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)

Acute administration of alpha-naphthylisothiocyanate (ANIT) to rats has been used as a model of intrahepatic cholestasis. The mechanism of toxicity of ANIT is unknown, although recent evidence suggests a causal or permissive role for glutathione (GSH) (Dahm LJ and Roth RA, Biochem Pharmacol 42: 1181-1188, 1991). In these studies, ANIT treatment elevated hepatic non-protein sulfhydryl (NPSH) content, an indicator of GSH content, when liver injury was evident. The purpose of the present study was to characterize the effects of ANIT on hepatic NPSH content and to relate these changes to the development of liver injury. In rats fasted for 24 hr, administration of ANIT (100 mg/kg, per os [p.o.]) did not change hepatic NPSH content, bile flow, or serum measurements of total bilirubin concentration, alanine aminotransferase (ALT) activity, or gamma-glutamyltransferase (GGT) activity by 12 hr post-treatment relative to corn oil vehicle controls. However, by 24 hr after ANIT treatment, rats exhibited cholestasis and elevations in serum markers of liver injury. These markers were associated temporally with an increase in hepatic NPSH content, which consisted entirely of GSH. To determine whether the cholestasis caused by ANIT treatment might have caused the elevation of hepatic NPSH content, an extrahepatic cholestasis in rats was produced by ligation of the common bile duct. Bile duct ligation elevated hepatic NPSH content between 6 and 12 hr after ligation. Administration to rats of a non-hepatotoxic analog of ANIT, beta-naphthylisothiocyanate, also elevated hepatic NPSH content 24 hr after treatment. Taken together, these results indicate that the elevation in hepatic NPSH content after ANIT treatment is associated temporally with the onset of liver injury, but this elevation does not appear to participate causally in the mechanism of injury.
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PMID:Relationship between alpha-naphthylisothiocyanate-induced liver injury and elevations in hepatic non-protein sulfhydryl content. 167 30

Otic medications containing triamcinolone or dexamethasone were administered twice daily for 21 days to 2 groups of 4 healthy dogs each. Serum alkaline phosphatase, gamma-glutamyltransferase, alanine transaminase, and aspartate transaminase activities, and serum bile acid and lipoprotein-X concentrations were assayed for 35 days. Increased serum activities for gamma-glutamyltransferase, alkaline phosphatase, and alanine transaminase were detected by day 7 and peaked at day 21. Increases were greater in dogs given the dexamethasone-containing medication. Enzyme activity returned to baseline by day 35. Serum aspartate transaminase activity and bile acid and lipoprotein-X concentrations did not increase.
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PMID:Effect of otic medications containing glucocorticoids on liver function test results in healthy dogs. 196 51

Glucocorticoid(GC)-induced hepatopathy in the dog is characterized by abnormal liver morphology and increases in serum alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), and the liver alkaline phosphatase isoenzyme (LALP) and by the appearance of an unusual isoenzyme of alkaline phosphatase known as the corticosteroid-induced alkaline phosphatase isoenzyme (CALP). It has not been shown whether the increases in serum ALT, GGT, and LALP are as a result of an increase in production of these enzymes or as a result of the GC-induced hepatocellular swelling and possible membrane alterations. Also, it has been assumed that the mechanism of production of CALP is via GC-induced gene derepression and de novo protein synthesis; however, this hypothesis has not been directly tested. Using isolated dog hepatocytes maintained in a confluent monolayer culture in the presence and absence of GC or cyclic AMP, no statistical increase in serum ALT, GGT, or LALP was observed. A combination of GC and cyclic AMP also caused no statistical increase in ALT and GGT; however, we demonstrate that these conditions clearly stimulated the de novo synthesis of LALP. These conditions do not induce the synthesis of CALP as determined by a sensitive immunoassay. The data obtained using this in vitro model suggest that the primary mechanism(s) of the in vivo increase of serum ALT and GGT in GC treated dogs may be other than that of de novo protein synthesis. Likewise, in vitro production of CALP may be a mechanism more complex than the conditions tested in this study.
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PMID:Effect of glucocorticoids on alkaline phosphatase, alanine aminotransferase, and gamma-glutamyltransferase in cultured dog hepatocytes. 197 72

