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Bile Formation (bile + formation)
Selected AbstractsBiliary physiology and disease: Reflections of a physician-scientist,HEPATOLOGY, Issue 4 2010Gustav Paumgartner A review is presented of Gustav Paumgartner's five decades of research and practice in hepatology focusing on biliary physiology and disease. It begins with studies of the excretory function of the liver including hepatic uptake of indocyanine green, bilirubin, and bile acids. The implications of these studies for diagnosis and understanding of liver diseases are pointed out. From there, the path of scientific research leads to investigations of hepatobiliary bile acid transport and the major mechanisms of bile formation. The therapeutic effects of the hydrophilic bile acid, ursodeoxycholic acid, have greatly stimulated these studies. Although ursodeoxycholic acid therapy for dissolution of cholesterol gallstones and some other nonsurgical treatments of gallstones were largely superseded by surgical techniques, ursodeoxycholic acid is currently considered the mainstay of therapy of some chronic cholestatic liver diseases, such as primary biliary cirrhosis. The major mechanisms of action of ursodeoxycholic acid therapy in cholestatic liver diseases are discussed. An attempt is made to illustrate how scientific research can lead to advances in medical practice that help patients. (HEPATOLOGY 2010:51:1095,1106.) [source] Secretin activation of the apical Na+ -dependent bile acid transporter is associated with cholehepatic shunting in rats,HEPATOLOGY, Issue 5 2005Gianfranco Alpini The role of the cholangiocyte apical Na+ -dependent bile acid transporter (ASBT) in bile formation is unknown. Bile acid absorption by bile ducts results in cholehepatic shunting, a pathway that amplifies the canalicular osmotic effects of bile acids. We tested in isolated cholangiocytes if secretin enhances ASBT translocation to the apical membrane from latent preexisting intracellular stores. In vivo, in bile duct,ligated rats, we tested if increased ASBT activity (induced by secretin pretreatment) results in cholehepatic shunting of bile acids. We determined the increment in taurocholate-dependent bile flow and biliary lipid secretion and taurocholate (TC) biliary transit time during high ASBT activity. Secretin stimulated colchicine-sensitive ASBT translocation to the cholangiocyte plasma membrane and 3H-TC uptake in purified cholangiocytes. Consistent with increased ASBT promoting cholehepatic shunting, with secretin pretreatment, we found TC induced greater-than-expected biliary lipid secretion and bile flow and there was a prolongation of the TC biliary transit time. Colchicine ablated secretin pretreatment-dependent bile acid,induced choleresis, increased biliary lipid secretion, and the prolongation of the TC biliary transit. In conclusion, secretin stimulates cholehepatic shunting of conjugated bile acids and is associated with increased cholangiocyte apical membrane ASBT. Bile acid transport by cholangiocyte ASBT can contribute to hepatobiliary secretion in vivo. (HEPATOLOGY 2005.) [source] A missense mutation in FIC1 is associated with greenland familial cholestasisHEPATOLOGY, Issue 6 2000Leo W. J. Klomp Greenland familial cholestasis is a severe form of intrahepatic cholestasis described among indigenous Inuit families in Greenland. Patients present with jaundice, pruritus, bleeding episodes, and steatorrhea, and die in childhood due to end-stage liver disease. We investigated the possibility that Greenland familial cholestasis is caused by a mutation in FIC1, the gene defective in patients with progressive familial intrahepatic cholestasis type 1 and many cases of benign recurrent intrahepatic cholestasis. Using single-strand conformation polymorphism analysis and sequencing of the FIC1 exons, a missense mutation, 1660 G,A (D554N), was detected and was shown to segregate with the disease in Inuit patients from Greenland and Canada. Examination of liver specimens from 3 Inuit patients homozygous for this mutation revealed bland canalicular cholestasis and, on transmission electron microscopy, coarsely granular Byler bile, as previously described in patients with progressive familial intrahepatic cholestasis type 1. These data establish Greenland familial cholestasis as a form of progressive familial intrahepatic cholestasis type 1 and further underscore the importance of unimpeded FIC1 activity for normal bile formation. [source] Role of mitogen-activated protein kinases in tauroursodeoxycholic acid-induced bile formation in cholestatic rat liverHEPATOLOGY RESEARCH, Issue 7 2008Gerald Ulrich Denk Aim:, Ursodeoxycholic acid exerts anticholestatic effects in various cholestatic disorders and experimental models of cholestasis. Its taurine conjugate (TUDCA) stimulates bile salt secretion in isolated perfused rat livers (IPRL) under physiological, non-cholestatic conditions, in part by mitogen-activated protein kinase (MAPK)-dependent mechanisms. The role of MAPK in the anticholestatic effect of TUDCA, however, is unclear. Therefore, we studied the role of MAPK in the anticholestatic effect of TUDCA in IPRL and isolated rat hepatocytes (IRH) in taurolithocholic acid (TLCA)-induced cholestasis. Methods:, Bile flow, biliary levels of 2,4-dinitrophenyl-S-glutathione (GS-DNP) as a marker of hepatobiliary organic anion secretion and activity of lactate dehydrogenase (LDH) in hepatovenous effluate as a marker of hepatocellular damage in IPRL perfused with TUDCA and/or TLCA were determined in the presence or absence of MAPK inhibitors. In addition, phosphorylation of Erk 1/2 and p38MAPK induced by TUDCA and/or TLCA was studied by Western immunoblot in IPRL and IRH. Results:, TUDCA-induced bile flow was impaired by the Erk 1/2 inhibitor PD98059 in normal livers (,28%), but not in livers made cholestatic by TLCA. GS-DNP secretion was unaffected by PD98059 under both conditions. TUDCA-induced bile formation and organic anion secretion both in the presence and absence of TLCA were unaffected by the p38MAPK inhibitor SB202190. Erk 1/2 phosphorylation in liver tissue was unchanged after bile salt exposure for 70 min, but was transiently enhanced by TUDCA in IRH. Conclusion:, MAPK do not mediate the anticholestatic effects of TUDCA in TLCA-induced cholestasis. [source] Comparative analysis of ATP-binding cassette (ABC) transporter gene expression levels in peripheral blood leukocytes and in liver with hepatocellular carcinomaCANCER SCIENCE, Issue 6 2004Mohsen A. Moustafa ATP-binding cassette (ABC) transporters comprise a superfamily of similar proteins involved in transmembrane transport of various substances. ABC transporter family members in the liver participate in bile formation and lipid metabolism. In order to assess whether peripheral blood leukocytes (PBL) are available as a surrogate for determination of the expression of ABC transporter genes in the liver, we compared ABC transporter gene expression levels in PBL with those in liver tissues from patients with hepatocellular carcinoma (HCC). We measured ABCA1, A2, B1-B4, C1°C5, G1 and G2 gene expression levels in PBL, and cancerous and non-cancerous portions of liver from patients with hepatocellular carcinoma by means of real time reverse-transcription (RT)-PCR. We could not detect ABCC5 expression in any tissue of the liver. Close correlations between ABCA2, C1 and 67 in PBL and in non-tumor tissues of the liver were found. Compared with the non-tumor part, HCC tissue expressed lower levels of ABCA1, B4 and G2. We think monitoring of ABCA2, C1 and G7 gene expression levels in PBL will be useful for selection of anti cancer agents and monitoring of drug resistance of HCC. Administration of chemotherapeutic agents which are substrates of ABCA1, B4 and G2 should be effective for the treatment of HCC. (Cancer Sci 2004; 95: 530,536) [source] | ||||||||||