Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intestinal ischemia/reperfusion (I/R) may induce bacterial translocation (BT). Glutamine (GLN)-enriched nutrition decreases BT. However, little is known about the effect of glucan (GL) in BT. This study investigated the combined effect of GL/GLN on BT, intestinal damage, and portal blood cytokines in animals under I/R. Four groups of 10 rats each were subjected to 60 min of intestinal ischemia and 120 min of reperfusion. The control group (group 1) received only rat food/water, group 2 received glutamine via gavage, group 3 received subcutaneuos soluble (1, 3)-d-glucan, and group 4 received GL + GLN. A sham group (group 5) served as a normal control. Bacterial cultures of ileum, mesenteric lymph nodes (MLN), liver and lung biopsies, histological changes of ileum, and serum cytokines variables were examined after I/R. Data were analyzed by analysis of variance (ANOVA) and the Newman-Keuls test. Results showed that GLN, GL, and GL/GLN significantly reduced BT to MLN, liver, and lung. BT was more attenuated after GL treatment than GLN (P < .05). Rats treated with both GL and GLN exhibited lower bacterial colony counts than the ones treated only with GLN or GL. Severe mucosal damage on histological findings was shown in group 1, but these findings were significantly ameliorated (P < .05) in groups 3 and 4. Tumor necrosis factor (TNF)-a and interleukin (IL)-6 levels in portal serum were significantly reduced and IL-10 was increased by GL and GLN treatment. In conclusion, the use of GL was more effective than GLN in reducing BT, intestinal damage, and cytokine levels after I/R. Additionally, the combination of GL and GLN improved results.
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PMID:Glucan and glutamine reduce bacterial translocation in rats subjected to intestinal ischemia-reperfusion. 1654 28

Leukocyte activation, inflammatory up-regulation, and microcirculatory disruption associated with ischemia-reperfusion injury are hallmarks in the pathogenesis of acute pancreatitis (AP). NO donors ensure microvascular integrity, while glucocorticoids act as anti-inflammatory and immune modulator drugs. AP was induced by the biliopancreatic duct outlet exclusion-closed duodenal loops (BPDOE-CDLs) model. Treatment with hydrocortisone (6 mg/kg) or prednisolone (0.5 mg/kg) alone or together with DETA-NO (0.5 mg/kg) was done (a)1 hr pre or (b)1 hr post, or (c) 1 hr pre and 4 hr post ,or (d) 4 hr post triggering AP. NOS inhibition by L-NAME (15 mg/kg) and glucocorticoid receptor blockage by mifepristone (3 mg/kg) was considered. AP severity was assessed by biochemical and histopathological analyses. Treatment with glucocorticoids together with DETA-NO 1 hr pre and 4 hr post BPDOE-CDLs reduced serum amylase, lipase, C-reactive protein, IL-6, IL-10, hsp72, and 8-isoprostane as well as pancreatic and lung myeloperoxidase. Acinar and fat necrosis, hemorrhage, and neutrophil infiltrate were also decreased. Hydrocortisone together with DETA-NO rendered the best results. We conclude that AP severity was significantly diminished by glucocorticoids associated with DETA-NO, with the optimal dose and time point of administration being crucial to provide adequate protection against AP.
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PMID:Influence of hydrocortisone, prednisolone, and NO association on the evolution of acute pancreatitis. 1668 59

Increased Troponin I levels and pro-inflammatory cytokines have been reported in most patients undergoing cardiac surgery, ascribed to the type and extent of surgery, reperfusion injury, and the method of myocardial protection. We investigated their levels in patients undergoing on-pump (CCAB) or off-pump (OPCAB) coronary artery bypass surgery and whether these correlated with the extent of myocardial injury. One hundred twenty patients were prospectively randomized to undergo OPCAB (n = 60) or CCAB (n = 60). Hemodynamic and respiratory data, as well as serum CK-MB mass fraction, Troponin I, and interleukin (IL)-6, IL-8, and IL-10 levels, were collected perioperatively. Demographic, hemodynamic, and respiratory parameters were similar between the two groups. Troponin I was significantly lower in the OPCAB than in the CCAB group, either at the end of ischemia, end of surgery, 6-hour and 24-hour postoperatively (4 +/- 3, 5 +/- 3, 7 +/- 5, and 8 +/- 3 microg/L, vs. 19 +/- 18, 27 +/- 19, 28 +/- 13.5, and 33 +/- 8.5 microg/L, respectively, p < 0.05). Serum cytokine levels in the OPCAB patients were lower compared to the CCAB group at the end of surgery (32 +/- 35, 25 +/- 30, and 40 +/- 30 pg/ml for IL-6, IL-8, and IL-10 vs. 230 +/- 30, 140 +/- 70, and 125 +/- 50 pg/ml, respectively, p < 0.05). Plasma IL-6 levels correlated with the Troponin I levels at the end of surgery in both groups (r = 0.45, p = 0.01). Thus, OPCAB surgery is associated with reduced levels of Troponin I and activation of cytokines, compared to those in the CCAB group. High levels of these factors could correlate with myocardial damage during coronary artery bypass surgery. This finding warrants further laboratory and clinical confirmation in the future.
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PMID:Higher levels of serum cytokines and myocardial tissue markers during on-pump versus off-pump coronary artery bypass surgery. 1684 20

