Chelation Therapy in the Treatment of Metal Intoxication

 
 
Academic Press
  • 1. Auflage
  • |
  • erschienen am 18. April 2016
  • |
  • 388 Seiten
 
E-Book | ePUB mit Adobe DRM | Systemvoraussetzungen
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978-0-12-803073-8 (ISBN)
 

Chelation Therapy in the Treatment of Metal Intoxication presents a practical guide to the use of chelation therapy, from its basic chemistry, to available chelating antidotes, and the application of chelating agents. Several metals have long been known to be toxic to humans, and continue to pose great difficulty to treat. These challenges pose particular problems in industrial settings, with lead smelting known to be associated with hemopoietic alterations and paralyses, and the inhalation of mercury vapor in mercury mining being extremely detrimental to the central nervous system.

Clinical experience has demonstrated that acute and chronic human intoxications with a range of metals can be treated efficiently by administration of chelating agents. Chelation Therapy in the Treatment of Metal Intoxication describes the chemical and biological principles of chelation in the treatment of these toxic metal compounds, including new chelators such as meso-2,3-dimercaptosuccinic acid (DMSA) and D,L-2,3-dimercapto-1-propanesulfonic acid (DMPS).


  • Presents all the current findings on the potential for chelation as a therapy for metal intoxication
  • Presents practical guidelines for selecting the most appropriate chelating agent
  • Includes coverage on radionuclide exposure and metal storage diseases
  • Describes the chemical and biological principles of chelation in the treatment of toxic metal compounds


