrence rate for cerebrovascular ischemic events in patients after a first TIA or CVA with an atrial septal defect type 2 (ASD2) remains unknown. At present, there are no guidelines with respect to appropriate treatment. The aim of this study was to determine incidence rates of re

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

    Directory of Open Access Journals (Sweden)

    Kevin Sam

    2016-01-01

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

  10. Awake craniotomy in a patient with ejection fraction of 10%: considerations of cerebrovascular and cardiovascular physiology.

    Science.gov (United States)

    Meng, Lingzhong; Weston, Stephen D; Chang, Edward F; Gelb, Adrian W

    2015-05-01

    A 37-year-old man with nonischemic 4-chamber dilated cardiomyopathy and low-output cardiac failure (estimated ejection fraction of 10%) underwent awake craniotomy for a low-grade oligodendroglioma resection under monitored anesthesia care. The cerebrovascular and cardiovascular physiologic challenges and our management of this patient are discussed.

  11. Cerebrovascular disease, associated risk factors and antithrombotic therapy in a population screening cohort

    DEFF Research Database (Denmark)

    Proietti, Marco; Mairesse, Georges H; Goethals, Peter;

    2017-01-01

    (4.0%) reported a positive clinical history for cerebrovascular disease. Logistic regression analysis found that age, hypertension, diabetes mellitus, history of vascular disease, history of heart failure and history of AF (all p ...-optimal antithrombotic therapy management was evident, with a low use of oral anticoagulant drugs among patients with AF and a low use of aspirin among subjects without AF....

  12. Outcomes With Edoxaban Versus Warfarin in Patients With Previous Cerebrovascular Events

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND AND PURPOSE: Patients with atrial fibrillation and previous ischemic stroke (IS)/transient ischemic attack (TIA) are at high risk of recurrent cerebrovascular events despite anticoagulation. In this prespecified subgroup analysis, we compared warfarin with edoxaban in patients with ver...... IS or TIA. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00781391....

  13. Glutamine synthetase desensitizes differentiated adipocytes to proinflammatory stimuli by raising intracellular glutamine levels.

    Science.gov (United States)

    Palmieri, Erika Mariana; Spera, Iolanda; Menga, Alessio; Infantino, Vittoria; Iacobazzi, Vito; Castegna, Alessandra

    2014-12-20

    The role of glutamine synthetase (GS) during adipocyte differentiation is unclear. Here, we assess the impact of GS on the adipocytic response to a proinflammatory challenge at different differentiation stages. GS expression at the late stages of differentiation desensitized mature adipocytes to bacterial lipopolysaccharide (LPS) by increasing intracellular glutamine levels. Furthermore, LPS-activated mature adipocytes were unable to produce inflammatory mediators; LPS sensitivity was rescued following GS inhibition and the associated drop in intracellular glutamine levels. The ability of adipocytes to differentially respond to LPS during differentiation negatively correlates to GS expression and intracellular glutamine levels. Hence, modulation of intracellular glutamine levels by GS expression represents an endogenous mechanism through which mature adipocytes control the inflammatory response.

  14. Significance of ultrasound evaluation of carotid atherosclerotic plaque for diagnosing ischemic cerebrovascular disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Carotid artery is the main source for craniocerebral blood supply. Its intimal plaque formation and arterial stenosis degree both are the risk factors for ischemic cerebrovascular disease.Therefore, the close relationship of carotid atherosclerotic plaque and ischemic cerebrovascular disease, and ultrasound evaluation of carotid atherosclerotic plaque have become the hot spot in studying ischemic cerebrovascular disease.OBJECTIVE: This study was to detect the degree of carotid atherosclerosis of ischemic cerebrovascular disease patients by ultrasonography, and to analyze the situation of carotid atherosclerosis and its relationship with clinic.DESIGN: Clinical randomized concurrent control experiment.SETTING: Lintong Convalescent Hospital of Lanzhou Military Area Command of Chinese PLA.PARTICIPANTS: Totally 60 outpatients and inpatients with ischemic cerebrovascular disease, 42 males and 18 females, admitted to Lintong Convalescent Hospital of Lanzhou Military Area Command of Chinese PLA between January 2006 and December 2006 were involved in the patient group. They met the diagnosis criteria of ischemic cerebrovascular disease constituted by the 4th Cerebrovascular Disease Conference in 1996, and were confirmed to suffer from ischemic cerebrovascular disease by skull CT and MRI. Another 20 subjects who received healthy examination concurrently in the same hospital, 12 males and 8 females, were involved in the control group. Informed consents of detected items were obtained from involved subjects.METHODS: The plaque thickness of mid portion, distal end and crotch of common carotid artery (CCA),internal carotid artery (ICA), external carotid artery (ECA) and vertebral artery (VA) of involved subjects,who received health examination was separately detected with color Doppler ultrasonograph (HDI-5000).Then, total integral of plaque was calculated. The intima-media thickness (IMT) was measured with two-dimensional ultrasonography. The inner diameter

  15. Epidemiologia dos acidentes cerebrovasculares em Joinville, Brasil: estudo institucional Epidemiology of cerebrovascular disease in Joinville, Brazil: an institutional study

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    Norberto L. Cabral

    1997-09-01

    Full Text Available A carência de dados epidemiológicos e a impressão prévia de elevada incidência de acidente vascular cerebral (AVC no Brasil criou o estímulo para estudo institucional prospectivo em Joinville. No período de 1-março-1995 a 1-março-1996, avaliamos o primeiro episódio e episódios recorrentes em AVC, incidência, mortalidade, taxa de fatalidade-caso em 30 dias (letalidade, freqüência de fatores de risco, tempo para admissão hospitalar e distribuição dos infartos cerebrais por subtipos patológicos. Registramos 429 pacientes no período, 320 destes com primeiro episódio. Tomografia de crânio foi realizada em 98% dos casos. A taxa de incidência anual ajustada por idade em primeiro episódio de AVC foi de 156/100000. A distribuição por diagnóstico foi: 73,4% para infarto cerebral, 18.4% para hemorragia cerebral e 7,5% para hemorragia subaracnóide. A taxa de mortalidade anual padronizada foi 25/100000. A letalidade foi 26%. Hipertensão, AVC prévio e diabetes foram os fatores de risco mais freqüentes. Somente 25% dos pacientes chegaram ao hospital nas primeiras três horas iniciais. Concluímos que a taxa de incidência em primeiro episódio de AVC em pacientes institucionalizados em Joinville, Brasil, é elevada. A taxa de mortalidade e letalidade são similares as de outras populações.The paucity of epidemiologic data, and the previous impression of high incidence of cerebrovascular disease in Brazil, made us elaborate a prospective institutional study in Joinville, Brazil, with the objective of identifying first and recurrent episodes in stroke. This study occurred from March 1995 to March 1996. We evaluated during the first episode of stroke: incidence, mortality and fatality-case rate (in 30 days letality, frequency of risk factor, time in hospital and distribution of cerebral infarcts by pathological subtypes. In this period, 429 patients with stroke were registered, 320 with the first episode. 98% of all the patients

  16. Diffusion tensor imaging of the brain in patients with Alzheimer's disease and cerebrovascular lesions

    Institute of Scientific and Technical Information of China (English)

    CHEN Shao-qiong; KANG Zhuang; HU Xi-quan; HU Bing; ZOU Yan

    2007-01-01

    Background: Recent autopsy study showed a high incidence ofcerebrovascular lesions in Alzheimer's disease (AD).To assess the impact of cerebrovascular pathology in AD, we used diffusion tensor imaging (DTI) to study AD patients with and without cerebrovascular lesions. Materials and Methods: Conventional and DTI scans were obtained from 10 patients with probable AD, 10 AD/V patients (probable AD with cerebrovascular lesions) and ten normal controls. Mean diffusivity (D) and fractional anisotropy (FA) values of some structures involved with AD pathology were measured. Results: D value was higher in AD patients than in controls in hippocampus and the cingulate gyrus. In AD/V patients, increased D value was found in the same structures and also in the thalamus and basal ganglia compared to controls. There was a significant difference of D value between AD and AD/V patients. FA value reduced in the white matter of left inferior temporal gyrus and in the bilateral middle cingulate gyrus in patients with AD/V compared with controls. The MMSE (mini-mental state examination) score significantly correlated with FA value in the right hippocampus (r=0.639, P<0.019), in the right anterior cingulate gyrus (r=0.587, P<0.035) and in left parahippocampal gyrus (r=0.559, P<0.047). Conclusion: Cerebrovascular pathology had stronger impact on the D value than the AD pathology alone did. Elevated D value in thalamic and basal ganglia may contribute to cognitive decline in AD/V patients.Reduced FA values in AD/V patients may indicate that cerebrovascular pathology induced more severe white matter damage than the AD pathology alone did.

  17. Care for patients with cerebrovascular disease in a general hospital. 2 years experience Atención a pacientes con enfermedad cerebrovascular en un hospital general. Experiencia de 2 años

    Directory of Open Access Journals (Sweden)

    Julio López Arguelles

    2010-08-01

    Full Text Available Background: The care of patients with cerebrovascular disease requires an organized system from pre-hospital care until discharge of the patient, to ensure the continuity of rehabilitation. In order to provide differentiated services to patients with this condition was created in the General Hospital Universitario "Dr. Gustavo Lima Aldereguía "a specialized room for attention to these diseases and the rehabilitation of patients. Objective: To determine the benefits obtained with differentiated services to patients with cerebrovascular disease in a general hospital. Methods: Descriptive case series that included 1038 patients admitted to the specialized chamber for cerebrovascular disease. We analyzed the following variables: stay, type of cerebrovascular disease, clinical classification, the Barthel index and discharge status. Results: 972 patients suffered from cerebrovascular disease, hospital stay was reduced by two days, the attention of specialized equipment increased from 51.75% to 79.2% patients were discharged with a mild degree of functional dependence. Conclusions: The differentiated services to cerebrovascular disease in general hospitals shows benefits for patients.Fundamento: la atención a pacientes con enfermedad cerebrovascular requiere un sistema organizado desde la atención prehospitalaria hasta el egreso del paciente, que asegure la continuidad de la rehabilitación. En aras de brindar una atención diferenciada a los pacientes con esta afección se creó en el Hospital General Universitario “Dr. Gustavo Aldereguía Lima” una sala especializada para la atención a estas enfermedades y la rehabilitación de los pacientes. Objetivo: determinar los beneficios que se obtienen con la atención diferenciada a pacientes con enfermedad cerebrovascular en un hospital general. Métodos: estudio

  18. Caregiver awareness of cerebrovascular risk of patients with dementia due to Alzheimer's disease in São Paulo, Brazil

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    Fabricio Ferreira de Oliveira

    2014-07-01

    Full Text Available Background Proper control of cerebrovascular risk is essential to prevent cognitive change in dementia due to Alzheimer’s disease (AD. Objective To investigate whether caregiver awareness to control cerebrovascular risk impacts the lifestyles of patients with AD. Methods Consecutive outpatients with AD were assessed for demographic features, Clinical Dementia Rating scores, cerebrovascular risk, pharmacotherapy, dietary therapy and practice of physical activities. Patients and caregivers were inquired on awareness of the importance of measures to control cerebrovascular risk. Chi-square test was employed for statistics, significance at ρ < 0.05. Results A total of 217 patients were included; whereas 149 caregivers (68.7% were aware of the need to control cerebrovascular risk, only 11 patients (5.1% simultaneously practiced physical activities and received pharmacological treatment and dietary therapy. Patients with hypertension and diabetes mellitus were more likely to receive dietary therapy (ρ = 0.007. Male patients were more engaged in physical activities (ρ = 0.018. Patients in earlier AD stages exercised (ρ = 0.0003 and received pharmacological treatment more often (ρ = 0.0072. Caregiver awareness of the need to control cerebrovascular risk was higher when patients had hypertension (ρ = 0.024 and/or hypercholesterolemia (ρ = 0.006, and influenced adherence to dietary therapy (ρ = 0.002 and to pharmacological treatment (ρ = 0.001. Discussion Caregiver awareness of the need to control cerebrovascular risk has positive impacts for patients with AD.

  19. Long-Term Arthralgia after Mayaro Virus Infection Correlates with Sustained Pro-inflammatory Cytokine Response.

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    Felix W Santiago

    Full Text Available Mayaro virus (MAYV, an alphavirus similar to chikungunya virus (CHIKV, causes an acute debilitating disease which results in the development of long-term arthralgia in more than 50% of infected individuals. Currently, the immune response and its role in the development of MAYV-induced persistent arthralgia remain unknown. In this study, we evaluated the immune response of individuals with confirmed MAYV infection in a one-year longitudinal study carried out in Loreto, Peru. We report that MAYV infection elicits robust immune responses that result in the development of a strong neutralizing antibody response and the secretion of pro-inflammatory immune mediators. The composition of these inflammatory mediators, in some cases, differed to those previously observed for CHIKV. Key mediators such as IL-13, IL-7 and VEGF were strongly induced following MAYV infection and were significantly increased in subjects that eventually developed persistent arthralgia. Although a strong neutralizing antibody response was observed in all subjects, it was not sufficient to prevent the long-term outcomes of MAYV infection. This study provides initial immunologic insight that may eventually contribute to prognostic tools and therapeutic treatments against this emerging pathogen.

  20. Long-Term Arthralgia after Mayaro Virus Infection Correlates with Sustained Pro-inflammatory Cytokine Response.

    Science.gov (United States)

    Santiago, Felix W; Halsey, Eric S; Siles, Crystyan; Vilcarromero, Stalin; Guevara, Carolina; Silvas, Jesus A; Ramal, Cesar; Ampuero, Julia S; Aguilar, Patricia V

    2015-01-01

    Mayaro virus (MAYV), an alphavirus similar to chikungunya virus (CHIKV), causes an acute debilitating disease which results in the development of long-term arthralgia in more than 50% of infected individuals. Currently, the immune response and its role in the development of MAYV-induced persistent arthralgia remain unknown. In this study, we evaluated the immune response of individuals with confirmed MAYV infection in a one-year longitudinal study carried out in Loreto, Peru. We report that MAYV infection elicits robust immune responses that result in the development of a strong neutralizing antibody response and the secretion of pro-inflammatory immune mediators. The composition of these inflammatory mediators, in some cases, differed to those previously observed for CHIKV. Key mediators such as IL-13, IL-7 and VEGF were strongly induced following MAYV infection and were significantly increased in subjects that eventually developed persistent arthralgia. Although a strong neutralizing antibody response was observed in all subjects, it was not sufficient to prevent the long-term outcomes of MAYV infection. This study provides initial immunologic insight that may eventually contribute to prognostic tools and therapeutic treatments against this emerging pathogen.

  1. Proinflammatory cytokines induce bronchial hyperplasia and squamous metaplasia in smokers: implications for chronic obstructive pulmonary disease therapy.

    Science.gov (United States)

    Herfs, Michael; Hubert, Pascale; Poirrier, Anne-Lise; Vandevenne, Patricia; Renoux, Virginie; Habraken, Yvette; Cataldo, Didier; Boniver, Jacques; Delvenne, Philippe

    2012-07-01

    Tracheobronchial squamous metaplasia is common in smokers, and is associated with both airway obstruction in chronic obstructive pulmonary disease (COPD) and increased risk of lung cancer. Although this reversible epithelial replacement is almost always observed in association with chronic inflammation, the role of inflammatory mediators in the pathogenesis of squamous metaplasia remains unclear. In the present study, we investigated the implication of cigarette smoke-mediated proinflammatory cytokine up-regulation in the development and treatment of tracheobronchial epithelial hyperplasia and squamous metaplasia. Using immunohistological techniques, we showed a higher epithelial expression of TNF-α, IL-1β, and IL-6, as well as an activation of NF-κB and activator protein-1/mitogen-activated protein kinase signaling pathways in the respiratory tract of smoking patients, compared with the normal ciliated epithelium of nonsmoking patients. In addition, we demonstrated that these signaling pathways strongly influence the proliferation and differentiation state of in vitro-generated normal human airway epithelial basal cells. Finally, we exposed mice to cigarette smoke for 16 weeks, and demonstrated that anti-TNF-α (etanercept), anti-IL-1β (anakinra), and/or anti-IL-6R (tocilizumab) therapies significantly reduced epithelial hyperplasia and the development of squamous metaplasia. These data highlight the importance of soluble inflammatory mediators in the pathogenesis of tracheobronchial squamous metaplasia. Therefore, the administration of proinflammatory cytokine antagonists may have clinical applications in the management of patients with COPD.

  2. Protein inhibitor of activated STAT 4 (PIAS4) regulates pro-inflammatory transcription in hepatocytes by repressing SIRT1.

    Science.gov (United States)

    Sun, Lina; Fan, Zhiwen; Chen, Junliang; Tian, Wenfang; Li, Min; Xu, Huihui; Wu, Xiaoyan; Fang, Mingming; Xia, Jun; Xu, Yong

    2016-07-12

    Excessive nutrition promotes the pathogenesis of non-alcoholic steatohepatitis (NASH), characterized by the accumulation of pro-inflammation mediators in the liver. In the present study we investigated the regulation of pro-inflammatory transcription in hepatocytes by protein inhibitor of activated STAT 4 (PIAS4) in this process and the underlying mechanisms. We report that expression of the class III deacetylase SIRT1 was down-regulated in the livers of NASH mice accompanied by a simultaneous increase in the expression and binding activity of PIAS4. Exposure to high glucose stimulated the expression PIAS4 in cultured hepatocytes paralleling SIRT1 repression. Estrogen, a known NASH-protective hormone, ameliorated SIRT1 trans-repression by targeting PIAS4. Over-expression of PIAS4 enhanced, while PIAS4 knockdown alleviated, repression of SIRT1 transcription by high glucose. Lentiviral delivery of short hairpin RNA (shRNA) targeting PIAS4 attenuated hepatic inflammation in NASH mice by restoring SIRT1 expression. Mechanistically, PIAS4 promoted NF-κB-mediated pro-inflammatory transcription in a SIRT1 dependent manner. In conclusion, our study indicates that PIAS4 mediated SIRT1 repression in response to nutrient surplus contributes to the pathogenesis of NASH. Therefore, targeting PIAS4 might provide novel therapeutic strategies in the intervention of NASH.

  3. MicroRNA-Regulated Proinflammatory Cytokines in Sarcopenia

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    Jingjing Fan

    2016-01-01

    Full Text Available Sarcopenia has been defined as the aging-related disease with the declined mass, strength, and function of skeletal muscle, which is the major cause of frailty and falls in elders. The activation of inflammatory signal pathways due to diseases and aging is suggested to reveal the critical impact on sarcopenia. Several proinflammatory cytokines, especially interleukin-6 (IL-6 and tumor necrosis factor-alpha (TNF-α, play crucial roles in modulation of inflammatory signaling pathway during the aging-related loss of skeletal muscle. MicroRNAs (miRNAs have emerged as the important regulators for the mass and functional maintenance of skeletal muscle through regulating gene expression of proinflammatory cytokines. In this paper, we have systematically discussed regulatory mechanisms of miRNAs for the expression and secretion of inflammatory cytokines during sarcopenia, which will provide some novel targets and therapeutic strategies for controlling aging-related atrophy of skeletal muscle and corresponding chronic inflammatory diseases.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    AIM: In this study, we aimed to investigate whether changes in cerebrovascular voltage-dependent calcium channels and non-selective cation channels contribute to the enhanced endothelin-1-mediated vasoconstriction in the delayed hypoperfusion phase after experimental transient forebrain ischaemia....... METHODS: Experimental forebrain ischaemia was induced in Wistar male rats by a two-vessel occlusion model, and the cerebral blood flow was measured by magnetic resonance imaging two days after reperfusion. In vitro vasoreactivity studies, immunofluorescence and quantitative PCR were performed on cerebral...... arteries from ischaemic or sham-operated rats to evaluate changes in vascular voltage-dependent calcium channels, transient receptor potential canonical channels as well as endothelin-1 receptor function and expression. RESULTS: The expression of transient receptor potential canonical channels 1 and 6...

  5. MicroRNA-Regulated Proinflammatory Cytokines in Sarcopenia

    OpenAIRE

    Jingjing Fan; Xianjuan Kou; Yi Yang; Ning Chen

    2016-01-01

    Sarcopenia has been defined as the aging-related disease with the declined mass, strength, and function of skeletal muscle, which is the major cause of frailty and falls in elders. The activation of inflammatory signal pathways due to diseases and aging is suggested to reveal the critical impact on sarcopenia. Several proinflammatory cytokines, especially interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), play crucial roles in modulation of inflammatory signaling pathway during the...

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

    Science.gov (United States)

    Lee, Ji Yun; Kim, Chang Jong

    2010-06-01

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

  7. Progesterone Prevents Traumatic Brain Injury-Induced Intestinal Nuclear Factor kappa B Activation and Proinflammatory Cytokines Expression in Male Rats

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    Chunhua Hang

    2007-08-01

    Full Text Available We have previously shown that traumatic brain injury (TBI can induce an upregulation of nuclear factor kappa B (NF-κB and proinflammatory cytokines in the gut, which play an important role in the pathogenesis of acute gut mucosal injury mediated by inflammation. In this work, we investigated whether progesterone administration modulated intestinal NF-κB activity and proinflammatory cytokines expression after TBI in male rats. As a result, we found that administration of progesterone following TBI could decrease NF-κB binding activity, NF-κB p65 protein expression, and concentrations of interleukin-1β (IL-1β, and tumor necrosis factor-α (TNF-α in the gut. TBI-induced damages of gut structure were ameliorated after progesterone injections. The results of the present study suggest that the therapeutic benefit of post-TBI progesterone injections might be due to its inhibitory effects on intestinal NF-κB activation and proinflammatory cytokines expression.

  8. Propionibacterium acnes and lipopolysaccharide induce the expression of antimicrobial peptides and proinflammatory cytokines/chemokines in human sebocytes.

    Science.gov (United States)

    Nagy, István; Pivarcsi, Andor; Kis, Kornélia; Koreck, Andrea; Bodai, László; McDowell, Andrew; Seltmann, Holger; Patrick, Sheila; Zouboulis, Christos C; Kemény, Lajos

    2006-07-01

    Acne is a common skin disorder of the pilosebaceous unit. In addition to genetic, hormonal and environmental factors, abnormal colonization by Propionibacterium acnes has been implicated in the occurrence of acne via the induction of inflammatory mediators. To gain more insight into the role that sebocytes play in the innate immune response of the skin, particularly in acne, we compared the antimicrobial peptide and proinflammatory cytokine/chemokine expression at mRNA and protein levels, as well as the viability and differentiation of SZ95 sebocytes in response to co-culture with representative isolates of P. acnes type IA and type IB as well as Escherichia coli-derived lipopolysaccharide (LPS). We found that, in vitro, P. acnes type IA and IB isolates and LPS induced human beta-defensin-2 and proinflammatory cytokine/chemokine expression, and influenced sebocyte viability and differentiation. Our results provide evidence that sebocytes are capable of producing proinflammatory cytokines/chemokines and antimicrobial peptides, which may have a role in acne pathogenesis. Furthermore, since P. acnes types IA and IB differentially affect both the differentiation and viability of sebocytes, our data demonstrate that different strains of P. acnes vary in their capacity to stimulate an inflammatory response within the pilosebaceous follicle.

  9. Nanostructured TiO2 surfaces promote polarized activation of microglia, but not astrocytes, toward a proinflammatory profile

    Science.gov (United States)

    de Astis, Silvia; Corradini, Irene; Morini, Raffaella; Rodighiero, Simona; Tomasoni, Romana; Lenardi, Cristina; Verderio, Claudia; Milani, Paolo; Matteoli, Michela

    2013-10-01

    Activation of glial cells, including astrocytes and microglia, has been implicated in the inflammatory responses underlying brain injury and neurodegenerative diseases including Alzheimer's and Parkinson's diseases. The classic activation state (M1) is characterized by high capacity to present antigens, high production of nitric oxide (NO) and reactive oxygen species (ROS) and proinflammatory cytokines. Classically activated cells act as potent effectors that drive the inflammatory response and may mediate detrimental effects on neural cells. The second phenotype (M2) is an alternative, apparently beneficial, activation state, more related to a fine tuning of inflammation, scavenging of debris, promotion of angiogenesis, tissue remodeling and repair. Specific environmental chemical signals are able to induce these different polarization states. We provide here evidence that nanostructured substrates are able, exclusively in virtue of their physical properties, to push microglia toward the proinflammatory activation phenotype, with an efficacy which reflects the graded nanoscale rugosity. The acquisition of a proinflammatory phenotype appears specific for microglia and not astrocytes, indicating that these two cell types, although sharing common innate immune responses, respond differently to external physical stimuli.

  10. Minocycline attenuates Aβ oligomers-induced pro-inflammatory phenotype in primary microglia while enhancing Aβ fibrils phagocytosis.

    Science.gov (United States)

    El-Shimy, Ismail Amr; Heikal, Ola Ahmed; Hamdi, Nabila

    2015-11-16

    Microglia, the brain innate immune cells, are activated in response to amyloid beta (Aβ) resulting in neuroinflammation in AD brains. Recently, two phenotypes have been described for microglia: the pro-inflammatory classical and the anti-inflammatory alternative. Changes in microglia phenotype that control their phagocytic function are yet to be determined. The highly neurotoxic Aβ oligomers (oAβ) formed at an early disease stage induce pro-inflammatory microglia activation releasing neurotoxic mediators and contributing to neurodegeneration. A novel strategy for AD treatment is to attenuate microglia-induced inflammation while maintaining efficient Aβ clearance. Minocycline effectively crosses the blood-brain barrier and has widely reported neuroprotective effects. Yet, its exact mechanism of neuroprotection and its effects on microglia are still unknown. The aim of this study is to investigate the effect of minocycline on the phagocytic uptake of fAβ by primary microglia in relation to their activation state in an inflammatory milieu generated by oAβ or LPS. The study shows that minocycline is able to attenuate oAβ-induced neuroinflammatory response of microglia by inhibiting their pro-inflammatory phenotype activation. In addition, a significant enhancement of fAβ phagocytosis by minocycline- treated microglia is reported for the first time, providing novel insight into its neuroprotective role in AD.

  11. FUCOIDIN INHIBITS OXIDIZED LOW DENSITY LIPOPROTEIN FROM INDUCING HUMAN PERIPHERAL BLOOD MONOCYTE EXPRESSION OF PROINFLAMMATORY CYTOKINES mRNA

    Institute of Scientific and Technical Information of China (English)

    雷新军; 马爱群; 任冰稳; 耿涛; 张葳; 白玲

    2003-01-01

    Objective To study the significance of scavenger receptor class A(SR-A)in mediating human peripheral blood monocyte to uptake oxidized low density lipoprotein(OxLDL) and promoting the atherosclerotic immuno-pathological lesion in the local blood vessel. Methods With the Digoxenin-labeled Oligonucleotide-probes In situ Hybridization, this research investigated the effects of OxLDL on the mRNA expression of proinflammatory cytokines including MCP-1, bFGF, PDGF and IL-10 in the human peripheral blood monocyte and whether fucoidin, a peculiarly inhibitory ligand for SR-A, would influence this process. Results Monocyte was significantly increased the mRNA expression of MCP-1, bFGF, PDGF and IL-10 in a dose-dependent manner after incubating with OxLDL (10,15,20,25,30·mg·L-1, respectively)for 24 hours(P<0.001). Fucoidin(50,100,150,200,250·mg·mL-1, respectively)completely inhibited OxLDL(20·mg·L-1)from inducing monocyte the mRNA expression of above proinflammatory cytokines(P<0.001). Conclusion OxLDL can stimulate human peripheral blood monocyte to give expression to proinflammatory cytokines mRNA in a dose-dependent manner, while a peculiarly inhibitory ligand for SR-A-fucoidin has an obviously opposed role.

  12. Pro-inflammatory Cytokines Impair Vitamin D-induced Host Defense in Cultured Airway Epithelial Cells.

    Science.gov (United States)

    Schrumpf, Jasmijn A; Amatngalim, Gimano D; Veldkamp, Joris B; Verhoosel, Renate M; Ninaber, Dennis K; Ordonez, Soledad R; van der Does, Anne M; Haagsman, Henk P; Hiemstra, Pieter S

    2017-02-23

    Vitamin D is a regulator of host defense against infections and induces expression of the antimicrobial peptide hCAP18/LL-37. Vitamin D deficiency is associated with chronic inflammatory lung diseases and respiratory infections. However, it is incompletely understood if and how (chronic) airway inflammation affects vitamin D metabolism and action. We hypothesized that long-term exposure of primary bronchial epithelial cells (PBEC) to pro-inflammatory cytokines alters their vitamin D metabolism, antibacterial activity and expression of hCAP18/LL-37. To investigate this, PBEC were differentiated at the air-liquid interphase for 14 days in presence of the pro-inflammatory cytokines TNF-α and IL-1β (TNF-α/IL-1β), and subsequently exposed to vitamin D (inactive 25(OH)D3 and active 1,25(OH)2D3). Expression of hCAP18/LL-37, vitamin D receptor (VDR) and enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1) was determined using qPCR, Western blot and immunofluorescence staining. Furthermore, vitamin D-mediated antibacterial activity was assessed using non-typeable Haemophilus influenzae (NTHi). We found that TNF-α/IL-1β treatment reduced vitamin D-induced expression of hCAP18/LL-37 and killing of NTHi. In addition, CYP24A1 (a vitamin D-degrading enzyme) was increased by TNF-α/IL-1β, whereas CYP27B1 (that converts 25(OH)D3 to its active form) and VDR expression remained unaffected. Furthermore, we demonstrated that the TNF-α/IL-1β-mediated induction of CYP24A1 was at least in part mediated by the transcription factor specific protein 1 (Sp1) and the EGFR-MAPK-pathway. These findings indicate that TNF-α/IL-1β decreases vitamin D-mediated antibacterial activity and hCAP18/LL-37 expression via induction of CYP24A1, and suggests that chronic inflammation impairs protective responses induced by vitamin D.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Adrian Nahirnyj

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

  15. Proinflammatory and cytotoxic effects of Mexico City air pollution particulate matter in vitro are dependent on particle size and composition.

