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

---

Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical and laboratory findings from 15 patients with icteric viral hepatitis during pregnancy (VHP) and from 22 patients with intrahepatic cholestasis during pregnancy (CJP) were evaluated statistically in order to find out which parameters might help in order to find out which parameters might help in differentiating the two diseases. Diagnosis was established by needle liver biopsy in all cases. The following data were considered: history, physical examination, erythrocyte sedimentation rate (ESR) serum cholesterol, prothrombin time, total serum bilirubin, SGOT, SGPT, serum alkaline phosphatase, serum protein, serum flocculation tests, BSP blood clearance and serum HB Ag. Vomiting, high GOT and GPT serum levels, and serum HB Ag positivity suggest VHP diagnosis. Otherwise a severe itching with scratching lesions, high ESR, elevated total cholesterol and serum alkaline phosphatase values mainly if occurring in the later stage of pregnancy are consistent with CJP diagnosis. When clinical and laboratory data from a jaundiced pregnant female do not allow diagnosis, this can be established only on the basis of needle liver biopsy.
...
PMID:The differential diagnosis between intrahepatic cholestatic jaundice and viral hepatitis during pregnancy. 122 May 7

The transaminases, alkaline phosphatase (AP) and gamma-glutamyl transferase (G-GT) are most widely used as indicators of hepatobiliary disease. Elevated serum levels of transaminases (AST and ALT) usually indicate hepatocellular damage. ALT elevations, however, can also be of extrahepatic origin (muscle). The ratio of the transaminases in serum (AST/ALT) and the mitochondrial isoenzyme of AST are frequently higher in alcoholic than in non-alcoholic liver diseases. Serum activities of AP and G-GT are elevated in cholestasis: Both enzymes, however, are not liver-specific and G-GT activity is induced by alcohol and certain drugs. A hepatic enzyme pattern (predominant transaminase elevation) should be discriminated from a cholestatic pattern (predominant AP and G-GT elevation). The most frequent diagnoses in asymptomatic patients with accidentally detected, mostly mild to moderate transaminase elevations are: alcoholic liver disease, (mostly chronic) viral hepatitis, and already much less frequently, drug induced liver disease and non-alcoholic steatosis. Solely if the respective investigations are negative or/and the transaminases stay elevated for greater than or equal to 6 months despite strict alcohol abstinence, omission of any potentially hepatotoxic drug or weight reduction are further steps justified.
...
PMID:[Increased liver enzymes: what should be done?]. 135 16

Twenty-two patients with clinical, biochemical, immunological and pathological characteristics compatible with primary biliary cirrhosis were studied. There were 17 women and 5 men with a mean age of 57.4 +/- 15.2 years and a mean follow-up of 24.1 +/- 20.1 months. Four of them expired during the follow-up and eighteen patients now survive. The most common complaints were fatigue (63.6%) and itching (59.1%). Only one case (4.5%) was asymptomatic in this series. The major physical findings were jaundice (50%) and hepatomegaly (50%). The significant laboratory findings were: elevation of alkaline phosphatase (91% of the cases greater than 3 times the upper limit of normal), gamma-glutamyl transpeptidase (100% of the cases greater than 4 times the upper limit of normal), aspartate transaminase (95%) and alanine transaminase (100%), presence of anti-mitochondrial antibodies (91%), antinuclear antibodies (73%) and the elevation of IgM (88%). One case was associated with ulcerative colitis. Pathological staging in this series revealed 57.9% of stage II, 26% of stage III, 10% of stage IV and 5.3% of stage I. All patients with granuloma survived but 4 of the 5 patients with cholestasis died during follow-up. The results show that the features in this series of PBC were similar to those observed in western countries. The very high ALP and gamma-GT level as well as only one asymptomatic case in this series, suggest that our patients were diagnosed at a late stage. The reason(s) for the higher positivity of ANA, particularly the speckled type and a lower rate of associated auto-immune disease requires further study. Liver biopsy in predicting a prognosis is valuable.
...
PMID:[A clinicopathological study in primary biliary cirrhosis]. 135 58

