Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bile duct obstruction was induced in 6 cats by surgical ligation and transection of the common bile duct. Clinical and laboratory changes were monitored weekly for 25 to 54 days. Clinical signs of obstruction were similar in all cats and included anorexia, pyrexia, lethargy, intermittent vomiting, weight loss, palpable gallbladder, hepatomegaly, and bleeding tendencies. Tissue jaundice and acholic feces were evident grossly as early as postsurgical day (PSD) 4 with a mean onset of jaundice at PSD 5.3 +/- 0.4. Hematologic changes were initially characterized by a mild neutrophilic leukocytosis that increased with the chronicity of bile duct obstruction. Regenerative anemia developed in 4 cats associated with gastrointestinal blood loss. Acute serum biochemical changes were characterized by a marked increase in the mean values of aspartate aminotransferase, alanine aminotransferase, total cholesterol, and copper. Comparatively, only moderate increases in mean serum alkaline phosphatase activity were observed. Mean total bilirubin values increased remarkably at postsurgical week (PSW) 1, reaching a maximal value of 23.1 +/- 4.4 mg/dl at PSW 3 with 71.6 +/- 2.7% direct bilirubin. With chronicity of bile duct obstruction ranging from PSW 3 to PSW 7, the mean serum values of aspartate aminotransferase, alanine aminotransferase, total cholesterol, serum alkaline phosphatase, and total and direct bilirubin stabilized and then declined, whereas the increased mean serum copper values persisted. At PSD 25 to 54, hepatic copper values and serum bile acids were markedly increased. Seemingly, clinicopathologic changes of induced cholestatic hepatic injury depended largely on the duration of biliary obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hematologic and biochemical abnormalities associated with induced extrahepatic bile duct obstruction in the cat. 663 41

Hepatic function tests were performed on 48 dogs that had been given primidone, phenytoin, or a combination of anticonvulsant drugs for 6 months or longer. Except for histories of seizures, 44 of the dogs were healthy at the time the tests were performed. Abnormal test results were observed most frequently in dogs given only primidone and in dogs given combinations of anticonvulsant drugs. The test results that were abnormal most often were those for alanine transaminase and alkaline phosphatase activities, and sulfobromophthalein excretion. The dosage of anticonvulsant drug was found to modify certain test results. Statistically significant positive correlations were found between the dosage of primidone and serum alanine transaminase activity and between the dosage of phenytoin and serum alkaline phosphatase activity. Four of the dogs were examined because of signs of weakness and anorexia and 2 also had ascites. Three of the 4 dogs were euthanatized 2 to 49 days after admission with clinical signs compatible with hepatic failure, and cirrhosis of the liver was confirmed at necropsy. The fourth dog died at home and was not necropsied. Four of the remaining 44 dogs that apparently were healthy at the time of examination had abnormalities in hepatic biochemical test results that were comparable with those in the 4 dogs with clinical illness. We concluded that, although results of hepatic biochemical tests frequently may be abnormal in dogs given anticonvulsant drugs long-term, severe hepatic injury is observed less often.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Compromised hepatic function in dogs treated with anticonvulsant drugs. 669 76

Animal experiments conducted in the late 1960s and early 1970s in various institutes of China showed that the effective antifertility agent in crude cottonseed oil was gossypol. Gossypol is a yellow substance which occurs in various parts of the cotton plant; its chemical structure is naphthol phenol. At the Capital Hospital gossypol was tested on 172 volunteers selected from hospital employees and workers from a nearby factory. All of the volunteers were under age 50, married and healthy with at least 1 child. Examinations required before treatment were general physical examination, a blood and urine analysis, an electrocardiogram, serum potassium concentration and serum analysis. 2 stages of gossypol treatment were required in the clinical study: the initial stage, the loading period, is of about 60 days. A daily dose of 20 mg gossypol was given successively for 60 days causing the sperms to become immotile, reduced in number or totally absent. A sperm count below 4 million/ml semen was considered to indicate infertility. The dosage in the 2nd stage, the maintenance period, was reduced to 1/3 of the original dose to maintain infertility. The volunteers were followed up every 2-3 months. Fatigue, decrease of libido and impaired appetite were the 3 main complaints. Serum glutamic-pyruvic transaminase (SGPT) activities showed that the transient symptoms of fatigue and loss of appetite were not related to disturbance of liver function. The mechanism of hypokalemia induced by gossypol is probably of renal origin. Infertility induced by gossypol in contraceptive doses over a relatively short period of administration was reversed about 3 months after stopping treatment. Gossypol used as a male antifertility agent has been found to be very effective and relatively safe.
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PMID:Clinical study of gossypol as a male contraceptive. 679 20

