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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

More than simply cataloging the numerous experimental models in which taurine plays a modulating role, this discussion aims at stimulating further investigation of the potential clinical value of this abundant sulfur amino acid. Both the biomedical investigator and clinician must be struck by the enormous amount of taurine floating freely in the intracellular water of the cells. In cardiac tissue alone, taurine levels of 20 mM or higher may be found. Given this abundance of taurine, why is our understanding of its function so elusive? Although it is clear taurine is important in conjugating bile acids to form water-soluble bile salts, only a fraction of available taurine is used for this function, predominantly in young animals and children. While taurine conjugation is the preferred route of bile acid conjugation in the young, changes in adults given 250 mg of taurine daily for two to three weeks are insignificant. Total pool size of bile acid and chenodeoxycholic acid declines. Unchanged are the rate of bile acid synthesis or the secretion rates of biliary cholesterol, bile acid and phospholipids. Biliary cholesterol saturation also stays the same. The finding that taurine availability protects against cholestasis induced by monohydroxy bile acids remains confined to guinea pigs. The abundance of taurine suggests it may be an osmoregulator of cell volume, and there is convincing evidence that it serves this function in fish. Taurine may play this role in the brain under high osmotic states such as hypernatremia, dehydration and uremia. Evidence is strong that taurine is vital in maintaining retinal function, which may explain why taurine is so abundant in human breast milk. Prolonged TPN feeding of infants demonstrates the importance of taurine in retinal development. We have begun to appreciate the role of the kidney in conserving taurine and how this is perturbed in the neonatal period. Taurine has recently been added to infant formulas (about 50 mg/L). Cataloging what we know of taurine function, however, produces a list of "maybes." Now is the time for exhaustive, careful taurine research that will produce more definite answers.
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PMID:Taurine: its biological role and clinical implications. 390 70

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

Somatostatin was administered intravenously to male Wistar rats, recovered for 3 h from an anesthesia during which the common bile duct and jugular vein were cannulated. Different bile acid-secretory rates were obtained by infusion of saline, or of Na+-taurocholate (150 nmol/min/100 g body wt), or by 8-h bile depletion. At the dose of 2 micrograms/h/100 g body wt, somatostatin causes a prompt decrease of bile flow (about 30%) and of bile acid secretion (32%-47%). The bile acid-independent fraction of canalicular bile is more decreased than the one associated with bile acid secretion. The changes are dose dependent and show a saturation pattern, with half-maximal saturation already at 2.2 ng/min/100 g body wt. Despite this cholestasis, endogenous bilirubin secretion remained unchanged, pointing to different secretory mechanisms for bilirubin and bile acids. In the isolated and perfused liver, somatostatin displays an anticholeretic effect, proportional to the amount of Na+-taurocholate present in the system. Hepatic blood flow and O2 consumption remained constant during perfusion, and were not affected by somatostatin. The hepatic transport of bile acid, and the water and electrolyte secretion are directly affected by somatostatin, and the experimentally-induced cholestasis seems a new and suitable model for studying mechanisms of bile secretion.
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PMID:Cholestatic action of somatostatin in the rat: effect on the different fractions of bile secretion. 611 14

Over a period of 20 weeks estradiol valerate (1.5 mg/kg body weight/week) was administered subcutaneously to male Wistar rats from which the livers were examined at four week intervals employing a freeze-fracture technique and colloidal lanthanum tracer studies. In connection with intrahepatic cholestasis, distinct alterations in the tight junctions were observed, consisting of disorganization, rarification and proliferation. Disruption of the tight junctions was not seen and colloidal lanthanum did not penetrate into the bile canalicular lumen. Holding the view that the term "leakiness" of tight junctions should be defined with reference to the tracer employed, we conclude that in the liver one tight junctional strand is sufficient to prevent the escape of larger bile constituents such as bile acids and that a back diffusion of bile acids over the tight junctional barrier does not play a role in the pathogenesis of the estrogen-induced cholestasis. Interruptions of tight junctions, as described by other authors, are interpreted as a secondary mechanical effect. On the other hand, we consider an increased permeability of the tight junctions to water and small solute molecules as probable; possibly this increased permeability is brought about by alterations in the microfilaments. A model for the pathogenesis of the estrogen-induced intrahepatic cholestasis is proposed.
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PMID:Ultrastructural study of cholestasis induced by longterm treatment with estradiol valerate. I. Tight junctional analysis and tracer experiments. 612 36

