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

We studied the effects of a transient elevation in biliary pressure on biliary glutathione and amino acids in rats. Other biliary solutes monitored were total bile salt, Pi, which is a putative marker of paracellular leakage, and glucose, which is reabsorbed from the biliary tract. Experiments were carried out on anesthetized rats intraduodenally infused with taurocholate to maintain bile flow during a 2-hr basal period, a 4-hr pressure period during which the bile duct cannula was elevated until bile flow decreased to 1/3 the basal rate, and a 2-hr period after release of hydrostatic biliary pressure. We found that pressure treatment caused biliary concentrations of glutathione to progressively decrease by 80%, while biliary Pi rapidly rose approximately 3- to 4-fold, bile salt gradually increased approximately 3-fold, and biliary glucose concentration progressively rose 15-fold. HPLC analysis of monobromobimane-derivatized biliary thiols indicated that the decline in biliary glutathione was not accompanied by an increase in its breakdown products, cysteine and cysteinylglycine. Pressure treatment led to four patterns of change in biliary amino acid concentrations: (1) increases of 29 to 76% for the basic amino acids lysine and arginine, which have very low bile/plasma ratios of about 0.1; (2) no change for the more water soluble amino acids with bile/plasma ratios close to 1.0, e.g., histidine and urea; (3) modest decreases of 16 to 48% for a variety of amino acids including serine, glutamate, and glycine; and (4) marked, progressive decreases of > 50% for aromatic and branched chain amino acids. By 2 hr after release of pressure, only the alterations in biliary glucose and some amino acids, particularly the branched chains, persisted. This is the first report of cholestasis-induced alterations in biliary amino acids.
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PMID:Biliary glutathione and some amino acids are markedly diminished when biliary pressure is elevated. 799 75

Liver specimens obtained immediately after death from eight severely malnourished children were examined by electron microscopy, and compared with seven liver biopsy specimens from children who had recovered from malnutrition. The liver cells from the fatal cases showed mitochondrial swelling, with coarse densities in the matrix, cholestasis, depletion of the endoplasmic reticulum and Golgi apparatus, diminished glycogen stores, prominent lipid deposits and focal cytoplasmic degradation. The nucleoli were enlarged. There was marked reduction in peroxisomes. In contrast, the biopsies from recovering children showed good cellular organisation, and a normal frequency of peroxisomes. Multiple factors, including sepsis, may lead to depletion of peroxisomes. Loss of peroxisomes may interrupt beta-oxidation of long-chain fatty acids and accentuate the accumulation of lipid. Moreover, a reduction in the concentration of catalase may remove one avenue for the detoxification of free radicals. As the concentration of other anti-oxidants, notably glutathione, is also reduced, free radical damage may occur, leading to lipid peroxidation of membranes, mitochondrial damage, pump failure and influx of water and electrolytes into the cell.
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PMID:Peroxisomes and the hepatic pathology of childhood malnutrition. 803 10

The effects of acute poisoning by cupric sulfate in a number of species are well known; however, the effects of chronic low-level ingestion of cupric sulfate are less well characterized. Because exposure of humans to cupric sulfate may occur through drinking water, food, soil, or ambient air, subchronic toxicity studies were conducted in male and female F344/N rats and B6C3F1 mice by the drinking water (2-week exposure) and dosed feed (2- and 13-week exposure) routes. Animals were evaluated for histopathology, clinical pathology, reproductive toxicity, and tissue metal accumulation, and target organs were examined by a variety of special stains and by electron microscopy to characterize the observed lesions. In drinking water, cupric sulfate concentrations of 300 to 100 ppm produced no ill effects, whereas concentrations of 3000 to 30,000 ppm were lethal to rats and mice within 2 weeks. In feed, cupric sulfate concentrations of 4000 to 16,000 ppm caused significant reductions in body weight gain in both species in the 2- and 13-week studies. Hyperplasia and hyperkeratosis of the limiting ridge of the forestomach were present in both species in the 2- and 13-week studies. Rats in the dosed feed studies had a dose-related increase in inflammation in the liver and changes in clinical chemistry parameters which were indicative of hepatocellular damage and cholestasis. Histologic changes in the kidneys of rats consisted of a dose-related increase in the number and size of eosinophilic protein droplets in the epithelial cytoplasm and the lumina of the proximal convoluted tubules. Droplets were larger and more numerous in males than in females. Urinalysis results were suggestive of renal tubular epithelial damage. Iron staining of spleens from treated animals indicated a marked depletion of iron stores in both male and female rats, but not in mice, while hematologic and clinical chemistry alterations in rats in the 13-week study, along with histologic changes in bone in the 2-week dosed feed study, were indicative of a microcytic anemia. Cupric sulfate produced no adverse effects on any of the reproductive parameters measured in rats or mice of either sex. These results indicate that cupric sulfate at high exposure levels is a hepatic and renal toxicant, as well as an inducer of anemia in rodents, with rats more sensitive than mice following subchronic exposure.
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PMID:Subchronic toxicity of cupric sulfate administered in drinking water and feed to rats and mice. 825 99

