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)

The study of patterns of serum AST, ALT, CPK, LDH, and glycogen phosphorylase (GP) activity following bicycle ergometry in 26 male patients 1 to 1.5 months after myocardial infarction demonstrated no increase in AST, ALT and CPK activity, whereas total LDH activity was increased, with a tendency to elevated LDH-1 and LDH-2 fractions, as compared to the baseline, in those cases where exercise was discontinued because of ST depression. Patients with favorable response to bicycle ergometry that continued until the submaximum heart rate for a given age was achieved showed a tendency to elevated LDH-5 that may be a physiological response to exercise. The demonstrated increase in total GP activity, both in patients with exercise-induced ST depression and in those with elevated ST from the leads corresponding to the site of myocardial infarction, may reflect stress-induced reversible ischemia.
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PMID:[Effect of physical loading on serum enzyme activity in post-myocardial infarct patients]. 370 99

Hind-limb ischemia secondary to infrarenal aortic ligation in the rat was evaluated as a traumatic injury model for the study of the effects of trauma on the two major hepatic microsomal drug-oxidizing enzyme systems. Ischemic injury resulted in a significant decrease in hepatic cytochrome P-450 content and FAD-containing monooxygenase activity. Bilateral lower leg fracture was used as a dissimilar traumatic injury model in order to confirm these results and produced similar effects on these enzyme systems. Both forms of injury appeared to be of only moderate severity, and neither injury caused significant histopathological changes in the liver. Moreover, both injuries caused only mild hepatic damage as indicated by relatively modest elevations in glutamic-pyruvic transaminase levels. The observed reductions of cytochrome P-450 content with both forms of model injury were paralleled by decreases in the in vivo metabolism of antipyrine. Thus, it appears that trauma may have a significant, and possibly selective, effect on hepatic drug metabolism, suggesting that careful monitoring and/or dosage adjustment may be in order in some cases of post-traumatic drug therapy. Moreover, the ischemic injury produced by infrarenal aortic ligation in the rat appears to be a suitable small mammal injury model for the further study of the effects of trauma on the various hepatic drug-metabolizing enzyme systems.
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PMID:Effects of model traumatic injury on hepatic drug metabolism in the rat. I. In vivo antipyrine metabolism. 614 Jan 33

The aim of this paper is to elucidate the cause of death after 90 min of normothermic partial (2/3) ischemia of the liver and to examine the effects of glucagon, somatostatin, insulin, prednisolone and oral administration of polymyxin B (PB). The animals 24 hr after partial ischemia for 90 min were divided into two groups; namely, animals with normal appearance and those with moribund state. There were no significant differences in the plasma level of S-GOT, S-GPT, amino acids, NH3 or insulin, or in morphometrically estimated volume ratio of necrotic hepatocytes between the two groups of rats. The blood glucose level, however, was significantly decreased (31 +/- 28 mg/100 ml, n = 6) in the moribund rats with a higher incidence of positive Limulus gelation tests as compared with the rats with normal appearance (149 +/- 19, n = 5). The 1-day and 1-week survival rates of the animals were 42/62 (69%) and 32/61 (53%), respectively. A glucagon injection (1.5 mg/kg, after ischemia) was effective to elevate the 1-day survival rate (14/14), but failed to increase the 1-week survival rate (11/14). On the other hand, a somatostatin injection (100 micrograms/kg, after ischemia) or PB treatment (15 mg/kg/day x 5-9, before ischemia) succeeded to increase the 1-week survival rate (20/22 p less than 0.01 and 17/17 p less than 0.01, respectively), although no significant amelioration in transaminase levels or volume ratio of necrosis was demonstrated. It could be seen that a moribund state after partial ischemia was accompanied by severe hypoglycemic shock, and that the injection of somatostatin after ischemia or the annihilation of gram-negative bacteria by means of oral administration of polymyxin B before ischemia prevented the occurrence of the hypoglycemic shock.
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PMID:Postischemic liver damage in rats: effect of some therapeutic interventions on survival rate. 629 17

