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)

Administration of trimethoprim-sulfadiazine in a dog was associated with vomiting, inappetence, and icterus, and high values of alanine transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyltransferase, and total bilirubin concentration. The clinical signs and biochemical abnormalities resolved after discontinuation of the treatment. Histologic examination of sections from a liver biopsy specimen revealed moderate, predominantly portal hepatitis with cholestasis.
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PMID:Presumptive trimethoprim-sulfadiazine-related hepatotoxicosis in a dog. 154 70

The efficacy and safety of ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy was investigated in an open pilot study. Five patients received 1 gm/day of ursodeoxycholic acid during 20 days and another three patients received two identical periods of treatment separated by a 14-day interval free of the drug. Pruritus and serum levels of total bile salts and glutamic-pyruvic transaminase improved significantly during treatment with ursodeoxycholic acid. In the three patients who received two periods of treatment with ursodeoxycholic acid, pruritus and the laboratory alterations relapsed in the second week after the drug was discontinued, but they improved again when ursodeoxycholic acid was readministered. No adverse reactions were detected in the mothers or in their babies. All newborns were thriving normally during a follow-up period that lasted 5 mo after delivery. It is concluded that UDCA appears to be safe when administered in late pregnancy; its promising efficacy in the treatment of intrahepatic cholestasis of pregnancy should now be confirmed in controlled clinical trials.
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PMID:Effects of ursodeoxycholic acid in patients with intrahepatic cholestasis of pregnancy. 159 42

In order to elucidate the frequency of hyperbilirubinemia associated with sepsis in the elderly, as well as in clinical and histological characteristics, a total of 117 autopsy cases with sepsis were analyzed retrospectively. Based on the clinico-pathological findings, 48 cases with primary hepato-biliary, cardiac, hematological and shock complications, were excluded because these disorders were thought to affect liver function tests. Four cases out of the remaining 69 cases, 5.8% of the total, showed hyperbilirubinemia above 2 mg/dl (average 4.1 mg/dl), which was thought to be associated with sepsis itself. In these 4 cases, disproportionately high levels of blood total bilirubin were characteristic compared to changes of GOT, GPT, LDH, ALP and gamma-GTP levels. Blood culture of these 4 cases revealed Gram-negative organisms in 3 cases and Gram-positive in 1 case. Histological findings of the liver included cholestasis, Kupffer cell hyperplasia and cell infiltration in the sinusoid and portal areas, however these findings were mild and nonspecific. It is important to recognize the presence of hyperbilirubinemia associated with sepsis in order to properly treat febrile elderly patients with hyperbilirubinemia.
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PMID:[Hyperbilirubinemia associated with sepsis in the elderly]. 159 86

We report the development of severe hepatotoxicity in a patient on zidovudine therapy who received 3.3 g of acetaminophen in less than 36 hours. Three days later, the patient's serum aspartate aminotransferase level was 5,724 U/L, alanine aminotransferase was 3,124 U/L, lactate dehydrogenase was 12,675 U/L, alkaline phosphatase was 84 U/L, and total bilirubin was 20 mumol/L. These values substantially improved over the ensuing 4 days. Serologic results for hepatitis B, hepatitis A, and cytomegalovirus were all negative. The pattern and time sequence of transaminase elevation in this patient are consistent with acute acetaminophen hepatotoxicity, especially since zidovudine-induced hepatotoxicity is described as producing cholestasis rather than acute hepatitis. We hypothesize that our patient's susceptibility to acetaminophen-dependent hepatotoxicity may have been augmented by competitive utilization of glucuronidation by other drugs such as zidovudine and/or trimethoprim-sulfamethoxazole with subsequent increased cytochrome P450-dependent metabolism of acetaminophen. Additionally, due to malnutrition and/or to human immunodeficiency virus infection per se, our patient may have had decreased hepatic reserves of glutathione with which to conjugate the toxic acetaminophen product of the P450 system. Although severe acetaminophen-associated hepatotoxicity has not previously been reported in patients receiving zidovudine, we suggest that clinicians be aware of this potential interaction and counsel malnourished patients, especially those with concomitant hepatic disease, to exercise caution when taking both these medications.
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PMID:Severe hepatotoxicity in a patient receiving both acetaminophen and zidovudine. 836 34

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

The aim of this study was to investigate the effect of the protein synthesis inhibitor cycloheximide on the serum activities of gamma-Glutamyltransferase, Glutamate dehydrogenase and Glutamate pyruvate transaminase after bile duct obstruction in rats. The results showed that the increase of these enzyme activities after bile duct obstruction is further augmented by cycloheximide. Determinations of total bile acids in serum and liver showed that also the bile acid concentrations rise to a higher level after bile duct obstruction + cycloheximide than after bile duct obstruction alone. It is concluded that the effect of cycloheximide on the serum enzyme activities in extrahepatic cholestasis is produced via an influence on the metabolism of bile acids. This stresses the central role of bile acids for alterations of enzyme activities in extrahepatic cholestasis. Further, the effect of cycloheximide on bile acids after bile duct obstruction has not been reported before.
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PMID:Activities of APh, gamma-GT, GlDH and GPT and bile acid concentrations in serum after bile duct obstruction and cycloheximide in the rat. 168 1

