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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent evidence suggests that neurons and glia can synthesize and secrete cytokines, which play critical roles in maintaining homeostasis in the central nervous system (CNS) by mediating the interaction between cells via autocrine or paracrine mechanisms. Circulating cytokines and soluble receptors also regulate neuronal function via endocrine mechanisms. Disturbance of the cytokine-mediated interaction between cells may lead to neuronal dysfunction and/or cell death and contribute to the pathogenesis of the CNS diseases (e.g., ischemia, Alzheimer's disease and HIV encephalopathy). Defining the molecular pathways of cytokine dysregulation and neurotoxicity may help to elucidate potential therapeutic interventions for many devastating CNS diseases.
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PMID:Cytokines in the central nervous system: regulatory roles in neuronal function, cell death and repair. 864 60

Our previous in vivo studies have implicated phospholipase A2 activation and platelet-activating factor (PAF) production as an important mediator of neutrophil (PMN) priming after mesenteric ischemia/reperfusion. Furthermore, our in vitro studies demonstrate that PAF priming of PMN enhances PMN respiratory burst and increases PMN adherence to human umbilical vein endothelial cell cultures (HUVEC). Others have shown that cytokine stimulated HUVEC can activate quiescent PMNs to provoke endothelial cell (EC) monolayer disruption via EC detachment by a noncytolytic PMN protease mechanism. Hypoxia and reoxygenation (H/R) of HUVEC can also directly stimulate PAF production. Consequently, we hypothesized that HUVEC H/R can activate quiescent PMNs to disrupt the EC monolayer (detachment) through a PAF mediated mechanism. HUVEC were labeled with 51 chromium (51Cr) and subjected to 45 min hypoxia (95% N2/5% CO2). PMNs freshly isolated by Percoll gradient centrifugation were added to HUVEC and reoxygenated for 120 min. Additionally, H/R HUVEC with PMN pretreated with WEB2170 (a PAF receptor antagonist) was compared to control (non-H/R HUVEC incubated with PMNs). Wells were washed at end incubation, and adherent ECs counted. Detachment = [total counts - sample counts]/total counts X 100. H/R HUVEC plus PMN provoked a 29.3 +/- 1.6% detachment of EC compared to 9.3 +/- 2.9% detachment in control (non-H/R HUVEC with PMNs). In contrast, H/R HUVEC with PMNs preincubated with WEB2170 had 9.9 +/- 3.8% detachment of EC. In summary, HUVEC H/R activated quiescent PMNs to disrupt an EC monolayer (detachment) via a PAF mechanism.
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PMID:Hypoxia/reoxygenation of human endothelium activates PMNs to detach endothelial cells via a PAF mechanism. 865 25

Intestinal ischemia-reperfusion (I/R) causes local and distant tissue injury via neutrophil (PMN) activation and adhesion. Endothelial cell adhesion molecules (E-selectin, ICAM-1) mediate the adhesion and transmigration of PMN in the microcirculation. Expression of these receptors is influenced by cytokines. To determine the physiologic concentrations of two specific cytokines involved in I/R, tumor necrosis factor (TNF) and interleukin-1 (IL-1), human intestinal segments were exposed to 30 min of ischemia followed by reperfusion. Venous effluent samples were obtained; enzyme immunoassays measured maximum concentrations of TNF (30.5 +/ 1.0 pg/ml) and IL-1 (59.0 +/- 6.0 pg/ml). Cultured human endothelial cells were then exposed to physiologic concentrations of human recombinant TNF (10 pg/ml) and IL-1 (10 pg/ml), individually and in combination. Flow cytometric analysis of receptor expression demonstrated upregulation of E-selectin as early as 2 hr (P < 0.05) with maximum effects at 4 hr. At 4 hr, E-selectin expression (% shift from baseline) was greater with TNF and IL-1 combined (50.9 +/- 2.9, P < 0.01) than with either cytokine alone (TNF 34.6 +/- 4.0; IL-1 23.5 +/- 4.0, P < 0.01). ICAM-1 receptor expression began at 4 hr with maximum effects at 24 hr. ICAM-1 expression after TNF and IL-1 exposure (15.4 +/- 1.3, P < 0.001) was also greater than TNF (10.9 +/- 0.3, P < 0.01) or IL-1 (3.1 +/- 1.5) alone. TNF and IL-1 are present in venous effluent in concentrations capable of increasing PMN adhesion in the microcirculation. These findings support a role for these cytokines in local and distant organ injury from I/R. Since combined effects are greater than either cytokine alone, antagonism of both TNF and IL-1 may be required for a therapeutic benefit in clinical applications.
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PMID:Physiologic concentrations of TNFalpha and IL-1beta released from reperfused human intestine upregulate E-selectin and ICAM-1. 866 Dec 21