Mixed micelles, with their main constituents lecithin and glycocholic acid, form a new principle for the parenteral administration of compounds which are poorly water-soluble. Their composition of mainly physiological substances as well as their comparatively good stability substantiate their attractivity in comparison to existing solvents. A decomposition due to physical influences such as heat or storage for several years will almost exclusively affect the lecithin component in the form of hydrolysis into free fatty acids and lysolecithin. Their toxicity was examined experimentally in various studies using both undecomposed and artificially decomposed mixed micelles. In these studies the mixed micelles were locally and systemically well tolerated and proved to be neither embryotoxic, teratogenic nor mutagenic. Only when comparatively high doses of the undecomposed mixed micelles were administered, corresponding to approximately 30 to 50 times the anticipated clinical injection volume (of e.g. diazepam mixed micelles), did some vomitus (dogs), slight liver enzyme elevation (rats and dogs), and slightly increased liver weights (dogs) occur. After repeated injections of the artificially decomposed formulation (approximately 25% of lecithin hydrolyzed to free fatty acids and lysolecithin) effects such as intravascular haemolysis, liver enzyme elevations and intrahepatic cholestasis (dogs only) were observed but only when doses exceeding a threshold of approximately 40 to 60 mg lysolecithin/kg body weight were administered. All alterations were reversible after cessation of treatment.
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PMID:Preclinical safety evaluation of intravenously administered mixed micelles. 654 26

Creation of a shunt between the common bile duct and vena cava, choledocho-caval shunt (CCS), causes biliary retention without obstruction. This in turn induces a marked choleresis (up to three times the normal bile flow) and increases bile acid output, both of which reach a plateau by 6 hours and remain elevated thereafter. In contrast, bile duct obstruction produces high biliary pressure and stoppage of bile flow and bile acid output. To compare the effect of biliary pressure and bile acid flux on permeability of the hepatocellular tight junction, we examined lanthanum permeation through tight junctions and bile to plasma concentration ratios of 3H-sucrose in these two models. In addition, we examined the effect of biliary pressure further by adjusting biliary pressure to 15 cm of H2O in modified CCS animals. At 6 hours after establishing these experimental models in male Sprague-Dawley rats, we infused lanthanum chloride (5 mM) in physiologic saline through the aorta (120 mm Hg) for 3 minutes, followed by perfusion fixation of the liver. Transmission electron microscopy on 144 bile canaliculi in each group (three rats each) revealed penetration of lanthanum in descending order of pressure rather than bile acid output: bile duct obstruction (50.7%), modified CCS (19.4%), CCS (13.2%), and control (5.6%). Bile to plasma concentration ratios of 3H-sucrose measured at 0, 2, and 6 hours in CCS and modified CCS animals revealed a marked increase of bile to plasma ratios only in the modified CCS group. These data lead us to conclude that biliary pressure is the significant determinant of biliary permeability and that bile acid output is important only insofar as the resultant choleresis elevates pressure.
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PMID:Effect of biliary pressure versus high bile acid flux on the permeability of hepatocellular tight junction. 671 70

The hypothesis that the amino acid used for the conjugation of sulfolithocholate (S-LCA) is a critical determinant of its cholestatic potential was tested in the guinea pig which conjugates 90% of its bile acids with glycine. Twelve groups of animals were used to study the effect of taurine feeding at a concentration of 0.5% in the drinking water for periods of 1, 3, and 5 days before an iv injection of 18 mumol/100 g body weight of S-LCA. Bile flow was monitored in 30-min aliquots over a 3-h period and the bile acid secretion as well as the glycine/taurine ratio of conjugated bile acids were determined. At the end of the various time periods, the livers were examined by light and electron microscopy. Within 3 days after taurine administration there was an increase in bile flow and a reversal of the glycine/taurine ratio with taurine conjugates becoming predominant. Liver morphology was unchanged except for a slight accumulation of lipids after 5 days of taurine feeding. In animals who were not pretreated with taurine, S-LCA injection led to a progressive decrease in bile flow such, that it was reduced to less than 20% at the end of the 3-h collection. S-LCA was conjugated almost exclusively with glycine. In contrast, in the groups fed taurine for 1, 3, and 5 days before the S-LCA injection, bile flow was comparable to that of the groups fed taurine alone. The S-LCA recovered in bile was to a large extent conjugated with taurine. S-LCA animals pretreated with taurine did not exhibit any liver cell changes while the group which had not received taurine before the S-LCA injection showed numerous cytoplasmic vacuoles with normal bile canaliculi. These data show that increasing the availability of taurine through dietary means may exert a protective effect against cholestasis induced by monohydroxy bile acids.
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PMID:Taurine prevents cholestasis induced by lithocholic acid sulfate in guinea pigs. 682 84