Several studies have stressed the involvement of inflammation in the pathophysiology of acute brain ischemia, but the role of immunoinflammatory activation in diabetic stroke patients has not yet been fully evaluated. The aim of our study was to evaluate immunoinflammatory activation of acute phase of stroke in relation to time of symptoms onset, diabetic state and diagnostic subtype. We enrolled 60 patients (32 diabetics; 28 non- diabetics) with acute ischemic stroke and 123 subjects without acute ischemic stroke, and measured levels of IL-1beta, TNF-alpha IL-6, IL-10, E-selectin, P-selectin, sICAM-1, sVCAM-1, VWF, 24-72 h and 7-10 days after stroke onset; TPA, PAI-1 plasma levels at 24-72h. Our stroke patients exhibited significantly higher plasma levels of cytokines, selectins, adhesion molecules and PAI-1, and diabetic stroke patients exhibited higher plasma levels of PAI-1 in comparison with non-diabetic ones. Lacunar strokes in comparison with those non-lacunar exhibited significantly lower levels of TNF-alpha and IL1-beta P-selectin and ICAM-1. Moreover, diabetic patients with lacunar strokes exhibited a minor grade of immunoinflammatory activation of the acute phase at 24-72h and 7-10 days after stroke onset. The minor grade of immunoinflammatory activation of patients with lacunar strokes, particularly diabetic ones, could be related to the minor extension of the infarct size, owing to the typical microvascular disease of diabetic subjects which could also explain the reported better outcome of this subtype of ischemic stroke.
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PMID:Immunoinflammatory activation during the acute phase of lacunar and non-lacunar ischemic stroke: association with time of onset and diabetic state. 1702 49

Endotoxin tolerance is defined as a reduced responsiveness to a lipopolysaccharide (LPS) challenge following a first encounter with endotoxin. Endotoxin tolerance protects against a lethal challenge of LPS and prevents infection and ischemia-reperfusion damage. Endotoxin tolerance is paralleled by a dramatic reduction of tumor necrosis factor (TNF) production and some other cytokines in response to LPS. Endotoxin tolerance involves the participation of macrophages and mediators, such as glucocorticoids, prostaglandins, IL-10, and transforming growth factor-beta. Endotoxin tolerance is accompanied by the up-regulation of inhibitory molecules that down-regulate the Toll-like receptor (TLR)4-dependent signaling pathway. Cross-tolerance between LPS and other TLR specific ligands, as well as IL-1 and TNF, has been regularly reported. A similar loss of LPS reactivity has been repeatedly reported in circulating leukocytes of septic patients and in patients with non-infectious systemic inflammation response syndrome (SIRS). Studies on cellular signaling within leukocytes from septic and SIRS patients reveal numerous alterations reminiscent of those observed in endotoxin tolerant cells. However, altered responsiveness to LPS of leukocytes from sepsis and SIRS patients is not synonymous with a global down-regulation of cellular reactivity. The term 'cellular reprogramming', which has been proposed to qualify the process of endotoxin tolerance, defines well the immune status of circulating leukocytes in septic and SIRS patients.
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PMID:Bench-to-bedside review: endotoxin tolerance as a model of leukocyte reprogramming in sepsis. 1704 47