Surgery in patients with obstructive jaundice is associated with significant infectious complications probably due to impaired immune function and malnutrition. Total parenteral nutrition (TPN) may alleviate malnutrition but may also promote bacterial translocation (BT) from the gut. To elucidate if TPN can prevent malnutrition without promotion of BT in obstructive jaundice, 40 dogs underwent laparotomy for tissue sampling and placement of a central venous line and were allocated into one of four groups: I (PO-control) received dog chow and water ad libitum; II (PO-CBDL) underwent ligation of common bile duct (CBDL) and was fed dog chow; III (TPN-control) received TPN; and IV (TPN-CBDL) underwent CBDL and received TPN. Body weight, blood samples for liver function tests and bacterial culture, and tissues from liver and mesenteric lymph nodes (MLN) for quantitative bacterial culture and for histology were obtained prior to and 2 weeks after the experiment. The incidence of BT to MLN was 40% in the PO-CBDL and TPN-CBDL animals, which was significantly different from the other two groups (0%; p < 0.05). The incidence of BT to liver was 70% (7/10) in the PO-CBDL animals, which was significantly higher than that in groups I, III, and IV (0%, 20%, 20%, respectively) (p < 0.05). The PO-CBDL animals showed a significant decrease in body weight and prealbumin compatible with malnutrition, whereas the TPN-CBDL animals showed a significant increase in alkaline phosphatase and a consistent cholestasis on histology. The data suggest that TPN can prevent jaundice-associated malnutrition and decrease BT to liver but should be administered cautiously because it may precipitate cholestasis.
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PMID:Role of parenteral nutrition in preventing malnutrition and decreasing bacterial translocation to liver in obstructive jaundice. 827 78

Fat-soluble vitamin deficiency is known to result in various complications that may be prevented if the problem is recognized and managed appropriately. In infants and children with chronic cholestasis, replacement therapy of the fat-soluble vitamins, vitamins A, D, E, and K, may prove extremely difficult because low concentrations of intraluminal bile acids lead to malabsorption of these compounds and other fat-soluble substances. Recent progress in the use of a water-soluble form of vitamin E, d-alpha-tocopheryl polyethylene glycol-1000 succinate, has enabled correction of vitamin E-deficiency states in these patients. It has also allowed for the admixture and coadministration of other fat-soluble vitamins and compounds in d-alpha-tocopheryl polyethylene glycol-1000 succinate to enhance their absorption. For managing vitamin K deficiency, similar success has been achieved using a vitamin K compound solubilized in glycocholate and lecithin. Vitamin A deficiency has been implicated in the higher incidence of childhood mortality and morbidity in Third World countries. Increased risk of childhood cancer has recently been associated with intramuscular injection of vitamin K to newborns. Finally, it is worth noting that among the pediatric population, exclusively breastfed infants, in general, are at risk for hypovitaminosis D, and at even greater risk in the absence of adequate exposure to sunlight or when the maternal diet is not sufficient to provide for vitamin D requirements.
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PMID:Fat-soluble vitamin deficiency in infants and children. 828 79

Protective effects of 41 Taiwan crude drugs on rat hepatic injuries caused by carbon tetrachloride (CCl4) and alpha-naphthylisothiocyanate (ANIT) were investigated. The methanol extracts of Elephantopi Herba and Lonicerae Flos inhibited the release of intrahepatic enzymes and histological changes by CCl4. The methanol extracts of Canarii Radix, Arecae Pericarpium, Cynomorii Caulis, Polygoni Cuspidati Radix, Phyllodii Herba, Junci Caulis Medulla, Rubiae Herba and Rhinacanthi Herba protected the hepatic injury by ANIT. Among them, the water extracts of Cymorii Caulis and Junci Caulis Medulla showed higher protective potency than the methanol extracts. And them this two crude drugs also protected the cholestasis by ANIT.
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PMID:[Protective effects of Taiwan crude drugs on experimental liver injuries]. 830 40

The objective of this study was to examine differences in plasma alpha-tocopherol concentrations after oral administration of pharmacologic doses of vitamin E to normal healthy subjects as RRR-alpha-tocopheryl glycol 1000 succinate (TPGS; water-miscible form) and RRR-alpha-tocopheryl acetate (TA; fat-soluble form). The study was designed to evaluate the administration of three different single doses and multiple doses for 4 wk with both preparations. Administration of 400 IU (269 mg), 800 IU (537 mg), and 1200 IU (807 mg) TPGS as a single dose resulted in slight elevation of plasma alpha-tocopherol concentrations. Administration of multiple daily doses at all three amounts of TPGS for 28 consecutive days resulted in a slight elevation of plasma alpha-to-copherol concentrations. A significant increase in plasma alpha-to-copherol concentrations was observed after ingestion of a single dose or equivalent multiple doses of TA at all three doses. As reported in the literature, in cases of cholestasis and other forms of lipid malabsorption, oral administration of TPGS is the treatment of choice. It appears that for normal adults and patients with normal lipid absorption, fat-soluble forms of vitamin E are preferable for therapeutic and prophylactic uses.
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PMID:Plasma alpha-tocopherol concentrations after supplementation with water- and fat-soluble vitamin E. 878 Mar 42

