Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Megaesophagus was diagnosed in 9 adult ferrets. Clinical history of the ferrets included regurgitation, difficulty in swallowing, partial anorexia, and lethargy. Cachexia, dehydration, weakness, and ptyalism were observed on physical examination. Radiography revealed the esophagus of each ferret to be dilated in the thoracic and cervical regions. Of 4 ferrets that had lymphocytopenia, 2 had concurrent leukopenia. Serum biochemical analysis revealed high activity of alanine transaminase (4 ferrets) and aspartate transaminase (3), and hypoglycemia (4). Treatment included administration of fluid, antibiotics, and agents directed against possible primary causes of megaesophagus. Treatments were ineffective, and all of the ferrets died or were euthanatized. All 6 ferrets that were submitted for necropsy had bronchopneumonia, hepatic lipidosis, mild esophagitis, and gastritis. The etiopathogenesis of megaesophagus in the ferrets was not determined.
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PMID:Megaesophagus in nine ferrets. 796 Oct 71

The metabolic response of the tumour-bearing host to methotrexate (MTX) therapy was investigated with particular attention to effects resulting from MTX-induced anorexia. Biochemical changes in female Dark Agouti rats bearing mammary adenocarcinomas and treated with MTX (0.5 mg/kg, 2 i.m. injections, 24 h apart) were compared with untreated (CON) tumour-bearing rats, and tumour-bearing rats pair-fed (PF) to the MTX group. MTX treatment halted progression of the tumour (tumour 6% of bodyweight) while the tumour burden doubled in the CON and PF groups. A number of biochemical and haematological changes were specific to MTX treatment and did not result from decreased food intake. MTX treatment was associated with significantly decreased plasma calcium, bilirubin, alkaline phosphatase, aspartate aminotransferase and the total white cell count. Decreases in plasma albumin and total protein concentrations were observed in both MTX and PF rats. Other parameters commonly used to assess renal and liver function were not significantly affected by MTX. MTX reversed the hypoglycaemia, hyperketonaemia and hypertriglyceridaemia induced by tumour-bearing. In contrast, PF rats had an even more pronounced hypoglycaemia and hyperketonaemia than the CON rats. Measurement of glucose uptake in vivo with 2-deoxy[U-14C]-glucose showed that MTX treatment halved the glucose requirement of the tumour (8.2% of bodyweight compared to 12.2% in the control). It is concluded that the potentially adverse effects of MTX treatment on host metabolism are outweighed by the beneficial effects of a reduced metabolic demand resulting from inhibition of tumour progression.
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PMID:Metabolic consequences of methotrexate therapy in tumour-bearing rats. 815 87

PD 132301-2 is a substituted urea hypolipidemic and antiatherosclerotic agent that is a potent inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT). To determine its subacute toxicity, PD 132301-2 was administered orally to beagle dogs at 0, 6, 12, 25, 50, 200, 400, or 800 mg/kg/day for 2 weeks. Clinico-pathologic evaluations were completed on all dogs. Liver and adrenal total and esterified cholesterol concentrations, adrenocorticotrophic hormone (ACTH) responsiveness, and adrenal ultrastructure were determined at 0, 6, 12, and 25 mg/kg. At 12 mg/kg or greater, salivation, epiphora, conjunctivitis, emesis, anorexia or decreased food consumption, and soft to mucoid feces and/or diarrhea were noted. Suppression of ACTH response occurred by Day 6 at all doses. Adrenocortical degeneration and/or necrosis in zona fasciculata and reticularis was seen at all doses; adrenal free and esterified cholesterol were normal at 6 mg/kg and decreased at 12 and 25 mg/kg. Increases in serum alanine aminotransferase (2- to 15-fold), aspartate aminotransferase (2- to 12-fold), and alkaline phosphatase (2- to 7-fold) were noted at 50 mg/kg or greater. Periportal hepatocellular hypertrophy and hypereosinophilia occurred at 50 mg/kg or greater; hepatic cholesterol values were not significantly affected by treatment. Dose-dependent ultrastructural alterations in adrenocortical cells included decreased numbers of mitochondria and smooth endoplasmic reticulum profiles, qualitative and quantitative changes in lipid globules, and increased numbers of autolysosomes. PD 132301-2 or one of its metabolites has potent adrenocorticolytic properties and limited hepatotoxic properties by mechanism(s) that are likely independent of systemic ACAT inhibition.
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PMID:Subacute toxicity of a novel inhibitor of acyl-CoA: cholesterol acyltransferase in beagle dogs. 838 21

