Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of cyclosporine on hepatic ischemia was investigated. Hepatic ischemia was produced for 90 min in mongrel dogs. Experimental dogs were divided into three groups as follows: group A (control group), group B (CsA pretreatment group), group C (CsA posttreatment group). CsA was administered at a dose of 10 mg/kg body weight/day for 3 days in the pre- or postoperative period. Survival rates were 61.5% in group A, 84.6% in group B, and 30.8% in group C. Enzymatic activity such as aspartate aminotransferase and lactate dehydrogenase was highest in group C, lowest in group B, and intermediate in group A. Opposite results were obtained for serum albumin concentrations. The mechanisms of the effect was investigated using a 60-min hepatic ischemia model. Serum levels of beta-glucosidase and beta-galactosidase in group B were lower than those in group A and group C. Electronmicroscopic specimens taken at 16 h after 60-min hepatic ischemia demonstrated that the extent of ischemic injury was mildest in group B. The present study demonstrated a beneficial effect on hepatic ischemia of CsA administered for 3 days prior to the ischemia. One of the mechanisms for this beneficial effect could be the stabilization of lysosomal membranes. These results suggest that CsA should be administered to a donor before organ harvesting for liver transplantation because of this beneficial effect.
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PMID:Beneficial effect of cyclosporine pretreatment in canine liver ischemia. Enzymatic and electronmicroscopic studies. 190 40

This study tests the importance of amino acid transamination in determining the tolerance of immature hearts to ischemic damage. Amino acid transamination was inhibited metabolically by pretreatment with aminooxyacetic acid. The aminooxyacetic acid dose and duration were determined by incubating in vitro tissue homogenate and showing that an 8 mmol/L AOA dose for 5 minutes blocked 90% of alanine aminotransferase and aspartate aminotransferase activity. Control studies in nonischemic hearts showed that coronary perfusion with aminooxyacetic acid for 5 minutes did not impair myocardial performance. In contrast, pretreatment of immature puppies with aminooxyacetic acid severely impaired recovery after 45 minutes of normothermic global ischemia (30% versus 85% recovery in untreated hearts, p less than 0.05). Biochemical analyses of hearts undergoing ischemia showed aminooxyacetic acid to limit lactate production, impair glutamate utilization, prevent alanine production, and limit succinate accumulation (p less than 0.05). These data suggest that amino acid transamination is an important adaptive process in the immature heart that improves its resistance to ischemic damage.
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PMID:Studies of myocardial protection in the immature heart. II. Evidence for importance of amino acid metabolism in tolerance to ischemia. 224 11

Hepatic ischemia induced in vivo by ligation of the left hepatic lobe of rats for up to 2 hr had no effect on cytochrome P-450, cytochrome c reductase, or lobe histology; however, cytochrome b5 increased with ischemia duration. Ethylmorphine demethylation decreased 35% after 2 hr of ischemia. Reperfusion of tissue previously made ischemic for up to 2 hr was associated with appreciable necrosis as well as decreases in cytochrome P-450, cytochrome b5, cytochrome c reductase, and ethylmorphine demethylation. Serum alanine transaminase and aspartate transaminase concentrations were increased by reperfusion of previously ischemic tissue. Reperfusion of the previously ischemic lobe for 18 hr was associated with a greater loss of cytochromes P-450 and b5, cytochrome c reductase, and ethylmorphine demethylation than reperfusion for 1 hr. The total decrease in cytochrome P-450 and b5 content was equal to the decrease in total microsomal heme content, although cytochrome P-450 decreased more than cytochrome b5. Ethoxyresorufin deethylation by hepatic microsomes from 3-methylcholanthrene-treated rats was decreased by ischemia-reperfusion; however, pentoxyresorufin dealkylation by hepatic microsomes from phenobarbital-treated rats was not, suggesting specific cytochrome P-450 isozyme loss. In vitro NADPH-dependent lipid peroxidation in hepatic microsomes from control and phenobarbital- and 3-methylcholanthrene-treated rats resulted in a selective decrease of ethoxyresorufin but not pentoxyresorufin dealkylation, similar to that observed in livers subjected to ischemia-reperfusion in vivo. These data suggest that cytochrome P-450, ethylmorphine demethylation, and ethoxyresorufin deethylation are more susceptible to ischemia-reperfusion injury than cytochrome b5 or pentoxyresorufin dealkylation.
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PMID:Effects of hepatic ischemia-reperfusion injury on the hepatic mixed function oxidase system in rats. 225 Jun 63