New antitumor anthracycline antibiotic, aclacinomycin A was given to dd-mice and Wistar rats for acute toxicity study. The LD50 values were 29 approximately 39 mg/kg (i.v., i.p. and s.c.) and 62 approximately 69 mg/kg (p.o.) in mice, and 18 approximately 28 mg/kg (i.v., i.p. and s.c.) and 58 approximately 59 mg/kg (p.o.) in rats, respectively, which were calculated by mortality rate during a 14 day observation period. Depression of spontaneous activity, anorexia, diarrhea and slight alopecia were observed. Autopsy findings in animals killed by drug included atrophy of the thymus and spleen, and hyperemia and hemorrhage in the stomach and intestines. But no remarkable change was found in animals which survived through the observation period. Mongrel dogs were given the drug intravenously at 3, 5, 7.5, 10 and 15 mg/kg, respectively. All dogs (3/3) in the three higher dose groups and 1/3 dog in 5 mg/kg dose group died within day 0 approximately 5. Others survived more than 27 days. Depression of spontaneous activity and anorexia were found from 30 minutes to 2 hours after administration, followed by vomiting and diarrhea. Increase of GOT, GPT and LDH and decrease of WBC count were detected in dogs which died. Hyperemia and hemorrhage of the lungs, stomach and intestine were found among the groups given higher doses, whereas no significant changes were recognized among the two lower dose groups.
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PMID:[Acute toxicity of aclacinomycin A in mice, rats and dogs (author's transl)]. 692 57

Advanced chronic hepatic disease was observed in 5 dogs that had received anticonvulsant drug therapy for 2 to 3 years. Clinical signs included anorexia, weakness, and restlessness, and 2 dogs also had ascites. There were remarkable increases in the serum activities of alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase. The total serum bile acid concentration was high in 3 of 4 dogs that were tested. Sulfobromophthalein excretion was delayed in all dogs. Histologic examination of liver specimens from 4 of the dogs demonstrated macronodular or micronodular cirrhosis.
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PMID:Hepatic cirrhosis associated with long-term anticonvulsant drug therapy in dogs. 711 8

KW2083 7-N-(p-hydroxyphenyl) mitomycin C is a mitomycin C derivative, but not its masked compound. KW2083 differs from mitomycin C in various points. A phase I study of KW2083 by single intravenous injection was performed in 21 patients with advanced solid tumor. The dose limiting factor of this drug is marrow depression, and 70mg/m2 causing marked thrombocytopenia was determined as maximum tolerated dose. The thrombocyte count and the WBC count reached to nadir the minimum 2 to 3 weeks after and 1 to 2 weeks after the administration and recovered in 1 to 2 weeks and in 2 to 3 weeks respectively. As gastrointestinal symptoms, nausea or vomiting (38.1%), and anorexia (28.6%) occurred soon after the administration, and stomatitis and diarrhea were also observed in one case each. In addition, petechia, hemorrhagic tendency and fever were found in one case each. Patients receiving 70mg/m2 showed slight alopecia and transient slight in GOT and GPT elevation.
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PMID:[Phase I study of KW2083 7-N-(p-hydroxyphenyl) mitomycin C]. 718 79

Mebendazole was administered to 7 adult Dachshunds and 2 adult Doberman Pinschers at 6-month intervals for routine parasite control. Two weeks after the 1st treatment, a 3-year-old Dachshund died of acute hepatic failure. Approximately 2 weeks following the 2nd treatment, two 5-year-old Dachshunds and one 3-year-old Dachshund had evidence of acute hepatic necrosis; 1 of these dogs died of fulminant hepatic failure. Typical clinical signs in affected dogs included anorexia, depression, vomiting, icterus, and hemorrhagic diarrhea. Two additional Dachshunds had biochemical evidence of hepatic dysfunction, ie. high serum alanine aminotransferase and serum alkaline phosphatase activities. One Dachshund and 2 Doberman Pinschers had no clinical or laboratory evidence of hepatic disease.
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PMID:Acute hepatic necrosis associated with the administration of mebendazole to dogs. 734 57

