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:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to evaluate the use of hepatic venous oxygen saturation (Shvo2) as a predictor of early graft function after liver transplantation. We examined the levels of Shvo2 and serum ALT after transplantation using the isogeneic rat orthotopic liver transplant model. Shvo2 levels 2 hr after reperfusion in the 6-hr cold ischemia (nonviable allograft) group were significantly lower than those in the 1-hr and 3-hr cold ischemia (viable allograft) groups. However, there was no significant difference in ALT levels among these groups. These results suggest that decreased hepatic blood flow due to microcirculatory disturbances may occur in the nonviable allograft even in the early phase of reperfusion and may be responsible for ischemic damage to parenchymal cells. Therefore, Shvo2 could provide a simple index of the initial graft status and be useful for a rapid etiological diagnosis of early postoperative graft dysfunction and for estimating the graft outcome after liver transplantation.
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PMID:Evaluation of early graft function by hepatic venous hemoglobin oxygen saturation following orthotopic liver transplantation in the rat. 895 78

We investigated the efficacy of a new rinse solution containing nafamostat mesilate (NM) (a serine protease inhibitor) for liver preservation with modulation of Kupffer cell function. Orthotopic liver transplantation (OLT) was performed in male Lewis rats after 24 h of cold storage in University of Wisconsin organ preservation solution. After OLT, survival was determined, together with assays of blood chemistry, tissue NM metabolites, and histology 3 h after OLT. NM rinse was found to have a cytoprotective effect on liver parenchymal cells, based on enzyme data showing that NM rinse reduced the release of serum alanine aminotransferase significantly in comparison with saline rinse (P < 0.05). However, the effect was not sufficient to improve the survival rate. In contrast, when the donor was treated with gadolinium chloride 24-30 h before graft harvest, NM rinse improved the survival rate to around 80% compared with 25% for saline. The assay of NM metabolites in grafted liver tissue showed that pretreatment of the donor rats with GdCl3 delayed the degeneration of NM in the liver tissue. These data demonstrate that NM rinse and Kupffer cell blockade exert synergistic effects, leading to increased survival after cold-preserved liver transplantation.
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PMID:Synergistic effects of nafamostat mesilate rinse and Kupffer cell blockade for rat liver preservation. 895 83

Eighty liver allografts were studied to determine the predictive value of intraoperative biopsies and postoperative liver function tests for the development of preservation injury (PI). Peak transaminase (aspartate transaminase [AST] and alanine transaminase [ALT]) and prothrombin time (PT) values achieved by each patient during postoperative days (POD) 1 through 7 were determined. PI in day 0 preperfusion biopsies (0Pre) (obtained immediately before implantation) and postperfusion biopsies (0Post) (obtained immediately after revascularization) was categorized by histological criteria as present or absent. PI in biopsies taken during POD 2 through 14 was histologically graded as either moderate-to-severe, mild, or absent. Of the 80 allografts, 8 were omitted because of primary nonfunction or postoperative complications. 0Pre and 0Post biopsies were available on 25 of 72 (35%) and 69 of 72 (96%) allografts, respectively. Only 2 (8%) of the 0Pre biopsies showed histological PI compared with 48 (70%) of the 0Post biopsies. Fifty-nine patients were biopsied between POD 2 through 14. Of these, 15, 28, and 16 patients developed moderate-to-severe, mild, or no evidence of PI, respectively. The presence of PI in the 0Post biopsy strongly correlated with the development of PI during POD 2 through 14 (P < .0005). Peak AST and ALT values in patients with moderate-to-severe PI on POD 2 through 14 were significantly elevated compared with those patients with either mild (P = .01 and .03) or no PI (P = .02 and .006). Because of extensive overlap in AST and ALT values between the three groups, however, transaminase values were not useful in predicting the presence or absence of PI in the individual case. The development of PI during POD 2 through 14 correlated with advanced donor age (P = .06) but was unassociated with 0Pre biopsy findings, cold ischemia time, or peak PT values. We conclude that the 0Post biopsy is a valuable tool for the prediction of subsequent PI in the early postoperative period. In contrast, 0Pre biopsy findings and peak AST and ALT values are not useful in the assessment of PI.
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PMID:Predictive value of intraoperative biopsies and liver function tests for preservation injury in orthotopic liver transplantation. 898 88

