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, De- cember 2nd_4th, 1996. Liver cirrhosis is one of the main causes of death in occidental countries. There are other hepatic dysfunctions such as fulminant hepatic failure, Reye's syndrome, or congenital deficiencies of urea cycle enzymes which can also lead to hepatic encephalopathy, coma and death. However, the molecular bases ofthe pathogenesis of hepatic encephalopathy remain unclear. One ofthe consequences of hepatic failure is the reduced ability to detoxify ammonia by incorporating it into urea. This leads to increased blood ammonia levels. Hyperam- monemia is considered one of the main factors responsible for the mediation of hepatic encephalopathy and classical clinical treatments are directed towards reducing blood ammo- nia levels. Altered neurotransmission is an essential step in the pathogenesis of hepatic encephalopathy. The first part of the book is devoted to the discussion of the recent advances in the understanding of the alterations of different neurotransmitter systems in hepatic encephalopathy. The alterations of tryptophan metabolism and neurotransmission in hepatic encephalopathy and the implications for the clinical use of neuropsychoactive drugs are reviewed. The alterations in glutamate transport and neurotransmission in hepatic encephal- opathy due to acute liver failure are also reviewed. The role of NMDA receptors in the molecular mechanism of acute ammonia toxicity is discussed as well as its modulation by metabotropic glutamate receptors and muscarinic receptors.

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.

Given the latest advances in cancer research, which includes basic research and its derived diagnostic, clinical, and therapeutic applications, the book New Trends in Cancer for the 21st Century is written by individuals such as molecular biologists, whose tasks are to decipher, after sequencing the human genome, those new genes and pathways involved in the carcinogenesis process; clinical and molecular pathologists, who apply these discoveries for the molecular diagnosis and characterization of the tumor; and clinical oncologists, who treat patients. Pharmacogenetics introduces new perspectives in the translational fields with the design of drugs against specific targets, which at this moment are in clinical trials phases. This book achieves a state of the art in every field of cancer research and discusses the new perspectives that will open the future for cancer treatment (basic research, new technologies, new drugs, therapies...). For this reason, the book is intended for pathologists, clinicians, and biologists, as well as fellows and students of physiology and medicine.

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.

This volume contains the text of the presentations delivered at the International Symposium on Rare Diseases "Inherited Neuromuscular Diseases: Translation from Pathomechanisms to Therapies," held in Valencia, Spain, from November 16 to 18, 2008. The symposium represents a part of the continuous efforts on dif- sion of science to the society of the Catedra Santiago Grisolia and the Fundacion Ciudad de las Artes y las Ciencias -Comunitat Valenciana. More than 200 inter- tional scientists from different countries of Europe, the USA, and Australia attended the meeting. The venue was the Auditorium of the Science Museum Principe Felipe. Ten years ago Alan Emery wrote in the preface of Neuromuscular Disorders: Clinical and Molecular Genetics the following comments: "It has been estimated that more than one person in every 3,000 has a serious disabling inherited n- romuscular disorder. The suffering caused by these disorders is considerable, but, until the last decade or so, virtually nothing was known of their pathogenesis. Any rationale approach to treatment was therefore out of the question. However, matters are now changing rapidly. The genes for many of these disorders have been localised and characterised and their gene products identi ed and studied. The detection of preclinical disease, the identi cation of heterozygous carriers and prenatal di- nosis are all becoming possible, and, hopefully, effective treatments may no be too far distant."

It is difficult to imagine anyone who has not heard of cancer. This disease can affect families, friends or any one of us at any time in our lives. Every year nearly 3 million Europeans are diagnosed with cancer, leading to around 800,000 deaths per year. These deaths occur not only in aging populations, but also in children and adults who are in the most active period of their lives. This represents a tremendous problem that cannot be ignored by politicians or citizens. Fortunately, there is a constantly growing awareness that although cancer is a problem to be dealt with by clinicians, it should also be the concern of everyone. This volume contains the lectures held at the International Symposium on Cancer "New Trends in Cancer for the 21st Century." Fundamental researchers, politicians and representatives from patient coalitions share here their knowledge and interests as well as their concerns and experiences. Not only do these papers provide state-of-the-art information on cancer, they are also an opportunity to look at the problem from different points of view. It can be encouraging to realise that we are not alone in this fight.

