Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dose- and time-related hepatotoxic effects of acetaminophen were investigated in rats using biochemical parameters as indices of hepatotoxicity supplemented by the histopathological examination of the livers. The acute or subacute (twice daily for 7 days) administration of 0.25 g/kg acetaminophen did not produce any noticeable hepatocellular damage. On the other hand, dose-dependent elevations in serum enzyme glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and sorbitol dehydrogenase (SDH) activities and hepatic triglyceride (TG) levels were observed following the administration of single doses of 0.5 and lg/kg acetaminophen. Maximal hepatic damage occurred 12-18 h after acute dosing, while the hepatic function returned to control levels by 48-72 h. In contrast with the acutely treated rats, the serum enzyme activities and the hepatic TG levels remained unchanged following 7-day treatment with 0.5 or 1 g/kg acetaminophen. Also, histopathologically the degree of acetaminophen-induced hepatic necrosis was found to be far less extensive in rats given 0.5 and 1 g/kg acetaminophen twice daily for up to one week, as compared with the animals sacrificed 18 h after administering single equivalent doses of this drug. The results suggest that the liver function is reversibly impaired following acetaminophen overdosage, and that the intensity of acetaminophen-induced hepatotoxicity becomes less severe after repeated exposure to this hepatotoxin.
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PMID:Serum enzyme activities and hepatic triglyceride levels in acute and subacute acetaminophen-treated rats. 94 Nov 68

Polyriboinosinic-polyribocytidylic acid (poly I - poly C), an interferon inducer, was administered in multiple doses of 0.3-75 mg/m2 to 26 patients with a variety of solid tumors, 9 with acute leukemia, and 2 with chronic myelogenous leukemia in blast crisis. Forty-four separate drug trials were comprised of various schedules and routes of administration. Toxic reactions included fever (in 66% of the trials), transient elevation of serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase (25%), minimal laboratory evidence of coagulation abnormalities (59%), and hypersensitivity (5%). These toxic manifestations did not relate to dose level or magnitude of interferon induction. Poly I - poly C administered iv induced low serum concentrations of interferon in 24/38 trials (63%), but the correlation between drug dose and peak interferon titer was not linear. Poly I - poly C administered iv or im was not effective as an inducer of interferon in the cerebrospinal fluid. Similarly, poly I - poly C administered im or by inhalation did not produce detectable serum levels of interferon. No patients experienced an objective tumor response to the administration of poly I - poly C, and most (76%) had progression of their disease while receiving the drug.
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PMID:A phase I-II trial of multiple-dose polyriboinosic-polyribocytidylic acid in patieonts with leukemia or solid tumors. 97 71

Glycylprolyl beta-naphthylamidase activities in sera from 40 normal subjects (18-81 years) were: 22.6 +/- 0.9 (S.E.) (11.8-38.2) I.U./1 serum at 37 degrees C. The enzyme activities did not differ significantly with age between the younger group under 40-years-old and the older group over 40-years-old. Males, especially under 40-years-old, had slight but significantly higher activities than females. The levels were decreased in patients with gastric cancer. The levels were elevated in patients with hepatobiliary diseases, and had significant correlations with the results of the serum tests in hepatic diseases such as glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, alkaline phosphatase and total bilirubin, but had no correlation with serum lactate dehydrogenase. In cellulose acetate electrophoresis, normal sera had a single peak at the beta-globulin region, but the sera in hepatitis or liver cirrhosis showed not only an increase in the normal peak at the beta-globulin region but also the appearance of the other one or two new peaks in the alpha1 and alpha2-globulin regions.
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PMID:Glycylprolyl beta-naphthylamidase activity in human serum. 114 81

The hydrogen exchange at the Beta-carbon of L-alanine, L-glutamate and L-asparate with water has been examined during transamination catalyzed by glutamic-oxaloacetic transaminase and by glutamic-pyruvic transaminase. A significant hydrogen exchange at the Beta-carbon has been demonstrated during incubation of L-[3-3H]alanine + glutamic-pyruvic transaminase, L-[3-3H]alanine + alpha-oxo-glutarate + glutamic-pyruvic transaminase, L-[3-3H]glutamate + glutamic-oxaloacetic transaminase, L-[3-3H]glutamate + oxaloacetate +glutamic-oxaloacetic transaminase, and L-[3-3H]glutamate + pyruvate + glutamic-pyruvic transaminase as shown by the appearance of 3H2O. No hydrogen exchange at the Beta-carbon of L-glutamate occurred during incubation of L-[3-3H]-glutamate with glutamic-pyruvic transaminase alone. The hydrogen exchaned at the Beta-carbon of L-glutamate coincides with transamination as demonstrated by nuclear magnetic resonance studies of 2H2O-L-glutamate exchange during transamination by glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase. No hydrogen exchange at the Beta-carbon occurred during transamination of L-aspartate by glutamic-oxaloacetic transaminase as shown by nuclear magnetic resonance spectroscopy and confirmed by nuclear magnetic resonance simulation studies. The results are discussed with special reference to the different equilibria between the pyridoxal form and the pyridoxamine form of glutamic-oxaloacetic transaminase and of glutamic-pyruvic transaminase.
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PMID:Hydrogen exchane at the beta-carbon of amino acids during transamination. 120 22

