BARTON und COHEN haben r9S7 in einer Arbeit "Some Biogenetic Aspects of Phenol Oxidation" (3) Dienone der allgemeinen Formel (I) als biogenetische Vorstufen bestimmter Aporphin-Alkaloide postuliert (S. 260). Strukturen dieses Typs wurden erstmals r963 fUr die Alkaloide D-( +)-Pronuciferin und D-( +)-Crotonosin bewiesen [BERNAUER (II); HAYNES, STUART, BARTON und KIRBY (35)]. Der fur solche Verbin- dungen vorgeschlagene Sammelname "Proaporphine" (23, 65) bringt den in zwischen experimentell bewiesenen* biogenetischen Zusammenhang mit der Gruppe der Aporphin-Alkaloide zum Ausdruck, ist aber auch vom praparativ-chemischen Standpunkt sinnvoll, da sich Proaporphine (I) leicht in Aporphine (2) umwandeln lassen (S. 2S0). AuBer den Alkaloiden mit Dienongruppierung sind auch solche be- kannt geworden, in welchen eine oder mehrere Doppelbindungen des Dienonsystems aushydriert sind; sie werden sinnvollerweise den Pro- aporphinen zugerechnet. Dieser Aufsatz berucksichtigt alle natiirlichen Alkaloide und ihre wichtigsten Derivate sowie alle synthetischen Ver- bindungen, die das Skelett (3) besitzen (Tabellen I-3, SS. 270-279). Er macht ausschlieBlich von der in (3) angegebenen Bezifferung Gebrauch, welche der Nomenklatur der IUPAC und der Chemical Abstracts ent- spricht. Verbindung (I, R = H) ist wie folgt zu bezeichnen: 2',3',8',8'a-Tetra- hydro-S',6'-dihydroxy-spiro[2,S-cyclohexadien-r,7'(r'H)-cyclopent[ij]-iso- chinolin ]-4-on. R2 (2) K=H oder Alkyl (I) R=H oder Alkyl Rt=H,OH oder O-Alkyl Proaporphine Aporphine In den Originalarbeiten sind verschiedene, von der in (3) angegebenen ab- weichende Bezifferungsarten verwendet worden. Keine hat sich allgemein durch- gesetzt. Auch die von SLAViK (69) fur das sauerstofffreie Grundgerust der Pro- aporphine vorgeschlagene Bezeichnung Mecambran hat keinen Eingang in die Literatur gefunden.

Before the late 1970s, interest in caffeine among both the general public and the scientific community was at a relatively low level for many years, even though it was recognized that caffeine was an al most universal component of the diet. The National Coffee Associa tion was supporting a continuing program of research, some re search was being conducted by a few of the largest companies selling coffee, and an occasional university researcher became inter ested in caffeine and conducted experiments, often on effects of caf feine in very high concentration in vitro on skeletal muscle fibres or on dividing cells. Since 1978, however, there has been a mighty up surge in both public and scientific interest in caffeine. It is interest ing to note that this was prompted not by discovery of hitherto un known effects or hazards of caffeine, but by the actions of a regulatory agency, the Food & Drug Administration (FDA) of the U. S. Public Health Service. The U. S. Congress passed new laws on foods and drugs in 1958. One of the provisions was for testing of food additives to assess risk to health. As it was clearly impracticable to require immediate test ing of all additives already in use, a list was drawn up of some hun dreds of additives that were generally recognized as safe (GRAS)."

The recent interest in the pharmacology of the skin and the treatment of its diseases has come about for two reasons. The first is a realisation that many aspects of pharmacology can be studied as easily in human skin, where they may be more relevant to human physiology and diseases, as in animal models. Examples of this are the action of various vasoactive agents and the isolation of mediators of inflammation after UV irradiation and antigen-induced dermatitis. The second reason is the fortuitous realisation that a pharmacological approach to the treatment of skin disease need not always await the full elucidation of etiology and mechanism. For example, whilst the argument continued unresolved as to whether the pilo-sebaceous infection which constitutes acne was due to a blocked duct or to a simple increase in sebum production, 13-cis-retinoic acid was found quite by chance totally to ablate the disease; again, whilst cyclosporin, fresh from its triumphs in organ transplantation, has been found able to suppress the rash of psoriasis, it has resuscitated the debate on etiology. We are therefore entering a new era in which the pharmacology and clinical pharmacology of skin are being studied as a fascinating new way of exploring questions of human physiology and pharmacology as well as an important step in the development and study of new drugs, use of which will improve disease control and at the same time help to define pathological mechanisms.