    Science.gov (United States)

    Osornio-Vargas, Alvaro R; Bonner, James C; Alfaro-Moreno, Ernesto; Martínez, Leticia; García-Cuellar, Claudia; Ponce-de-León Rosales, Sergio; Miranda, Javier; Rosas, Irma

    2003-08-01

    Exposure to urban airborne particulate matter (PM) is associated with adverse health effects. We previously reported that the cytotoxic and proinflammatory effects of Mexico City PM10 (less than or equal to 10 micro m mean aerodynamic diameter) are determined by transition metals and endotoxins associated with these particles. However, PM2.5 (less than or equal to 2.5 micro m mean aerodynamic diameter) could be more important as a human health risk because this smaller PM has the potential to reach the distal lung after inhalation. In this study, we compared the cytotoxic and proinflammatory effects of Mexico City PM10 with those of PM2.5 using the murine monocytic J774A.1 cell line in vitro. PMs were collected from the northern zone or the southeastern zone of Mexico City. Elemental composition and bacterial endotoxin on PMs were measured. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) production by J774A.1 cells was measured in the presence or absence of recombinant endotoxin-neutralizing protein (rENP). Both northern and southeastern PMs contained endotoxin and a variety of transition metals. Southeastern PM10 contained the highest endotoxin levels, 2-fold higher than that in northern PM10. Northern and southeastern PM2.5 contained the lowest endotoxin levels. Accordingly, southeastern PM10 was the most potent in causing secretion of the proinflammatory cytokines TNF-alpha and IL-6. All PM2.5 and PM10 samples caused cytotoxicity, but northern PMs were the most toxic. Cytokine secretion induced by southeastern PM10 was reduced 50-75% by rENP. These results indicate major differences in PM10 and PM2.5. PM2.5 induces cytotoxicity in vitro through an endotoxin-independent mechanism that is likely mediated by transition metals. In contrast, PM10 with relatively high levels of endotoxin induces proinflammatory cytokine release via an endotoxin-dependent mechanism.

  16. Influence of steep Trendelenburg position and CO(2) pneumoperitoneum on cardiovascular, cerebrovascular, and respiratory homeostasis during robotic prostatectomy

    NARCIS (Netherlands)

    Kalmar, A. F.; Foubert, L.; Hendrickx, J. F. A.; Mottrie, A.; Absalom, A.; Mortier, E. P.; Struys, M. M. R. F.

    2010-01-01

    The steep (40 degrees) Trendelenburg position optimizes surgical exposure during robotic prostatectomy. The goal of the current study was to investigate the combined effect of this position and CO(2) pneumoperitoneum on cardiovascular, cerebrovascular, and respiratory homeostasis during these proced

  17. The relationship between cerebrovascular complications and previously established use of antiplatelet therapy in left-sided infective endocarditis

    DEFF Research Database (Denmark)

    Snygg-Martin, Ulrika; Rasmussen, Rasmus Vedby; Hassager, Christian;

    2011-01-01

    Cerebrovascular complications (CVC) in infective endocarditis (IE) are common. The only established treatments to reduce the incidence of CVC in IE are antibiotics and in selected cases early cardiac surgery. Potential effects of previously established antiplatelet therapy are under debate....

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

  19. Risk of cerebrovascular events in persons with and without HIV: a Danish nationwide population-based cohort study

    DEFF Research Database (Denmark)

    Rasmussen, Line D; Engsig, Frederik N; Christensen, Hanne;

    2011-01-01

    To assess the risk of cerebrovascular events (CVEs) in HIV-infected individuals and evaluate the impact of proven risk factors, injection drug abuse (IDU), immunodeficiency, HAART and family-related risk factors.......To assess the risk of cerebrovascular events (CVEs) in HIV-infected individuals and evaluate the impact of proven risk factors, injection drug abuse (IDU), immunodeficiency, HAART and family-related risk factors....

  20. Clinical and Paraclinical Findings of Cerebrovascular Accidents in Children Admitted to Pediatric Medical Center from 1993 till 2003

    OpenAIRE

    M. Dehghani; H Montazer Lotfe Elahi; M Ashrafi

    2011-01-01

    Introduction: Stroke is a clinical diagnosis which brings up cerebrovascular diseases. Stroke includes any cerebrovascular accident which leads to local neural defect and lasts more than 24 hours. Stroke has severe and irreversible complications and high rates of recurrence after first episode, therefore we decided to study clinical and paraclinical findings of this disease for better diagnosis and prevention of it. Methods: We prepared a case series study to review medical files of the patie...

  1. The rapid antidepressant effect of ketamine in rats is associated with down-regulation of pro-inflammatory cytokines in the hippocampus

    OpenAIRE

    Wang, Nan; Yu, Hai-Ying; Shen, Xiao-Feng; Gao, Zhi-Qin; Yang, Chun; Yang, Jian-Jun; Zhang, Guang-Fen

    2015-01-01

    Objectives. Active inflammatory responses play an important role in the pathogenesis of depression. We hypothesized that the rapid antidepressant effect of ketamine is associated with the down-regulation of pro-inflammatory mediators. Methods. Forty-eight rats were equally randomized into six groups (a control and five chronic unpredictable mild stress (CUMS) groups) and given either saline or 10 mg/kg ketamine, respectively. The forced swimming test was performed, and the hippocampus was sub...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    .8(1.4 to 5.7) for -1072 AA versus GG genotype, 0.6(0.4 to 0.9) for -444 CC versus AA genotype, 2.5(1.2 to 5.4) for combined AA-AA versus GG-AA genotype, and 0.6(0.4 to 0.9) for combined GG-CC versus GG-AA genotype. Genotype did not associate with risk of deep venous thrombosis or severe carotid...... atherosclerosis, or with levels of platelets and coagulation factors. CONCLUSIONS: Leukotriene C(4) synthase -1072 AA genotype predict increased risk, whereas -444 CC genotype predict decreased risk of ischemic cerebrovascular disease.......OBJECTIVE: Cysteinyl leukotrienes are involved in inflammation and possibly in early carotid atherosclerosis. We tested the hypothesis that the -444 A/C and -1072 G/A polymorphisms of the leukotriene C(4) synthase associate with risk of ischemic cerebrovascular disease. METHODS AND RESULTS: We...

  3. Trypanosoma cruzi-associated cerebrovascular disease: a case-control study in Eastern Colombia.

    Science.gov (United States)

    Leon-Sarmiento, Fidias E; Mendoza, Eder; Torres-Hillera, Martin; Pinto, Neyla; Prada, Janette; Silva, Clara A; Vera, Silvia J; Castillo, Erwin; Valderrama, Vladimir; Prada, Didier G; Bayona-Prieto, Jaime; Garcia, Ingrid

    2004-01-15

    Trypanosoma cruzi infection is a common cause of cardiopathy in South America leading it eventually to an established stroke; however, the association between T. cruzi infection itself and cerebrovascular disease is still unknown. We did a case-control study at Eastern Colombia and found that T. cruzi infection was more frequent and statistically significant in stroke cases (24.4%) than controls (1.9%), (Chi square: 21.72; OR: 16.13; 95% confidence interval (CI): 3.64-71.4; p<0.00001). After removing the seropositive patients with cardiological abnormalities, the significance still remained by multivariate analysis (p<0.05). This is the first case-control study that demonstrated a significant link between this infection and symptomatic cerebrovascular disease, mainly ischemic, regardless of cardiac abnormalities. Therefore, we recommend that patients with stroke must be screened for T. cruzi infection if they currently live or have lived in places where this parasite is considered endemic.

  4. Apolipoprotein E gene polymorphism in cerebrovascular diseases of the Chinese Naxi populations from Yunnan province

    Institute of Scientific and Technical Information of China (English)

    Hong Xu; Qihong Yuan; Xijun Fan; Guoqiang He

    2011-01-01

    Currently it is not well known whether apolipoprotein E (ApoE) is a genetic susceptibility factor for cerebrovascular diseases in the Chinese Naxi population. The present study detected and sequenced ApoE polymorphisms of 90 patients with cerebrovascular diseases (58 cases of cerebral infarction and 32 cases of intracerebral hemorrhage), and 50 normal people of Naxi nationality from Yunnan province, China. The populations were used to analyze the relationship of ApoE polymorphisms with cerebral infarction and intracerebral hemorrhage. Results showed an association between ApoE gene polymorphism and the onset of cerebral infarction, and a possibility that the ε4 allele is a susceptibility locus for the risk of cerebral infarction. However, there was no evidence of a relationship between the ApoE gene polymorphism and cerebral hemorrhage.

  5. Long-Term Exposure to Ambient Air Pollution and Incidence of Cerebrovascular Events

    DEFF Research Database (Denmark)

    Stafoggia, Massimo; Cesaroni, Giulia; Peters, Annette

    2014-01-01

    BACKGROUND: Few studies have investigated effects of air pollution on the incidence of cerebrovascular events. OBJECTIVES: We assessed the association between long-term exposure to multiple air pollutants and the incidence of stroke in European cohorts. METHODS: Data from 11 cohorts were collected...... and occurrence of a first stroke was evaluated. Individual air pollution exposures were predicted from land-use regression models developed within the "European Study of Cohorts for Air Pollution Effects" (ESCAPE). The exposures were: PM2.5 (particulate matter [PM] below 2.5 µm in diameter), coarse PM (PM...... found suggestive evidence of an association between fine particles and incidence of cerebrovascular events in Europe, even at lower concentrations than set by the current air quality limit value....

  6. Acetylsalicylic acid provides cerebrovascular protection from oxidant damage in salt-loaded stroke-prone rats.

    Science.gov (United States)

    Ishizuka, Toshiaki; Niwa, Atsuko; Tabuchi, Masaki; Ooshima, Kana; Higashino, Hideaki

    2008-03-26

    Inflammatory processes may play a pivotal role in the pathogenesis of cerebrovascular injury in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Recent reports revealed that acetylsalicylic acid (aspirin) has anti-oxidative properties and elicits nitric oxide release by a direct activation of the endothelial NO synthase. The present study was designed to determine whether low-dose aspirin might prevent cerebrovascular injury in salt-loaded SHRSP by protecting oxidative damage. Nine-week-old SHRSP were fed a 0.4% NaCl or a 4% NaCl diet with or without treatment by naproxen (20 mg/kg/day), salicylic acid (5 mg/kg/day), or aspirin (5 mg/kg/day) for 5 weeks. Blood pressure, blood brain barrier impairment, mortality, and the parameters of cerebrovascular inflammation and damage were compared among them. High salt intake in SHRSP significantly increased blood brain barrier impairment and early mortality, which were suppressed by treatment with aspirin independent of changes in blood pressure. Salt loading significantly increased superoxide production in basilar arteries of SHRSP, which were significantly suppressed by treatment with aspirin. Salt loading also significantly decreased NOS activity in the basilar arteries of SHRSP, which were significantly improved by treatment with aspirin. At 5 weeks after salt loading, macrophage accumulation and matrix metalloproteinase-9 activity at the stroke-negative area in cerebral cortex of SHRSP were significantly reduced by treatment with aspirin. These results suggest that low-dose aspirin may exert protective effects against cerebrovascular inflammation and damage by salt loading through down-regulation of superoxide production and induction of nitric oxide synthesis.

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

    OpenAIRE

    Lucero López-Díaz; Fabiola Castellanos-Soriano; Esperanza Muñoz-Torres

    2016-01-01

    Introducción: el accidente cerebrovascular afecta a numerosas personas en el mundo y se constituye en la principal causa de muer- te. Los sobrevivientes pueden padecer discapacidad y sufrir modificaciones en las actividades cotidianas. La familia es el principal apoyo del sobreviviente y al ser parte de una misma cultura, construye acciones de cuidado en búsqueda del bienestar. Objetivo: describir las acciones del cuidado popular de las familias con un adulto mayor sobreviviente del prim...

  8. High prevalence of peripheral arterial disease in patients with previous cerebrovascular or coronary event

    DEFF Research Database (Denmark)

    Mehlsen, Jesper; Wiinberg, Niels; Joergensen, Bjarne S;

    2010-01-01

    The presence of peripheral arterial disease (PAD) in patients with other manifestations of cardiovascular disease identifies a population at increased risk of complications both during acute coronary events and on a long-term basis and possibly a population in whom secondary prevention...... of cardiovascular events should be addressed aggressively. The present study was aimed at providing a valid estimate on the prevalence of PAD in patients attending their general practitioner and having previously suffered a cardio- or cerebrovascular event....

  9. TYPES OF TREMOR IN PATIENTS WITH CEREBROVASCULAR DISEASES AND CARDIOVASCULAR EVENTS

    Directory of Open Access Journals (Sweden)

    Petrov Igor

    2016-03-01

    Full Text Available Introduction: Tremor can occur as a part of the clinical feature of cerebrovascular diseases. Many patients with cerebral stroke have cardiovascular diseases as a comorbidity or complication of stroke; sometimes cardiovascular events can lead to embolic stroke. Aim: To present types of tremor in patients with cerebrovascular diseases and cardiovascular events and diabetes mellitus type 2, clinical characteristics of tremor and investigations used. Material and methods: In our study we included 36 patients, 24 men and 12 women, that were examined and followed for 3 years, from 2012-2015. All patients were subjected to the following investigations: neurological examination, laboratory analysis, computerized tomography of brain, magnetic resonance imaging and electroencephalography. In cardiovascular patients we also performed Doppler sonography of carotid arteries, electrocardiography, cardiac ultrasound. The patients were examined and treated by cardiologists. Results: Of all patients 22% had cerebral infarction, 41% atherosclerosis, 36% multiple lacunar infarctions and 28% diabetes mellitus type 2. Three patients with cerebral infarction had chorea, hemiballismus, dystonia and dystonic tremor, three had postural tremor and two cerebellar intention tremor. Atherosclerotic patients had atherosclerotic action tremor, while diabetic patients predominantly presented with action-type tremor. Electroencephalography showed irritative basic brain activity with slow waves, while carotid arteries stenosis was diagnosed by Doppler sonography. Computerized tomography of the brain and magnetic resonance imaging revealed cerebrovascular diseases in certain areas. Patients with cardiomyopathy, rhythm disorders, high blood pressure, hyperlipidemia was investigated and medically treated by a cardiologist. Conclusion: In cerebrovascular diseases different types of tremor can occur as the result of the damage of the extrapyramidal system.

  10. Nuclear medicine imaging in cerebrovascular disorders; Nuklearmedizinische Bildgebung bei zerebrovaskulaeren Erkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Barthel, H. [Universitaetsklinikum Leipzig A.oe.R. (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Leipzig Univ. (Germany). Translationszentrum fuer Regenerative Medizin; Hesse, S.; Sabri, O. [Universitaetsklinikum Leipzig A.oe.R. (Germany). Klinik und Poliklinik fuer Nuklearmedizin

    2007-09-15

    For diagnosing cerebrovascular disorders, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) employing blood flow and oxygen consumption markers is applied. Currently, competing imaging techniques which do not rely on radiotracers are more dominant in clinical routine. However, brain SPECT and PET substantially contribute towards diagnosis and therapy monitoring in acute and chronic cerebral ischemia. Furthermore, cerebral vasculitis, vasospasm after subarachnoid hemorrhage, brain tolerance during balloon occlusion tests and brain death can be accurately diagnosed. (orig.)

  11. Endovascular external carotid artery occlusion for brain selective targeting: a cerebrovascular swine model

    OpenAIRE

    Mangla, Sundeep; Choi, Jae H.; Barone, Frank C.; Novotney, Carol; Libien, Jenny; Lin, Erwin; Pile-Spellman, John

    2015-01-01

    Background The choice of an animal model for cerebrovascular research is often determined by the disease subtype to be studied (e.g. ischemic stroke, hemorrhage, trauma), as well as the nature of the intervention to be tested (i.e. medical device or pharmaceutical). Many initial studies are performed in smaller animals, as they are cost-effective and their encephalic vasculature closely models that of humans. Non-human primates are also utilized when confirmation or validation is required on ...

  12. [Solcoseryl--new preparation for the pathogenetic treatment of patients with paroxysmal forms of cerebrovascular pathology].

    Science.gov (United States)

    Rudenko, A Iu; Bashkirova, L M

    2003-01-01

    The central goal of the investigation was to study Solcoseryl (SolcoSwitzerland) therapeutic efficacy for patients suffering from early or chronic cerebrovascular diseases complicated with different forms of paroxysms. 29 patients were examined. (14 of them were with vegetovascular dystonia, 7 with discirculatory encephalopathy of degree of 1 and 8 with discirculatory encephalopathy of degree of II). The authors revealed Solcoseryl to be positive in decreasing incidence and duration of vegetovascular fits, complaints, pathologic symptoms.

  13. Cerebral blood flow and cerebrovascular reserve capacity: estimation by dynamic magnetic resonance imaging.

    Science.gov (United States)

    Schreiber, W G; Gückel, F; Stritzke, P; Schmiedek, P; Schwartz, A; Brix, G

    1998-10-01

    We have developed a new method for estimation of regional CBF (rCBF) and cerebrovascular reserve capacity on a pixel-by-pixel basis by means of dynamic magnetic resonance imaging (MRI). Thirteen healthy volunteers, 8 patients with occlusion and/or high grade stenosis of the internal carotid artery (ICA), and 2 patients with acute stroke underwent dynamic susceptibility-weighted contrast enhanced MRI. Using principles of indicator dilution theory and deconvolution analysis, maps of rCBF, regional cerebral blood volume, and of the mean transit time (MTT) were calculated. In patients with ICA occlusion/stenosis, cerebrovascular reserve capacity was assessed by the rCBF increase after acetazolamide stimulation. Mean gray and white matter rCBF values in normals were 67.1 and 23.7 mL x 100 g(-1) x min(-1), respectively. Before acetazolamide stimulation, six of eight patients with ICA occlusions showed decreased rCBF values; and in seven patients increased MTT values were observed in tissue ipsilateral to the occlusion. After acetazolamide stimulation, decreased cerebrovascular reserve capacity was observed in five of eight patients with ICA occlusion. In acute stroke, rCBF in the central core of ischemia was less than 8 mL x 100 g(-1) x min(-1). In peri-infarct tissue, rCBF and MTT were higher than in unaffected tissue but rCBF was normal. Dynamic MRI provides important clinical information on the hemodynamic state of brain tissue in patients with occlusive cerebrovascular disease or acute stroke.

  14. CD163-L1 is an endocytic macrophage protein strongly regulated by mediators in the inflammatory response

    DEFF Research Database (Denmark)

    Moeller, Jesper B; Nielsen, Marianne J; Reichhardt, Martin P

    2012-01-01

    -phase mediator IL-6 and the anti-inflammatory mediator IL-10 but is suppressed by the proinflammatory mediators IL-4, IL-13, TNF-α, and LPS/IFN-γ. Furthermore, we show that CD163-L1 is an endocytic receptor, which internalizes independently of cross-linking through a clathrin-mediated pathway. Two cytoplasmic...

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

    Directory of Open Access Journals (Sweden)

    Lucero López-Díaz

    2016-01-01

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

  16. Crowdsourcing Precision Cerebrovascular Health: Imaging and Cloud Seeding A Million Brains Initiative™

    Directory of Open Access Journals (Sweden)

    David S Liebeskind

    2016-11-01

    Full Text Available Crowdsourcing, an unorthodox approach in medicine, creates an unusual paradigm to study precision cerebrovascular health, eliminating the relative isolation and non-standardized nature of current imaging data infrastructure, while shifting emphasis to the astounding capacity of big data in the cloud. This perspective envisions the use of imaging data of the brain and vessels to orient and seed A Million Brains Initiative™ that may leapfrog incremental advances in stroke and rapidly provide useful data to the sizable population around the globe prone to the devastating effects of stroke and vascular substrates of dementia. Despite such variability in the type of data available and other limitations, the data hierarchy logically starts with imaging and can be enriched with almost endless types and amounts of other clinical and biological data. Crowdsourcing allows an individual to contribute to aggregated data on a population, while preserving their right to specific information about their own brain health. The cloud now offers endless storage, computing prowess and neuroimaging applications for post-processing that is searchable and scalable. Collective expertise is a windfall of the crowd in the cloud and particularly valuable in an area such as cerebrovascular health. The rise of precision medicine, rapidly evolving technological capabilities of cloud computing and the global imperative to limit the public health impact of cerebrovascular disease converge in the imaging of A Million Brains Initiative™. Crowdsourcing secure data on brain health may provide ultimate generalizability, enable focused analyses, facilitate clinical practice and accelerate research efforts.

  17. Genetic polymorphisms and cerebrovascular disease in children with sickle cell anemia from Rio de Janeiro, Brazil

    Directory of Open Access Journals (Sweden)

    Isaac Lima da Silva Filho

    2011-06-01

    Full Text Available The aim of the present work was to examine possible genetic risk factors related to the occurrence of cerebrovascular disease (CVD in Brazilian population, the frequency of βS-globin gene haplotypes and co-inheritance with α-thalassemia (-α3.7kb and single nucleotide polymorphism of methylenetetrahydrofolate reductase (MTHFR-C677T, Factor V Leiden (FV-G1691A and prothrombin (PT-G20210A genes in children from Rio de Janeiro. Ninety four children with sickle cell anemia (SCA were included, 24 patients with cerebrovascular involvement and 70 patients without CVD as control group. The mean age of children at the time of the cerebrovascular event was similar to the control group. The frequency of -α3.7kb thalassemia was similar in both groups (p=0.751. Children with Bantu/Atypical βS-globin gene haplotype presented 15 times more chance (OR=15.4 CI 95% 2.9-81.6 of CVD than the other βS-globin gene haplotypes. The C677T polymorphism of MTHFR gene was similar in both groups (p=0.085. No mutation in the FV Leiden or PT genes was found. A large study seems necessary to establish the role of these genetic polymorphisms in Brazilian miscegenated population.

  18. Characterization and prognosis factors of cerebro-vascular disease in Cienfuegos province.

    Directory of Open Access Journals (Sweden)

    Rubén Bembibre Taboada

    2004-08-01

    Full Text Available Fundaments: Cerebrovascular disease constitutes the third cause of death and the first cause of severe discapacity in adults in those countries that have a developed health system like ours. Objective: To characterise the patients with cerebrovascular disease and to determine the variables that influence upon their prognosis once it is established. Method: Prospective, descriptive, longitudinal study of a series of cases developed at the University Hospital ¨Dr. Gustavo Aldereguía Lima¨. Questionnaires were applied to the patients that fitted the inclusion criteria (n 1318 Results: The mean age was 66,08 years with a predominance of white patients ( 75,26 %, mainly males ( 56,67%. The risk factor of highest frequency was hypertension ( 43,24 % The evolution for alive patients without discapacities was 14,71%, alive with discapacities ( 57,96% and death 27,31%. There was a predominance of ischemic cerebrovascular disease (46,13 % of aterothrombotic infarcts and 14,94 % cardioembolic disease. In regards to hemorrhagic disease 13,42 % were intracerebral hemorrhage and 4,55% subarachnoid hemorrhage. There was a prognostic correlation between the clinical variables: consciousness, sight, sensibility, language, tone, Babinski , osteotendious reflexes and muscular force. For the general variables cerebral edema, bacterial bronchopneumonia , displacement of the medial line, diagnosis is some values, CT scan diagnoses in some values for diabetes mellitus and convulsions.

  19. Cognitive impairments in cerebrovascular disease: What is between health and dementia?

    Directory of Open Access Journals (Sweden)

    A. Yu. Emelin

    2015-01-01

    Full Text Available The problem of cerebrovascular lesions takes on even greater significance with the higher prevalence of both acute and chronic forms of cerebrovascular diseases (CVD. Cognitive dysfunctions that have a pronounced negative impact on the quality of life in patients hold a special place among the various neurological symptoms resulting from cerebrovascular lesions. The incidence of vascular dementia increases with age. The paper considers the main issues of the etiology, pathogenesis and classification of vascular cognitive impairments (VCIs. It proposes criteria for the diagnosis of VCIs in the early stages of the disease. Potentially modifiable factors, such as hypertension, coronary heart disease, orthostatic hypotension, diabetes mellitus, hypercholesterolemia, hyperhomocysteinemia, obesity, et al., are indicated to have a special place among the main etiological causes of VCIs. The timely detection of etiological factors and the assessment of their role in the development of cognitive impairments (CI in CVD form the basis for managing these patients. The issues of treating CI no dementia in patients with CVD are considered. These included the administration of nootropic, vasoactive drugs, as well as agents that exert a modulatory effect on the cholinergic and glutamatergic systems. The use of neuroprotective and neurotrophic drugs is noted to be promising in terms of the multicomponent mechanism of their action. 

  20. Two-dimensional thick-slice MR digital subtraction angiography for assessment of cerebrovascular occlusive diseases

    Energy Technology Data Exchange (ETDEWEB)

    Aoki, S.; Yoshikawa, T.; Hori, M.; Ishigame, K.; Nambu, A.; Kumagai, H.; Araki, T. [Dept. of Radiology, Yamanashi Medical Univ. (Japan)

    2000-12-01

    Although spatial resolution of current MR angiography is excellent, temporal resolution has remained unsatisfactory. We evaluated clinical applicability of 2D thick-slice, contrast-enhanced subtraction MR angiography (2D-MR digital subtraction angiography) with sub-second temporal resolution in cerebrovascular occlusive diseases. Twenty-five patients with cerebrovascular occlusive diseases (8 moyamoya diseases, 10 proximal internal carotid occlusions, and 2 sinus thromboses) were studied with a 1.5-T MR unit. The MR digital subtraction angiography (MRDSA) was performed per 0.97 s continuously just after a bolus injection of 15 ml of gadolinium chelates up to 40 s in sagittal (covering hemisphere) or coronal planes. Subtraction images were generated at a workstation. We evaluated imaging quality and hemodynamic information of MRDSA in comparison with those of routine MR imaging, non-contrast MR angiography, and X-ray intra-arterial DSA. Major cerebral arteries, all of the venous sinuses, and most tributaries were clearly visualized with 2D MRDSA. Also, pure arterial phases were obtained in all cases. The MRDSA technique demonstrated prolonged circulation in sinus thromboses, distal patent lumen of proximal occlusion, and some collateral circulation. Such hemodynamic information was comparable to that of intra-arterial DSA. Two-dimensional thick-slice MRDSA with high temporal resolution has a unique ability to demonstrate cerebral hemodynamics equivalent to that of intra-arterial DSA and may play an important role for evaluation of cerebrovascular occlusive diseases. (orig.)

  1. Heterogeneous Impact of ROCK2 on Carotid and Cerebrovascular Function.

    Science.gov (United States)

    De Silva, T Michael; Kinzenbaw, Dale A; Modrick, Mary L; Reinhardt, Lindsey D; Faraci, Frank M

    2016-09-01

    Rho kinase (ROCK) has been implicated in physiological and pathophysiological processes, including regulation of vascular function. ROCK signaling is thought to be a critical contributor to cardiovascular disease, including hypertension and effects of angiotensin II (Ang II). Two isoforms of ROCK (1 and 2) have been identified and are expressed in vascular cells. In this study, we examined the importance of ROCK2 in relation to vessel function using several models and a novel inhibitor of ROCK2. First, incubation of carotid arteries with the direct RhoA activator CN-03 or Ang II impaired endothelium-dependent relaxation by ≈40% to 50% (PROCK2 inhibitor SLX-2119. In contrast, SLX-2119 had little effect on contraction of carotid arteries to receptor-mediated agonists (serotonin, phenylephrine, vasopressin, or U46619). Second, in basilar arteries, SLX-2119 inhibited constriction to Ang II by ≈90% without significantly affecting responses to serotonin or KCl. Third, in isolated pressurized brain parenchymal arterioles, SLX-2119 inhibited myogenic tone in a concentration-dependent manner (eg, 1 μmol/L SLX-2119 dilated by 79±4%). Finally, SLX-2119 dilated small pial arterioles in vivo, an effect that was augmented by inhibition of nitric oxide synthase. These findings suggest that ROCK2 has major, but heterogeneous, effects on function of endothelium and vascular muscle. The data support the concept that aberrant ROCK2 signaling may be a key contributor to select aspects of large and small vessel disease, including Ang II-induced endothelial dysfunction.

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

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Shuai [Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012 (China); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States); Lv, Jiaju [Department of Urology, Shandong Provincial Hospital, Shandong University, Jinan 250021 (China); Han, Liping; Ichikawa, Tomonaga; Wang, Wenjuan; Li, Siying [Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States); Wang, Xing Li [Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012 (China); Tang, Dongqi, E-mail: tangdq@pathology.ufl.edu [Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610-0275 (United States); Cui, Taixing, E-mail: taixing.cui@uscmed.sc.edu [Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States)

    2012-03-30

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

  3. Age-associated pro-inflammatory adaptations of the mouse thoracic aorta.

    Science.gov (United States)

    Hemmeryckx, Bianca; Hoylaerts, Marc F; Deloose, Eveline; Van Hove, Cor E; Fransen, Paul; Bult, Hidde; Lijnen, H Roger

    2013-10-01

    Arterial ageing may be associated with a reduction in vasodilation due to increased reactive oxygen species (ROS) production, whereas endothelial cell activation induces procoagulant changes. However, little is known on the effect of ageing on expression of anticoagulant endothelial markers such as endothelial protein C receptor (EPCR). To study age-associated alterations in smooth muscle cell (SMC) and endothelial cell (EC) structure and function, the aorta was isolated from 10-week- and 12- and 24-month-old C57BL/6J mice and analysed for its expression of genes involved in senescence, oxidative stress production, coagulation and matrix remodelling. In addition, vasorelaxation experiments were performed using 10-week- and 24-month-old thoracic aortic ring segments in organ chamber baths. The media thickness of the thoracic aorta progressively increased with age, associated with hypertrophy of vascular SMCs. Basal nitric oxide production and sensitivity to acetylcholine-mediated vasodilation in thoracic aorta rings was reduced with age, whereas no significant differences in ROS production could be demonstrated. Gene expression of tissue factor, EPCR and von Willebrand factor was not affected by ageing of the aorta, whereas that of thrombomodulin was mildly reduced and that of xanthine dehydrogenase, NADPH oxidase 4, tumour necrosis factor-α and vascular cell adhesion molecule-1 significantly enhanced. In conclusion, a reduction in endothelial cell-mediated vasodilation in aged thoracic aortas of C57BL/6J mice was accompanied by a shift towards a pro-inflammatory state of the endothelium.