The disposition and adverse effects of the anti-trypanosomal drug isometamidium in pigs were evaluated. Following intramuscular administration of the drug at doses of 0.5, 15 and 35 mg kg-1, the drug was rapidly absorbed within 15 to 30 minutes to reach maximum plasma concentrations of 12 to 477 (n = 6), 302 to 655 (n = 4) and 1620 (n = 1) ng ml-1, respectively. No drug was detectable in plasma (less than 5 ng ml-1) 24 hours after drug administration at the three doses used. The half-lives of disappearance of the drug from plasma during the terminal phase were 7.12 h for the pigs given a dose of 15 mg kg-1, and 7.20 h for the pig which received a dose of 35 mg kg-1. At all the intramuscular injection sites, high drug concentrations were found six weeks after administration. The most dramatic adverse reactions observed were: one death after intramuscular administration at a dose of 35 mg kg-1 to two animals, and two deaths after intravenous administration at a dose of 2 mg kg-1 to two animals. For all these cases, the immediate cause of death was acute cardiovascular collapse. Biochemical analyses and gross and histological examinations showed that the animals that tolerated the high doses of 15 and 35 mg kg-1 given intramuscularly had extensive and severe tissue damage at the injection sites. Significant increases in plasma gamma-glutamyltransferase and alanine aminotransferase following drug administration suggested a degree of hepatobiliary damage.
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PMID:Isometamidium in pigs: disposition kinetics, tissue residues and adverse reactions. 204 93

Liver and biliary abnormalities are well-known complications of inflammatory bowel disease (IBD). It has been suggested that using total parenteral nutrition (TPN) may further impair liver function in these patients; this seems not to be so with total enteral nutrition (TEN). However, prospective trials comparing the incidence of liver function test (LFT) abnormalities with either TPN or TEN have not been carried out. Twenty-nine IBD inpatients with normal LFT, randomized to receive either TEN with a polymeric diet or isocaloric, isonitrogenous "all-in-one" TPN because of protein-energy malnutrition and/or severe disease, were included in the study. Sixteen patients (five with ulcerative colitis and 11 with Crohn's disease) received TEN, and 13 patients (eight ulcerative colitis and five Crohn's disease) were on TPN. All patients were on systemic steroids, and nine of them were on oral metronidazole. Both groups were homogeneous regarding age, sex, diagnosis, disease activity, nutritional status, daily nutrient supply, and days on artificial nutrition. Serum albumin levels significantly increased with TEN (32 +/- 1 to 38.2 +/- 1.6 g/liter, p less than 0.01), but not with TPN (32.1 +/- 2.2 to 33.9 +/- 1.4 g/liter, NS). Clinical improvement occurred in both groups of patients as shown by the change in the disease activity indexes. In all cases, measurements of serum alkaline phosphatase, serum bilirubin, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase were performed weekly. There were no significant differences in the initial LFT between both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Liver function tests abnormalities in patients with inflammatory bowel disease receiving artificial nutrition: a prospective randomized study of total enteral nutrition vs total parenteral nutrition. 212 46

Serum alcohol dehydrogenase activity was estimated at pH 10.4 (optimum for the typical liver isoenzyme), 8.8 (optimum for atypical liver isoenzyme), at the physiological serum pH of 7.4, and at pH 9.2, with a view to obtaining the greatest possible difference between patients and controls. Measurements were performed on the sera of 39 children aged from 2 to 13 years, using the Technicon analyzer RA-1000 with the continuously measuring method of Bonnichsen & Brink. Blood sera were tested at the onset of viral hepatitis, in the first week of hospitalization, and three times thereafter at intervals of 7 to 9 days. During the illness, the activity of serum alcohol dehydrogenase, measured at different pH-values, was higher than that of controls. The ratio of activity at pH 10.4 to activity at pH 8.8 in the sera differed from that previously reported for liver cells. The highest increase in alcohol dehydrogenase activity was at pH 9.2. The diagnostic sensitivity of alcohol dehydrogenase determination at this pH is lower than that of alanine aminotransferase, gamma-glutamyltransferase and aspartate amino-transferase, but higher than that of lactate dehydrogenase, alkaline phosphatase and bilirubin; alcohol dehydrogenase activity also shows the best correlation with the activity of gamma-glutamyltransferase.
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PMID:Measurement of serum alcohol dehydrogenase activity at different pH-values during the course of viral hepatitis in children. 223 Jun 70

