Hepatic Transport Of Organic Substances

Hepatic cells are involved in the metabolization and elimination of a variety of endogenous and exogenous substances. They mediate the uptake, processing and subsequent secretion of biliary compounds, such as various drugs or hormones, and the passage of metabolites to be released into different blood compartments. To perform vectorial passages hepatocytes show a strong polarity with sites for endocytotic processes or specific carrier molecules, and a specified system of organelles for intracellular transport and sorting, metabolization and secretion of compounds. Several aspects, e.g. regulation, control and mechanisms of hepatic traffic are reported in detail - complemented by methodological approaches to analyse and monitor these processes.

In the early 1980s, two water-supply systems on the Marine Corps Base Camp Lejeune in North Carolina were found to be contaminated with the industrial solvents trichloroethylene (TCE) and perchloroethylene (PCE). The water systems were supplied by the Tarawa Terrace and Hadnot Point watertreatment plants, which served enlisted-family housing, barracks for unmarried service personnel, base administrative offices, schools, and recreational areas. The Hadnot Point water system also served the base hospital and an industrial area and supplied water to housing on the Holcomb Boulevard water system (full-time until 1972 and periodically thereafter). This book examines what is known about the contamination of the water supplies at Camp Lejeune and whether the contamination can be linked to any adverse health outcomes in former residents and workers at the base.

This volume aims to give a comprehensive overview of the cellular mechanisms underlying the process of secretion in vertebrate, particularly mammalian, exocrine glands. The subject matter is divided into two sections. The first section deals with general aspects of secretion, including chapters on the roles of ion channels in secretion. Signal transduction is also covered, and several chapters deal with recently developed investigative techniques that offer promise as tools for the further investigation of exocrine secretory processes. The second section deals with secretion in a selection of exocrine organs: salivary glands, lacrimal glands, the pancreas, gastric mucosa, liver, epididymis, and vertebrate salt glands. A final chapter deals with cystic fibrosis, the common, fatal, inherited disease, which affects exocrine glands particularly severely.

In response to the tremendous increase in the number of protein and peptide drugs, this treatise critically reviews transport and metabolism mechanisms relating to the delivery of endogenous and recombinant proteins to mammalian organs, tissues, and cells. It will promote fruitful collaboration among academic and industrial scientists in the fields of pharmacology, cell biology, biochemistry, physiology, and immunology.

The second edition of Physiology of Membrane Disorders represents an extensive revision and a considerable expansion of the first edition . Yet the purpose ofthe second edition is identical to that of its predecessor, namely, to provide a rational analysis of membrane transport processes in individual membranes, cells, tissues, and organs, which in tum serves as a frame of reference for rationalizing disorders in which derangements of membrane transport processes playa cardinal role in the clinical expression of disease. As in the first edition, this book is divided into a number of individual, but closely related, sections. Part V represents a new section where the problem of transport across epithelia is treated in some detail. Finally, Part VI, which analyzes clinical derangements, has been enlarged appreciably. THE EDITORS xi Preface to the First Edition The purpose of this book is to provide the reader with a rational frame of reference for assessing the pa thophysiology of those disorders in which derangements of membrane transport processes are a major factor responsible for the clinical manifestations of disease. In the present context, we use the term "membrane transport to refer to those molecular processes whose cardinal function, broadly speaking, is processes" in a catholic sense, the vectorial transfer of molecules-either individually or as ensembles-across biological interfaces, the latter including those interfaces which separate different intracellular compartments, the cellular and extracellular com partments, and secreted fluids-such as glomerular filtrate-and extracellular fluids.

Hepatology -- a systematic overview The 1st edition was sold out within one year and a reprint became necessary. The 2nd edition has been updated, revised and extended to include some 900 pages. Unique - 477 top-quality coloured figures containing clinical and immunological findings, laparoscopic and and histologic features as well as imaging procedures - all figures directly integrated in the respective text; this results in a new form of learning from "seeing" to "understanding" Attractive - 306 tables in colour - coloured highlighting of important principles and statements for better reading - well-structured and systematic approaches support the content - derived from clinical hepatology for practical use by specialists and in hospital Instructive - detailed presentation of morphology and its integration in liver disease - precise recommendations for therapy and summarized descriptions of special forms of treatment (inlcuding a separate chapter on "Therapy" Manual - about 7,000 references are listed in full; quotations of significant historical publications - first authors of therapy procedures, methods, medical techniques and invasive measures are given as far as possible - comprehensive subject index and register of abbreviations

Around one third of all biologically relevant small molecules are organic cations. These include endogenous substances like catecholamines and other neurotransmitters, toxins and drugs designed to affect signaling processes. The organic cation transporter 1 (OCT1) is among the strongest expressed membrane transporters at the sinusoidal (blood-facing) side of liver cells and contributes substantially to the clearance of the blood from numerous organic cations. A most striking feature of OCT1 is its pronounced genetic diversity. Between 1 and 10% of all human populations have little to no OCT1 activity. With several of the OCT1 substrates up to 10% of Europeans are functionally OCT1 deficient. Apparently, the lack of OCT1 do not lead to apparent substantial pathological changes in these individuals. It thus appears that this transporter is not essential to human life, but does it means that OCT1 is irrelevant? In the last 25 years since the first cloning of this transporter, data on its pharmacological and physiological relevance is steadily accumulating. Numerous clinically relevant drugs (e.g. metformin, morphine, fenoterol, sumatriptan, tramadol and tropisetron) have been shown to be substrates of OCT1, and OCT1 deficiency has been shown to affect the pharmacokinetics, efficacy, or toxicity of these drugs. Also vitamin B1 has been shown to be a substrate of OCT1, and in genetically modified mice OCT1 substantially modulated hepatic lipid metabolism, total body fat and systemic glucose and lipid concentrations. Still, numerous important questions remain unsolved: For which drugs, toxins, or other endogenous or exogenous substances is OCT1 relevant? How can we predict the relevance of OCT1 from in vitro studies? What determines the substrate selectivity of OCT1 in comparison to other transporters or transport processes for organic cations? What regulates the expression of OCT1 in the liver and possibly in other tissues? What is the impact of OCT1 variation in different areas of medicine, including the therapies for cancer as well as for pulmonary, cardiovascular, or neurological diseases? How can evolutionary biology contribute to a better understanding of the roles of OCT1? And, importantly, what types of research are likely to significantly further the knowledge on OCT1 in the next decades?

Completely revised new edition of the premier reference on pediatric liver disease. Liver Disease in Children, 3rd Edition provides authoritative coverage of every aspect of liver disease affecting infants, children, and adolescents. The book offers an integrated approach to the science and clinical practice of pediatric hepatology and charts the substantial progress in understanding and treating these diseases. Chapters are written by international experts and address the unique pathophysiology, manifestations, and management of these disorders in the pediatric population. The third edition has been thoroughly updated and features new contributions on liver development, cholestatic and autoimmune disorders, fatty liver disease, and inborn errors of metabolism. With the continued evolution of pediatric hepatology as a discipline, this text remains an essential reference for all physicians involved in the care of children with liver disease.