  4. Epigenetic synergies between biotin and folate in the regulation of pro-inflammatory cytokines and repeats.

    Science.gov (United States)

    Xue, J; Zempleni, J

    2013-11-01

    The protein biotin ligase, holocarboxylase synthetase (HLCS), is a chromatin protein that interacts physically with the DNA methyltransferase DNMT1, the methylated cytosine-binding protein MeCP2 and the histone H3 K9-methyltransferase EHMT1, all of which participate in folate-dependent gene repression. Here we tested the hypothesis that biotin and folate synergize in the repression of pro-inflammatory cytokines and long-terminal repeats (LTRs), mediated by interactions between HLCS and other chromatin proteins. Biotin and folate supplementation could compensate for each other's deficiency in the repression of LTRs in Jurkat and U937 cells. For example, when biotin-deficient Jurkat cells were supplemented with folate, the expression of LTRs decreased by >70%. Epigenetic synergies were more complex in the regulation of cytokines compared with LTRs. For example, the abundance of TNF-α was 100% greater in folate- and biotin-supplemented U937 cells compared with biotin-deficient and folate-supplemented cells. The NF-κB inhibitor curcumin abrogated the effects of folate and biotin in cytokine regulation, suggesting that transcription factor signalling adds an extra layer of complexity to the regulation of cytokine genes by epigenetic phenomena. We conclude that biotin and folate synergize in the repression of LTRs and that these interactions are probably mediated by HLCS-dependent epigenetic mechanisms. In contrast, synergies between biotin and folate in the regulation of cytokines need to be interpreted in the context of transcription factor signalling.

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

    Directory of Open Access Journals (Sweden)

    Kishore V L Parsa

    2006-07-01

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

  6. Changes in pro-inflammatory cytokines in association with exposure to moisture-damaged building microbes.

    Science.gov (United States)

    Purokivi, M K; Hirvonen, M R; Randell, J T; Roponen, M H; Meklin, T M; Nevalainen, A L; Husman, T M; Tukiainen, H O

    2001-12-01

    Several epidemiological studies have described an association between adverse health effects and exposure to mould and microbes present in the indoor air of moisture-damaged buildings. However, the biochemical linkage between microbial exposure and the large variety of reported respiratory symptoms is poorly understood. In the present study, the authors compared the respiratory symptoms, the production of inflammatory mediators interleukin (IL)-1, IL-4, IL-6, tumour necrosis factor-alpha (TNF-alpha) and cell count in nasal lavage fluid and induced sputum samples of subjects working in moisture-damaged and control school buildings. The sampling was performed and the questionnaires were completed at the end of the spring term, at the end of the summer vacation (2.5 months), during the winter term and after a 1-week winter holiday. The authors found a significant elevation of IL-1, TNF-alpha and IL-6 in nasal lavage fluid and IL-6 in induced sputum during the spring term in the subjects from the moisture-damaged school building compared to the subjects from the control building. The exposed workers reported sore throat, phlegm, eye irritation, rhinitis, nasal obstruction and cough in parallel with these findings. The present data suggests an association between microbial exposure, and symptoms as well as changes in pro-inflammatory mediators detected from both the upper and lower airways.

  7. Role in proinflammatory response of YghJ, a secreted metalloprotease from neonatal septicemic Escherichia coli.

    Science.gov (United States)

    Tapader, Rima; Bose, Dipro; Basu, Pallabi; Mondal, Moumita; Mondal, Ayan; Chatterjee, Nabendu Sekhar; Dutta, Pujarini; Basu, Sulagna; Bhadra, Rupak K; Pal, Amit

    2016-11-01

    Neonatal sepsis is the invasion of microbial pathogens into blood stream and is associated with a systemic inflammatory response with production and release of a wide range of inflammatory mediators. The increased serum levels of cytokines were found to correlate with the severity and mortality in course of sepsis. There have been no reports on the role of microbial proteases in stimulation of proinflammatory response in neonatal sepsis. We have identified YghJ, a secreted metalloprotease from a neonatal septicemic Escherichia coli (NSEC) isolate. The protease was partially purified from culture supernatant by successive anion and gel filtration chromatography. MS/MS peptide sequencing of the protease showed homology with YghJ. YghJ was cloned, expressed and purified in pBAD TOPO expression vector. YghJ was found to be proteolytically active against Methoxysuccinyl Ala-Ala-Pro-Met-p-nitroanilide oligopeptide substrate, but not against casein and gelatin. YghJ showed optimal activity at pH 7-8 and at temperatures 37-40°C. YghJ showed clear changes in cellular morphologies of Int407, HT-29 and HEK293 cells. YghJ stimulated the secretion of cytokines IL-1α, IL-1β and TNF-α in murine macrophages (RAW 264.7) and IL-8 from human intestinal epithelial cells (HT-29). YghJ also down-regulated the production of anti-inflammatory cytokines such as IL-10. YghJ is present in both septicemic (78%) and fecal E. coli isolates (54%). However, expression and secretion of YghJ is significantly higher among the septicemic (89%) than the fecal isolates (33%). This is the first study to show the role of a microbial protease, YghJ in triggering proinflammatory response in NSEC.

  8. Fatigue in primary Sjögren's syndrome is associated with lower levels of proinflammatory cytokines

    Science.gov (United States)

    Howard Tripp, Nadia; Tarn, Jessica; Natasari, Andini; Gillespie, Colin; Mitchell, Sheryl; Hackett, Katie L; Bowman, Simon J; Price, Elizabeth; Pease, Colin T; Emery, Paul; Lanyon, Peter; Hunter, John; Gupta, Monica; Bombardieri, Michele; Sutcliffe, Nurhan; Pitzalis, Costantino; McLaren, John; Cooper, Annie; Regan, Marian; Giles, Ian; Isenberg, David A; Saravanan, Vadivelu; Coady, David; Dasgupta, Bhaskar; McHugh, Neil; Young-Min, Steven; Moots, Robert; Gendi, Nagui; Akil, Mohammed; Griffiths, Bridget; Lendrem, Dennis W; Ng, Wan-Fai

    2016-01-01

    Objectives This article reports relationships between serum cytokine levels and patient-reported levels of fatigue, in the chronic immunological condition primary Sjögren's syndrome (pSS). Methods Blood levels of 24 cytokines were measured in 159 patients with pSS from the United Kingdom Primary Sjögren's Syndrome Registry and 28 healthy non-fatigued controls. Differences between cytokines in cases and controls were evaluated using Wilcoxon test. Patient-reported scores for fatigue were evaluated, classified according to severity and compared with cytokine levels using analysis of variance. Logistic regression was used to determine the most important predictors of fatigue levels. Results 14 cytokines were significantly higher in patients with pSS (n=159) compared to non-fatigued healthy controls (n=28). While serum levels were elevated in patients with pSS compared to healthy controls, unexpectedly, the levels of 4 proinflammatory cytokines—interferon-γ-induced protein-10 (IP-10) (p=0.019), tumour necrosis factor-α (p=0.046), lymphotoxin-α (p=0.034) and interferon-γ (IFN-γ) (p=0.022)—were inversely related to patient-reported levels of fatigue. A regression model predicting fatigue levels in pSS based on cytokine levels, disease-specific and clinical parameters, as well as anxiety, pain and depression, revealed IP-10, IFN-γ (both inversely), pain and depression (both positively) as the most important predictors of fatigue. This model correctly predicts fatigue levels with reasonable (67%) accuracy. Conclusions Cytokines, pain and depression appear to be the most powerful predictors of fatigue in pSS. Our data challenge the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions. Instead, we hypothesise that mechanisms regulating inflammatory responses may be important. PMID:27493792

  9. Irsogladine maleate suppresses indomethacin-induced elevation of proinflammatory cytokines and gastric injury in rats

    Institute of Scientific and Technical Information of China (English)

    Xin Zhang; Koyuki Tajima; Kiyoto Kageyama; Takashi Kyoi

    2008-01-01

    AIM: To investigate the mucosal protective effect and the mechanisms of action of the anti-ulcer drug irsogladine maleate in gastric injury induced by indomethacin in rats.METHODS: Gastric mucosal injury was induced in male Hos:Donryu rats by oral administration of indomethacin at a dose of 48 mg/kg.One hour before indomethacin treatment,animals were orally pretreated with irsogladine maleate at doses of 1 mg/kg,3 mg/kg or 10 mg/kg.Four hours after indomethacin administration,the animals were sacrificed and their stomachs were rapidly removed and processed for the evaluation of gastric mucosal damage and the determination of the concentrations of tumor necrosis factor-α (TNF-α),interleukin-1β(IL-1β),IL-8 and myeloperoxidase (MPO) in mucosal tissues.RESULTS: Linear hemorrhagic mucosal lesions were observed primarily in the glandular stomach 4 h after oral administration of indomethacin.Pretreatment with irsogladine maleate markedly reduced the number and severity of these lesions in a dosedependent manner.The mucosal concentrations of proinflammatory cytokines (TNF-β,IL-1β,and IL-8)and MPO,which indicates the degree of mucosal infiltration by neutrophils,increased concomitantly with the occurrence of gastric injury in the indomethacintreated rats.Pretreatment with irsogladine maleate significantly decreased the levels of these inflammatory factors in gastric tissue elicited by indomethacin.CONCLUSION: The mucosal protective effects afforded by irsogladine maleate on gastric injury induced by indomethacin are mediated by inhibition of mucosal proinflammatory cytokine production and neutrophil infiltration,leading to suppression of mucosal inflammation and subsequent tissue destruction.

  10. REDUCED TISSUE OSMOLARITY INCREASES TRPV4 EXPRESSION AND PRO-INFLAMMATORY CYTOKINES IN INTERVERTEBRAL DISC CELLS

    Science.gov (United States)

    Walter, B.A.; Purmessur, D; Moon, A.; Occhiogrosso, J.; Laudier, D.M.; Hecht, A.C.; Iatridis, J.C.

    2016-01-01

    The mechanical behaviour and cellular metabolism of intervertebral discs (IVDs) and articular cartilage are strongly influenced by their proteoglycan content and associated osmotic properties. This osmotic environment is a biophysical signal that changes with disease and may contribute to the elevated matrix breakdown and altered biologic response to loading observed in IVD degeneration and osteoarthritis. This study tested the hypothesis that changes in osmo-sensation by the transient receptor potential vallinoid-4 (TRPV4) ion channel occur with disease and contribute to the inflammatory environment found during degeneration. Immunohistochemistry on bovine IVDs from an inflammatory organ culture model were used to investigate if TRPV4 is expressed in the IVD and how expression changes with degeneration. Western blot, live-cell calcium imaging, and qRT-PCR were used to investigate whether osmolarity changes or tumour necrosis factor α (TNFα) regulate TRPV4 expression, and how altered TRPV4 expression influences calcium signalling and pro-inflammatory cytokine expression. TRPV4 expression correlated with TNFα expression, and was increased when cultured in reduced medium osmolarity and unaltered with TNFα-stimulation. Increased TRPV4 expression increased the calcium flux following TRPV4 activation and increased interleukin-1β (IL-1β) and IL-6 gene expression in IVD cells. TRPV4 expression was qualitatively elevated in regions of aggrecan depletion in degenerated human IVDs. Collectively, results suggest that reduced tissue osmolarity, likely following proteoglycan degradation, can increase TRPV4 signalling and enhance pro-inflammatory cytokine production, suggesting changes in TRPV4 mediated osmo-sensation may contribute to the progressive matrix breakdown in disease. PMID:27434269

  11. β-Catenin promotes colitis and colon cancer through imprinting of proinflammatory properties in T cells.

    Science.gov (United States)

    Keerthivasan, Shilpa; Aghajani, Katayoun; Dose, Marei; Molinero, Luciana; Khan, Mohammad W; Venkateswaran, Vysak; Weber, Christopher; Emmanuel, Akinola Olumide; Sun, Tianjao; Bentrem, David J; Mulcahy, Mary; Keshavarzian, Ali; Ramos, Elena M; Blatner, Nichole; Khazaie, Khashayarsha; Gounari, Fotini

    2014-02-26

    The density and type of lymphocytes that infiltrate colon tumors are predictive of the clinical outcome of colon cancer. High densities of T helper 17 (T(H)17) cells and inflammation predict poor outcome, whereas infiltration by T regulatory cells (Tregs) that naturally suppress inflammation is associated with longer patient survival. However, the role of Tregs in cancer remains controversial. We recently reported that Tregs in colon cancer patients can become proinflammatory and tumor-promoting. These properties were directly linked with their expression of RORγt (retinoic acid-related orphan receptor-γt), the signature transcription factor of T(H)17 cells. We report that Wnt/β-catenin signaling in T cells promotes expression of RORγt. Expression of β-catenin was elevated in T cells, including Tregs, of patients with colon cancer. Genetically engineered activation of β-catenin in mouse T cells resulted in enhanced chromatin accessibility in the proximity of T cell factor-1 (Tcf-1) binding sites genome-wide, induced expression of T(H)17 signature genes including RORγt, and promoted T(H)17-mediated inflammation. Strikingly, the mice had inflammation of small intestine and colon and developed lesions indistinguishable from colitis-induced cancer. Activation of β-catenin only in Tregs was sufficient to produce inflammation and initiate cancer. On the basis of these findings, we conclude that activation of Wnt/β-catenin signaling in effector T cells and/or Tregs is causatively linked with the imprinting of proinflammatory properties and the promotion of colon cancer.

  12. Manumycin A downregulates release of proinflammatory cytokines from TNF alpha stimulated human monocytes.

    Science.gov (United States)

    Cecrdlova, Eva; Petrickova, Katerina; Kolesar, Libor; Petricek, Miroslav; Sekerkova, Alena; Svachova, Veronika; Striz, Ilja

    2016-01-01

    Macrolide antibiotics such as azithromycin or clarithromycin are known to have potent anti-inflammatory and immunomodulatory effects but these properties cannot be widely used due to a risk of bacterial resistance. We studied another polyketide antibiotic, structurally related manumycin A known as a streptomycete derived farnesyltransferase inhibitor with limited antibacterial effects, with respect to its potential regulation of mRNA expression of several genes associated with proinflammatory responses. Downregulation of mRNA for IL-6, TLR-8, IL-1 beta and IL-10 was found in THP-1 cells after 4h stimulation with TNF alpha in the presence of manumycin A and downregulated TLR-8 and EGR-1 genes were observed after 8h. Among the genes upregulated in response to manumycin were HMOX-1, TNFRSF10A, IL-1R1, TICAM2, NLRP12 after 4h and only IL-1R1 after 8h. Furthermore, manumycin A was found to inhibit IL-1beta, IL-6, and IL-8 production in TNF alpha stimulated THP-1 cells and peripheral blood monocytes in a dose dependent manner (0.25-1 μM of manumycin A) without affecting cell viability. Cell viability of blood monocytes decreased by about 30% at manumycin A doses of 2-5 μM. Manumycin A also inhibited IL-18 release from THP-1 cells, while in cultures of blood monocytes, this cytokine was not detectable. That manumycin A mediated downregulation of proinflammatory genes in human monocytes confirmed by a measurement of cytokine levels in culture supernatants, together with a very limited effect on cell viability, might suggest potential anti-inflammatory properties of this polyketide antibiotic.

  13. Store-operated calcium channels and pro-inflammatory signals

    Institute of Scientific and Technical Information of China (English)

    Wei-chiao CHANG

    2006-01-01

    In non-excitable cells such as T lymphocytes,hepatocytes,mast cells,endothelia and epithelia,the major pathway for calcium(Ca2+)entry is through store-operated Ca2+ channels in the plasma membrane.These channels are activated by the emptying of intracellular Ca2+ stores,however,neither the gating mechanism nor the downstream targets of these channels has been clear established.Here,I review some of the proposed gating mechanisms of store-operated Ca2+ channels and the functional implications in regulating pro-inflammatory signals.

  14. FUNDAMENTAL IMMUNOBIOLOGY OF PRO-INFLAMMATORY CYTOKINES AND MIF

    Directory of Open Access Journals (Sweden)

    A. P. Suslov

    2006-01-01

    Full Text Available Fundamental immunobiology of proinflammatory cytokines and MIFThere are a lot of similarity as well as differences when we compare cytokines with MIF according their biological properties. MIF characteristics are unique structure, organs and tissues ubiquity, extremely wide variety of functions (proinflammatory cytokine, enzyme, hormone, ability to be induced by glucocorticoid hormones and affects as their immunosuppressive effects antagonist. MIF exists in preformed condition in lymphocytes, macrophages and endothelium cells. It secrets by these cells and operates as a mobilizing defense system factor in the first minutes of foreign invasion. MIF exhibits the properties of super-ligand binding with many biologically important molecules. This factor carries out the functions that are important for cell activation, proliferation and death, using a variety of intracellular signaling pathways. Some of MIF homologues exists in plants and bacteria earlier than innate and adaptive immune systems appears in evolution. In ontogenesis MIF appears at the stage of firsts cell divisions. MIF has a lot of functions, variety of ligand bindings, many effector pathways, it appears early in ontogeny and phylogeny. MIF takes part into protective reactions at any levels – from cell up to whole organism. All these MIF features taking together into account make it possible to possess it as a particular type of cytokine – eocytokine (from Greek word “eo” – early. It is assumed that MIF may function as some kind of cells and organisms "natural stability" key factor.

  15. Glucocorticoid Receptor-Mediated Repression of Pro-Inflammatory Genes in Rheumatoid Arthritis

    Science.gov (United States)

    2015-10-01

    ongoing, the Pol II ChIP-seq tracks of the two stereotypic representatives of the ‘initiation-controlled’ and ‘elongation-controlled’ groups of genes...Barbara Volcker Center for Women and Rheumatic Disease (role: PI; 5% effort) - this support is no longer active 3) Rheumatology Research Foundation (role...1) American Heart Association SGD #11SDG5160006 (role: PI, 44% effort) – this support is no longer active. 2) Barbara Volcker Center for Women and

  16. Involvement of monoamines and proinflammatory cytokines in mediating the anti-stress effects of Panax quinquefolium.

    Science.gov (United States)

    Rasheed, Naila; Tyagi, Ethika; Ahmad, Ausaf; Siripurapu, Kiran Babu; Lahiri, Shawon; Shukla, Rakesh; Palit, Gautam

    2008-05-08

    Panax quinquefolium (PQ) is well acclaimed in literature for its effects on central and peripheral nervous system. The present study explores the effects of PQ on stress induced changes of corticosterone level in plasma, monoamines (NA, DA and 5-HT) and interleukin (IL-2 and IL-6) levels in cortex and hippocampus regions of brain and also indicate their possible roles in modulating stress. Mice subjected to chronic unpredictable stress (CUS, for 7 days) showed significant increase in plasma corticosterone level and depletion of noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) levels in cortex and hippocampal regions along with an increased level of IL-2 and IL-6 in the same areas. Aqueous suspension of PQ was administered daily at a dose of 100 and 200mg/kg p.o. prior to the stress regimen and its effects on selected stress markers in plasma and brain was evaluated. PQ at a dose of 200mg/kg p.o. was found to be effective in normalizing the CUS induced elevation of plasma corticosterone and IL-2, IL-6 levels in brain. Moreover, it was significantly effective in reinstating the CUS induced depletion of NA, DA and 5-HT in hippocampus, while NA and 5-HT in cortex of brain. However, PQ at a dose of 100mg/kg p.o. was found ineffective in regulating any of these CUS induced changes. Present study provides an insight into the possible role of PQ on hyperactive HPA axis in the regulation of immediate stress effectors like corticosterone, cytokines and brain monoamines. In this study, PQ has emerged as a potential therapeutic in the cure of stress related disorders and needs to be evaluated in clinical studies to ascertain its efficacy.

  17. MAPK and pro-inflammatory mediators in the walls of brain blood vessels following cerebral ischemia

    OpenAIRE

    Maddahi, Aida

    2012-01-01

    INTRODUCTION Stroke is a serious neurological disease which may lead to death and severe disability [1, 2]. There are two major types of stroke: ischemic and hemorrhagic stroke. Both are associated with disruption of blood flow to a part of the brain with rapid depletion of cellular energy and oxygen, resulting in ionic disturbances and eventually neuronal cell death [3]. The pathologic process that develops after stroke is divided into acute (within hours), sub-acute (hours to days), ...

  18. Selection for pro-inflammatory mediators produces chickens more resistant to Campylobacter jejuni

    Science.gov (United States)

    Campylobacter spp. are the second leading cause of bacterial-induced foodborne illnesses with an estimated economic burden of nearly $2 billion per year. Most human illness associated with campylobacteriosis is due to infection by C. jejuni and chickens are recognized as a reservoir, which could le...

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Increased serum C-reactive protein level in Japanese patients of psoriasis with cardio- and cerebrovascular disease.

    Science.gov (United States)

    Takahashi, Hidetoshi; Iinuma, Shin; Honma, Masaru; Iizuka, Hajime

    2014-11-01

    Psoriasis is a chronic inflammatory skin disease, which may be associated with metabolic syndrome accompanied by cardio- and cerebrovascular diseases. We investigated the relation between serum C-reactive protein (CRP) and cardio- and cerebrovascular diseases in Japanese psoriasis vulgaris patients. Ninety-seven psoriasis vulgaris patients and 79 healthy controls were assessed for serum CRP levels by immunoturbidimetry. The data were analyzed in terms of Psoriasis Area and Severity Index (PASI) scores, and comorbidity of cardio- and cerebrovascular disease and metabolic syndrome. Serum CRP levels in psoriasis vulgaris patients were significantly higher than those of healthy controls. There was no significant difference between male and female CRP levels in either psoriasis or healthy controls. No correlation was detected between PASI scores and serum CRP levels, either. Psoriasis with cardio- and cerebrovascular disease showed significantly higher CRP levels compared with those without the diseases. Furthermore, psoriasis with metabolic syndrome showed significantly higher serum CRP levels than those without the metabolic syndrome. In conclusion, serum CRP level is increased in psoriasis, and may be a useful marker for the prediction of the future risk of cardio- and cerebrovascular disease.

  1. Inhibitor of apoptosis proteins (IAPs) and their antagonists regulate spontaneous and tumor necrosis factor (TNF)-induced proinflammatory cytokine and chemokine production.

    Science.gov (United States)

    Kearney, Conor J; Sheridan, Clare; Cullen, Sean P; Tynan, Graham A; Logue, Susan E; Afonina, Inna S; Vucic, Domagoj; Lavelle, Ed C; Martin, Seamus J

    2013-02-15

    Inhibitor of apoptosis proteins (IAPs) play a major role in determining whether cells undergo apoptosis in response to TNF as well as other stimuli. However, TNF is also highly proinflammatory through its ability to trigger the secretion of multiple inflammatory cytokines and chemokines, which is arguably the most important role of TNF in vivo. Indeed, deregulated production of TNF-induced cytokines is a major driver of inflammation in several autoimmune conditions such as rheumatoid arthritis. Here, we show that IAPs are required for the production of multiple TNF-induced proinflammatory mediators. Ablation or antagonism of IAPs potently suppressed TNF- or RIPK1-induced proinflammatory cytokine and chemokine production. Surprisingly, IAP antagonism also led to spontaneous production of chemokines, particularly RANTES, in vitro and in vivo. Thus, IAPs play a major role in influencing the production of multiple inflammatory mediators, arguing that these proteins are important regulators of inflammation in addition to apoptosis. Furthermore, small molecule IAP antagonists can modulate spontaneous as well as TNF-induced inflammatory responses, which may have implications for use of these agents in therapeutic settings.

  2. The Pro-inflammatory Role of TGFβ1: A Paradox?

    Directory of Open Access Journals (Sweden)

    Gangwen Han, Fulun Li, Tej Pratap Singh, Peter Wolf, Xiao-Jing Wang

    2012-01-01

    Full Text Available TGFβ1 was initially identified as a potent chemotactic cytokine to initiate inflammation, but the autoimmune phenotype seen in TGFβ1 knockout mice reversed the dogma of TGFβ1 being a pro-inflammatory cytokine to predominantly an immune suppressor. The discovery of the role of TGFβ1 in Th17 cell activation once again revealed the pro-inflammatory effect of TGFβ1. We developed K5.TGFβ1 mice with latent human TGFβ1 overexpression targeted to epidermal keratinocytes by keratin 5. These transgenic mice developed significant skin inflammation. Further studies revealed that inflammation severity correlated with switching TGFβ1 transgene expression on and off, and genome wide expression profiling revealed striking similarities between K5.TGFβ1 skin and human psoriasis, a Th1/Th17-associated inflammatory skin disease. Our recent study reveals that treatments alleviating inflammatory skin phenotypes in this mouse model reduced Th17 cells, and antibodies against IL-17 also lessen the inflammatory phenotype. Examination of inflammatory cytokines/chemokines affected by TGFβ1 revealed predominantly Th1-, Th17-related cytokines in K5.TGFβ1 skin. However, the finding that K5.TGFβ1 mice also express Th2-associated inflammatory cytokines under certain pathological conditions raises the possibility that deregulated TGFβ signaling is involved in more than one inflammatory disease. Furthermore, activation of both Th1/Th17 cells and regulatory T cells (Tregs by TGFβ1 reversely regulated by IL-6 highlights the dual role of TGFβ1 in regulating inflammation, a dynamic, context and organ specific process. This review focuses on the role of TGFβ1 in inflammatory skin diseases.

  3. The Pro-inflammatory Role of TGFβ1: A Paradox?

    Science.gov (United States)

    Han, Gangwen; Li, Fulun; Singh, Tej Pratap; Wolf, Peter; Wang, Xiao-Jing

    2012-01-01

    TGFβ1 was initially identified as a potent chemotactic cytokine to initiate inflammation, but the autoimmune phenotype seen in TGFβ1 knockout mice reversed the dogma of TGFβ1 being a pro-inflammatory cytokine to predominantly an immune suppressor. The discovery of the role of TGFβ1 in Th17 cell activation once again revealed the pro-inflammatory effect of TGFβ1. We developed K5.TGFβ1 mice with latent human TGFβ1 overexpression targeted to epidermal keratinocytes by keratin 5. These transgenic mice developed significant skin inflammation. Further studies revealed that inflammation severity correlated with switching TGFβ1 transgene expression on and off, and genome wide expression profiling revealed striking similarities between K5.TGFβ1 skin and human psoriasis, a Th1/Th17-associated inflammatory skin disease. Our recent study reveals that treatments alleviating inflammatory skin phenotypes in this mouse model reduced Th17 cells, and antibodies against IL-17 also lessen the inflammatory phenotype. Examination of inflammatory cytokines/chemokines affected by TGFβ1 revealed predominantly Th1-, Th17-related cytokines in K5.TGFβ1 skin. However, the finding that K5.TGFβ1 mice also express Th2-associated inflammatory cytokines under certain pathological conditions raises the possibility that deregulated TGFβ signaling is involved in more than one inflammatory disease. Furthermore, activation of both Th1/Th17 cells and regulatory T cells (Tregs) by TGFβ1 reversely regulated by IL-6 highlights the dual role of TGFβ1 in regulating inflammation, a dynamic, context and organ specific process. This review focuses on the role of TGFβ1 in inflammatory skin diseases. PMID:22253566

  4. Osteoprotegerin CGA haplotype protection against cerebrovascular complications in anti-CCP negative patients with rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Fernanda Genre

    Full Text Available Rheumatoid arthritis is an inflammatory disease with high incidence of cardiovascular disease due to accelerated atherosclerosis. Osteoprotegerin (OPG has been associated with increased risk of atherosclerotic disease in the general population. Several polymorphisms in the OPG gene with functional effects on cardiovascular disease in non-rheumatic individuals have been described. Therefore, we aimed to analyze the effect of three of these functional OPG polymorphisms on the risk of cardiovascular disease in a large and well-characterized cohort of Spanish patients with rheumatoid arthritis.Three OPG gene variants (rs3134063, rs2073618 and rs3134069 were genotyped by TaqMan assays in 2027 Spanish patients with rheumatoid arthritis. Anti-cyclic citrullinated peptide (anti-CCP antibody testing was positive in 997 of 1714 tested. Also, 18.3% of the whole series had experienced cardiovascular events, including 5.4% with cerebrovascular accidents. The relationship between OPG variants and cardiovascular events was assessed using Cox regression.No association between OPG gene variants and cardiovascular disease was observed in the whole group of rheumatoid arthritis patients or in anti-CCP positive patients. Nevertheless, a protective effect of CGA haplotype on the risk of cardiovascular disease in general, and specifically in the risk of cerebrovascular complications after adjusting for sex, age at disease diagnosis and traditional cardiovascular risk factors was disclosed in anti-CCP negative patients (HR = 0.54; 95%CI: 0.31-0.95; p = 0.032 and HR = 0.17; 95%CI: 0.04-0.78; p = 0.022, respectively.Our results indicate a protective effect of the OPG CGA haplotype on cardiovascular risk, mainly due to a protective effect against cerebrovascular events in anti-CCP negative rheumatoid arthritis patients.

  5. Trends in Mortality from Cerebrovascular and Hypertensive Diseases in Brazil Between 1980 and 2012

    Directory of Open Access Journals (Sweden)

    Paolo Blanco Villela

    2016-01-01

    Full Text Available Abstract Background: Cerebrovascular and hypertensive diseases are among the main causes of death worldwide. However, there are limited data about the trends of these diseases over the years. Objective: To evaluate the temporal trends in mortality rates and proportional mortality from cerebrovascular and hypertensive diseases according to sex and age in Brazil between 1980 and 2012. Methods: We evaluated the underlying causes of death between 1980 and 2012 in both sexes and by age groups for circulatory diseases (CD, cerebrovascular diseases (CBVD, and hypertensive diseases (HD. We also evaluated death due to all causes (AC, external causes (EC, and ill-defined causes of death (IDCD. Data on deaths and population were obtained from the Department of Information Technology of the Unified Health System (Departamento de Informática do Sistema Único de Saúde, DATASUS/MS. We estimated crude and standardized annual mortality rates per 100,000 inhabitants and percentages of proportional mortality rates. Results: With the exception of EC, the mortality rates per 100,000 inhabitants of all other diseases increased with age. The proportional mortality of CD, CBVD, and HD increased up to the age range of 60-69 years in men and 70-79 years in women, and reached a plateau in both sexes after that. The standardized rates of CD and CBVD declined in both sexes. However, the HD rates showed the opposite trend and increased mildly during the study period. Conclusion: Despite the decline in standardized mortality rates due to CD and CBVD, there was an increase in deaths due to HD, which could be related to factors associated with the completion of the death certificates, decline in IDCD rates, and increase in the prevalence of hypertension.

