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

The effects of amphotericin B (AmB) on the hepatic excretory function and the colloid clearance capacity were investigated in the perfused rat liver. AmB at 5 or 10 microM caused dose-dependent reductions in bile and perfusate flow rates and in biliary bile acid (BA) excretion. BA concentration in bile tended to increase, due to a prominent reduction in bile water induced by the drug. At 5 microM, AmB also caused an increase in [14C]sucrose clearance by the liver and a release of hepatocytic enzymes into the perfusate. These alterations were not related to the decrease in the perfusate flow induced by AmB. In addition, the drug, at 5 microM, caused a significant decrease in the colloidal carbon clearance by the liver. In this case also, the effect was independent of the reduction in the perfusate flow induced by the drug. The toxic effects of AmB on the rat liver could be interpreted as a derangement of the cell membrane functional integrity, which causes cholestasis, enzyme leakage and an impairment of the reticuloendothelial system function. This latter effect deserves careful evaluation of its clinical implications.
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PMID:Effects of amphotericin B on the excretory function and the colloid clearance capacity of the perfused rat liver. 273 48

Cardiovascular function was studied in anesthetized rats at weekly intervals following their pretreatment with single i.p. doses of BCNU (20 mg/kg). Over the first two weeks post-treatment the predominant effects were on total peripheral resistance. Femoral artery diastolic and mean pressures increased with a corresponding decrease in pulse pressure. Thereafter, apparent cardiac effects were also manifest by decreases in systolic and mean pressures, and possibly heartrate. Diastolic and pulse pressures also declined in this second phase. The water content of caudal artery segments from these rats decreased from 82.3 +/- 0.6% in controls to 78.4 +/- 0.6% (P less than 0.05) at 4 weeks post treatment. The total collagen content of these segments had increased 35% over controls as early as 2 weeks after BCNU while total protein content remained unchanged. Whole body responsiveness to the pressor effects of bolus injections of norepinephrine was significantly diminished only at the 4-week sampling time. The cardiovascular toxicity of BCNU may be a complex of direct effects of the drug on vascular endothelia and secondary effects associated with the cholestasis which develops over a similar time course.
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PMID:Cardiovascular performance in anesthetized rats pretreated with 1,3-bis(2-chloroethyl)-1-Nitrosourea (BCNU). 278 Nov 38

Newborns have limited reserve supplies of vitamin A. Infants with chronic cholestasis are in a precarious nutritional state because of their limited ability to build these stores even though the vitamin is present in their diet. In this study, we investigated liver concentrations of vitamin A in 30 children with extrahepatic biliary atresia. We demonstrate that correction of the deficiency occurs after intramuscular administration of a water-miscible solution of retinyl palmitate (100,000 IU, or 30 mg retinol equivalent). Furthermore, we evaluated the effect of vitamin A injections on liver and blood concentrations in nine children with chronic cholestasis over a 1-y period. We conclude this treatment is efficient and is well tolerated.
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PMID:Short- and long-term vitamin A treatment in children with cholestasis. 335 95

In view of the effect of taurine feeding on the cholestasis induced by sulfated lithocholate in the guinea pig, it was of interest to explore the influence of taurine on the bile acid secretory maximum (SRm) of chenodeoxycholic acid and of its glycine and taurine conjugates. Bile acid secretory rate measured in response to stepwise increasing rates showed for chenodeoxcholic acid an SRm of 147 +/- 6 nmol/min/g liver and any SRm that was higher (p less than 0.01) for taurine than for glycine (426 +/- 21 versus 327 +/- 24 nmol/min/g liver). Pretreatment for 3 days with taurine 0.5% in drinking water led to a 70% increase of the SRm for chenodeoxycholic acid. Analysis of the biliary bile acids after supplemental taurine demonstrated a large increment of tauroconjugates and no change in the percent of free bile acids or of sulfated forms. Experiments with labeled chenodeoxycholic acid showed no difference in the distribution of radioactivity between total liver, blood, bile, and urine on and off taurine thereby suggesting that neither sinusoidal uptake nor translocation across the cell were factors responsible for the difference in SRm. Inasmuch as taurine feeding increased the SRm for glycine by 30% and for taurine by 25%, it is suggested that taurine augments the canalicular excretion of bile acids that represents the rate-limiting step in the transfer of bile acids from blood into bile through a mechanism that cannot be explained only by a modification of the conjugation pattern.
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PMID:The influence of taurine on the bile acid maximum secretory rate in the guinea pig. 341 47