We analyzed the long-term clinical course of 71 patients with RNA-positive hepatitis C virus (HCV) infection after liver transplantation. Patients with reinfection after transplantation for HCV-related liver disease, or de novo infection at transplantation were followed for up to 12 years. Cumulative survival for patients with HCV infection at 2, 5, and 10 years after transplantation was 67%, 62%, and 62%, respectively. It was not significantly different from that in patients transplanted for other nonmalignant diseases without HCV infection. The main factor determining long-term survival was the presence or absence of hepatocellular carcinoma (HCC) at transplantation. The 5-year survival rate for HCV patients with or without HCC was 35% versus 73%, respectively (P < .05). No deaths because of viral hepatitis of the graft were observed. Deaths in the first year after transplantation were caused by infectious complications, cardiovascular problems, or rejection; deaths after more than 12 months were exclusively because of recurrence of HCC. Biochemical and histological evidence of hepatitis was found in the majority of the patients, only 16% had normal alanine aminotransferase (ALT) values throughout. Twenty-two percent of patients complained of symptoms, with hepatitis C being the cause in 82% of these. Two patients lost their HCV-RNA for prolonged, ongoing periods of time. The severity of the posttransplantation hepatitis was unrelated to age, sex, severity of liver disease before transplantation, cold ischemic time of the graft, duration of the operation, transfusions, the number of rejection episodes, or the long-term immunosuppressive regime. Only initial short-term therapy with interleukin 2 (IL2) receptor antibodies adversely influenced inflammatory activity. Viral genotype did not influence the course of the graft hepatitis in our series. Histology showed inflammation in 88% of the biopsies and signs of fibrosis in 24%. Mean ALT values correlated with inflammation but not with fibrosis in the biopsies. Porto-portal bridging was observed in six patients, one patient developed cirrhosis within 2 years after orthotopic liver transplantation (OLT). We conclude that chronic hepatitis develops in the majority of patients with HCV infection after liver transplantation. Carrier states without significant laboratory abnormalities are observed in approximately 16%, biochemical abnormalities without symptoms are seen in 60%, and symptomatic disease develops in a quarter of the patients. The disease course closely resembles that seen in nontransplanted hepatitis C patients. It is generally mild but little over 10% of patients develop signs of fibrosis of the graft during the first decade.
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PMID:Long-term outcome of hepatitis C virus infection after liver transplantation. 898 91

Summaries of the interactions caused by altering adrenoreceptor activity in conjunction with the administration of selected hepatotoxicants are provided in Table 2 and Fig. 1. These hepatotoxicants can be divided into two groups, one whose toxicity is increased by adrenergic agonist drugs (group I) and the other whose toxicity is decreased by adrenergic antagonists (group II). Group I includes carbon tetrachloride, acetaminophen, and methylphenidate. Perhaps the most remarkable aspect these chemicals have in common is the striking potentiation that occurs with cotreatment with certain adrenergic agonist drugs. For each of these, cotreatment with the appropriate adrenergic agent can result in massive hepatocellular necrosis from an otherwise nontoxic dose. In terms of the specific adrenoreceptors involved and mechanisms of potentiation, however, they have little in common. Potentiation of carbon tetrachloride hepatotoxicity appears to be mediated by alpha(2)-adrenoceptor stimulation, acetaminophen is potentiated by alpha(1)-adrenoreceptor agonists, and methylphenidate responds to beta(2)-adrenoreceptor stimulation. Studies of the potentiation of carbon tetrachloride and acetaminophen agree that the timing of adrenergic stimulation relative to the hepatotoxicant dose is critically important to the interaction but markedly different for these two toxicants. Acetaminophen was potentiated only when the adrenergic drug was administered as a 3-h pretreatment. This is apparently a consequence of a mechanism of potentiation that involves adrenergic depression of hepatic glutathione content and a requirement that peak effects on glutathione of both the adrenergic agent and acetaminophen be coincident. The mechanism of potentiation of carbon tetrachloride hepatotoxicity is uncertain but clearly does not involve hepatic glutathione content. In contrast to acetaminophen, adrenergic effects must occur within a time window a few hours after the carbon tetrachloride dose for potentiation to occur. The importance of dose timing has not been evaluated for adrenergic potentiation of methylphenidate hepatotoxicity, but it is clear that this interaction is based on yet a third mechanism. While only three hepatotoxicants of the group I type have been examined in detail, the diversity of receptor types and mechanisms involved suggest that this phenomenon may be relevant for a wide variety of hepatotoxic drugs and chemicals. This interaction is also of interest because factors or events that lead to increased adrenergic stimulation are common in everyday life. Most over-the-counter cold and allergy preparations contain sympathomimetic drugs, and many prescription drugs produce adrenergic effects as either an extension of the intended therapeutic effect or as a side effect. Stress and some disease states can also lead to significant increases in peripheral adrenergic activity, creating the potential for increased susceptibility to hepatic injury from exposure to certain drugs or chemicals. Cocaine and bromobenzene represent group II, chemicals whose hepatotoxicity is diminished by cotreatment with adrenergic antagonist drugs. In the case of cocaine, adrenergic antagonist cotreatment was capable of reducing serum alanine aminotransferase activities by approximately 50%. For bromobenzene, the protection afforded by adrenergic antagonist cotreatment was more profound, with minimal hepatic lesions resulting from doses of bromobenzene that otherwise produced lethal hepatic necrosis. For the chemicals in group II, experimental observations are consistent with a phenomenon in which adrenergic potentiation of toxicity is supplied by the hepatotoxicant itself. Both cocaine and bromobenzene, in hepatotoxic doses increase endogenous catecholamine levels. When the effects of the elevated catecholamines are removed with the appropriate adrenergic antagonist, much lower toxicity (presumably due only to the direct hepatotoxic effects of the drug or chemical) is obse
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PMID:Adrenergic modulation of hepatotoxicity. 918 24

