Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A tiletamine hydrochloride/zolazepam hydrochloride combination was used successfully to immobilize captive untamed wild dogs (Lycaon pictus) (n = 16) at dosage rates ranging from 2.3 to 32.3 mg/kg. Animals remained immobilized for periods ranging from 35 min to 24 hr 14 min. There was a significant positive correlation (r = 0.85, P less than 0.01) between dosage rate and the time immobilized. Profuse salivation and intermittent mild myoclonal contractions were observed in some wild dogs. Mildly reduced partial oxygen and carbon dioxide pressures as well as reduced concentrations of bicarbonate were observed in arterial blood at 10 and 20 min after administration of the drug. Serum concentrations of sodium, potassium, chloride, phosphorus, calcium, magnesium, urea, creatinine, glucose, proteins, albumin, gammaglutamyltransferase, creatinine kinase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase, insulin, cortisol and thyroxine are presented. These concentrations were found to be in agreement with values previously reported for wild dogs.
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PMID:Immobilization of wild dogs (Lycaon pictus) with a tiletamine hydrochloride/zolazepam hydrochloride combination and subsequent evaluation of selected blood chemistry parameters. 206 44

Coleonol, a diterpine prevented biochemical changes induced by coronary artery ligation in rabbits at a dose of 10 mg/kg, iv. It increased the heart mitochondrial oxygen uptake and O ratio, which may be responsible for the stabilization of heart membrane. The decrease in serum creatine phosphokinase, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase phospholipase and lipid peroxide and increase in cytochrome P450, glycogen and superoxide dismutase activity by coleonol treatment could have contributed to restore myocardial integrity and cardiac function disturbed by coronary artery ligation. The cardioprotective activity of coleonol was found to be comparable to propranolol.
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PMID:Protective effect of coleonol on biochemical changes produced in coronary ligation induced ischemia. 227 71

The three-dimensional structure of a complex between the dodecanucleotide d(CGCGAATTCGCG) and the anti-trypanocidal drug berenil, has been determined to a resolution of 2.5 A. The structure has been solved by molecular replacement and refined to an R factor of 0.177. A total of 49 water molecules have been located. The drug is bound at the 5'-AAT-3' region of the oligonucleotide. At one end of the drug the amidinium group is in hydrogen-bonded contact with N3 of the adenine base complementary to the thymine of the AAT. The other amidinium group does not make direct interactions with the DNA. Instead, a water molecule mediates between them. This is in hydrogen-bonded contact with an amidinium nitrogen atom, N3 of the 5' end adenine base and the ring oxygen atom of an adjacent deoxyribose. Molecular mechanics calculations have been performed on this complex, with the drug at various positions along the sequence. These show that the observed position is only 0.8 kcal/mol higher in energy than the best position. It is suggested that there is a broad energy well in the AATT region for this drug, and that water molecules as well as the neighbouring sequence, will determine precise positioning. More general aspects of minor groove binding are discussed.
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PMID:Crystal structure of a berenil-dodecanucleotide complex: the role of water in sequence-specific ligand binding. 232 43

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

Hepatocyte monolayer cultures were exposed to 6000 ppm styrene vapor at 20%, 2%, or 1% O2 and assayed for signs of cell damage immediately following the 2-hr exposure and then 24 hr later. Oxygen concentrations were used that were previously shown to maximize lipid peroxidation and to predispose hepatocyte monolayers to chemical injury. The use of two time points allowed assessment of acute injury as well as injury that requires several hours to manifest itself. The uptake of styrene into the buffer in the culture dishes was measured by gas chromatography and was found to be 0.49, 0.68, and 0.74 mM at 15, 60, and 120 min, respectively. However, as measured by release of aspartate aminotransferase and inclusion of trypan blue, no toxicity was evident at either time point, irrespective of the oxygen concentration. This study shows that despite the weakening of hepatocyte defense mechanisms by hypoxia, styrene is not acutely toxic to these cells. Furthermore, if any damage to DNA, RNA, or the capability for protein synthesis occurs during exposure to styrene, it is insufficient to cause lysis within 24 hr.
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PMID:Toxicity of styrene vapor in hepatocyte monolayers at low oxygen tensions. 235 Nov 22

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

The technique of normal and retrograde rat liver perfusion has been widely used to probe zonal differences in drug-metabolizing activities. The validity of this approach mandates the same tissue spaces being accessed by substrates during both normal and retrograde perfusions. Using the multiple-indicator dilution technique, we presently examine the extent to which retrograde perfusion alters the spaces accessible to noneliminated references. A bolus dose of 51Cr-labeled red blood cells, 125I-albumin, 14C-sucrose and 3H2O was injected into the portal (normal) or hepatic (retrograde) vein of rat livers perfused at 10 ml per min per liver. The outflow perfusate was serially collected over 220 sec to characterize the transit times and the distribution spaces of the labels. During retrograde perfusion, red blood cells, albumin and sucrose profiles peaked later and lower than during normal perfusion, whereas the water curves were similar. The transit times of red blood cells, albumin and sucrose were longer (p less than 0.005), whereas those for water did not change. Consequently, retrograde flow resulted in significantly larger sinusoidal blood volumes (45%), albumin Disse space (42%) and sucrose Disse space (25%) than during normal flow, whereas the distribution spaces for total and intracellular water remained unaltered. The distension of the vascular tree was confirmed by electron microscopy, by which occasional isolated foci of widened intercellular recesses and spaces of Disse were observed. Cellular ultrastructure was otherwise unchanged, and there was no difference found between normal and retrograde perfusion for bile flow rates, AST release, perfusion pressure, oxygen consumption and metabolic removal of ethanol, a substrate with flow-limited distribution, which equilibrates rapidly with cell water (hepatic extraction ratios were virtually identical: normal vs. retrograde, 0.50 vs. 0.48 at 6 to 7.4 mM input concentration). These findings suggest that the functional and metabolic capacities of the liver remain unperturbed during retrograde perfusion, rendering the technique suitable for the investigation of zonal differences in drug-metabolizing enzymes.
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PMID:The multiple-indicator dilution technique for characterization of normal and retrograde flow in once-through rat liver perfusions. 264 47