Animal studies suggest that acute phase reactant cytokines and polymorphonuclear leukocytes (PMN) may play a critical role in ischemia-reperfusion injury. To evaluate whether similar mechanisms are operative in human liver, six cirrhotic and nine noncirrhotic patients undergoing right hepatectomy were randomized for utilization of hepatic vascular exclusion (HVE) as a model of ischemia-reperfusion injury. Portal and systemic levels of acute reactant cytokines (interleukin 6 [IL-6], interleukin 1 [IL-1], tumor necrosis factor alpha [TNF-alpha]) and neutrophil adhesion in serial liver biopsy specimens were studied. Correlations among mediators, leukocyte adhesion, and markers of liver injury were also evaluated. Hepatic vascular exclusion resulted in substantial and reproducible changes in portal and arterial IL-6 levels in both cirrhotic and noncirrhotic patients. Portal and systemic cytokine levels were comparable in most instances, whereas levels were usually higher in cirrhotic patients than in noncirrhotic patients. Negative correlations were found between IL-6 levels at the time of reperfusion and later TNF-alpha levels. IL-6 levels correlated negatively with numerous markers of hepatocellular injury and the number of postoperative complications. Hepatic vascular exclusion increased neutrophils adhesion after reperfusion in cirrhotic patients but not in noncirrhotic patients. In cirrhotic patients, the degree of leukocyte adhesion after reperfusion correlated with several postoperative markers of liver injury. This study in humans shows that acute reactant cytokines are released during liver ischemia and, interestingly, that IL-6 levels strongly correlate with clinical and laboratory measures of injury. Further studies to evaluate possible causal relationship with hepatic injury are warranted, with emphasis on the role of IL-6 and PMN adhesion.
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PMID:Acute reactant cytokines and neutrophil adhesion after warm ischemia in cirrhotic and noncirrhotic human livers. 867 64

Although platelet-activating factor (PAF) is implicated as an important mediator in the pathogenesis of hepatic ischemia-reperfusion (IR) injury, the precise mechanism of its action has not been studied. We examined the hypothesis that PAF may influence neutrophils by promoting the production of tumor necrosis factor alpha (TNF-alpha) and cytokine-induced neutrophil chemoattractant (CINC), a member of the interleukin-8 (IL-8) family, and may be associated with liver and lung injury during the early phase of reperfusion after total hepatic ischemia. Rats pretreated with a specific PAF receptor antagonist exhibited suppression of the increase in plasma TNF-alpha and CINC levels, as well as the priming of peripheral neutrophils for superoxide production after reperfusion when compared with animals pretreated with physiological saline. These effects resulted in a reduction of plasma liver enzymes and of hepatic and pulmonary neutrophil sequestration, as well as an increased survival rate. There was a strong correlation between the time course of CINC release and hepatic or pulmonary neutrophil sequestration. We concluded that PAF activates neutrophils, either directly or by promoting the production of TNF-alpha and CINC, and is involved in hepatic IR injury.
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PMID:Involvement of platelet-activating factor in cytokine production and neutrophil activation after hepatic ischemia-reperfusion. 867 90

We investigated whether anticoagulation would diminish ischemia-reperfusion injury of the liver. Liver ischemia was induced in rats by occluding the portal vein for 30 min. Anticoagulant was injected intravenously 10 min before occlusion. Serum concentrations of cytokine-induced neutrophil chemoattractant (CINC) in untreated rats increased following reperfusion, reaching a peak at 6 hr, then decreasing gradually to control levels by 24 hr. CINC levels in rats pretreated with heparin (50 units/kg), AT-III (250 units/kg), or DEGR-Xa (10 mg/kg) peaked at 3 hr after reperfusion and declined to baseline within 12 hr; peak CINC values were significantly lower than in untreated control rats. Expression of CINC mRNA in liver tissue paralleled the CINC serum levels. Both myeloperoxidase activity and the number of neutrophils in the liver were decreased in the anticoagulant groups. In addition, significant correlations were observed between the maximum values of AST, ALT, and LDH versus the peak CINC levels following ischemia-reperfusion. These results indicate that the release of CINC after ischemia-reperfusion of the liver is mediated by activation of coagulation within the hepatic microcirculation.
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PMID:Anticoagulant pretreatment attenuates production of cytokine-induced neutrophil chemoattractant following ischemia-reperfusion of rat liver. 868 28

