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)

The activity of 1-alkyl-sn-glycero-3-phosphate (AGP) acetyltransferase was studied using microsomal fractions isolated from cerebral cortices of 15-day-old rabbits. Fraction P3A was isolated using buffered 0.32 M sucrose containing mercaptoethanol, EDTA and NaF. This fraction had specific AGP acetyltransferase activities which were 4.9-times those of microsomal fraction P3B isolated in 0.32 M sucrose alone. This P3B activity was increased 2.4-times after a preincubation in the presence of ATP, MgCl2 and a high-speed supernatant fraction from cerebral cortex. Further, the activities of both P3A and P3B were almost completely eliminated by preincubation in the presence of alkaline phosphatase. Thus an activation of the AGP acetyltransferase by phosphorylation was indicated. While there was little inhibition of the P3A AGP acetyltransferase in the presence of added ATP, the magnesium salt form of ATP (1 mM) was severely inhibitory, bringing about 86% inhibition for P3A and 91% for P3B. The inhibitory effects of MgADP and MgAMP were smaller, and MgATP was a much more effective inhibitor than MgCTP, MgGTP and MgUTP which brought about 20-38% inhibitions of P3A activity at 1 mM concentrations. The effect of MgATP may be of particular relevance to the synthesis of platelet activating factor (PAF) following a period of ischemia in brain. Falling MgATP levels during energy failure could relieve the inhibition of AGP acetyltransferase seen in healthy cells and allow the formation of 1-alkyl-2-acetyl-sn-glycero-3-phosphate, which is the first committed intermediate in the de novo pathway of PAF synthesis.
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PMID:MgATP inhibits the synthesis of 1-alkyl-2-acetyl-sn-glycero-3-phosphate by microsomal acetyltransferase of immature rabbit cerebral cortex. 801 76

The objective of this study was to correlate nitric oxide production with time of reperfusion of the post-ischemic feline small intestine. Epithelial permeability, quantitated as blood-to-lumen clearance of 51Cr-EDTA, following 1 hr of ischemia and 4 hr of reperfusion of the small intestine, increased approximately 10-fold. This increase was further augmented by L-NAME infusion between 60 and 120 min but not at 240 min. Ca(2+)-dependent nitric oxide synthase activity was reduced by approximately 50% at 3 and 4 hr of reperfusion, whereas Ca(2+)-independent nitric oxide synthase activity was undetectable throughout the experiment. Administration of L-arginine at the start of reperfusion attenuated the reperfusion-induced epithelial barrier dysfunction for the first 120 min but not at 180 or 240 min. Continuous infusion of a nitric oxide donor (CAS 754) following 1 hr of reperfusion reduced epithelial permeability at 4 hr of reperfusion. In conclusion, a reduction in nitric oxide production was observed with time of reperfusion, possibly due to reduced nitric oxide synthase levels.
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PMID:Time course of nitric oxide production and epithelial dysfunction during ischemia/reperfusion of the feline small intestine. 802 78

Tissue damage in cerebral ischemia may be produced by acidosis-induced delocalization of intracellular iron which acts as a catalyst in oxidative reactions. Acidosis was induced either by homogenization and incubation of rat cortical homogenates in acidified buffers or by submitting hyperglycemic rats to complete ischemia, a procedure that leads to intracellular lactic acidosis. The level of low molecular weight species (LMWS) iron was measured after filtration of tissue homogenates through a 10,000 Mr ultrafiltration membrane. When cortical tissue was homogenized in buffer pH 7, the level of LMWS iron was equal to 0.21 microgram/g. It was significantly enhanced by acidification of the homogenization medium, reaching 0.34 microgram/g at pH 6 and 0.75 microgram/g at pH 5. When the tissue was homogenized in water, the LMWS iron level reached 0.17 microgram/g in normoglycemic rats and 0.38 microgram/g (p < .05) in hyperglycemic rats. Both aerobic incubation of homogenates for 1 h at 37 degrees C and inclusion of EDTA in the homogenization medium led to further increases in the iron level. In order to demonstrate the deleterious role of iron in brain ischemia, the effect of treatment with bipyridyl, an iron-chelating agent, was assessed by measuring regional brain edema by the specific gravity method, 24 h following induction of thrombotic brain infarction. The treatment significantly attenuated the development of brain edema, reducing the water content of the infarcted area by about 2.5%. Taken together, these results support the hypothesis that a significant component of brain ischemic injury involves an iron-dependent mechanism.
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PMID:Ischemia-induced brain iron delocalization: effect of iron chelators. 807 Jun 93

