Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diagnostic usefulness of fasting total serum bile acids (SBA/F) in the detection of liver diseases and assessment of different aspects of hepatic function alteration was evaluated in 61 healthy subjects and 186 patients with liver disease. The value of SBA/F was compared with other routine tests. In 49 healthy subjects and 92 patients, serum bile acids were also measured after the im administration of Ceruletide as a cholecystokinetic agent (SBA/C). The diagnostic efficacy for the detection of disease states was better with aspartate-aminotransferase (EC 2.6.1.1) and alanine-aminotransferase (EC 2.6.1.2) than with SBA/F. When SBA/C was also determined the diagnostic efficacy was not substantially better than the SBA/F test. In the assessment of hepatocellular necrosis SBA/F showed a higher rate of misclassification errors compared to alanine-aminotransferase (mean error 45% vs 17%), whereas SBA/F gave similar results with direct bilirubin and pseudocholinesterase (EC 3.1.1.8) in the evaluation of cholestasis (mean error 40% vs 41%) and impaired biosynthesis (mean error 39% vs 40%), respectively. Serum bile acid determination did not show any significant diagnostic advantage with respect to the other routine liver tests.
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PMID:Evaluation of the diagnostic value of serum bile acid in the detection and functional assessment of liver diseases. 286 50

In the diagnosis of chronic (as opposed to acute) liver diseases, combinations of indicators are needed to improve specificity. Alanine aminopeptidase (AAP; microsomal aminopeptidase, EC 3.4.11.2) activity in serum reportedly is a very sensitive indicator of intrahepatic cholestasis and biliary obstruction; it is also particularly useful in diagnosing chronic liver disease when combined with an indicator of hepatocyte damage such as aspartate aminotransferase or alanine aminotransferase. We optimized the assay of AAP in serum, automated the assay by using a centrifugal analyzer, then used this automated assay to determine activity in 202 individuals, ages one to 73 years. The preliminary results were analyzed in terms of the effects of age, sex, smoking, and alcohol consumption on AAP activity in serum. Striking sex-related differences were observed: AAP activity in males declined 2.5 times more rapidly with age than did that in females; indeed, activity in adult females remained essentially constant. Moreover, AAP values were higher in men who smoked than in those who did not, the difference being of borderline significance by analysis of covariance (p = 0.0865) but significant by partial correlations (p = 0.02). No similar differences were seen for women smokers and non-smokers. When the effects of other variables were held constant, alcohol consumption alone did not significantly correlate with AAP activity in men or women.
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PMID:Alanine aminopeptidase in serum: automated optimized assay, and effects of age, sex, smoking, and alcohol consumption in a selected population. 288 Jun 80

An in vivo model of liver hyperplastic noduligenesis was induced in rats by long-term administration of thioacetamide (TAM) (50 mg/kg/day i.p.). Three doses of 50 mg/kg of an antitumoral Rh(III) complex were administered at 14, 9 and 5 days before the end of TAM treatment. Plasma and urine were obtained from either TAM or Rh(III) complex or TAM plus Rh(III) complex treated rats to determine the interactions of both substances with the biochemical parameters related to liver function. The rise in alkaline phosphatase (ALP), leucine aminopeptidase (LAP), gamma-glutamyl transferase (GGT) and the unchanged activities in the aspartate and alanine aminotransferases (AST, ALT) in plasma of TAM-treated rats indicated that the disease induced by this substance can be considered as a chronic obstructive biliary disease with indices of cell proliferation and tumors. The increased concentration of bilirubin both in the plasma and urine of TAM-treated rats suggested liver cholestasis and hepatobiliary obstruction. The very low values of creatinine clearance indicated that there was some degree of kidney failure due to the effect of TAM. The increased concentration of ammonia both in plasma and urine were probably a consequence of the decreased flux in the urea cycle in the liver. The Rh(III) complex alone did not produce significant changes in the plasma enzyme activities. The only significant changes were found in the concentrations of uric acid and ammonia in the urine. When the Rh(III) complex was administered to TAM-treated rats, significant restoration of the following parameters were observed: plasma enzymatic activities, blood bilirubin and ammonia, uric acid and creatinine in the urine and the creatinine clearance. These results suggest that the altered liver function induced by TAM can be restored by Rh(III) complex. The mechanisms by which this complex acts to counteract the TAM-induced changes are not yet established.
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PMID:Effect of a rhodium complex on alterations of hepatic function in thioacetamide-induced hyperplastic noduligenesis in rats. 288 38