Adenosine is an endogenous purine nucleoside that, following its release into the extracellular space, binds to specific adenosine receptors expressed on the cell surface. Adenosine appears in the extracellular space under metabolically stressful conditions, which are associated with ischemia, inflammation, and cell damage. There are 4 types of adenosine receptors (A(1), A(2A), A(2B) and A(3)) and all adenosine receptors are members of the G protein-coupled family of receptors. Adenosine receptors are expressed on monocytes and macrophages and through these receptors adenosine modulates monocyte and macrophage function. Since monocytes and macrophages are activated by the same danger signals that cause accumulation of extracellular adenosine, adenosine receptors expressed on macrophages represent a sensor system that provide monocytes and macrophages with information about the stressful environment. Adenosine receptors, thus, allow monocytes and macrophages to fine-tune their responses to stressful stimuli. Here, we review the consequences of adenosine receptor activation on monocyte/macrophage function. We will detail the effect of stimulating the various adenosine receptor subtypes on macrophage differentiation/proliferation, phagocytosis, and tissue factor (TF) expression. We will also summarize our knowledge of how adenosine impacts the production of extracellular mediators secreted by monocytes and macrophages in response to toll-like receptor (TLR) ligands and other inflammatory stimuli. Specifically, we will delineate how adenosine affects the production of superoxide, nitric oxide (NO), tumor necrosis factor-alpha, interleukin (IL)-12, IL-10, and vascular endothelial growth factor (VEGF). A deeper insight into the regulation of monocyte and macrophage function by adenosine receptors should assist in developing new therapies for inflammatory diseases.
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PMID:Shaping of monocyte and macrophage function by adenosine receptors. 1705 21

Ischemia reperfusion injury is characterized by local and systemic inflammation leading to considerable mortality. Previously, we have reported that soluble T1/ST2 (sST2), a member of the IL-1 receptor gene family, inhibits LPS-induced macrophage proinflammatory cytokine production. Here, we report the therapeutic effect of sST2-Fc in a murine model of intestinal ischemia reperfusion-induced injury. Administration of sST2-Fc fusion protein i.v., 10 min before reperfusion, reduced the production of TNF-alpha dose-dependently in the intestine and in the lungs. The sST2-Fc treatment with the highest dose (100 mug) resulted in inhibited vascular permeability, neutrophilia, and hemorrhage in the intestine and the lungs compared with controls treated with normal IgG. This was associated with down-regulated tissue levels of proinflammatory cytokines, markedly reduced serum TNF-alpha levels, and increased survival of mice from the sST2-Fc-treated group after ischemia and reperfusion injury. The beneficial effect of sST2-Fc treatment was associated with elevated IL-10 production in intestine and lung. sST2-Fc was not able to prevent the inflammatory response associated with intestinal ischemia and reperfusion in IL-10-deficient mice, suggesting that sST2 exerts its anti-inflammatory effect in a IL-10-dependent manner. These results also demonstrate that sST2-Fc may provide a novel, complementary approach in treating ischemic reperfusion injury.
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PMID:ST2, an IL-1R family member, attenuates inflammation and lethality after intestinal ischemia and reperfusion. 1709 2

Mitochondria play a central role in both the physiological and pathophysiological regulation of cell survival/death. Increasing evidence places mitochondrial dysfunction at the center of many neuropathological conditions. The present study investigates the extent of mitochondrial dysfunction in cortical, hippocampal and cerebellar tissues in a rat model of hypoxia-ischemia (HI). We hypothesized that; mitochondrial dysfunction in situ may be prevented by treatment with clomethiazole (CMZ), a GABA(A) receptor agonist. Assessment of mitochondrial FAD-linked respiration at both 1- and 3-day post-HI revealed a marked decrease in activity from ipsilateral cortical and hippocampal regions (P<0.001). In addition, small changes were seen in contralateral cortical and hippocampal tissues as well as in the cerebellum at 3-days (P<0.05). Assessment of the mitochondrial electron transport chain (complexes I-V), and mitochondrial markers of integrity (citrate synthase) and oxidative stress (aconitase) confirmed mitochondrial impairment in ipsilateral regions following HI. Complexes I, II-III, V and citrate synthase were also impaired in contralateral regions and cerebellum 3-days post-HI. Treatment with CMZ (414 mg/kg/day via minipumps) provided marked protection to all aspects of neuronal tissue assessed. Circulating cytokine (interleukin [IL]-1alpha, IL-1beta, tumor necrosis factor [TNF]-alpha, granulocyte macrophage colony-stimulating factor [GM-CSF], IL-4 and IL-10) levels were also assessed in these animals 3-days post-HI. Plasma IL-1alpha, IL-1beta, TNF-alpha and GM-CSF levels were significantly increased post-HI. Treatment with CMZ ameliorated the increases in IL-1alpha, IL-1beta, TNF-alpha and GM-CSF levels while increasing plasma IL-4 and IL-10 levels. This study provides evidence of the extent of mitochondrial damage following an HI-insult. In addition, we have shown that protection afforded by CMZ extends to preservation of mitochondrial function and integrity via anti-inflammatory mediated pathways.
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PMID:Mitochondrial involvement in transhemispheric diaschisis following hypoxia-ischemia: Clomethiazole-mediated amelioration. 1711 78