The Eurocollins (EC) and University of Wisconsin (UW) preservation solutions were compared in a rat liver transplant model. After hepatectomy, 48 rat livers were flushed with either EC or UW preservation solution and were randomly assigned to 1, 12, 24, and 30 h of preservation at 4 degrees C, resulting in eight groups each containing six livers. Following preservation, orthotopic liver transplantation with reconstruction of the hepatic artery was performed. The efficacy of the preservation solution was assessed at 48 h post-transplantation by survival histological features and aspartate transaminase assay (AST) values. None of the rats survived 30 h of liver preservation with EC whereas five out of six rats did with UW preservation. After 24 h of liver preservation, three of the six rats in the EC group survived, compared to all six rats in the UW group. Histological evidence of severe ischemia was found in both groups in all but one survivor (UW, 24 h). After 12 h of EC preservation, one rat died within 48 h and severe ischemic changes were found in the remaining five rats. Among the rats with 12 h of UW preservation, only two out of six showed ischemic changes, and all six rats survived beyond 48 h. Without preservation (1 h), ischemic damage was found in two out of six rats in each group and all rats survived. The median AST values were higher in the EC groups than in the UW groups; the difference became significant after 12-h preservation (EC 900 IU/l versus UW 465 IU/l) and 24-h preservation (EC 5220 IU/l versus UW 631 IU/l).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of University of Wisconsin (UW) and Eurocollins (EC) preservation solutions in a rat liver transplant model. 227 Oct 85

Scarcity of small donors results in a high mortality rate for children on liver transplant waiting lists. To alleviate this problem, we have recently started to reduce the size of livers from older donors to use in children. In the last year, a total of 20 liver transplants were performed in 17 patients, including seven reduced-size liver transplants (RSLT) in six children. Mortality on the waiting list has been reduced to negligible amounts compared with a mortality rate of 25% before starting RSLT in patients with acute liver failure or those whose weight was less than 10 kg. Children undergoing RSLT weighed 10.8 +/- 8.5 kg compared with 20.9 +/- 20.3 for all others (NS). Cold ischemia time was significantly longer in the RSLT group (9.5 +/- 3.0 v 6.0 +/- 2.8 hours, P less than .05) as was intraoperative blood loss (9.4 +/- 9.4 v 3.0 +/- 3.5 blood volumes). There was no significant difference in postoperative aspartate aminotransferase and prothrombin time between the two groups. Four children received a RSLT as a primary procedure and three have survived with good liver function. Two patients were retransplanted with RSLT after a failed first transplant and both died of nonhepatic complications. This compares with 11 of 13 survivors in the whole liver transplant group. Causes of death in children who died after RSLT include cytomegalovirus sepsis (2) and myocardial infarction(1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early experience with reduced-size liver transplants. 227 30

The records of 215 liver transplant recipients were reviewed and the degree of preservation injury was estimated by the initial aminotransferase levels. This was compared with the incidence of rejection found in the subsequent 30 days. Those with aspartate aminotransferase greater than 2000 U/L were classified as having severe preservation injury while those with ASAT less than 600 U/L were considered to have had minimal preservation injury. There were no significant differences between these groups in recipient age, sex, cold ischemia time, preoperative physical status, panel-reactive antibodies, or cytotoxic crossmatch. The solution used for organ preservation and the donor age were the only factors that were found to be significantly different between the groups. Older donors were more common in the severe preservation injury group. Severe preservation injury was found more frequently in grafts preserved in Eurocollins solution and the group with minimal preservation injury more frequently used Wisconsin solution. There was significantly more rejection seen in the severe preservation injury group (71%) than in the group without preservation injury (33%). Although there was more rejection in the severe preservation injury group, the rejections were not more severe as judged by the need for multiple courses of therapy or the need for OKT3. Recurrent rejection was also not more frequent in either group. Graft survival was worse in the severe preservation injury group, with a significant increase in early graft loss, but no difference in the frequency of chronic rejection. Recovery of graft function was also delayed in the preservation injury group.
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PMID:The influence of preservation injury on rejection in the hepatic transplant recipient. 230 Sep 99