It has been suggested that the quantity of amino acids perfused is a pathogenetic factor in total parenteral nutrition (TPN)-associated hepatotoxicity. However, the effect of the qualitative pattern of amino acid solutions has not been studied. Rats on parenteral nutrition for 5 days received 10.2 g of dextrose and 3.4 g of amino acids daily. Bile flow (microliter/min/g liver protein) after administration of Vamin was 16.2 +/- 0.8, which was similar to that in controls given chow and dextrose iv, but it was significantly higher (p less than 0.001) than those on Travasol (12.3 +/- 0.8). The decrease in bile flow was not related to the large concentrations of alanine and glycine present in Travasol. However, the addition to Travasol of serine present only in Vamin increased bile flow significantly. Bile acid secretion rate, biliary lipid constituents, calcium, sodium, and glucose showed little change. In contrast, alpha-amino nitrogen was increased (p less than 0.05) in Vamin-perfused animals. Steatosis was noted in only a few animals in the Travasol group, and was not associated with an increase in the triglycerides content of the liver. Glycogen and protein content of the livers did not differ. The data show that the composition of amino acid solutions may be a determinant of TPN-induced cholestasis and suggest that the presence of methyl donor amino acids may have a protective effect.
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PMID:Total parenteral nutrition-associated cholestasis in rats: comparison of different amino acid mixtures. 310 84

This study was designed to determine portal blood flow and mitochondrial and hepatic function during extrahepatic obstruction. Twenty-two male Wistar rats which had undergone bile duct ligation were compared 7 days later to 20 sham-operated controls. Portal flow and mitochondrial respiratory control ratio were reduced by 50% and 35%, respectively (P less than 0.01), and serum alanine-aminotransferase levels increased significantly (P less than 0.01) in the extrahepatic cholestatic group. These results suggest that cholestasis may cause an imbalance between the energy supply and the high demand of the liver leading to a state of partial ischemia.
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PMID:Portal flow and mitochondrial function during extrahepatic cholestasis. 322 50

Surgical management of extrahepatic cholestasis is frequently complicated by sepsis, which can be explained in part by diminished function of the reticuloendothelial system. We have explored the possibility that the metabolic response to infection may also be abnormal. Fischer 344 rats underwent either bile duct ligation (BDL) or sham operation and were studied 3 days after operation. Hepatic amino acid uptake measured in vivo by the accumulation of 14C-alpha-aminoisobutyric acid or in vitro by the rate of transport of 14C-alanine by isolated hepatocytes was unaltered in the BDL animals, while gluconeogenesis from alanine by viable hepatocytes from BDL rats was actually enhanced. However, the expected increase in hepatic amino acid uptake in response to endotoxin was diminished in the BDL animals. In addition, we observed impaired responses of the jaundiced animals to glucagon and interleukin-1, two mediators of the hepatic acute phase response to endotoxin. These data suggest that while hepatic amino acid transport is normal in the basal state, the rat with extrahepatic biliary obstruction does not respond appropriately to stress and that this defect cannot be explained solely on the basis of altered handling of endotoxin by the reticuloendothelial system.
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PMID:Impaired metabolic response to endotoxin in obstructive jaundice. 352 8