We previously showed that alterations of the bile canalicular membrane are likely to occur following a cholestatic regimen composed sequentially of manganese and bilirubin. The present study was designed primarily to investigate the biliary excretion of organic bile constituents following administration of the manganese-bilirubin combination. Experiments in hyperbilirubinemic Gunn rats were also performed to determine whether the unconjugated or the conjugated form of bilirubin is involved in this cholestatic interaction. Male Sprague-Dawley rats and male homozygous Gunn rats were given the following (i.v.): (a) manganese (4.5 mg per kg); (b) unconjugated bilirubin (25 mg per kg); (c) bilirubin ditaurate (38 mg per kg); (d) manganese-unconjugated bilirubin, or (e) manganese-bilirubin ditaurate. Bile flow was measured and bile was analyzed for manganese, total bilirubin, bile salts, cholesterol and phospholipid content. The results show that: (i) manganese-unconjugated bilirubin treatment caused about a 50% reduction in bile flow in Sprague-Dawley rats, whereas in Gunn rats the manganese-bilirubin ditaurate treatment resulted in about a 75% reduction, and (ii) in both strains, bile salt excretion was not appreciably modified during the cholestatic phase, as biliary bile salt concentration increased. The results suggest that although important differences regarding the form of bilirubin apparently exist, unconjugated bilirubin could be implicated in the cholestatic interaction in both strains of rats. Manganese-bilirubin-induced cholestasis is not related to a defect in bile salt excretion. The latter supports our contention that diminished canalicular membrane permeability to water is likely to be a key factor in this form of experimental cholestasis.
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PMID:Biliary excretion in Sprague-Dawley and Gunn rats during manganese-bilirubin-induced cholestasis. 341 27

Treatment of vitamin E deficiency during chronic childhood cholestasis is hampered by the poor intestinal absorption of available oral preparations of vitamin E when bile flow is severely impaired; thus parenteral vitamin E has been the only effective therapy for many children with this problem. We studied the intestinal absorption, efficacy, and safety of a water-soluble oral form of vitamin E, d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), in 22 children (7 mo to 19 yr old) with severe cholestasis and vitamin E deficiency who were unresponsive to massive oral doses (100-200 IU/kg.day) of dl-alpha-tocopherol. The results of oral vitamin E tolerance tests showed that TPGS was well absorbed in virtually all study subjects, that TPGS intestinal absorption was superior to that of dl-alpha-tocopherol, and that TPGS absorption in teenage children with chronic cholestasis was similar to that of normal adults. In addition, 1.7% +/- 1.6% (mean +/- SD) of the administered polyethylene glycol 1000 contained in the TPGS was absorbed and excreted in the urine of the 13 subjects analyzed, compared with 3.0% +/- 1.3% in 4 normal adults. A chronic oral dose of 15-25 IU/kg.day of TPGS corrected the biochemical vitamin E deficiency state over 1-19 mo (mean, 10.6 mo) of TPGS therapy. No clinical or biochemical evidence of gastrointestinal, renal, hepatic, or hematologic toxicity was demonstrated. This study suggests that TPGS administered orally in a dose of 15-25 IU/kg.day may be a safe and effective form of vitamin E for prevention and correction of vitamin E deficiency during severe childhood cholestasis.
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PMID:Treatment of vitamin E deficiency during chronic childhood cholestasis with oral d-alpha-tocopheryl polyethylene glycol-1000 succinate. 365 46

