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 crude protein levels as well as the activities of various enzymes were studied in certain tissues of fetuses (80th through 114th days of development), piglets of different age groups, and pigs for slaughter. In most of the tissues tested the postnatal activities of Na-K-ATPase were beyond those recorded from fetuses. The highest GOT activities were recorded from the liver, myocardium, and kidneys. Activities were found to rise sizeably in some tissues after birth. The activity of GPT, too, exhibited age-dependent variations. The activity of leucine-aminopeptidase increased strongly after birth in liver and kidneys. Acid phosphatase activity was less markedly influenced by development phases. Those enzymes which are involved in the formation of fructose and glucose (aldolreductase, glucuronate-reductase, and sorbite-dehydrogenase) had their highest activities, all age-dependent, in liver and kidneys.
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PMID:[Enzyme arrangement of various tissues in swine. 3. Studies of pre- and postnatal activities of various enzymes (ATPase, GOT, GPT, leucine aminopeptidase, acid and alkaline phosphatases, aldose reductase, glucuronate reductase, sorbitol dehydrogenase) in various tissues]. 22 27

This paper reports a study of changes in red blood cell enzymes and some serum parameters during and after treatment of protein-calorie malnutrition. The red cell GSH levels were low during the crisis, together with the levels of GSSG:NADPH reductase, GSH:H2O2 peroxidase, aspartate aminotransferase and alanine aminotransferase. After treatment the levels of all these enzymes increased significantly to normal values. Of the serum parameters investigated, significant reduction in the activity of the enzymes cholinesterase, catecholamine oxidase, total proteins, albumin, urea and electrolytes were obvious, and returned to normal values after treatment. Ceruloplasmin activity remained low even after three weeks' treatment and could not be related to copper levels. The results are discussed in relation to anemia and liver damage that may accompany the syndrome.
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PMID:Protein-calorie malnutrition: a study of red blood cell and serum enzymes during and after crisis. 82 Apr 94

Liver injury by 30-min ischemia following reperfusion was examined biochemically and histopathologically. A greater increase in the level of LDH was observed after 1-hr reperfusion. However, the level of LDH decreased in proportion to the period of reperfusion, while the levels of GOT and GPT were also increased rapidly and reached its peak at 12 hr following reperfusion and were almost restored to the control level by 48 hr. A similar increase was obtained in the lipid peroxides of the liver. In addition, cyt. P-450 content and NADPH cyt. c reductase activity decreased in proportion to the period of reperfusion up to 12 hr and then recovered by 96 hr. On the other hand, heme oxygenase activity was significantly increased by ischemia-reperfusion. The ischemia-reperfused liver resulted in various morphological changes with the period of reperfusion. The destruction of Disse's space, vacuolization of the cytoplasm and nonviable hepatocytes were observed after 12-hr reperfusion. These results indicate the greatest damages of the liver induced by 30-min ischemia following reperfusion is observed after 12-hr or 24-hr reperfusion. The liver injury by ischemia-reperfusion could be a useful experimental model to develop for future studies.
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PMID:[An injury of the liver caused by ischemia-reperfusion in rat liver. Report 2: Relationship between the damage of the liver and during the period of reperfusion]. 146 2

Cellular damage of various organs by ischemia following reperfusion is assumed to be at least in part due to lipid peroxidation in biomembranes, and oxygen-derived free radicals play a major role. The level of lipid peroxides in liver tissue increased during 90-min ischemia. When reflow of hepatic blood was allowed, a greater increase in the lipid peroxides was observed. Similar increases were obtained in several serum markers (GOT, GPT and LDH) during the period of ischemia or ischemia-reperfusion. In addition, levels of cytochrome p-450 and NADPH cyt. c reductase activity decreased in proportion to the decrease in microsomal proteins during ischemia or ischemia-reperfusion. On the other hand, superoxide dismutase in blood was significantly increased by ischemia-reperfusion. Rats died within 2 days after liver ischemia of 90 min, while all animals subjected to 30-min ischemia survived. Histopathological examinations indicated that extensive coagulation with erythrocytes occurred and the extent was dependent on the time of ischemia. The liver injury by ischemia-reperfusion could be a useful experimental model for studying liver injury induced by free radicals, for developing hepatoprotective drugs, or for investigating liver transplantation.
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PMID:[An injury of the liver caused by ischemia-reperfusion in rat liver]. 190 28