To investigate the effect of extrahepatic cholestasis on integrity of the inner mitochondrial membrane, a study was conducted on two groups of rats: sham-operated control animals (N = 10) and rats subjected to extrahepatic cholestasis (EHC, N = 10) by double ligation of the hepatic duct. The animals were observed for 7 days and then sacrificed. The EHC group presented significantly higher serum levels of alanine aminotransferase, total bilirubins and alkaline phosphatase than the controls (P less than 0.01). Basal mitochondrial respiration (state IV), analyzed separately using either alpha-ketoglutarate or alpha-ketoglutarate + pyruvate as substrates, was similar in the two groups (P greater than 0.01). ADP-activated respiration, state III, diminished significantly in the EHC group. The results show that the decrease in mitochondrial function that has been reported by several investigators to occur in EHC is due to mitochondrial alterations not related to the ability of these organelles to maintain the proton gradient, since the inner mitochondrial membrane continued to be energized throughout the observation period.
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PMID:Integrity of liver inner mitochondrial membrane in rats with extrahepatic cholestasis. 182 30

In an open, pilot study, the efficacy and safety of ursodeoxycholic acid (UDCA) in the treatment of intrahepatic cholestasis of pregnancy was investigated. Four patients received 1 g/day of UDCA during 20 days and another 2 patients received 2 identical periods of treatment separated by a 14-day interval free of drug. Pruritus and serum levels of total bile salts and glutamic-pyruvic transaminase improved significantly during treatment with UDCA. Although pruritus and the laboratory alterations had a relapse in the second week after UDCA was discontinued, they improved again in the 2 patients who received a second treatment with UDCA. No adverse reactions were detected in the mothers or in their babies. All newborns are thriving normally, in a follow-up that lasted 3 to 6 months after delivery. It is concluded that UDCA appears to be safe when administered in late pregnancy; its promising efficacy in the treatment of intrahepatic cholestasis of pregnancy should now be confirmed in controlled clinical trials.
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PMID:[Effects of ursodeoxycholic acid in patients with cholestasis of pregnancy]. 182 60

Doppler umbilical velocimetry is a useful clinical tool for antepartum fetal surveillance of pregnancies at risk of fetal compromise. Intrahepatic cholestasis of pregnancy is associated with an increased incidence of fetal death, which might due to the toxic effect of elevated maternal serum concentrations of bile acids. To study a possible effect of the concentration of bile acids on the umbilical circulation we performed pulse-wave Doppler velocimetry of the umbilical artery in 15 patients with intrahepatic cholestasis between 34 and 38 weeks of gestation. The findings were compared to the Doppler flow velocities of the umbilical artery of 129 normal pregnancies. Peak-systolic (A) and end-diastolic (B) velocities of two to three cardiac cycles were measured by electronic calipers and the Pourcelot (PR)-index (PR = (A - B)(A)) was calculated. Two of 29 Doppler measurements in patients with intrahepatic cholestasis were above two standard deviations (2 SD) of the values in normal pregnancies. No significant correlation was found between Doppler flow velocities and serum levels of bile acids (r = 0.20) or the levels of alanine aminotransferase (ALAT) (r = -0.05). The mean level of bile acids was 24 mumol/l with a maximum of 98 mumol/l. The mean level of ALAT was 165 IU/l with a maximum of 576 IU/l. Since even high levels of bile acids do not influence umbilical circulation, Doppler investigations of the umbilical artery seem to be of little value in studying the disease-specific risk of fetal compromise in pregnancies complicated by intrahepatic cholestasis.
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PMID:Doppler umbilical artery velocimetry in pregnancies complicated by intrahepatic cholestasis. 183 56

In samples collected from 170 dogs suspected of having hepatobiliary disease, preprandial serum bile acids (PRSBA) and postprandial serum bile acids (POSBA) concentrations were measured, using a spectrophotometric enzymatic method. Dogs were assigned to 8 disease groups and 1 control group on the basis of hepatic histopathologic findings. Pre- and postprandial SBA concentrations and results of routine biochemical analyses (including total bilirubin, albumin, and BUN concentrations, and serum alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST) activities) were expressed, using 4 indices: sensitivity, specificity, positive predictive value, and negative predictive value. Single tests and combinations of tests in series were evaluated. For diagnosis of hepatobiliary disease, the specificity of PRSBA was 100% at values greater than 20 mumol/L and of POSBA was 100% at values greater than 25 mumol/L. Test combinations with the best sensitivity for diagnosing the following diseases were: PRSBA-POSBA for cirrhosis, portosystemic vascular anomaly, and glucocorticoid hepatopathy; PRSBA-POSBA or PRSBA-ALP for cholestasis; PRSBA-POSBA or ALT-AST for chronic hepatitis; PRSBA-ALT for hepatic necrosis and passive congestion; and PRSBA-ALP for neoplasia. Test combinations with the overall highest sensitivity and positive predictive value for the fewest number of tests were PRSBA-POSBA, and either PRSBA or POSBA combined with an enzyme activity (ALT, AST, or ALP). The overall test efficacy for PRSBA vs POSBA was nearly identical: for PRSBA, it was 82.4%, and for POSBA, it was 82.3%. On the basis of the results of this study, PRSBA greater than 20 mumol/L or POSBA greater than 25 mumol/L (measured by use of an enzymatic procedure) indicates histopathologic abnormalities of the hepatobiliary system or portosystemic vascular anastomosis. Seemingly, determination of SBA concentrations can be used to indicate the propriety for hepatic biopsy. Pre- and postprandial serum bile acids concentrations should be evaluated in conjunction with routinely used hepatobiliary screening tests for best diagnostic advantage.
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PMID:Evaluation of twelve-hour preprandial and two-hour postprandial serum bile acids concentrations for diagnosis of hepatobiliary disease in dogs. 189 31


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