Treatment of the vitamin E deficiency neurologic syndrome in children with chronic cholestasis is hampered by the very poor intestinal absorption of available forms of vitamin E, thus requiring prolonged treatment with intramuscular injections of vitamin E in many patients. D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) is a water-soluble investigational form of vitamin E that is well absorbed during cholestasis. We studied the effect of TPGS therapy on the neurologic function in 12 children with vitamin E deficiency (aged 9 months to 6 years) with prolonged forms of neonatal cholestasis. Each child had failed to respond to up to 100 to 200 IU/kg/d of standard oral preparations of vitamin E. Treatment with 15 to 25 IU/kg/d TPGS for a mean of 19.3 months normalized the biochemical indices of vitamin E status and was well tolerated by all patients. Neurologic function, assessed by serial neurologic examinations, remained normal during therapy in the two children with no neurologic symptoms younger than age 3 years at onset of therapy. Neurologic function, which had deteriorated before this study, improved in six of seven patients with symptoms who were younger than 3 years and in all three with symptoms older than 3 years. TPGS appears to be a safe and effective form of orally administered vitamin E for use in children with chronic cholestasis who are unresponsive to available oral preparations of vitamin E.
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PMID:Tocopheryl polyethylene glycol 1000 succinate therapy for vitamin E deficiency during chronic childhood cholestasis: neurologic outcome. 368 46

Oral administration of vitamin E (100 mg tocopherol X kg-1 X day-1) as tocopheryl polyethylene glycol 1000 succinate (TPGS) to a child with congenital hepatic cholestasis (unresponsive to oral administration of dl-alpha-tocopheryl acetate) promoted an increase of tocopherol in plasma and adipose tissue while tocopheryl acetate emulsified with medium chain triglycerides and polysorbate 80 (MCT-E) did not. alpha-Tocopherol absorption, quantitated in thoracic duct-cannulated rats receiving intraduodenal infusions of soybean oil and saline, was similar for TPGS, MCT-E, and dl-alpha-tocopheryl acetate; gamma-tocopherol absorption from soybean oil was not affected by the presence of the supplemental alpha-tocopherol. Following bile duct ligation in one rat, TPGS promoted the absorption of alpha-tocopherol while absorption of gamma-tocopherol from soybean oil was decreased 30 fold, demonstrating that TPGS, which forms a micellar solution, delivers alpha-tocopherol through the unstirred water layer to enterocytes, while free tocopherol (alpha or gamma) absorption requires the presence of bile salts.
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PMID:Absorption of water-miscible forms of vitamin E in a patient with cholestasis and in thoracic duct-cannulated rats. 378 38

A personal case series triggers an examination of surgical risk in patients with uncomplicated cirrhosis of the liver. After a general introduction the conditions that increase surgical risk in cirrhotic patients are analysed. These include generally poor resistance, altered haemostasis, a tendency towards cholestasis, water retention and hepatic encephalopathy. The conditions most often requiring surgical treatment are then considered. They include associated pathologies (cholelithiasis, hernias, tooth extractions, bleeding haemorrhoids etc) and complications of cirrhosis variceal bleeding, intractable ascites, splenomegaly, hepatocytoma).
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PMID:[Internal medicine evaluation of the surgical risk in cirrhosis patients]. 382 13

To elucidate the role of calcium in regulation of canalicular bile flow, we studied biliary sucrose permeability and the transport kinetics of taurocholate in the in situ perfused rat liver. Calcium deprivation did not adversely affect viability or ultrastructural appearances of the liver. Removal of calcium led to initial choleresis followed by cholestasis dependent on external ionized calcium concentration. Biliary recovery of [14C]sucrose relative to that of tritiated water was determined by a biliary multiple-indicator dilution technique. Analysis in terms of irreversible thermodynamics suggested that biliary permeability to sucrose increased due to a change in the sieving coefficient from 0.135 to 0.435. Biliary recovery of taurocholate was significantly (P less than 0.001) reduced in low-calcium medium (from 79.6 +/- 6.5 to 17.6 +/- 11.8%). This was not due to a defect in hepatocellular uptake of taurocholate as determined in the perfused rat liver by a multiple-indicator dilution technique and in isolated hepatocytes. We conclude that calcium deprivation-induced cholestasis is characterized by an increased biliary permeability, a defect in cellular translocation and/or canalicular secretion of bile salts, and a defect in bile salt-independent bile flow.
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PMID:Characterization of calcium deprivation-induced cholestasis in the perfused rat liver. 389 57


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