Jan Aaseth was born in 1943 in Norway. He graduated in medicine in 1968 from University of Oslo. After the internship period he became authorized physician in 1970. In the period 1970-77 he worked at department of clinical chemistry and Institute of clinical biochemistry, Oslo University Hospital, with a grant from the National Research Council. He completed his doctoral thesis on metal chelation in 1976, and became an authorized specialist in medical biochemistry. In the period 1977-83 he continued his research on biochemical toxicology at the National Institute of Occupation Health of Norway. During this time he specialized in occupational medicine, and he chaired the Department of Experimental Toxicology for two years. After a subsequent period of specialization also in internal medicine, he was appointed as chair and professor of the Department of Occupational Medicine, University of Tromsø, Norway. Later, he has been head of department of clinical chemistry and section on endocrinology at Innlandet Hospital, and in recent years professor at Hedmark University College.
Professor Aaseth is an enthusiastic teacher. During his carrier he has lectured on medical biochemistry, toxicology, occupational and environmental medicine, internal medicine, nutrition and endocrinology, and he has been supervisor to numerous undergraduate, graduate and postgraduate students during their research projects. He has published some 200 papers.
Professor Aaseth is chair of the Nordic Trace Element Society and vice chair of the Committee for Geomedicine of The Norwegian Academy of Science. He has served on the organizing or scientific committees of several international conferences, including as chair of the First International Symposium on 'Trace Elements in Human Health and Disease' in Loen, Norway, 1985, and also of the subsequent Nordic symposia on this topic in 1993 and in 2013. He served in the scientific committee of the International Conference on Chelation, Paphos, Cyprus 2012, and in the organizing committee of the Conference of the International Society of Trace Element Research in Humans, Dubrovnik, October 2015.
  • Englisch
  • San Diego
  • |
  • USA
Elsevier Science
  • 7,35 MB
978-0-12-803073-8 (9780128030738)
0128030739 (0128030739)
weitere Ausgaben werden ermittelt
  • Cover
  • Title Page
  • Copyright Page
  • Contents
  • Contributors
  • Preface
  • List of Abbreviations
  • Chapter 1 - General Chemistry of Metal Toxicity and Basis for Metal Complexation
  • 1.1 - General chemistry of metals
  • 1.2 - Essential and nonessential elements
  • 1.3 - Effects of toxic exposure of an essential or nonessential metal
  • 1.3.1 - Basic Concepts in Chemical Toxicity Testing
  • 1.3.2 - Exposure Patterns and Mechanisms of Metal Toxicity
  • 1.3.3 - Gastrointestinal Effects of Metal Exposure
  • 1.3.4 - Respiratory Effects of Metal Exposure
  • 1.3.5 - Hepatic and Renal Effects
  • 1.3.6 - Effects on the Nervous System
  • 1.3.7 - Hematological Effects
  • 1.3.8 - Cardiovascular Effects
  • 1.3.9 - Metal Allergies
  • 1.3.10 - Carcinogenic Effects
  • 1.4 - Basis for metal complex formation with endogenous and exogenous ligands
  • 1.5 - Endogenous complexing and detoxification compounds
  • 1.5.1 - Albumin
  • 1.5.2 - Transferrin and Ferritin
  • 1.5.3 - Glutathione
  • 1.5.4 - Metallothionein
  • 1.5.5 - Selenoproteins
  • 1.6 - Conclusions
  • References
  • Chapter 2 - Chelating Agents as Therapeutic Compounds-Basic Principles
  • 2.1 - Chemical and biological principles for in vivo chelation
  • 2.1.1 - Stability
  • 2.1.2 - Selectivity
  • 2.1.3 - Kinetic Aspects of Chelation
  • 2.1.4 - Absorption and Bioavailability of Chelating Agents
  • 2.2 - Chelating agents: chemistry, kinetics, and toxicology
  • 2.2.1 - BAL, DMPS, DMSA
  • 2.2.2 - D-penicillamine
  • 2.2.3 - Triethylenetetramine
  • 2.2.4 - Deferoxamine, Deferiprone, and Deferasirox
  • 2.2.5 - EDTA and DTPA
  • 2.2.6 - Prussian Blue
  • References
  • Chapter 3 - Diagnosis and Evaluation of Metal Poisonings and Chelation Therapy
  • 3.1 - Introduction
  • 3.2 - History of symptoms and exposure
  • 3.3 - Clinical findings
  • 3.4 - Genetic disorders with systemic metal accumulation
  • 3.5 - Toxicological analyses
  • 3.6 - Biochemical measurements
  • 3.7 - Physiological, radiological, and ultrasonographic investigations
  • References
  • Chapter 4 - Chelation Treatment During Acute and Chronic Metal Overexposures-Experimental and Clinical Studies
  • 4.1 - Introduction
  • 4.2 - Aluminum
  • 4.2.1 - Selected Representative Animal Studies
  • 4.2.2 - Selected Representative Clinical Studies
  • 4.2.3 - Conclusions
  • 4.3 - Antimony
  • 4.3.1 - Animal Experiments
  • 4.3.2 - Clinical Cases
  • 4.3.3 - Conclusion
  • 4.4 - Arsenic
  • 4.4.1 - Selected Animal Experiments
  • 4.4.2 - Clinical Studies
  • 4.4.3 - Discussion and Conclusion
  • 4.5 - Beryllium
  • 4.5.1 - Experimental Chelation Studies
  • 4.5.2 - Clinical Experience
  • 4.5.3 - Conclusion
  • 4.6 - Bismuth
  • 4.6.1 - Animal Chelation Studies
  • 4.6.2 - Clinical Chelation Studies
  • 4.6.3 - Conclusion
  • 4.7 - Cadmium
  • 4.7.1 - Animal Chelation Experiments
  • 4.7.2 - Clinical Chelation Studies
  • 4.7.3 - Conclusion
  • 4.8 - Chromium
  • 4.8.1 - Animal Experimental Studies
  • 4.8.2 - Clinical Cases
  • 4.8.3 - Conclusion
  • 4.9 - Cobalt
  • 4.9.1 - Chelation, Animal Experiments