Cyclic nucleotides are intimately involved in the consequences of either stimulation or blockade of receptors; therefore, an understanding of the biochemistry of cyclic nucleotides ought to be important for pharmacologists. Pharmacology is a science that among other things investigates chemical compounds that affect the physiology of cells, tissues and organs. Frequently pharmacologists account for the effect of low concentrations of a drug upon a tissue by invoking the presence of a receptor upon the surface of the cell. Traditional pharmacologists excelled at identifying and classifying the properties of receptors. A. J. CLARK'S monograph in the earlier series of the Handbook of Experimental Pharmacology (CLARK 1937) summarized the mathematics underlying the traditional pharmacological approach towards receptors. By its nature, however, classic pharmacology provided little useful information about the intracellular events occurring as a consequence of occupying a receptor; for example, ALQUIST (1948) identified the beta-adrenocep tor, but he did not provide any insight into how stimulation of the receptor produces tissue-specific physiological responses. The discovery of cyclic AMP by RALL and SUTHERLAND (see RALL, Vol. I) led to biochemical investigations of many different receptors (including ALQUIST'S beta-adrenoceptor) that share a cyclic nucleotide as a common factor in the biochemical mechanisms that translate the occupancy of receptors into physiological effects. Ten years ago, in the introduction to their monograph on cyclic nucleotides, ROBISON et al. (1971) commented on the rapid growth of interest in cyclic nucleotides over the preceding years."

Starting in 1986, the European School of Oncology has expanded its activities in post graduate teaching, which consisted mainly of traditional disease-orientated courses, by promoting new educational initiatives. One of these is the cloister seminars, short meet ings intended for highly qualified oncologists and dealing with specific, controversial aspects of clinical practice and research. Another is the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on developments and treatment in specific fields of oncology. This series of ESO Monographs was designed with the specific purpose of disseminat ing the results of the most interesting of the seminars and study groups, and providing concise and updated reviews of the subjects discussed. It was decided to keep the layout very simple in order to keep costs to a minimum and make the monographs available in the shortest possible time, thus overcoming a com mon problem in medical literature: that of the material being outdated even before publication. Umberto Veronesi Chairman, Scientific Committee European School of Oncology Position Paper on the Application of Human Tumour Xenografts as a Model for Preclinical Phase" Studies in the Evaluation of New Anticancer Compounds Outcome of a seminar on Human Tumour Xenografts organised by the European School of Oncology, Milan, 26th-27th May, 1986.

The author's general aim has been to survey as wide a field of evidence as possible and this had involved excursions into subjects of which he has little first hand knowledge. This width of range also has necessitated a somewhat arbitrary selection of evidence and has prevented full discussion of any indi- vidual problem. The author trusts that he has not misrepresented anyone's results or opinions, and if this has occurred, he can only plead in excuse the peculiar difficulty of giving a brief and yet accurate account of evidence of such a wide variety. The diagrams reproduced in the article have all been redrawn and in many cases the original figures or diagrams have been modified as, for instance, by recalculating dosage on the logarithmic scale. The original authors therefore have no direct responsibility for the diagrams in their present form. The author desires to thank Messrs Arnold and Co. for permitting the repro- duction of Figs. 9 and 23 from similar figures which appeared in his book "The Mode of Action of Drugs on Cells"; portions of other figures from this book also have been reproduced in modified form. The author also desires to thank Dr. J. M. ROBSON for help in correction of the proofs. Edinburgh, July, 1937. A. J. CLARK. Contents.

The volumes of this classic series have appeared under the Springer imprint ever since L. Zechmeister founded the series in 1938. The volumes contain contributions on various topics related to the origin, distribution, chemistry, synthesis, biochemistry, function or use of various classes of naturally occurring substances ranging from small molecules to biopolymers. Each contribution is written by a recognized authority in his field and provides a comprehensive and up-to-date review of the topic in question. Addressed to biologists, technologists and chemists alike, the series can be used by the expert as a source of information and literature citations and by the non-expert as a means of orientation in a rapidly developing discipline.