L-645, 164, a potent inhibitor of hydroxymethylglutarylcoenzyme A (HMG-CoA) reductase, is a structurally unique, synthetic monofluorinated-biphenyl that was administered to beagle dogs at dosages of 2, 10, or 50 mg/kg/day for 14 weeks to evaluate its toxic potential. Previously tested HMG-CoA reductase inhibitors from this laboratory have either been semisynthetic or fermentation-derived products containing a hexahydronaphthalene ring structure (i.e., lovastatin and simvastatin). Administration of L-645, 164 produced a significant spectrum of lesions, some of which have been previously associated with compounds of this pharmacological class, while others were unique to this monofluorinated-biphenyl inhibitor. Subcapsular lenticular opacities were produced in six of eight of the dogs receiving 50 mg/kg/day of L-645, 164 within 8 weeks of dosing. One dog receiving this dosage level experienced increases in serum alanine aminotransferase activity to levels 10 times those in concurrent control dogs. Light and electron microscopy of a wedge biopsy obtained within 3 days of this transaminase elevation failed to reveal any significant changes and the elevation resolved spontaneously despite continued drug administration. Lesions of the optic nerve and acoustic-vestibular tract and trapezoid decussation were observed in several dogs receiving 50 mg/kg/day. In addition, similar changes were observed in the optic tract in several of the dogs receiving 50 mg/kg/day and in one dog receiving 2 mg/kg/day of L-645,164. These were unique to L-645,164 and have not been observed after the administration of other HMG-CoA reductase inhibitors in this laboratory. Optic tract changes were generally mild, consisting of small to medium vacuoles without apparent myelin loss. Lesions in the other areas ranged from very slight to prominent vacuolation. No clinical signs were observed. Peak plasma drug levels of L-645,164 at 50 mg/kg were greater than 5 micrograms/ml, about one order of magnitude greater than those attained after administration of pharmacologically equipotent doses of lovastatin and simvastatin. These findings support previous observations that HMG-CoA reductase inhibitors producing high plasma drug levels are associated with a significant degree of systemic toxicity. In addition, the drug-induced CNS lesions attributed to L-645,164 appear also to be related to its chemical structure since similar lesions have not been observed after the administration of other structurally unrelated HMG-CoA reductase inhibitors that produce high plasma drug concentrations and comparable degrees of serum cholesterol lowering.
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PMID:The toxicity of a fluorinated-biphenyl HMG-CoA reductase inhibitor in beagle dogs. 205 62

The interaction of thinner and carbon tetrachloride (CCl4) induced hepatotoxicity was studied in the rats using the activity of plasma GOT and GPT, liver triglyceride and histopathologic changes of liver necrosis as indices. The animals were housed in a chamber with the continuous flow of thinner vapour (1.11 g/litre/hr) for 2 hrs prior to i.p. administration of CCl4 (0.1 ml/kg BW) at 18 hrs after thinner inhalation. Thinner inhalation potentiated CCl4 induced hepatotoxicity in a dose-dependent manner. The maximal enhanced effect was observed at 24 hrs after CCl4 administration by which the activities of PGOT and PGPT were significantly increased (3 folds). Thinner itself caused an additive effect on CCl4 induced liver triglyceride accumulation. At 18 hrs after thinner inhalation, the activity of NADPH cytochrome C reductase was markedly increased (2.2 folds) but no change in the activity of aminopyrine N-demethylase which was able to increase the 14.CCl3 free radicals and binding to both the hepatic microsomal proteins (1.8 folds) and lipids (1.4 folds). In addition, thinner pretreatment somehow increased hepatic lipid peroxidation by 1.4 folds. These results suggest that thinner pretreatment causes an increase in mixed function oxidases to activate the formation of .CCl3 free radicals and binding to the microsomal proteins and lipids, which in turn stimulate hepatic damage via lipid peroxidation in the membrane.
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PMID:Potentiation of carbon tetrachloride induced hepatotoxicity by thinner inhalation. 239 82

Several subpopulations of hepatocytes with increasing cell diameters were isolated, the smaller cells were attributed to the periportal area, the larger ones to the perivenous region. Profiles of total cytochrome P-450, benzphetamine N-demethylation and ethoxyresorufin O-deethylation, cytochrome c-reductase, glucose-6-phosphatase and GPT activities were determined. With adult hepatocytes an increasing cytochrome P-450 concentration with increasing cell diameter could be observed, paralleled by increasing activities of monooxygenases. Glucose-6-phosphatase and GPT also revealed increasing activities with increasing cell diameter, but cytochrome c-reductase did not show a distinct zonation. Immature hepatocytes (age 11-15 days) were smaller, more fragile, and could not be isolated with the same enzyme solution as adult hepatocytes. They did not show any zonation of cytochrome P-450 whereas the zonation of the monooxygenases was almost fully developed. For cytochrome c-reductase a zonation with higher activities in the perivenous cells could be demonstrated, in contrast to the lack of zonation in adult rats. Glucose-6-phosphatase showed a decline with increasing cell diameter in immature hepatocytes, whereas GPT did not show any zonation. In rats aged 20 days the zonation of these parameters in liver was in between younger and older animals.
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PMID:Separation of immature and adult rat hepatocytes into distinct subpopulations by centrifugal elutriation. 300 35