The toxicity of carbon tetrachloride (CCl4) in monolayer cultures of primary hepatocytes was investigated at oxygen concentrations that prevail in the liver under conditions that range from normoxia to hypoxia: 0.5, 1, 2, and 20% O2. CCl4 was administered in the vapor phase at concentrations that produce aqueous concentrations at 37 degrees C of 0.4, 2.0, and 4.0 mM. Damage was assayed by leakage of aspartate transaminase and the inclusion of Trypan Blue immediately after the 2-hr incubation and after an additional 6-hr incubation in 20% O2. Only in the case of 0.5% O2 and 4 mM CCl4 were the monolayers damaged (18%) immediately after the 2-hr exposure; all other exposed cells were undamaged at that time point and the dose response of cell death as a function of CCl4 and oxygen concentration was not evident until the 6-hr time point. The monolayers exposed to 4 mM CCl4 and 1, 2, or 20% O2 exhibited little immediate damage but were all 100% dead 6 hr later. The monolayers exposed to 2 mM CCl4 and 0.5, 1, 2, or 20% O2 were 53, 48, 40, and 22 +/- 2% dead after 6 hr, respectively. These results suggest that effects of CCl4 exposure, for example alterations in the function or synthesis of essential proteins, require several hours to affect cell viability.
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PMID:Interaction of hypoxia and carbon tetrachloride toxicity in hepatocyte monolayers. 270 81

Function and stability of vascularly perfused, recirculating in situ rat intestine (I) and intestine-liver (IL) preparations were evaluated in fasted and nonfasted rats because these techniques may be readily applied in drug metabolism studies. The rat intestine was perfused with blood medium (7.5 ml/min) via the superior mesenteric artery, with the venous outflow draining into the portal vein, which, together with hepatic arterial flow (2.5 ml/min), constituted the total blood flow (10 ml/min) to the liver. Maintenance of intestinal membrane integrity was observed. Rapid [14C]glucose absorption against a concentration gradient and a lack of [3H]-polyethylene glycol 4000 (PEG 4000, less than 4%) and Evans blue absorption by the recirculating I and IL preparations resulted after bolus injections of these markers into the pyloric end of the duodenum. Other indexes that revealed stable intestinal and liver functions were the following: preservation of reservoir perfusate volume, constancy in perfusion pressure, bile flow, and hemoglobin concentrations, evidence of intestinal glucose utilization and liver glucose production, and a lack of significant leakage of serum glutamic oxalic transaminase. The intestine and liver consumed oxygen at relatively constant rates, but the consumption rates for the fasted tissues (I or L) were significantly higher than those for nonfasted tissues. These results indicate that the vascularly perfused I and IL preparations were maintained in a viable and stable state for a 2-h perfusion period.
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PMID:Viability of the vascularly perfused, recirculating rat intestine and intestine-liver preparations. 276 10

To determine whether iron toxicity is caused by iron-catalyzed radical production, the in vivo effect of ferric citrate was studied in paraquat-intoxicated mice. Intraperitoneally injected Fe3+-citrate complex was distributed mainly in the liver and kidney, and promoted lipid peroxidation, as measured by expiratory ethane in both normal and paraquat-intoxicated mice. Plasma glutamic-oxaloacetic transaminase (L-aspartate: 2-oxoglutarate aminotransferase, EC 2.6.1.1) activity increased significantly only in paraquat and Fe3+-citrate-injected mice (PFe group). The rate of ethane production increased prior to the elevation of plasma glutamic-oxaloacetic transaminase levels, and was greater in the PFe group than in the mice, that were injected Fe3+-citrate alone. Pretreatment of animals with desferrioxamine mesylate inhibited both ethane production and elevation of plasma glutamic-oxaloacetic transaminase levels in the PFe group. Administration of 100% oxygen or glucose, which is expected to increase cellular NADPH, to the PFe group further elevated the plasma glutamic-oxaloacetic transaminase level, but had little effect on ethane production, indicating that tissue injury occurs independently of lipid peroxidation. These results suggest that iron toxicity is due to radical production and that, although iron stimulated lipid peroxidation, it might not be the only cause of tissue injury.
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PMID:Lipid peroxidation and tissue injury by ferric citrate in paraquat-intoxicated mice. 282 71


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