The International Life Sciences Institute (ILSI), a nonprofit, public foundation, was established in 1978 to advance the sciences of nutrition, toxicology, and food safety. ILSI promotes the resolution of health and safety issues in these areas by sponsoring research, conferences, publications, and educational programs. Through ILSI's programs, scientists from government, academia, and industry unite their efforts to resolve issues of critical importance to the public. As part of its commitment to understanding and resolving health and safety issues, ILSI is pleased to sponsor this series of monographs that consolidates new scientific knowledge, defines research needs, and provides a background for the effective application of scientific advances in toxicology and food safety. Alex Malaspina President International Life Sciences Institute Contents Series Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . xiii . . . . . . . . . . . . . Part I. Integrative Approach to Assessing Human Health Risk: Two Contemporary Problems Chapter 1. Integrating Diverse Data Sets to Assess the Risks of Airborne Pollutants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 R.o. McClellan, R.G. Cuddihy, w.e. Griffith, and J. L. Mauderly Chapter 2. Risk Assessment for Radon Inhalation Based on Animal Exposure Data and Human Epidemiology . . . . . . . 23 . F. Steinhausler Part II. Types of Evidence: General Strengths and Weaknesses Section 1. Epidemiological Chapter 3. Inhalation Hazards: The Interpretation of Epidemiologic Evidence. . . . . . . . . . . . . . . . . . . . 39 . . . . . . . J.e. Bailar Chapter 4. Problems in Interpreting Epidemiological Data 49 P.N. Lee Section 2. Animal Chapter 5. Rodent Carcinogenicity Studies: Their Value and Limitations. . . . . . . . . . . . . . . . . . . . . . . . . . 61 . . . . . . . . . .

To comment at length on the importance of the benzodiazepines seems superfluous within the scope of this preface. No other class of active substances has experienced an even approximately compa rable advance in the past two decades. It is therefore not surprising that the formerly dominant barbiturates and bromocarbamides have had to give way in many fields to the benzodiazepines, which now rank first (Proudfoot and Park 1828]). Closely linked with the great therapeutic importance of the benzodia zepines are analytical problems. Detection and the determination of blood levels can be necessary under therapeutic aspects, for instance in working out optimally effective levels in the treatment of epileptic conditions ("drug monitoring"), but also in connection with questions at issue in toxicology and traffic medicine. A toxicological analysis can be subdivided into the following steps: Detection (identification including screening) Determination (e. g. blood, plasma or serum levels) Interpretation of the analytical results. This book is intended as a contribution to each of these chapters: The part "Analytical Data" (pp.I-122) gives a comprehensive collec tion of data, e.g. general and chromatographic data (TLC, GLC) as well as spectra (UV, IR, MS) of 19 commercial preparations, 23 important metabolites and 18 hydrolysis derivatives. Information about biotransformation and the possible formation of aminobenzo phenone derivatives is also given. The most important analytical methods are presented in an extensive review on pp.123-204 in order to make it possible to select the optimum method on the basis of the essential data."

Plants are a major source of medicines, flavors, fragrances, and various pharmaceutical and industrial products. Biotechnology is being put to the service for mass clonal propagation of plants, and to produce impor- tant secondary products in cell cultures. In some cases cell cultures ac- cumulate higher amounts of products than the intact plant cells in situ, and such cultures can be stored through immobilization and cryopreser- vation. An in vitro-produced anti-inflammatory drug, shikonin, has been commercialized, and the recent observations on the increased pro- duction of atropine and hyoscyamine by Agrobacterium rhizogenes- mediated transformed "hairy roots" have encouraged the acceptance of such biotechnologies by the pharmaceutical industry. In an earlier volume, Medicinal and Aromatic Plants I, various aspects of in-vitro culture of cells, bioreactors, micropropagation, im- mobilization, and cryopreservation were discussed. The present volume concerns the application of these biotechnologies to 29 genera of medicinal and aromatic plants. It deals with the distribution, economic importance, conventional propagation, micro propagation, review of tissue culture studies, and the in-vitro production of important medicinal and pharmaceutical compounds in various species of Angelica, Anisodus, Basel/a, Bupleurum, Camellia, Co ix, Coptis, Cryp- tomeria, Datura, Dioscorea, Foeniculum, Gardenia, Geigeria, Heimia, Humulus, Hyoscyamus, Jasminum, Macleaya, Mucuna, Nicotiana, Pimpinel/a, Rauwolfia, Ruta, Salvia, So/anum, Saponaria, Stevia, Tabernaemontana, and Zingiber. The potential role of biotechnology for industrial production is discussed. Biotechnology enables the production and isolation of products of higher purity and also opens the possibility of making desired molecular alterations in products.