Glucose metabolism and plasma amino acid pattern were investigated in relation to arterial blood ketone body ratio (acetoacetate/3-hydroxybutyrate), which reflects liver mitochondrial redox state, in rabbits subjected to graded hepatectomy (25, 70 and 93%) and 70% hepatectomy with common bile duct obstruction. After partial hepatectomy, blood ketone body ratio decreased according to the extent of resected mass. Common bile duct ligation induced a further decrease in blood ketone body ratio in 70% hepatectomized rabbits. During a 6-hour hypertonic glucose infusion (0.7 g glucose/kg/h) which started 24 h after the operation, the blood glucose level remained between 230 and 280 mg/dl in 25 and 70% hepatectomized groups, while it increased linearly in 93% and jaundiced 70% hepatectomized groups. The plasma concentrations of alanine and proline as well as other amino acids increased as the blood ketone body ratio decreased. It is suggested that Krebs cycle and gluconeogenesis activities are inhibited as blood ketone body ratio decreases markedly resulting in an impaired glucose tolerance and amino acid imbalance.
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PMID:Glucose intolerance and amino acid imbalance in relation to changes in blood ketone body ratio in hepatectomized rabbits. 394 39

Primary biliary cirrhosis (PBC) is a chronic nonsuppurative, destructive cholangitis, whose etiology is unknown. Morbidity arises early from pruritus and later from hypercholesterolemia with xanthoma formation. Therapy is supportive and directed at the complications of cholestasis. Plasmapheresis has been reported to benefit patients with hyperlipidemia and PBC; thus a pilot study of plasmapheresis utilizing the Haemonetics Model 30 with replacement by albumin and saline was conducted. Five patients (four female and one male) with a mean age of 43 (range 29-58) and a mean duration of illness of 9.5 years (range 6-21) with marked jaundice, xanthomas, xanthelasma, hepatomegaly, fatigability, anorexia, and pruritus, as well as mild nausea were studied. Peripheral neuropathy was present in two patients. Two patients had splenomegaly. Two patients had an associated Sjogren syndrome. All patients had high serum bilirubin, alkaline phosphatase, and cholesterol levels and mild elevations in aspartate amino transferase and alanine amino transferase activities. Immune complexes measured in four patients were present. Antimitochondrial antibody titers were significant in all patients. Patients underwent a mean of 63 plasmapheresis procedures over a mean of 112 weeks removing a mean of 94.7 liters of plasma. No serious toxicity was seen. All patients showed a reduction in pruritus, xanthomas, xanthelasmas, and serum cholesterol values. The two patients who had evidence of Sjogren syndrome noted subjective improvement. All patients who had fatigue, anorexia and nausea also noted moderate improvement. There was no change in hepatomegaly or splenomegaly in patients demonstrating such organomegaly. Liver function did not change significantly. Overall, four patients had improvement in their condition and one patient achieved stability.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The clinical effectiveness and safety of chronic plasmapheresis in patients with primary biliary cirrhosis. 403 Jul 9

In experimental bile obstruction in dogs, the most sensitive change in blood plasma composition is the increase in alkaline phosphatase activity which occurs after eight hours. Maximum alkaline phosphatase activities (approximately 100 times normal values) occur between the fifth and the 14th day. The increase in activity is accompanied by smaller increases in gamma-glutamyl transferase activity, and total bilirubin concentration also increases to a smaller extent and less regularly. Cholestasis also induces an intense cytolysis which is demonstrated mainly by increases in glutamate dehydrogenase and alanine amino transferase activities which are more intense and lasting than those induced by 0.5 ml/kg carbon tetrachloride.
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PMID:Value of so called cholestasis markers in the dog: an experimental study. 613 May 88

Simultaneous administration of medroxyprogesterone acetate (MPA) and tamoxifen markedly elevated the serum alanine and aspartate aminotransferase activities in 4 out of 30 patients with endometrial or ovarian carcinoma; and also slightly increased the activities of gamma-glutamyl transferase in 2 of the patients. These pathological changes spontaneously returned to normal in 1 patient, and after the cessation of tamoxifen or tamoxifen plus MPA treatment in 3 patients. This kind of hepatic impairment was thought to be caused by reversible damage of liver cells possibly associated with slight intrahepatic cholestasis. It is suggested that special attention be paid to liver function during simultaneous MPA and tamoxifen administration; in case of adverse liver reaction during the combined treatment, a formula of sequential administration of the drugs could be implemented.
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PMID:Hepatic impairment during simultaneous administration of medroxyprogesterone acetate and tamoxifen in the treatment of endometrial and ovarian carcinoma. 623 70


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