The activities of ornithine carbamyl transferase, arginase and glutamic-pyruvic transaminase increase in the liver of the rat if the biological value of the dietary protein decreases. Experiments with pigs revealed in the blood serum an analogous high correlation between the biological value of the dietary protein and the activities of arginase, glutamic-pyruvic transaminase, leucine aminopeptidase and glutamic-oxalacetic transaminase. The most favourable possibility of protein evaluation on the basis of criteria of the intermediary protein metabolism consists in the determination of the blood urea concentration provided that the protein carrier supply is standardized. This procedure which has been elaborated by BERGNER and co-workers in 1968 for the determination of the protein quality was confirmed by TAYLOR and co-workers in 1974 on healthy individuals as a reliable and elegant measuring technique with highly significant correlation. It is concluded that the true biological value of protein carriers or protein mixtures which are intended for human nutrition can on principle be determined only in studies with healthy individuals.
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PMID:[Protein evaluation based on intermediary protein metabolism criteria]. 122 18

Seventeen patients who had been admitted to hospital for wasp/bee sting were studied. Mild pyrexia was encountered in 7 patients, rash/urticaria in 3, angioneurotic oedema in 2, oliguria in 2, microscopic haematuria and albuminuria in 3, transient hypotension in 1. However, there were frequent elevations of serum glutamic-oxaloacetic transaminase (9 out of 17 patients), serum creatine phosphokinase (14 out of 17 patients) and serum lactate dehydrogenase (8 out of 14 patients), indicating presence of damage to muscle fibres. This was confirmed by the histological findings of a muscle-biopsy from the most severe case. Elevation of serum glutamic-pyruvic transaminase was found in 6, and elevation of serum isocitrate dehydrogenase in 5 out of 14 patients, suggesting presence of liver damage. The above enzyme elevations appeared short-lived except in the clinically most severe patient (case 9) who developed acute tubular necrosis. All patients except the latter suffered no clinical sequelae and there was no correlation between their clinical condition and the presence or degree of elevations of serum enzymes.
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PMID:Elevated serum enzymes in patients with wasp/bee sting and their clinical significance. 124 43

Sparfloxacin (SPFX), a new oral quinolone antimicrobial, was studied for the bacterial response, pharmacokinetics and clinical efficacy in the treatment of bacterial prostatitis. The minimum inhibitory concentration (MIC) values for 48 strains isolated from expressed prostatic secretion were measured. The values for 8 out of 12 strains of S. epidermidis were below 0.05 microgram/ml and those for all 6 strains of E. coli were below 0.025 microgram/ml. The SPFX concentrations in prostatic fluid (PF) were 0.33 to 0.49 microgram/ml at 1 to 3 hours after oral administration of 200 mg, the PF/serum ratio being 1.15 to 1.47. SPFX was administered at a dose of 200 to 400 mg daily for an average of 14.1 days to 14 patients with prostatitis (5, acute: 9, chronic). The clinical efficacy judged by physician in charge was effective in 12 cases with an efficacy rate of 85.7%. The bacterial eradication rate was 93.3% (14/15 strains), and eradication was complete in all 7 cases infected with gram-negative rods. SPFX-related abnormal laboratory values were observed in one case with transient increase of glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase and alkaliphosphatase activities, and decrease of platelet. As side effects, one case with gastrointestinal symptoms and the other case with photosensitivity skin rash accompanied by sensory abnormality of palms were observed. The abnormal values or side effects in these patients recovered to normal or disappeared after completion of the treatment without any treatments. In view of the higher concentrations in PF than the MIC values with long remaining in the tissues, SPFX is considered to be effective in the treatment of bacterial prostatitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical and bacteriological study of sparfloxacin on bacterial prostatitis]. 131 92

