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MeSH Review


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Disease relevance of Cholestasis


High impact information on Cholestasis

  • Its protein product is likely to play an essential role in enterohepatic circulation of bile acids; further characterization of FIC1 will facilitate understanding of normal bile formation and cholestasis [6].
  • A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis [6].
  • Transient, asymptomatic cholestasis was observed in the ketoconazole group [7].
  • Improved neurologic function after long-term correction of vitamin E deficiency in children with chronic cholestasis [8].
  • These FXR complexes provide direct insights into the design of therapeutic bile acids for treatment of hyperlipidemia and cholestasis [9].

Chemical compound and disease context of Cholestasis

  • Deconjugation may also account, at least in part, for the presence of increased concentrations of unconjugated bilirubin in the plasma of patients with cholestasis [10].
  • In addition, speculations concerning the role of parenteral nutrition in the induction of cholestasis in premature infants should be made with caution [11].
  • This lipoprotein has a high content of unesterified cholesterol and phospholipids and appears to be ineffective in suppressing the enhanced hepatic cholesterogenesis of cholestasis [12].
  • These data show that in addition to the previously demonstrated sinusoidal transport abnormalities ethinylestradiol-induced cholestasis is also associated with multiple canalicular membrane transport alterations in rat liver [13].
  • Finally, studies in livers from rats with endotoxin- or estrogen-induced cholestasis show that glybenclamide retains its stimulatory effects on bile flow and bicarbonate excretion even under these conditions [14].

Biological context of Cholestasis

  • However, cholestasis provoked a 10-fold increase in the number of hepatic mitoses and in the incorporation of thymidine into liver DNA of cholestatic animals [15].
  • In controls, activation of the Fas receptor resulted in rapid dephosphorylation of Bid and its subsequent cleavage, whereas Bid remained phosphorylated and uncleaved in chronic cholestasis and other models of hepatic apoptosis resistance [16].
  • Liver histology demonstrated a comparative improvement in cholestasis in patients on penicillamine, but the degree of inflammation, necrosis, and the histological stage of disease remained similar in both groups [17].
  • Raised P3NP levels also correlated with the degree of cholestasis as evaluated by serum bilirubin, serum alkaline phosphatase, and copper binding protein deposition in the liver [18].
  • CONCLUSIONS: These data suggest that an increase in mitochondria cardiolipin content occurs during cholestasis as an adaptive phenomenon to resist cell death by the MPT [19].

