This volume places more emphasis on endogenous mediators of gut motility than on drugs used to treat patients with deranged motility. In this respect it resembles most other books on gastroenterology, for while only a relatively small number of drugs are really useful for a rational therapy, a tremendous amount of data is available on neural and hormonal factors regulating the motility of the alimentary canal. Moreover, it must be considered that some of the drugs which can routinely be employed to modify deranged motility of the digestive system are represented by pure or slightly modified endogenous compounds (e. g. , cholecystokinin, its C terminal octapeptide and caerulein), and it is easy to foresee that their number is destined to increase in the near future. Other drugs are simply antagonists of physiological substances acting on specific receptors (e. g. , histamine H -blockers 2 and opioid compounds). The real explosion of research in this field and the extreme specialization often connected with the use of very sophisticated techniques and methodologies would probably have required a larger number of experts to cover some very specific fields from both an anatomical (lower esophageal sphincter, stomach, pylorus, small and large intestine) and a biochemical (hormones, candidate hormones, locally active substances, neurotransmitters etc. ) point of view.

Three distinct types of contractions perform colonic motility functions. Rhythmic phasic contractions (RPCs) cause slow net distal propulsion with extensive mixing/turning over. Infrequently occurring giant migrating contractions (GMCs) produce mass movements. Tonic contractions aid RPCs in their motor function. The spatiotemporal patterns of these contractions differ markedly. The amplitude and distance of propagation of a GMC are several-fold larger than those of an RPC. The enteric neurons and smooth muscle cells are the core regulators of all three types of contractions. The regulation of contractions by these mechanisms is modifiable by extrinsic factors: CNS, autonomic neurons, hormones, inflammatory mediators, and stress mediators. Only the GMCs produce descending inhibition, which accommodates the large bolus being propelled without increasing muscle tone. The strong compression of the colon wall generates afferent signals that are below nociceptive threshold in healthy subjects. However, these signals become nociceptive; if the amplitudes of GMCs increase, afferent nerves become hypersensitive, or descending inhibition is impaired. The GMCs also provide the force for rapid propulsion of feces and descending inhibition to relax the internal anal sphincter during defecation. The dysregulation of GMCs is a major factor in colonic motility disorders: irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and diverticular disease (DD). Frequent mass movements by GMCs cause diarrhea in diarrhea predominant IBS, IBD, and DD, while a decrease in the frequency of GMCs causes constipation. The GMCs generate the afferent signals for intermittent short-lived episodes of abdominal cramping in these disorders. Epigenetic dysregulation due to adverse events in early life is one of the major factors in generating the symptoms of IBS in adulthood.

Since the exhaustive Handbook of Physiology (Alimentary Canal, Section 6, Motility) edited by CHARLES F. CODE in 1968, no complete survey of the morphological basis and the physiological control of intestinal motility has been published, in spite of the enormous amount of new data in the literature on this topic. The new techniques and methodologies, the use of electron microscopy, radioimmunoassay and binding techniques, as weIl as ever more sophisticated electrophysiological procedures have made possible areal flood of discoveries in this field. Moreover, the possibility ofnew studies ofthe endocrine cells in biopsies of human intestinal mucosa even during routine endoscopies, has opened new horizons for gastroenterologists and generated a number of important contribu tions to our knowledge of the morphology and physiopathology of the gut. As usual, new discoveries have also revealed both ignorance and many new problems. For tbis reason, although many of the data reported in this volume can be considered as firmly established, others still require confirmation, and the results of new research in this field are awaited with extreme interest. Since advances are occurring so rapidly, even experts in the specific topics need frequent comprehensive reviews. To avoid an excessively large volume, considera tions ofthe pancreas, liver, and biliary system were not included in this Handbook, which, nevertheless, has attempted to off er the reader the essence of more than 1,500 papers.

First published in 1943, Vitamins and Hormones is the longest-running serial published by Academic Press. The Editorial Board now reflects expertise in the field of hormone action, vitamin action, X-ray crystal structure, physiology, and enzyme mechanisms. Under the capable and qualified editorial leadership of Dr. Gerald Litwack, Vitamins and Hormones continues to publish cutting-edge reviews of interest to endocrinologists, biochemists, nutritionists, pharmacologists, cell biologists, and molecular biologists. Others interested in the structure and function of biologically active molecules like hormones and vitamins will, as always, turn to this series for comprehensive reviews by leading contributors to this and related disciplines. This volume focuses on insulin and IGFs. - Longest running series published by Academic Press - Contributions by leading international authorities

Oral Drug Absorption, Second Edition thoroughly examines the special equipment and methods used to test whether drugs are released adequately when administered orally. The contributors discuss methods for accurately establishing and validating in vitro/in vivo correlations for both MR and IR formulations, as well as alternative approaches for MR an