Intracellular enzyme activities can be greatly influenced by alterations of pH, and non-physiologic pH may inhibit cell metabolism. The study was undertaken to examine the influence of pH values in preservation solution on ischemic tolerance time of the liver. BDE rat livers were used. Livers were preserved for 20 min or 2 h in warm ischemia after an initial perfusion with Ringer's solution at pH 9.0, 7.4, and 6.0. The values of total adenine nucleotide (TAN) and energy reserve (ER) in the livers were determined at the end of the preservation. After 20 min of warm ischemia, TAN values at pH 9.0 and 7.4 fell to 2.727 +/- 0.255 and 2.410 +/- 0.164 mumol/g, respectively (normal values: 3.414 +/- 0.270 mumol/g) and ER values to 0.786 +/- 0.186 mumol/g at pH 9.0 and to 0.446 +/- 0.095 mumol/g at pH 7.4 (normal values: 2.962 +/- 0.214 mumol/g). A similar trend was also observed after 2 h of warm ischemia. The preservation with a solution at pH 6.0 did not present any difference as compared to that at pH 7.4. Four-hour preservation in cold ischemia with Ringer's solution at pH 9.0 rendered higher values of TAN (2.635 +/- 0.085 mumol/g) and ER (0.336 +/- 0.026 mumol/g) than those in preservation at pH 7.4. No significant difference between TAN and ER values was found when 4-h preservation at pH 7.4 and 6.0 was compared. In another group an intermittent liver perfusion at 1-h interval was performed with chilled Ringer's solution; afterwards GOT, GPT, beta-glucuronidase, and acid phosphatase values in the effluents were evaluated. All of these enzymes showed higher concentration in the effluent with solution at pH 7.4 than that at 9.0. These results suggested that better intracellular energy reserve and organ viability can be maintained by preservation with alkaline solution. Furthermore, ER values seemed to be an excellent indicator of the organ viability during preservation. These were also confirmed by orthotopic hepatic transplantation in pigs. Livers were successfully preserved with alkaline Ringer's solution for up to 12 h. However, without change of pH, livers could not be preserved for more than 4.5 h.
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PMID:[Prolongation of ischemic tolerance time of donor livers by alkaline preservation solutions]. 647 1

Following the clamping of the afferent vessels of the left lateral and median lobes in rat liver, a considerable part of these lobes show signs of necrosis 24 h after 90 min of ischemia, whereas no necrotic areas can be detected after 30 min interruption of the blood flow. The purpose of this study was to examine the value of an analysis of the leakage of enzymes from the liver parenchyma in the early phase after restoration of the blood flow after ischemia for a prediction of the occurrence of necrosis. Leakage of the enzymes GPT, GOT and LDH can be detected in the blood plasma with a maximum activity between 1 and 5 h both following 30 and 90 min of ischemia; a considerable difference in clearance is observed, however, in the period afterwards, the normal situation being reached after 24 h with the 30-min ischemic period, but not following the 90-min period. With use of an enzyme histochemical reaction, in situ a depletion of LDH-activity in the hepatocytes could be detected within a short period of time after 30 min temporary ischemia and a restoration during the following period of 24 h; the decrease in LDH-activity persisted during 24 h with a 90-min period of ischemia. Electronmicroscopically cytoplasmic blebs arisen from hepatocytes are observed in the lumen of sinusoids immediately after 30 min of ischemia, whereas after 90 min of ischemia actual leakage of cytoplasmic material takes place through the damaged surface of the hepatocytes. Enzyme leakage probably takes place via these both types of shedding of cytoplasm. It is concluded that the enzyme leakage as such cannot be used as a discriminating test between reversible and irreversible damage of the liver parenchyma.
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PMID:The value of enzyme leakage for the prediction of necrosis in liver ischemia. 661 12

We examined the polyamine metabolism in liver transplanted after cold ischemia and effects of putrescine administration on liver injury, liver regeneration, and survival rate after orthotopic liver transplantation in the rat. Male Wistar rats were used as donors and recipients. Grafts were stored in Euro-Collins solution for 6 h at 4 degrees C. Orthotopic liver transplantation was performed by the three cuff technique. The activities of aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase elevated and peaked 4 h after liver transplantation. Hepatic ornithine decarboxylase and spermidine/spermine N1-acetyltransferase activities were also elevated and peaked 8 h after the operation. In agreement with the increases in ornithine decarboxylase and spermidine/spermine N1-acetyltransferase activities, the putrescine content increased and spermidine content decreased in the transplanted liver. Putrescine administrated intraperitoneally improved the survival rate, decreased serum transaminase level and increased the [3H]thymidine incorporation into the liver DNA. These findings suggest that both biosynthetic and biodegradative pathways are stimulated in liver transplantation, resulting in the increase in the formation of putrescine from ornithine and from spermidine, and that putrescine administration improve the survival rate by protecting the damaged graft after cold ischemia and reperfusion and by stimulating liver regeneration.
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PMID:Polyamine metabolism in the rat liver after orthotopic liver transplantation. 749 79

