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      Anemia and leukopenia following intravenous colloidal silver infusions—Clinical and hematological features, unique peripheral blood film appearance and effective therapy with supplemental oral copper and apheresis

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          Abstract

          Alternative medical therapy with multiple intravenous colloidal silver infusions may cause severe illness, including profound copper deficiency‐induced anemia and hepatic toxicity. No chelating agent for silver poisoning exists and effective therapy requires apheresis in combination with continuous administration of oral copper.

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          A Pharmacological and Toxicological Profile of Silver as an Antimicrobial Agent in Medical Devices

          Alan B. G. Lansdown (2010)
          Silver is used widely in wound dressings and medical devices as a broad-spectrum antibiotic. Metallic silver and most inorganic silver compounds ionise in moisture, body fluids, and secretions to release biologically active Ag+. The ion is absorbed into the systemic circulation from the diet and drinking water, by inhalation and through intraparenteral administration. Percutaneous absorption of Ag+ through intact or damaged skin is low. Ag+ binds strongly to metallothionein, albumins, and macroglobulins and is metabolised to all tissues other than the brain and the central nervous system. Silver sulphide or silver selenide precipitates, bound lysosomally in soft tissues, are inert and not associated with an irreversible toxic change. Argyria and argyrosis are the principle effects associated with heavy deposition of insoluble silver precipitates in the dermis and cornea/conjunctiva. Whilst these changes may be profoundly disfiguring and persistent, they are not associated with pathological damage in any tissue. The present paper discusses the mechanisms of absorption and metabolism of silver in the human body, presumed mechanisms of argyria and argyrosis, and the elimination of silver-protein complexes in the bile and urine. Minimum blood silver levels consistent with early signs of argyria or argyrosis are not known. Silver allergy does occur but the extent of the problem is not known. Reference values for silver exposure are discussed.
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            Copper deficiency anemia: review article

            Zin Myint, Thein Oo, Kyaw Z Thein … (2018)
            Copper is a crucial micronutrient needed by animals and humans for proper organ function and metabolic processes such as hemoglobin synthesis, as a neurotransmitter, for iron oxidation, cellular respiration, and antioxidant defense peptide amidation, and in the formation of pigments and connective tissue. Multiple factors, either hereditary or acquired, contribute to the increase in copper deficiency seen clinically over the past decades. The uptake of dietary copper into intestinal cells is via the Ctr1 transporter, located at the apical membrane aspect of intestinal cells and in most tissues. Copper is excreted from enterocytes into the blood via the Cu-ATPase, ATP7A, by trafficking the transporter towards the basolateral membrane. Zinc is another important micronutrient in animals and humans. Although zinc absorption may occur by direct interaction with the Ctr1 transporter, its absorption is slightly different. Copper deficiency affects physiologic systems such as bone marrow hematopoiesis, optic nerve function, and the nervous system in general. Detailed pathophysiology and its related diseases are explained in this manuscript. Diagnosis is made by measuring serum copper, serum ceruloplasmin, and 24-h urine copper levels. Copper deficiency anemia is treated with oral or intravenous copper replacement in the form of copper gluconate, copper sulfate, or copper chloride. Hematological manifestations are fully reversible with copper supplementation over a 4- to 12-week period. However, neurological manifestations are only partially reversible with copper supplementation.
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              Chelation: Harnessing and Enhancing Heavy Metal Detoxification—A Review

              Margaret E. Sears (2013)
              Toxic metals such as arsenic, cadmium, lead, and mercury are ubiquitous, have no beneficial role in human homeostasis, and contribute to noncommunicable chronic diseases. While novel drug targets for chronic disease are eagerly sought, potentially helpful agents that aid in detoxification of toxic elements, chelators, have largely been restricted to overt acute poisoning. Chelation, that is multiple coordination bonds between organic molecules and metals, is very common in the body and at the heart of enzymes with a metal cofactor such as copper or zinc. Peptides glutathione and metallothionein chelate both essential and toxic elements as they are sequestered, transported, and excreted. Enhancing natural chelation detoxification pathways, as well as use of pharmaceutical chelators against heavy metals are reviewed. Historical adverse outcomes with chelators, lessons learned in the art of using them, and successes using chelation to ameliorate renal, cardiovascular, and neurological conditions highlight the need for renewed attention to simple, safe, inexpensive interventions that offer potential to stem the tide of debilitating, expensive chronic disease.
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                Author and article information

                Contributors
                Ethan A. Natelson:
                ORCID: https://orcid.org/0000-0002-1449-609X
                eanatelson@att.net
                Journal
                Journal ID (nlm-ta): Clin Case Rep
                Journal ID (iso-abbrev): Clin Case Rep
                Journal ID (doi): 10.1002/(ISSN)2050-0904
                Journal ID (publisher-id): CCR3
                Title: Clinical Case Reports
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Electronic): 2050-0904
                Publication date (Electronic): 09 August 2019
                Publication date Collection: September 2019
                Volume: 7
                Issue: 9 ( doiID: 10.1002/ccr3.v7.9 )
                Pages: 1757-1762
                Affiliations
                [ 1 ] Department of Clinical Medicine Weill Cornell Medical College New York NY USA
                [ 2 ] Department of Academic Medicine Houston Methodist Hospital, Methodist Hospital Research Institute Houston TX USA
                [ 3 ] Houston Methodist Hospital Houston TX USA
                [ 4 ] School of Public Health University of Colorado Boulder CO USA
                [ 5 ] School of Pharmacy University of Colorado Boulder CO USA
                [ 6 ] Summit Technology, LLP West Hartford CT USA
                Author notes
                [*] [* ] Correspondence

                Ethan A. Natelson, Department of Academic Medicine, Houston Methodist Hospital, Houston, TX, USA.

                Email: eanatelson@ 123456att.net

                Author information
                https://orcid.org/0000-0002-1449-609X
                Article
                Publisher ID: CCR32316
                DOI: 10.1002/ccr3.2316
                PMC ID: 6745401
                SO-VID: ea03a1d7-55de-43bd-b8b5-0b427c09c50a
                Copyright © © 2019 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 06 April 2019
                Date revision received : 06 May 2019
                Date accepted : 20 June 2019
                Page count
                Figures: 3, Tables: 0, Pages: 6, Words: 4007
                Categories
                Subject: Case Report
                Subject: Case Reports
                Custom metadata
                source-schema-version-number 2.0
                component-id ccr32316
                cover-date September 2019
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.9 mode:remove_FC converted:16.09.2019

                Keywords: apheresis,colloidal silver,copper,ineffective myelopoiesis
                Data availability:
                Keywords: apheresis, colloidal silver, copper, ineffective myelopoiesis

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