This volume contains the papers presented in the International Summer Course on "Cirrhosis, Hyperammonemia and Hepatic Encephalopathy," which was one of the prestigious Summer Course, of the Complutense University of Madrid held in EI Escorial, Spain, during August 10-14, 1992. Liver cirrhosis is one of the main causes of death in western countries. In addition there is a series of liver dysfunctions including fulminant hepatic failure, Reye's syndrome and congenital defects of urea cycle enzymes that could lead to hepatic encephalopathy, coma and death. As a consequence of impaired liver function, the ability to detoxify ammonia by its incorporation into urea is diminshed, resulting in increased ammonia levels in blood and brain. Hyperammonemia is considered one of the main factors in the mediation of hepatic encephalopathy and the classical clinical treatments are directed towards reducing blood ammonia levels. A part of the book is therefore devoted to the study of certain aspects of ammonia metabolism such as the regulation of the urea cycle, the main mechanism of ammonia detoxification in mammals, which is located mainly in the liver. The metabolism of ammonia in other tissues, including brain, is also presented, as well as the effects of hyperammonemia on brain metabolism and function and on brain microtubules. The control of cerebral protein breakdown is reviewed. The classical and some recently proposed clinical treatments as well as nutritional considerations in the management of patients with liver failure are also discussed.

This volume contains the papers presented at the International Symposium on "Cirrhosis, Hyperammonemia and Hepatic Encephalopathy," held in Valencia, Spain, January 24th-27th, 1994. Liver cirrhosis and other hepatic dysfunctions such as fulminant hepatic failure and congenital defects of urea cycle enzymes can lead to hepatic encephalopathy, coma and death. Hepatic encephalopathy is one of the main causes of death in western countries. The ability to detoxify ammonia by its incorporation into urea is diminished by impaired liver function, resulting in increased ammonia levels in blood and brain. Hyperammonemia is considered one of the main factors in the mediation of hepatic encephalopathy and the classical clinical treatments are directed towards reducing blood ammonia levels. However, the molecular bases of the pathogenesis of hepatic encephalopathy and the role of hyperammonemia in this process remain unclear and several hypotheses have been proposed. To clarify the mechanisms involved in hepatic encephalopathy and hyperammonemia suitable animal models are necessary. The animal models available and the ideal features of an animal model are presented in the initial part of the book.

This volume contains the papers presented at the Inter- national Symposium on "Cirrhosis, Hepatic Encephalopathy and Ammonium Toxicity", held in Valencia, Spain, November 27-29, 1989. Hepatic cirrhosis as well as other liver failures usual- ly lead to hepatic encephalopathy which is an important cause of death in occidental countries. However the molecular bases of the pathogenesis of hepatic encephalopathy remain unclear and several hypotheses have been proposed. Hyperammonemia is considered one of the main factors responsible for the mediation of hepatic encephalopathy. Therefore, a part of the book is devoted to the effects of hyperammonemia on cerebral function, ammonia and amino acid metabolism, brain microtobules, astrocytes and synaptic trans- mission and their possible role in the pathogenesis of hepatic encephalopathy. Carnitine has a remarkable protective effect against acute ammonium intoxication. Thus some results regarding this effect are also presented, as well as the clinical use of car- nitine. The alterations of the metabolism of ammonia and of seda- tives in liver diseases and their clinical implications are also discussed. The possible role of altered GABA-ergic neurotransmission on the pathogenesis of hepatic encephalopathy has received considerable attention recently. Results of these studies and those on benzodiazepine receptor ligands are presented as well as those on the hypothesis of the role of altered synaptic plasma membrane on the pathogenesis of hepatic encephalopathy.

Animal Models of Hepatic Encephalopathy and Hyperammonemia.- Brain Metabolism in Encephalopathy Caused by Hyperammonemia.- In Vivo Brain Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) in Hepatic Encephalopathy.- Role of the Cellular Hydration State for Cellular Function: Physiological and Pathophysiological Aspects.- Astrocyte-Neuron Interactions in Hyperammonemia and Hepatic Encephalopathy.- Spinal Seizures in Ammonia Intoxication.- Molecular Mechanism of Acute Ammonia Toxicity and of its Prevention by L-Carnitine.- Portal-Systemic Encephalopathy: a Disorder of Multiple Neurotransmitter Systems.- The GABA Hypothesis: State of the Art.- Neuropharmacologic Modulation of Hepatic Encephalopathy: Experimental and Clinical Data.- S-Adenosyl-L-Methionine Synthetase and Methionine Metabolism Deficiencies in Cirrhosis.- Diagnosis and Therapy of Hepatic Encephalopathy.- Neomycin Reduces the Intestinal Production of Ammonia from Glutamine.- N-Acetylglutamate Synthetase (NAGS) Deficiency.- Ornithine Transcarbamylase Deficiency: A Model for Gene Therapy.- Retroviral Gene Transfer for LDL Receptor Deficiency into Primary Hepatocytes.- The Carnitine System: Recent Aspects.- Use of Hepatocyte Cultures for Liver Support Bioreactors.- Hepatitis C Viral infection after Orthotopic Liver Transplantation.- Exercise-Induced Hyperammonemia: Skeletal Muscle Ammonia Metabolism and the Peripheral and Central Effects.- Possible Role of Ammonia in the Brain in Dementia of Alzheimer Type.- Contributors.

Control of Urea Synthesis and Ammonia Detoxification.- Brain Metabolism in Hepatic Encephalopathy and Hyperammonemia.- Ammonia Metabolism in Mammals: Interorgan Relationship.- Clinical Manifestations and Therapy of Hepatic Encephalopathy.- Nutritional Considerations in Patients with Hepatic Failure.- Do Benzodiazepine Ligands Contribute to Hepatic Encephalopathy?.- Effects of Hyperammonemia on Neuronal Function: NH4+, IPSP Cl-Extrusion.- Activation of NMDA Receptor Mediates the Toxicity of Ammonia and the Effects of Ammonia on the Microtubule-Associated Protein MAP-2.- Modulation of the Exocytotic Release of Neurotransmitter Glutamate by Protein Kinase C.- Controls of Cerebral Protein Breakdown.- Two Different Families of NMDA Receptors in Mammalian Brain: Physiological Function and Role in Neuronal Development and Degeneration.- Glanglioside GM1 and its Semisynthetic Lysogangliosides Reduce Glutamate Neurotoxicity by a Novel Mechanism.- Contributors.