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)

Twenty-five patients were treated for retained, recurrent, or primary common duct stones by permanent drainage of the biliary tract with external choledochoduodenostomy. Twenty-one patients had common duct stones which became evident two to fifty years after the initial biliary tract procedure and which may represent stones formed in the common duct. Three recent patients had a clinical history of primary common duct stones, had stones which were soluble in chloroform-methanol solution, and had hepatic bile which was lithogenic as determined by evaluating the molar percentage of cholesterol, phospholipid, and bile salt in bile samples obtained at the time of choledochoduodenostomy. These data suggest that further stone formation is possible and that permanent bypass of the sphincter of Oddi is indicated to prevent recurrent bile duct obstruction. Long-term evaluation of the results of external choledochoduodenostomy indicates that the procedure is safe and effective in the prevention of recurrent biliary tract calculi.
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PMID:Evaluation of the results of external choledochoduodenostomy for retained, recurrent, or primary common duct stones. 10 40

Total parenteral nutrition (TPN) is associated with cholestasis and hepatic steatosis, which can be lethal in infants who cannot be fed orally. It was determined that route of administration was not the critical variable in the development of hepatic steatosis. Two groups of young rats received equivalent amounts of a standard TPN solution either orally or intravenously for an 8- to 10-day period during which they received no other nutrition. Both groups gained equivalent weight and developed marked hepatic steatosis. To test whether the solution was toxic or deficient, three groups of rats were given TPN solution orally and a fraction of their usual daily intake of rat chow. Rats receiving less than 10% of their usual chow intake developed steatosis; rats receiving more than that did not. To determine the solubility of the protective material in chow, two groups of rats were given TPN solution orally and chow that been extracted with either water or the organic solvent chloroform. Rats eating the water-extracted chow developed steatosis, rats eating chloroform-extracted chow did not. Although the protective component in chow was apparently water soluble, addition of a water soluble extract of chow to the TPN solution fed another two groups of rats did not prevent steatosis at 0.1 mg/mL and only partially, if at all, at 10 mg/mL. TPN-related hepatic dysfunction, as measured by the development of hepatic steatosis in this model, may be due to a deficiency in the TPN solution. The missing constituent(s) appears to be present in rat chow and can be extracted with water, but not with an organic solvent.
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PMID:A proposed cause for the hepatic dysfunction associated with parenteral nutrition. 211 78

Potentiation of haloalkane hepatonecrosis by various ketones is a well-documented observation. The present study investigates the hepatobiliary effects of such treatments. Male Sprague-Dawley rats were pretreated with acetone (A), 2-butanone (MEK), 2-hexanone (MBK), 15 mmol/kg (po), or chlordecone (CD) and its nonketonic analog, mirex (M), 50 mg/kg (po). Following the pretreatment at various time intervals ranging from 10 to 96 hr, groups of animals received a challenging dosage of CHCl3 (0.5 ml/kg, po). In a collateral experiment, groups of animals were pretreated with vehicle and 18 hr later received either 0.50, 0.75, or 1.00 ml/kg CHCl3 (po). In each case hepatobiliary function was evaluated 24 hr later using bile flow rate and plasma bilirubin concentration. The results showed (1) that the ketones alone had no effect; mirex alone increased bile flow; (2) CHCl3 alone had no effect on bile flow but slightly increased plasma bilirubin; (3) all pretreatments potentiated the effect of CHCl3 on plasma bilirubin; (4) combinations of A, MBK, or CD plus CHCl3 were cholestatic within a restricted time frame. A study of biliary tree permeability by the segmented retrograde intrabiliary injection technique, using mannitol and inulin as marker compounds, suggested that cholestasis may result from potentiation of CHCl3-induced alterations in canalicular membrane permeability.
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PMID:Modifications in rat hepatobiliary function following treatment with acetone, 2-butanone, 2-hexanone, mirex, or chlordecone and subsequently exposed to chloroform. 242 88