  6. The balance between cognitive reserve and brain imaging biomarkers of cerebrovascular and Alzheimer's diseases.

    Science.gov (United States)

    Murray, Alison D; Staff, Roger T; McNeil, Christopher J; Salarirad, Sima; Ahearn, Trevor S; Mustafa, Nazahah; Whalley, Lawrence J

    2011-12-01

    The cognitive reserve hypothesis explains the disparity between clinical and pathological phenotypes and why, in two individuals with the same extent of neuropathology, one may be demented while the other remains cognitively intact. We examined the balance between brain magnetic resonance imaging measures of the two most common pathologies associated with brain ageing, cerebrovascular disease and Alzheimer's disease, and parameters of cerebral reserve in well-characterized participants born in 1936, for whom childhood intelligence is known. Brain magnetic resonance imaging was carried out at 1.5T using fluid attenuation inversion recovery and T(1)-weighted volumetric sequences in 249 participants. Cerebrovascular disease was quantified by measuring brain white matter hyperintensities on fluid attenuation inversion recovery images using Scheltens' scale and Alzheimer's disease was measured from volumetric data using FreeSurfer to extract whole brain volume and hippocampal volumes in turn. The effect of these measures of brain burden on life-long cognitive ageing from the age of 11 to 68 years was compared with the effect of educational attainment and occupational grade using structural equation modelling. Complete brain burden and reserve data were available in 224 participants. We found that educational attainment, but not occupation, has a measurable and positive effect, with a standardized regression weight of +0.23, on late life cognitive ability in people without cognitive impairment aged 68 years, allowing for the influence of childhood intelligence and the two most common subclinical brain pathological burdens in the ageing brain. In addition, we demonstrate that the magnitude of the contribution of education is greater than the negative impact of either neuropathological burden alone, with standardized regression weights of -0.14 for white matter hyperintensities and -0.20 for hippocampal atrophy. This study illustrates how education counteracts the

  7. Trends in Mortality from Cerebrovascular and Hypertensive Diseases in Brazil Between 1980 and 2012

    Science.gov (United States)

    Villela, Paolo Blanco; Klein, Carlos Henrique; de Oliveira, Gláucia Maria Moraes

    2016-01-01

    Background Cerebrovascular and hypertensive diseases are among the main causes of death worldwide. However, there are limited data about the trends of these diseases over the years. Objective To evaluate the temporal trends in mortality rates and proportional mortality from cerebrovascular and hypertensive diseases according to sex and age in Brazil between 1980 and 2012. Methods We evaluated the underlying causes of death between 1980 and 2012 in both sexes and by age groups for circulatory diseases (CD), cerebrovascular diseases (CBVD), and hypertensive diseases (HD). We also evaluated death due to all causes (AC), external causes (EC), and ill-defined causes of death (IDCD). Data on deaths and population were obtained from the Department of Information Technology of the Unified Health System (Departamento de Informática do Sistema Único de Saúde, DATASUS/MS). We estimated crude and standardized annual mortality rates per 100,000 inhabitants and percentages of proportional mortality rates. Results With the exception of EC, the mortality rates per 100,000 inhabitants of all other diseases increased with age. The proportional mortality of CD, CBVD, and HD increased up to the age range of 60-69 years in men and 70-79 years in women, and reached a plateau in both sexes after that. The standardized rates of CD and CBVD declined in both sexes. However, the HD rates showed the opposite trend and increased mildly during the study period. Conclusion Despite the decline in standardized mortality rates due to CD and CBVD, there was an increase in deaths due to HD, which could be related to factors associated with the completion of the death certificates, decline in IDCD rates, and increase in the prevalence of hypertension. PMID:27355586

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

    Directory of Open Access Journals (Sweden)

    Zhang Jiaxing

    2011-09-01

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

  9. Avoidable 30-Day Readmissions Among Patients With Stroke and Other Cerebrovascular Disease

    Science.gov (United States)

    Nahab, Fadi; Takesaka, Jennifer; Mailyan, Eugene; Judd, Lilith; Culler, Steven; Webb, Adam; Frankel, Michael; Choi, Dennis; Helmers, Sandra

    2012-01-01

    Background: There are limited data on factors associated with 30-day readmissions and the frequency of avoidable readmissions among patients with stroke and other cerebrovascular disease. Methods: University HealthSystem Consortium (UHC) database records were used to identify patients discharged with a diagnosis of stroke or other cerebrovascular disease at a university hospital from January 1, 2007 to December 31, 2009 and readmitted within 30 days to the index hospital. Logistic regression models were used to identify patient and clinical characteristics associated with 30-day readmission. Two neurologists performed chart reviews on readmissions to identify avoidable cases. Results: Of 2706 patients discharged during the study period, 174 patients had 178 readmissions (6.4%) within 30 days. The only factor associated with 30-day readmission was the index length of stay >10 days (vs <5 days; odds ratio [OR] 2.3, 95% CI [1.4, 3.7]). Of 174 patients readmitted within 30 days (median time to readmission 10 days), 92 (53%) were considered avoidable readmissions including 38 (41%) readmitted for elective procedures within 30 days of discharge, 27 (29%) readmitted after inadequate outpatient care coordination, 15 (16%) readmitted after incomplete initial evaluations, 8 (9%) readmitted due to delayed palliative care consultation, and 4 (4%) readmitted after being discharged with inadequate discharge instructions. Only 5% of the readmitted patients had outpatient follow-up recommended within 1 week. Conclusions: More than half of the 30-day readmissions were considered avoidable. Coordinated timing of elective procedures and earlier outpatient follow-up may prevent the majority of avoidable readmissions among patients with stroke and other cerebrovascular disease. PMID:23983857

  10. Effects of yokukansan on anxiety-like behavior in a rat model of cerebrovascular dementia.

    Science.gov (United States)

    Nogami, Ai; Sakata, Yuri; Uchida, Naoki; Yamaguchi, Kazuko; Kawasaki, Chihiro; Shindo, Taro; Kubota, Kaori; Katsurabayashi, Shutaro; Takasaki, Kotaro; Mishima, Kenichi; Nishimura, Ryoji; Fujiwara, Michihiro; Iwasaki, Katsunori

    2011-04-01

    Behavioral and psychological symptoms of dementia (BPSD) are commonly seen in patients with dementia. Current pharmacological approaches to treatment are inadequate, despite the availability of serotonergic agents to ameliorate anxiety, one of the symptoms of BPSD. The herbal medicine yokukansan has been demonstrated to improve BPSD in a randomized, single-blinded, placebo-controlled study. However, the mechanisms of the anxiolytic effect of yokukansan have not been clarified. There are also no reports on the anxiolytic effect of yokukansan in cerebrovascular ischemia models. In this study, we examined whether rats subjected to repeated cerebral ischemia exhibited anxiety-like behavior in a plus-maze task, a light/dark box test and an open-field task. We then investigated the effect of yokukansan on anxiety-like behavior in ischemic rats. Repeated ischemia was induced by the four-vessel occlusion method in which a 10-min ischemic episode was repeated once after 60 min. Yokukansan was orally administered once a day for 14 days from 7 days before ischemia induction. The last administration was performed 1 h before the behavioral experiments. The ischemic rats showed anxiety-like behavior in all three tasks, suggesting that this rat may be a good model for anxiety in cerebrovascular dementia. Yokukansan exhibited anxiolytic effects on the anxiety-like behavior in rats subjected to repeated cerebral ischemia, and exerted antagonistic effects on the wet-dog shakes induced by 1-(2,5-dimethoxy-4-indophenyl)-2-amino propane, a serotonin receptor (5-HT(2A)) agonist. This study revealed that yokukansan shows anxiolytic effects not only in normal animals but also in cerebrovascular model rats.

  11. Uric acid levels and their relation to incapacities in acute cerebrovascular disease Los niveles de ácido úrico y su relación con la discapacidad en la fase aguda de la enfermedad cerebrovascular.

    Directory of Open Access Journals (Sweden)

    Ricardo Verdecia Fraga

    2010-02-01

    Full Text Available Background: cerebrovascular disease and ischemic cardiopathy can be considered as an epidemic and constitute the first cause of incapacities in developed countries. Multiple studies have shown the association between uric acid levels and cerebrovascular diseases. Objective: To correlate the levels of serum uric acid and incapacities in the acute phase of cerebrovascular disease. Methods: A correlational study was carried out with 217 patients with acute cerebrovascular disease. The patient’s incapacity level was measured by using the Barthel Index and those results were related with the serum uric acid levels and other variables. Results: Male patients have higher levels of uric acid (p=0, 04; r=0, 13. Age and Barthel index were p < 0,001; r = -0, 30 and uric acid levels and Barthel Index were p=0, 03; r=-0, 14. The principal predicting factors of incapacity in the acute phase of cerebrovascular disease were the high levels of uric acid, age and diabetes mellitus. Conclusions: It is shown that the highest is the level of uric acid at advanced age; the greatest is the risk of suffering from incapacity in acute phases of cerebrovascular diseases.Fundamento: la enfermedad cerebrovascular y la cardiopatía isquémica pueden considerarse una epidemia, y constituyen además la primera causa de discapacidad en los países desarrollados. Numerosos estudios han demostrado la asociación de los niveles de ácido úrico con la enfermedad cerebrovascular. Objetivo: determinar la relación entre los niveles de ácido úrico sérico y la discapacidad en la fase aguda de la enfermedad cerebrovascular. Métodos: se realizó un estudio correlacional a 217 pacientes con enfermedad cerebrovascular en su fase aguda, en el que se midió el grado de discapacidad mediante el índice de Barthel y se relacionó dicho valor con los

  12. Pro-inflammatory and pro-oxidant status of pancreatic islet in vitro is controlled by TLR-4 and HO-1 pathways.

    Directory of Open Access Journals (Sweden)

    Kevin Vivot

    Full Text Available Since their isolation until implantation, pancreatic islets suffer a major stress leading to the activation of inflammatory reactions. The maintenance of controlled inflammation is essential to preserve survival and function of the graft. Identification and targeting of pathway(s implicated in post-transplant detrimental inflammatory events, is mandatory to improve islet transplantation success. We sought to characterize the expression of the pro-inflammatory and pro-oxidant mediators during islet culture with a focus on Heme oxygenase (HO-1 and Toll-like receptors-4 signaling pathways. Rat pancreatic islets were isolated and pro-inflammatory and pro-oxidant status were evaluated after 0, 12, 24 and 48 hours of culture through TLR-4, HO-1 and cyclooxygenase-2 (COX-2 expression, CCL-2 and IL-6 secretion, ROS (Reactive Oxygen Species production (Dihydroethidine staining, DHE and macrophages migration. To identify the therapeutic target, TLR4 inhibition (CLI-095 and HO-1 activation (cobalt protoporphyrin,CoPP was performed. Activation of NFκB signaling pathway was also investigated. After isolation and during culture, pancreatic islet exhibited a proinflammatory and prooxidant status (increase levels of TLR-4, COX-2, CCL-2, IL-6, and ROS. Activation of HO-1 or inhibition of TLR-4 decreased inflammatory status and oxidative stress of islets. Moreover, the overexpression of HO-1 induced NFκB phosphorylation while the inhibition of TLR-4 had no effect NFκB activation. Finally, inhibition of pro-inflammatory pathway induced a reduction of macrophages migration. These data demonstrated that the TLR-4 signaling pathway is implicated in early inflammatory events leading to a pro-inflammatory and pro-oxidant status of islets in vitro. Moreover, these results provide the mechanism whereby the benefits of HO-1 target in TLR-4 signaling pathway. HO-1 could be then an interesting target to protect islets before transplantation.

  13. Terapéuticas intervencionistas para el accidente cerebrovascular isquémico

    OpenAIRE

    Rabadán, Alejandra T.; Luciano Sposato; Claudio Mazia

    2010-01-01

    En los últimos 20 años se han desarrollado nuevas opciones para el tratamiento y para la prevención del accidente cerebrovascular (ACV) isquémico, muchas de ellas de carácter intervencionista, tales como la endarterectomía carotídea y la trombolisis intravenosa con activador tisular del plasminógeno. La evidencia científica ha llevado a su difusión y utilización en países desarrollados mientras que en naciones emergentes se observa un retraso en su adopción. Otras modalidades terapéuticas que...

  14. Cerebrovascular disease in South Asia – Part II: Risk factors and prevention

    Directory of Open Access Journals (Sweden)

    2012-11-01

    Full Text Available In South Asian countries, conventional vascular risk factors like hypertension, diabetes mellitus, cardiac disease, smoking, obesity, atrial fibrillation are the dominant ones, while other aetiologies like rheumatic heart disease, infective meningitis-related infarcts and postpartum cerebral venous thrombosis also constitute a big fraction. This review discusses the evidence of prevalence of various risk factors in South Asian countries and possible measures to combat the rising burden of cerebrovascular disease. The last part of the review discusses prevention and identification of risk factors that are unique to or especially found in patient population of South Asia.

  15. Utilidad de los biomarcadores en el diagnóstico de la enfermedad cerebrovascular silente

    OpenAIRE

    Vilar Bergua, Andrea

    2016-01-01

    Hoy en día, las enfermedades cerebrovasculares tienen un impacto muy importante en la sociedad en países desarrollados, en el nuestro, son una causa muy frecuente de hospitalización, muerte y discapacidad. Además, el envejecimiento de la población conlleva un incremento en la incidencia de estas enfermedades, así como del coste sanitario asociado. Desde hace años, sabemos que los infartos cerebrales pueden darse en ausencia de síntomas acompañantes sugestivos de ictus y en ese caso, hablamos ...

  16. Tratamiento de la heminegligencia tras un accidente cerebrovascular. Revisión sistemática.

    OpenAIRE

    Serrano Galiano, Sara

    2013-01-01

    La heminegligencia es una alteración cognitiva que se caracteriza por la falta de atención del individuo hacia el lado contralateral a la lesión cerebral y suele adquirirse como consecuencia de un trastorno cerebrovascular. Habitualmente va a ir aparejada con otras alteraciones derivadas del origen de la misma como problemas en el área motora. (1) Los síntomas de la heminegligencia se observan al menos en el 25-30% los pacientes con lesión cerebral derecha aguda (2) y aunque la mayor parte...

  17. Transferencia del aprendizaje motor en pacientes con antecedentes de accidente cerebrovascular: serie de casos

    OpenAIRE

    Karen Castro-Medina; Mayra Pérez-Páez; Fabiola Moscoso-Alvarado; Clarice Tanaka

    2015-01-01

    Antecedentes. La rehabilitación es un proceso de reaprendizaje motor, que mejora el desempeño en términos de adquisición de nuevas habilidades y adaptación o refinamiento de habilidades aprendidas previamente. A pesar de este conocimiento, existen, considerablemente, pocos estudios que describan el aprendizaje motor después de un accidente cerebrovascular (ACV) y la relevancia del mismo en los procesos de rehabilitación y recuperación. Objetivo. Describir la transferencia del aprendizaje moto...

  18. Muertes por enfermedades cardiacas y accidentes cerebrovasculares prevenibles - (Preventable Deaths from Heart Disease and Stroke)

    Centers for Disease Control (CDC) Podcasts

    2013-09-03

    Este podcast se basa en la edición de septiembre del 2013 del informe Signos Vitales de los CDC. Más de 800,000 personas en los Estados Unidos mueren cada año a causa de enfermedades cardiacas y accidentes cerebrovasculares. Aprenda cómo controlar todos los principales factores de riesgo.  Created: 9/3/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 9/3/2013.

  19. Subjective and objective knowledge and decisional role preferences in cerebrovascular patients compared to controls

    Directory of Open Access Journals (Sweden)

    Riechel C

    2016-08-01

    Full Text Available Christina Riechel,1,* Anna Christina Alegiani,1,* Sascha Köpke,2 Jürgen Kasper,3,4 Michael Rosenkranz,1,5 Götz Thomalla,1 Christoph Heesen1,4 1Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 2Nursing Research Unit, Institute of Social Medicine and Epidemiology, University of Lübeck, Lübeck, Germany; 3Department of Health and Caring Sciences, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway; 4Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 5Department of Neurology, Albertinen-Krankenhaus, Hamburg, Germany *These authors contributed equally to this work Background: Risk knowledge and active role preferences are important for patient involvement in treatment decision-making and adherence. Although knowledge about stroke warning signs and risk factors has received considerable attention, objective knowledge on secondary prevention and further self-esteem subjective knowledge have rarely been studied. The aim of our study was to investigate knowledge and treatment decisional role preferences in cerebrovascular patients compared to controls. Methods: We performed a survey on subjective and objective stroke risk knowledge and autonomy preferences in cerebrovascular patients from our stroke outpatient clinic (n=262 and from pedestrians on the street taken as controls during a “World Stroke Day” (n=274. The questionnaire includes measures for knowledge and decisional role preferences from previously published questionnaires and newly developed measures, for example, subjective knowledge, revealed on a visual analog scale. Results: The overall stroke knowledge was low to moderate, with no differences between patients and controls. Knowledge about secondary prevention was particularly low. Only 10%–15% of participants correctly estimated the stroke absolute risk reduction potential of aspirin. The medical data

  20. Congenital spine deformities: a new screening indication for blunt cerebrovascular injuries after cervical trauma?

    Science.gov (United States)

    Capone, Christine; Burjonrappa, Sathyaprasad

    2010-12-01

    Blunt cerebrovascular injuries (BCVI) carry significant morbidity if not diagnosed and treated early. A high index of clinical suspicion is needed to recognize the injury patterns associated with this condition and to order the requisite imaging studies needed to diagnose it accurately. We report of BCVI associated with a congenital cervical spine malformation after blunt trauma. We recommend inclusion of cervical spine malformations to the current Eastern Association for the Surgery of Trauma screening criteria for BCVI and explain our rationale for the same.

  1. Warfarin therapy and incidence of cerebrovascular complications in left-sided native valve endocarditis

    DEFF Research Database (Denmark)

    Snygg-Martin, U; Rasmussen, Rasmus Vedby; Hassager, C;

    2011-01-01

    Anticoagulant therapy has been anticipated to increase the risk of cerebrovascular complications (CVC) in native valve endocarditis (NVE). This study investigates the relationship between ongoing oral anticoagulant therapy and the incidence of symptomatic CVC in left-sided NVE. In a prospective...... factors for CVC, while warfarin on admission (aOR 0.26, 95% CI 0.07-0.94), history of congestive heart failure (adjusted OR 0.22, 95% CI 0.1-0.52) and previous endocarditis (aOR 0.1, 95% CI 0.01-0.79) correlated with lower CVC frequency....

  2. Transmembrane oligomeric form of Vibrio cholerae cytolysin triggers TLR2/TLR6-dependent proinflammatory responses in monocytes and macrophages.

    Science.gov (United States)

    Khilwani, Barkha; Mukhopadhaya, Arunika; Chattopadhyay, Kausik

    2015-02-15

    Vibrio cholerae cytolysin (VCC) kills target eukaryotic cells by forming transmembrane oligomeric β-barrel pores. Once irreversibly converted into the transmembrane oligomeric form, VCC acquires an unusual structural stability and loses its cytotoxic property. It is therefore possible that, on exertion of its cytotoxic activity, the oligomeric form of VCC retained in the disintegrated membrane fractions of the lysed cells would survive within the host cellular milieu for a long period, without causing any further cytotoxicity. Under such circumstances, VCC oligomers may potentially be recognized by the host immune cells. Based on such a hypothesis, in the present study we explored the interaction of the transmembrane oligomeric form of VCC with the monocytes and macrophages of the innate immune system. Our study shows that the VCC oligomers assembled in the liposome membranes elicit potent proinflammatory responses in monocytes and macrophages, via stimulation of the toll-like receptor (TLR)2/TLR6-dependent signalling cascades that involve myeloid differentiation factor 88 (MyD88)/interleukin-1-receptor-associated kinase (IRAK)1/tumour-necrosis-factor-receptor-associated factor (TRAF)6. VCC oligomer-mediated proinflammatory responses critically depend on the activation of the transcription factor nuclear factor-κB. Proinflammatory responses induced by the VCC oligomers also require activation of the mitogen-activated protein kinase (MAPK) family member c-Jun N-terminal kinase, which presumably acts via stimulation of the transcription factor activator protein-1. Notably, the role of the MAPK p38 could not be documented in the process.

  3. Maintenance of a positive outlook during acute stress protects against pro-inflammatory reactivity and future depressive symptoms

    Science.gov (United States)

    Aschbacher, K.; Epel, E.; Wolkowitz, O.M.; Prather, A.A.; Puterman, E.; Dhabhar, F.S.

    2014-01-01

    Cognitive and affective responses to acute stress influence pro-inflammatory cytokine reactivity, and peripheral cytokines (particularly lnterleukin-1 beta (IL-1β)), can act on the brain to promote depressive symptoms. It is unknown whether acute stress-induced changes in positive affect and cognitions (POS) and pro-inflammatory reactivity predict future depressive symptoms. We examined acute stress responses among women, to determine prospective predictors of depressive symptoms. Hypotheses: 1) Stress-induced decreases in POS will be associated with stress-related increases in circulating IL-1β. 2) Acute stress-induced decreases in POS and increases in IL-1β reactivity will predict increases in depressive symptoms one year later. Thirty-five post-menopausal women were exposed to acute stress with the Trier Social Stress Task (TSST) and provided blood samples under resting conditions and 30 minutes after the conclusion of the TSST, which were assayed for IL-1β. IL-1β reactivity was quantified as post minus pre-TSST. Failure to maintain POS was quantified as the decrease in POS during the TSST. Change in depressive symptoms from the study baseline to the following year was determined. Greater acute stress-induced declines in POS were significantly associated with increased IL-1β reactivity (p≤.02), which significantly predicted increases in depressive symptoms over the following year (p<.01), controlling for age, body mass index, chronic stress, antidepressant use and baseline depressive symptoms. IL-1β reactivity was a significant mediator of the relationship between POS decline and future increases in depressive symptoms (p=.04). Difficulty maintaining positivity under stress and heightened pro-inflammatory reactivity may be markers and/or mechanisms of risk for future increases in depressive symptoms. PMID:22119400

  4. Pro-inflammatory human Th17 cells selectively express P-glycoprotein and are refractory to glucocorticoids.

    Science.gov (United States)

    Ramesh, Radha; Kozhaya, Lina; McKevitt, Kelly; Djuretic, Ivana M; Carlson, Thaddeus J; Quintero, Maria A; McCauley, Jacob L; Abreu, Maria T; Unutmaz, Derya; Sundrud, Mark S

    2014-01-13

    IL-17A-expressing CD4(+) T cells (Th17 cells) are generally regarded as key effectors of autoimmune inflammation. However, not all Th17 cells are pro-inflammatory. Pathogenic Th17 cells that induce autoimmunity in mice are distinguished from nonpathogenic Th17 cells by a unique transcriptional signature, including high Il23r expression, and these cells require Il23r for their inflammatory function. In contrast, defining features of human pro-inflammatory Th17 cells are unknown. We show that pro-inflammatory human Th17 cells are restricted to a subset of CCR6(+)CXCR3(hi)CCR4(lo)CCR10(-)CD161(+) cells that transiently express c-Kit and stably express P-glycoprotein (P-gp)/multi-drug resistance type 1 (MDR1). In contrast to MDR1(-) Th1 or Th17 cells, MDR1(+) Th17 cells produce both Th17 (IL-17A, IL-17F, and IL-22) and Th1 (IFN-γ) cytokines upon TCR stimulation and do not express IL-10 or other anti-inflammatory molecules. These cells also display a transcriptional signature akin to pathogenic mouse Th17 cells and show heightened functional responses to IL-23 stimulation. In vivo, MDR1(+) Th17 cells are enriched and activated in the gut of Crohn's disease patients. Furthermore, MDR1(+) Th17 cells are refractory to several glucocorticoids used to treat clinical autoimmune disease. Thus, MDR1(+) Th17 cells may be important mediators of chronic inflammation, particularly in clinical settings of steroid resistant inflammatory disease.

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

    Science.gov (United States)

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

    2016-02-01

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

  6. Transitional changes in the CRP structure lead to the exposure of proinflammatory binding sites

    Science.gov (United States)

    Braig, David; Nero, Tracy L.; Koch, Hans-Georg; Kaiser, Benedict; Wang, Xiaowei; Thiele, Jan R.; Morton, Craig J.; Zeller, Johannes; Kiefer, Jurij; Potempa, Lawrence A.; Mellett, Natalie A.; Miles, Luke A.; Du, Xiao-Jun; Meikle, Peter J.; Huber-Lang, Markus; Stark, G. Björn; Parker, Michael W.; Peter, Karlheinz; Eisenhardt, Steffen U.

    2017-01-01

    C-reactive protein (CRP) concentrations rise in response to tissue injury or infection. Circulating pentameric CRP (pCRP) localizes to damaged tissue where it leads to complement activation and further tissue damage. In-depth knowledge of the pCRP activation mechanism is essential to develop therapeutic strategies to minimize tissue injury. Here we demonstrate that pCRP by binding to cell-derived microvesicles undergoes a structural change without disrupting the pentameric symmetry (pCRP*). pCRP* constitutes the major CRP species in human-inflamed tissue and allows binding of complement factor 1q (C1q) and activation of the classical complement pathway. pCRP*–microvesicle complexes lead to enhanced recruitment of leukocytes to inflamed tissue. A small-molecule inhibitor of pCRP (1,6-bis(phosphocholine)-hexane), which blocks the pCRP–microvesicle interactions, abrogates these proinflammatory effects. Reducing inflammation-mediated tissue injury by therapeutic inhibition might improve the outcome of myocardial infarction, stroke and other inflammatory conditions. PMID:28112148

  7. Impaired macrophage autophagy increases the immune response in obese mice by promoting proinflammatory macrophage polarization.

    Science.gov (United States)

    Liu, Kun; Zhao, Enpeng; Ilyas, Ghulam; Lalazar, Gadi; Lin, Yu; Haseeb, Muhammad; Tanaka, Kathryn E; Czaja, Mark J

    2015-01-01

    Recent evidence that excessive lipid accumulation can decrease cellular levels of autophagy and that autophagy regulates immune responsiveness suggested that impaired macrophage autophagy may promote the increased innate immune activation that underlies obesity. Primary bone marrow-derived macrophages (BMDM) and peritoneal macrophages from high-fat diet (HFD)-fed mice had decreased levels of autophagic flux indicating a generalized impairment of macrophage autophagy in obese mice. To assess the effects of decreased macrophage autophagy on inflammation, mice with a Lyz2-Cre-mediated knockout of Atg5 in macrophages were fed a HFD and treated with low-dose lipopolysaccharide (LPS). Knockout mice developed systemic and hepatic inflammation with HFD feeding and LPS. This effect was liver specific as knockout mice did not have increased adipose tissue inflammation. The mechanism by which the loss of autophagy promoted inflammation was through the regulation of macrophage polarization. BMDM and Kupffer cells from knockout mice exhibited abnormalities in polarization with both increased proinflammatory M1 and decreased anti-inflammatory M2 polarization as determined by measures of genes and proteins. The heightened hepatic inflammatory response in HFD-fed, LPS-treated knockout mice led to liver injury without affecting steatosis. These findings demonstrate that autophagy has a critical regulatory function in macrophage polarization that downregulates inflammation. Defects in macrophage autophagy may underlie inflammatory disease states such as the decrease in macrophage autophagy with obesity that leads to hepatic inflammation and the progression to liver injury.

  8. Comparison of pro-inflammatory cytokines of non-healing and healing cutaneous leishmaniasis.

    Science.gov (United States)

    Moafi, M; Rezvan, H; Sherkat, R; Taleban, R; Asilian, A; Hamid Zarkesh-Esfahani, S; Nilforoushzadeh, M A; Jaffary, F; Mansourian, M; Sokhanvari, F; Ansari, N

    2017-04-01

    Cutaneous leishmaniasis (CL) heals spontaneously within several weeks or months, but, in rare cases, CL-active lesions last for many years. In this study, we assessed cell-mediated immunity in non-healing CL through the measurement of three pro-inflammatory cytokines: Interferon-γ (IFN-γ), IL-17a and CXCL-11. For this, 32 patients afflicted with healing or non-healing CL were recruited in this study. Peripheral blood mononuclear cells (PBMCs) of every patient were treated with three antigens: purified protein derivative (PPD), soluble Leishmania antigen (SLA) and phytohaemagglutinin (PHA). Cytokine quantification was performed using enzyme-linked immunosorbent assay (ELISA) method. Results of our study showed that neither cytokine produced in the presence of a PPD stimulator (as an irrelevant antigen) significantly differed between the healing and non-healing groups (P-value ≥0.05 for all of them). However, IFN-γ, CXCL-11 and IL-17a levels produced in the presence of PHA or SLA were significantly higher within the healing than in the non-healing group (P-value <0.01 for all of them). It seems that appropriate levels of IFN-γ, as well as IL-17a and CXCL-11, contribute to the control of Leishmania infection.

  9. Euglena gracilis paramylon activates human lymphocytes by upregulating pro-inflammatory factors.

    Science.gov (United States)

    Russo, Rossella; Barsanti, Laura; Evangelista, Valter; Frassanito, Anna M; Longo, Vincenzo; Pucci, Laura; Penno, Giuseppe; Gualtieri, Paolo

    2017-03-01

    The aim of this study was to verify the activation details and products of human lymphomonocytes, stimulated by different β-glucans, that is Euglena paramylon, MacroGard(®), and lipopolysaccharide. We investigated the gene expression of inflammation-related cytokines and mediators, transactivation of relevant transcription factors, and phagocytosis role in cell-glucan interactions, by means of RT-PCR, immunocytochemistry, and colorimetric assay. Our results show that sonicated and alkalized paramylon upregulates pro-inflammatory factors (NO, TNF-α, IL-6, and COX-2) in lymphomonocytes. A clear demonstration of this upregulation is the increased transactivation of NF-kB visualized by immunofluorescence microscopy. Phagocytosis assay showed that internalization is not a mandatory step for signaling cascade to be triggered, since immune activity is not present in the lymphomonocytes that have internalized paramylon granules and particulate MacroGard(®). Moreover, the response of Euglena β-glucan-activated lymphomonocytes is much greater than that induced by commercially used β-glucans such as MacroGard(®). Our in vitro results indicate that linear fibrous Euglena β-glucan, obtained by sonication and alkaline treatment can act as safe and effective coadjutant of the innate immune system response.

