Medical uses of silver

The medical uses of silver include its incorporation into wound dressings to treat external infections, and its use as an antiseptic and disinfectant in medical appliances. Silver is also promoted within alternative medicine in the form of colloidal silver, although it has not been proven to be safe or effective.

The silver ion (Ag⁺) is bioactive and in sufficient concentration readily kills bacteria in vitro. Silver also kills bacteria in external wounds in living tissue, so physicians use wound dressings containing silver sulfadiazine (Ag-SD) or silver nanomaterials to treat external infections.^{[1][2][3][4][5]} Wound dressings containing silver are increasing in importance due to the recent increase of antibiotic-resistant bacteria, such as MRSA.^[6] The disinfectant properties of silver are used in medical applications, such as urinary catheters and endotracheal breathing tubes, where the silver content is effective in reducing incidences of catheter-related urinary tract infections and ventilator-associated pneumonia (VAP), respectively.^{[7][8][9][10]} Silver is also used in bone prostheses, reconstructive orthopaedic surgery and cardiac devices,^[11] as well as on surfaces and fabrics to reduce the spread of infection.^[12][13]

Since the 1990s, "colloidal silver", a liquid suspension of microscopic silver particles, has been marketed as an alternative medicine, often claiming impressive "cure-all" qualities. The effectiveness of these products has never been scientifically proven, and in some jurisdictions, it is currently illegal to include such claims in product advertisements.^[14] Medical authorities and publications advise against the ingestion of colloidal silver preparations, because of their lack of proven effectiveness and because of the risk of adverse side effects, such as argyria.^{[2][15][16][17]} Historically, colloidal silver was also used as an internal medication to treat a variety of diseases. Their use was largely discontinued in the 1940s, due to the development of safe and effective modern antibiotics and concern about adverse side effects.^[17][18]

Historically

Silver has had some medicinal uses going back for centuries. The Phoenicians are said to have stored water, wine, and vinegar in silver bottles to prevent spoiling.^[19] In the early 1900s, people would put silver coins in milk bottles to prolong the milk's freshness.^[19] Hippocrates, the "father of medicine",^[20] wrote that silver had beneficial healing and antidisease properties.^[19] In the early 1900s, silver gained regulatory approval as an antimicrobial agent. Prior to the introduction of antibiotics, colloidal silver was used as a germicide and disinfectant.^[21] Physicians used it as an eyedrop for ophthalmic problems,^[22] for various infections,^[23][24] and sometimes internally for diseases such as tropical sprue, epilepsy, gonorrhea, and the common cold.^[2][16][25] Colloidal silver preparations (CSP) were used to treat or prevent gonorrhea and gonorrheal conjunctivitis.^[17] Although "silver products were infrequently promoted for oral use, benefits have been even more questionable."^[17] With the introduction of antibiotics in the 1940s, the use of silver as an antimicrobial agent diminished.^[6] One well known, highly successful, brand name, silver colloid product in the period before 1940 was Argyrol.

Antiseptic

Silver and most silver compounds have an oligodynamic effect and are toxic for bacteria, algae, and fungi in vitro. The oligodynamic effect is typical for heavy metals, such as lead and mercury, but, among the elements that have this effect, silver is the least toxic for humans. The antibacterial action of silver is dependent on the silver ion.^[12] The effectiveness of silver compounds as an antiseptic is based on the ability of the biologically active silver ion (Ag+) to irreversibly damage key enzyme systems in the cell membranes of pathogens.^[12] The antibacterial action of silver has long been known to be enhanced by the presence of an electric field. Applying a few volts of electricity across silver electrodes drastically enhances the rate bacteria in solution are killed. The antibacterial action of silver electrodes is greatly improved if the electrodes are covered with silver nanorods.^[26]

Disinfectant

Electrolytically-dissolved silver has been used as a water disinfecting agent, for example, the drinking water supplies of the Russian Mir orbital station and the International Space Station.^[27] The World Health Organization includes silver in a colloidal state produced by electrolysis of silver electrodes in water, and colloidal silver in water filters as two of a number of water disinfection methods specified to provide safe drinking water in developing countries.^[28] Along these lines, a ceramic filtration system coated with silver particles has been created by Ron Rivera of Potters for Peace and used in developing countries for water disinfection.^[29][30][31]

