Bücher der Reihe Agents and Actions Supplements

Since the rheumatic diseases are among the most prevalent of conditions, the anti-rheumatic drugs make up one of the largest groups of drugs prescribed.

The Eighth International Conference of the Inflammation Research Association was held on October 27 to 31, 1996 at Hershey Lodge and Convention Center in Hershey, Pennsylvania. As have others in this series, the conference focused on understanding the molecular mechanisms involved in acute and chronic inflammatory reactions as well as on therapeutic approaches to treating inflammatory diseases. One outstanding symposium focused on new drugs and was de­ signed as a forum for the dissemination of early clinical results on new anti-inflammatory agents. Other symposia spotlighted exciting advances being made in defining intracellular signaling path­ ways and the potential for future therapeutics that target cytokines and costimulatory pathways. This conference was characterized by a high level of participation by attendees, who represent both the academic and industrial sectors. It was gratifying to note that a large proportion of the attending scientists presented their latest findings during workshops, poster discussions, and pos­ ter se.ssions. This volume covers many of the highlights of the Eighth International Conference and should become a valuable resource for scientists involved in inflammation research and drug discovery.

In previous studies (1,2) we demonstrated the occurrence of a foetal protein after injury in the rat. This protein, behaving as an acute phase protein, proved to be already known as slow a2 glo­ bulin (3), or reproduction associated protein (4). Furthermore it is identical to aM foetoprotein (also known as a2FP or aMFP (5) ). This protein is quite different to the well-known a-foetoprotein (aFP), occurring in man and other species during liver carcinoge­ nesis and some other tumours. aMfoetoprotein (aMFP) is a glycoprotein with a mol.w. of 800.000. It is produced in the liver (6,2) and in the normal adult rat the plasma concentrations are rather low, about 0 - 40 ~g/ml. During fetal development the plasma level in the fetus is much higher (about 6000 ~g/ml), diminishing rapidly after birth to adult levels. But after injury (laparotomy, deep incision, partial hepatectomy followed by regeneration, BaS04 or CdS04 intraperitoneally), plasma levels increase fastly, reaching peak values of 1000 - 8000 ~g/ml after 24 - 48 hrs, declining thereafter gradually. Also very small lesions, as orbital punction, venasection, cannulations, small infections and so on, cause moderate rises of plasma levels up to 80 - 120 ~g/ml. During fetal stage the inflammatory reaction often lacks some of its characteristic features: oedema and infiltration of leucocytes are often rather scanty (7). Also is known that in exudates proteins occur, inhibiting experimen­ tal inflammations (8,9).

pert knowledge and didactic capacity of the con The history of this Course goes back to tributors, we hope the book will be of some use in 1972, when a small, loosely connected group of making research views accessible to those Dutch researchers, who were fascinated by in engaged in clinical practice.

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed groups of drugs in the community. There exists at present a conflict between the pharmaceutical industry with its attempts to introduce new NSAIDs and drug regulatory authorities who are generally not convinced of the need for additional drugs of_ this class.

Ten years ago interest in leukocyte chemotaxis was restricted to a relatively small group of scientists whose interests were quite circumscribed. It is now apparent that leukocytes are particularly useful for studies of the locomotory behavior of all cell types and of mechanisms controlling cell movement and orientation.

On May 24-27,1992 the European Society ofOsteoarthrology (ESOA) held its 19th sympo­ sium in Noordwijkerhout, The Netherlands. The symposium was entitled "Joint destruction in arthritis and osteoarthritis" and sought to combine both clinical and experimental studies in this field. The present volume contains the proceedings of this meeting. The ESOA has organized most of its symposia in the eastern part of Europe, thanks to major input from Stanislav Havelka, who in recent years has been supported by Heikki Helminen. In appreciation of his efforts Stan Havelka was granted Honorary Presidentship of the ESOA at the meeting. In the era of European unification it seemed desirable to create a strong Uni­ fied European Society, which would organize major meetings in both parts of Europe. Cartilage and bone research is expanding rapidly and the number of meetings in this field is continually growing. In line with these developments discussions took place with the recent­ Iy founded "Eular Workshop on Bone and Cartilage Research" and the "Osteoarthritis Re­ search Society (OARS)".

The purpose of the papers is to summarize recent research results, to provide an update on the current approach to therapeutic interventions and to alert readers to the psychosomatic aspects of asthma.

Werner Kaufmann we organized the international symposium on "VASODEPRESSOR HORMONES IN HYPERTENSION - PROSTAGLANDINS AND KININS" held in Nuremberg (FRG) as an official satellite symposium to the Meeting of the International Society of Hypertension 1986.

Bronchial asthma is a disease with many unsolved problems and despite an increased availabili ty of anti-asthma drugs, morbidi ty and mortality from this disease are not improving.

On June 28-29, 1990 in Noordwijk, The Netherlands, the International Association of Inflammation societies (IAIS) organized their first symposium on Drugs in Inflammation.