Granulocytes play a significant role in vascular diseases. The mechanisms of neutrophil-mediated vascular injury include their increased endothelial adhesion and activation with release of inflammatory mediators. Pentoxifylline (PTX) has a well-demonstrated ability to act on the activated neutrophils. It increases chemotaxis and decreases their adherence to endothelial cells, oxidative burst, and enzyme release. In this preliminary study, we investigated the effects of PTX on ischemia-induced changes in polymorphonuclear neutrophils (PMN) activation and cytokine release. A double-blind, randomized, placebo-controlled trial was carried out in 14 patients (age range 46-86 years) suffering from critical ischemia, as defined by the European Consensus Document, or subacute ischemia due to occlusive arterial disease of the lower limb. Femoral and antecubital venous blood samples on the side of the ischemic leg were obtained from patients immediately before (TO) and after infusion (T24) of PTX or placebo. PMN activation was evaluated by study of cell migration, beta 2 integrin expression (CD11b/ CD18), oxidative burst, and elastase release. Inflammation proteins were analyzed, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), C-reactive protein (CRP), and fibrinogen. Before treatment, our results demonstrate an important activation in both femoral and antecubital venous blood. PMN activation markers, cytokine release, and other inflammation proteins were significantly increased compared with normal subjects. In the experimental group there was no significant difference between femoral and antecubital venous blood. Six patients received PTX infusion and seven patients were in the placebo group. The effect of PTX was evaluated after 24 h of treatment (1,200 mg). In the PTX group the following variables were improved compared with the placebo group: CD11b expression on PMNs, elastase released from PMNs, fibrinogen, CRP, TNF-alpha, and IL6 in plasma. These preliminary results should be interpreted with caution because of the small sample size. Further trials may contribute to more complete understanding.
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PMID:Leukocyte activation study during occlusive arterial disease of the lower limb: effect of pentoxifylline infusion. 869 73

Renal transplantation is currently standard therapy for end-stage kidney disease for children. Despite the considerable improvement in short-term results, the expected allograft half-life has remained the same. This is due to chronic rejection/late graft dysfunction which has proved resistant to therapeutic attempts. During the last few years the multifactorial pathogenesis of chronic renal allograft rejection has been clarified to some extent. Early injury by immunological and non-immunological mechanisms is followed by vascular remodelling due to repetitive cycles of cytokine release, upregulation of growth factors, and vascular smooth muscle cell proliferation. This leads to typical concentric arteriosclerosis and ischemia. Secondary kidney-specific mechanisms are initiated by the reduction in functioning renal mass and lead to gradual progression of chronic rejection. There is no single optimal therapy. Several attempts to influence the pathophysiological cascade have been promising. Attention should be focused on minimizing early immunological/non-immunological injury in order to attenuate future progression of chronic rejection. A significant prolongation of allograft half-life may be achieved during the next decade with the introduction of new therapeutic agents and comprehensive approach to treatment. This would be especially beneficial for pediatric recipients, reducing the need for retransplantation in adulthood.
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PMID:Chronic rejection and late renal allograft dysfunction. 870 19

The effects of transient global ischemia using bilateral carotid artery occlusion on regional cytokine levels in gerbil brain were investigated using enzyme-linked immunoassay techniques. Brain concentrations of interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) were increased during the early recirculation period ( < 6 h) after 10 min of ischemia, with lesser degrees of elevation following only 5 min of ischemia. TNF-alpha levels in the hippocampus and striatum were significantly increased as early as 1 h after recirculation, declining sharply to control levels by 12 h, then transiently increasing at 24 h. Elevated levels of IL-1 beta and IL-6 were not seen until 3-6 h post-occlusion. No significant increases in cytokine concentrations were observed in the cerebellum or thalamus. These results suggest that regionally selective increases in cytokines may be involved in the pathophysiological changes in hippocampus and striatum following transient cerebral ischemia.
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PMID:Early increases in TNF-alpha, IL-6 and IL-1 beta levels following transient cerebral ischemia in gerbil brain. 871 Jan 73

A certain number of elements suggest a link between arteriosclerosis and osteoporosis. Generally, osteoporosis in women is considered to result from altered secretion of sexual hormones after menopause and in elderly subjects from hyperparathyroidism secondary to calcium and vitamin D deficiency. As for the heart, the brain, the kidney or muscle, bone tissue could also be altered by vascular aging and arteriosclerosis. Large epidemiological studies have demonstrated a relationship between bone mineral density, measured by monophotonic absorptiometry and mortality due to cerebral vascular events. Several hypotheses have been proposed to explain this relationship including lower endogenous estrogen levels and arteriosclerosis of the renal vessels favoring perturbed vitamin D metabolism. Arteriosclerosis could also have a direct effect on bone tissue via an ischemic mechanism. The pathophysiolojical mechanisms are not fully understood, but could involve hormone and cytokine-dependent bone remodeling and the complementary actions of bone tissue and the hematopoietic bone marrow functioning as an unit. Further epidemiological studies would be useful to confirm the relationship between arteriosclerosis and osteoporosis. The efficacy of vasodilator drugs on osteoporosis could be tested and histology and immunochemical studies could help in our understanding of the effect of ischemia on bone metabolism.
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PMID:[Arteriosclerosis and osteoporosis]. 874 17


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