A Pacific white-sided dolphin (Lagenorhynchus obliquidens) developed clinical signs, serum biochemical values, and serologic viral markers consistent with chronic persistent hepatitis caused by a hepatitis B-like virus. The hepatitis had a sporadic cyclical pattern of lethargy, inappetance, and icterus, with leukocytosis and increased serum activities of alanine transaminase, aspartate transaminase, and gamma-glutamyltransferase. The serum from this dolphin contained hepatitis B virus core antibodies, hepatitis B surface antibodies, and hepatitis B viral DNA. Supportive treatment consisted of administration of antibiotics, cimetidine, menadiol sodium diphosphate, and vitamin/dextrose supplementation. A clinically normal killer whale (Orcinus orca) housed in the same pool had serum hepatitis B surface antibodies, suggesting immunologic responsiveness and that this disease was not species-specific.
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PMID:Hepatitis B-like infection in a Pacific white-sided dolphin (Lagenorhynchus obliquidens). 229 47

The systemic administration of interleukin-2 (IL-2) can lead to significant antitumor responses in some patients with metastatic cancer in whom standard therapy has failed. A limitation of this immunotherapy is the toxicity associated with IL-2 infusion. To assess toxicity, we determined aspartate aminotransferase (AST; EC 2.6.1.1), alanine aminotransferase (ALT; EC 2.6.1.2), gamma-glutamyltransferase (GGT; EC 2.3.2.2), lactate dehydrogenase (LD; EC 1.1.1.27), alkaline phosphatase (ALP; EC 3.1.3.1), creatine kinase (CK; EC 2.7.3.2), total bilirubin (TBI), direct bilirubin (DBI), creatinine, urea nitrogen, and C-reactive protein in serum from 21 patients before and during five consecutive days of IL-2 treatment. Ten patients were followed for an additional five days after the end of IL-2 therapy. The IL-2 infusion caused liver toxicity and prerenal azotemia, as evidenced by significant increases (P less than 0.05) of all analytes except CK by day 1. There was a progressive increase in the results (except CK) for these tests until IL-2 treatment was stopped. Seven tests related to liver function (AST, ALT, GGT, LD, ALP, DBI, and TBI) showed increases, but the test results indicated significant improvement and moved toward the baseline value five days after the end of IL-2 therapy. Concentrations of creatinine and urea nitrogen in serum were normal three days after the cessation of IL-2 therapy.
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PMID:Changes in laboratory results for cancer patients treated with interleukin-2. 231 Dec 9

In an open, exploratory study, the safety of ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis (PBC) was investigated. Seven patients in stages I to III and two patients in stage IV were treated for 1 year with 1 g/day of UDCA. Clinical symptoms, and alkaline phosphatase, gamma-glutamyltransferase, alanine aminotransferase (GOT) and aspartate aminotransferase (GTP) levels improved significantly within three months and remained at the lower levels for the period of observation. Results of the galactose elimination capacity (4.7 +/- S.D. 1.4 mg/min per kg) and the aminopyrine breath test (0.60 +/- 0.33% dose/kg per mmol CO2) remained unchanged for 1 year. In all patients total serum bile acids increased and quantitatively UDCA became the most important bile acid. In patients in stages I to III this increase, however, was modest, whereas in patients in stage IV, total serum bile acids reached levels of 140 and 157 mumol/l and UDCA, levels of 90 and 103 mumol/l, respectively. It is concluded that UDCA appears to be safe only in stages I to III and that prognostic stratification based on bile acid levels or on the histological stage of the disease should be an important aspect of controlled clinical trials.
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PMID:Ursodeoxycholic acid in primary biliary cirrhosis: no evidence for toxicity in the stages I to III. 236 81

The course and magnitude of spontaneous increase in ammonia concentration in plasma on standing were investigated with EDTA-treated blood specimens from 36 healthy subjects with use of a sensitive and precise enzymic method. Over 90 min, the rates of increase were virtually constant at fixed temperature. The mean (and SE) rates at 0, 20, and 37 degrees C were 3.9 (0.23), 5.2 (0.23), and 25.2 (0.59) mumol/L per hour, respectively. At these temperatures, the plasma contributed at most 7%, 15%, and 10%, respectively, to the formation of ammonia in whole blood. In view of the medical needs and the measured rates of ammonia increase, an interval of 15 min between blood sampling and the start of centrifugation may be tolerated at a specimen temperature of 0 degree C. Rates of ammonia increase showed significant correlations with erythrocyte and platelet count as well as with the plasma activities of gamma-glutamyltransferase (EC 2.3.2.2) and alanine aminotransferase (EC 2.6.1.2).
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PMID:Preanalytical increase of ammonia in blood specimens from healthy subjects. 238 46


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