External infections

In World War I, before the advent of antibiotics, silver compounds were used to prevent and treat infections. Silver compounds continue to be used in external preparations as antiseptics,^[16] including silver nitrate, which can be used in dilute solution as eyedrops to prevent conjunctivitis in newborn babies. Silver nitrate is also sometimes used in dermatology in solid stick form as a caustic ("lunar caustic") to treat certain skin conditions, such as corns and warts.^[2]

According to Atiyeh et al. (2007), "The gold standard in topical burn treatment is silver sulfadiazine (Ag-SD), a useful antibacterial agent for burn wound treatment". They do note, however, that silver-impregnated dressings do sometimes result in a slower healing process.^[1] Silver sulfadiazine cream (SSD Cream) replaced colloidal silver as the most common delivery system for using silver on the surface of burn wounds to control infection in the 1970s.^[1][2]

The US Food and Drug Administration has approved the use of a range of different silver-impregnated wound dressings.^[32]

Laboratory studies at the Biochemical Materials Research and Development Center of Jiaxing College, China, have shown silver-containing alginate fibres provide a sustained release of silver ions when in contact with wound exudates, and are “highly effective against bacteria”.^[3] A study administered by the Hull York Medical School found an antimicrobial barrier dressing containing silver provided “a highly effective and reliable barrier to the spread of MRSA into the wider hospital.”^[4][33]

More recently, dressings incorporating nanocrystalline silver or activated silver-impregnated substances have become available,^[1] which deliver higher concentrations of the active silver ion.^[12] As of 2006, more "than 10 dressings containing pure silver" were available.^[5] In particular, silver is being used with alginate, a naturally occurring biopolymer derived from seaweed, in a range of products designed to prevent infections as part of wound management procedures, particularly applicable to burn victims.^[5]

Wound dressings containing silver are increasing in importance due to the increase of antibiotic-resistant bacteria, which has imposed clinical limits on the use of antibiotics. Chopra^[34] states topical silver is regaining popularity in the management of open wounds, “due largely to the spread of methicillin-resistant Staphylococcus aureus and the resultant reduction in first-line antibiotic prescribing”, and “[s]ome silver-based dressings appear to provide an effective alternative to antibiotics in the management of wound infection.”^[6] Silver has proven broad-spectrum antimicrobial activity that includes antibiotic-resistant bacteria, with minimal toxicity toward mammalian cells at low concentrations, and has a less likely tendency than antibiotics to induce resistance due to its activity at multiple bacterial target sites.^{[6][35][36][37][38]}

However, some sources still hold that the evidence for the effectiveness of silver-treated dressings is mixed, as the evidence is marred by the poor quality of the trials used to assess these products.^[39] Consequently, a systematic review by the Cochrane Collaboration found insufficient evidence to recommend the use of silver-treated dressings to treat infected wounds.^[40]

In medical appliances

The disinfectant properties of silver are used in some other medical applications, such as catheters and endotracheal breathing tubes.^[41][42] A study on the use of silver-alloy catheters by the University of Michigan School of Medicine concluded “The data supporting the use of silver alloy urinary catheters to reduce urinary catheter-related bacteriuria is reasonably strong.”^[7] The study also concluded silver alloy catheters are more effective than standard catheters for reducing bacteriuria in adults in hospital having short-term catheterization, and, although they cost about $6 more than standard urinary catheters, they may be worth the extra cost, since catheter-related infection is a common cause of nosocomial infection and bacteremia. Related meta-analysis also clarified discrepant results among earlier trials of silver-coated urinary catheters by revealing silver alloy catheters are significantly more effective in preventing urinary tract infections than are silver oxide catheters.^[8] These conclusions are supported by, among others, studies by the University Hospitals Leuven, Belgium^[12] and the University Hospital for Anesthesiology and Surgical Intensive Care, Halle, Germany.^[43]

In 2007, AGC Flat Glass Europe introduced the first antibacterial glass to fight hospital-acquired infection; it is covered with a thin layer of silver.^[44] Ionizable silver is also incorporated into fabrics to reduce the spread of bacteria.^[12]

