Progress in Clinical Biochemistry and Medicine – serie

Scientific progress, more and more, makes it possible to relate disease to irreg­ ularities on a molecular basis. Both, diagnosis and cure can be targeted to a well defined biological structure. Modern medical research aims at the investigation of the interaction of molecules and bio-macro-molecules, formerly the area of chemis­ try, biochemistry and pharmacology. This series was founded to provide a vehicle for the dissemination of results in a multidisciplinary area of contemporary research. It will publish extensive review articles at a high level, that will relate a particular subject to the scopes of medical chemistry. Thus, information and useful references will be spread among the schol­ ars. Table of Contents Toxicity and Carcinogenicity of Essential and Non-essential Metals M. Costa, A. J. Kraker and S. R. Patierno (USA) .......... 1 Secondary Metabolites with Antibiotic Activity from the Primary Metabolism of Aromatic Amino Acids R. G. Werner (FRG) . . . . . . . . . . . . . . . . . . . . . .. . . 47 . . . . Clinical Pharmacology of Benzodiazepines U. Klotz (FRG) .............. .

l Tumor transformation produces numerous antigenic alterations ), particularly 2 among the glycoconjugates, sugars linked to each other, to lipids and to proteins , 3). Many blood group antigens are identified as glycoconjugates; they include the 4 ABO(H) , MNT, Lewis, Ii and P antigens ). These determinants are particularly valuable since they can be understood in terms of their serology, chemical structure and biochemical genetics4-7). Their specific functions are not well understood; how­ ever, their position as terminal or penultimate sugars may assign them a special role lO as protective or informational moleculesS- ). Ordinarily, these antigens, equally 4lO described on erythrocytes ), persist unchanged throughout the lifetime of the indi­ vidual, but they may be susceptible to alterations in the presence of certain hematopoietic diseases and solid tissue tumors, primarily carcinomas. A review of 11 this topic was published by one of us in 1980 ). New data has accumulated rapidly since then, particularly in the areas of structural analysis, biochemical genetics, and immunologic and tumor marker relationships. The purpose of this review is to provide an update of progress realized in these areas. Other reviews with emphasis 12 l5 on special areas are also available - ). Current and prospective experimental studies should be of use in regard to the following questions: 1.

The close association between blood glucose control and the well-being of the patient, as well as the risk for the development of the "late" complications of 3 diabetes, make it necessary to attain near normalisation of blood glucosel- ). Signifi­ cant progress has been made in this direction in the last few years because of the advancement of analytical techniques for the monitoring of both metabolic status and the functional state of the pancreas and the kidneys, organs involved in the disease process. The respective methodologies are the test strips for self-monitoring of glucose in blood and urine, the measurement of the nonenzymatic glycosylation of hemoglobin and serum proteins, the C-peptide assay, and the determination of small amounts of albumin in urine. The test strip methodology for determination of glucose in blood and urine has made possible home blood glucose monitoring which enables the patient to aim for treatment targets near the physiological range. To this information on short term glycemia obtained by the patient, the determination of hemoglobin glycosylation in the clinical chemistry laboratory adds quantitative information about averaged long­ term glycemic control. The C-peptide assay allows evaluation of the residual pancreatic function in the presence of exogenous insulin. Results of a C-peptide assay are helpful in selecting the appropriate treatment for poorly controlled maturity-onset diabetes. The detection of microalbuminuria, an abnormal albumin excretion below the level of "Albustix" detection, establishes nephropathy before renal damage becomes irreversible.

Cholesterol is essential for normal cellular function. It is found in all cells of the body and is a major constituent of cell membranes. In addition, certain specialized tissues use cholesterol as the basic substrate for the synthesis of more complicated sterols such as bile acids and the steroid hormones. Like most lipids cholesterol has a very low solubility in water. Therefore, in order for these molecules to be transported be­ tween different organs of the body a series of lipid carriers known as lipoproteins has evolved. Over the last several years epidemiological evidence has accumulated suggest­ ing a strong relationship between the risk of atherosclerosis and high plasma concen­ trations of one of these lipoproteins, low density lipoprotein (LDL) 1). Thus, in popula­ tions with high plasma concentrations of LDL-cholesterol a correspondingly high incidence of vascular disease is seen. Since it has been demonstrated that reducing the steady-state plasma LDL-cholesterol concentration produces a proportional decrease in the risk of developing atherosclerosis 2), a major effort is now underway to develop safe and effective lipid lowering agents. In the past, these efforts have been hampered by a lack of knowledge concerning the physiological regulation of the plasma LDL-cholesterol concentration. However, recently there have been several major advances in these areas and it is now possible to precisely determine those factors that have the greatest effect on either increasing or decreasing the plasma LDL-cholesterol concentration.

