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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.
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.
Since the last International Bile Acid Meeting in Stockholm in
2004, bile acid research has continued to flourish and therapeutic
use of bile acids has attained a broader role. New insights have
been gained into the mechanisms responsible for maintenance of bile
acid homeostasis, and effects of bile acids on the cell signalling
pathways have been further elucidated. Knowledge of the genetic
basis of bile acid physiology has further increased. Therapy of
chronic cholestatic liver diseases with ursodeoxycholic acid and
new aspects of its chemopreventive properties continue to stimulate
basic and clinical research and contribute to the understanding of
underlying modes of action and to optimized treatment schedules.
Chapters reflect 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...
The pathogenesis of cell death and necrosis in the liver is a
central topic of research in liver disease. A molecular
understanding of events and sequences leading to cellular death
provides the basis for preventive and therapeutic efforts. This
volume originates from a "Workshop on Experimental Liver Injury"
held on November 9 and 10, 1974, in Freiburg, Germany. Recent
progress in the elucidation of the mode of action includes agents
inducing liver cell necrosis by a primary dis- turbance of
nucleotide and nucleic acid metabolism as well as hepa- totoxins
characterized by a primary attack on cellular membranes. I hope
that this book will contribute to an increasing understanding of
disease mechanisms. Freiburg im Breisgau Dietrich Keppler June 1975
Acknowledgments The generous support from Dr. H. Falk, Freiburg,
has been a prereqUIsite for the organisation and publication of the
meeting on "Pathogenesis and Mechanisms of Liver Cell Necrosis". I
wish to express my sincere thanks for this sponsorship. I am
indebted to those who acted as chairmen during the meeting:
Professors H. Remmer (Tilbingen), M. Frimmer (Giessen), W. Gerok
(Freiburg), H. Popper (New York), H. Schimassek (Heidelberg), and
K. Decker (Freiburg).
This book is the proceedings of the 18th International Bile Acid
Meeting, held as the Falk Symposium 141 in Stockholm, Sweden, on
June 18-19, 2004. The International Bile Acid Meetings have become
some of the most important meetings in the bile acid field
worldwide since Herbert Falk decided to sponsor these Symposia in
biannual sequence in 1970. The 17 International Bile Acid Meetings
in the past have been a great stimulus for new ideas and methods as
well as the development of therapeutic applications of bile acids.
They have always been a forum where basic scientists and clinicians
interact. Many novel results of bile acid research were first
presented at these meetings. The meeting in Stockholm again
attracted a large number of basic and clinical scientists
interested in bile acid and biliary research from all over the
world. Knowledge about the regulation of bile acid synthesis, bile
acid transport and enterohepatic circulation in health and in
disease has increased considerably during recent years.
Accordingly, bile acid research is alive as ever. A new chapter of
bile acid research was opened by the finding that bile acids are
ligands of nuclear receptors which regulate synthesis, metabolism
and transport of bile acids and steroids. A large part of the book
is devoted to these topics. The 18th International Bile Acid
Meeting was again a truly interdisciplinary symposium at the
highest scientific level. Its participants enjoyed hearing the
latest reports on bile acid research in the city where so many
seminal studies on bile acids were performed. It is hoped that the
readers of this book will share the enjoyment.
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