The objective of this study was to determine whether ischemia-reperfusion (I/R) of the small bowel activated mast cells and, if so, to determine whether this event contributed to granulocyte infiltration and mucosal barrier dysfunction. Autoperfused segments of the jejunum were exposed to 30 min of ischemia followed by 60 min of reperfusion. Epithelial permeability was assessed by the clearance of 51Cr-labeled EDTA from plasma to lumen. Plasma rat mast cell protease II (RMCP II) was measured and used as an index of mucosal mast cell degranulation, whereas myeloperoxidase (MPO) activity was used as an index of granulocyte infiltration. I/R caused a significant increase in plasma RMCP II levels, MPO activity, and epithelial permeability. The mucosal mast cell stabilizer doxantrazole prevented the I/R-induced increase in all three parameters. The connective tissue mast cell stabilizer ketotifen had no effect. To determine whether oxidants were involved in mast cell degranulation, some animals were pretreated with superoxide dismutase and catalase. This regimen completely abolished the I/R-induced rise in plasma RMCP II levels and attenuated mucosal MPO activity and epithelial permeability. Selective inhibitors of two mast cell-derived mediators, platelet-activating factor and histamine, did not attenuate the rise in epithelial permeability. These data suggest that oxidant-induced mucosal mast cell degranulation is a key event in the granulocyte infiltration and tissue dysfunction associated with reperfusion of the ischemic intestine.
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PMID:Mast cells contribute to ischemia-reperfusion-induced granulocyte infiltration and intestinal dysfunction. 807 30

We evaluated the damage to the gastric epithelium produced by local ischemia-reperfusion (IR) with or without luminal perfusion with 0.1 N HCl. Local gastric ischemia was induced by clamping the left gastric artery. Use of radioactive microsphere technique revealed a significant reduction in blood flow induced only in the corpus (67% reduction). Because no measurable gross lesion was observed in this model, the blood-to-lumen clearance of 51Cr-labeled EDTA (51Cr-EDTA) served as an index of epithelial damage. In the absence of exogenous acid, the histological damage was minimum and could not be quantified. However, a significant increase in 51Cr-EDTA clearance was observed shortly after reperfusion in a manner that depended on the duration of ischemia. This increase in clearance reached a maximum approximately 10 min after reperfusion and returned rapidly toward control levels within 40-50 min after reperfusion. In the presence of exogenous acid, EDTA clearance increased significantly during ischemia, increased further during reperfusion, and did not recover for at least 60 min after reperfusion. The acid infused after reperfusion (no acid before reperfusion) did not significantly aggravate the mucosal damage that followed reperfusion. However, the acid infused before reperfusion (no acid after reperfusion) showed an effect on EDTA clearance similar to that induced by continuous acid perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gastric epithelial damage induced by local ischemia-reperfusion with or without exogenous acid. 814

Increased mucosal permeability may represent an important factor in the etiology of necrotizing enterocolitis (NEC). In the present study we used an immature rat model to assess the permeability effects of a number of stresses commonly seen in infants with NEC. In 10-day-old rats, mucosal permeability to 51Cr EDTA was measured after subjecting the animals to 10-minute ischemia-reperfusion injury, 30 minutes of hypoxia (14% oxygen), cold stress (4 degree C for 4 minutes), and intraperitoneal indomethacin (0.2 or 2.0 mg/kg) or theophylline (40 or 200 mg/kg). When compared with appropriate controls, mucosal permeability was found to be significantly increased by ischemia-reperfusion injury, hypoxia, and high-dose indomethacin, but not by cold, theophylline, or low-dose indomethacin. Renal clearance studies confirmed that elevated blood levels of 51Cr EDTA were due to increased permeability rather than decreased renal excretion of the probe. These studies confirm that mucosal permeability in the immature rat is increased by a variety of insults, and may represent a "common pathway" in the etiology of NEC.
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PMID:Mucosal permeability in the immature rat intestine: effects of ischemia-reperfusion, cold stress, hypoxia, and drugs. 826 5

Recent data have demonstrated that inhibition of nitric oxide synthesis exacerbated the mucosal injury associated with reperfusion of the postischemic intestine. In this study, using a feline 1-h intestinal ischemia followed by reperfusion model, we tested the possibility that exogenous sources of nitric oxide may prevent the reperfusion-induced mucosal barrier disruption and examined the mechanisms involved. Mucosal barrier integrity was assessed by determining 51Cr-EDTA clearance from blood to lumen. Intestinal blood flow and resistance were also determined. Reperfusion after 1 h of ischemia significantly increased 51Cr-EDTA clearance (0.05 +/- 0.01 to 0.35 +/- 0.07 ml.min-1.100 g-1) and decreased intestinal blood flow by 50%. Exogenous sources of nitric oxide including SIN-1, CAS-754, and nitroprusside as well as exogenous L-arginine all reduced reperfusion-induced mucosal barrier dysfunction without improving intestinal blood flow. Inhibition of endogenous nitric oxide with NG-nitro-L-arginine methyl ester between 1 and 2 h of reperfusion further augmented the rise in mucosal permeability associated with ischemia-reperfusion. Addition of the permeable analogue of guanosine 3',5'-cyclic monophosphate, 8-bromoguanosine 3',5'-cyclic monophosphate, improved reperfusion-induced intestinal blood flow significantly but did not provide protection against mucosal barrier disruption associated with the first hour of ischemia-reperfusion. Exogenous sources of nitric oxide can reduce reperfusion-induced mucosal barrier dysfunction independent of alterations in intestinal blood flow.
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PMID:Nitric oxide donors reduce the rise in reperfusion-induced intestinal mucosal permeability. 839 97