  10. Mycobacterium tuberculosis Prolyl Oligopeptidase Induces In vitro Secretion of Proinflammatory Cytokines by Peritoneal Macrophages

    Science.gov (United States)

    Portugal, Brina; Motta, Flávia N.; Correa, Andre F.; Nolasco, Diego O.; de Almeida, Hugo; Magalhães, Kelly G.; Atta, Ana L. V.; Vieira, Francisco D.; Bastos, Izabela M. D.; Santana, Jaime M.

    2017-01-01

    Tuberculosis (TB) is a disease that leads to death over 1 million people per year worldwide and the biological mediators of this pathology are poorly established, preventing the implementation of effective therapies to improve outcomes in TB. Host–bacterium interaction is a key step to TB establishment and the proteases produced by these microorganisms seem to facilitate bacteria invasion, migration and host immune response evasion. We presented, for the first time, the identification, biochemical characterization, molecular dynamics (MDs) and immunomodulatory properties of a prolyl oligopeptidase (POP) from Mycobacterium tuberculosis (POPMt). POP is a serine protease that hydrolyzes substrates with high specificity for proline residues and has already been characterized as virulence factor in infectious diseases. POPMt reveals catalytic activity upon N-Suc-Gly-Pro-Leu-Gly-Pro-AMC, a recognized POP substrate, with optimal activity at pH 7.5 and 37°C. The enzyme presents KM and Kcat/KM values of 108 μM and 21.838 mM-1 s-1, respectively. MDs showed that POPMt structure is similar to that of others POPs, which consists of a cylindrical architecture divided into an α/β hydrolase catalytic domain and a β-propeller domain. Finally, POPMt was capable of triggering in vitro secretion of proinflammatory cytokines by peritoneal macrophages, an event dependent on POPMt intact structure. Our data suggests that POPMt may contribute to an inflammatory response during M. tuberculosis infection. PMID:28223969

  11. Fucoidan delays apoptosis and induces pro-inflammatory cytokine production in human neutrophils.

    Science.gov (United States)

    Jin, Jun-O; Yu, Qing

    2015-02-01

    Although some immune modulatory effects of fucoidan have been elucidated, the effects of fucoidan on the apoptosis and activation of human neutrophils have not been investigated. In this study, we demonstrated that fucoidan purified from the brown seaweed Undaria pinnatifilda delays spontaneous apoptosis of human neutrophils and induces their activation. Fucoidan treatment inhibited apoptotic nuclei changes and phosphatidyl serine (PS) exposure on neutrophils cultured in vitro for 24h. The delay in neutrophil apoptosis mediated by fucoidan was associated with increased levels of the anti-apoptotic protein Mcl-1 and decreased levels of activated caspase-3. Screening of the signaling pathways by specific inhibitors indicated that fucoidan-induced delay in neutrophil apoptosis was dependent on the activation of PI3K/AKT signaling pathway, whereas MAPK signaling pathway was not critical. In addition, fucoidan enhanced the production of IL-6, IL-8 and TNF-α from neutrophils in an AKT-dependent manner. Taken together, these results demonstrated that fucoidan delays human neutrophil apoptosis and induces their production of pro-inflammatory cytokines. This knowledge could facilitate the development of novel therapeutic strategies for infectious diseases and neutropenia by controlling neutrophil homeostasis and function with fucoidan.

  12. Differential regulation of trophic and proinflammatory microglial effectors is dependent on severity of neuronal injury.

    Science.gov (United States)

    Lai, Aaron Y; Todd, Kathryn G

    2008-02-01

    Microglial activation has been reported to promote neurotoxicity and also neuroprotective effects. A possible contributor to this dichotomy of responses may be the degree to which proximal neurons are injured. The aim of this study was to determine whether varying the severity of neuronal injury influenced whether microglia were neuroprotective or neurotoxic. We exposed cortical neuronal cultures to varying degrees of hypoxia thereby generating mild (70% death, 6 h hypoxia) injuries. Twenty-four hours after hypoxia, the media from the neuronal cultures was collected and incubated with primary microglial cultures for 24 h. Results showed that the classic microglial proinflammatory mediators including inducible nitric oxide synthase, tumor necrosis factor alpha, and interleukin-1-beta were upregulated only in response to mild neuronal injuries, while the trophic microglial effectors brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor were upregulated in response to all degrees of neuronal injury. Microglia stimulated with media from damaged neurons were co-cultured with hypoxic neurons. Microglia stimulated by moderate, but not mild or severe damage were neuroprotective in these co-cultures. We also showed that the severity-dependent phenomenon was not related to autocrine microglial signaling and was dependent on the neurotransmitters released by neurons after injury, namely glutamate and adenosine 5'-triphosphate. Together our results show that severity of neuronal injury is an important factor in determining microglial release of "toxic" versus "protective" effectors and the resulting neurotoxicity versus neuroprotection.

  13. Nutritionally Mediated Oxidative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Alexandra Muñoz

    2013-01-01

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

  14. Infection with Theiler's murine encephalomyelitis virus directly induces proinflammatory cytokines in primary astrocytes via NF-kappaB activation: potential role for the initiation of demyelinating disease.

    Science.gov (United States)

    Palma, JoAnn P; Kwon, Daeho; Clipstone, Neil A; Kim, Byung S

    2003-06-01

    Theiler's virus infection in the central nervous system (CNS) induces a demyelinating disease very similar to human multiple sclerosis. We have assessed cytokine gene activation upon Theiler's murine encephalomyelitis virus (TMEV) infection and potential mechanisms in order to delineate the early events in viral infection that lead to immune-mediated demyelinating disease. Infection of SJL/J primary astrocyte cultures induces selective proinflammatory cytokine genes (interleukin-12p40 [IL-12p40], IL-1, IL-6, tumor necrosis factor alpha, and beta interferon [IFN-beta]) important in the innate immune response to infection. We find that TMEV-induced cytokine gene expression is mediated by the NF-kappaB pathway based on the early nuclear NF-kappaB translocation and suppression of cytokine activation in the presence of specific inhibitors of the NF-kappaB pathway. Further studies show this to be partly independent of dsRNA-dependent protein kinase (PKR) and IFN-alpha/beta pathways. Altogether, these results demonstrate that infection of astrocytes and other CNS-resident cells by TMEV provides the early NF-kappaB-mediated signals that directly activate various proinflammatory cytokine genes involved in the initiation and amplification of inflammatory responses in the CNS known to be critical for the development of immune-mediated demyelination.

  15. Transmembrane TNF-α Reverse Signaling Inhibits Lipopolysaccharide-Induced Proinflammatory Cytokine Formation in Macrophages by Inducing TGF-β: Therapeutic Implications.

    Science.gov (United States)

    Pallai, Anna; Kiss, Beáta; Vereb, György; Armaka, Marietta; Kollias, George; Szekanecz, Zoltán; Szondy, Zsuzsa

    2016-02-01

    TNF-α, a potent proinflammatory cytokine, is generated in a precursor form called transmembrane (m)TNF-α that is expressed as a type II polypeptide on the surface of certain cells. mTNF-α was shown to act both as a ligand by binding to TNF-α receptors, as well as a receptor that transmits outside-to-inside (reverse) signals back into the mTNF-α-bearing cells. In this study, we show that nonactivated macrophages express basal levels of mTNF-α and respond to anti-TNF-α Abs by triggering the MAPK kinase 4 signaling pathway. The pathway induces TGF-β. Based on inhibitory experiments, the production of TGF-β1 is regulated via Jun kinases, whereas that of other TGF-βs is regulated via p38 MAPKs. Exposure to LPS further induced the expression of mTNF-α, and triggering of mTNF-α strongly suppressed the LPS-induced proinflammatory response. Neutralizing TGF-β by Abs prevented the mTNF-α-mediated suppression of LPS-induced proinflammatory cytokine formation, indicating that the immune-suppressive effect of mTNF-α is mediated via TGF-β. Although apoptotic cells are also known to suppress LPS-induced proinflammatory cytokine formation in macrophages by upregulating TGF-β, we show that they do not use the mTNF-α signaling pathway. Because TGF-β possesses a wide range of immune-suppressive effects, our data indicate that upregulation of TGF-β synthesis by those TNF-α-targeting molecules, which are able to trigger mTNF-α, might contribute to their therapeutic effect in the treatment of certain inflammatory diseases such as Crohn's disease, Wegener's granulomatosis, or sarcoidosis. Additionally, none of the TNF-α-targeting molecules is expected to interfere with the immune-silencing effects of apoptotic cells.

  16. Apoptosis and pro-inflammatory cytokine response of mast cells induced by influenza A viruses.

    Directory of Open Access Journals (Sweden)

    Bo Liu

    Full Text Available The pathogenesis of the influenza A virus has been investigated heavily, and both the inflammatory response and apoptosis have been found to have a definitive role in this process. The results of studies performed by the present and other groups have indicated that mast cells may play a role in the severity of the disease. To further investigate cellular responses to influenza A virus infection, apoptosis and inflammatory response were studied in mouse mastocytoma cell line P815. This is the first study to demonstrate that H1N1 (A/WSN/33, H5N1 (A/Chicken/Henan/1/04, and H7N2 (A/Chicken/Hebei/2/02 influenza viruses can induce mast cell apoptosis. They were found to do this mainly through the mitochondria/cytochrome c-mediated intrinsic pathway, and the activation of caspase 8-mediated extrinsic pathway was here found to be weak. Two pro-apoptotic Bcl-2 homology domain 3 (BH3 -only molecules Bim and Puma appeared to be involved in the apoptotic pathways. When virus-induced apoptosis was inhibited in P815 cells using pan-caspase (Z-VAD-fmk and caspase-9 (Z-LEHD-fmk inhibitors, the replication of these three subtypes of viruses was suppressed and the secretions of pro-inflammatory cytokines and chemokines, including IL-6, IL-18, TNF-α, and MCP-1, decreased. The results of this study may further understanding of the role of mast cells in host defense and pathogenesis of influenza virus. They may also facilitate the development of novel therapeutic aids against influenza virus infection.

  17. Regulation of Viral Replication, Apoptosis and Pro-Inflammatory Responses by 17-AAG during Chikungunya Virus Infection in Macrophages

    Directory of Open Access Journals (Sweden)

    Tapas K. Nayak

    2017-01-01

    Full Text Available Chikungunya virus (CHIKV infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively. Moreover, host immune modulation and apoptosis were studied through flow cytometry, Western blot and ELISA. Our current findings suggest that expression of CHIKV proteins were maximum at 8 hpi and the release of new viral progenies were remarkably increased around 12 hpi. The induction of Annexin V binding, cleaved caspase-3, cleaved caspase-9 and cleaved caspase-8 in CHIKV infected macrophages suggests activation of apoptosis through both intrinsic and extrinsic pathways. The pro-inflammatory mediators (TNF and IL-6 MHC-I/II and B7.2 (CD86 were also up-regulated during infection over time. Further, 17-AAG, a potential HSP90 inhibitor, was found to regulate CHIKV infection, apoptosis and pro-inflammatory cytokine/chemokine productions of host macrophages significantly. Hence, the present findings might bring new insight into the therapeutic implication in CHIKV disease biology.

  18. Regulation of Viral Replication, Apoptosis and Pro-Inflammatory Responses by 17-AAG during Chikungunya Virus Infection in Macrophages

    Science.gov (United States)

    Nayak, Tapas K.; Mamidi, Prabhudutta; Kumar, Abhishek; Singh, Laishram Pradeep K.; Sahoo, Subhransu S.; Chattopadhyay, Soma; Chattopadhyay, Subhasis

    2017-01-01

    Chikungunya virus (CHIKV) infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively. Moreover, host immune modulation and apoptosis were studied through flow cytometry, Western blot and ELISA. Our current findings suggest that expression of CHIKV proteins were maximum at 8 hpi and the release of new viral progenies were remarkably increased around 12 hpi. The induction of Annexin V binding, cleaved caspase-3, cleaved caspase-9 and cleaved caspase-8 in CHIKV infected macrophages suggests activation of apoptosis through both intrinsic and extrinsic pathways. The pro-inflammatory mediators (TNF and IL-6) MHC-I/II and B7.2 (CD86) were also up-regulated during infection over time. Further, 17-AAG, a potential HSP90 inhibitor, was found to regulate CHIKV infection, apoptosis and pro-inflammatory cytokine/chemokine productions of host macrophages significantly. Hence, the present findings might bring new insight into the therapeutic implication in CHIKV disease biology. PMID:28067803

  19. Pro-inflammatory role of Anti-Ro/SSA autoantibodies through the activation of Furin-TACE-amphiregulin axis.

    Science.gov (United States)

    Lisi, Sabrina; Sisto, Margherita; Lofrumento, Dario Domenico; Cucci, Liana; Frassanito, Maria Antonia; Mitolo, Vincenzo; D'Amore, Massimo

    2010-09-01

    Prolonged inflammation can be detrimental because it may cause host toxicity and tissue damage. Indeed, excessive production of inflammatory cytokines is often associated with many autoimmune diseases. In this study we demonstrate that the anti-Ro/SSA autoantibodies (Abs) stimulate the production of pro-inflammatory cytokines IL-6 and IL-8 by human healthy salivary gland epithelial cells (healthy SGEC). The secretion of these cytokines is due to amphiregulin (AREG) that is overexpressed in healthy SGEC treated with anti-Ro/SSA Abs and in Sjögren's syndrome. We have discovered that the up-regulation of AREG occurs through TNF-alpha produced following anti-Ro/SSA Abs treatment. The gene silencing technique was used to study the AREG-TNF-alpha-IL-6/IL-8 secretion pathway, demonstrating that: (i) TNF-alpha gene silencing provokes a significant decrease of proinflammatory cytokines production and AREG expression in anti-Ro/SSA Abs-treated healthy SGEC; (ii) AREG gene silencing has a potent inhibitory effect on TNF-alpha-induced IL-6 and IL-8 secretion in healthy SGEC treated with anti-Ro/SSA Abs. These findings indicate that TACE-mediated AREG shedding plays a critical role in TNF-alpha-induced IL-6 and IL-8 secretion by the human healthy salivary gland epithelial cells, suggesting that this may be one of the possible intracellular mechanisms involved in the salivary glands inflammatory response in Sjögren's syndrome.

  20. Statins decrease expression of the proinflammatory neuropeptides calcitonin gene-related peptide and substance P in sensory neurons.

    Science.gov (United States)

    Bucelli, Robert C; Gonsiorek, Eugene A; Kim, Woo-Yang; Bruun, Donald; Rabin, Richard A; Higgins, Dennis; Lein, Pamela J

    2008-03-01

    Clinical and experimental observations suggest that statins may be useful for treating diseases presenting with predominant neurogenic inflammation, but the mechanism(s) mediating this potential therapeutic effect are poorly understood. In this study, we tested the hypothesis that statins act directly on sensory neurons to decrease expression of proinflammatory neuropeptides that trigger neurogenic inflammation, specifically calcitonin gene-related peptide (CGRP) and substance P. Reverse transcriptase-polymerase chain reaction, radioimmunoassay, and immunocytochemistry were used to quantify CGRP and substance P expression in dorsal root ganglia (DRG) harvested from adult male rats and in primary cultures of sensory neurons derived from embryonic rat DRG. Systemic administration of statins at pharmacologically relevant doses significantly reduced CGRP and substance P levels in DRG in vivo. In cultured sensory neurons, statins blocked bone morphogenetic protein (BMP)-induced CGRP and substance P expression and decreased expression of these neuropeptides in sensory neurons pretreated with BMPs. These effects were concentration-dependent and occurred independent of effects on cell survival or axon growth. Statin inhibition of neuropeptide expression was reversed by supplementation with mevalonate and cholesterol, but not isoprenoid precursors. BMPs signal via Smad activation, and cholesterol depletion by statins inhibited Smad1 phosphorylation and nuclear translocation. These findings identify a novel action of statins involving down-regulation of proinflammatory neuropeptide expression in sensory ganglia via cholesterol depletion and decreased Smad1 activation and suggest that statins may be effective in attenuating neurogenic inflammation.

  1. Adipocytes from New Zealand Obese Mice Exhibit Aberrant Proinflammatory Reactivity to the Stress Signal Heat Shock Protein 60

    Directory of Open Access Journals (Sweden)

    Tina Märker

    2014-01-01

    Full Text Available Adipocytes release immune mediators that contribute to diabetes-associated inflammatory processes. As the stress protein heat shock protein 60 (Hsp60 induces proinflammatory adipocyte activities, we hypothesized that adipocytes of diabetes-predisposed mice exhibit an increased proinflammatory reactivity to Hsp60. Preadipocytes and mature adipocytes from nonobese diabetic (NOD, New Zealand obese (NZO, and C57BL/6J mice were analyzed for Hsp60 binding, Hsp60-activated signaling pathways, and Hsp60-induced release of the chemokine CXCL-1 (KC, interleukin 6 (IL-6, and macrophage chemoattractant protein-1 (MCP-1. Hsp60 showed specific binding to (pre-adipocytes of NOD, NZO, and C57BL/6J mice. Hsp60 binding involved conserved binding structure(s and Hsp60 epitopes and was strongest to NZO mouse-derived mature adipocytes. Hsp60 exposure induced KC, IL-6, and MCP-1 release from (pre-adipocytes of all mouse strains with a pronounced increase of IL-6 release from NZO mouse-derived adipocytes. Compared to NOD and C57BL/6J mouse derived cells, Hsp60-induced formation of IL-6, KC, and MCP-1 from NZO mouse-derived (pre-adipocytes strongly depended on NFκB-activation. Increased Hsp60 binding and Hsp60-induced IL-6 release by mature adipocytes of NZO mice suggest that enhanced adipocyte reactivity to the stress signal Hsp60 contributes to inflammatory processes underlying diabetes associated with obesity and insulin resistance.

  2. Fibroblast growth factor signalling in multiple sclerosis: inhibition of myelination and induction of pro-inflammatory environment by FGF9.

    Science.gov (United States)

    Lindner, Maren; Thümmler, Katja; Arthur, Ariel; Brunner, Sarah; Elliott, Christina; McElroy, Daniel; Mohan, Hema; Williams, Anna; Edgar, Julia M; Schuh, Cornelia; Stadelmann, Christine; Barnett, Susan C; Lassmann, Hans; Mücklisch, Steve; Mudaliar, Manikhandan; Schaeren-Wiemers, Nicole; Meinl, Edgar; Linington, Christopher

    2015-07-01

    Remyelination failure plays an important role in the pathophysiology of multiple sclerosis, but the underlying cellular and molecular mechanisms remain poorly understood. We now report actively demyelinating lesions in patients with multiple sclerosis are associated with increased glial expression of fibroblast growth factor 9 (FGF9), which we demonstrate inhibits myelination and remyelination in vitro. This inhibitory activity is associated with the appearance of multi-branched 'pre-myelinating' MBP+ / PLP+ oligodendrocytes that interact with axons but fail to assemble myelin sheaths; an oligodendrocyte phenotype described previously in chronically demyelinated multiple sclerosis lesions. This inhibitory activity is not due to a direct effect of FGF9 on cells of the oligodendrocyte lineage but is mediated by factors secreted by astrocytes. Transcriptional profiling and functional validation studies demonstrate that these include effects dependent on increased expression of tissue inhibitor of metalloproteinase-sensitive proteases, enzymes more commonly associated with extracellular matrix remodelling. Further, we found that FGF9 induces expression of Ccl2 and Ccl7, two pro-inflammatory chemokines that contribute to recruitment of microglia and macrophages into multiple sclerosis lesions. These data indicate glial expression of FGF9 can initiate a complex astrocyte-dependent response that contributes to two distinct pathogenic pathways involved in the development of multiple sclerosis lesions. Namely, induction of a pro-inflammatory environment and failure of remyelination; a combination of effects predicted to exacerbate axonal injury and loss in patients.

  3. Long-term effects of pioglitazone on first attack of ischemic cerebrovascular disease in older people with type 2 diabetes: A case-control study in Taiwan.

    Science.gov (United States)

    Lai, Shih-Wei; Lin, Hsien-Feng; Lin, Cheng-Li; Liao, Kuan-Fu

    2016-08-01

    Long-term studies demonstrating the effect of pioglitazone use on primary prevention of ischemic cerebrovascular disease in older people with type 2 diabetes mellitus are lacking. This study investigated the relationship between pioglitazone use and first attack of ischemic cerebrovascular disease in Taiwan.We conducted a case-control study using the database of the Taiwan National Health Insurance Program. There were 2359 type 2 diabetic subjects aged ≥65 years with newly diagnosed ischemic cerebrovascular disease from 2005 to 2011 as the case group and 4592 sex- and age-matched, randomly selected type 2 diabetic subjects aged ≥65 years without ischemic cerebrovascular disease as the control group. The odds ratio (OR) with 95% confidence interval (CI) of ischemic cerebrovascular disease associated with pioglitazone use was measured by the multivariable unconditional logistic regression model.After adjustment for confounding factors, the multivariable logistic regression analysis disclosed that the adjusted ORs of first attack of ischemic cerebrovascular disease associated with cumulative duration of using pioglitazone were 3.34 for pioglitazone use does not have a protective effect on primary prevention for ischemic cerebrovascular disease among older people with type 2 diabetes mellitus during the first 3 years of use. Whether using pioglitazone for >3 years would have primary prevention for ischemic cerebrovascular disease needs a long-term research to prove.

  4. Prevention of Stroke in Patients With Silent Cerebrovascular Disease : A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

    NARCIS (Netherlands)

    Smith, Eric E; Saposnik, Gustavo; Biessels, Geert Jan; Doubal, Fergus N; Fornage, Myriam; Gorelick, Philip B; Greenberg, Steven M; Higashida, Randall T; Kasner, Scott E; Seshadri, Sudha

    2017-01-01

    Two decades of epidemiological research shows that silent cerebrovascular disease is common and is associated with future risk for stroke and dementia. It is the most common incidental finding on brain scans. To summarize evidence on the diagnosis and management of silent cerebrovascular disease to

  5. Prescripción facilitada de drogas antihipertensivas y disminución de la muerte prematura por accidente cerebrovascular

    OpenAIRE

    Javier Mariani; Marina Ridao; Gabriel González; Mauricio Monsalvo; Alejandro Macchia

    2016-01-01

    Introducción: Desde 2003, el programa Remediar (+Redes) distribuye gratuitamente medicación antihipertensiva. Durante este período, la mortalidad por accidente cerebrovascular disminuyó, aunque con inequidades entre grupos socioeconómicos. Objetivos: Evaluar la asociación entre la mortalidad por accidente cerebrovascular y la provisión de fármacos antihipertensivos. Estudiar la posible interacción entre los efectos de los antihipertensivos sobre la mortalidad y el nivel socioeconómico. ...

  6. [Variants of the clinical course of cerebrovascular diseases in various biogeochemical regions of the Ukrainian Carpathian Mountains].

    Science.gov (United States)

    Buletsa, B A; Fatula, M I; Fabri, Z I

    1990-01-01

    A total of 417 patients with cerebral circulatory disorders were examined in two biogeochemical regions of the UkrainianCarpathian Mountains. The first one is a region with iodine insufficiency; the second one is a region where the people use table salt in excess. It has been established that iodine insufficiency and excessive iodine concentration in the body of man are risk factors of the development of cerebrovascular disease. Besides, in persons with abnormal iodine metabolism, cerebrovascular diseases run a graver course than in those with normal content in the body of these trace elements.

  7. Función pulmonar en sujetos con hemiparesia crónica secundaria a un accidente cerebrovascular

    OpenAIRE

    Guerrero Gómez, Alba

    2016-01-01

    Antecedentes: las Enfermedades Cerebrovasculares se sitúan como la primera causa de muerte entre las mujeres y la tercera en hombres a nivel nacional. Son numerosas las secuelas que pueden sufrir los supervivientes, entre las que se encuentran las alteraciones del control motor y del tono muscular. Estas son las que hacen plantearse el grado de afectación de la musculatura implicada en la ventilación tras un Accidente Cerebrovascular, ya sea de manera directa o mediante la alteración de las c...

  8. Muerte prematura por accidente cerebrovascular y condición socioeconómica en la Argentina

    OpenAIRE

    Mauricio Monsalvo; Anabel Fernández Prieto; Alejandro Macchia

    2016-01-01

    Introducción: La asociación entre mortalidad por accidente cerebrovascular y el nivel socioeconómico está escasamente descripta en Argentina. Objetivos: Describir la evolución temporal de la mortalidad por accidente cerebrovascular y su asociación con el nivel socioeconómico en Argentina entre 2000 y 2011. Material y métodos: Se realizó un estudio ecológico longitudinal. La mortalidad se cuantificó mediante tasas estandarizadas por edad y sexo, y el nivel socioeconómico mediante quint...

  9. [Research on distribution of patents' holders for Chinese herbal compounds in treating cardiovascular and cerebrovascular based on cluster analysis].

    Science.gov (United States)

    YANG, Xu-Jie; XIAO, Shi-Ying

    2015-09-01

    To discuss the distribution of patents' holders for Chinese herbal compounds in treating cardiovascular and cerebrovascular, the patents' holders for Chinese herbal compounds in treating cardiovascular and cerebrovascular were cluster analyzed by means of simple statistics and cluster analysis. Clustering variables were composed of patent applications, patent maintained number, related papers' quantity, etc. Chinese herbal compound patents' holders were divided into four categories according to their different scientific research and patent strength. It is the magic weapon for Chinese herbal compound patents' holders that have scientific research patents' transforming and make coordination of patent protection and scientific innovation.

  10. Estudio clínico del proceso conductual de la emergencia del coma grave por accidente cerebrovascular

    OpenAIRE

    2007-01-01

    Objetivos: Estudiar el proceso de la emergencia del coma en pacientes en coma grave por accidente cerebrovascular (ACV). Método: Se han evaluado a 32 pacientes ingresados en una unidad de cuidados intensivos por un coma de origen cerebrovascular. Se ha realizado un seguimiento diario por neuropsicólogos e intensivistas y monitorizado el despertar del coma mediante 8 escalas de evalua ... ción clínica de los niveles de coma. Se han analizado las variables: edad, género, residencia, índice prem...

  11. SPECT with N-isopropyl-p iodoamphetamine in occlusive cerebrovascular diseases.

    Science.gov (United States)

    Higa, T; Tanaka, T; Ikekubo, K; Komatsu, T; Torizuka, K

    1986-12-01

    The role of SPECT imaging with N-isopropyl-p iodoamphetamine (I-123 IMP) in the detection of angiographically documented occlusive cerebrovascular diseases was evaluated in 24 patients, and the results of regional cerebral blood flow (rCBF) were compared with x-ray CT. Twelve patients had internal carotid occlusion, ten had intracranial occlusion beyond the circle of Willis, one had common carotid occlusion, and one had basilar artery occlusion. SPECT images were obtained with a gamma camera, which was rotated 360 degrees around the patient's head 30 minutes after an intravenous injection of 3 mCi of I-123 IMP. CT images in the transverse plane were obtained, and the regions of reduced attenuation were identified for comparison of topographic extension of the lesion with the regions of decreased rCBF seen on SPECT. In six cases, the lesions seen on the SPECT images were distinctly more extensive than those seen on CT. In the remaining 18 cases, the extent of the lesion was identical on both CT and SPECT images. Radiochemical and radionuclide impurities, the distance of the detector from the head, and the nature of the collimator affected the SPECT results. I-123 IMP SPECT imaging complements CT findings in detecting the ischemic zones beyond the regions identified on CT images, and may have a major rule in the management of patients with occlusive cerebrovascular diseases.

  12. Principles and Clinical Application of Dual-energy Computed Tomography in the Evaluation of Cerebrovascular Disease

    Science.gov (United States)

    Hsu, Charlie Chia-Tsong; Kwan, Gigi Nga Chi; Singh, Dalveer; Pratap, Jit; Watkins, Trevor William

    2016-01-01

    Dual-energy computed tomography (DECT) simultaneously acquires images at two X-ray energy levels, at both high- and low-peak voltages (kVp). The material attenuation difference obtained from the two X-ray energies can be processed by software to analyze material decomposition and to create additional image datasets, namely, virtual noncontrast, virtual contrast also known as iodine overlay, and bone/calcium subtraction images. DECT has a vast array of clinical applications in imaging cerebrovascular diseases, which includes: (1) Identification of active extravasation of iodinated contrast in various types of intracranial hemorrhage; (2) differentiation between hemorrhagic transformation and iodine staining in acute ischemic stroke following diagnostic and/or therapeutic catheter angiography; (3) identification of culprit lesions in intra-axial hemorrhage; (4) calcium subtraction from atheromatous plaque for the assessment of plaque morphology and improved quantification of luminal stenosis; (5) bone subtraction to improve the depiction of vascular anatomy with more clarity, especially at the skull base; (6) metal artifact reduction utilizing virtual monoenergetic reconstructions for improved luminal assessment postaneurysm coiling or clipping. We discuss the physical principles of DECT and review the clinical applications of DECT for the evaluation of cerebrovascular diseases. PMID:27512615

  13. Possibilities of using naftidrofuryl in the therapy of cerebrovascular diseases: Literature review and the authors’ observations

    Directory of Open Access Journals (Sweden)

    A. N. Belova

    2015-01-01

    Full Text Available The efficacy of naftidrofuryl in treating cerebrovascular diseases is analyzed on the basis of a review of the Russian and foreign literature. Naftidrofuryl is a seroton 5-HT2 receptor antagonist and acts on brain energy metabolism mainly during hypoxia or ischemia. The results of preclinical studies proving the antispasmodic and neuroprotective properties of the drug and its capacity to normalize microcirculation in hypoxia are briefly considered. Experimental findings served as a basis for further studies of the efficacy of naftidrofuryl in patients with stroke, chronic cerebral ischemia, or vascular dementia. The use of naftidrofuryl (dusopharm was demonstrated to statistically significantly enhance the efficiency of rehabilitation in post-stroke patients and to be followed by significant psychoemotional improvement. According to a Cochrane review, the naftidrofuryl-treated patients with vascular dementia showed a tendency towards better executive and cognitive functions, behavior, and mood. The drug was noted to have a positive effect on the health of patients with chronic cerebral ischemia.The authors provide the data of their trial of naftidrofuryl used in patients with dyscirculatory encephalopathy, which have confirmed its efficacy in this category of patients. The data available in the literature suggest that oral naftidrofuryl has a good tolerability and safety profile in patients with cerebrovascular diseases.