Chronic administration of cyclosporin A may induce cholestasis in a few patients. The purpose of this study was to examine the effect of chronic administration of cyclosporin A on serum bile acid levels, serum bilirubin concentration, and bromosulfophthalein plasmatic fractional clearance. Twenty heart-transplanted patients with normal serum alanine aminotransferase activity receiving cyclosporine A during a mean duration of 33 months (range 7-54) were compared to 20 matched kidney-transplanted patients with normal serum alanine aminotransferase receiving azathioprine for a mean duration of 34 months (range 6-72). As compared to azathioprine-treated patients, patients treated with cyclosporin A had an increase in serum bile acid levels of 32% (P < 0.01), an increase in serum bilirubin concentration of 100% (P < 0.001), and a decrease in bromosulfophthalein plasmatic fractional clearance of 60% (P < 0.001). These results suggest that cyclosporin A induces a decrease in hepatic excretory function in man.
...
PMID:Chronic administration of cyclosporin A induces a decrease in hepatic excretory function in man. 139 91

This report discusses a unique drug-induced hepatotoxicity in cynomolgus monkeys treated orally with a novel potassium sparing experimental diuretic, [2,6-bis(4-chlorophenyl)-4-pyridinecarboxylic acid]. Groups of 6 adult male and female monkeys were treated orally with vehicle diluent, modified vehicle #122 or a suspension of the drug at 5.0, 12.5, or 32.0 mg/kg/day for 2 weeks. Another group of 5 monkeys were treated orally with 25.0 mg/kg/day of the drug for 2 weeks. Disposition of the drugs was evaluated in 2 monkeys in the later group that received 27.4 mg/kg of radiolabelled drug on the 1st and last day of dosing. Hepatic toxicity was characterized biochemically, light and electron microscopically, histochemically, immunocytochemically, and toxico-kinetically. Conjugated serum bilirubin, alanine transaminase, and aspartate transaminase levels were increased in monkeys treated with over 12.5 mg/kg/day of the diuretic. The periacinar hepatic plates of monkeys treated with 25.0 or 32.0 mg/kg/day were distorted by accumulation of PAS and oil red-O positive multinucleated Kupffer cells. The cytosol of these cells was expanded by phagolysosomes containing granular materials of varying electron densities. Granular electron dense materials were also in endothelial cells and bile canaliculi. Fatty change, cholestasis, and rare piecemeal hepatic necrosis were minimal. The drug was primarily excreted through urine. Plasma concentration and half life of the drug were increased with multiple dosing. The highest concentration of unexcreted parent drug was in the liver. Drug-induced noninflammatory hepatic microgranulomatosis, apparently caused by sequestered drug-lipid/mucopolysaccharide complex in the phagocytic cells of the liver, can occur in any species, including humans, if orally administered xenobiotics are presented to the liver in particulate form.
...
PMID:Drug-induced hepatic microgranulomatosis in cynomolgus monkeys. 141 Nov 33

Hepatocyte growth factor (HGF) is a potent stimulator of DNA synthesis in cultured hepatocytes. To determine whether HGF has any activity in vivo, we have tested HGF in rats in which intrahepatic cholestasis was induced by acute administration of alpha-naphthylisothiocyanate (ANIT). The hepatotoxic effects of a single injection of ANIT were manifested 48 h later as large increases in serum bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. These biochemical changes were accompanied by widespread periportal edema, hypertrophy of bile duct epithelium, and randomly scattered areas of liquifaction necrosis in the hepatic parenchyma. The increases in bilirubin, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were markedly attenuated when HGF was administered 30 min before ANIT and again at 6, 12, 24, 30, and 36 h after ANIT. In addition, this HGF dosing regimen completely prevented the occurrence of parenchymal lesions, although it had no effect on periportal histopathology. The effect of ANIT was dose dependent; a maximal response was observed at 320 micrograms/kg per injection, with an intermediate response at 105 micrograms/kg. Delaying the administration of HGF until 12 h after ANIT was as effective as when administration was begun 30 min before ANIT. Taken together these results show that HGF can prevent some aspects of ANIT hepatotoxicity.
...
PMID:Reduction of alpha-naphthylisothiocyanate-induced hepatotoxicity by recombinant human hepatocyte growth factor. 144 96

The use of a cholecystostomy catheter for temporary bile diversion was investigated in four cats with experimentally induced extrahepatic bile duct obstruction. Eighteen days after ligation of the common bile duct, a 6.5 F accordion catheter was placed in the gallbladder with a 22 g Hawkins needle-guide system through a paracostal incision. Biochemical parameters and fasting serum bile acids were monitored for 16 days. There were significant decreases in mean total bilirubin, aspartate aminotransferase, and fasting serum bile acids within 72 hours of bile diversion, and in mean alanine aminotransferase within 96 hours. Attitude and appetite improved, and the catheter was tolerated well. Positive bile cultures developed in three cats. Histologic changes in the gallbladder included mucosal ulcerations, a mixed inflammatory cellular infiltration, and fibrosis of the submucosa.
...
PMID:Temporary bile diversion in cats with experimental extrahepatic bile duct obstruction. 145 47