In a group of 276 consecutive liver transplants 8 primary graft nonfunctions were identified (2.9%). Recipients showed a progressive elevation of transferases (mean maximum value ALT: 5000 +/- 1892 U/l) and bilirubin (mean maximum value: 20 +/- 11.8 mg/dl) and a decrease in the percent prothrombin time (mean minimum value 26 +/- 13 min.) in the post-implantation survival time of the 8 grafts (range 1-5 days). No statistically significant differences were observed between mean cold and warm-ischemia times for these 8 donor organs and those of a control group of 92 consecutive grafts. All organs except one were ABO isogroup and all except another one displayed negative lymphocytotoxic crossmatch. Predominantly small-droplet hepatocytic vacuolization with no nuclear displacement was observed in plastic-embedded semithin sections of all post-primary nonfunction liver tissues (severe in 4 grafts, centri-mediozonal in 2, and centrolobular in 2). In 3 cases where fresh liver tissue was available the lipidic nature of the vacuoles was confirmed with electron microscopy and with frozen sections stained with Sudan III. Other microscopic lesions were also observed: spotty monocellular coagulative necroses, variable extension of zonal coagulative necroses and hemorrhages, cholestasis and minor mixed inflammatory infiltrate. Comparative microscopic study of these tissues with the protocol biopsy specimens obtained 2-4 hours after reperfusion demonstrated previous liver cell-vacuolization in only 3 cases. In conclusion, an acute progressive microvascular steatosis developed in this primary nonfunction series. No specific etiopathogenic factors were identified.
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PMID:A clinopathologic review of 8 liver graft primary nonfunctions. 759 May 68

The liver has been judged relatively resistant to ischemia, but prolonged inflow occlusion at normothermic conditions can produce evidence of reversible or irreversible hepatocellular damage. Cytoprotective agents have been used both experimentally and clinically to afford extended viability of hepatocytes under reduced perfusion. One agent, prostaglandin E1, has been described clinically as effective in sustaining liver function under ischemic conditions. We have sought to verify this observation in an experimental model using prolonged normothermic inflow occlusion. Twenty miniature pigs were anesthetized and subjected to subtotal normothermic hepatic inflow occlusion (portal vein, hepatic artery, choledochal vessels) to allow for sufficient splanchnic decompression. Half of the animals received pretreatment with prostaglandin E1 (alprostadil) 500 micrograms intravenously. Inflow occlusion was maintained for 2 hours followed by reperfusion and killing 24 hours later. As a measure of functional preservation, the tissue adenine nucleotides adenosine monophosphate, diphosphate, and triphosphate (AMP, ADP, ATP) were measured in ischemic liver by freeze-clamping and high-performance liquid chromatography during occlusion and after reperfusion. Cytosolic enzyme determinations (aspartate transaminase, alanine transaminase, lactate dehydrogenase) were also made before occlusion and after reperfusion. As a possible indicator of cellular injury, blood ionized Ca++ was measured before inflow occlusion and after reperfusion. Although no difference was found in levels of AMP and ADP between prostaglandin E1 and control animals, ATP levels rose significantly higher during recovery in prostaglandin E1 animals at 60 minutes and 24 hours after reperfusion (13.97 +/- 1.29 and 13.60 +/- 0.91 mumoles/gm dry weight prostaglandin E1 vs. 9.25 +/- 0.97 and 9.80 +/- 0.85 mumoles/gm dry weight co control, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of prostaglandin E1 on liver adenine nucleotides and cytoplasmic enzymes in a porcine model of normothermic hepatic ischemia. 759 Jun 75