A 2-year-old spayed female Siamese cat was presented with clinical liver disease characterized by anorexia; depression; elevations in serum levels of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase; hyperbilirubinemia; and icterus. Liver biopsy diagnosed hepatocellular degeneration with marked centrilobular hepatocellular accumulation of rhodanine-positive brown granules. Subsequent postmortem examination revealed similar granular material in the epithelium of the proximal convoluted tubules and collecting ducts of the kidney and alveolar epithelium and macrophages in the lung. The liver and kidney copper concentrations were 4,074 and 792 ppm dry weight, respectively. Hepatic degeneration in this cat apparently was due to excessive accumulation of copper.
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PMID:Hepatopathy associated with excessive hepatic copper in a Siamese cat. 748 20

Chronic hepatitis C is a common cause of viral liver disease in kidney transplant (KT) recipients. To assess the efficacy and safety of therapy with interferon alpha we conducted a prospective study where 14 cadaveric KT recipients with chronic hepatitis C received recombinant interferon alpha-2b (IFNa) 3 million units three times weekly (scheduled) for 6 months (group A). 14 KT recipients with chronic hepatitis C were not treated and served as controls for the study period (group B). All the patients in both groups had had stable renal function for at least one year. All patients in both groups had a positive HCV viremia at the beginning of the study. Patients of group A were treated for 142 +/- 34.8 days (range 65-168); elevated serum aminotransferase (ALT) levels decreased rapidly and significantly from 100.3 +/- 48.9 to 37.7 +/- 13.9 IU/L (P = 0.001); 10 patients (77%) were "responders," whereas the others experienced a decrease in ALT values but without reaching the normal ranges. With a mean follow-up of twelve months after discontinuation of IFNa therapy, 8 responders--i.e., 80%--relapsed within 1-20 weeks. Only 4 patients had no detectable HCV viremia at the end of the IFNa; two of them already have abnormal values of ALT. Moreover HCV viremia was present in all patients one month after the cessation of IFNa treatment. Side effects of IFNa (fatigue, anorexia, weight loss) were frequent, and 3 patients decided to drop out of the treatment. The hematological tolerance was good although there was a significant decrease in hemoglobin (11.9 +/- 1.7 vs. 13.4 +/- 1.7 g/dl; P = 0.0044). In group B, serum ALT levels did not significantly decrease (84.2 +/- 47.6 vs. 105.2 +/- 68.8 IU/L). At the end of the study period serum ALT levels were significantly lower in group A than in group B (37.7 +/- 13.9 vs. 84.2 +/- 47.6 IU/L, P = 0.013). The major concern in group A was the occurrence of 5 renal failures. Kidney transplant biopsies showed edema, no significant tubulitis, scarcely scattered interstitial inflammatory cellular infiltration, and mesangial thickening. Four patients received methylprednisolone pulses but renal function improved in only two cases. We were not able to discover predictive factors of renal failure. We conclude that IFNa therapy is effective in controlling disease activity--i.e., reducing amino-transferase levels in KT patients with chronic hepatitis C, although relapse and detection of HCV RNA after the cessation of treatment were observed, respectively, in 80% and 100% of patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Treatment of chronic hepatitis C with recombinant interferon alpha in kidney transplant recipients. 777 Sep 30

The medical and necropsy records of 41 cats diagnosed with nonlymphomatous hepatobiliary (NLHB) masses, including neoplasia and cysts, were reviewed. Overall, benign masses (n = 27) were more common than malignant ones (n = 14). The single most common malignancy was cholangiocellular carcinoma. The median age at diagnosis was significantly lower (P < .01) for cats with malignant rather than benign disease. Clinical signs associated with hepatobiliary neoplasia were usually vague and included lethargy, vomiting, and anorexia, often present for at least 2 weeks before presentation. Benign masses were an incidental finding in significantly more (P < .01) of the cases than were malignant masses. Median values for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin were significantly higher (P < .05) in cats with malignant versus benign masses. The prognosis for malignant disease was poor, with 86% of the cats dying or being euthanatized during hospitalization. Cats with benign disease that underwent exploratory celiotomy were more likely to recover and warranted a more favorable prognosis than cats with malignant tumors. Factors associated with malignancy included age at presentation, presence of clinical signs at presentation, and specific serum chemistry changes.
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PMID:Nonlymphomatous hepatobiliary masses in cats: 41 cases (1972 to 1991). 783 94


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