Ventilator-associated pneumonia (VAP) causes substantial morbidity. A 2008 study by Kollef et al. concluded, “Patients receiving a silver-coated endotracheal tube had a statistically significant reduction in the incidence of VAP and delayed time to VAP occurrence compared with those receiving a similar, uncoated tube.”^[9] In addition, the U.S. Food and Drug Administration (FDA) has recently approved an endotracheal tube with a fine coat of silver for use in mechanical ventilation, after studies found it reduced the risk of ventilator-associated pneumonia.^[10]

The use of these devices is contraindicated for persons who are allergic to silver,^[12] and although they are widely used in hospitals, no thorough testing and standardization of these products has yet been undertaken.^[6]

Effectiveness

A meta-analysis of 26 studies by the Cochrane Collaboration found that, while most were small and of poor quality, there was not enough evidence to support the use of silver-containing dressings or creams, as generally these treatments did not promote wound healing or prevent wound infections. Some evidence suggested that silver sulphadiazine had no effect on infection, and actually slowed healing.^[45]

Alternative medicine

Since about 1990, there has been a resurgence of the promotion of colloidal silver as an alternative medicine treatment, marketed with claims of it being an essential mineral supplement, or that it can prevent or treat numerous diseases, such as cancer, diabetes, HIV/AIDS, and herpes,^[17] as well as tuberculosis.^[2][18][46] Silver is not an essential mineral in humans; there is no dietary requirement for silver, and no such thing as a silver "deficiency".^[2] No medical evidence supports colloidal silver as being effective for any of these claimed indications.^[47][48]

The commercial product referred to as "colloidal silver", includes solutions that contain various concentrations of ionic silver compounds, silver colloids or silver compounds bound to proteins in water. Such products with concentrations of 30 parts per million (ppm) or less are typically manufactured using an electrolysis process, whereas those with higher concentrations of 50 ppm or more are usually silver compounds that have been bound with a protein. Colloidal silver preparations primarily deliver inactive metallic silver, rather than the active microbicidal silver ion.^[49]

No scientific evidence supports the effectiveness of colloidal silver in vivo.^[2] Some in vitro studies demonstrate an antibacterial effect of colloidal silver,^[50] although one study in 2004 of a colloidal silver solution marketed on the Internet showed no such antimicrobial activity.^[51] No clinical studies in humans demonstrate effectiveness, and a few report toxicity.^[16] The U.S. National Center for Complementary and Alternative Medicine has issued an advisory indicating the marketing claims made about colloidal silver are scientifically unsupported, the silver content of marketed supplements varies widely, and colloidal silver products can have serious side effects to the consumer, including "argyria,... neurologic problems (such as seizures), kidney damage, stomach distress, headaches, fatigue, and skin irritation. Colloidal silver may interfere with the body's absorption of some drugs, such as penacillamine, quinolones, tetracyclines, and thyroxine."^[2]

Although colloidal silver products are legally available at health food stores in the United States and Australia and are marketed over the Internet as a dietary supplement, it is illegal in the U.S. and Australia for marketers to make claims of medical effectiveness for colloidal silver. Ingestion of colloidal silver may result in argyria.^{[52][53][54][55][56]}

Adverse health effects

Further information: Silver and Argyria

According to Lansdown, the risk expected due to clinical exposure to silver is "minimal", as only chronic ingestion or inhalation of silver preparations leads to an accumulation of silver in the human body that can cause argyria, argyrosis (accumulation of silver in the eye), and other conditions.^[12] Silver-based products are contraindicated for people who are allergic to silver.^[12] The reference dose, published by the United States Environmental Protection Agency in 1991, which recommends the estimated daily exposure that is unlikely to incur an appreciable risk of deleterious effects during a lifetime, is 5 µg/kg/d; meaning 5 micrograms of silver per kilo of weight per person each day – about 1 liter of 10 ppm colloidal silver per month for a 66 kg person.^[17] An article from the National Center for Complementary and Alternative Medicine points out silver nitrate and silver sulfadiazine can have negative side effects, and they must be applied to the body externally and not taken internally.^[2]

