Few pathologie phenomena, as shock, can originate from so many causes and involve so many complex physiologie mechanisms: The complexity of the phenomenon, thus, has resulted in extensive study and raised many uncertainties. Different conditions, such as hemorrhage, trauma, burns, bacterial infection, and anaphylaxis, can cause a shock state which initiates a chain of biochemical events that tends to maintain the shock. Recent progress in bio chemistry, physiology, and pharmacology has tended to clarify this chain of events, and elucidate the possible trigger mechanism. Besides the hormonal and catecholamine involvement, the possible intervention of various protease and lysosomal enzyme septems and kinin release introduces new elements into the characteristic mosaic of the shock state. This International Symposium, organized at Lake Corno by the Italian Society of Clinical Pharmacology and the International Society of Biochemical Pharmacology, is another in aseries of symposia under the joint auspices of the School of Pharmacy, State University of New York at Buffalo, and the Institute of Pharma cology, University of Milan, Italy. The Symposium has gathered together eminent scientists from such varied disciplines as surgery and pharmacology, internal medicine and biochemistry, physiology and pathology, all focusing on the question of shock. The many researchers in these specialities had the possibility of meeting and discussing together in a multidisciplinary fashion the many theories and experiences associated with this problem.

A decade ago, for most scientists investigating various issues in life sciences the word "NO" was used in a negative context. It is astounding to observe how recently researchers are addressing the issue of NO, namely, nitric oxide, in over fifty publications weekly. Science journal, while naming nitric oxide: "Molecule of the Year" (December 1992), said it all: "NO news is good news. " For a long period of time NO was considered as a pollutant and every ecology minded person tried to eliminate it. It was the discovery of NO involvement in the process of host killing by macrophages and several years later the finding that EDRF is none else but NO, that promoted this field. Nitric oxide's major role in the control of blood pressure is merely one factor of an extensive list of effects and functions attributed to it. NO is implicated in long-term potentiation (LPT), a principal process involved in memory consolidation and it is considered as the main biochemical substance responsible for penile erection. It should be noted that additional roles for NO are discovered continuously as many laboratories join the quest for the mystery of this small molecule. The observation that NO is involved in various biological processes is not unique, as other second messengers (i. e. , cyclic AMP), participate in a diverse set of functions.

Research, to which so much discussion and thought will be devoted at this symposium, appears to have been downgraded in our society. Yet, learning and education per se rank high in our set of values, from the point of view of both lay people and profes sional workers. For some reason, we fail to detect the illogic inherent in this value system--for, what is research but the learning of new information? Apparently our society associates "learning" only with known, long-gathered information. This symposium, I believe, will generate new information about shock through the integration of knowledge of many investi gators, who have come to share a common meeting ground. Hopefully, the worth of this and similar endeavors will gain the recognition and, more important, the support of the public. In the next decade or so, I believe that shock research workers will be channeling their efforts more and more into investigating the repair of damaged cells. The individual cell and its products must be scrutinized just as carefully as we examine the whole organism or its collections of cells. Shock is an exciting area of research, but it involves years of painstaking work. Moreover, the society which will reap its fruits must be persuaded to share the burden of its support. John A. Sehilling~ M.D. lAbstracted from Dr. John A. Schilling's Opening Statement at the symposium on October I, 1971.

This text contains the scientific contributions to the Fourth International Symposium on Sphingolipids, Sphingo lipidoses and Allied Disorders held at the Kingsbrook Jewish Medical Center on October 25-27, 1971. These meetings were conducted under the auspices of the Isaac Albert Research Institute of the Kingsbrook Jewish Medical Center and the National Tay-Sachs and Allied Diseases Association, Inc. Four symposia, held in 1958, 1961, 1965 and 1971 were designed to gather the most relevant and innovative of the laboratory and field studies concerned with these hereditary disorders. The texts generated by these periodic meetings have mirrored the increasing absorption of the scientific community in the problems of sphingolipid metabolism. The first meeting in 1958 consisted of but twelve pre sentations, the majority emanating from local laboratories. The current sessions contain 48 scientific presentations by scientists from nine countries and demonstrate the increas ingly diversified techniques and approaches employed in the study of these diseases. Many of the authors, in exploring data on the mucopolysaccharidoses and leucodystrophies, as well as the sphingolipidoses, have given recognition to those biochemical areas held in common by these otherwise diverse disease processes. The problems of prevention and therapy of these diseases have been considered by some of the contributors. Laboratory screening procedures designed to detect carriers of the va rious lipidoses are now available and the experiences of some laboratories in this area are summarized within this volume. The prospective identification of heterozygotes may indeed become a powerful adjunct in genetic counseling.

Howard G. Knuttgen of Biology, Boston University, 2 Cummington Department Street, Boston, 02215 Massachusetts, USA The relationship of the formation of lactate acid to skeletal muscle energy release in exercising humans was first explored by A. V. Hill and co-workers (2l, 22). The term "oxygen debt" was suggested by them to describe the excess oxygen consumption of recovery which they felt was closely related. A combination of their work and the earlier work of Krogh and Lindhard (35) re sulted at that time in the belief that a certain amount of energy release during the transition from rest to exercise was provided by a non-aerobic source, glycolysis. The resulting accumulation of lactic acid (as lactate) in the body required an extra con sumption during recovery for its oxidative removal. Jervell (24) subsequently showed that, in exercise, the greatest accumulation in blood took place during the first few minutes. He felt that the blood lactate increase was due to a shortage of oxygen during the transition period. The observation was also made for the first time that the increased level of lac tate due to exercise could be made to fall faster if mild exercise was employed by the subjects in place of sedentary recovery. The work of Margaria, Edwards and Dill (40) appeared in 1933. They observed that exercise (treadmill running) could be carried on at low levels without significant changes in resting levels of blood lactate.

The OHOLO Conferences have been convened annually from the Spring of 1956; the wide areas they have covered, from different and overlapping disciplines, can be seen from the following list: 1956 Bacterial Genetics (not published) 1957 Tissue Cultures in Virological Research (not published) 1958 Inborn and Acquired Resistance to Infection in Animals (not published) 1959 Experimental Approach to Mental Diseases (not published) 1960 Cryptobiotic Stages in Biological Systems* 1961 Virus-Cell Relationships** 1962 Biological Synthesis and Function of Nucleic Acids** 1963 Cellular Control Mechanism of Macromolecular Synthesis** 1964 Molecular Aspects of Immunology** 1965 Cell Surfaces** 1966 Chemistry and Biology of Psychotropic Agents (not published) 1967 Structure and Mode of Action of Enzymes** 1968 Growth and Differentiation of Cells In Vitro** 1969 Behaviour of Animal Cells in Culture** 1970 Microbial Toxins** 1971 Interaction of Chemical Agents with Cholinergic Mechanisms** 1972 Immunity in Viral and Rickettsial Diseases*** The participants who attend these Conferences are drawn from dif ferent scientific institutions in Israel and from many foreign countries; they are engaged in fields of study which represent widely divergent approaches to biology. Thus a distinguishing feature of the OHOLO meetings has been their multi-disciplinary nature. Published by Elsevier Publishing Co. , Amsterdam (1960). * ** Published by the Israel Institute for Biological Research, Ness Ziona. *** Published by Plenum Press, New York (1972). ix PREFACE x These small international conferences are also characterized by their relaxed atmosphere, with ample time for informal as well as formal discussions.