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)

Apolipoproteins A-I, A-II and E were determined in the plasma of nine patients (five females, four males) with cholestatic liver disease (eight patients with primary biliary cirrhosis and one patient with sclerosing cholangitis). Plasma concentrations were measured by electroimmunoassay in the fasting state, postprandially after ingestion of either 100 g fat as whipping cream or a light mixed meal with or without addition of wheat fibre. Concentrations of apolipoproteins A-I and A-II were low in patients with cholestatic liver disease and A-I levels correlated inversely with the severity of liver disease as measured by bilirubin levels (r = -0.66). No changes in plasma apolipoprotein A-I, A-II or E concentrations occurred postprandially. There was an inverse correlation between plasma concentrations of apolipoproteins A-I and E (p less than 0.05, r = -0.68). A close relation existed between the ratio of apolipoprotein E to apolipoprotein A-I and plasma bile salt concentration (r = 0.80, p less than 0.01) and serum bilirubin (r = 0.76, p less than 0.01). This implies that in cholestatic liver disease apolipoprotein E and A-I levels reflect the degree of cholestasis.
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PMID:Apolipoproteins A-I, A-II and E in cholestatic liver disease. 392 5

To assess the basis of cholestasis associated with total parenteral nutrition (TPN), we studied the short-term effect of the component solutions on bile flow and bile salt secretion in infant and adult rabbits. Groups of four to six adult and infant rabbits received intravenously 154 mM NaCl (control), 2.5% amino acid, 10% glucose, or 10% fat emulsion alone or in combination. Bile was collected directly from the common bile duct for 3 h. Solutions containing both amino acids and glucose significantly (p less than 0.05) reduced bile flow and bile salt secretion in both age groups. Glucose alone also decreased bile flow and bile salt secretion, whereas amino acids as the sole infusate significantly (p less than 0.05) decreased bile flow only. The suppressive effect of the amino acid-glucose solutions on bile flow was more pronounced in infants than in adults. Fat emulsion alone had no effect on bile formation. Our findings demonstrate that short-term intravenous administration of nutrient solutions containing amino acids and glucose reduces bile flow and bile salt secretion, suggesting that these components are responsible for TPN-associated cholestasis.
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PMID:Total parenteral nutrition-associated cholestasis: acute studies in infant and adult rabbits. 392 64

We investigated the effects of ethinyl estradiol (5 mg/kg body wt daily for 5 days, orally) and/or iron sorbitol (50 mg/kg body wt daily for 5 days, i.m.) on bile flow, bile salt independent fraction (BSIF), hepatic delta-aminolevulinate synthase (ALA-S) and uroporphyrinogen decarboxylase (URO-D) in female rats. Ethinyl estradiol administration was associated with a significant decrease of bile flow and BSIF and an increase in URO-D activity in comparison to control values. Iron alone did not modify biliary parameters, but significantly increased the activity of ALA-S. Combined treatment with ethinyl estradiol plus iron partially corrected the reduction of BSIF and restored the activity of ALA-S and URO-D to control levels. Thus iron appears to exert a partially protective effect against ethinyl estradiol-induced cholestasis. No porphyrinogenic effect was observed.
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PMID:Effects of iron overload on bile secretion and hepatic porphyrin metabolism in ethinyl estradiol-treated rats. 394 69

A number of different chronic diseases affect the intrahepatic bile radicles or cholangioles. They include primary and secondary sclerosing cholangitis, primary biliary cirrhosis, chronic cholestatic drug jaundice, atresia, and carcinoma. Aetiological factors include infection, immunological changes, hormones, and congenital defects.Patients with chronic cholestasis have decreased bile salts in the intestinal contents and suffer from a bile salt deficiency syndrome. Failure to absorb dietary fat is managed by a low-fat diet and by medium-chain trigly-cerides which are absorbed in the absence of intestinal bile salts. Fat-soluble vitamin deficiencies are prevented by parenteral vitamins A, D, and K(1). Calcium absorption is defective, and improvement may follow intramuscular vitamin D, medium-chain triglycerides, a low-fat diet, and oral calcium supplements.In partial intestinal bile salt deficiency the anionic bile-salt-chelating resin cholestyramine controls pruritus though steatorrhoea increases. Pruritus associated with total lack of intestinal bile salts is managed by methyl-testosterone or norethandrolone, though the jaundice increases.
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PMID:Chronic cholangitides: aetiology, diagnosis, and treatment. 497 Oct 54