The chronic intake of silver products and the silver buildup from colloidal silver can result in an accumulation of silver or silver sulfide particles in the hair, skin, kidneys, liver, heart and muscles due to high methionine-containing proteins, such as keratin, myosin, tropomyosin, troponin, and key dipeptide glutathione. Serious neurologic (such as seizures), renal, or hepatic complications, as well as headaches, stomach distress, fatigue, and skin irritation have been reported.^[57][58] if ingested, colloidal silver may react with certain drugs, such as Penicillamine, thyroxine, quinolones, and tetracyclines.^[59] One death has been reported in the medical literature which the authors felt was due to silver toxicity resulting from repeated oral ingestion of colloidal silver.^[60] Colloidal silver can reduce the absorption of some medications, including tetracycline and quinolone antibiotics and can bind to penicillamine, thereby reducing the effectiveness of those medications.^[16]

As in photography (where silver is used due to its reactivity with light), silver particles in the skin darken with exposure to sunlight, resulting in a blue or gray discoloration of the skin. This condition is known as argyria, which is a dermatological condition characterized by grayish-blue pigmentation of the skin, nails, gums, and deep tissues; and, in similar manner, it can lead to silver in the eye (argyrosis) and in other organs.^[12] Localized argyria can occur as a result of topical use of substances containing silver, while generalized argyria results from the chronic ingestion of such substances.^[57] Argyria was long believed to be irreversible,^[49] but recently, laser therapy has been used to treat it with satisfactory cosmetic results.^[61][62][63] The Agency for Toxic Substances and Disease Registry (ATSDR) describes argyria as a "cosmetic problem",^[64] although some people consider it to be socially debilitating.^[65][66]

Regulation

In August 1999, the FDA banned colloidal silver sellers from claiming any therapeutic or preventive value for the product, noting colloidal silver was being marketed for numerous diseases without evidence of safety or effectiveness.^[48] As a result, the product now has the status of a dietary supplement in the US; it can be promoted with general "structure-function" claims, but cannot be marketed as preventing or treating any illness.^[48] Following this ruling, the FDA has issued numerous Warning Letters to Internet sites that have continued to promote colloidal silver as an antibiotic or for other medical purposes.^[67][68]

In 2002, the Australian Therapeutic Goods Administration (TGA) found there were no legitimate medical uses for colloidal silver and no evidence to support its marketing claims. Given the associated safety risks, the TGA concluded "efforts should be made to curb the illegal availability of colloidal silver products, which is a significant public health issue."^[69]

Environmental effects

Silver that enters the environment from discarded medical sources can have detrimental effects on micro-organisms and animals (including humans).^[70]