The previous volume on Antihypertensive Agents in the Handbook of Experi mental Pharmacology, published in 1977, was edited by the late Franz Gross from the Department of Pharmacology in Heidelberg, who was one of the grand old men in hypertension research. Now, more than 10 years later, it is necessary to update this volume. From the early days of antihypertensive drug treatment, starting about 30 years ago with drugs such as reserpine and guanethidine, the pharmacology of cardiovas" cular therapy has evolved into a highly sophisticated and effective therapeutic regimen. The major breakthroughs in the 1960s were the introduction of diuretics and beta-blockers. Then, in the 1980s, came the calcium antagonists and con verting enzyme inhibitors. It can be anticipated that the next decade will see a further expansion and sophistication of blood pressure lowering drugs. This book provides a state-of-the-art discussion of chemical, experimental, and clinical pharmacological data as well as of practical experience with drugs which are presently being used or which are going to be introduced on the market in the near future. The purpose of this volume is to provide a complete discussion of antihypertensive agents. Each major class of antihypertensive drugs is treated exhaustively in a separate chapter, fully referenced with chemical formulae, and richly illustrated with figures and tables. International authorities were asked to contribute in their respective fields of expertise."

According to most studies, allergic reactions represent 35%-50% of all untoward reactions to drugs, yet the pharmacological literature concerning the clinical aspects, diagnosis, and pathophysiological mechanisms of drug allergy is markedly less extensive than reports dealing with the toxicological or pharmacological effects of drugs. The main reasons for this state of affairs may be on the one hand that until a few years ago the pathophysiological mechanisms of the various types of allergic reactions were not well understood, and on the other hand that objective diagnosis of a drug allergy is still fraught with serious difficulties. Drug allergy is still an unpopular topic for most allergologists and pharmacologists; this is reflected by the fact that despite their frequency, allergic reactions to drugs still occupy a relatively small proportion of space in most pharmacology handbooks and in classical books devoted to the side effects of drugs. There has recently been considerable progress in research into the immunologi cal and pathophysiological events occurring in allergic reactions, and on that basis investigations of various drug allergies have also yield d new objective findings. Consequently, it was natural to attempt a review of the most frequent and important drug allergies in the form of a handbook. We originally intended to present a comprehensive review of all drug allergies, but the realization of this goal soon became more difficult than we had at first imagined."

A wide variety of hormones, neurotransmitters and growth factors exert their cellular effects by reacting first with membrane receptors resulting in an increase of intracellular calcium and the cellular response. The calcium signal in the cell is mediated by the high-affinity calcium binding proteins (characterized by the EF-hand structural element), and by the calcium and phospholipid dependent proteins. Many of these have been discovered most recently. Their purification, distribution, protein and gene structures as well as their physiological roles are discussed. The book is of interest to biochemists and molecular biologists as well as to clinicians and the pharmaceutical industry who can apply the results in this field.

This volume collects the invited lectures and some selected contributions presented at the 5th International Meeting on Clinical Pharmacology in Psychiatry, which was held 26-30 June 1988 at the University of Troms0, Norway. The 24 h of daylight at the northernmost university in the world al lowed for long, pleasant and productive sessions. The title of the conference as well as a number of the topics covered represent a continuation of four previous conferences, the first held in Chicago in 1979 and organized by the late Earl U sdin and colleagues. The earlier conferences have been documented in Clinical Pharmacology in Psychiatry, edited by E. Usdin (Elsevier, New York, 1981), Clinical Pharmacology in Psychiatry. Neuroleptic and Antidepressant Research, edited by E. Usdin, S. G. Dahl, L. F. Gram and o. Lingjrerde (Macmillan Publishers Ltd., London, 1981), Clinical Pharmacology in Psychiatry. Bridging the Experimental-Therapeutic Gap, edited by LF. Gram, E. Usdin, S.G. Dahl, P. Kragh-Sorensen, P. L. Morselli and F. Sjoqvist (Macmillan Publishers Ltd., London, 1983), and Clinical Pharmacology in Psychiatry. Selectivity in Psychotropic Drug Action - Promises or Problems? edited by S. G. Dahl, L.F. Gram, S.M. Paul and W.Z. Potter (Psychopharmacology Series 3, Springer, Heidelberg, 1987)."

