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)

Reactive oxygen metabolites generated from the enzyme xanthine oxidase (XO) play an important role in the pathogenesis of ischemia-induced tissue injury. The observation that intracellular proteins such as aspartate transaminase (AST) and alcohol dehydrogenase (ADH) are released from the ischemic liver during reperfusion led us to postulate that XO could be released into the systemic circulation. Livers from fasted rats were extirpated, perfused with oxygenated Krebs-Henseleit buffer, and subjected to 2 h ischemia followed by 2 h reperfusion. Reperfusion increased AST in the perfusate from 1 +/- 1 to 830 +/- 280 U/l, whereas ADH increased from 0.3 +/- 0.1 to 95 +/- 26 U/l. Concomitantly, xanthine dehydrogenase (XDH) + XO activity in the perfusate increased from 0 to 4.1 +/- 1.0 mU/ml. A 64% decrease in endogenous tissue XDH + XO activity paralleled release of XDH + XO. The XDH + XO activity predicted to appear in the circulation after hepatic ischemia was sufficient, when supplied with substrate, to produce severe vascular endothelial injury in vitro, even in the presence of serum or whole blood. These results suggest that massive quantities of XDH and XO are released into the circulation after hepatic ischemia and that the resulting reactive oxygen metabolites could produce widespread tissue injury.
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PMID:Circulating xanthine oxidase: potential mediator of ischemic injury. 233 69

We examined the effects of two degrees of hypothermia on hepatic oxygen delivery and uptake, hepatic lactate uptake as a marker of hepatic function, and the effect of hypothermia on ischemia-reperfusion injury in the liver in miniature pigs (n = 18, 21-30 kg body wt). Hepatic arterial and portal venous blood flows were measured while hepatic oxygen delivery was progressively decreased without venous congestion in the preportal area. With decreases in hepatic blood and oxygen supply, oxygen extraction gradually increased from 50 to 90% in the normothermic group and from 25 to 70 and 84% in the hypothermic (30. and 34 degrees C, respectively) groups. The values of critical hepatic oxygen delivery were between 7.3 and 11.9 ml O2.min-1.100 g-1 without significant differences among the groups. During reperfusion after ischemic insult, hepatic oxygen uptake returned to base-line values in both hypothermic groups but remained substantially below base-line values in normothermic groups of animals. Hepatic enzyme concentrations (lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, and alcohol dehydrogenase) were substantially increased (up to 30-fold) in normothermic animals, but the concentrations did not increase in either of the hypothermic groups. These results demonstrated that hypothermia per se does not affect hepatic oxygen delivery but decreases hepatic oxygen demand and uptake, provides an effective protection from hepatic oxygen deprivation, and lessens reperfusion injury.
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PMID:Hypothermia, hepatic oxygen supply-demand, and ischemia-reperfusion injury in pigs. 236 Jun 37

On the material of early autopsies of the above patients the activity of the following myocardial enzymes was undergone the quantitative histochemical study: succinate, lactate, (beta-oxybutyrate, d-glycerophosphate, glucose 6-phosphate and alcohol dehydrogenase, NAD-diaphorase, catalase, phosphorylase. The increase of the activity of practically all enzymes studied was observed in the myocardial areas with no circulation disturbances. This increase was due to the moderate myocardial hypertrophy. On the contrary, in the areas with a non-even blood supply (ischemia) the decrease of the activity of all oxidative-reductive enzymes was observed. The presence of such foci in the myocardium which occur in 70% cases studied facilitates the development of the ventricular fibrillation with a fatal outcome. The enzyme depression is particularly pronounced against the background of a high alcoholic content.
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PMID:[A histochemical study of enzyme activity in the myocardium of victims of sudden death with small-focal cardiosclerosis]. 259 77

The mechanisms by which elevated levels of vasopressin (ADH) in man and animals cause serious myocardial dysfunction, evidenced by arrhythmias, reduction in cardiac output and coronary blood flow, are not settled. Experiments were conducted in 16 isolated working left ventricles to examine their metabolic and hemodynamic responses to the infusion of vasopressin and the combination of vasopressin and epinephrine. Contractile performance was evaluated by analysis of positive dP/dt, contractile element velocities, and ventricular work-curves using stroke work/end-diastolic pressure. Relaxation parameters, including negative dP/dt and the early diastolic relaxation time constant, were also studied. Coronary blood flow was reduced 22% or less by vasopressin while cardiac output was maintained at a constant level. Myocardial oxygen consumption, lactate and potassium balances were determined from arterial and coronary sinus concentrations. Vasopressin produced myocardial dysfunction indicated by decrements in contractile and relaxation indices, without evidence of global ischemia. Epinephrine restored the mechanical performance to normal without significant change in coronary blood flow, myocardial oxygen consumption, or lactate and potassium balance.
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PMID:Mechanisms of impaired cardiac function by vasopressin. 736 15

Evidence is increasing that individuals vary in their susceptibility to alcoholic pancreatitis. Numerous investigators have attempted to account for this individual susceptibility by studying associations between alcoholic pancreatitis and potential risk factors. Those studies, reviewed here, have focused on the amount, type, and pattern of alcohol consumption, genetic markers (such as blood groups, HLA phenotypes, alpha 1-antitrypsin, and alcohol dehydrogenase isoenzyme distribution), diet, hypertriglyceridemia, tobacco consumption, and pancreatic ischemia. Associations between pancreatitis and several of these factors have been reported, but many studies offer conflicting conclusions. A number of studies are difficult to interpret because of methodologic problems, particularly with regard to inadequate controls and small numbers of index subjects. At present, the evidence is insufficient for one to conclude that any of the above-mentioned factors are well-established risk factors for pancreatitis. As a result, individual susceptibility to alcoholic pancreatitis remains unexplained. Clarification of potential risk factors may ultimately lead to the ability to prevent this relatively common disorder, but additional, appropriately designed studies are required.
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PMID:Individual susceptibility to alcoholic pancreatitis: still an enigma. 789 93