Total parenteral nutrition (TPN) is associated with cholestasis and gallstones. Gallbladder stasis may be important in the development of gallstones, and cholecystokinin (CCK) to stimulate gallbladder contraction has been proposed as a treatment to prevent this complication. We studied in vivo bile acid synthesis and bile acid output in miniswine on TPN to test whether daily CCK improves bile acid output and normalizes bile acid profiles with TPN. Nine miniswine were nutritionally maintained with TPN for 4 weeks; four pigs received CCK (0.1 mg/kg) iv daily. In vivo bile acid synthesis was measured with injection of 7 alpha-tritiated cholesterol. An increase in tritiated water reflects the activity of 7 alpha-hydroxylation, the rate-limiting step in bile acid synthesis. At the end of 4 weeks, bile was collected and bile acid output and bile salt profiles were determined. One of five animals on TPN developed gallstones while two of four receiving daily CCK developed stones. In vivo bile acid synthesis decreased with TPN (controls, 63 +/- 9 mg/24 hr versus TPN, 13 +/- 4 mg/24 hr) and increased in TPN animals with CCK treatment (TPN-CCK, 105 +/- 35 mg/24 hr). Bile acid profiles are changed with TPN with more secondary bile acids, this was not improved with CCK. CCK improved bile acid synthesis and bile acid output but failed to prevent gallstone formation or normalize bile salt profiles. In addition to promoting gallbladder contraction, CCK may have a stimulatory effect on bile acid synthesis. CCK alone did not prevent gallstone formation.
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PMID:Cholecystokinin increases bile acid synthesis with total parenteral nutrition but does not prevent stone formation. 907 Jan 87

Cholangiocytes, the epithelial cells that line intrahepatic bile ducts, participate in bile secretion via basal and agonist-stimulated transport of solutes and water. On the basis of subtle structural differences between cholangiocytes lining small vs. large bile ducts, as well as known phenotypic variations among transporting epithelia in other organs, we demonstrated that cholangiocytes are functionally heterogeneous along the intrahepatic biliary tree of normal rats. In studies reported here, we confirm and extend the concept of functional heterogeneity of cholangiocytes by employing the bile duct-ligated (BDL) rat model of cholestasis associated with selective cholangiocyte proliferation. Using novel isolation and separatory techniques, we prepared subpopulations of pure small, medium, and large cholangiocytes from BDL rats and compared them with regard to gene expression and basal or agonist-responsive transport activities. Although transcripts for gamma-glutamyl transpeptidase and cytokeratin 19, two cholangiocyte-specific proteins, and glyceraldehyde-3-phosphate dehydrogenase, a housekeeping gene, were in all three subpopulations, genes for several proteins involved in solute transport [Cl-/HCO3- exchanger, cystic fibrosis transmembrane conductance regulator (CFTR), and secretin receptor] were expressed only in medium and large cholangiocytes. Consistent with these findings, secretin increased intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) and 36Cl- efflux rates in medium and large cholangiocytes but not in small cholangiocytes. Also, forskolin/8-(4-chlorophenylthio)-cAMP stimulated 36Cl- efflux rates only in medium and large cholangiocytes, consistent with selective functional expression of CFTR in these subpopulations. These results support the molecular and functional heterogeneity of cholangiocytes within the intrahepatic biliary ductal system and are consistent with the notion that hormone-regulated transport of solutes after BDL occurs principally in medium and large cholangiocytes in a fashion similar to that observed in normal rat liver.
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PMID:Molecular and functional heterogeneity of cholangiocytes from rat liver after bile duct ligation. 912 53

The authors investigated whether a depletion of sodium with furosemide enhanced the water and 0.3 M NaCl intakes of rats with experimental cholestasis, portal hypertension or congestive heart failure. These were induced, respectively, by bile duct ligation (BDL), portal vein constriction or vena cava constriction. BDL alone increased daily saline intake. In BDL rats, but not in sham-ligated controls, experience with a prior depletion of sodium enhanced the 2-h saline intake and the retention of water and sodium after a subsequent depletion. Chronic cava constriction, but not portal constriction, enhanced sodium intake and retention after sodium depletion during a 2-h test and enhanced water intake overnight after the test. The results suggest that the ingestion of sodium by BDL and cava-constricted rats may share a common mechanism.
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PMID:Drinking in sodium-depleted rats with bile duct, vena cava or portal vein obstruction. 933 11


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