Copper and the skin

reface . . . . v Acknowledgment . . . . vii Contributors . . . . xv 1. Copper and Copper Alloys . . . . . . . . . . . . . . . . . . . . . . . . 1 Harold T. Michels Introduction . . . . 1 Copper: Properties of the Element . . . . 1 Pure Copper . . . . 2 Copper Alloys . . . . 2 Properties of Copper Alloys . . . . 2 Copper Alloy Families . . . . 4 The High Coppers . . . . 4 Conclusions . . . . 6 2. Corrosion Chemistry of Copper: Formation of Potentially Skin-Diffusible Compounds . . . . . . . . . . . . . . . . . . . . . . . . 7 Jurij J. Hosty´ nek Introduction . . . . 7 Electron Configuration and Reactivity of Copper . . . . 8 Corrosion of Copper in the Environment . . . . 8 Corrosion of Copper in Physiologic Media . . . . 9 Conclusions . . . . 15 Glossary . . . . 16 Abbreviations . . . . 16 References . . . . 16 ix 3. Basics of Metal Skin Penetration: Scope and Limitations . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Jurij J. Hosty´ nek and Howard I. Maibach Introduction . . . . 21 Structure of Skin and Its Function as Diffusion Barrier . . . . 23 Descriptors of Dermal Absorption . . . . 25 Permeant Categories and Paths of Diffusion . . . . 28 Compounds Formed by Metals in Contact with the Skin . . . . 31 Variables Determining Skin Diffusion of Metal Compounds . . . . 35 Methods for Measuring Percutaneous Absorption . . . . 45 Analytical Methods for Metal Detection . . . . 53 Summary and Conclusions . . . . 56 Abbreviations . . . . 57 References . . . . 58 4. Percutaneous Absorption of Copper Compounds . . . . . . . . 67 Jurij J. Hosty´ nek and Howard I. Maibach Introduction . . . . 67 Qualitative Diffusion Data . . . . 68 Semiquantitative Data . . . . 70 Quantitative Data . . . . 71 Discussion and Conclusions . . . . 73 Limitations in Measuring Copper Absorption In Vivo . . . . 74 Interdependence of Systemic Copper and Zinc Levels . . . . 75 Recommendations for Research to Fill Existing Data Gaps . . . . 76 Conclusions . . . . 77 Glossary . . . . 78 Abbreviations . . . . 78 References . . . . 79 5. Diffusion of Copper Through Human Skin In Vivo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 Jurij J. Hosty´ nek, Howard I. Maibach, and Frank Dreher Introduction . . . . 81 Experimental . . . . 84 Results . . . . 85 x Contents Discussion . . . . 88 Conclusions . . . . 92 Glossary . . . . 93 Abbreviations . . . . 93 References . . . . 94 6. Irritation Potential of Copper Compounds . . . . . . . . . . . . 97 Jurij J. Hosty´ nek and Howard I. Maibach Introduction . . . . 97 Exposure to Copper . . . . 97 Solubilization of Copper Metal . . . . 98 Incidence and Epidemiology of Irritation Due to Copper . . . . 100 Pharmacology of Copper . . . . 101 Copper Irritancy in Skin and Mucosa . . . . 103 Conclusions . . . . 111 Abbreviations . . . . 112 References . . . . 112 7. Copper Hypersensitivity: Dermatologic Aspects—Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 Jurij J. Hosty´ nek and Howard I. Maibach Introduction . . . . 115 Metallurgy of Copper and Its Alloys, and Its Role as Sensitizer . . . . 117 Predictive Immunology Test Results for Copper . . . . 119 Diagnostic Tests for Hypersensitivity . . . . 119 Test Concentrations for Copper ACD . . . . 123 Immunogenic Potential of Copper . . . . 123 Summaries of Population-Based Studies . . . . 134 Summary of Selected Case Reports of Immune Reactions to Copper . . . . 138 Selection of Individual Reports of Immune Reactions to Copper . . . . 138 Comments . . . . 140 Conclusions . . . . 140 Abbreviations . . . . 141 References . . . . 141 Contents xi 8. Copper in Medicine and Personal Care: A Historical Overview . . . . . . . . . . . . . . . . . . . . . . . . . 149 Roberto Milanino Introduction . . . . 149 The Sumeric Culture: Circa 4000–2300 B.C. . . . . 150 The Ancient Egyptian Culture . . . . 150 The Babylonian–Assyrian Culture: Circa 1750–539 B.C. . . . . 152 The Ancient Indian Culture: Circa 2800–1000 B.C. . . . . 152 The Ancient Chinese Culture: Circa 3000 B.C. to 1100 A.D. . . . . 152 The Pre-Columbian Meso- and South-American Cultures: Circa 600 B.C. to 1500 A.D. . . . . 153 The Ancient Greek Culture . . . . 153 The Ancient Roman Culture: Circa 600 B.C. to 476 A.D. . . . . 155 From the High-Medieval Age to the Early 20th Century . . . . 156 Beginning of the Scientific Age for Copper: 1928–1976 . . . . 157 Conclusions . . . . 158 Abbreviations . . . . 159 References . . . . 159 9. The Role of Copper in Onset, Development, and Control of Acute and Chronic Inflammation . . . . . . . . . . 161 Roberto Milanino Introduction . . . . 161 Studies on Copper-Deficient, Experimentally Inflamed Animals . . . . 163 Laboratory Animals: Studies on ‘‘Endogenous’’ Copper Metabolism in Acute and Chronic Inflammation . . . . 170 Human Subjects: Studies on ‘‘Endogenous’’ Copper Metabolism in Acute and Chronic Inflammations, with a Particular Reference to Rheumatoid Arthritis . . . . 179 Effects of ‘‘Exogenous’’ Copper Administration on the Inflammatory Process . . . . 184 Copper Anti-inflammatory Activity: Hypotheses Explaining the Possible Mechanisms of Action . . . . 203 Conclusions . . . . 216 xii Contents Abbreviations . . . . 219 References . . . . 220 10. Copper Jewelry and Arthritis . . . . . . . . . . . . . . . . . . . . 237 Brenda J. Harrison Introduction . . . . 237 The Copper Bracelet ‘‘Myth’’ and Hypothesis . . . . 239 The Copper Bracelet Trial . . . . 243 The Present State of the Copper Bracelets ‘‘Issue’’ . . . . 251 Is There Likely to Be a Future for Copper Bracelets in Arthritis Care? . . . . 256 Appendix A: Position Statements of Support Organizations, Government Agencies, Etc. . . . . 257 Appendix B: Miscellany . . . . 259 References . . . . 261 11. Role of Copper in Anti-inflammatory Therapy and the Potential for Its Transdermal Application . . . . . . . . . . . . 267 Jurij J. Hosty´ nek and Roberto Milanino Introduction . . . . 267 Traditional and Modern Therapies for RA and Related Disorders . . . . 268 Drug Therapy . . . . 271 Precedents in Topical Delivery of Anti-inflammatory Agents . . . . 275 Role of Copper in AI Activity . . . . 275 Past Use of Copper Chelates in the Treatment of Rheumatoid Arthritis . . . . 278 Transdermal Delivery of Anti-inflammatory Copper Chelates vs. Conventional (Systemic) Anti-inflammatory Therapy . . . . 278 Conclusions . . . . 286 Outlook . . . . 288 Abbreviations . . . . 288 References . . . . 289 Index . . . . 295