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

The effect of global ischemia and reperfusion on the expression of cytokine genes and cell adhesion molecules by myocardial tissues and neutrophils was studied by using the Langendorff model. Although cardiac function deteriorated after reperfusion of ischemic hearts, there was no evidence of inflammation and myocardial degeneration, which is in contrast to previous findings that neutrophil-mediated inflammation is a critical step in post-ischemic reperfusion injury in regional ischemia. Flow cytometry analysis demonstrated that the global ischemia and reperfusion did not affect the expression of adhesion molecules on neutrophils. We also examined the expression of various cytokines which are involved in inflammatory responses. Only interleukin 1 alpha was induced after the reperfusion of the ischemic hearts. These results suggest that neutrophils barely contribute to the myocardial dysfunction and IL-1 alpha may play a role in post-ischemic myocardial dysfunction during the early stage of reperfusion.
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PMID:Neutrophil-independent myocardial dysfunction during an early stage of global ischemia and reperfusion of isolated hearts. 762 55

The response to trauma begins in the immune system at the moment of injury. The loci are the wound, with activation of macrophages and production of proinflammatory mediators, and the microcirculation with activation of endothelial cells, blood elements, and a capillary leak. These processes are potentiated by ischemia and impaired oxygen delivery and by the presence of necrotic tissue, each exacerbating the inflammatory response. Hemorrhage alone may be a sufficient stimulus. Inflammation once was considered to be a host reaction to bacteria or other irritants. This concept was expanded by the discovery of autoimmune diseases, and we are now aware that some illnesses are the result of the body's response to an invader rather than the direct effect of the invader itself. The discoveries about the response to trauma described here add another dimension, showing inflammation to be a fundamental life process that begins at the molecular level at the moment of injury and that, depending on the severity of the stimulus and the effectiveness of initial treatment, may spread to include every cell, tissue, and organ in the body, for good or ill. An important part of these expanding concepts is the notion that all noxious stimuli activate the cytokine system as a final common pathway. Sepsis, hemorrhage, ischemia, ischemia-reperfusion, and soft tissue trauma all share an ability to activate macrophages and produce proinflammatory cytokines that may initiate the SIRS. Second-message compounds and effector molecules mediate the observed clinical phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The immune response to trauma. 763 53

The overall goal of this study was to compare the effects of systemic hypotension (hemorrhagic shock) versus local gut ischemia (superior mesenteric artery (SMA) occlusion) on cytokine production and bacteria/endotoxin translocation. Sham or actual SMA occlusion led to an increase in tumor necrosis factor (TNF), which was greatest at the end of the occlusion period, while the IL-6 response peaked 3 h post-SMA occlusion. The TNF and IL-6 response after hemorrhagic shock differed from that observed after SMA occlusion in that the peak response occurred later and was of lower magnitude (p < .05). Although the animals subjected to SMA occlusion had a significantly increased incidence of bacterial translocation to both the mesenteric lymph nodes and systemic organs compared to rats subjected to hemorrhagic shock, in neither group was the blood level of endotoxin elevated and there was no association between bacterial translocation and cytokine levels. These results suggest that different models of intestinal ischemia have different cytokine profiles and that the early TNF response associated with SMA occlusion model is primarily due to the laparotomy.
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PMID:Comparison of plasma cytokine levels in rats subjected to superior mesenteric artery occlusion or hemorrhagic shock. 764 38

We have previously proposed that cytokine-stimulated nitric oxide (NO) production is responsible for reversible myocardial depression in sepsis, trauma and ischemia. NO previously has been found to inhibit mitochondrial activity in other cell types. Accordingly, we sought to determine if cytokine-stimulated NO production inhibited cardiac myocyte mitochondrial activity. Treatment of neonatal rat cardiac myocytes with interleukin-beta (IL-1) resulted in the expression of mRNA for inducible NO synthase (iNOS) and stained positively for iNOS protein by immunohistochemistry. No iNOS staining was detected in untreated cells. IL-1 treatment resulted in significant nitrite levels vs control over 48 hrs (4.2 +/- 0.7 vs 0.3 +/- 0.2 nmol/1.25 x 10(5) cells, respectively) (n = 12) that was inhibited by 1mM NMA (0.3 +/- 0.2 nmoles; p < .01; n = 12). Mitochondrial activity was assessed by the MTT colorimetric assay using (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and OD 570-630. Mitochondrial activity was significantly inhibited by IL-1 vs control cells (0.436 +/- 0.01 vs 0.608 +/- 0.03) and reversed by 1mM NMA (0.549 +/- 0.03) or removal of IL-1 (0.662 +/- 0.02) (p < .01; n = 12 for each). These data strongly suggest that cytokine-stimulated NO production by cardiac myocytes results in reversible inhibition of mitochondrial activity.
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PMID:Cytokine-stimulated nitric oxide production inhibits mitochondrial activity in cardiac myocytes. 765 17