Clinical studies demonstrate that acute renal failure (ARF) is associated with increased mortality, which may be due to pulmonary complications. ARF may affect the lung via increased renal production or impaired clearance of mediators of lung injury, such as proinflammatory cytokines. Bilateral nephrectomy is a method to examine directly the deleterious systemic effects of absent renal clearance in ARF without the confounding effects that are associated with ischemia-reperfusion injury (e.g., ischemic ARF) or systemic toxicity (e.g., cisplatin-induced ARF). This study contrasts the effects of ischemic ARF and bilateral nephrectomy on serum cytokines and lung injury. It demonstrates that the acute absence of kidney function after both ischemic ARF and bilateral nephrectomy is associated with an increase in multiple serum cytokines, including IL-6 and IL-1beta, and that the cytokine profiles were distinct. Lung injury after ischemic ARF and bilateral nephrectomy was similar and was characterized by pulmonary vascular congestion and neutrophil infiltration. For investigation of the role of proinflammatory cytokines in pulmonary injury after ARF, the anti-inflammatory cytokine IL-10 was administered before bilateral nephrectomy. IL-10 treatment improved pulmonary architecture and was associated with a reduction in inflammatory markers, including bronchoalveolar lavage fluid total protein, pulmonary myeloperoxidase activity (a biochemical marker of neutrophils), and the chemokine macrophage inflammatory protein 2. These data demonstrate for the first time that the acute absence of kidney function results in pulmonary injury independent of renal ischemia and highlight the critical role of the kidney in the maintenance of serum cytokine balance and pulmonary homeostasis.
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PMID:Acute renal failure after bilateral nephrectomy is associated with cytokine-mediated pulmonary injury. 1716 17

We hypothesized that the ischemic reperfused (I/R) lung expresses and liberates tumor necrosis factor-alpha (TNF-alpha) to injure the nonischemic lung, and that a TNF-alpha-converting enzyme inhibitor (TACEI) prevents injury of the nonischemic lung by blocking TNF-alpha liberation from the I/R lung. In isolated ventilated rat lungs in which differential perfusion to the right (RL) or left (LL) lung was feasible, LLs were selectively made ischemic (60 min) while maintaining perfusion to RLs, then reperfused (30 min) in a nonrecirculating manner with buffer solution (non-R; n = 18) or in a recirculating manner with buffer containing TACEI (TACEI[+]; n = 18) or without TACEI (TACEI[-]; n = 18). Ischemia reperfusion induced TNF-alpha messenger RNA expression in the ischemic LLs; the expression was highest in TACEI(+) group (P < 0.01). The expression of TNF-alpha, which was detected as immunofluorescence signals on CD34-positive endothelial cells, was observed in ischemic LLs; the highest expression being that in the TACEI(+) group. Wet/dry ratio and protein content in bronchoalveolar lavage fluid were higher in LLs than in RLs, and among the RLs, these 2 parameters were significantly increased in the TACEI(-) group (P < 0.01) in which the RLs were exposed to the TNF-alpha-rich perfusate. On the other hand, protein content in bronchoalveolar lavage fluid of the TACEI(+) group in which RLs were exposed to recirculating perfusate containing little TNF-alpha was decreased to a level close to but still higher than that in the non-R group (P < 0.05). The unilateral I/R lung affected the permeability of the nonischemic lung by liberating mainly TNF-alpha and induced TNF-alpha, interleukin (IL)-1beta, IL-6, and IL-10 messenger RNA expression in the nonischemic lung. These findings support the idea of organ-organ interaction in which an injured organ affects a remote organ by liberating humoral mediators.
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PMID:Nonischemic lung injury by mediators from unilateral ischemic reperfused lung: ameliorating effect of tumor necrosis factor-alpha-converting enzyme inhibitor. 1717 85


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