Amlodipine, a long acting calcium antagonist, was used to reduce the adverse effects of ischemic/reperfusion injury studied in isolated perfused rat livers. Amlodipine (10 mumol/L) was added to University of Wisconsin (UW) solution in which the liver was stored for 24 hr at 4 degrees C and incorporated in the saline flush used to displace the UW solution before 20 min of warm ischemia (at 37 degrees C) and reperfusion. Initial median blood flow at 15 min was significantly higher after amlodipine treatment (2.78 vs. 1.41 ml/min/g of liver without amlodipine treatment, P = 0.013) as was the area under the curve of blood flow for the entire 3-hr perfusion (472 vs. 316 ml/g of liver, P = 0.003). Amlodipine treatment induced corresponding increases in oxygen delivery (1302 vs. 896 mumol of O2/g of liver over 3 hr of perfusion, P = 0.003) and oxygen consumption (279 vs. 242 mumol of O2/g of liver over 3 hr, P = 0.06). Initial bile flow at 15 min was increased 4-fold by amlodipine treatment (17.27 vs. 4.59 mg/hr/g of liver for sequential cold and warm ischemia, P = 0.013), and the median area under the curve of bile flow for the entire perfusion increased to 92.2 vs. 53.9 mg/g of liver (P = 0.0006). Amlodipine treatment also reduced glucose release into the perfusate (116 vs. 149 mmol/L/g of liver min over 3 hr, P = 0.03) and prevented hepatocyte injury by reducing alanine aminotransferase release both initially (0.43 vs. 0.96 IU/L/g of liver, P = 0.055) and overall (343 vs. 797 IU/L/g of liver min, P = 0.048). When amlodipine was added only to the UW solution, blood flow increased by 66% initially (P = 0.02) and 32% overall (P = 0.013), but there was no corresponding improvement in hepatic function. Amlodipine may reduce hepatic ischemic/reperfusion injury by cytoprotective effects on parenchymal and non-parenchymal hepatocytes during both preservation and reperfusion leading to an improvement in liver microcirculation and an inhibition of the release of toxic mediators.
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PMID:Amlodipine improves hepatic hemodynamic and metabolic function in the isolated perfused rat liver after sequential cold and warm ischemia. 762 39

We investigated whether intraportal injection of 150 mg/kg N-acetylcysteine (NAC) into rats reduced hepatic ischemia-reperfusion injury after 48 hours of cold storage and 2 hours of reperfusion. The organ was isolated and perfused to evaluate liver function. The control group received an intraportal injection of 5% dextrose. NAC increased L-cysteine concentrations 15 minutes after injection (1.29 +/- 0.11 mumol/g vs. 2.68 +/- 0.4 mumol/g, P < .05). However, neither treatment modified glutathione liver concentrations relative to preinjection values. After 48 hours of cold storage and 2 hours of reperfusion, livers from NAC-treated rats produced larger amounts of bile than those in the control group (5.04 +/- 1.92 vs. 0.72 +/- 0.37 microL/g liver; P < .05), and showed a significant reduction in liver injury, as indicated by reduced release of lactate dehydrogenase (679.4 +/- 174.4 vs. 1891.3 +/- 268.3 IU/L/g; P < .01), aspartate transaminase (AST) (13.94 +/- 3.5 vs. 38.75 IU/L/g; P < .01), alanine transaminase ALT) (14.92 +/- 4.09 vs. 45.91 +/- 10.58 IU/L/g; P < .05), and acid phosphatase, a marker of Kupffer cell injury (344.4 +/- 89.6 vs. 927.3 +/- 150.8 IU/L/g; P < .01) in the perfusate. Reduced glutathione concentrations in the perfusate were similar in the two groups (805 +/- 69 vs. 798 +/- 252 nmol/L/g), whereas oxidized glutathione (GSSG) concentrations were higher in the control group (967 +/- 137 vs. 525 +/- 126 nmol/L/g; P < .05). Reduced glutathione (GSH) concentrations in liver tissue collected at the end of perfusion were significantly higher in the NAC group (7.3 +/- 0.9 vs. 4.1 +/- 1.0 mumol/g; P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effects of N-acetylcysteine on hypothermic ischemia-reperfusion injury of rat liver. 763 22


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