Conjugates of bilirubin were studied in normal bile of man and rat, and in bile of liver patients. In general human bile was obtained by duodenal intubation. In addition T-tube bile was examined in patients operated on for mechanical obstruction. The bile pigment compositions of duodenal and T-tube bile were similar in two patients where comparison was possible. Obstruction of the bile duct in rats was used as an animal model for obstructive jaundice. Diazotized ethyl anthranilate was used for determination of total conjugated bile pigment and for thin-layer chromatography (t.l.c.) analysis of the derived azopigments. The available t.l.c. procedures are versatile and allow rapid and quantitative analysis. A variety of conjugated azopigments can be distinguished. With chloroform, negligible amounts of unconjugated bilirubin are extracted from bile of man. Therefore, the percentage of monoconjugated bile pigments present in the initial bile sample can be calculated from the percentage of azodipyrrole found after diazotization. Normal bile from man and rat yields similar azopigment patterns. The dominant component is azopigment-delta (azodipyrrole beta-D-monoglucuronoside). Small amounts of azopigments with complex conjugating structures (gamma-azopigments) are present in both cases. Human bile further yields small amounts of azopigments containing xylose or glucose (called azopigments-alpha(2) and -alpha(3), respectively). Monoconjugated bilirubin (estimated from the percentage of azodipyrrole) amounts of 22% of total bile pigments in human bile and to 39% in murine bile. In both, the bulk of bile pigment is bilirubin diglucuronoside. From bile of patients with acquired liver diseases a new azopigment group (beta-azopigment) was derived. The gamma-azopigment group was increased; the delta-azopigment group (containing azodipyrrole beta-D-monoglucuronoside) was decreased. No differentiation was possible between intra- and extrahepatic cholestasis. The percentage of beta-azopigment showed a positive correlation with serum bilirubin concentration (r = 0.6). Recovery of the diseases was accompanied by normalization of the azopigment patterns. In rats, hydrostatic or mechanical obstruction induced increases in beta- and gamma-azopigments and a decrease in delta-azopigment similar to the changes observed in bile of liver patients. Complete normalization was obtained 6 hr after relieving the hydrostatic obstruction (duration 15-21 hr). In contrast, with man after surgery for extrahepatic obstruction, T-tube bile was not normalized when the T-tube was withdrawn (10 days after operation). Hydrostatic obstruction in rats provides an easy model when postobstructive bile pigment composition and parameters have to be investigated. The present investigations stress the importance of the physiopathological state when studying bilirubin conjugation. Hindrance to bile secretion induced heterogeneity of bilirubin conjugates and stimulated the formation of complex structures.
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PMID:Bilirubin conjugates in bile of man and rat in the normal state and in liver disease. 463 28

Following the earlier observation that inhalation of volatile lipid solvents and of narcotic gases causes cholestasis, we studied the effects of various organic solvents on bile flow, plasma membrane fluidity and potassium movement in rat liver. Both in vivo and in the isolated perfused liver, applications of CCl4, CHCl3, dichloromethane, trichloroethylene, halothane, benzene and cyclohexane elicited rapid and sustained but reversible cholestasis. A transient phase of choleresis was observed prior to and after cholestasis, during the increase and fall in liver tissue solvent concentrations, respectively. Tissue concentrations required to produce cholestasis were lower the higher the lipophilicity of the solvent. Membrane fluidity was measured in isolated basolateral liver cell membranes by fluorescence polarization. Fluidity increased with increasing solvent concentration, the increase being associated with either biphasic stimulation and inhibition of membrane enzymes (Na+,K(+)-ATPase, 5'nucleotidase) or with inhibition alone (Mg(2+)-ATPase). In the isolated perfused liver, application of organic solvents caused hepatic uptake of K+ that was followed by K+ release upon withdrawal of the solvent. The magnitude of K+ uptake elicited by the solvent was comparable with the effect of blocking K+ channels with 2 mM Ba2+, but Ba2+ was ineffective in the presence of the solvent. In contrast, application of ouabain caused K+ release in equal amounts in the absence and presence of the solvent, indicating that K+ uptake elicited by the solvent results from inhibition of K+ efflux through K+ channels rather than stimulation of the Na+,K+ pump. The data show that cholestasis elicited by lipid solvents is associated with an increase in membrane fluidity and with disturbance of liver K+ homeostasis. The significance of these observations is discussed with respect to other models of experimental cholestasis.
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PMID:Organic solvents increase membrane fluidity and affect bile flow and K+ transport in rat liver. 821 71

The metabolite profiles from livers of toxin-treated rats were investigated using high resolution 1H NMR spectroscopy of aqueous (acetonitrile/water), lipidic (chloroform/methanol) extracts and magic angle spinning (MAS)-NMR spectroscopy of intact tissue. Rats were treated with the model cholestatic hepatotoxin, alpha-naphthylisothiocyanate (ANIT, 150 mg/kg) and NMR spectra of liver were analysed using principal components analysis (PCA) to extract novel toxicity biomarker information. 1H NMR spectra of control aqueous extracts showed signals from a range of organic acids and bases, amino acids, sugars, and glycogen. Chloroform/methanol extracts showed signals from a range of saturated and unsaturated triglycerides, phospholipids and cholesterol. The MAS 1H NMR spectra of livers showed a composite of signals found in both aqueous and lipophilic extracts. Following ANIT treatment, 1H NMR-PCA of aqueous extracts indicated a progressive reduction in glucose and glycogen, together with increases in bile acid, choline, and phosphocholine signals. 1H NMR-PCA of chloroform/methanol extracts showed elevated triglyceride levels. The 1H MAS-NMR-PCA analysis allowed direct detection of all of the ANIT-induced tissue perturbations revealed by 1H NMR of extracts, enabling metabolic characterisation of the lesion, which included steatosis, bile duct obstruction and altered glucose/glycogen metabolism. MAS-NMR spectroscopy requires minimal sample preparation and, unlike 1H NMR spectroscopy of tissue extracts, does not discriminate metabolites based on their solubility in a particular solvent and so this is a particularly useful exploratory tool in biochemical toxicology.
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PMID:NMR and pattern recognition studies on liver extracts and intact livers from rats treated with alpha-naphthylisothiocyanate. 1210 7