Calcium Entry Blockers (CEBs) are a new class of drugs which have been pushing back the frontiers of science and medicine for almost two decades. This report reviews some of the wealth of chemical, biological and clinical data describing the discovery and development of these compounds. The scientific importance, therapeutic benefit and marketing potential of these compounds have caused an explosion of scientific literature describing their effects in many preclinical and clinical settings. The definitional characteristics of these compounds suggest a certain predictability of their biological profile but their therapeutic usefulness varies widely dependent upon their physical properties, net hemodynamic effects, duration of action and incidence of side effects. CEBs appear uniquely suited to the treatment of the underlying complexity of cardiovascular disease. The CEBs of the future may live up to the expectations of pathophysiologically based therapeutics and allow the heart and blood vessels to outlive the cells which they support. The development of CEBs is an evolving story of epic proportions and represents the cooperative efforts of individuals in all areas of science.

Das Buch enthalt Kapitel uber: M. B. Bottorff, W. E. Evans, Memphis, TN, USA: Uberwachung der Medikament-KonzentrationE. Truscheit, I. Hillebrand, B. Junge, L. Muller, W. Puls, D. D. Schmidt, Wuppertal, FRG: Inhibitoren der mikrobiellen alpha-Glucosidase: Chemie, Biochemie und potentielle therapeutische AnwendungenH. Will, Berlin-Buch, GDR: Plasminogen-Aktivatoren: Molekuleigenschaften, biologische Zellfunktion und klinische Anwendung

The clinical biochemistry ofhepatobiliary diseases is very widely studied, and publica­ tions abound on this topic. However, there is no recent publication that provides a comprehensive collection of the various leading aspects that go to make up this complex theme. Therefore, we thought it useful to gather together a few scientists whose work has focused on the various clinical biochemistry-aspects of these disorders in order that they might discuss their experience and expertise. The aim of the International Satellite Symposium on Clinical Biochemistry in Hepatobiliary Disease, in addition to reviewing the individual aspects, was to describe the state-of-the-art so as to provide useful data for laboratory scientists and also for physicians working in the field of hepatobiliary diseases, and these two aims are clearly reflected in the chapters of this volume. The volume opens with an introductory chapter that gives a general overview of the various aspects of the clinical biochemistry of these disorders, while the closing chapter deals with an important aspect that deserves to be increasingly emphasized in laboratory medicine, i.e., strategies to integrate information coming from the laboratory to make them more useful for clinical diagnosis.

Das Buch enthalt Kapitel uber: M. Azria, Basel, CH: Calcitonin - Physiologische und Pharmakologische AspekteU. Niemeyer, J. Engel, P. Hilgard, M. Peukert, J. Pohl, H. Sindermann, Bielefeld, FRG: Mafosfamid - Ein Derivat des 4-HydroxycyclophosphamidsS. Grunwald, G.P. Pfeifer, Frankfurt, FRG: Enzymatische DNA Methylierung

Contents/Information: N.P. Johnson, J.-L. Butour, G. Villani, F.L. Wimmer, M. Defais, V. Pierson, Toulouse, France; V. Brabec, Kralovopolska, CSSR: Metal Antitumor Compounds: The Mechanism of Action of Platinum Complexes Pertaining to the Design of Anticancer AgentsB.K. Keppler, M. Henn, U.M. Juhl, M.R. Berger, R. Niebl, Heidelberg; F.E. Wagner, Garching, FRG: New Ruthenium Complexes for the Treatment of CancerG. Mestroni, E. Alessio, Trieste, M. Calligaris, Pavia, Italy; W.M. Attia, Ismailia, Egypt; F. Quadrifoglio, S. Cauci, Udine, Italy; G. Sava, S. Zorzet, S. Pacor, C. Monti-Bragadin, M. Tamaro, L. Dolzani, Trieste, Italy: Chemical, Biological and Antitumor Properties of Ruthenium (II) Complexes with DimethylsulfoxideN. Farrell, Burlington/VT, USA: Metal Complexes as RadiosensitizersS.C. Srivastava, L.F. Mausner, M.J. Clarke, Upton/NY, and Chestnut Hill/MA, USA: Radioruthenium-Labeled Compounds for Diagnostic Tumor ImagingP. Kopf-Maier, Berlin, FRG: The Antitumor Activity of Transition and Main-Group Metal Cyclopentadienyl ComplexesE.V. Scott, G. Zon, L.G.Marzilli, Atlanta/GA and Foster City/CA, USA: NMR Relaxation Footprinting: The ACr(NH3)6U3+ Cation as a Probe for Drug Binding Sites on OligonucleotidesJ.E. Schurig, H.A. Meinema, K. Timmer, Wallingford/CT, USA; B.H. Long, A.M. Casazza, Zeist, NL: Antitumor Activity of BisABis(Diphenylphosphino)Alkane and AlkeneU Group VIII Metal ComplexesM.E. Heim, H. Flechtner, Mannheim; B.K. Keppler, Heidelberg, FRG: Clinical Studies with Budotitane - A New Non-Platinum Metal Complex for Cancer Therapy