Histological changes in the stunned myocardium are believed to be minimal. This study examined whether cytoskeletal structures of microtubules are disrupted in the stunned myocardium. In 38 dogs, the left anterior descending coronary artery was occluded for 15 minutes and reperfused to produce the stunned myocardium. Microtubules were stained immunohistochemically. In intact myocardium, microtubules appeared as a filamentous network throughout the cytoplasm and encircled the nucleus. This pattern was not affected by 15 minutes of ischemia. One hour of reperfusion, however, disrupted microtubular structure substantially (disruption score in the endocardium, 53.4 +/- 6.0%) although actin filaments remained intact. Microtubular structures were reconstituted 1-3 days after reperfusion, showing supernormal immunoreactivity. Five days after reperfusion, the pattern of microtubular staining was normal. In another protocol, the role of Ca2+ during reperfusion in microtubular disruption was examined. When intracoronary infusion of EDTA (1.67 mumol/kg body wt per minute) was performed during the initial 10 minutes of reperfusion, myocardial stunning was attenuated. The fractional shortening in the perfused area after 1 hour of reperfusion was 20.1 +/- 1.2% versus 11.5 +/- 0.5% in the control condition (p < 0.05), and the microtubular disruption score was lower (12.6 +/- 1.4%). Although intracoronary infusion of calcium chloride (9 mumol/kg body wt per minute) for 10 minutes in nonischemic hearts increased contractile function (fractional shortening, 25.3 +/- 2.0%), it severely disrupted microtubular networks (microtubular disruption score, 64.0 +/- 10.6%). We conclude that microtubules supporting the structural integrity of myofibrils and other organelles are reversibly disrupted by reperfusion after brief ischemia probably through calcium overload.
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PMID:Reperfusion after brief ischemia disrupts the microtubule network in canine hearts. 841 89

The objective of this study was to assess whether nitric oxide synthesis inhibition affects intestinal barrier function after ischemia-reperfusion of the feline small bowel. Local intra-arterial infusion of the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 25 nmol.ml-1.min-1) was performed in autoperfused segments of cat ileum for 60 min after 90 min of ischemia and 60 min of reperfusion. Epithelial permeability was quantitated by measuring blood-to-lumen clearance of 51Cr-labeled EDTA, and microvascular dysfunction was assessed by measuring the clearance of protein from the vasculature into the interstitium. 125I-labeled albumin clearance from blood to lumen and histology were performed to further characterize the extent of intestinal dysfunction after reperfusion of the postischemic intestine in the presence and absence of L-NAME. Ischemia-reperfusion-induced mucosal and microvascular permeability increases were dramatically augmented by L-NAME infusion, and this effect was reversed by infusion of L-arginine (125 nmol.ml-1.min-1). Initiating L-arginine (but not D-arginine) infusion alone 10 min before reperfusion provided protection against ischemia-reperfusion-induced mucosal barrier dysfunction; however, this was not associated with a reduction in endogenous levels of L-arginine during ischemia-reperfusion. These data suggest that basal nitric oxide production is important in minimizing mucosal and microvascular barrier dysfunction associated with reperfusion of postischemic intestine.
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PMID:Ischemia-reperfusion in feline small intestine: a role for nitric oxide. 843 Jul 97

The reactivity of cysteine presents a paradox: although regarded as an antioxidant, cysteine interacts with oxygen in a metal-catalyzed reaction to produce reactive species. Because ischemia provokes the appearance of millimolar amounts of cysteine and increased amounts of transition metals, we studied whether cysteine, in the presence of transition metals, consumes oxygen, generates hydrogen peroxide, and is toxic. Using fluorescence cytometry, we provide direct evidence that hydrogen peroxide is copiously generated during cysteine autoxidation. Pyruvate attenuates such generation of hydrogen peroxide and cytotoxicity. Cysteine oxidation is stimulated by an EDTA-chelatable diethyl-dithiocarbamate-chelatable constituent of kidney extract; this suggests that copper is the catalytically active metal. The toxicity resulting from cysteine oxidation is less than that induced by amounts of reagent hydrogen peroxide that produce comparable fluorescence. Cysteine also prevents hydrogen peroxide-induced toxicity. Thus, although cysteine generates hydrogen peroxide, it can guard against hydrogen peroxide toxicity, possibly by binding metals on which the toxicity of hydrogen peroxide is dependent. Thus the behavior of cysteine can be salutary or pernicious; the net effect of cysteine, within this wide ambit of actions, is decisively influenced by the conditions to which cysteine is exposed.
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PMID:Autoxidation of cysteine generates hydrogen peroxide: cytotoxicity and attenuation by pyruvate. 844 40


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