  14. High-intensity interval exercise and cerebrovascular health: curiosity, cause, and consequence.

    Science.gov (United States)

    Lucas, Samuel J E; Cotter, James D; Brassard, Patrice; Bailey, Damian M

    2015-06-01

    Exercise is a uniquely effective and pluripotent medicine against several noncommunicable diseases of westernised lifestyles, including protection against neurodegenerative disorders. High-intensity interval exercise training (HIT) is emerging as an effective alternative to current health-related exercise guidelines. Compared with traditional moderate-intensity continuous exercise training, HIT confers equivalent if not indeed superior metabolic, cardiac, and systemic vascular adaptation. Consequently, HIT is being promoted as a more time-efficient and practical approach to optimize health thereby reducing the burden of disease associated with physical inactivity. However, no studies to date have examined the impact of HIT on the cerebrovasculature and corresponding implications for cognitive function. This review critiques the implications of HIT for cerebrovascular function, with a focus on the mechanisms and translational impact for patient health and well-being. It also introduces similarly novel interventions currently under investigation as alternative means of accelerating exercise-induced cerebrovascular adaptation. We highlight a need for studies of the mechanisms and thereby also the optimal dose-response strategies to guide exercise prescription, and for studies to explore alternative approaches to optimize exercise outcomes in brain-related health and disease prevention. From a clinical perspective, interventions that selectively target the aging brain have the potential to prevent stroke and associated neurovascular diseases.

  15. Study of nanosensor systems for hypertension associated cerebrovascular and cardiovascular disorders

    Science.gov (United States)

    Ramasamy, Mouli; Varadan, Vijay K.

    2015-04-01

    Hypertension and hypertension associated cerebrovascular and cardiovascular diseases are on a rise. At-least 970 million people in the world and Seventy percent of the American adults are affected by high blood pressure, also known as hypertension. Even though blood pressure monitoring systems are readily available, the number of people being affected has been increasing. Most of the blood pressure monitoring systems require cumbersome approaches. Even the noninvasive techniques have not lowered the number of people affected nor did at-least increase the user base of these systems. Uncontrolled or untreated hypertension may lead to various cerebrovascular disorders including stroke, hypertensive crisis, lacunar infarcts intracerebral damage, microaneurysm, and cardiovascular disorders including heart failure, myocardial infraction, and ischemic heart disease. Hypertension is rated as the one of the most important causes of premature death in spite of the technical advances in biomedical technology. This paper briefs a review of the widely adopted blood pressure monitoring methods, research techniques, and finally, proposes a concept of implementing nanosensors and wireless communication for real time non-invasive blood pressure monitoring.

  16. Cardiovascular and cerebrovascular outcomes in elderly hypertensive patients treated with either ARB or ACEI

    Institute of Scientific and Technical Information of China (English)

    Cong Ma; Jian Cao; Xue-Chun Lu; Xin-Hong Guo; Yan Gao; Xian-Feng Liu; Li Fan

    2012-01-01

    Background Although angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are equally important in the treatment of hypertension, there is less evidence whether they have equal cardiovascular and cerebrovascular protective effects, especially in elder hypertensive patients. This study aims to clarify this unresolved issue. Methods This cross-sectional study included clinical data on 933 aged male patients with hypertension who received either an ARB or ACEI for more than two months between January 2007 and May 2011. The primary outcome was the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary endpoints were unstable angina, new atrial fibrillation, and transient ischemic attack. Results The median follow-up time was 24 months. Age, drug types, cerebral infarction history, renal dysfunction history were the independent predictors of the primary endpoint. The risk of an occurrence of a primary endpoint event was higher in the ARB group than the ACEI group [P = 0.037, hazard ratios occurrence was higher in the ARB group than the ACEI group (P = 0.04). In regard to the secondary endpoints, there were no significant were independent predictors of the secondary endpoint. Conclusion ACEI were more effective than ARB in reducing cardiovascular and cerebrovascular morbidity and mortality in aged patients with hypertension.

  17. Use of various CT imaging methods for diagnosis of acute ischemic cerebrovascular disease

    Institute of Scientific and Technical Information of China (English)

    Gang Wang; Xue Cheng; Xianglin Zhang

    2013-01-01

    Thirty-four patients with cerebral infarction and 18 patients with transient ischemic attack were examined by multi-slice spiral CT scan, CT perfusion imaging, and CT angiography within 6 hours after onset. By CT perfusion imaging, 29 cases in the cerebral infarction group and 10 cases in the transient ischemic attack group presented with abnormal blood flow perfusion, which corresponded to the clinical symptoms. By CT angiography, various degrees of vascular stenosis could be detected in 41 patients, including 33 in the cerebral infarction group and eight in the transient ischemic attack group. The incidence of intracranial artery stenosis was higher than that of extracranial artery stenosis. The intracranial artery stenosis was located predominantly in the middle cerebral artery and carotid artery siphon, while the extracranial artery stenosis occurred mainly in the bifurcation of the common carotid artery and the opening of the vertebral artery. There were 34 cases (83%) with convict vascular stenosis and perfusion abnormalities, and five cases (45%) with perfusion abnormalities but without convict vascular stenosis. The incidence of cerebral infarction in patients with National Institutes of Health Stroke Scale scores ≥ 5 points during onset was significantly higher than that in patients with National Institutes of Health Stroke Scale scores < 5 points. These experimental findings indicate that the combined application of various CT imaging methods allows early diagnosis of acute ischemic cerebrovascular disease, which can comprehensively analyze the pathogenesis and severity of acute ischemic cerebrovascular disease at the morphological and functional levels.

  18. Clinical study on magnetic resonance imaging of lacunar infarcts and cerebrovascular high-risk group

    Energy Technology Data Exchange (ETDEWEB)

    Hironaka, Masatoshi (Hiroshima Univ. (Japan). School of Medicine)

    1990-04-01

    Magnetic resonance imaging (MRI) study was performed in 32 patients with recent lacunar stroke. T2-weighted images showed ischemic lesions more clearly than T1-weighted images. Sixty-six percent of 32 patients had periventricular lesions. Eighty-four percent had subcortical white matter lesions. Sixty-nine percent had lesions in basal ganglia. Twenty-eight percent had lesions in brainstem. Periventricular lesions were revealed symmetrically. On the other hand, lesions in other areas were not detected symmetrically. Severe periventricular lesions on MRI were similar to those of Binswanger's disease. Patients with severe periventricular lesions had often hypertension. Moreover, two of them had dementia. Twenty-three patients with transient ischemic attack had less remarkable lesions than patients with lacunar stroke. Thirty-seven patients with a history of cerebrovascular risk factors (hypertension, diabetes mellitus) had severer lesions compared with normal controls. Sixty-one percent of controls, who had no cerebrovascular symptoms and signs, had MRI lesions. These results suggest that MRI is useful for detection of cerebral ischemic lesions with no associated clinical symptoms or signs. (author).

  19. Clinical application of dynamic digital subtraction angiography in cerebrovascular ischemic diseases

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-09-01

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

  20. Cranial MR angiography in children with cerebrovascular diseases; Evaluation of new phase contrast technique

    Energy Technology Data Exchange (ETDEWEB)

    Sumida, Masayuki; Uozumi, Tohru; Kuwabara, Satoshi; Kurisu, Kaoru; Ikawa, Fusao; Satoh, Hideki; Yukawa, Osamu; Migita, Keisuke; Hada, Hiroshi (Hiroshima Univ. (Japan). School of Medicine)

    1993-06-01

    We evaluated the phase contrast (PC) method, a new type of MR angiography (MRA), in children with cerebrovascular diseases, and compared it with the time of flight (TOF) method and conventional angiography. The patients were nine children with the following diagnoses: two with arteriovenous malformations (AVM), one with Galenic AVM, one with cavernous angioma, four with moyamoya disease, and one with cerebral infarction. A 1.5 T Signa Advantage and a 3-D PC were used. In AVM and Galenic AVM, feeder, nidus and drainer were demonstrated separately by changing velocity encoding (VENC). In the patient with cavernous angioma, the cortical veins were well demonstrated. In moyamoya disease and infarction, stenosis or obstruction of the main arteries and revascularization after surgery were clearly demonstrated. PC is useful in the diagnosis and follow up of cerebrovascular diseases in children because PC is superior in demonstrating veins and scanning in any direction is possible. However, MRA alone cannot demonstrate small vessels and direction of flow, so preoperative conventional angiography is still necessary. (author).

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

    Lifescience Database Archive (English)

    Full Text Available 15075353 Post-transcriptional regulation of proinflammatory proteins. Anderson P, P...hillips K, Stoecklin G, Kedersha N. J Leukoc Biol. 2004 Jul;76(1):42-7. Epub 2004 Apr 1. (.png) (.svg) (.html) (.csml) Show Post...-transcriptional regulation of proinflammatory proteins. PubmedID 15075353 Title Post-tr

  2. Comparison of Proinflammatory Gene Expression in Lesions Caused by either Burn Injuries or Cutaneous Leishmaniasis

    OpenAIRE

    Akhzari; Rezvan; Zolhavarieh; Moafi

    2016-01-01

    Background Leishmaniasis is a worldwide disease prevalent in tropical and sub-tropical countries in the world. Characterization of inflammatory responses produced in cutaneous Leishmaniasis has not yet been completed. The current study aims to assess and compare pro-inflammatory cytokines between burning injuries and Leishmania infection. Methods the specific primers were designed for 10 proinflammatory genes including CCL4, CCL3,...

  3. Cerebrovascular disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008482 Risk factors for ischemic lacunar stroke associated headache. HU Wei(胡伟), et al. Dept Neurol, Nanjing General Hosp, Nanjing Milit Command, Nanjing 210002. Chin J Nerv Ment Dis 2008;34(5):262-265. Objective To analyze risk factors of stroke-associated headache (SH) and explore its underlying mechanisms. Methods First-ever lacunar infarction patients (n=371) were extracted from Nanjing Stroke Registration Program.

  4. Cerebrovascular disease

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920743 A prospective trial of hemodilutiontherapy in acute cerebral infarction. DINGMingchen(丁铭臣), et al. Dept Neurol, XuanwuHosp, Capital Instit Med, Beijing, 100053. ChinJ Neurol & Psychiat 1992; 25(3): 146-148. Ninety two patients with acute (<72hours) cerebral infarction involving middle

  5. Cerebrovascular disorder

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930179 A study on senescence of red blood cellin patients with stroke.QIAN Caiyun(钱采韵),et al.Dept Neurol,1st Affili Hosp ZhongshanMed Univ,Guangzhou,510080.Chin J NervMent Dis 1992;18(3):146-148.Measurements of malonyldialdehyde(MDA)and superoxide dismutase(SOD)were per-formed on the patients with cerebral infarction(27 cases),cerebral hemorrhage(18 cases)and42 age-matched healthy controls.The resultsshowed that MDA content increased significant-

  6. Cerebrovascular disease

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950404 Operative treatment of multiple intracranialaneurvsms in one stage.GAO Yongzhong(高永中),etal.Dept Neurosurg.Tianjin Med Coll Hosp.Tianjin,300052.Chin J Nerv & Ment Dis 1994;20(6):329-331In this study,seven patients with intracranial multi-ple aneurysms are reported.Every patient sufferedfrom two aneurysms simultaneously.Totally,therewere fourteen aneurysms(thirteen saccular and onefusiform aneurysm).There was one patient with bilat-eral arterior chorioid artery aneurysms.All of the sac-cular aneurysms were clipped through a single pterion-al approach and the fusiform aneurysm was wrappedwith muscle tissue.After clipping,some of the a-neurysmal sacs were punctured or an angiographical

  7. Doença cerebrovascular: aquisição de linguagem em pré-escolares Cerebrovascular disease: language acquisition in preschool children

    Directory of Open Access Journals (Sweden)

    Karina Tamarozzi de Oliveira

    2005-09-01

    Full Text Available São descritos 10 casos de crianças com idade cronológica entre 5 anos e 1 mês e 5 anos e 11 meses, divididas em grupo de doença cerebrovascular, (G-DCV e grupo controle (Gc. As crianças do G-DCV apresentaram DCV confirmada na fase aguda através de exame neurológico clínico e de imagem na UNICAMP. Nas avaliações utilizou-se triagem audiológica, protocolo de avaliação da linguagem infantil, teste de vocabulário por imagens Peabody, com o objetivo de avaliar os diversos subsistemas lingüísticos e as noções perceptivo-cognitivas. Na análise qualitativa do G-DCV, do ponto de vista fonoaudiológico e neurológico, quando comparado ao Gc, mostrou recuperação completa do distúrbio adquirido de linguagem (DAL em 2 crianças e alterações de linguagem em 3. O estudo dos casos revelou que os diversos aspectos que constituem a linguagem em desenvolvimento na criança pré-escolar devem ser analisados de forma individual, quantitativa e qualitativamente para achados conclusivos.We describe ten children, aging 5 years and 1 month until 5 years and 11 months, when the phonoaudiological assessment was conducted. They are divided according to cerebrovascular disease, in CVD group (CVD-G and control group (cG. Children were seen and CVD was confirmed in the acute phase at UNICAMP hospital. Audiologic assessment, protocol for Infant language assessment, and Peabody picture vocabulary test were used in the evaluations. The qualitative analysis of the subjects from a phonoaudiological and neurological point of view has shown the recovery of acquired language desorder (ALD with no influence whatsoever in the development of 2 subjects and subtle language and/or learning process alterations for 3 subjects. The cases study has revealed that all aspects of language development in preschool children should be analyzed in an individual, quantitative, and qualitative basis to lead to conclusive findings.

  8. Hipertensión arterial sistólica. Impacto sobre la enfermedad cerebrovascular.

    Directory of Open Access Journals (Sweden)

    María C. Valle Campo

    2011-08-01

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

    SYSTOLIC HYPERTENSION. IMPACT ON CEREBROVASCULAR DISEASE

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

  9. A multidisciplinary stroke clinic for outpatient care of veterans with cerebrovascular disease

    Directory of Open Access Journals (Sweden)

    Moran E

    2011-04-01

    Full Text Available Arlene A Schmid1,2,3,4, John R Kapoor5, Edward J Miech1, Deborah Kuehn6, Mary I Dallas7, Robert D Kerns8, Albert C Lo9,10, John Concato11,12, Michael S Phipps13,14,15, Cody D Couch13, Eileen Moran13, Linda S Williams1,2,3,16, Layne A Goble17,18, Dawn M Bravata1,2,3,191Department of Veteran Affairs (VA Health Services Research & Development (HSR&D Center of Excellence on Implementing Evidence-Based Practice (CIEBP, 2VA HSR&D Stroke Quality Enhancement Research Initiative (QUERI Program, Richard L Roudebush VA Medical Center, Indianapolis, IN, USA; 3Regenstrief Institute, Indianapolis, IN, USA; 4Department of Occupational Therapy, Indiana University, IN, USA; 5Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, IL, USA; 6Nursing Service, 7Physical Medicine and Rehabilitation Service, 8Psychology Service, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA; 9Departments of Neurology, Community Health, and Engineering at Brown University, Providence, RI, USA; 10Providence Veterans Administration Medical Center, Providence, RI, USA; 11Clinical Epidemiology Research Center (CERC, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA; 12Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA; 13Department of Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA; 14Robert Wood Johnson Clinical Scholars Program, 15Department of Neurology, Yale University School of Medicine, New Haven, CT, USA; 16Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA; 17Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston, SC, USA; 18Veterans Administration Medical Center, Charleston, SC, USA; 19Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, IN, USABackground: Managing cerebrovascular risk factors is complex and difficult. The objective of this

  10. Induction of STAT1 phosphorylation at serine 727 and expression of proinflammatory cytokines by porcine reproductive and respiratory syndrome virus.

    Directory of Open Access Journals (Sweden)

    Ying Yu

    Full Text Available Porcine reproductive and respiratory syndrome virus (PRRSV is a viral pathogen that causes acute respiratory illnesses in young pigs. Since 1987, PRRSV has contributed substantial economic losses to the swine industry. Elevation of proinflammatory cytokines in PRRSV-infected pigs is thought to contribute to PRRSV pathogenesis. In this study, PRRSV VR-2385, a Type 2 strain with moderate virulence, was found to induce phosphorylation of signal transducer and activator of transcription 1 (STAT1 at serine 727 (pSTAT1-S727 in MARC-145 cells. No phosphorylated STAT1 at tyrosine 701 was detected, which indicates that the pSTAT1-S727 elevation was interferon-independent. The PRRSV-induced pSTAT1-S727, however, was dose-dependent and its levels increased with infection time. IngelVac PRRS MLV strain had a minimal effect on pSTAT1-S727. Compared to MLV-infected cells, VR-2385 infection caused significantly higher level of expression of proinflammatory cytokines, including interleukin 1 beta (IL-1beta and IL-8. The VR-2385-induced pSTAT1-S727 and cytokine expression were reduced after SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK, or methylthioadenosine (MTA, a methyl transferase inhibitor, was added to the cells. The SB203580 and MTA-mediated inhibition suggested that the virus-induced pSTAT1-S727 was dependent on p38 MAPK pathway. In primary porcine alveolar macrophages (PAMs, VR-2385 also induced pSTAT1-S727 and expression of proinflammatory cytokines and chemokines, including IL-1beta, IL-8, chemokine ligand 2 (CCL2 and chemokine (C-X-C motif ligand 10 (CXCL10. Similarly, SB203580 treatment of PAM cells blocked the elevation of pSTAT1-S727 and cytokine expression. Overexpression of individual viral proteins showed that non-structural protein 12 (nsp12 was able to induce elevation of pSTAT1-S727 and the expression of IL-1β and IL-8. These results indicated that PRRSV VR-2385 induces pSTAT1-S727 and the expression of

  11. Glutathione S-transferase pi modulates NF-κB activation and pro-inflammatory responses in lung epithelial cells

    Directory of Open Access Journals (Sweden)

    Jane T. Jones

    2016-08-01

    Full Text Available Nuclear Factor kappa B (NF-κB is a transcription factor family critical in the activation of pro- inflammatory responses. The NF-κB pathway is regulated by oxidant-induced post-translational modifications. Protein S-glutathionylation, or the conjugation of the antioxidant molecule, glutathione to reactive cysteines inhibits the activity of inhibitory kappa B kinase beta (IKKβ, among other NF-κB proteins. Glutathione S-transferase Pi (GSTP is an enzyme that has been shown to catalyze protein S-glutathionylation (PSSG under conditions of oxidative stress. The objective of the present study was to determine whether GSTP regulates NF-κB signaling, S-glutathionylation of IKK, and subsequent pro-inflammatory signaling. We demonstrated that, in unstimulated cells, GSTP associated with the inhibitor of NF-κB, IκBα. However, exposure to LPS resulted in a rapid loss of association between IκBα and GSTP, and instead led to a protracted association between IKKβ and GSTP. LPS exposure also led to increases in the S-glutathionylation of IKKβ. SiRNA-mediated knockdown of GSTP decreased IKKβ-SSG, and enhanced NF-κB nuclear translocation, transcriptional activity, and pro-inflammatory cytokine production in response to lipopolysaccharide (LPS. TLK117, an isotype-selective inhibitor of GSTP, also enhanced LPS-induced NF-κB transcriptional activity and pro-inflammatory cytokine production, suggesting that the catalytic activity of GSTP is important in repressing NF-κB activation. Expression of both wild-type and catalytically-inactive Y7F mutant GSTP significantly attenuated LPS- or IKKβ-induced production of GM-CSF. These studies indicate a complex role for GSTP in modulating NF-κB, which may involve S-glutathionylation of IKK proteins, and interaction with NF-κB family members. Our findings suggest that targeting GSTP is a potential avenue for regulating the activity of this prominent pro-inflammatory and immunomodulatory transcription factor.

  12. Pro-Inflammatory Cytokine Levels in HIV Infected and Uninfected Pregnant Women with and without Preeclampsia

    Science.gov (United States)

    Maharaj, Niren Ray; Phulukdaree, Alisa; Nagiah, Savania; Ramkaran, Prithiksha; Tiloke, Charlette; Chuturgoon, Anil Amichund

    2017-01-01

    Introduction Preeclampsia and HIV/AIDS are inflammatory conditions that contribute significantly to adverse maternal and foetal outcomes. The immune reconstitution effects of HAART on inflammatory mediators has not been adequately studied in pregnancy and may impact on the inflammatory cytokine network in women with co-morbid preeclampsia. Our study evaluated changes in pro-inflammatory cytokines IL-2, TNF-α, IFN-γ and IL-6 in HIV infected preeclamptic women on HAART. Methods A prospective experimental study was conducted at Prince Mshiyeni Memorial Hospital between July 2013 and September 2014. One hundred and ninety three pregnant women were recruited into 4 groups: uninfected normotensive (50; 26%), infected normotensive (45; 23%), uninfected preeclamptic (53; 28%) and infected preeclamptic women (45; 23%). Serum levels of cytokines TNF-α, IFN- γ, IL-2 and IL-6 were determined using commercially available kits and a Cytometric Bead Array (CBA). Comparative data was recorded and analysed descriptively. Results In the control groups (normotensive), significantly lower values were found in IL-2 (p = 0.010), TNF-α (p = 0.045), and IL-6 (p = 0.005); and a non-significant decrease was observed in IFN-γ (p = 0.345) in HIV infected women on HAART compared to uninfected controls. In the experimental group (preeclamptic) women, significantly reduced levels were observed in IL-2 and TNF-α (p = 0.001; p = 0.000) and non-significant decreases were observed in IFN-γ and IL-6 (p = 0.023; p = 0.086) in HIV infected women on HAART compared with uninfected preeclamptic women. Non-significant differences were observed between uninfected preeclamptic and normotensive women. Conclusion In uncomplicated/normotensive pregnancies, HIV/HAART is associated with significant decreases in IL-2, TNF-α and IL-6, and in preeclamptic women significant decreases in IL-2 and TNF-α were observed. These findings suggest that HIV/HAART impacts on pro-inflammatory cytokines in women with co

  13. Follicular Proinflammatory Cytokines and Chemokines as Markers of IVF Success

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    Aili Sarapik

    2012-01-01

    Full Text Available Cytokines are key modulators of the immune system and also contribute to regulation of the ovarian cycle. In this study, Bender MedSystems FlowCytomix technology was used to analyze follicular cytokines (proinflammatory: IL-1β, IL-6, IL-18, IFN-γ, IFN-α, TNF-α, IL-12, and IL-23;, and anti-inflammatory: G-CSF, chemokines (MIP-1α, MIP-1β, MCP-1, RANTES, and IL-8, and other biomarkers (sAPO-1/Fas, CD44(v6 in 153 women undergoing in vitro fertilization (IVF. Cytokine origin was studied by mRNA analysis of granulosa cells. Higher follicular MIP-1α and CD44(v6 were found to correlate with polycystic ovary syndrome, IL-23, INF-γ, and TNF-α with endometriosis, higher CD44(v6 but lower IL-β and INF-α correlated with tubal factor infertility, and lower levels of IL-18 and CD44(v6 characterized unexplained infertility. IL-12 positively correlated with oocyte fertilization and embryo development, while increased IL-18, IL-8, and MIP-1β were associated with successful IVF-induced pregnancy.

  14. Stimulation of pro-inflammatory responses by mebendazole in human monocytic THP-1 cells through an ERK signaling pathway.

    Science.gov (United States)

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

    2011-03-01

    Oral helminthic mebendazole (MBZ) has been reported to cause liver injury with inflammatory responses. However, the underlying mechanism remains unknown. To examine the inflammatory reactions, we investigated whether MBZ and other helminthic drugs increase the release of pro-inflammatory cytokines and chemokines using human monocytic cells. The release of interleukin (IL)-8 and tumor necrosis factor (TNF) α from human monocytic THP-1 cells was significantly increased by treatment with MBZ, albendazole (ABZ), fenbendazole (FBZ), or oxibendazole (OBZ), but not by albendazole sulfoxide or praziquantel, suggesting that MBZ and structurally similar drugs can stimulate monocytes and increase the release of pro-inflammatory cytokines. MBZ also significantly increased the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) 1/2 in THP-1 cells. Pretreatment with the MAP kinase/ERK kinase 1/2 inhibitor U0126 significantly suppressed the increase of IL-8 and TNFα levels by MBZ, ABZ, FBZ, or OBZ treatment in THP-1 cells, but the p38 mitogen-activated protein kinase inhibitor SB203580 or JNK1/2 inhibitor SP600125 did not. These results suggested that an ERK1/2 pathway plays an important role in the release of IL-8 and TNFα in THP-1 cells treated with MBZ and structurally similar drugs. In conclusion, the release of inflammatory mediators by MBZ might be one of the mechanisms underlying immune-mediated liver injury. This in vitro method may be useful to predict adverse inflammatory reactions that lead to hepatotoxicity.

  15. Pro-inflammatory action of MIF in acute myocardial infarction via activation of peripheral blood mononuclear cells.

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    David A White

    Full Text Available OBJECTIVES: Macrophage migration inhibitory factor (MIF, a pro-inflammatory cytokine, has been implicated in the pathogenesis of multiple inflammatory disorders. We determined changes in circulating MIF levels, explored the cellular source of MIF, and studied the role of MIF in mediating inflammatory responses following acute myocardial infarction (MI. METHODS AND RESULTS: We recruited 15 patients with MI, 10 patients with stable angina and 10 healthy volunteers and measured temporal changes of MIF in plasma. Expression of MIF, matrix metalloproteinase-9 (MMP-9 and interleukin-6 (IL-6 in cultured peripheral blood mononuclear cells (PBMCs and the media were measured by ELISA or real-time PCR. Compared to controls, plasma levels of MIF and IL-6 were significantly elevated at admission and 72 h post-MI. In contrast, expression of MIF, MMP-9 and IL-6 by PBMCs from MI patients was unchanged at admission, but significantly increased at 72 h. Addition of MIF activated cultured PBMCs by upregulating expression of inflammatory molecules and also synergistically enhanced stimulatory action of IL-1β which were inhibited by anti-MIF interventions. In a mouse MI model we observed similar changes in circulating MIF as seen in patients, with reciprocal significant increases in plasma MIF and reduction of MIF content in the infarct myocardium at 3 h after MI. MIF content in the infarct myocardium was restored at 72 h post-MI and was associated with robust macrophage infiltration. Further, anti-MIF intervention significantly reduced inflammatory cell infiltration and expression of monocyte chemoattractant protein-1 at 24 h and incidence of cardiac rupture in mice post-MI. CONCLUSION: MI leads to a rapid release of MIF from the myocardium into circulation. Subsequently MIF facilitates PBMC production of pro-inflammatory mediators and myocardial inflammatory infiltration. Attenuation of these events, and post-MI cardiac rupture, by anti-MIF interventions suggests

  16. Proinflammatory Cytokines, Adiponectin, and Increased Risk of Primary Cardiovascular Events in Diabetic Patients With or Without Renal Dysfunction

    Science.gov (United States)

    Schöttker, Ben; Herder, Christian; Rothenbacher, Dietrich; Roden, Michael; Kolb, Hubert; Müller, Heiko; Brenner, Hermann

    2013-01-01

    OBJECTIVE Inflammatory processes contribute to both diabetes and cardiovascular risk. We wanted to investigate whether circulating concentrations of proinflammatory immune mediators and adiponectin in diabetic patients are associated with incident cardiovascular events. RESEARCH DESIGN AND METHODS In 1,038 participants with diabetes of the population-based ESTHER study, of whom 326 showed signs of renal dysfunction, Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for the association of increasing concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), IL-18, macrophage migration inhibitory factor (MIF), adiponectin, and leptin with cardiovascular events (myocardial infarction, stroke, or fatal cardiovascular event) during a follow-up period of 8 years. RESULTS During follow-up, 161 subjects with diabetes experienced a primary cardiovascular event. Proinflammatory markers were not associated with a higher risk for primary cardiovascular events in the total study population after adjustment for multiple confounders. However, IL-6 and MIF were associated with cardiovascular events in subjects with renal dysfunction (HR for the comparison of top vs. bottom tertile 1.98 [95% CI 1.12–3.52], P [trend] = 0.10 for IL-6; 1.48 [0.87–2.51], P [trend] = 0.04 for MIF). Adiponectin levels were associated with cardiovascular events in the total population (1.48 [1.01–2.21], P [trend] = 0.03), and the association was even more pronounced in the subgroup with renal dysfunction (1.97 [1.08–3.57], P [trend] = 0.02). CONCLUSIONS In particular, the absence of an association between CRP and a U-shaped association of adiponectin levels with incident cardiovascular events show that associations between circulating immune mediators and cardiovascular risk differ between diabetic patients and subjects of the general population. PMID:23378623

  17. Cerebrovascular illness in the province of Cienfuegos. Tendency lines. A six years study Enfermedades cerebrovasculares en la provincia de Cienfuegos. Líneas de tendencia. Estudio de seis años

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    Juan E. Domínguez Suárez

    2006-10-01

    Full Text Available Background: The cerebrovascular diseases constitute the third cause of death and first of handicap in Cuba. They are inside the tasks prioritized by the World Health Organization and they receive special interest in Cienfuegos province, that is one of the populations of more longevity of the country and shows high rates of mortality. Objective: To define the tendency lines, according to the type of cerebrovascular diseases in Cienfuegos province, over the last six years. Methods: There was realized a retrospective, and descriptive study, of a series of cases. The mortality was analyzed for the different types of cerebrovascular diseases. The data were obtained, of the monthly and annual reports of the Commission of cerebrovascular diseases. Results: A half rate of morbidity of 108, 89, was verified by 100 000 habitants; the mortality due to infarct and subarachnoid hemorrhages diminishes. It was not the same in presence of intracerebral hemorrhage, in which was observed an increment. Increased the number of alive patients after the discharge from the hospital, which due to infarct and other cerebrovascular diseases, were handicapped and for their condition generated a load to the society. Conclusions: The intracerebral hemorrhage constitutes the main problem for the mortality and the infarct for the morbidity.