The popular seafood squid contains high levels of naturally occurring amines such as dimethylamine (DMA) trimethylamine and trimethylamine-N-oxide (TMAO). The hepatotoxicity and hepatocarcinogenicity of squid with or without exogenous nitrite were investigated in rats. Acute necrosis including polymorphogenic neutrophil infiltration, haemorrhage and cholangiofibrosis were observed in the livers of most rats fed squid. Hepatocellular carcinoma (HCC) was induced in two out of 12 rats (16%) by feeding 10% squid in Purina rat chow for 10 months. The incidence of HCC was increased to four out of 10 rats (33%) when 0.3% NaNO2 was added to the above diet. At the end of the experiment a marked elevation of serum gamma-glutamate transferase was observed in treated groups, but no significant changes in the activities of serum glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase were detected. Vitamin C (0.3%) gave partial protection against hepatic damage. The concentration of DMA in squid is estimated to be 0.19%; this concentration did not induce HCC under the experimental conditions used. Therefore it is suggested that another major naturally occurring amine in squid, TMAO, could be one of the important factors involved in the induction of hepatotoxicity and hepatocarcinogenicity in rats.
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PMID:Hepatotoxicity and hepatocarcinogenicity in rats fed squid with or without exogenous nitrite. 132 3

The effect of ethanol on the initiation of diethylnitrosamine- (DEN) induced liver carcinogenesis was investigated in rats. In the first experiment, eight-week-old male Wistar rats were maintained on four liquid diets: a basal diet (Group 1), a low-carbohydrate (low-CHO) diet (Group 2), a basal diet+ethanol (Group 3), or a low-CHO diet+ethanol (Group 4). After three weeks on these diets, 50 mg/kg of DEN was injected intraperitoneally. The plasma glutamic-oxaloacetic transaminase activity in Group 4 was higher 24 hours after DEN administration than in Groups 1 and 3. The plasma glutamic-pyruvic transaminase activity in Groups 3 and 4 was higher than in Groups 1 and 2. The number of gamma-glutamyltranspeptidase-positive foci per unit liver area 41 weeks after DEN administration was higher in Group 4 than in Group 1. The area of gamma-glutamyltranspeptidase-positive foci was greater in Groups 2 and 4 than in Group 1. In the second experiment, Groups 1 and 4 were given DEN orally (25 or 75 mg/kg). Plasma glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase activities 24 hours after DEN administration were significantly higher in Group 4 than in Group 1, but only when the dose of DEN was 75 mg/kg. In contrast, the number and area of placental glutathione S-transferase-positive foci per unit liver area were greater in Group 4 than in Group 1 only after 25 mg/kg of DEN. Thus the severity of hepatotoxicity and the incidence of precancerous liver lesions were not necessarily correlated. These findings together indicate that a combination of ethanol and a low-CHO diet enhances DEN-induced liver carcinogenesis in rats by increasing the bioactivation of DEN in the liver.
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PMID:Ethanol ingestion combined with lowered carbohydrate intake enhances the initiation of diethylnitrosamine liver carcinogenesis in rats. 135 84

Predictors of the development of hypertension were examined in a 10-year follow-up study of normotensive Japanese adults. Subjects (n = 265), aged 30-69 years at entry, normotensive and with no past history of antihypertensive treatment at entry, were studied in terms of the relationship of various physical, biochemical, dietary, and lifestyle data to the subsequent development of hypertension (defined as systolic blood pressure (SBP) more than 140 mmHg and/or diastolic blood pressure (DBP) more than 90 mmHg and/or starting antihypertensive treatment) with analysis accomplished using univariate and multivariate life table methods. Univariate analyses by the generalized Wilcoxon test showed significantly higher incidence of hypertension in those subjects with SBP 120 mmHg or more (p < 0.001), DBP 75 mmHg or more (p < 0.001), serum glutamate oxaloacetate transaminase (GOT) 20 KU or more (p < 0.001), serum glutamate pyruvate transaminase (GPT) 15 KU or more (p < 0.001), serum gamma-glutamyl transpeptidase (gamma-GTP) 10 IU/l or more (p < 0.001), age 50 or older (p = 0.002), body mass index 22 kg/m2 or more (p = 0.012), and serum creatinine less than 1.2 mg/dl (p = 0.020) than in the other subjects. Multivariate analysis by the Cox proportional hazards model confirmed that relatively higher SBP (p < 0.001), lower serum creatinine (p < 0.001), higher gamma-GTP (p = 0.002), and higher age (p = 0.041) were independent and significant predictors of future hypertension.
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PMID:[Predictors of the development of hypertension: ten-year follow-up study in a community]. 139 30


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