This volume contains the text of the presentations delivered at the International Symposium on Rare Diseases "Inherited Neuromuscular Diseases: Translation from Pathomechanisms to Therapies," held in Valencia, Spain, from November 16 to 18, 2008. The symposium represents a part of the continuous efforts on dif- sion of science to the society of the Catedra Santiago Grisolia and the Fundacion Ciudad de las Artes y las Ciencias -Comunitat Valenciana. More than 200 inter- tional scientists from different countries of Europe, the USA, and Australia attended the meeting. The venue was the Auditorium of the Science Museum Principe Felipe. Ten years ago Alan Emery wrote in the preface of Neuromuscular Disorders: Clinical and Molecular Genetics the following comments: "It has been estimated that more than one person in every 3,000 has a serious disabling inherited n- romuscular disorder. The suffering caused by these disorders is considerable, but, until the last decade or so, virtually nothing was known of their pathogenesis. Any rationale approach to treatment was therefore out of the question. However, matters are now changing rapidly. The genes for many of these disorders have been localised and characterised and their gene products identi ed and studied. The detection of preclinical disease, the identi cation of heterozygous carriers and prenatal di- nosis are all becoming possible, and, hopefully, effective treatments may no be too far distant."

It is difficult to imagine anyone who has not heard of cancer. This disease can affect families, friends or any one of us at any time in our lives. Every year, nearly 3 million Europeans are diagnosed with cancer, leading to around 800,000 deaths per year. These deaths occur not only in aging populations, but also in children and adults who are in the most active period of their lives. This represents a tremendous problem that cannot be ignored by politicians or citizens. Fortunately, there is a constantly growing awareness that although cancer is a problem to be dealt with by clinicians, it should also be the concern of everyone. This volume contains the lectures held at the International Symposium on Cancer New Trends in Cancer for the 21st Century. Fundamental researchers, politicians and representatives from patient coalitions share here their knowledge and interests as well as their concerns and experiences.

Given the latest advances in cancer research, which includes basic research and its derived diagnostic, clinical, and therapeutic applications, the book New Trends in Cancer for the 21st Century is written by individuals such as molecular biologists, whose tasks are to decipher, after sequencing the human genome, those new genes and pathways involved in the carcinogenesis process; clinical and molecular pathologists, who apply these discoveries for the molecular diagnosis and characterization of the tumor; and clinical oncologists, who treat patients. Pharmacogenetics introduces new perspectives in the translational fields with the design of drugs against specific targets, which at this moment are in clinical trials phases. Several organizations such as the EORTC (European Organization for Research and Treatment of Cancer) and the OECI (Organization of European Cancer Institutes) and comprehensive cancer centers play a crucial role in focusing cancer research on all these areas.
This book achieves a state of the art in every field of cancer research and discusses the new perspectives that will open the future for cancer treatment (basic research, new technologies, new drugs, therapies...). For this reason, the book is intended for pathologists, clinicians, and biologists, as well as fellows and students of physiology and medicine.

Brain Tryptophan Perturbation in Hepatic Encephalopathy: Implications for Effects by Neuropsychoactive Drugs in Clinical Practice; F. Bengtsson, et al. Hepatic Encephalopathy in Acute Liver Failure: Role of the Glutamate System; A. Michalak, et al. Glutamate and Muscarinic Receptors in the Molecular Mechanisms of Acute Ammonia Toxicity and of Its Prevention; M.D. Minana, et al. Studies on the Pharmacological Properties of Oxindole (2-Hydroxyindole) and 5-Hydroxyindole: Are They Involved in Hepatic Encephalopathy?; F. Moroni, et al. The Involvement of Ammonia with the Mechanisms That Enhance GABA-ergic Neurotransmission in Hepatic Failure; E.A. Jones, A.S. Basile. Direct Enhancement of GABA-ergic Neurotransmission by Ammonia; J.-H. Ha, et al. The Peripheral Benzodiazepine Receptor and Neurosteroids in Hepatic Encephalopathy; M.D. Norenberg, et al. Ornithine Aminotransferase as a Therapeutic Target in Hyperammonemias; N. Seiler. Sparse-Fur (spf) Mouse as a Model of Hyperammonemia: Alterations in the Neurotransmitter Systems; I.A. Qureshi, K.V.R. Rao. Abnormal Gene Expression Causing Hyperammonemia in Carnitine-Deficient Juvenile Visceral Steatosis (JVS) Mice; T. Saheki, et al. 7 Additional Articles. Index.

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.