Laboratory-reared Aedes aegypti mosquitoes were employed in the successful transmission of Hepatozoon mocassini from a cotton-mouth moccasin (Agkistrodon piscivorus leucostoma) to 3 lizard species (Sceloporus undulatus, Eumeces obsoletus and Sceloporus poinsetti). Marked to severe lethargy and anorexia developed in the S. undulatus, E. obsoletus and S. poinsetti at 15, 38, and 96 days postinfection (PI), respectively. All 3 lizards developed a leukocytosis and had increased plasma aspartate aminotransferase activity (AST) by 14 days PI. Multifocal random hepatocellular necrosis and intrahepatic aggregates of heterophils centered on mature H. mocassini meronts were demonstrated in all 3 lizards. The pulmonary interstitium was multifocally thickened by aggregates of heterophils centered on meronts. No comparable clinical or anatomical pathological changes were demonstrated in naturally infected snakes. The results of this study suggest that H. mocassini is capable of inducing necrotizing inflammatory by lesions in unnatural reptilian hosts.
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PMID:Characterization of the clinical and anatomical pathological changes associated with Hepatozoon mocassini infections in unnatural reptilian hosts. 869 May 37

There are no available biochemical analyses that will reliably identify malnourished cats or enable monitoring them during supportive alimentation. Studies in people indicate that creatine kinase (CK) activity is high in malnourished patients and may decrease in response to nutritional intervention. The purpose of this study was to determine the value of quantifying serum CK activities in anorectic cats and to assess the usefulness of this test in monitoring nutritional support in these patients. Serum CK activity was evaluated in nonanorectic cats (Group 1, n = 25), and in hospitalized, anorectic cats that received nutritional support through a nasoesophageal tube (Group 2, n = 25). Anorectic cats had a significantly higher serum CK activity (median = 2,529 U/ L, range 88 to 153,000 U/L) than the control group (median = 175 U/L, range 81 to 363 U/L, P < .001). There were significant positive correlations between serum CK and both aspartate transaminase (AST) (P < .05; r = .59) and lactate dehydrogenase (LDH) (P < .05; r = .41) activities. Serum CK activity was significantly lower in anorectic cats after 48 hours of nutritional support than at time 0 (P < .001) and eventually returned to normal with continued support. Serum CK activity may serve as a useful marker in assessing and monitoring nutritional status in cats.
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PMID:Correlation between serum creatine kinase activities and anorexia in cats. 913 84

The possible adverse effects of chronic, high-dose fluconazole therapy are detailed from analysis of a multicenter, dose-escalating study of the therapy of invasive mycoses. Ninety-three adult patients were studied, 48 of these received > or = 6 months therapy and 20 received > or = 1 year. Fifty-eight patients received > or = 300 mg/day, and 7 received > or = 600 mg/day. One patient received 1,997 g over 86 months. Twenty-seven percent experienced possible symptomatic side effects, which resulted in 2 patients discontinuing therapy, and 42% had asymptomatic laboratory abnormalities, none of which were progressive. Headache, hair loss and anorexia were the most common symptoms experienced (each by 3% of patients), and eosinophilia and aspartate aminotransferase increases were the most common laboratory findings (12 and 10%, respectively). Fluconazole appears well tolerated and safe in these doses and durations.
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PMID:Safety evaluation of chronic fluconazole therapy. Fluconazole Pan-American Study Group. 930 72

The toxicity of the combination of salinomycin (sal.) and tiamulin (tia.) was investigated in dependence upon dosage and feeding method. In addition the efficacy of a safe dose for prophylactic treatment of dysentery was controlled. Following feed medications were tested for toxic effects in pigs: a) 3 mg sal. + 5 mg tia./kg BW, b) 3 mg sal. + 3 mg tia./kg BW, c) 3 mg sal. + 1 mg tia./kg BW, d) 3 mg sal./kg BW, e) 10 mg tia./kg BW, f) 30 mg tia./kg BW. The daily dose was given for 2 weeks by restricted feeding (twice a day) either as bolus or mixed in the whole ration or by feeding ad libitum. Animals were controlled for clinical symptoms and activities of creatine phosphokinase (CK) and aspartate aminotransferase (ASAT) were evaluated daily. Main clinical signs of poisoning were loss of appetite and locomotor disturbances and could be noticed for dosages of 8, 6 and 4 mg sal. + tia./kg BW. Activities of CK and ASAT were increased dose-related, the feeding method also had an influence on the degree of intoxication. Some animals showed locomotor disturbances without any corresponding changes of CK and ASAT levels. Single pigs remaining without any symptoms even at high dosage pointed to differences in individual susceptibility. Toxicity was not found to be age dependent. Feed medication with 60 ppm sal. + 20 ppm tia. (feeding ad libitum) did not result in any signs of toxicity, however, the transmission of Serpulina hyodysenteriae from infected pigs to healthy, treated control animals could not be inhibited efficiently. Therefore the simultaneous application of salinomycin and tiamulin should be avoided generally, because the risk of intoxication is high and subtherapeutical dosage has an insufficient effectiveness against Serpulina hyodysenteriae.
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PMID:[Toxicity of the combination of salinomycin and tiamulin in swine]. 941 Jul 34

