In 1928, it was discovered that copper was essential for normal human metabolism. Ten years later, 1938, it was observed that patients with rheumatoid arthritis had a higher than normal serum copper concentration, which returned to normal wi th remission of this disease. Thirteen years later, it was found that copper complexes were effective in treating arthritic diseaseS. The first report that copper complexes had antiinflammatory activity in an animal model of in­ flammation appeared twenty-two years after the discovery of essen­ tiality. In 1976, it was suggested that the active forms of the anti­ arthritic drugs are their copper complexes formed in vivo. This suggestion was confirmed and extended in the interim with over 1000 recent publications, and many of these were addressed in the proceed­ ings of our first symposium, published in 1982. The present symposium was organized to present new normal physiological, nutritional, and biochemical aspects of essential metal­ loelement metabolism as well as variations in metabolism associated with disease states. In addition new data concerning antimicrobial, antiinflammatory, antiulcer, anticancer, anticarcinogenic, analgesic, and radioprotectant activities of copper complexes were presented. These activities are consistent with the notion that they represent the facilitation of normal copper-dependent metabolic processes in dis­ ease states. The presentations and interactive discussions that fol­ lowed are contained in these proceedings. John R. J. Sorenson Dedication These proceedings are dedicated to those who made this truly memorable scientific and social Arkansas experience possible.

Inhalt

Physiologic Aspects of Copper Complexes.- A Physiological Basis for Pharmacological Activities of Copper Complexes: An Hypothesis.- Regulation of Ceruloplasmin Synthesis by Retinoic Acid and Interleukin-1.- Role of Ceruloplasmin in Copper Transport.- Copper and the Regulation of Superoxide Dismutase Activity in Aortic Tissue.- Biochemical Aspects of Copper Complexes.- Influence of Diet and Inflammation on Serum Copper Enzymes.- Copper and Connective Tissue: The Mechanism of Lysyl Oxidase.- Copper-A Modulator of Peptide Release in the Brain.- Copper-Dependent ?-Amidations in the Synthesis of Neuroendocrine Peptide Hormones.- General Discussion.- Copper Complexes in Essential Metalloelement Nutriture and Disease States.- Indices for Assessing Copper Nutriture in Animals and Humans.- Dietary Simple Sugars Increase the Severity of Copper Deficiency in Experimental Animals.- Hypertension Induced Alterations in Copper and Zinc Metabolism: A Link to Vascular Disease?.- Manifestations of Copper Deficiency in Dairy Cattle.- Observations on Biological Effects of Low Dietary Copper in Nebraska Beef Cattle.- Cuprous Sebacate Treatment in Menkes' Disease.- Biological Aspects of Copper and Iron in Inflammation.- Role of Neutrophils in Inflammatory Tissue Injury.- Effect of Cu-DIPS on Ischemia-Reperfusion Injury.- Modulation of Lymphocyte Function by Copper and Thiols.- Copper Regulation of Macrophage Eicosanoid and Cyclic-Amp Synthesis.- Antiinflammatory Activities of Copper Complexes.- Antiinflammatory and Antiulcer Activities of Non-Steroidal Antiinflammatory Agent Copper Complexes.- Comparative Pharmacokinetics of Salicylic Acid and Cop-per-Salicylate in Rats.- Iamin: A Human Growth Factor with Multiple Wound-Healing Properties.- Peroxide Scavenging by Cu(II) Sulfate and Cu(II) (3,5-Diisopropylsalicylate)2.- Analgesic and Antimicrobial Activities of Copper Complexes.- Copper Complexes Have Potent Analgesic Activity and They May Activate Opioid Receptors.- Peptides and Opiates in Copper Deficiency.- Mechanism of the Antimycoplasmal Activity of 2,2?-Bipyridyl Copper Complexes.- Copper(I)-Nicotinic Acid Complex: An Immunopotentiator in Chickens Vaccinated Against Newcastle Disease.- General Discussion.- Anticancer Activities of Copper Complexes and Iron Chelators.- Anticancer Effects of Cu(II) (3, 5-Diisopropylsalicylate)2 in Mice Inoculated Intramuscularly with Ehrlich Ascites Carcinoma Cells.- Effect of Cu(II)(3,5-DIPS)2 on the Solid Ehrlich Tumor Growth in Mice: A Pathological Study.- Copper and Copper Enzymes in the Development and Treatment of Cancer.- Catecholamide Iron Chelators: Antiproliferative Activity on Human Pathogens and Neoplasm.- Anticarcinogenic and Radioprotectant Activities of Copper Complexes.- Effects of Copper Complexes on Multistage Carcinogenesis.- Modulation of Benzopyrene Dependent Mutagenesis and Xanthine Oxidase Activity by Copper Complexes.- Radioprotectant Effects of Cu(II) (3,5-DIPS)2.- General Discussion.- Accelerated Recovery of Immunocompetence with Radioprotective Cu-DIPS.- Other Biological Effects of Complexes and Complexing Agents.- pH-Dependent Superoxide Dismutase-Mimetic Reactivity of Copper (II) Ethylenediaminetetraacetate.- Nutritional Iron Bioavailability and Characterization of the Iron Binding Components of Pinto Beans.- Poster Presentations.- A Model Study for Transport of Metallo-Drugs Within Lipid Bilayers.- Copper, Ceruloplasmin and Superoxide Dismutase in Tumor Bearing Mice.- Structure Optimization of Amides and Amidines Derived from 1-Amino-3-(2-Pyridyl) Isoquinoline Concerning An-timycoplasmal Activity.- The Role of Cu(II) in the Addition of Ethanol to the Cyano Group and the Preparation of Novel Organic Compounds.- Superoxide Dismutase Activity of Heart and Liver Tissue from Copper Deficient Rats.- Synthesis and Biocidal Activity of Some Copper-Tridentate Shiff Bases.- Determination of Human Maternal Serum Copper Levels by AAS and DCP Spectra-Span VI(TM) Techniques.- Modulation of Immune Function as a Consequence of Copper Deprivation.- Accelerated recovery of Hematopoiesis with Radioprotective Cu-DIPS.- Antiasthmatic Activity of some Copper Complexes.- The Effect of Copper on the Polyamine Oxidase Reaction.- Snovial Fluid Copper, Zinc and Selenium in Relation to Inflammatory Parameters in Rheumatic Diseases.