It is not known whether the histopathology of the liver allograft can be predicted from biochemical measurements in serum with the same confidence as in the native liver. To answer this question we compared the histopathological diagnoses in 170 biopsy specimens from 70 adult transplant recipients obtained during the first 180 days, with the concentrations of the serum bilirubin and the activities of AST, ALT and alkaline phosphatase measured at the same time. The most frequent diagnosis was cholestasis (n = 45), which was mild, moderate or severe and which may have been complicated by rejection (n = 28) or ischemia (n = 14). Hepatitis (n = 14), ischemia with rejection (n = 6) and spotty focal necrosis (n = 6) were diagnosed less frequently. Fifteen biopsy specimens were reported as histopathologically normal. In general, biochemical measurements discriminated poorly between different histopathological diagnoses. The histopathologically normal liver often showed an abnormal pattern of enzymes and an increase in the serum bilirubin level. As a result histopathologically normal biopsy specimens were indistinguishable biochemically from those with hepatitis. When two pathological conditions were found to coexist (e.g., cholestasis with either rejection or ischemic necrosis, or ischemic necrosis with rejection), the effect on the serum biochemistry was usually not additive and in some instances returned the biochemical abnormalities toward normal. With the exception of the serum bilirubin level, which increased with the severity of uncomplicated cholestasis, we could not identify a specific pattern of biochemical changes corresponding to a given histopathological diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Biochemical and histopathological correlation in liver transplant: the first 180 days. 150 12

The disposition of bromosulfophthalein was studied in chronically bile duct obstructed rats. In this model a catheter was inserted into the common bile duct and the distal tip was sealed. Resumption of bile flow was achieved with great ease. Obstruction of bile duct for 18 days in rats resulted in elevated bilirubin, ALT, AST, and alkaline phosphatase levels. Portal hypertension developed within this period (11.6 +/- 0.5 in obstructed rats vs. 8.6 +/- 0.6 mm Hg in sham-operated group). After the bile duct obstruction was opened, the half-life time for elimination of bromosulfophthalein (42.30 +/- 6.47 min) was longer than in sham-operated rats (21.23 +/- 3.34 min). Plasma clearance was reduced by 70% in bile duct obstructed rats. In spite of increased bile flow rate, biliary excretion of the dye was reduced by 40% in chronically bile duct obstructed rats. Hepatic glutathione levels were significantly reduced by 20% in this model. The specific activity of glutathione S-transferase with chlorodinitrobenzene and styrene oxide, as substrates, was reduced by 50% and 30%, respectively. However, the percent of conjugated bromosulfophthalein in bile was similar to that of sham-operated rats.
...
PMID:Bromosulfophthalein disposition in chronically bile duct obstructed rats. 150 59

The purpose of this study was to determine the chronic toxicity of methidathion, an organophosphate insecticide, in dogs. Groups of beagle dogs, four/sex/dose, were fed methidathion at constant dietary concentrations of 0, 0.5, 2, 4, 40, or 140 ppm for 1 year. The equivalent daily dosages were approximately 0, 0.02, 0.07, 0.15, 1.4, and 4.7 mg/kg. There were no deaths or adverse clinical signs associated with the treatment. Weekly body weights and weight gains were not affected. Mean daily food consumption was reduced in male dogs given the 140-ppm diet. Major treatment-related effects were cholestasis, chronic inflammation in the liver, and cholinesterase (ChE) inhibition. The liver effects were indicated by gross and microscopic pathologic findings as well as moderate increases in serum bile acids and enzyme activities (alanine aminotransferase, aspartate aminotransferase, sorbitol dehydrogenase, and alkaline phosphatase) in all dogs receiving greater than or equal to 40 ppm. RBC ChE was inhibited in males at greater than or equal to 40 ppm and in females and 140 ppm. Brain ChE was inhibited in both sexes at 140 ppm; the magnitude of inhibition relative to control was slightly greater with the cerebellar fraction than with the cerebral fraction. Serum ChE was not affected at any dose level. In conclusion, liver was the target organ in beagle dogs given greater than or equal to 40 ppm (equivalent to 1.4 mg/kg/day) methidathion in diet for 1 year. The no-observable-effect level was 4 ppm (0.15 mg/kg/day) for both liver cholestasis and ChE inhibition.
...
PMID:One-year dietary toxicity study with methidathion in beagle dogs. 151 89


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---