Sodium taurolithocholate and sodium taurocholenate were infused intravenously into rats and hamsters. Each bile acid salt was given alone or in combination with varying amounts of a primary bile salt, either sodium taurocholate or sodium taurochenodeoxycholate. Bile flow, total bile acid salt excretion, and the excretion of sodium taurolithocholate were quantitatively determined. In addition, mannitol excretion in bile was determined at various flow rates. Sodium taurolithocholate was found to be rapidly excreted in bile in concentrations greater than its aqueous solubility. When the endogenous excretion rate of bile salt or the infusion of primary bile salt was less than the molar amount of administered sodium taurolithocholate, cholestasis always occurred. Increasing molar amounts of primary bile salt prevented cholestasis and enhanced the excretion rate of sodium taurolithocholate. Infusion of sodium taurocholenate, a nonhemolytic bile salt, caused an effect on bile flow and bile acid salt excretion qualitatively similar to sodium taurolithocholate. The induction of cholestasis can be attributed to the physical properties of these poorly water soluble bile salts. The reduction in bile flow could not be shown to be related to water reabsorption from the biliary tree since there was no increase in mannitol concentration in bile during cholestasis. Reduction in bile flow may be related to obstruction of segments of the biliary tree by precipitates of sodium taurolithocholate and possibly to a decrease in water entry into the biliary tree during infusion of this bile acid salt.
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PMID:Effect of sodium taurolithocholate on bile flow and bile acid exeretion. 564 47

Ethynylestradiol impairs bile flow and bile salt maximum secretory rate in rats, implying a secretory defect. In addition, Na-K-ATPase activity is decreased in liver surface membranes, suggesting abnormalities at the sinusoidal as well as the canalicular membrane. We investigated whether ethynylestradiol pretreatment affects bile salt uptake and Na-K pump function in isolated rat hepatocytes. Ethynylestradiol-treated cells were functionally intact as assayed with trypan blue exclusion, lactate dehydrogenase release, and oxygen consumption. Initial taurocholate uptake velocity was reduced by 73% in ethynylestradiol-treated hepatocytes [Vmax, 1.0 +/- 0.1 vs. 3.7 +/- 0.2 mumol X min-1 X (10(6) cells)-1; P less than 0.001; Km, 34 +/- 5 vs. 33 +/- 3 microM]. Na-K-ATPase activity in cell homogenates (36 +/- 5 vs. 27 +/- 4 mumol Pi X h-1 X mg prot-1; P less than 0.05), ouabain-suppressible rubidium-86 influx [6.8 +/- 1.1 vs. 4.8 +/- 1.0 nmol K+ X min-1 X (10(6) cells)-1; P less than 0.05], and intracellular potassium concentration (126 +/- 10 vs. 110 +/- 16 mmol/l; P less than 0.05) were reduced after ethynylestradiol. Taurocholate uptake measured at different temperatures between 25 degrees and 37 degrees was linear when plotted according to Arrhenius. The energy of activation was increased by 40% in ethynylestradiol-treated hepatocytes [17 +/- 4 vs. 23 +/- 4 kcal X mol-1 X (10(6) cells)-1; P less than 0.05], consistent with decreased membrane fluidity. These data suggest the possibility that during ethynylestradiol-induced cholestasis a disorder of the sinusoidal domain, caused perhaps by ethynylestradiol-induced alterations in membrane lipid composition, is an important contributing factor.
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PMID:Ethynylestradiol impairs bile salt uptake and Na-K pump function of rat hepatocytes. 609 53

