D. Keppler – författare

There has been a tremendous amount of scientific progress in our understanding of the molecular mechanisms of transport processes in the liver within the last few years. Cloning of various members of organic anion and cation transporters has provided the necessary tools to study their regulation under physiological and pathophysiological conditions and has advanced our knowledge about bile formation. Mutations of various hepatic organic anion transporters have been identified in humans as hereditary defects leading to the heterogenous syndrome of progressive familial intrahepatic cholestasis (PFIC). Various mouse models including knockout animals have given us the opportunity to gain insight into lipid transport by the liver and the genetics of cholesterol gallstone formation. The physiology of bile duct cells and the molecular mechanisms leading to various cholangiopathies have been a main scientific focus in hepatology in recent years. Drug targeting to the liver by hepatic organic anion transporters represents an attractive way of selective delivery of pharmaceutical agents in humans. Ursodeoxycholic acid is successfully used in the treatment of patients with chronic cholestatic liver disease and major advances have been made in understanding its mode of action in liver and bile duct cells. This book, the proceedings of the Falk Workshop held in Aachen, Germany, on 25-26 January 2001, contains chapters on all important aspects of biliary transport by well-known experts in this field. It is an essential resource for new developments in the field of biliary transport, both in basic science and clinical medicine.

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.

Since the International Bile Acid Meeting in The Hague in 2000, bile acid research has continued to flourish and therapeutic use of bile acids has attained a broader role. Bile acid research has been stimulated by the discovery that bile acids specifically bind to receptors of the cell nucleus. Thereby, they regulate the transcription of transport proteins and enzymes involved in synthesis, transport and metabolism of bile acids and maintain cholesterol homeostasis. Knowledge about genetic defects of bile acid transport which may cause cholestasis or intestinal malabsorption has also increased impressively. Therapy of chronic cholestatic liver diseases, especially of primary biliary cirrhosis, with ursodeoxycholic acid represents an important advance in modern hepatology and has stimulated basic and clinical research to unravel the underlying mechanisms of action and to optimize treatment schedules.This book is the proceedings of Falk Symposium 129, the XVII International Bile Acid Meeting held in Freiburg, Germany, May 30-June 1, 2002, which was again dedicated to both basic and clinical aspects of bile acid research, with a focus on the role of bile acids in hepatobiliary and intestinal diseases. The most up-to-date findings are presented by leading scientists and clinicians in the field.

This book reflects the recent progress in bile acid metabolism and transport, nuclear receptor regulation and signaling by bile acids, as well as mechanisms of bile acid-induced cellular injury. Coverage examines bile acids as therapeutic agents, particularly for the treatment of cholestatic liver diseases. This volume in the Falk Symposium series brings together basic science and clinical hepatology in the field of bile acids.