This book contains the proceedings of the 2nd Cologne Ath~roscle­ rosis Conference (CAC) which was devoted to lipids, in particular lipoproteins. The object of the conference series, organised by A. Nattermann & Cie. GmbH, Cologne, is to provide an overview of various fields either directly related to or associated with the process of atherosclerosis. Having considered the associated field of inflammation in the first conference, the 2nd CAC dealt with a subject intimately related to the atherosclerotic process per see The recent demonstration in an extensive clinical study of a close link between high plasma cholesterol and coronary mortality has awakened both the medical and the lay communities to the importance of research into lipoprotein biochemistry and physiology. This can only be good news since more intensive research into lipoprotein functions is vital for future therapy of atherosclerosis and other lipid disorders. The status of research on lipoproteins is reflected in the contributions to this book, which are of an interdisciplinary nature, including both reviews and shorter research reports by acknowledged experts in the field. Special thanks are due to Margret Leffin for her organisational and secretarial assistance at all stages and to Dr. D. Bowyer and Prof. W. Stoffel for their advice and assist­ ance with the programme. Cologne, July 1984 Michael J ¿. Parnham Lipoprotein Synthesis and Receptor Interactions 17 AAS 16: 2nd Cologne Atherosclerosis Conference 1984 © 1984 Birkhiiuser Verlag Basel APOLIPOPROTEIN GENES, DNA POLYMORPHISMS AND HYPERLIPIDEMIA c. c. Shoulders and F. E.

This involves both the molecular design of new drugs as well as an improved understanding of how established drugs act.

Proteases, Protease-Derived Peptides and Protease Inhibitors Many physiological as weil as pathophysiological processes are mediated by proteases and the products of their actions, protease-derived peptides. However, the uncontrolled activity of proteases can be extraordinarily destructive and dangerous to normal biologie systems. As a result, biology has gone to great lengths to control the activities of the proteases involved in these systems by developing aseries of both highly specific (regulatory) and non-specific (protective) anti-proteases. The protease/anti-protease balancing activities include the normal homeostatic processes of clotting and clot lysis, hormonal regulation of blood pressure and the control of the inflammatory response represented by both the humoral (the kallikrein-kinin and complement systems) and cellular (neutrophil and macrophage derived proteases) components of the inflammation. Examples of successful therapies directed at these protease dependent systems include the use of warfarin and heparin to control thrombosis and streptokinase or tissue plasminogen activator (tPA) for the acceleration of clot dissolution. Similarly, the use of angiotensin converting enzyme (ACE, a type of limited activity protease or peptidase) inhibitors has made a significant impact on the treatment of hypertension. Lastly, the restitution of normal antiprotease levels by the infusion of the purified protein in patients with genetic alpha-1-antiprotease deficiency is regularly being used to reduce the rate of lung function 1055 caused by the unopposed activity of human neutrophil elastase in these individuals.

The Seventh International Conference of the Inflammation Research Association, entitled "Inflammation, Mechanisms and Therapeutics" was held on September 25-29,1994 in White Haven, Pennsylvania.

This volume brings together the latest developments in our understanding of the mechanisms of asthma, considers the safety ofbeta-adrenoceptor agonists, and explores latest developments in the use of phosphodiesterase (PDE) inhibitors in asthma therapy.

The role of histamine as a neurotransmitter, the existence of a presynaptic receptor (H ) controlling the release of histamine 3 and other neurotransmitters, and the particular character of this receptor became important as the possibilities to design new therapeutic agents were realized.

I shall review the problems of unwanted effects and dependence, mainly from an epidemiological view point, and then relate the pharmacological properties of the newer com pounds to possible differences in their clinical profile of adverse effects.

The Eighth International Conference of the Inflammation Research Association was held on October 27 to 31, 1996 at Hershey Lodge and Convention Center in Hershey, Pennsylvania.

Epidemiological studies of Chronic Bronchitis/ Chronic Obstructive Airway Disease (CB/COAD) have demonstrated that hypersecretory glandular activity, as weIl as infections, are not the most important risk factors determining the serious decline in lung function in this disease.

The contri buti ons to the workshops inc 1 uded short revi ews by i nvi ted speakers as well as research papers sel ected by the Chai nnen from the poster abstracts received. The afternoons were free for discussion and recreation but delegates reassanbled with the help of Hunter Valley Wines two hours before dinner to review the many posters presented. On the evenings of the 27th and 28th May, four review lectures were given by J. Dingle (The role of messengers of the IL-I/Catabolin type in cartilage turnover), R. Poole (Immunochemistry as applied to the study of connective tissues), W. Comper (Biophysical aspects of fluid movement in proteoglycan matrices) and P. Roughl ey (Cha nges in proteoglycan structure duri ng cartil age agei ng - ori gi n and effects). The workshop sessions and review lectures, while intense, provided much new data in the areas defined and provided useful debates on controversial issues, which in some instances still remain unresolved. However, the relaxed, informal atmosphere of the Salamander Bay resort provided the greatest incentive for open discussion, the renewal of old, and establishment of new, friendships, all of which are important aspects of our scientific community. While it was not possible to publish all the papers presented at the Salamander Bay Symposium, I trust that those contained herei n will provide some indication of the overall quality and scope of the meeting. Peter Ghosh President C.T.S.A.N.Z.

In July 1994, the Canadian Inflammation Society in Toronto hosted a symposium entitled "Novel molecular approaches to anti-inflammatory therapy" as a satellite of the xnth International Congress of Pharmacology.

The last twenty years have witnessed enormous efforts by the pharmaceutical industry in the search for new drugs for the treatment of asthma.

Uncontrolled proliferation of vascular smooth muscle cells (SMC) in response to vessel injury is a problem with a considerable therapeutic impact. There is also evidence for a markedly increased endogenous prostaglandin production during neointirna formation under the influence of growth factors which includes induction of COX-2.

Since prostaglandins were first proposed as mediators of in flammation some eight years ago, there have been a variety of arachidonic acid metabolites discovered including the thromboxa nes, prostacyclin, prostaglandin endoperoxides and lipoxygenase products such as SRS-A.