The recent symposium and the appearance of this new book on Drugs Affecting Lipid Metabolism take place at a very unusual time for the development of this area. After the publication and wide acceptance of the results of the cholestyramine study by the Lipid Clinics in the USA, showing for the first time a direct association between drug induced reduction of plasma levels of total and LDL cholesterol and coronary heart disease in a high risk population, an unparalleled interest in drugs and other procedures able to control plasma cholesterol levels has been activated. Two other significant events occurred during 1986 and 1987: the availability of compact instruments for the immediate determination of total cholesterol in plasma or total blood and the developments of new agents such as the inhibitors of HMG-CoA (hydroxymethyl glutaryl CoA) reductase and ACAT inhibitors, with potentially great effect on plasma lipid levels after oral administration. These new advances, together with the combined efforts of cell biologists and lipoprotein chemists, have set the pace for an exciting period of research and clinical applications of diets and drugs af fecting lipids. This volume, which includes the work of many of the leading world laboratories, represents an authoritative and up-to-date ap praisal of the status of the art and a stimulus to future research at laboratory and clinical level in an area of opportunity for clinical and preventive medicine."

Two aspects of the biotechnology of medicinal and aromatic plants are of immediate application. (1) Micropropagation under controlled germ- free conditions which enables their fast multiplication and availability throughout the year irrespective of external environment - this is specially useful for elite and rare plants. (2) A large-scale culture and low-temperature storage of cells enables retention of their biosynthetic potential for the production of important secondary metabolites, med- icines, flavours and other pharmaceutical products. This book has been compiled with a view to bringing together information and literature on the biotechnology and the present state of the art of plant cell cultures for their potential use in the pharmaceutical industry. This volume comprises 29 chapters on the biotechnology of med- icinal and aromatic plants grouped into three sections, (1) microprop- agation, immobilization, cryopreservation, bioreactors, production of secondary metabolites and their impact in pharmacy, (2) production through cell cultures of antitumour compounds, lrDopa, shikonin, an- thraquinone, morphinan alkaloids, caffeine, berberine, valeoptriates, rosmarinic acid, quinine, tropanes, hypoxoside, ellipticine, paeoniflorin, saponins, cardenolides etc, and (3) distribution, economic importance, conventional propagation, review of the tissue culture work on micropropagation and the in vitro production of compounds of medicinal and pharmaceutical interest in various species of Cannabis, Centaurium, Cinchona, Digitalis, Duboisia, Hypoxia, Lithospermum, Ochrosia, Paeonia, Panax, Papavar, Rehmannia, Rhamnus and Rhaza.

Die Befruchtung spielt eine bedeutende Rolle im Entwicklungsgang der Organismen. In ihrem Verlauf werden die Gametenkerne, und damit das genetische Material zweier Individuen, vereinigt. Durch die Meiose (Reduktionsteilung) wird der Ausgangszustand wiederhergestellt, jedoch in einer solchen Weise, daB die elterlichen Erbfaktoren in den verschiedensten Kombinationen neu verteilt werden konnen. Die Beob- achtung von Befruchtungsvorgangen zeigt, daB der eigentlichen Ver- schmelzung der Geschlechtszellen Reaktionen vorausgehen, an denen offensichtlich chemische Wechselwirkungen beteiligt sind. Besonders deutlich lassen sich solche stoffiichen Wechselwirkungen bei niederen Pflanzen beobachten, bei denen beispielsweise Geschlechtsorgane nur gebildet werden, wenn der entsprechende Partner oder Filtrate seines Kulturmediums vorhanden sind. In anderen Fallen kann man beobachten, daB Geschlechtsorgane durch Luft oder Wasser gerichtet aufeinander zu- wachsen oder, daB freibewegliche mannliche Gameten sich gezielt zu stationaren weiblichen Gameten hinbewegen. Solche biologischen Reak- tionen sind auBerordentlich empfindlich, und die Konzentration der beteiligten Stoffe ist entsprechend gering. Dies macht die Ansammlung von gentigenden Mengen fUr die StrukturaufkIarung zu einem auBerst mtih- samen Unternehmen. Obwohl auch in der alteren Literatur zahlreiche Hinweise auf chemische Wechselwirkungen zwischen Sexualpartnern vor- handen sind (42, 43), konnten bisher erst wenige derartige Geschlechts- stoffe identifiziert werden. Erst die hochleistungsnihigen modernen Ana- lysenmethoden, wie Massen- und Kernresonanz-Spektroskopie, haben hierbei die Forschung wesentlich vorangetrieben. Man kennt heute die Molekularstruktur von vier Sexualhormonen, die nunmehr auch synthe- tisch zuganglich sind.