A diagnosis of hepatocellular toxicosis attributable to carprofen administration was made in 21 dogs on the basis of development of clinical signs and clinicopathologic abnormalities associated with hepatic disease and histopathologic documentation of hepatic necrosis. Clinical signs of toxicosis were anorexia, vomiting, and icterus. Hyperbilirubinemia and high serum activities of alanine transaminase, alkaline phosphatase, and aspartate transaminase were the most notable clinicopathologic abnormalities. In 7 of 9 dogs in which urinalyses were performed, abnormalities suggestive of renal tubular disease were detected. Clinical course of toxicosis was variable; however, most dogs had resolution of clinical signs and improvement or resolution of biochemical abnormalities with discontinuation of the drug and administration of supportive care. As with any medication, clients should be informed of possible adverse effects and reactions associated with administration of carprofen. In the event of those signs, clients should be instructed to immediately discontinue administration of carprofen to their dog and contact their veterinarian.
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PMID:Hepatocellular toxicosis associated with administration of carprofen in 21 dogs. 963 89

The safety of tacrine (Cognex), a centrally active, reversible acetylcholinesterase inhibitor approved in 1993 for the treatment of mild to moderate dementia of the Alzheimer type, was evaluated in 2,706 patients with Alzheimer disease (AD) in clinical trials and in 9861 patients with AD in a treatment investigational new drug (TIND) program. More than 190,000 patients in the United States received tacrine during the first 2 years following marketing approval. The most common tacrine-associated adverse events were elevated liver transaminase levels [alanine aminotransferase (ALT) and, to a lesser degree, aspartate aminotransferase] and peripheral cholinergic events involving primarily the digestive system (nausea, vomiting, diarrhea, dyspepsia, anorexia, and weight loss). Based on clinical trial experience, potentially clinically significant (>3 x upper limit of normal) ALT elevations occurred in 25% of patients, requiring routine monitoring early in treatment. The elevations were almost always asymptomatic, rarely accompanied by significant increases in bilirubin, and related to time on drug rather than to dose (90% occurred within the first 12 weeks of treatment). Gastrointestinal events were related to dose and generally of mild to moderate intensity. Tacrine-associated events, including ALT elevations, were reversible. Cholinergic events were manageable with dosage adjustment. Tacrine was not associated with permanent liver injury in clinical trials or a TIND setting.
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PMID:Safety of tacrine: clinical trials, treatment IND, and postmarketing experience. 965 Nov 38

A 9-year-old spayed female Poodle was admitted because of vomiting of 3 weeks' duration, lethargy, and anorexia. Palpation of the cranial portion of the abdomen elicited signs of pain. Principal laboratory abnormalities included mild segmented neutrophilia, lymphopenia, high serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activities, and hyperbilirubinemia. Radiography revealed foamy appearing areas of mineral opacity in the region of the gallbladder. Ultrasonographically, a hyperechoic structure with acoustic shadowing was seen in the same region, and extrahepatic bile ducts were distended. Cholecystectomy was performed. The gallbladder wall felt thicker than normal and was bluish-white. Multiple choleliths were found in the gallbladder and extrahepatic bile ducts. Histologic examination revealed chronic proliferative lymphoplasmacytic cholecystitis with mineralization and a well-differentiated adenocarcinoma of the gallbladder neck. A diagnosis of porcelain gallbladder was made. The dog recovered without complications and was healthy 14 months after surgery. To our knowledge, porcelain gallbladder has not been reported in dogs. In human patients, it is defined as intramural mineralization of the gallbladder commonly associated with gallbladder neoplasia. Early recognition is important for appropriate surgical treatment.
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PMID:Porcelain gallbladder associated with primary biliary adenocarcinoma in a dog. 978 80


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