Anatomical context of Cholestasis


Gene context of Cholestasis


Analytical, diagnostic and therapeutic context of Cholestasis


  1. Ondansetron for pruritus due to cholestasis. Raderer, M., Müller, C., Scheithauer, W. N. Engl. J. Med. (1994) [Pubmed]
  2. Vasculopathic hepatotoxicity associated with E-Ferol syndrome in low-birth-weight infants. Bove, K.E., Kosmetatos, N., Wedig, K.E., Frank, D.J., Whitlatch, S., Saldivar, V., Haas, J., Bodenstein, C., Balistreri, W.F. JAMA (1985) [Pubmed]
  3. Manganese toxicity in children receiving long-term parenteral nutrition. Fell, J.M., Reynolds, A.P., Meadows, N., Khan, K., Long, S.G., Quaghebeur, G., Taylor, W.J., Milla, P.J. Lancet (1996) [Pubmed]
  4. Effect of phenobarbital in a case of extrahepatic cholestasis. Metreau, J.M., Bismuth, H., Franco, D., Dhumeaux, D. Gastroenterology (1975) [Pubmed]
  5. Intestinal failure-associated liver disease: what do we know today? Kelly, D.A. Gastroenterology (2006) [Pubmed]
  6. A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis. Bull, L.N., van Eijk, M.J., Pawlikowska, L., DeYoung, J.A., Juijn, J.A., Liao, M., Klomp, L.W., Lomri, N., Berger, R., Scharschmidt, B.F., Knisely, A.S., Houwen, R.H., Freimer, N.B. Nat. Genet. (1998) [Pubmed]
  7. Ketoconazole to reduce the need for cyclosporine after cardiac transplantation. Keogh, A., Spratt, P., McCosker, C., Macdonald, P., Mundy, J., Kaan, A. N. Engl. J. Med. (1995) [Pubmed]
  8. Improved neurologic function after long-term correction of vitamin E deficiency in children with chronic cholestasis. Sokol, R.J., Guggenheim, M.A., Iannaccone, S.T., Barkhaus, P.E., Miller, C., Silverman, A., Balistreri, W.F., Heubi, J.E. N. Engl. J. Med. (1985) [Pubmed]
  9. Structural basis for bile acid binding and activation of the nuclear receptor FXR. Mi, L.Z., Devarakonda, S., Harp, J.M., Han, Q., Pellicciari, R., Willson, T.M., Khorasanizadeh, S., Rastinejad, F. Mol. Cell (2003) [Pubmed]
  10. Bilirubin kinetics in intact rats and isolated perfused liver. Evidence for hepatic deconjugation of bilirubin glucuronides. Gollan, J., Hammaker, L., Licko, V., Schmid, R. J. Clin. Invest. (1981) [Pubmed]
  11. Postnatal physiologic hypercholemia in both premature and full-term infants. Barnes, S., Berkowitz, G., Hirschowitz, B.I., Wirtschafter, D., Cassady, G. J. Clin. Invest. (1981) [Pubmed]
  12. Role of lipoprotein-X in the pathogenesis of cholestatic hypercholesterolemia. Uptake of lipoprotein-X and its effect on 3-hydroxy-3-methylglutaryl coenzyme A reductase and chylomicron remnant removal in human fibroblasts, lymphocytes, and in the rat. Walli, A.K., Seidel, D. J. Clin. Invest. (1984) [Pubmed]
  13. Ethinylestradiol treatment induces multiple canalicular membrane transport alterations in rat liver. Bossard, R., Stieger, B., O'Neill, B., Fricker, G., Meier, P.J. J. Clin. Invest. (1993) [Pubmed]
  14. Stimulation of bile duct epithelial secretion by glybenclamide in normal and cholestatic rat liver. Nathanson, M.H., Burgstahler, A.D., Mennone, A., Dranoff, J.A., Rios-Velez, L. J. Clin. Invest. (1998) [Pubmed]
  15. Adrenergic regulation of glycogenolysis in rat liver after cholestasis. Modulation of the balance between alpha 1 and beta 2 receptors. Aggerbeck, M., Ferry, N., Zafrani, E.S., Billon, M.C., Barouki, R., Hanoune, J. J. Clin. Invest. (1983) [Pubmed]
  16. Sustained phosphorylation of Bid is a marker for resistance to Fas-induced apoptosis during chronic liver diseases. Vogel, A., Aslan, J.E., Willenbring, H., Klein, C., Finegold, M., Mount, H., Thomas, G., Grompe, M. Gastroenterology (2006) [Pubmed]
  17. A controlled trial of D-penicillamine therapy in primary biliary cirrhosis. Jain, S., Scheuer, P.J., Samourian, S., McGee, J.O. Lancet (1977) [Pubmed]