The description of the pharmacology of psychotomimetics, cannabis, and alcohol in this third volume concludes the discussion on psychotropic agents. As psychomotor stimulants these groups of psychotropic agents are of little or no therapeutic relevance, but since they are used in a nonmedical manner, or are even considered by some groups of the population as social commodities, their behavioral effects and psychopharmacological properties are not the concern of the pharmacol ogist alone. The same is true of psychotomimetics, as well as cannabis and its components. Psychotomimetics have a social history going back many hundreds of years and are among the most potent psychotropic agents known to man. The closing description of psychopharmacology also deals with the psychotropic effects of a number of drugs not primarily considered to be psychotropic. Their psychotropic effects are either an inherent constituent of their therapeutic profile, as is the case with opiates, hypnotics, and caffeine, or they may occur indirectly as side effects or accompanying effects during therapy. This applies to p-adrenoreceptor antagonists and anticholinergics. The editors are also aware that a description of psychotropic agents would not have been complete without discussing the medical, ethical, and legal aspects of the development, clinical testing, and use of such drugs."

Responding to the dramatic scientific and technological developments in the agro-food sector and to the enormous public concern about novel food production and novel food ingredients this volume focusses on defining, classifying and reassessing the quality of food towards human nutritional needs aimed at health. It is designed for all those actively involved in the food sector and for interested lay persons and responsible consumers interested in getting information about the driving forces of the present and future food market, the food industry, and the food policy and the consumer association.

The study of the biological effects of foreign chemicals (whether therapeutic drugs or chemicals present at work or in the environment) interests the biologist from a number of different and complementary viewpoints. Apart from the more obvious pharmacological and toxicological interest, the experimentalist often uses foreign chemicals to produce in experimental animals disease states similar to naturally occurring diseases, so that their pathogenetic mechanisms and therapy can be studied under controlled conditions. In addition - as Claude Bernard pointed out over a century ago - foreign chemicals can be employed as instruments to analyze the most delicate vital processes; much can be learned about the physiological processes themselves by a careful study of the mechanisms by which these are altered by chemicals. The field of heme and hemoproteins offers an example of the interplay of these different approaches. Their metabolism can be altered by therapeutic drugs and other foreign chemicals and this results in a variety of biological responses that transcend the boundaries of pharmacology into the confines of clinical medi cine, genetics, toxicology, biochemistry and physiology. In this book a multidisciplinary approach to the study of heme metabolism is presented including the effect of chemicals on heme metabolism in patients, the results of experimental work in the whole animal, as well as in vitro studies."

This book provides a unique and up-to-date insight into the biopharmaceutical industry. Largely written by industrial authors, its scope is multidisciplinary, rendering it an ideal reference source for students undertaking advanced undergraduate or postgraduate courses in biotechnology, pharmaceutical science, biochemistry, or medicine.

Calorimetry is one of the oldest areas of physical chemistry. The date on which calorimetry came into being may be taken as 13 June 1783, the day on which Lavoisier and Laplace presented a contribution entitled, Memoire de la Chaleur" at a session of the Academie Francaise. Throughout the existence of calorimetry, many new methods have been developed and the measuring techniques have been improved. At p- sent, numerous laboratories worldwide continue to focus attention on the development and applications of calorimetry, and a number of com- nies specialize in the production of calorimeters. The calorimeter is an instrument that allows heat effects in it to be determined by directly measurement of temperature. Accordingly, to determine a heat effect, it is necessary to establish the relationship - tween the heat effect generated and the quantity measured in the ca- rimeter. It is this relationship that unambiguously determines the mathematical model of the calorimeter. Depending on the type of ca- rimeter applied, the accuracy required, and the conditions of heat and mass transfer that prevail in the device, the relationship between the measured and generated quantities can assume different mathematical forms."

This advanced text-cum-reference book presents a comprehensive account of the syntheses, reactions, properties and applications of all the most significant classes of heterocyclic compounds. This second volume in the series is an essential tool not only for advanced undergraduates and graduates, but also for academic and industrial researchers in organic, medicinal, pharmaceutical, dye and agricultural chemistry.