    Fundamento: Las enfermedades cerebrovasculares constituyen la tercera causa de muerte y primera de discapacidad en Cuba. Se encuentran dentro de las tareas priorizadas por la Organización Mundial de la Salud y reciben especial interés en la provincia de Cienfuegos, por encontrarse en ella una de las poblaciones más longevas del país y mostrar tasas elevadas de mortalidad. Objetivo: Definir las líneas de tendencia según el tipo de enfermedades cerebrovasculares en la provincia de Cienfuegos

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  19. Low pH Environmental Stress Inhibits LPS and LTA-Stimulated Proinflammatory Cytokine Production in Rat Alveolar Macrophages

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    Stanley F. Fernandez

    2013-01-01

    Full Text Available Gastric aspiration increases the risks for developing secondary bacterial pneumonia. Cytokine elaboration through pathogen recognition receptors (PRRs is an important mechanism in initiating innate immune host response. Effects of low pH stress, a critical component of aspiration pathogenesis, on the PRR pathways were examined, specifically toll-like receptor-2 (TLR2 and TLR4, using isolated rat alveolar macrophages (aMØs. We assessed the ability of aMØs after brief exposure to acidified saline to elaborate proinflammatory cytokines in response to lipopolysaccharide (LPS and lipoteichoic acid (LTA stimulation, known ligands of TLR4 and TLR2, respectively. Low pH stress reduced LPS- and LTA-mediated cytokine release (CINC-1, MIP-2, TNF-, MCP-1, and IFN-. LPS and LTA increased intracellular Ca2+ concentrations while Ca2+ chelation by BAPTA decreased LPS- and LTA-mediated cytokine responses. BAPTA blocked the effects of low pH stress on most of LPS-stimulated cytokines but not of LTA-stimulated responses. In vivo mouse model demonstrates suppressed E. coli and S. pneumoniae clearance following acid aspiration. In conclusion, low pH stress inhibits antibacterial cytokine response of aMØs due to impaired TLR2 (MyD88 pathway and TLR4 signaling (MyD88 and TRIF pathways. The role of Ca2+ in low pH stress-induced signaling is complex but appears to be distinct between LPS- and LTA-mediated responses.

  20. Clinical Characteristics of Cerebrovascular Pathology with Patients Suffering from Ph-Negative Myeloproliferative Disease

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    Marine M. Tanashyan

    2016-09-01

    Full Text Available Background: Disturbances of microcirculation play a significant role in the development and progression of both acute and chronic cerebrovascular diseases (CVD and may be associated with different hemogram abnormalities. One of the reasons of the prothrombogenic state of the endothelium is the increase in the number of blood corpuscles leading to (non-Ph myeloproliferative disorders (MPD including essential thrombocythemia (ET, polycythemia vera (PV, and primary myelofibrosis (PM. Materials and Methods: The study included 167 patients: 102 patients with Ph-MPD and the control group comprising 65 patients with CVD. According to MPD subtype, the patients were divided into three groups: patients with ET (37%, n = 38, male/female 7/31, age 52 ± 7 years, those with PV (40%, n = 41, male/female 20/21, age 50 ± 6 years and those with PM (23%, n = 23, male/female 5/18, age 54 ± 4 years. Results: In 79% (n = 81 of cases in the study group (with Ph-MPD, patients had chronic CVD, with the most frequently identified symptoms being asthenia (92% and headache (72%. Headache in Ph-MPD patients was more frequently (86% associated with PM, while in patients with PV and ET it was equally distributed (70%. Neurological symptoms in 53% of cases were associated with focal changes of the brain on MRI localized in the subcortical area of the frontal and parietal lobes. Twenty-one (21% patients suffered an acute cerebrovascular accident, 8 of them had thrombotic occlusion of one of the internal carotid arteries leading to hemispheric infarcts. Endothelial function (as measured by flow-dependent dilation of the brachial artery was severely impaired in all study groups (median 5% with normal cut-off at 10%, the lowest degree of vasodilator activity being specific for patients with a history of stroke (p = 0.011. Conclusion: Patients suffering from MPD had asymptomatic focal changes in the brain in the absence of concomitant vascular disease (hypertension

  1. The family – care sponsor of patients suffering from cerebrovascular accidents

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    Ourania Govina

    2007-07-01

    Full Text Available The purpose of this bibliographical review is to show the role of the family in the application of care of a patient suffering from a cerebrovascular accident (CVA. CVA's are, second to arthritis, one of the most impairing illnesses in terms of ability that creates the need for training the patient on a new basis and giving the family information on new roles. One of the dimensions of holistic family care is the increased support the patient receives from family care givers. Studies and clinical research both show that informing families on care giver roles is inadequate or non‐existent. Adequate training of nurses to prepare care givers via specialized programs stimulates the family to respond to the new challenge and take on roles that are multidimensional and complicated. It is important that family care givers of people with CVA's are given new information and taught new skills in order for these patients to maximize their own self‐care potential. CVA patients, following the acute phase of their illness and rehabilitation in specialized centers are nursed at home, mainly by their families with the help of healthcare services. Usually, the responsibilities the family takes on are mainly those of self‐care needs of the patient and his motivation, so that he will organize and carry out basic life activities via learning new ways to face everyday life, always within his impaired abilities. Care guidance is a most important nursing intervention so that activities of daily living problems can be addressed. The interventions are tailored according to the care givers' educational level and the patients' needs. CONCLUSIONS The most important findings of the study are: Patients with cerebrovascular accidents have impaired ability concerning mobility, communication and socialization and need special attention and education in order to improve daily life activities. The education of hemiplegic patients with informative intervention, awareness and

  2. Clinical values of intraoperative indocyanine green fluorescence video angiography with Flow 800 software in cerebrovascular surgery

    Institute of Scientific and Technical Information of China (English)

    YE Xun; LIU Xing-ju; MA Li; LIU Ling-tong; WANG Wen-lei; WANG Shuo; CAO Yong

    2013-01-01

    Background Microscope-integrated near-infrared indocyanine green video angiography (ICG-VA) has been used in neurosurgery for a decade.This study aimed to assess the value of intraoperative indocyanine green (ICG) video angiography with Flow 800 software in cerebrovascular surgery and to discover its hemodynamic features and changes of cerebrovascular diseases during surgery.Methods A total of 87 patients who received ICG-VA during various surgical procedures were enrolled in this study.Among them,45 cases were cerebral aneurysms,25 were cerebral arteriovenous malformations (AVMs),and 17 were moyamoya disease (MMD).A surgical microscope integrating an infrared fluorescence module was used to confirm the residual aneurysms and blocking of perforating arteries in aneurysms.Feeder arteries,draining veins,and normal cortical vessels were identified by the time delay color mode of Flow 800 software.Hemodynamic parameters were recorded.All data were analyzed by SPSS version 18.0 (SPSS Inc.,USA).T-test was used to analyze the hemodynamic features of AVMs and MMDs,the influence on peripheral cortex after resection in AVMs,and superficial temporal artery to middle cerebral artery (STA-MCA) bypass in MMDs.Results The visual delay map obtained by Flow 800 software had more advantages than the traditional playback mode in identifying the feeder arteries,draining veins,and their relations to normal cortex vessels.The maximum fluorescence intensity (MFI) and the slope of ICG fluorescence curve of feeder arteries and draining veins were higher than normal peripheral vessels (MFI:584.24±85.86 vs.382.94±91.50,slope:144.95±38.08 vs.69.20±13.08,P <0.05).The artefiovenous transit time in AVM was significantly shorter than in normal cortical vessels ((0.60±0.27) vs.(2.08±1.42) seconds,P <0.05).After resection of AVM,the slope of artery in the cortex increased,which reflected the increased cerebral flow.In patients with MMD,after STA-MCA bypass,cortex perfusion of

  3. Carbon dioxide induced changes in cerebral blood flow and flow velocity: Role of cerebrovascular resistance and effective cerebral perfusion pressure

    NARCIS (Netherlands)

    F. Grüne (Frank); S. Kazmaier (Stephan); R.J. Stolker (Robert J.); G.H. Visser (Gerhard Henk); A. Weyland (Andreas)

    2015-01-01

    textabstractIn addition to cerebrovascular resistance (CVR) zero flow pressure (ZFP), effective cerebral perfusion pressure (CPPe) and the resistance area product (RAP) are supplemental determinants of cerebral blood flow (CBF). Until now, the interrelationship of PaCO2 -induced changes in CBF, CVR,

  4. Influence of remote ischemic preconditioning on cerebral oxygen metabolism and cerebral blood flow indexes of patients with ischemic cerebrovascular disease

    Institute of Scientific and Technical Information of China (English)

    Hui Lu; Ning-Ning Cui; Bin-Cheng Wang

    2016-01-01

    Objective:To study the influence of remote ischemic preconditioning on cerebral oxygen metabolism and cerebral blood flow indexes of patients with ischemic cerebrovascular disease. Methods:A total of 58 patients with ischemic cerebrovascular disease in our hospital from April 2015 to January 2016 were selected as the study object, and 58 patients were randomly divided into two groups, 29 patients in control group were treated with routine treatment, 29 patients in observation group were treated with remote ischemic preconditioning on the basic treatment of control group, then the cerebral oxygen metabolism and cerebral blood flow indexes of two groups before the treatment and at first, third and sixth month after the treatment were respectively detected and compared.Results:The cerebral oxygen metabolism and cerebral blood flow indexes of two groups before the treatment all showed no significant differences (allP>0.05), while the cerebral oxygen metabolism and cerebral blood flow indexes of observation group at first, third and sixth month after the treatment were all significantly better than those before the treatment, and the results were all significantly better than those of control group at the same time too (allP>0.05).Conclusions: The influence of remote ischemic preconditioning on cerebral oxygen metabolism and cerebral blood flow indexes of patients with ischemic cerebrovascular disease are better, and its application value for the patients with ischemic cerebrovascular disease is higher.

  5. Association between ALT level and the rate of cardio/cerebrovascular events in HIV-positive individuals

    DEFF Research Database (Denmark)

    Sabin, Caroline A; Ryom, Lene; Kovari, Helen;

    2013-01-01

    An inverse association between serum alanine aminotransferase (ALT) levels and the risk of myocardial infarction (MI) has been reported in the general population. We investigated associations between ALT levels and the risk of various cardiovascular and cerebrovascular outcomes in a large cohort...

  6. Inhibition of cerebrovascular raf activation attenuates cerebral blood flow and prevents upregulation of contractile receptors after subarachnoid hemorrhage

    DEFF Research Database (Denmark)

    Ansar, Saema; Maddahi, Aida; Edvinsson, Lars

    2011-01-01

    of mitogen-activated protein kinase (MAPK) of the extracellular signal-regulated kinase (ERK)1/2 signal pathway. We hypothesize that SAH initiates cerebrovascular ERK1/2 activation, resulting in receptor upregulation. The raf inhibitor will inhibit the molecular events upstream ERK1/2 and may provide...

  7. Cerebrovascular disease in newborn infants: report of three cases with clinical follow-up and brain SPECT imaging

    Energy Technology Data Exchange (ETDEWEB)

    Moura-Ribeiro, Maria Valeriana L. de; Ciasca, Sylvia Maria; Vale-Cavalcanti, Mariza; Etchebehere, Elba C.S.C.; Camargo, Edwaldo E. [Universidade Estadual de Campinas, SP (Brazil). Faculdade de Ciencias Medicas

    1999-07-01

    The clinical and neurological findings of three neonates with the diagnosis of cerebrovascular disease are reported. The neuropsychological evaluation disclosed impairment of fine motor function, coordination, language, perception and behavioral disturbances. Brain SPECT imaging revealed perfusional deficits in the three cases. (author)

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

    Science.gov (United States)

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

    2012-11-01

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

  9. Autophagy activity is up-regulated in adipose tissue of obese individuals and modulates proinflammatory cytokine expression

    NARCIS (Netherlands)

    Jansen, H.J.; Essen, P. van; Koenen, T.; Joosten, L.A.B.; Netea, M.G.; Tack, C.J.J.; Stienstra, R.

    2012-01-01

    Autophagy, an evolutionary conserved process aimed at recycling damaged organelles and protein aggregates in the cell, also modulates proinflammatory cytokine production in peripheral blood mononuclear cells. Because adipose tissue inflammation accompanied by elevated levels of proinflammatory cytok

  10. Brain Activity of Thioctic Acid Enantiomers: In Vitro and in Vivo Studies in an Animal Model of Cerebrovascular Injury

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    Seyed Khosrow Tayebati

    2013-02-01

    Full Text Available Oxidative stress is an imbalance between the production of free radicals and antioxidant defense mechanisms, potentially leading to tissue damage. Oxidative stress has a key role in the development of cerebrovascular and/or neurodegenerative diseases. This phenomenon is mainly mediated by an enhanced superoxide production by the vascular endothelium with its consequent dysfunction. Thioctic, also known as alpha-lipoic acid (1,2-dithiolane-3-pentanoic acid, is a naturally occurring antioxidant that neutralizes free radicals in the fatty and watery regions of cells. Both the reduced and oxidized forms of the compound possess antioxidant ability. Thioctic acid has two optical isomers designated as (+- and (−-thioctic acid. Naturally occurring thioctic acid is the (+-thioctic acid form, but the synthetic compound largely used in the market for stability reasons is a mixture of (+- and (−-thioctic acid. The present study was designed to compare the antioxidant activity of the two enantiomers versus the racemic form of thioctic acid on hydrogen peroxide-induced apoptosis in a rat pheochromocytoma PC12 cell line. Cell viability was evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay and free oxygen radical species (ROS production was assessed by flow cytometry. Antioxidant activity of the two enantiomers and the racemic form of thioctic acid was also evaluated in spontaneously hypertensive rats (SHR used as an in vivo model of increased oxidative stress. A 3-h exposure of PC12 cells to hydrogen peroxide (H2O2 significantly decreased cell viability and increased levels of intracellular ROS production. Pre-treatment with racemic thioctic acid or (+-enantiomer significantly inhibited H2O2-induced decrease in cell viability from the concentration of 50 μmol/L and 20 μmol/L, respectively. Racemic thioctic acid and (+-salt decreased levels of intracellular ROS, which were unaffected by (−-thioctic acid. In the brain of

  11. Intracerebroventricular Administration of Streptozotocin as an Experimental Approach to Depression: Evidence for the Involvement of Proinflammatory Cytokines and Indoleamine-2,3-Dioxygenase.

    Science.gov (United States)

    Souza, Leandro Cattelan; Jesse, Cristiano R; de Gomes, Marcelo Gomes; Viana, Cristini Escobar; Mattos, Etiara; Silva, Neici Cáceres; Boeira, Silvana Peterini

    2017-02-02

    There is a lack of information about the molecular events underlying the depressive-like effect of an intracerebroventricular injection of streptozotocin (ICV-STZ) in mice. Elevated activity of the tryptophan-degrading enzyme indoleamine-2,3-dioxygenase (IDO) has been proposed to mediate depression in inflammatory disorders. In this study, we report that ICV-STZ activates IDO in the hippocampus of mice and culminates in depressive-like behaviors, measured by an increased duration in immobility time in the forced swimming test and decreased total time of grooming in the splash test. Indirect blockade of IDO activation with the cytokine inhibitor minocycline prevents the development of depressive-like behaviors and attenuates STZ-induced upregulation of proinflammatory cytokines in the hippocampus. Minocycline abrogates the increase in tryptophan and kynurenine levels as well as prevents serotonin dysfunction in the hippocampus of STZ-injected mice. These results suggest that hippocampal IDO activation in STZ-associated depressive-like behavior is mediated by proinflammatory cytokine-dependent mechanisms. Our study not only extends the evidence that IDO has a critical role in mediating inflammation-induced depression but also supports the notion that neuroinflammation and the kynurenine pathway are important targets of novel therapeutic drugs for depression. In addition, our study provides new insights into the neurobiological mechanisms underlying ICV-STZ and indicates that this model could be employed in the preclinical research of depression.

  12. Ozone induces a proinflammatory response in primary human bronchial epithelial cells through mitogen-activated protein kinase activation without nuclear factor-κB activation.

    Science.gov (United States)

    McCullough, Shaun D; Duncan, Kelly E; Swanton, Samantha M; Dailey, Lisa A; Diaz-Sanchez, David; Devlin, Robert B

    2014-09-01

    Ground-level ozone (O3) is a ubiquitous environmental air pollutant that is a potent inducer of airway inflammation and has been linked with respiratory and cardiovascular morbidity and mortality. Some studies using transformed or immortalized cells have attributed O3-mediated expression of inflammatory cytokines with activation of the canonical NF-κB pathway. In this study, we sought to characterize the O3-mediated activation of cellular signaling pathways using primary human bronchial epithelial cells obtained from a panel of donors. We demonstrate that the O3-induced expression of proinflammatory cytokines requires the activation of the epidermal growth factor receptor/MEK/ERK and MKK4/p38 mitogen-activated signaling pathways but does not appear to involve activation of canonical NF-κB signaling. In addition to providing a novel mechanistic model for the O3-mediated induction of proinflammatory cytokines, these findings highlight the importance of using primary cells over cell lines in mechanistic studies.

  13. Endovenous Laser Ablation of Varicose Veins Preserves Biological Properties of Vascular Endothelium and Modulates Proinflammatory Agent Profile More Favorably Than Classic Vein Stripping

    Directory of Open Access Journals (Sweden)

    Paweł Uruski

    2017-01-01

    Full Text Available Here we compared effect of serum from varicose patients undergoing endovenous laser ablation (EVLA and classic vein stripping (CVS on biological properties of endothelial cells and on the local and systemic profiles of proinflammatory agents. Results showed that serum from EVLA patients improved proliferation and reduced senescence and oxidative stress in the endothelial cells, as compared with the serum from CVS patients. These effects were related to a suppressed activity of TGF-β1, the level of which in the serum from the EVLA patients was decreased. Medium generated by the cells subjected to EVLA serum contained decreased amounts of ICAM-1, VCAM-1, and E-selectin and increased amount of uPA, whereas the serum itself contained decreased concentrations of ICAM-1, E-selectin, and P-selectin and increased concentrations of uPA, PAI-1, and TFPI. Both EVLA and CVS resulted in diversified patients’ reaction with respect to a direction of postprocedure changes in proinflammatory factors’ serum level. Analysis of proportions showed that the groups differed remarkably in case of ICAM-1 and ET-1, the level of which declined in a higher fraction of patients treated endovenously. Our findings indicate that EVLA preserves better than CVS the functionality of vascular endothelium and modulates better both local and systemic profile of proinflammatory mediators.

  14. Endovenous Laser Ablation of Varicose Veins Preserves Biological Properties of Vascular Endothelium and Modulates Proinflammatory Agent Profile More Favorably Than Classic Vein Stripping

    Science.gov (United States)

    Uruski, Paweł; Aniukiewicz, Krzysztof; Mikuła-Pietrasik, Justyna; Sosińska, Patrycja; Tykarski, Andrzej; Krasiński, Zbigniew

    2017-01-01

    Here we compared effect of serum from varicose patients undergoing endovenous laser ablation (EVLA) and classic vein stripping (CVS) on biological properties of endothelial cells and on the local and systemic profiles of proinflammatory agents. Results showed that serum from EVLA patients improved proliferation and reduced senescence and oxidative stress in the endothelial cells, as compared with the serum from CVS patients. These effects were related to a suppressed activity of TGF-β1, the level of which in the serum from the EVLA patients was decreased. Medium generated by the cells subjected to EVLA serum contained decreased amounts of ICAM-1, VCAM-1, and E-selectin and increased amount of uPA, whereas the serum itself contained decreased concentrations of ICAM-1, E-selectin, and P-selectin and increased concentrations of uPA, PAI-1, and TFPI. Both EVLA and CVS resulted in diversified patients' reaction with respect to a direction of postprocedure changes in proinflammatory factors' serum level. Analysis of proportions showed that the groups differed remarkably in case of ICAM-1 and ET-1, the level of which declined in a higher fraction of patients treated endovenously. Our findings indicate that EVLA preserves better than CVS the functionality of vascular endothelium and modulates better both local and systemic profile of proinflammatory mediators. PMID:28316983

  15. Ozone oxidative postconditioning ameliorates joint damage and decreases pro-inflammatory cytokine levels and oxidative stress in PG/PS-induced arthritis in rats.

    Science.gov (United States)

    Vaillant, Jaqueline Dranguet; Fraga, Angela; Díaz, María Teresa; Mallok, A; Viebahn-Hänsler, Renate; Fahmy, Ziad; Barberá, Ariana; Delgado, Liván; Menéndez, Silvia; Fernández, Olga Sonia León

    2013-08-15

    Rheumatoid Arthritis (RA) is the most prevalent chronic condition present in ~1% of the adult population. Many pro-inflammatory mediators are increased in RA, including Reactive Oxygen Species such as nitric oxide NO, pro-inflammatory cytokines as tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β) and other molecules. Ozone oxidative postconditioning has regulatory effects on some pathological targets associated with RA. Thus, the aim of this study was to investigate the efficacy of ozone therapy in PG/PS-induced arthritis in rats in point of joints inflammation and morphology. Moreover, cytokines, nitric oxide and oxidative stress levels in spleen homogenates were evaluated. Ozone treatment ameliorated joint damage, reduced TNF-α concentrations as well as TNF-α and IL-1β mRNA levels. Besides, cellular redox balance, nitric oxide and fructolysine levels were reestablished after ozone oxidative postconditioning. It was concluded that pleiotropic ozone's effects clarify its therapeutic efficacy in RA. Decreasing inflammation and joint injury, reduction of pro-inflammatory cytokines, TNF-α and IL-1β transcripts and re-establishment of cellular redox balance after ozone treatment were demonstrated.

  16. Crosstalk between androgen and pro-inflammatory signaling remodels androgen receptor and NF-κB cistrome to reprogram the prostate cancer cell transcriptome

    Science.gov (United States)

    Malinen, Marjo; Niskanen, Einari A.; Kaikkonen, Minna U.; Palvimo, Jorma J.

    2017-01-01

    Inflammatory processes and androgen signaling are critical for the growth of prostate cancer (PC), the most common cancer among males in Western countries. To understand the importance of potential interplay between pro-inflammatory and androgen signaling for gene regulation, we have interrogated the crosstalk between androgen receptor (AR) and NF-κB, a key transcriptional mediator of inflammatory responses, by utilizing genome-wide chromatin immunoprecipitation sequencing and global run-on sequencing in PC cells. Co-stimulation of LNCaP cells with androgen and pro-inflammatory cytokine TNFα invoked a transcriptome which was very distinct from that induced by either stimulation alone. The altered transcriptome that included gene programs linked to cell migration and invasiveness was orchestrated by significant remodeling of NF-κB and AR cistrome and enhancer landscape. Although androgen multiplied the NF-κB cistrome and TNFα restrained the AR cistrome, there was no general reciprocal tethering of the AR to the NF-κB on chromatin. Instead, redistribution of FOXA1, PIAS1 and PIAS2 contributed to the exposure of latent NF-κB chromatin-binding sites and masking of AR chromatin-binding sites. Taken together, concomitant androgen and pro-inflammatory signaling significantly remodels especially the NF-κB cistrome, reprogramming the PC cell transcriptome in fashion that may contribute to the progression of PC. PMID:27672034

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

    Science.gov (United States)

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

    2009-02-05

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

  18. INDICATORS OF DYNAMICAL PROINFLAMMATORY CYTOKINES IN WOMEN USING INTRAUTERINE CONTRACEPTIVES

    Directory of Open Access Journals (Sweden)

    Umida Yusupova

    2015-06-01

    Full Text Available Birth rate regulation is a major problem of modern medicine. Unfortunately, frequency of artificial abortions is still high not only in developing, but also in developed countries. Abortion results in severe gynecologic and endocrine complications in the woman’s body (Alieva, 2001.Use of intrauterine devices (IUDs is a most effective method of contraception. A great number of studies in the field of utilization and possible complications of IUDs revealed the occurrence of inflammatory diseases of small pelvis organs (IDSPO.With this in mind, we studied the data obtained from 77 women using copper IUDs in maternity facility №2 of the city of Andizhan (Uzbekistan. Duration of patients’ follow-up ranged 40 days to 6 months. Women did not have contraindications for IUDs according to WHO medical eligibility criteria. Blood was a material for study; it was taken in 40 days, 3 and 6 months following IUD insertion. After insertion of copper IUDs to women, a cytokine cascade was studied in dynamics. The serum content of IL-1, IL-6 and concentration of TNFα was measured in all patients according to the instruction attached to immunoenzymatic analyzer "АТ-858" manufactured in China. The minimum concentration of TNFα reliably identified in this test system made 4 pg/ml.During the study, the women of the test group showed increased proinflammatory cytokines. The further study of vaginal smears confirmed development of bacterial vaginoses in them that suggests a relation of complications due to IUDs with imbalance of the cytokine cascade.Elevated serum concentration of cytokines was revealed in women with IUDs already on the first days of their application.Sharp increase in IL-1 on days 40 and 90 after insertion of IUDs is associated with presence of complications in the form of expulsions and possible development of inflammatory diseases of small pelvis organs.

  19. The Role of Proinflammatory Cytokine Interleukin-18 in Radiation Injury.

    Science.gov (United States)

    Xiao, Mang

    2016-08-01

    Massive radiation-induced inflammatory factors released from injured cells may cause innate and acquired immune reactions that can further result in stress response signal activity-induced local and systemic damage. IL-1 family members IL-1β, IL-18, and IL-33 play key roles in inflammatory and immune responses and have been recognized to have significant influences on the pathogenesis of diseases. IL-1β, IL-18, and IL-33 share similarities of cytokine biology, but differences exist in signaling pathways. A key component of the inflammatory reaction is the inflammasome, which is a caspase-1-containing multiprotein oligomer. Pathological stimuli such as radiation can induce inflammasome and caspase-1 activation, and subsequently cause maturation (activation) of pro-forms of IL-1 and IL-18 upon caspase-1 cleavage. This caspase-1 dependent and IL-1 and IL-18 associated cell damage is defined as pyroptosis. Activated IL-1 and IL-18 as proinflammatory cytokines drive pathology at different immune and inflammatory disorders through Toll-like receptor (TLR) signaling. While the mechanisms of IL-1β-induced pathophysiology of diseases have been well studied, IL-18 has received less attention. The author recently reported that gamma radiation highly increased IL-1β, IL-18 and IL-33 expression in mouse thymus, spleen and/or bone marrow cells; also circulating IL-18 can be used as a radiation biomarker to track radiation injury in mice, minipigs, and nonhuman primates. This mini-review focuses on the role of IL-18 in response to gamma radiation-induced injury.

  20. Intercultural Mediation

    OpenAIRE

    Dragos Marian Radulescu; Denisa Mitrut

    2012-01-01

    The Intercultural Mediator facilitates exchanges between people of different socio-cultural backgrounds and acts as a bridge between immigrants and national and local associations, health organizations, services and offices in order to foster integration of every single individual. As the use mediation increases, mediators are more likely to be involved in cross-cultural mediation, but only the best mediators have the opportunity to mediate cross border business disputes or international poli...

  1. l-arginine and l-NMMA for assessing cerebral endothelial dysfunction in ischaemic cerebrovascular disease: A systematic review.

    Science.gov (United States)

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

    2017-01-01

    Endothelial dysfunction (ED), in particular cerebral ED, may be an essential biomarker for ischaemic cerebrovascular disease. However, there is no consensus on methods to best estimate cerebral ED. In this systematic review, we evaluate the use of l-arginine and N(G) -monomethyl-l-arginine (l-NMMA) for assessment of cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was done. We included studies investigating cerebrovascular response to l-arginine or l-NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular disease. Seven studies (315 subjects) were eligible according to inclusion and exclusion criteria. Studies investigated the effect of age (n=2), type 2 diabetes mellitus (DM) (n=1), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (n=1), leukoaraiosis (n=1), and prior ischaemic stroke or transient ischaemic attack (TIA) (n=2) on cerebral ED. Most studies applied transcranial Doppler to quantify cerebral ED. Endothelium-dependent vasodilatation (EDV) induced by l-arginine was impaired in elderly and subjects with leukoaraiosis, but enhanced in CADASIL patients. Studies including subjects with prior ischaemic stroke or TIA reported both enhanced and impaired EDV to l-arginine. Responses to l-NMMA deviated between subjects with type 2 DM and the elderly. We found only few studies investigating cerebral endothelial responses to l-arginine and l-NMMA in subjects with vascular risk factors or ischaemic cerebrovascular disease. Inconsistencies in results were most likely due to variations in methods and included subject populations. In order to use cerebral ED as a prognostic marker, further studies are required to evaluate the association to cerebrovascular disease.

  2. Neuroimaging: biochemical principles and its application in the cerebrovascular ischemic disease.

    Directory of Open Access Journals (Sweden)

    Zenaida Milagros Hernández Díaz

    2009-07-01

    Full Text Available The knowledge of neurobiochemical principles has allowed understanding the ischemic cascade that takes place after the decrease of cerebral blood flow and the findings that are visualized in neuroimaging studies in cerebrovascular ischemic disease. The need for early diagnosis of acute events to reestablish the cerebral blood flow to reduce neurological sequels, has led to the development of advanced imaging techniques, which allows following the histochemical and morphological changes that take place within the brain in vivo, in a non-invasive way, as well as its development, extent of the cerebral damage and damaged cerebral structures. The present bibliographic review has the objective of supporting the importance of neuroimaging studies in the diagnosis of acute cerebral ischemia.