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

To assess the severity of ischemic liver injury, we examined release of mitochondrial aspartate aminotransferase (EC 2.6.1.1) and its cytoplasmic isozyme from the ischemic rat liver into the circulation. Their patterns of leakage were quite different: the level of cytoplasmic aspartate aminotransferase reached a peak soon after the circulation to the ischemic liver was restored, while that of mitochondrial aspartate aminotransferase increased slowly, reaching a maximum after more than 10 hr. On anoxic incubation of mitochondria isolated from the normal liver, oxidative phosphorylation capacity was lost within 2 hr, at which time no leakage of matrix enzymes was observed: more than 10 hr after-loss-of-oxidative phosphorylation were needed for the matrix enzymes to leak out of the mitochondrial membrane. Since the viability of cells is considered to depend on the capacity of oxidative phosphorylation, it is highly likely that the delayed appearance of mitochondrial aspartate aminotransferase in blood indicates the postmortem changes of injured cells. In fact, the cumulative activity of mitochondrial aspartate aminotransferase but not cytoplasmic aspartate aminotransferase in circulation after ischemic liver injury correlated fairly well with the decrease of total adenine nucleotides which were monitored to measure viable cells. The difference between mitochondrial aspartate aminotransferase and cytoplasmic aspartate aminotransferase as quantitative indices of hepatic necrosis may be due to the relative stability of the former and significant inactivation of the latter during hepatic ischemia. Therefore, the determination of mitochondrial aspartate aminotransferase in blood may be useful in the assessment of liver necrosis after ischemic injury.
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PMID:Blood level of mitochondrial aspartate aminotransferase as an indicator of the extent of ischemic necrosis of the rat liver. 242 71

The effects of aprotinin on canine myocardium subjected to cardioplegia and global ischemia for 4 hours and then reperfused for 1 hour were investigated. Lysosomal and mitochondrial enzymes and cyclic nucleotides (adenosine cyclic monophosphate and guanosine cyclic monophosphate) were measured in coronary sinus blood. Aprotinin was given intravenously before cardiopulmonary bypass at total doses of 10 X 10(3) kallikrein units per kilogram (group A, six dogs) and 20 X 10(3) KU/kg (group B, six dogs). In group A, three dogs survived but with poor cardiac function; all dogs in group B survived and had better cardiac function. Lysosomal (N-acetyl-beta-D-glucosaminidase) and mitochondrial (aspartate aminotransferase) enzymes in coronary sinus blood at 60 minutes of reperfusion were significantly (p less than 0.05) lower in group B than in group A. In both groups, guanosine cyclic monophosphate was significantly (p less than 0.01) lower during reperfusion than before cardiopulmonary bypass; however, the values were significantly (p less than 0.05) higher in group B than in group A. Serum adenosine cyclic monophosphate was lower during reperfusion than before bypass in both groups, but it recovered during reperfusion in group B. Myocardial adenosine triphosphate was well preserved in both groups but creatine phosphate was decreased (p less than 0.01) in group A. These results suggest that aprotinin at a dose of 20 X 10(3) KU/kg may be effective in preserving myocardial viability and function after prolonged cardioplegia.
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PMID:Role of protease inhibition in myocardial preservation in prolonged hypothermic cardioplegia followed by reperfusion. Effect of aprotinin in an experimental model. 245 28


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