The effect of pretreatment with pentoxifylline on normothermic liver ischemia was studied in rats. This drug, a dimethylxanthine and fosfodiesterase inhibitor, improves microcirculation, decreases neutrophil activity in experimental sepsis and hemorrhagic shock, and inhibits "in vitro" cytokine production by isolated Kupffer cells. Partial liver ischemia was induced by occlusion of afferent vessels to the median and left lateral lobes for 60', followed by resection of nonischemic lobes just before reperfusion. The rats were divided in 4 groups: I (n = 6) sham operation, II (n = 6) resection of right and caudate lobes, III (n = 42) normal saline pretreatment and 60' ischemia, IV (n = 42) pentoxyfilline pretreatment (50mg/K/i.p. 2 h before clamping) and 60' ischemia. 12 animals were sacrificed 1 h and 6 h after reperfusion respectively (gr III and IV), and 20 rats were observed for a maximum of 24 h after reperfusion. Serum transaminases, LDH, CK (isoenzymes), bilirubin, and total bile acids were determined in each animal. A sample of the left lobe was taken for histological examination. Extent of necrosis 24 h after reperfusion was assessed. Bile output was measured before ischemia and during the first hour of reperfusion. Pentoxifylline pretreatment was associated with a lower rise in serum transaminases and LDH after reperfusion, but it did not modify the changes in either serum CK activity (mainly CKBB), or total bile acid concentration. A reduction of bile output was not avoided by pentoxifylline pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Liver damage due to normothermic ischemia and reperfusion in the rat. The effects of pentoxifylline pretreatment]. 766 19

The expression of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) mRNAs was significantly increased in the rat ischemic cortex following temporary occlusion of the middle cerebral artery (TMCAO) with reperfusion. Northern blot analysis demonstrated that the induction of TNF-alpha and IL-1 beta mRNAs occurred as early as 1 h after reperfusion, exhibiting a 4.6-fold increase (p < 0.05, n = 4) and 6.8-fold increase (p < 0.05, n = 4) in the ischemic cortex over control, respectively. TNF-alpha mRNA reached its peak at 3 h (8.0-fold, p < 0.05), whereas IL-1 beta mRNA reached its peak at 6 h (29.5-fold, p < 0.05). Both cytokine mRNA levels remained elevated for up to 2 d after reperfusion. In contrast to the time course of these cytokine mRNAs, c-fos and zif268 mRNAs, two early response genes, displayed a greater and earlier time-response profile. The early induction of c-fos and zif268 mRNAs in temporary brain ischemia with reperfusion suggests their roles in transcriptional regulation. The later concomitant expression of TNF-alpha and IL-1 beta suggests that these cytokines play an important role in the inflammatory response associated with focal ischemia.
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PMID:Concomitant cortical expression of TNF-alpha and IL-1 beta mRNAs follows early response gene expression in transient focal ischemia. 770 1

The pathologic picture in ischemic tissue injury shares features with the inflammatory response, including production of proinflammatory cytokines. Hypoxia-mediated induction of interleukin-6 (IL-6), a cytokine with anti-inflammatory properties, could set in motion mechanisms limiting inflammation in ischemia. Exposure of cultured endothelial cells (ECs) to H (pO2 approximately 12-16 torr) increased transcription of IL-6, elevated levels of IL-6 mRNA, and induced elaboration of IL-6 antigen in a time-dependent manner. Exposure of mice to hypoxia increased IL-6 transcripts in the lung, and immunostaining revealed a striking increase in IL-6 antigen in pulmonary vasculature. Transfection of ECs with deletion chimeric IL-6 promoter-chloramphenicol acetyl-transferase (CAT) constructs showed hypoxia-mediated 9-11-fold induction with -1200/+13, -596/+13, and -225/+13 but no induction with -111/+13. Electrophoretic mobility shift assays (EMSAs) using -225/-111 as the labeled probe demonstrated enhanced binding activity in nuclear extracts of hypoxic ECs and lung; the appearance of the gel shift band was prevented by excess unlabeled probe (-225/-111), and hypoxia-mediated enhancement of the band was blocked by a probe corresponding to the nuclear factor (NF)-IL-6 site (-158/-145). The hypoxia-enhanced band on EMSA displayed a supershift with antibody to CCAAT-enhancer-binding protein beta (C/EBP-beta), but antibody to C/EBP-alpha or -delta was without effect. Transfection of ECs with a construct comprising thymidine kinase promoter, -225/-111 in either the 5' to 3' to 5' orientation, and the reporter CAT showed this region to be an enhancer (approximately 8-fold) under hypoxia. EMSA with the NF-IL-6 probe revealed a prominent induction of binding activity with nuclear extracts from hypoxic ECs and whole lung. Constructs with -158/-145 and the CAT reporter gene showed induction when transfected into hypoxic ECs, whereas a similar construct with the NF-IL-6 motif mutationally inactivated failed to display hypoxia-induced expression. Furthermore, the tumor necrosis factor (TNF) gene, whose product contributes to ischemic pathology and contains a putative regulatory NF-IL-6 site, demonstrated enhanced binding activity for its NF-IL-6 motif and induction of TNF mRNA based on analysis of hypoxic lung. These data indicate that hypoxia induces expression of IL-6, most likely a result of hypoxic activation at the NF-IL-6 site, and suggest that other genes with regulatory NF-IL-6 sites may also be induced by a similar mechanism.
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PMID:Induction of interleukin 6 (IL-6) by hypoxia in vascular cells. Central role of the binding site for nuclear factor-IL-6. 774 84