  18. Type III procollagen peptide: a marker of disease activity and prognosis in primary biliary cirrhosis. Babbs, C., Smith, A., Hunt, L.P., Rowan, B.P., Haboubi, N.Y., Warnes, T.W. Lancet (1988) [Pubmed]
  19. Cholestasis confers resistance to the rat liver mitochondrial permeability transition. Lieser, M.J., Park, J., Natori, S., Jones, B.A., Bronk, S.F., Gores, G.J. Gastroenterology (1998) [Pubmed]
  20. The metabolism of 3alpha, 7alpha, 12alpha-trihydorxy-5beta-cholestan-26-oic acid in two siblings with cholestasis due to intrahepatic bile duct anomalies. An apparent inborn error of cholic acid synthesis. Hanson, R.F., Isenberg, J.N., Williams, G.C., Hachey, D., Szczepanik, P., Klein, P.D., Sharp, H.L. J. Clin. Invest. (1975) [Pubmed]
  21. Effect of cholestasis and bile acids on interferon-induced 2',5'-adenylate synthetase and NK cell activities. Podevin, P., Calmus, Y., Bonnefis, M.T., Veyrunes, C., Chereau, C., Poupon, R. Gastroenterology (1995) [Pubmed]
  22. Tetracycline-induced bile duct paucity and prolonged cholestasis. Hunt, C.M., Washington, K. Gastroenterology (1994) [Pubmed]
  23. MDR3 gene defect in adults with symptomatic intrahepatic and gallbladder cholesterol cholelithiasis. Rosmorduc, O., Hermelin, B., Poupon, R. Gastroenterology (2001) [Pubmed]
  24. Cholestasis: Pump failure, microvilli defect, or both? Erlinger, S. Lancet (1978) [Pubmed]
  25. Reduced activity of 11 beta-hydroxysteroid dehydrogenase in patients with cholestasis. Quattropani, C., Vogt, B., Odermatt, A., Dick, B., Frey, B.M., Frey, F.J. J. Clin. Invest. (2001) [Pubmed]
  26. Trafficking of the bile salt export pump from the Golgi to the canalicular membrane is regulated by the p38 MAP kinase. Kubitz, R., Sütfels, G., Kühlkamp, T., Kölling, R., Häussinger, D. Gastroenterology (2004) [Pubmed]
  27. Vascular endothelial growth factor stimulates rat cholangiocyte proliferation via an autocrine mechanism. Gaudio, E., Barbaro, B., Alvaro, D., Glaser, S., Francis, H., Ueno, Y., Meininger, C.J., Franchitto, A., Onori, P., Marzioni, M., Taffetani, S., Fava, G., Stoica, G., Venter, J., Reichenbach, R., De Morrow, S., Summers, R., Alpini, G. Gastroenterology (2006) [Pubmed]
  28. Nuclear receptors constitutive androstane receptor and pregnane X receptor ameliorate cholestatic liver injury. Stedman, C.A., Liddle, C., Coulter, S.A., Sonoda, J., Alvarez, J.G., Moore, D.D., Evans, R.M., Downes, M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  29. Reduced hepatic expression of farnesoid X receptor in hereditary cholestasis associated to mutation in ATP8B1. Alvarez, L., Jara, P., Sánchez-Sabaté, E., Hierro, L., Larrauri, J., Díaz, M.C., Camarena, C., De la Vega, A., Frauca, E., López-Collazo, E., Lapunzina, P. Hum. Mol. Genet. (2004) [Pubmed]
  30. Metronidazole in prevention of cholestasis associated with total parenteral nutrition. Capron, J.P., Gineston, J.L., Herve, M.A., Braillon, A. Lancet (1983) [Pubmed]
  31. Effect of cholestasis produced by bile duct ligation on hepatic heme and hemoprotein metabolism in rats. Schacter, B.A., Joseph, E., Firneisz, G. Gastroenterology (1983) [Pubmed]
  32. Loss of inositol 1,4,5-trisphosphate receptors from bile duct epithelia is a common event in cholestasis. Shibao, K., Hirata, K., Robert, M.E., Nathanson, M.H. Gastroenterology (2003) [Pubmed]
  33. Scanning electron microscopy of the rat liver. Studies of the effect of taurolithocholate and other models of cholestasis. Layden, T.J., Schwarz, n.u.l.l., Boyer, J.L. Gastroenterology (1975) [Pubmed]
  34. Prevalence of liver disease and contributing factors in patients receiving home parenteral nutrition for permanent intestinal failure. Cavicchi, M., Beau, P., Crenn, P., Degott, C., Messing, B. Ann. Intern. Med. (2000) [Pubmed]
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