We measured enzyme activities along a heterothermic tissue, the visceral retia mirabilia of the bluefin tuna, to test current theories of enzyme temperature adaptation. The heterothermic tissue model is ideal for the study of fundamental temperature adaptation because it eliminates confounding effects of whole animal acclimation. Enzymes were measured at six positions along the rete at four temperatures (15, 20, 25, and 30 degrees C). Five enzymes (aspartate aminotransferase, citrate synthase, glucose-6-phosphate dehydrogenase, glutamate dehydrogenase, and pyruvate kinase) exhibited a significant positive compensatory effect, with activity at the cold end of the rete 1.2-3.1 times higher than at the warm end. Two enzymes (alanine aminotransferase and lactate dehydrogenase) exhibited no significant compensation. On the basis of activation energies of enzymes along the rete, differences in activity were due to differences in enzyme concentration and not isozymes or enzyme modification. Analysis of the compensatory responses of the enzymes in light of their thermal sensitivities leads us to conclude that the pentose phosphate shunt is especially enhanced at the cold end of the rete.
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PMID:Enzyme adaptation along a heterothermic tissue: the visceral retia mirabilia of the bluefin tuna. 922 97

A high positivity of cold activation of complement has been reported in Japanese patients having hepatitis B virus-negative chronic hepatitis. Although the cause of cold activation of complement is unknown, the involvement of hepatitis C virus (HCV) has been suspected. We studied the positivity of cold activation of complement in 253 patients, including 93 patients with chronic hepatitis C infection who received 6MU natural interferon-alpha per day for 24 continuous weeks. Cold activation was positive in 38% of patients with chronic hepatitis C and in 46% of patients with liver cirrhosis C. We did not detect cold activation in asymptomatic HCV carriers; patients with chronic hepatitis B, liver cirrhosis B, or alcohol-related liver damage; or in the controls. Cold activation was also negative in HCV-RNA-negative patients who responded completely to interferon-alpha, and in HCV-RNA-positive patients who responded partially whose serum alanine transaminase levels were normalized after interferon treatment. In the patients who had a relapse of hepatitis C after interferon treatment, positivity of cold activation increased sharply. We conclude that HCV-associated liver damage is related to the development of cold activation of complement. Cold activation is useful for monitoring the response to interferon in patients with chronic hepatitis C infection.
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PMID:Hepatitis C virus-related liver damage is related to cold activation of complement. 941 71

Gut-derived substances can activate Kupffer cells to provoke hepatic necrosis after partial hepatectomy in rats. A similar situation may occur during orthotopic liver transplantation (OLT), as congestion in the intestinal wall, caused by portal vein occlusion, is inevitable during the operation. The contribution of such substances to liver injury following OLT was investigated in rats. Oral administration of polymyxin B sulfate for 7 days significantly altered intestinal bacterial flora in rats; Enterobacteriaceae diminished and anaerobes such as Bifidobacterium , Lactobacillus, Bacteroides, and Eubacterium increased in number, compared with the control rats. Also, this treatment significantly reduced endotoxin concentration in the portal blood 30 minutes after blood reflow following portal vein occlusion. When OLT was performed in rats using the liver preserved in cold University of Wisconsin solution for 18 hours, tissue factor activity in Kupffer cells (KC) isolated from the transplanted liver 1 hour after the operation was significantly higher than in that of normal rats. This increase was significantly reduced by pretreatment of the recipients with polymyxin B sulfate. In these recipients, serum alanine aminotransferase activity, tumor necrosis factor alpha (TNF alpha) concentration, and histological extent of liver necrosis were significantly attenuated at 24 hours after the operation compared with those of control rats. We conclude that the substances derived from bacilli sensitive to polymyxin B sulfate in the gut may be a contributing factor to liver injury following OLT in rats; we feel that this probably occurs by entering of the substances into the portal blood during the ahepatic phase of the operation to activate KC. Selective bowel decontamination of recipients with polymyxin B sulfate would be a candidate for protection against early graft failure following OLT.
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PMID:Selective bowel decontamination of recipients for prevention against liver injury following orthotopic liver transplantation: evaluation with rat models. 942 27