The expression of interleukin-6 (IL-6) mRNA in the focal ischemic rat cortex was studied by means of Northern hybridization. IL-6 mRNA was induced after permanent occlusion of the middle cerebral artery, reached a significant level at 3 h, and peaked at 12 h, i.e., approximately 10-fold increase in the ischemic zone compared with the nonischemic cortex or sham-operated controls. The increased IL-6 mRNA was elevated for at least 24 h. Low levels of IL-6 mRNA were detected in sham-operated rats or in the contralateral nonischemic cortex. The expression of c-fos and zif268 mRNAs, two early response genes, was rapid (increased by 1 h postischemia) and transient (returned to basal levels by 24 and 12 h, respectively), clearly having different kinetic patterns from that of IL-6 mRNA. The early response kinetic pattern of c-fos and zif268 mRNAs in focal ischemia suggests their transcriptional regulatory roles in response to ischemic insult, while the delayed induction pattern of IL-6 mRNA suggests a role for this pleiotropic cytokine in the inflammatory response to the focal ischemic damage of the brain.
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PMID:Expression of interleukin-6, c-fos, and zif268 mRNAs in rat ischemic cortex. 779 34

Although chronic rejection remains the most crucial cause of organ graft loss over the long term, its etiology is not well defined. Early injury to graft endothelial cells caused by alloantigen-independent factors, such as ischemia or reperfusion, as well as alloantigen-dependent events, such as acute rejection, have been implicated. Macrophages and their products, peptide growth factors and adhesion molecules are all thought to play an important role in this process via the cytokine-adhesion molecule cascade. Although new immunosuppressive agents, including RS61443 or rapamycin, may be effective in preventing antigen-driven components of this condition, risk factors for initial non-immune injury must also be considered and, if possible, countered.
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PMID:Chronic graft rejection. 782 33

While the role of cytokines in mediating injury during hind limb skeletal muscle ischemia followed by reperfusion has recently been described, the role of cytokines in myocardial infarction and ischemia/reperfusion have remained relatively unexplored. We hypothesize that cytokines play an important role in the regulation of postischemic myocardial inflammation. This study reports the temporal sequence of proinflammatory cytokine gene expression in postischemic/reperfused myocardium and localizes interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha)-protein by immunostaining. Rats were subjected to either permanent left anterior descending (LAD) occlusion or to 35 minutes of LAD occlusion followed by reperfusion and sacrificed up to 7 days later. Rat-specific oligonucleotide probes were used to semiquantitatively assess the relative expression of mRNA for TNF-alpha, IL-1 beta, IL-2, IL-6, interferon-gamma (IFN-gamma), and transforming growth factor-beta 1 (TGF-beta 1) utilizing the reverse transcriptase-polymerase chain reaction amplification technique. Increased cardiac mRNA levels for all cytokines except IL-6 and IFN-gamma were measurable within 15 to 30 minutes of LAD occlusion and increased levels were generally sustained for 3 hours. During early reperfusion, mRNA levels for IL-6 and TGF-beta 1 were significantly reduced compared with permanent LAD occlusion. In both groups, cytokine mRNA levels all returned to baseline levels at 24 hours, while IL-1 beta, TNF-alpha, and TGF-beta 1 mRNA levels again rose significantly at 7 days only in animals with permanent LAD occlusion. Immunostaining for IL-1 beta and TNF-alpha protein revealed two patterns of reactivity: 1) microvascular staining for both IL-1 beta and TNF-alpha protein only in postischemic reperfused myocardium in early post-reperfusion time points; and 2) staining of infiltrating macrophages in healing infarct zones which was most prominent at 7 days after permanent LAD occlusion. These results provide evidence for local expression of cytokine mRNA in postischemic myocardium and suggest that regulation of local cytokine release is altered during the postischemic period.
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PMID:Cytokine mRNA expression in postischemic/reperfused myocardium. 785 52


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