The long-term efficacy and tolerability of simvastatin, a 3-hydroxy-3-methylglutaryl-co-enzyme A (HMG-CoA) reductase inhibitor, was assessed during a 24-month follow-up period in 168 elderly hypercholesterolemic patients. After completing a 4 week double blind dose ranging study with simvastatin, 47 males and 122 females over 62 years of age with type II hyperlipidemia, a total cholesterol level above 6.5 mmol/l and clinically manifest cardiovascular disease were included in this extended study. A total of 159 patients completed the 12-month follow-up period and 141 patients were monitored over the full 24 months. All patients were started on 10 mg simvastatin once daily and the dosage was increased until the target levels of low density lipoprotein (LDL) cholesterol between 2.3 mmol/l (90 mg/dl) and 3.6 mmol/l (140 mg/dl) were reached. Fifty percent of patients reached the targeted LDL cholesterol goal of < 3.6 mmol/l (140 mg/dl) during the study. At study completion, 65 patients (39%) were taking 40 mg simvastatin per day, 56 patients (33%) 20 mg, 42 patients (25%) 10 mg and 5 patients (3%) only used 5 mg per day. Sixteen patients (9%) received concomitant lipid lowering therapy. Over 2 years, the mean decrease in LDL cholesterol ranged from 36% to 38%, the median decrease in triglycerides was 12% to 19% and the mean increase in high density lipoprotein (HDL) cholesterol ranged from 9% to 10%, respectively. Seven patients discontinued simvastatin because of adverse clinical or laboratory events, but only in two (1.1%) was this considered to be drug-related. Side-effects were mild and most frequently gastrointestinal in nature. Mean changes in asparate aminotransferase (AST) were not significantly different from zero and mean changes in alanine aminotransferase (ALT) and creatine phosphokinase (CPK) showed a small increase. We conclude that simvastatin is an efficacious and well-tolerated treatment for hypercholesterolemia in elderly individuals for extended periods.
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PMID:Long-term efficacy and tolerability of simvastatin in a large cohort of elderly hypercholesterolemic patients. 757 71

The coexistence of hypercholesterolemia and hypertension often requires concomitant drug treatments. Thus, it is interesting to evaluate the efficacy, safety, and tolerability of the new lipid-lowering agent fluvastatin, a 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA)-reductase inhibitor, in patients receiving concomitant antihypertensive/cardiovascular drug treatments. A retrospective analysis was based on data from controlled clinical trials in which 1815 patients were treated with fluvastatin and 783 patients received placebo. The daily dose of fluvastatin was > or = 20 mg. At least one of the following drug treatments was taken by 445 of the fluvastatin-treated patients (24.5%) and 181 of those receiving placebo (23.1%): beta-adrenergic-receptor blockers (fluvastatin: n = 182; placebo: n = 84); diuretics (fluvastatin: n = 168; placebo: n = 72); calcium antagonists (fluvastatin: n = 161; placebo: n = 69); and angiotensin-converting enzyme (ACE) inhibitors (fluvastatin: n = 101; placebo: n = 30). The majority of patients received monotherapy with one of the above-mentioned antihypertensive agents (fluvastatin: 69%; placebo: 65%). The efficacy of fluvastatin in modifying low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol and triglyceride levels was not consistently different in patients taking a given antihypertensive compared with the overall group and the patients not taking the antihypertensive agent. In patients taking fluvastatin and antihypertensives, confirmed (measured at two consecutive occasions) increases more than three times the upper limit of normal in aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) occurred in only two patients. One case involved the concomitant use of a beta-blocker (ASAT and ALAT) and the other a diuretic (ALAT).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Safety and tolerability of fluvastatin with concomitant use of antihypertensive agents. An analysis of a clinical trial database. 790 74

1. GR95030X, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was administered daily to marmosets by gavage. In a Maximum Repeatable Dose (MRD) study, doses of up to 30 mg kg-1 day-1 were administered for 49 days. In a chronic study, animals received dosages equivalent to 0, 1, 2.5, 7.5 and 20 mg kg-1 day-1 for 204 or 205 days. Some animals were maintained without treatment for a recovery period of 29 or 30 days. 2. Clinical signs included poor coat condition, weakness with impaired coordination, lethargy and other behavioural changes. There was also alimentary disturbance, and some deaths occurred at doses of 20 mg kg-1 day-1 and above. 3. Adverse effects upon body weight were seen although some recovery was apparent after the cessation of treatment. 4. Serum cholesterol concentrations were reduced. Very large increases in serum ALT, AST and CK activities were recorded with CK-MM isoenzymes accounting for 80% or more of the total CK enzyme activity. 5. Treatment was associated with muscle fibre atrophy and a sarcolemmal response with little evidence of regeneration. Histological examination revealed vascular changes, glial proliferation and cell death in the brain, with no consistent distribution. Alveolar capillary congestion and alveolar proteinosis indicated that there may have been a reduction in cardiac function. 6. HMG-CoA reductase inhibitors have evident potential to cause myopathy in marmosets. This is believed to be the first report of such an effect.
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PMID:Toxicity of a novel HMG-CoA reductase inhibitor in the common marmoset (Callithrix jacchus). 804 18


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