Continuous warm blood cardioplegia was widely used, as an effective means of myocardial preservation, in open heart surgery. The comparisons of myocardial protective effects between traditional cold crystalloid and warm blood cardioplegia, however, have been based mainly on hemodynamics, cardiac function and myocardial metabolism, other than clinical outcome. The present study was designed to examine myocardial protective effects by assessing clinical outcome, enzyme levels and myocardial cytochemistry. Twenty patients undergoing heart valve replacement were divided randomly into two groups: Group I was given intermittent perfusion of cold crystalloid (St. Thomas Hospital solution) with hypothermic cardiopulmonary bypass (CPB) and Group II was given continuous administration of warm blood cardioplegia with normothermic CPB. The groups were similar with respect to sex, age, body surface area and preoperative ventricular function. Blood samples were obtained from an indwelling radial arterial catheter or from the arterial end of the oxygenator. Biopsy specimens from the right atrium were obtained immediately before aortic declamping (ischemic period) and 30 minutes after crossclamp removal (reperfusion period). Serum enzymes, including alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and its isoenzymes and creatine phosphokinase (CK) and its isoenzyme, were determined. Myocardial cytochemistry were chiefly assessed by grey-scale image processing of adenosine triphosphatase (ATPase), succinate dehydrogenase (SDH) and cytochrome oxidase (CCO) examinations. Relations among the results were discussed. Reperfusion time was reduced and ventilation support time decreased in Group II (33.50 +/- 3.78 min vs. 25.00 +/- 4.46 min, p < 0.05; 38.98 +/- 16.55 h vs. 19.84 +/- 1.11 h, p < 0.05). Rates of atrial beating during aortic crossclamp and spontaneous recovery to normal sinus rhythm were much higher in Group II than in Group I (80% vs. 20%, p < 0.05; 70% vs. 10%, p < 0.05). Differences in hospital morbidity and mortality between groups were nonsignificant. Serum AST, ALT, LDH and LDH1 + LDH2 all showed no significant intergroup differences. There was a higher serum CK-MB level with a delayed peak in Group II. The cytochemistry activities of ATPase was not different between groups and periods and SDH was the highest during reperfusion period in Group I and of CCO significantly much promoted in Group II in both periods. Continuous warm blood cardioplegia resulted in higher spontaneous recovery to sinus rhythm, shorter reperfusion and ventilation support time. Damage to the myocardium, skeletal muscle and liver always occur in warm blood cardioplegic patients. However, warm blood cardioplegia is still a practical method for myocardial preservation in open heart surgery.
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PMID:A generalized consideration of myocardial preservation with cold crystalloid versus warm blood cardioplegia in heart valve replacement. 961 11

The isolated perfused rat liver model was used to assess graft viability after 24 h of cold preservation. Two solutions were compared for liver preservation: Belzer's original UW solution (high-K+ UW) and a solution containing the same components but with inverted concentrations of sodium and potassium (high-Na+ UW). During the 120 min of normothermic reperfusion, livers preserved in the high-Na+ UW solution released lower levels of creatine kinase-BB isoenzyme, transaminases (ALT and AST), and potassium than those preserved in the high-K+ UW solution. Bile flow and biliary excretion of indocyanine green increased when livers were preserved in the high-Na+ UW solution. We found no statistical differences for oxygen consumption and tissue ATP concentration. The results of this study support the concept that a high-Na+ UW solution is a more effective means of preserving rat livers, at least after 24 h of cold-storage and 120 min of reperfusion in the isolated perfused model, than the original high-K+ UW solution. Liver preservation in the high-Na+ UW solution reduces damage to sinusoidal endothelial and hepatocellular cells. The use of an extracellular-like Belzer cold storage solution eliminates potassium-related problems in cold preservation and subsequent normothermic reperfusion while keeping all the qualities of the original UW solution.
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PMID:High-Na+ low-K+ UW cold storage solution reduces reperfusion injuries of the rat liver graft. 963 53


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