The study of tumour resistance to anticancer drugs has been the subject of many publications since the initial discovery of the phenomenon by J. H. Burchenal and colleagues in 1950. Many papers have been published since then reporting development of resistance to most of the well-known anticancer agents in many different animal tumour systems, both in vivo and in vitro. Many different mechanisms of resistance have been described, and it is clear that the tumour cell has a wide diversity of options in overcoming the cell-killing activity of these agents. Definition of the magnitude of the...

The intestine, particularly the small bowel, represents a large surface (in the adult 2 human approximately 200m ) through which the body is exposed to its environment. A vigorous substrate exchange takes place across this large surface: nutrients and xenobiotics are absorbed from the lumen into the bloodstream or the lymph, and simultaneously, the same types of substrate pass back into the lumen. The luminal surface of the intestine is lined with a "leaky" epithelium, thus the passage of the substrates, in either direction, proceeds via both transcellular and intercellular routes. Simple and...

The intestine, particularly the small bowel, represents a large surface (in the adult 2 human approximately 200 m ) through which the body is exposed to its environ- ment. A vigorous substrate exchange takes place across this large surface: nutrients and xenobiotics are absorbed from the lumen into the bloodstream or the lymph, and simultaneously, the same types of substrate pass back into the lumen. The luminal surface of the intestine is lined with a "leaky" epithelium, thus the passage of the substrates, in either direction, proceeds via both transcellular and intercellular routes. Simple...

Contrast media are drugs by default. Had there been no default, there would be no need for a related pharmacology, and thus no need for this book. Radiographic contrast media (CM) are substances whose primary purpose is to enhance diagnostic information of medical imaging systems. The position of CM in pharmacology is unique. First, there is the unusual requirement of biological inertness. An ideal CM should be completely biologically inert, i.e., stable, not pharmacologically active, and efficiently and innocuously excretable. Because they fail to meet these requirements, CM must be...

This book deals with the methods and scientific basis of inhalation toxicology. It describes devices and facilities needed to expose animals to inhaled particles and gases as well as approaches to estimating or measuring the fraction of the inhaled material that is retained in the respiratory tract. The book then reviews the evergrowing repertoire of techniques that can be used to measure the responses elicited by the exposure. Quantitative and qualitative anatomical, physiological, and biochemical strategies are discussed in detail. We believe that the toxicology of inhaled materials is an...

Parasitic diseases are the most widespread of all the major diseases, currently 9 affecting about 3 x 10 people and innumerable domestic animals. There is no doubt that among these parasitic diseases, the helminthic infections of the gastrointestinal tract are about the most important because of their global distribution, their high prevalence, their effects on the nutritional status of men and animals, their effects on the physical and mental development of children, and their economic effects on the production of animals. Anthelmintics are important elements in the control of these...

The history of antibiotics may weIl have begun with the ancient Sudanese-Nubian civilization (see Chapter 1, "Historical Introduction"), but this volume reflects a more contemporary appraisal of the antibiotic era. We have compiled a comprehensive review of the tetracyclines which includes all the major sub- divisions of these chemically important and clinically useful antibiotics. There can be little doubt about the contribution of antibiotics to both the increase in human life span and the alleviation of much human suffering. The tetracyclines are still playing an important role in these...

The problems associated with the pharmacologic and physiologic regulation of neuromuscular transmission and of the morphofunctional organization of neuromuscular junctions have attracted a wide range of investigators. Numerous handbooks, monographs, and reviews are devoted to this subject. At the same time, many fundamental and applied aspects of this trend continue to progress succesfully. In recent years, new experimental and clinical data on the structure and function of neuromuscular junctions have been gained, and new, more perfect neuromuscular blocking agents have been designed. It is...

The toxic properties of cadmium compounds have been well recognized in many species. There is little evidence to suggest a physiologic role for the metal. Rather, because of its long biologic half-life, cadmium acts as a cumulative poison, and even at quite low ambient concentrations, it can accumulate in mammals to values not insignificant in terms of critical toxic levels. The problem of cadmium toxicity has become especially important, as cadmium concentrations in the environment have begun to rise owing to a variety of human activities such as mining, the metallurgical industry, coal...

Fungal diseases have been with us from antiquity; interest in the chemo- therapy of fungal disease has exploded in the past decade. To plan and pro- duce a book on the topic of antifungal chemotherapy has come as a personal challenge - and something of an eye-opener - towards the end of my re- search career. A landmark publication which still merits reading is Antifungal Chemotherapy (John Wiley & Sons, Chichester, UK), edited by David Speller, which appeared in 1980. However, the fact that ketoconazole, the first of the modern, orally active, wide-spectrum antifungals, attracted no more than...