  • 4.9.2 - Chelation, Clinical Studies
  • 4.9.3 - Conclusion
  • 4.10 - Copper
  • 4.10.1 - Animal Chelation Studies
  • 4.10.2 - Human Clinical Chelation Studies
  • 4.10.3 - Conclusions
  • 4.11 - Gallium
  • 4.11.1 - Experimental Animal Chelation Studies
  • 4.11.2 - Clinical Chelation
  • 4.11.3 - Conclusions
  • 4.12 - Gold
  • 4.12.1 - Animal Experimental Studies
  • 4.12.2 - Clinical Studies
  • 4.12.3 - Conclusions
  • 4.13 - Iron
  • 4.13.1 - Selected Animal Studies
  • 4.13.2 - Clinical Chelation Cases
  • 4.13.3 - Clinical Reviews
  • 4.13.4 - Conclusions
  • 4.14 - Lead
  • 4.14.1 - Animal Chelation Studies
  • 4.14.2 - Clinical Studies
  • 4.14.3 - Summary and Conclusions
  • 4.15 - Manganese
  • 4.15.1 - Animal Experimental Chelation Studies
  • 4.15.2 - Clinical Chelation Studies
  • 4.15.3 - Conclusion
  • 4.16 - Mercury
  • 4.16.1 - Experimental Animal Studies
  • 4.16.2 - Clinical Studies
  • 4.16.3 - Conclusions
  • 4.17 - Nickel
  • 4.17.1 - Experimental Chelation Studies
  • 4.17.2 - Clinical Studies
  • 4.17.3 - Conclusions
  • 4.18 - Platinum
  • 4.18.1 - Experimental Animal Studies
  • 4.18.2 - Clinical Studies
  • 4.18.3 - Conclusions
  • 4.19 - Silver
  • 4.20 - Thallium
  • 4.20.1 - Animal Studies
  • 4.20.2 - Clinical Cases
  • 4.20.3 - Conclusions
  • 4.21 - Tin
  • 4.21.1 - Animal Experimental and Clinical Studies
  • 4.21.2 - Conclusions
  • 4.22 - Zinc
  • 4.22.1 - Experimental and Clinical Chelation Studies
  • 4.22.2 - Conclusions
  • 4.23 - Summary, conclusions, and perspectives
  • References
  • Chapter 5 - Decorporation of Radionuclides
  • 5.1 - Introduction
  • 5.2 - Americium
  • 5.3 - Cesium
  • 5.4 - 60Cobalt
  • 5.5 - Plutonium
  • 5.6 - Polonium
  • 5.7 - Radium
  • 5.8 - Strontium
  • 5.9 - Technetium
  • 5.10 - Thorium
  • 5.11 - Uranium
  • 5.12 - Development of new chelators and off-label use of chelating agents
  • 5.13 - Conclusions and perspectives
  • References
  • Chapter 6 - Chelating Therapy in Metal Storage Diseases
  • 6.1 - Introduction
  • 6.2 - Wilson's disease
  • 6.2.1 - Penicillamine in Wilson's Disease
  • 6.2.2 - Trientine Treatment-The Treatment of Choice Today?
  • 6.2.3 - Ammonium Tetrathiomolybdate-An Alternative Agent?
  • 6.2.4 - Zinc-An Agent for Maintenance Therapy
  • 6.2.5 - Dimercaptosuccinic Acid (DMSA)-Useful in Wilson's Disease?
  • 6.2.6 - Liver Transplantation
  • 6.2.7 - Conlusive Guidelines for Therapeutic Monitoring of Wilson's Disease
  • 6.3 - Other neurodegenerative diseases
  • 6.3.1 - Friedreich's Ataxia
  • 6.3.2 - Aceruloplasminemia
  • 6.3.3 - Pantothenate Kinase Associated Neurodegeneration
  • 6.3.4 - Other Neurodegenerations with Brain Iron Accumulation
  • 6.3.5 - Parkinson's Disease
  • 6.3.6 - Demyelinating Disorders and Neuroinflammation
  • 6.4 - Transfusional and hereditary siderosis-including thalassemias
  • 6.4.1 - Deferoxamine (Desferrioxamine) in Transfusional Siderosis
  • 6.4.2 - Deferiprone Therapy
  • 6.4.3 - Deferasirox
  • 6.4.4 - Bone Marrow Transplantation in Thalassemia
  • 6.4.5 - Hemochromatosis-and Therapeutic Elimination by the Endogenous "Heme chelate"
  • 6.5 - Concluding remarks
  • Acknowledgments
  • References
  • Chapter 7 - Guidance for Clinical Treatment of Metal Poisonings-Use and Misuse of Chelating Agents
  • 7.1 - Introduction
  • 7.2 - Reducing the absorbed dose
  • 7.2.1 - Removal From Exposure
  • 7.2.2 - Removal of Toxic Element From the Gastrointestinal Tract
  • 7.2.3 - Use of Gastric Lavage, Activated Charcoal, or Unabsorbed Resins
  • 7.3 - General supportive therapy
  • 7.3.1 - Maintenance of Respiration and Circulation
  • 7.3.2 - Maintenance of Water and Electrolyte Balance
  • 7.3.3 - Control of Cerebral Functions
  • 7.4 - Elimination of absorbed poison
  • 7.4.1 - Diuresis
  • 7.4.2 - Biliary Excretion
  • 7.4.3 - Dialysis
  • 7.4.4 - Exchange Transfusion
  • 7.5 - Detoxification by inactivation of the absorbed poison
  • 7.6 - Chelation therapy
  • 7.6.1 - Dimercaprol (BAL)-A Classic Agent, but Now Obsolete?
  • 7.6.2 - Sodium 2,3-Dimercaptopropane-1-Sulfonate (DMPS
  • Dimaval)-In Clinical Use
  • 7.6.3 - Meso-2,3-Dimercaptosuccinic Acid (DMSA
  • Succimer)-Clinical Use and Misuse
  • 7.6.4 - Calcium Disodium Edetate (CaNa2EDTA)-Clinical Use and Misuse
  • 7.6.5 - Diethylenetriaminepentaacetic Acid (DTPA)-and Radionuclide Chelation
  • 7.6.6 - Penicillamine (Cuprimine)-Old but Not Outdated
  • 7.6.7 - Triethylenetetramine (Trientine, TETA)-Clinical Usefulness
  • 7.6.8 - Deferoxamine (DFO)-The Classical Iron Chelator
  • 7.6.9 - Deferiprone (Ferriprox)-An Oral Agent for Iron Detoxification
  • 7.6.10 - Deferasirox (Exjade)-A New Efficient Tablet for Iron Detoxification
  • 7.6.11 - Diethyldithiocarbamate (DDC)
  • 7.6.12 - Combinations of Chelating Agents
  • 7.7 - Experimental chelation treatment in atherosclerosis and in Alzheimer dementia
  • 7.7.1 - Atherosclerosis
  • 7.7.2 - Alzheimer's Disease
  • 7.8 - Modification of toxic effects of metals
  • 7.8.1 - Modification of Inflammatory Response in Tissues
  • 7.8.2 - Modification of Biochemical Functions
  • Acknowledgments
  • References
  • Chapter 8 - Conclusions and Guidelines for Future Research
  • 8.1 - Conclusions on clinical chelation treatment and indications of important research needs
  • 8.2 - Guidelines for future research
  • References
  • Subject Index
  • Back cover

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