Normal human meconium has been shown to contain short-chain (C20-C22) bile acids and, recently, these compounds have been identified in sera of patients with cholestasis. This suggests that shortchain bile acids may be secreted in bile. We have examined this point by studying the hepatic metabolism and biliary secretion of one naturally occurring C20 bile acid, 3 alpha-hydroxy-5 beta-etianic acid (3 alpha-hydroxy-5 beta-androstan-17 beta-carboxylic acid). [3-3H]-3 alpha-hydroxy-5 beta-etianic acid was prepared and administered intravenously to rats prepared with an external biliary fistula. 85.5 +/- 1.2% of the administered dose was recovered in bile over 20 h with 71.5 +/- 1.3% appearing in the first hour. 11.9 +/- 1.6% of the dose was estimated to be distributed in body water and 0.6 +/- 0.2% was recovered as organic matter in urine. Total recovery of label was 98.0 +/- 2.6%. Administration of milligram quantities of 3 alpha-hydroxy-5 beta-etianic acid produced an increase in bile flow (58.9 +/- 7.1% over basal levels) within 20 min after injection of the steroid. The radiolabeled material in bile was shown by thin-layer chromatography (TLC) to be a polar conjugate which, after beta-glucuronidase hydrolysis, cochromatographed with authentic free 3 alpha-hydroxy-5 beta-etianic acid. After purification, and derivatization, the steroid moiety was proven by gas chromatography-mass spectrometry to be identical to 3 alpha-hydroxy-5 beta-etianic acid. Characterization of the conjugate by TLC and by 3 alpha-hydroxysteroid dehydrogenase assay, before and after beta-glucuronidase hydrolysis, indicated that the steroid was secreted in bile as the 3-O-beta-glucuronide. It is concluded that 3 alpha-hydroxy-5 beta-etianic acid is cleared from the plasma, conjugated with glucuronic acid, and secreted into bile rapidly and in high concentration. The choleretic properties of this shortchain bile acid contrast with the cholestatic effects of lithocholic acid, its C24 analog. Both the form of conjugation of etianic acid and its effect on bile flow suggest that the shortened side chain of this steroid markedly alters its hepatic metabolism and physiology.
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PMID:Hepatic metabolism of 3 alpha-hydroxy-5 beta-etianic acid (3 alpha-hydroxy-5 beta-androstan-17 beta-carboxylic acid) in the adult rat. 684 61

Using precipitating antibodies to human liver alkaline phosphatase (L-AP), a quantitative method is evaluated for the determination of L-AP-activity in feces. Normal controls (n = 42) exhibit a logarithmic normal distribution. Patients with intrahepatic cholestasis (n = 36) demonstrate an increase, patients with extrahepatic cholestasis (n = 23) a decrease of the fecal L-AP-activity. Variations of fecal L-AP-activities due to a varying water content of the stools could be excluded by simultaneous determination of intestinal AP-activity. Prae- and postoperative determinations in 12 patients with extrahepatic cholestasis yielded an increase of L-AP-activity after reconstructive surgery. In intrahepatic cholestasis, high fecal L-AP-activities are found together with relative low total AP-activities in the serum whereas in extrahepatic cholestasis low fecal L-AP-activities are associated with relative high total AP-activities in the serum.
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PMID:[A method for the determination of liver alkaline phosphatase in feces and their activity in intra- and extrahepatic cholestasis (author's transl)]. 719 30

The methanol extract and water extract from the stem of Berchemia racemosa (Rhamnaceae) showed protective effects on liver injuries induced by carbon tetrachloride (CCl4) and alpha-naphthylisothiocyanate (ANIT) in rats. The acetone extract of B. racemosa protected the liver injury induced by CCl4. One of the protective substances was identified as carpusin. Some fractions showed significant protective effects against the liver injury and cholestasis induced by ANIT.
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PMID:[Protective effects of the stem of Berchemia racemosa Sieb. et Zucc. on experimental liver injuries]. 760 96


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