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Biology of Bile Acids in Health and Disease / Edition 1

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Beginning in 1970, the International Bile Acid Meeting has taken place every two years and each time new progress in our understanding of the complex role of bile acids in many metabolic processes of the liver and the intestine has been revealed by a selected group of leading scientists from all over the world.
Although originally mainly physiological data on bile acid synthesis and transport were emphasized, and later on also the therapeutic benefit of bile acids in gallstone disease and cholestasis was discovered, we have come now to the molecular biology and genetic era with major discoveries in transport defects and related diseases. This book is the proceedings of Falk Symposium No. 120, held in The Hague, The Netherlands, on October 12-13, 2000 - the 16th International Bile Acid Meeting.
One of the main discoveries recently has been the identification of nuclear receptors for bile acids, which gives them a much broader perspective than previously anticipated. It even suggests that bile acids can regulate their biosynthesis and enterohepatic circulation transcriptionally. It will therefore not be surprising that this topic, together with the molecular regulation of cholesterol 7alpha-hydroxylase and cholesterol homeostasis, has a dominant place in these proceedings. Another important topic is the progress in our molecular understanding of hepatic (both at the basolateral and canalicular sites), cholangiocytic and intestinal bile acid transport processes. Further insights into genetic defects causing cholestasis or intestinal malabsorption in animal models and in human diseases are also discussed by a number of well-known authors. Finally the last section deals with new findings on the role of bile acid therapy in cholestatic syndromes or chemoprevention and with the potential benefit of bile acid inhibitors. All contributors provide an update on the most recent developments in their field.

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Product Details

  • ISBN-13: 9780792387688
  • Publisher: Springer Netherlands
  • Publication date: 5/28/2001
  • Series: Falk Symposium Series , #120
  • Edition description: 2001
  • Edition number: 1
  • Pages: 368
  • Product dimensions: 6.34 (w) x 9.20 (h) x 1.00 (d)

Table of Contents

List of Principal Contributors x
Preface xiii
Section I Bile Acid Synthesis and Its Regulation
1 Pathways of bile acid biosynthesis 3
2 Molecular genetics of 3[beta]-hydroxy-[Delta superscript 5]-C[subscript 27]-steroid dehydrogenase deficiency in a patient with progressive intrahepatic cholestasis 10
3 Nuclear receptor regulation of the human cholesterol 7[alpha]-hydroxylase, sterol 27-hydroxylase and sterol 12[alpha]-hydroxylase genes in bile acid synthesis 17
4 Presentation of the Adolf Windaus Prize 2000 26
5 Adolf Windaus Prize lecture: Nuclear orphan receptor regulation of cholesterol and bile acid homeostasis 28
6 Human/mouse BSEP promoter is transactivated by farnesoid X-receptor/bile acid receptor (FXR/BAR) in the presence of bile acids 37
7 The peroxisome proliferator-activated receptor alpha (PPAR[alpha]) is involved in bile acid biosynthesis 43
8 Farnesoid X receptor is a more powerful regulator of cholesterol 7[alpha]-hydroxylase than liver X receptor alpha 54
9 Bile acid-activated cell signalling cascades and the regulation of cholesterol 7[alpha]-hydroxylase in primary rat hepatocytes in culture 59
10 Importance of cholesterol 7[alpha]-hydroxylase in the coordinate molecular regulation of hepatic cholesterol homeostasis in humans 71
11 From brain cholesterol to bile acids: a novel mechanism for removal of cholesterol from the human brain 73
Section II Hepatocyte Transport
12 Bile salt transport by organic anion transporting polypeptides 85
13 New organic anion-transporting polypeptides in the human hepatocyte basolateral membrane 88
14 Bile acid-mediated feedback inhibition of the ntcp gene promoter 95
15 Hepatocellular extrusion of bile acids by ABC transporters 105
Section III Hepatocyte and Cholangiocyte Transport, Biliary Lipid Secretion
16 Molecular identification and functional characterization of the bile export pump (Bsep) in a marine vertebrate - evidence that this liver-specific transporter is highly conserved in evolution 113
17 The role of biliary lipid secretion in lipid homeostasis 116
18 Differential distribution of sphingomyelin and phosphatidylcholine between micellar and vesicular phases: potential implications for biliary lipid secretion
19 Bile acid uptake by microperfused rat intrahepatic bile ducts 128
20 Bile acids stimulate proliferative and secretory events in rat cholangiocytes 137
21 Regulation of biliary epithelial cell secretion by bile acids 152
Section IV Bile Acids and the Intestine
22 Intestinal bile acid transport: new insights from mouse and human models 161
23 Elucidation of the ligand-binding sites of the subunits of the ileal Na[superscript +]/bile acid cotransport system 169
24 The effect of SC-635, a potent inhibitor of the ileal apical sodium co-dependent bile acid transporter, on cholesterol metabolism in rats 183
25 Effects of colesevelam HCI (WelChol), a novel, potent bile acid-binding polymer, on sterol and bile acid metabolism in type lla hypercholesterolaemic subjects 198
26 The limited utility of conjugated bile acid replacement therapy in short bowel syndrome 205
27 Effect of bile acids on the inflammatory activity in animal models of inflammatory bowel disease 227
Section V Bile Acids as Therapeutic Agents: Mechanisms of Action and Results
28 Effects of tauroursodeoxycholic acid on protein kinase C isoforms and on canalicular Mrp2 in experimental cholestasis 245
29 Taurochenodeoxycholate inhibits hepatocyte apoptosis through suppression of Bid translocation to mitochondria 249
30 The neuroprotective characteristics of ursodeoxycholic acid and its conjugates 255
31 Liver targeting of cisplatin-derived cytostatic drugs (Bamets) by coupling to bile acids 271
32 Long-term effects of bile acid therapy in children with defects of primary bile acid synthesis: 3[beta]-hydroxy-C27-steroid-dehydrogenase/isomerase and [Delta superscript 4]-3-oxosteroid 5[beta]-reductase deficiencies 278
Section VI Cholestatic Syndromes
33 FIC1 disease (BRIC and PFIC1) 285
34 Genetic analysis of progressive familial intrahepatic cholestasis 288
35 FIC1: a 140-kDa protein localized in the canalicular membrane of the hepatocyte 301
36 Greenland familial cholestasis is caused by a missense mutation in ATP8B1 (FIC1) 306
37 Ursodeoxycholic acid treatment in cystic fibrosis-associated liver disease 311
38 Treatment options in patients with primary biliary cirrhosis, incompletely responding to ursodeoxycholic acid 317
39 Treatment options in primary sclerosing cholangitis 326
Index 331
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