  3. Acute exercise stress reveals cerebrovascular benefits associated with moderate gains in cardiorespiratory fitness.

    Science.gov (United States)

    Brugniaux, Julien V; Marley, Christopher J; Hodson, Danielle A; New, Karl J; Bailey, Damian M

    2014-12-01

    Elevated cardiorespiratory fitness improves resting cerebral perfusion, although to what extent this is further amplified during acute exposure to exercise stress and the corresponding implications for cerebral oxygenation remain unknown. To examine this, we recruited 12 moderately active and 12 sedentary healthy males. Middle cerebral artery blood velocity (MCAv) and prefrontal cortical oxyhemoglobin (cO(2)Hb) concentration were monitored continuously at rest and throughout an incremental cycling test to exhaustion. Despite a subtle elevation in the maximal oxygen uptake (active: 52±9 ml/kg per minute versus sedentary: 33±5 ml/kg per minute, Pexercise. Collectively, these findings indicate that the long-term benefits associated with moderate increase in physical activity are not observed in the resting state and only become apparent when the cerebrovasculature is challenged by acute exertional stress. This has important clinical implications when assessing the true extent of cerebrovascular adaptation.

  4. Neurosonological examination: A non-invasive approach for the detection of cerebrovascular impairment in AD

    Directory of Open Access Journals (Sweden)

    Barbora eUrbanova

    2014-01-01

    Full Text Available There has been a growing interest in vascular impairment associated with Alzheimer’s disease (AD. This interest was stimulated by the findings of higher incidence of vascular risk factors in AD. Signs of vascular impairment were investigated notably in the field of imaging methods. Our aim was to explore ultrasonographic studies of extra- and intracranial vessels in patients with AD and mild cognitive impairment (MCI and define implications for diagnosis, treatment and prevention of the disease. The most frequently studied parameters with extracranial ultrasound are intima-media thickness in common carotid artery, carotid atherosclerosis, and total cerebral blood flow. The transcranial ultrasound concentrates mostly on flow velocities, pulsatility indices, cerebrovascular reserve capacity, cerebral microembolization. Studies suggest there is morphological and functional impairment of cerebral circulation in AD compared to healthy subjects. Ultrasound as a non-invasive method could be potentially useful in identifying individuals in a higher risk of progression of cognitive decline.

  5. Multimodal CT techniques for cerebrovascular and hemodynamic evaluation of ischemic stroke: occlusion, collaterals, and perfusion.

    Science.gov (United States)

    Jia, Baixue; Scalzo, Fabien; Agbayani, Elijah; Woolf, Graham W; Liu, Liping; Miao, Zhongrong; Liebeskind, David S

    2016-05-01

    Neuroimaging of cerebrovascular status and hemodynamics has vastly improved our understanding of stroke mechanisms and provided information for therapeutic decision-making. CT techniques are the most commonly used techniques due to wide availability, rapid acquisition and acceptable tolerance. Numerous multimodal CT techniques have been developed in the last few years. We summarize and explain the various multimodal CT acquisition techniques within three categories based on the scanning mode, namely static mode (single-phase CTA), multiple static mode (multi-phase CTA) and continuous mode (CT perfusion and dynamic CTA). Post-processing methods based on different acquisition modes are also introduced in an easy manner by focusing on the information extracted and products generated. We also describe the applications for these techniques along with their advantages and disadvantages.

  6. Cardiovascular and cerebrovascular pharmacology%心脑血管药理学

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@心脑血管药理学 文献标识码:D Cardiovascular and cerebrovascular pharmacology 024 Effect of flavones of Mukdenia rossiikoidz on cardiac infarction in rats   LI Yan1, LUO Ji-Hua2   (1. National Institutes of Pharmaceutical Research and Development, Beijing 102206, China; 2. Medical College, Beihua University, Jilin 132001, China)   AIM: To study the effect of flavones of Mukdenia ross ii koidz on cardiac infarction caused by coronary artery ligation. M ETH ODS: Coronary artery ligation. RESULTS: Flavones of Mukd enia rossiikoidz reduced the area of infarction and attenuated the change in S-T section. CONCLUSION: Flavones of M. rossiikoidz has protective effects against myocardial ischemia.   Key words: Mukdenia rossiikoidz; coronary artery

  7. Cerebrovascular response to CO/sub 2/ inhalation in unanesthetized goats

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, M.C.; Lopez de Pablo, A.L.; Dieguez, G.; Gomez, B.; Lluch, S.

    1979-02-01

    The effects on cerebral blood flow of inhalation of 9% CO/sub 2/ in air were examined in unanesthetized goats. This procedure increased mean cerebral blood flow from 118 to 185 ml/min per 100 g and was accompanied by a rise in Pco/sub 2/ from 33 to 50 mmHg and a fall in pH from 7.41 to 7.26. Administration of phentolamine, propranolol, or atropine into the internal maxillary artery did not modify the normal cerebrovascular response to CO/sub 2/ inhalation. It is concluded that blockade of vascular adrenergic of cholinergic atropine-sensitive receptors in the goat has no effect on the cerebral vasomotor response to hypercapnia.

  8. The TCM-Combined Treatment for Aphasia Due to Cerebrovascular Disorders

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To evaluate the therapeutic effects of scalp acupuncture (with the cluster needling, a long needle-retention and an intermittent manipulation) combined with the Schuell's stimulation and psychological care for treatment of aphasia due to cerebrovascular disorders. Method: 36 eligible cases of aphasia were randomly assigned into a treatment group and a control group. The scoring system for assessment of aphasia in speaking Chinese set by CMA Neurological Branch and that of BADE were adopted for grading the severity/degree of aphasia before and after the treatment. Results: The total effective rate in the treatment group was 84.21%, and that in the control group was 70.59%, with a very statistically significant difference (P<0.01). Conclusion: The combined scheme produced a better therapeutic effect.

  9. Computerized three-dimensional reconstruction reveals cerebrovascular regulatory subregions in rat brain stem.

    Science.gov (United States)

    Underwood, M D; Arango, V; Smith, R W; Bakalian, M J; Mann, J J

    1993-09-01

    Three-dimensional wireframe reconstructions were used to examine the relationship between the anatomical localization of electrode sites and the cerebrovascular response which was elicited by electrical stimulation of the dorsal raphe nucleus (DRN). Reconstructions of the rat brain and DRN were done from atlas plates and from Nissl-stained coronal sections (100-micron increments). Data points were entered and three-dimensional reconstructions were performed using commercially available software and a personal computer. Display of the entire brain yielded views which obscured visualization of the DRN. The data file was edited to reduce the number of contours without affecting the display resolution of the DRN. Selective display of the DRN and electronic rotation from the coronal to a sagittal view revealed a functional organization of the cerebral blood flow responses which was not apparent in two-dimensional coronal sections.

  10. Treatment of migraine attacks based on the interaction with the trigemino-cerebrovascular system

    DEFF Research Database (Denmark)

    Link, A.S.; Kuris, A.; Edvinsson, L.

    2008-01-01

    Primary headaches such as migraine are among the most prevalent neurological disorders, affecting up to one-fifth of the adult population. The scientific work in the last decade has unraveled much of the pathophysiological background of migraine, which is now considered to be a neurovascular...... disorder. It has been discovered that the trigemino-cerebrovascular system plays a key role in migraine headache pathophysiology by releasing the potent vasodilator calcitonin gene-related peptide (CGRP). This neuropeptide is released in parallel with the pain and its concentration correlates well...... with the intensity of the headache. The development of drugs of the triptan class has provided relief for the acute attacks but at the cost of, mainly cardiovascular, side effects. Thus, the intention to improve treatment led to the development of small CGRP receptor antagonists such as olcegepant (BIBN4096BS...

  11. Characterization of (/sup 3/H)5-hydroxytryptamine uptake within rat cerebrovascular tree

    Energy Technology Data Exchange (ETDEWEB)

    Amenta, F.; Rossi, M. de; Mione, M.C.; Geppetti, P.

    1985-06-07

    The in vitro uptake of tritiated serotonin ((/sup 3/H)5HT) was studied in a preparation of rat extracerebral arteries. The uptake of (/sup 3/H)5HT was time- and temperature-dependent and of high affinity; linear regression analysis gave a Ksub(m) value of 6.48 X 10/sup 7/ M for the specific uptake. Histoautoradiographic studies showed the highest density of silver grains at the level of the adventitial-medial border of the basilar artery. Fluoxetine inhibited the accumulation of silver grains within the adventitial-medial border in the blood vessel studied. The present data further support the view that a neuronal serotonergic system may play a role in the control of blood flow in the cerebrovascular tree.

  12. REHABILITACIÓN DEL ACCIDENTE CEREBRO-VASCULAR EN ADULTOS MAYORES

    Directory of Open Access Journals (Sweden)

    Facchín RJ

    2015-05-01

    Full Text Available Cerebrovascular disease (CVA or stroke is one of the most important problems of public health as it is the second leading cause of death worldwide according to WHO and the first permanent disability of sudden onset in patients over 65 years. It should always be considered functional recovery after stroke reflect the reparative processes in the area adjacent to peri ischemic damage. This is thought to occur early, perhaps in the first 3-4 weeks post-stroke. Then it considered the repetitive training is a critical stimulus for new functional connections within the healthy brain tissue and remaining. The begining of rehabilitation should be started as soon as the patient is clinically stable. The functional results depend on this early onset, of course considering the patient's tolerance to stress. We conclude that neuromuscular rehabilitation undertaken in early and interdisciplinary therapeutic instance is crucial for the patient affected by stroke, especially in the elderly.

  13. Microwave Tomographic Imaging of Cerebrovascular Accidents by Using High-Performance Computing

    CERN Document Server

    Tournier, P -H; Bonazzoli, M; de Buhan, M; Darbas, M; Dolean, V; Hecht, F; Jolivet, P; Kanfoud, I El; Migliaccio, C; Nataf, F; Pichot, C; Semenov, S

    2016-01-01

    The motivation of this work is the detection of cerebrovascular accidents by microwave tomographic imaging. This requires the solution of an inverse problem relying on a minimization algorithm (for example, gradient-based), where successive iterations consist in repeated solutions of a direct problem. The reconstruction algorithm is extremely computationally intensive and makes use of efficient parallel algorithms and high-performance computing. The feasibility of this type of imaging is conditioned on one hand by an accurate reconstruction of the material properties of the propagation medium and on the other hand by a considerable reduction in simulation time. Fulfilling these two requirements will enable a very rapid and accurate diagnosis. From the mathematical and numerical point of view, this means solving Maxwell's equations in time-harmonic regime by appropriate domain decomposition methods, which are naturally adapted to parallel architectures.

  14. Clinical value of dipyridamole brain perfusion imaging in the diagnosis of ischemic cerebrovascular disease

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Using dipyridamole stress test to evaluate cerebral blood flow reserve in cerebrovascular disease (CVD). Dipyridamole stress tests were performed first, the baseline SPECT images were obtained under similar conditions 2-5 days later. By visual and semiquantitative analysis, the responses of cerebral blood flow to dipyridamole were divided into the following four patterns: A: The dipyridamole SPECT showed an expanded area of hypoperfusion, Asymmetry Index(AI) and Uptake Rate(UR) were all decreased; B: Rest images was normal but new hypoperfused areas appeared on stress test with decreased Al and UR; C: Hypoperfused areas were decreased in size or disappeared after stress test with increased Al and UR; D: No changes showed in cerebral perfusion imaging patterns, and in Al and UR between stress and rest studies. Dipyridarnole brain perfusion imaging may be helpful to the diagnosis of CVD, to the decision the therapeutic plan, and to predicting the therapeutic effect.

  15. rCBF to distant areas in the acute and chronic stages of unilateral cerebrovascular disease

    Energy Technology Data Exchange (ETDEWEB)

    Onoda, Toru; Tamada, Tsutomu; Gyoten, Masayuki; Imai, Shigeki; Kajihara, Yasumasa [Kawasaki Medical School, Kurashiki, Okayama (Japan). School of Medicine; Fukuda, Atsuhiro [Kawasaki Medical School, Kurashiki, Okayama (Japan). Clinical Care Center; Miyanoki, Syo [Kobe Univ. (Japan). School of Medicine

    2002-09-01

    In 14 patients with unilateral cerebrovascular disease, regional cerebral blood flow (CBF) to distant areas in the acute and chronic stages was evaluated by SPECT with {sup 123}I-IMP. In the acute stage, rCBF in distant areas was decreased in all patients. In the chronic stage, a decrease in rCBF was observed in the contralateral cerebellar hemisphere in 50% of unilateral cerebral hemispheric lesions, in the ipsilateral thalamus in 42.9% of cerebral cortical lesions, and in the ipsilateral cortex in 57.1% of subcortical lesions. The decreased rCBF in distant areas even in the chronic stage suggested the involvement of organic changes in the pathologic condition in this stage. (author)

  16. Moyamoya Disease – a Vasculopahty and an Uncommon Cause of Recurrent Cerebrovascular Accidents

    Directory of Open Access Journals (Sweden)

    Yasmin S Hamirani

    2008-09-01

    Full Text Available

    Moyamoya disease is a very rare chronic cerebrovascular disease of unknown etiology characterized by recurrent ischemic or hemorrhagic strokes. Initially diagnosed in Japan and named after finding puff of smoke like collateral blood vessels around the occluded blood vessels of circle of Willis. With increase awareness this disease is now diagnosed more often. Medical and surgical treatment have been used to treat the disease, with surgical treatment been mostly experimental. Special attention should be given to the surgical treatment which has shown to have an edge over the medical treatment in some clinical trials especially in young patients with recurrent strokes to prevent progressive cognitive decline and to improve their quality of life. In our patient, who is a young man, the diagnosis was picked up late and when surgical evaluation was performed, it was considered to be fruitless with findings of nonviable brain tissue on MRI imaging.

  17. Proinflammatory responses in the murine brain after intranasal delivery of cholera toxin: implications for the use of AB toxins as adjuvants in intranasal vaccines.

    Science.gov (United States)

    Armstrong, Michelle E; Lavelle, Ed C; Loscher, Christine E; Lynch, Marina A; Mills, Kingston H G

    2005-11-01

    Intranasal delivery of vaccines provides an attractive alternative to parenteral delivery, but it requires appropriate mucosal adjuvants. Cholera toxin (CT) is a powerful mucosal adjuvant, but it can undergo retrograde transport to the brain via the olfactory system after intranasal delivery. We demonstrate that intranasal delivery of CT increases the expression of interleukin-1 beta , cyclooxygenase-2, and chemokine messenger RNA in the murine hypothalamus, whereas parenterally delivered CT has little effect. Our findings suggest that CT can induce proinflammatory mediators in the brain when it is administered intranasally but not parenterally, and they raise concerns about the use of AB toxins as adjuvants in intranasal vaccines.

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

    Science.gov (United States)

    Barone, Frank C; Gustafson, Deborah; Crystal, Howard A; Moreno, Herman; Adamski, Mateusz G; Arai, Ken; Baird, Alison E; Balucani, Clotilde; Brickman, Adam M; Cechetto, David; Gorelick, Philip; Biessels, Geert Jan; Kiliaan, Amanda; Launer, Lenore; Schneider, Julie; Sorond, Farzaneh A; Whitmer, Rachel; Wright, Clinton; Zhang, Zheng Gang

    2016-02-13

    As the human population continues to age, an increasing number of people will exhibit significant deficits in cognitive function and dementia. It is now recognized that cerebrovascular, metabolic and neurodegenerative diseases all play major roles in the evolution of cognitive impairment and dementia. Thus with our more recent recognition of these relationships and our need to understand and more positively impact on this world health problem, "The Leo and Anne Albert Charitable Trust" (Gene Pranzo, Trustee with significant support from Susan Brogan, Meeting Planner) provided generous support for this inaugural international workshop that was held from April 13-16, 2015 at the beautiful Ritz Carlton Golf Resort in North Naples, Florida. Researchers from SUNY Downstate Medical Center, Brooklyn, NY organized the event by selecting the present group of translationally inclined preclinical, clinical and population scientists focused on cerebrovascular disease (CVD) risk and its progression to vascular cognitive impairment (VCI) and dementia. Participants at the workshop addressed important issues related to aging, cognition and dementia by: (1) sharing new data, information and perspectives that intersect vascular, metabolic and neurodegenerative diseases, (2) discussing gaps in translating population risk, clinical and preclinical information to the progression of cognitive loss, and (3) debating new approaches and methods to fill these gaps that can translate into future therapeutic interventions. Participants agreed on topics for group discussion prior to the meeting and focused on specific translational goals that included promoting better understanding of dementia mechanisms, the identification of potential therapeutic targets for intervention, and discussed/debated the potential utility of diagnostic/prognostic markers. Below summarizes the new data-presentations, concepts, novel directions and specific discussion topics addressed by this international

  19. A novel distinctive cerebrovascular phenotype is associated with heterozygous Arg179 ACTA2 mutations

    Science.gov (United States)

    Munot, Pinki; Saunders, Dawn E.; Milewicz, Dianna M.; Regalado, Ellen S.; Ostergaard, John R.; Braun, Kees P.; Kerr, Timothy; Lichtenbelt, Klaske D.; Philip, Sunny; Rittey, Christopher; Jacques, Thomas S.; Cox, Timothy C.

    2012-01-01

    Mutations in the ACTA2 gene lead to diffuse and diverse vascular diseases; the Arg179His mutation is associated with an early onset severe phenotype due to global smooth muscle dysfunction. Cerebrovascular disease associated with ACTA2 mutations has been likened to moyamoya disease, but appears to have distinctive features. This study involved the analysis of neuroimaging of 13 patients with heterozygous missense mutations in ACTA2 disrupting Arg179. All patients had persistent ductus arteriosus and congenital mydriasis, and variable presentation of pulmonary hypertension, bladder and gastrointestinal problems associated with this mutation. Distinctive cerebrovascular features were dilatation of proximal internal carotid artery, occlusive disease of terminal internal carotid artery, an abnormally straight course of intracranial arteries, and absent basal ‘moyamoya’ collaterals. Patterns of brain injury supported both large and small vessel disease. Key differences from moyamoya disease were more widespread arteriopathy, the combination of arterial ectasia and stenosis and, importantly, absence of the typical basal ‘moyamoya’ collaterals. Evaluation of previously published cases suggests some of these features are also seen in the ACTA2 mutations disrupting Arg258. The observation that transition from dilated to normal/stenotic arterial calibre coincides with where the internal carotid artery changes from an elastic to muscular artery supports the hypothesis that abnormal smooth muscle cell proliferation caused by ACTA2 mutations is modulated by arterial wall components. Patients with persistent ductus arteriosus or congenital mydriasis with a label of ‘moyamoya’ should be re-evaluated to ensure the distinctive neuroimaging features of an ACTA2 mutation have not been overlooked. This diagnosis has prognostic and genetic implications, and mandates surveillance of other organ systems, in particular the aorta, to prevent life-threatening aortic dissection

  20. Cardiovascular and cerebrovascular effects in response to red bull consumption combined with mental stress.

    Science.gov (United States)

    Grasser, Erik Konrad; Dulloo, Abdul G; Montani, Jean-Pierre

    2015-01-15

    The sale of energy drinks is often accompanied by a comprehensive and intense marketing with claims of benefits during periods of mental stress. As it has been shown that Red Bull negatively impacts human hemodynamics at rest, we investigated the cardiovascular and cerebrovascular consequences when Red Bull is combined with mental stress. In a randomized cross-over study, 20 young healthy humans ingested either 355 ml of a can Red Bull or water and underwent 80 minutes after the respective drink a mental arithmetic test for 5 minutes. Continuous cardiovascular and cerebrovascular recordings were performed for 20 minutes before and up to 90 minutes after drink ingestion. Measurements included beat-to-beat blood pressure (BP), heart rate, stroke volume, and cerebral blood flow velocity. Red Bull increased systolic BP (+7 mm Hg), diastolic BP (+4 mm Hg), and heart rate (+7 beats/min), whereas water drinking had no significant effects. Cerebral blood flow velocity decreased more in response to Red Bull than to water (-9 vs -3 cm/s, p <0.005). Additional mental stress further increased both systolic BP and diastolic BP (+3 mm Hg, p <0.05) and heart rate (+13 beats/min, p <0.005) in response to Red Bull; similar increases were also observed after water ingestion. In combination, Red Bull and mental stress increased systolic BP by about 10 mm Hg, diastolic BP by 7 mm Hg, and heart rate by 20 beats/min and decreased cerebral blood flow velocity by -7 cm/s. In conclusion, the combination of Red Bull and mental stress impose a cumulative cardiovascular load and reduces cerebral blood flow even under a mental challenge.

  1. Assessment of cerebrovascular reactivity during major depression and after remission of disease

    Directory of Open Access Journals (Sweden)

    Vakilian Alireza

    2010-01-01

    Full Text Available Background: There are a growing number of studies suggesting that depression may increase the risk of stroke. Impaired autoregulation of vascular tone may contribute to a higher risk of developing cerebrovascular diseases. Cerebrovascular reactivity (CVR reflects the compensatory dilatory capacity of cerebral arterioles to a dilatory stimulus and is an important mechanism that ensures constant cerebral blood flow. There is a hypothesis that CVR is reduced in major depression, which would explain the association between depression and stroke. Objectives: The aim of this study was to investigate the effect of depression on CVR in cerebral vessels by comparing CVR during the depression phase with that during remission. Material and Methods: Using the apnea test, we assessed CVR in 16 patients with unipolar depression during disease and after remission of disease by calculating the increase in cerebral blood flow velocity after breath-holding (the apnea test. Blood flow velocities were measured by transcranial Doppler ultrasound (TCD. Results: CVR was significantly reduced in the depression phase in comparison to that in the remission phase. However, this change was not seen in all the patients. Conclusion: CVR was reduced in most of the depressed patients. The decreased CVR, as indicated by the changes in peak systolic velocity (PSV and mean flow velocity (MFV of the middle cerebral artery, in depressed patients was more marked on the right side, which could point to a vascular basis for some kinds of depression. We recommend that other studies, with larger samples, be done; future studies should assess whether the changes in the CVR varies with the severity and type of depression.

  2. Collateral blood flow in different cerebrovascular hierarchy provides endogenous protection in cerebral ischemia.

    Science.gov (United States)

    Luo, Chuanming; Liang, Fengyin; Ren, Huixia; Yao, Xiaoli; Liu, Qiang; Li, Mingyue; Qin, Dajiang; Yuan, Ti-Fei; Pei, Zhong; Su, Huanxing

    2016-11-15

    Collateral blood flow as vascular adaptions to focal cerebral ischemia is well recognized. However, few studies directly investigate the dynamics of collateral vessel recruitment in vivo and little is known about the effect of collateral blood flow in different cerebrovascular hierarchy on the neuropathology after focal ischemic stroke. Here, we report that collateral blood flow is critically involved in blood vessel compensations following regional ischemia. We occluded a pial arteriole using femtosecond laser ablating under the intact thinned skull and documented the changes of collateral flow around the surface communication network and between the surface communication network and subsurface microcirculation network using in vivo two photon microscopy imaging. Occlusion of the pial arteriole apparently increased the diameter and collateral blood flow of its leptomeningeal anastomoses, which significantly reduced the cortical infarction size. This result suggests that the collateral flow via surface communicating network connected with leptomeningeal anastomoses could greatly impact on the extent of infarction. We then further occluded the target pial arteriole and all of its leptomeningeal anastomoses. Notably, this type of occlusion led to reversals of blood flow in the penetrating arterioles mainly proximal to the occluded pial arteriole in a direction from the subsurface microcirculation network to surface arterioles. Interesting, the cell death in the area of ischemic penumbra was accelerated when we performed occlusion to cease the reversed blood flow in those penetrating arterioles, suggesting that the collateral blood flow from subsurface microcirculation network exerts protective roles in delaying cell death in the ischemic penumbra. In conclusion, we provide the first experimental evidence that collateral blood vessels at different cerebrovascular hierarchy are endogenously compensatory mechanisms in brain ischemia. This article is protected by

  3. LIPOMA CEREBRAL EN CUERPO CALLOSO: HALLAZGO INCIDENTAL EN PACIENTE CON EVENTO CEREBROVASCULAR

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    Gloria Cárcamo-Portillo

    2016-07-01

    Full Text Available Los lipomas intracraneales son lesiones infrecuentes y benignas que representan el 0,03 al 0,08% de todas las masas intracraneales. Estos se encuentran relacionados a un defecto de la línea media debido a un mal cierre del tubo neural; lo que conlleva a una mala diferenciación y una persistencia anormal de la meninge primitiva con posterior diferenciación al tejido adiposo. La mitad de los casos permanecen asintomáticos y son diagnosticados como un hallazgo incidental en los estudios imagenológicos. Sin embargo, otros casos se asocian a sintomatología neurológica como retraso psicomotor, cefalea, epilepsia y parálisis cerebral. Se presenta el caso de una paciente de 46 años de edad, con antecedentes de hipertensión arterial y diabetes mellitus tipo 2; que cursa con sintomatología de Evento Cerebrovascular Isquémico por lo que le realizan –una Tomografía Computarizada (TC y una Resonancia Magnética (RM. En el reporte se describen múltiples infartos a nivel del hemisferio cerebral izquierdo mientras que al nivel de la línea media se observó una imagen compatible con lipoma cerebral que afectaba el rostro, la rodilla y la porción anterior del cuerpo calloso. La identificación de este hallazgo fue incidental. Palabras claves: Lipoma Cerebral; Cuerpo Calloso; Resonancia Magnética; Accidente Cerebrovascular. (Fuente: DeCS BIREME.

  4. Evaluation of the relative risk of stroke in patients with hypertension using cerebrovascular hemodynamic accumulative score

    Institute of Scientific and Technical Information of China (English)

    HUANG Jiuyi; WANG Guiqing; GUO Jiping; CAO Yifeng; WANG Yan; YANG Yongju; YU Xuehai

    2007-01-01

    The relative risk(RR)of stroke in patients with hypertension was evaluated by using synthetic index of cerebrovascular hemodynamics.A total of 7,371 patients with hypertension with ages≥40 years were selected from a population-based cohort study of the risk factors for stroke.The data on the baseline investigation of risk factors,the determination of cerebrovascular hemodynamic parameters (CVHP),and stroke follow-up were analyzed.The RR of stroke in patients with hypertension was evaluated by CVHP scores.Univariate analysis indicated that hypertension,complicated by other risk factors,had significant statistical association with the onset of stroke.RRS for stroke when hypertension complicated with decrease of hemodynamic scores,heart disease,cigarette smoking and alcohol consumption were 4.93(95%CI,3.26-7.45),1.90(95%CI,1.36-2.66),1.99(95%CI,1.42-2.79)and 1.73(95%CI,1.19-2.53)respectively.In multivariate analysis,hemodynamic score,age,sex,cigarette smoking,family history of stroke and systolic blood pressure were selected by the Cox regression for inclusion in the final analysis.Among them,the RR of hemodynamic score was highest.The analysis of doseresponse relationships indicated that when the hemodynamic scores in patients with hypertension were lower than 75 points,the RR of stroke at 75,60,45,30 and 15 points were 2.85,4.43,4.54,5.40 and 9.88,respectively.The risk of stroke in patients with hypertension is closely associated with hemodynamic impairment and the hemodynamic score may be used for quantitative evaluation of relative risks of stroke.

  5. The Comparison of Continuous and Intermittent Enteral Nutrition In Cerebrovascular Patients

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    Levent Güngör

    2011-06-01

    Full Text Available OBJECTIVE: Dysphagia and malnutrition are not so rare in stroke patients, and have an unfavorable influence on recovery. Nutritional support may reduce infections, duration of hospital stay and mortality. However, there is no clear evidence about the modality of nasogastric nutrition. In this study, intermittent and continuous enteral nutrition is compared by means of pulmonary infections and gastrointestinal tolerance, among acute cerebrovascular patients. METHODS: Sixty two acute cerebrovascular patients with dysphagia were included the study. The same volume of nutrition product was infused 4 times daily to 31 patients, and continuously for 24 hours to the remaining 31. After 10 days of follow-up, the rates of pulmonary infections, diarrhea, increased gastric residual volumes, vomiting and tube occlusion were compared between two groups. RESULTS: Twenty patients developed pneumonia (32% and 8 diarrhea (13%. Mortality due to complications associated with tube feeding was 6%. Aspiration and related pneumonia was present in 11 patients in the intermittent nutrition group (35%, and in 9 patients in the continuous nutrition group (29%. The rate of pulmonary infection was not statistically different between two groups (p>0.05. Diarrhea was observed in 7 intermittently fed patients (23%, while was present only in 1 patient (3% in the continuously fed group. Diarrhea was more common in the intermittent nutrition group, just at the statistical border (p=0.05. None of the patients developed tube occlusion, vomiting and gastric retention. The rate of mortality and the interruption of feeding was not significantly different between two groups (p>0.05. CONCLUSION: Diarrhea and pulmonary infections are more prevalent with intermittent tube feeding with respect to continuous enteral nutrition, though the difference is not so conspicuous. The reason may be contamination of the equipments and the feeding solution because of frequent manipulation and

  6. Effects of hypoxia-inducible factor 1 on ischemic cerebrovascular disease

    Institute of Scientific and Technical Information of China (English)

    Yongjie Luo; Xiaoping Wang; Hongbin Sun

    2008-01-01

    Hypoxia-inducible factor I, a nuclear transcription factor, is induced by hypoxia. Hypoxia-inducible factor I, a heterodimeric DNA-binding protein, is composed of hypoxia-inducible factor 1α and hypoxia-inducible factor 1 β subunits, which are family members of the basic helix-loop-helix-PER, ARNT, SIM (PAS) protein. O2 concentration regulates hypoxia-inducible factor 1 activity via this subunit. Hypoxia-inducible factor 1α plays a major role in response to hypoxia and transcriptional activation, as well as in the target gene specificity of the DNA enhancer. Hypoxia-inducible factor 1β cannot be induced by hypoxia. This effect may be due to hypoxia-inducible factor 1 stability and activated conformation due to dimerization. Previous studies have shown that hypoxia-inducible factor 1 mRNA expression increases in the penumbra following ischemia/hypoxia. Hypoxia-inducible factor 1 plays an important role in brain tissue injury alter ischemia by affecting a series of target genes, elevating tolerance to hypoxia, and ensuring survival of neural cells. This article summarizes the structure, function, expression, regulatory mechanisms, biological effects, and significance of hypoxia-inducible factor 1 in patients with ischemic cerebrovascular disease. As a transcriptional activator, hypoxia