The neuromuscular blocking effects of Org 6368 and Org NC 45 were studied in rats with experimental cholestasis and in controls. The effect of Org NC 45 during infusion of taurocholate was investigated. In cholestatic rats we observed a three-fold increase of the duration of action of Org 6368 and Org NC 45. The same was observed for Org NC 45 with taurocholate. In the rat phrenic nerve-hemidiaphragm preparation taurocholate potentiated the neuromuscular blockade of Org 6368, pancuronium and gallamine, but not Org NC 45. Increased bile salt concentrations caused strong inhibition of hepatic uptake and biliary excretion of Org 6368 and tubocurarine in isolated perfused livers. Taurocholate and glycocholate were more potent than cholate and chenodeoxycholate. Cholestatic livers exhibited a clearance of Org 6368 which was 50% of control. We conclude that the prolonged duration of action of certain muscle relaxants because of cholestasis results from both inhibition of hepatic uptake by the accumulated bile salts and a general deterioration of liver transport function.
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PMID:Mechanisms underlying the prolonged duration of action of muscle relaxants caused by extrahepatic cholestasis. 611 Apr 32

The influence of the primary bile salts taurocholate and chenodeoxycholate on the neuromuscular blockade of the non-depolarizing drugs Org 6368, pancuronium, Org NC 45 and hexafluorenium was studied in cats. An increase in the effects of these agents, all possessing widely varying molecular structures, was found following administration of the bile salts. The bile salt concentrations in plasma were similar to those obtained after 9-10 days of extrahepatic cholestasis in cats. The effect of Org NC 45, a new monoquaternary analogue of pancuronium, was increased more than that of pancuronium. This increase in effect is probably a result of inhibition of the hepatic uptake of the neuromuscular blocking drugs. The neuromuscular blocking effect of gallamine was not influenced significantly by the administration of bile salts.
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PMID:Bile salts and neuromuscular blocking agents. 611 11

In experimental bile obstruction the serum activities of the membrane-bound liver enzymes, alkaline phosphatase, 5'-nucleotidase and gamma-glutamyltransferase are greatly increased, whereas in the liver only the alkaline phosphatase activity is elevated. After partial hepatectomy or tetrachloride poisoning the alkaline phosphatase activity in the regenerating live is increased to the same extent as in cholestasis without an accompanying elevation in serum activity. The following results support the hypothesis of a bile salt-mediated solubilization of membrane-bound enzymes in cholestatic liver: (1) 30 min after bile duct ligation the total bile acids in the liver were increased 5-fold, 2 h later as much as 10-fold. After 1 day, the bile acid concentration was still 4 times above normal. (2) Isolated plasma membranes from normal and obstructed livers were incubated in vitro with increasing amounts of tri- and dihydroxycholanic acids. At a final concentration of 1 mmol/l taurochenodeoxycholate significant amounts of membrane-bound enzymes were released into the 12,000-g supernatant. (3) In the regenerating liver, where tissue phsophatase activity was high and serum phosphatase activity unchanged, the bile salt concentration was not increased.
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PMID:Studies on the mechanism of the increase in serum alkaline phosphatase activity in cholestasis: significance of the hepatic bile acid concentration for the leakage of alkaline phosphatase from rat liver. 612 56

Short-term experiments were performed on adult mongrel dogs (15 to 25 kg) anesthetized with sodium pentobarbital. The operative procedure included cholecystectomy, side-to-side mesocaval shunt with ligation of the portal vein, and cannulation of the common bile duct. Intravenous sodium taurocholate (500 mg/hr) was administered to prevent depletion of bile salts. Somatostatin (125 micrograms over 30 minutes) was given to six dogs after 2 hours of bile salt infusion, while six additional dogs received saline to serve as control. Bile flow decreased significantly during administration of somatostatin (206 +/- 28 to 150 +/- 21 microliters kg-1 15 min-1, P less than 0.001) and was unchanged during administration of saline (216 +/- 45 to 216 +/- 46 microliters kg-1 15 min-1). This decrease persisted for 1/2 hour after cessation of the somatostatin infusion. Bile salt outputs were similar for both groups throughout the experiment. The data demonstrate that somatostatin-induced cholestasis can be independent of portal blood flow.
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PMID:Somatostatin-induced cholestasis can be independent of portal blood flow. 613 63


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