Although alcohol is likely to have direct effects on the subcellular integrity of the pancreas, other factors arising outside the pancreas may modulate or potentiate alcohol-induced damage. Among these factors are the hepatic metabolism of ethanol to acetaldehyde (via isoenzymes of ADH), the hepatic production of free radicals, the release of G.I. hormones, pancreatic ischemia (and reperfusion injury), hyperlipemia, diet and smoking. This article summarises what is known about these extrapancreatic factors. It is suggested that the pathogenesis of alcoholic pancreatitis is multifactorial but that many studies in this field are difficult to interpret because of methodological problems, particularly with regard to inadequate controls.
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PMID:An overview of extrapancreatic factors in the pathogenesis of alcoholic pancreatitis. 897 59

Many new lines of evidence implicate both superoxide anion radical (O2*-) and biogenic amine neurotransmitters in the pathological mechanisms that underlie neuronal damage caused by methamphetamine (MA), glutamate-mediated oxidative toxicity, ischemia-reperfusion, and other neurodegenerative brain disorders. In this investigation the oxidation of 5-hydroxytryptamine (5-HT, serotonin) by an O2*--generating system (xanthine/xanthine oxidase) in buffered aqueous solution at pH 7.4 has been studied. The major product of the O2*--mediated oxidation of 5-HT is tryptamine-4,5-dione (T-4, 5-D). However, O2*- and H2O2, cogenerated by the xanthine oxidase-mediated oxidation of xanthine to uric acid, together react with trace levels of iron that contaminate buffer constituents to give a chemically ill-defined oxo-iron species. This species mediates the oxidation of 5-HT to a C(4)-centered carbocation intermediate that reacts with 5-HT to give 5,5'-dihydroxy-4, 4'-bitryptamine (4,4'-D) and with uric acid to give 9-[3-(2-aminoethyl)-5-hydroxy-1H-indol-4-yl]-2,6,8-triketo-1H,3H, 7H-purine (7) as the major products. These products differ from those formed in the HO*-mediated oxidation of 5-HT under similar conditions. When the reaction is carried out in the presence of the intraneuronal nucleophile glutathione (GSH), T-4,5-D is scavenged to give 7-(S-glutathionyl)tryptamine-4,5-dione, whereas the putative carbocation intermediate is scavenged to give 4-(S-glutathionyl)-5-hydroxytryptamine. T-4,5-D also reacts with the sulfhydryl residues of a model protein, alcohol dehydrogenase, and inhibits its activity. Previous investigators have proposed that T-4, 5-D is a serotonergic neurotoxin. This raises the possibility that T-4,5-D and perhaps other putative intraneuronal metabolites formed by the O2*-/H2O2/oxo-iron-mediated oxidations of 5-HT might be endotoxins that contribute to neurodegeneration in brain regions innervated by serotonergic neurons caused by MA, ischemia-reperfusion, and other neurodegenerative brain disorders.
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PMID:Oxidation of serotonin by superoxide radical: implications to neurodegenerative brain disorders. 962 32

Amyloid beta-peptide-binding alcohol dehydrogenase (ABAD) is a member of the family of short chain dehydrogenase/reductases whose distinctive properties include the capacity to bind amyloid beta-peptide and enzymatic activity toward a broad array of substrates including n-isopropanol and beta-estradiol. In view of the wide substrate specificity of ABAD and its high activity on l-beta-hydroxyacyl-CoA derivatives, we asked whether it might also catalyze the oxidation of the ketone body d-3-hydroxybutyrate. This was indeed the case, and oxidation proceeded with K(m) of approximately 4.5 mm and V(max) of approximately 4 nmol/min/mg protein. When placed in medium with d-beta-hydroxybutyrate as the principal energy substrate, COS cells stably transfected to overexpress wild-type ABAD (COS/wtABAD) better maintained 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide reduction, cellular energy charge, and morphologic phenotype compared with COS/vector cells. Using a severe model of metabolic perturbation, transgenic mice with targeted neuronal expression of ABAD subjected to transient middle cerebral artery occlusion showed strokes of smaller volume and lower neurologic deficit scores in parallel with increased brain ATP and decreased lactate, compared with nontransgenic controls. These data suggest that ABAD contributes to the protective response to metabolic stress, especially in the setting of ischemia.
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PMID:Amyloid beta -peptide-binding alcohol dehydrogenase is a component of the cellular response to nutritional stress. 1086 39

The highest activities of leucyl aminopeptidase(LAP, cytosol aminopeptidase, EC 3.4.11.1) in sera have been found in patients with acute hepatitis(Kanno et al., Am J Clin Path, 82: 700-705, 1984). I observed inpatients with very high activities of LAP and alcohol dehydrogenase(AD) in sera. However, only slight elevations of serum pseudo leucine aminopeptidase(PLA), that is, membrane alanyl aminopeptidase(MAA, microsomal aminopeptidase, EC 3.4.11.2) activities for hydrolysis of leucyl-4-nitroanilide were observed in these patients. They were patients in critical care unit with ischemia caused by a cardiopulmonary arrest, multiple trauma, acute myocardial infarction or operation. Therefore, we should measure LAP activities in sera rather than PLA(MAA) activities in these patients.
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PMID:[Comparison between leucyl aminopeptidase and pseudo leucine aminopeptidase activities in sera]. 1106 3