References

1. ^ ^{a b c d} Atiyeh BS, Costagliola M, Hayek SN, Dibo SA (2007). "Effect of silver on burn wound infection control and healing: review of the literature". Burns 33 (2): 139–48. doi:10.1016/j.burns.2006.06.010. PMID 17137719. 
2. ^ ^{a b c d e f g h i j} "Colloidal Silver Products". National Center for Complementary and Alternative Medicine. December 2006. http://nccam.nih.gov/health/silver/. Retrieved 2008-10-06. 
3. ^ ^{a b} Qin Y (June 2005). "Silver-containing alginate fibres and dressings". International Wound Journal 2 (2): 172–6. doi:10.1111/j.1742-4801.2005.00101.x. PMID 16722867. 
4. ^ ^{a b} 1 May 2007 (2007-05-01). "Combatting the bug | News". The Engineer. http://www.theengineer.co.uk/Articles/299472/Combatting%20the%20bug.htm. Retrieved 2010-07-10. 
5. ^ ^{a b c} Hermans MH (2006). "Silver-containing dressings and the need for evidence". The American journal of nursing 106 (12): 60–8; quiz 68–9. doi:10.1097/00000446-200612000-00025. PMID 17133010. 
6. ^ ^{a b c d e} Chopra I (April 2007). "The increasing use of silver-based products as antimicrobial agents: a useful development or a cause for concern?". The Journal of Antimicrobial Chemotherapy 59 (4): 587–90. doi:10.1093/jac/dkm006. PMID 17307768. 
7. ^ ^{a b} http://www.ahrq.gov/Clinic/ptsafety/chap15a.htm^{[dead link]}
8. ^ ^{a b} Saint S, Elmore JG, Sullivan SD, Emerson SS, Koepsell TD (September 1998). "The efficacy of silver alloy-coated urinary catheters in preventing urinary tract infection: a meta-analysis". The American Journal of Medicine 105 (3): 236–41. doi:10.1016/S0002-9343(98)00240-X. PMID 9753027. 
9. ^ ^{a b} Kollef MH, Afessa B, Anzueto A et al. (August 2008). "Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: the NASCENT randomized trial". JAMA 300 (7): 805–13. doi:10.1001/jama.300.7.805. PMID 18714060. 
10. ^ ^{a b} "FDA Clears Silver-Coated Breathing Tube For Marketing". 2007-11-08. http://www.fda.gov/bbs/topics/NEWS/2007/NEW01741.html. Retrieved 2007-11-11. 
11. ^ Lansdown, Alan B.G. (2006). Silver in Health Care: Antimicrobial Effects and Safety in Use. "Biofunctional Textiles and the Skin". Current problems in dermatology. Current Problems in Dermatology 33: 17–34. doi:10.1159/000093928. ISBN 3-8055-8121-1. PMID 16766878. 
12. ^ ^{a b c d e f g h i j} Lansdown AB (2006). "Silver in health care: antimicrobial effects and safety in use". Current Problems in Dermatology. Current Problems in Dermatology 33: 17–34. doi:10.1159/000093928. ISBN 3-8055-8121-1. PMID 16766878. 
13. ^ Antimicrobial efficacy of a silver-zeolite matrix coating on stainless steel J Ind Microbiol Biotechnol (2003) 30: 102–106 DOI 10.1007/s10295-002-0022-0
14. ^ Federal Register /Vol. 64, No. 158 /Tuesday, August 17, 1999 /Rules and Regulations
15. ^ "Over-the-counter drug products containing colloidal silver ingredients or silver salts. Department of Health and Human Services (HHS), Public Health Service (PHS), Food and Drug Administration (FDA). Final rule". Federal Register 64 (158): 44653–8. August 1999. PMID > 10558603 >. 
16. ^ ^{a b c d e} "About Herbs: Colloidal Silver". Memorial Sloan-Kettering Cancer Center. 2008-07-25. http://www.mskcc.org/mskcc/html/69189.cfm. Retrieved 2008-10-03. 
17. ^ ^{a b c d e f} Fung MC, Bowen DL (1996). "Silver products for medical indications: risk-benefit assessment". Journal of Toxicology 34 (1): 119–26. doi:10.3109/15563659609020246. PMID 8632503. 
18. ^ ^{a b} Wadhera A, Fung M (2005). "Systemic argyria associated with ingestion of colloidal silver". Dermatology Online Journal 11 (1): 12. PMID 15748553. http://dermatology.cdlib.org/111/case_reports/argyria/wadhera.html. 
19. ^ ^{a b c} Salt Lake Metals: Antibacterial effects of silver
20. ^ Grammaticos PC, Diamantis A (2008). "Useful known and unknown views of the father of modern medicine, Hippocrates and his teacher Democritus". Hellenic Journal of Nuclear Medicine 11 (1): 2–4. PMID 18392218. 
21. ^ Searle, A.B. (1920). "Chapter VIII: Germicides and Disinfectants". The Use of Colloids in Health and Disease. Gerstein - University of Toronto : Toronto Collection: London Constable & Co.. http://www.archive.org/stream/useofcolloidsinh00searuoft#page/70/mode/2up. 
22. ^ Roe, A. L. (1915). "COLLOSOL ARGENTUM AND ITS OPHTHALMIC USES". BMJ 1 (2820): 104. doi:10.1136/bmj.1.2820.104. PMC 2301624. PMID 20767446. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2301624. 
23. ^ MacLeod, C (1912). "ELECTRIC METALLIC COLLOIDS AND THEIR THERAPEUTICAL APPLICATIONS". The Lancet 179 (4614): 322. doi:10.1016/S0140-6736(01)66545-0. 
24. ^ Searle, A.B. (1920). "Chapter IX: Colloidal Remedies and Their Uses". The Use of Colloids in Health and Disease. Gerstein - University of Toronto : Toronto Collection: London Constable & Co.. http://www.archive.org/stream/useofcolloidsinh00searuoft#page/83/mode/1up. 
25. ^ "EIGHTY-FIRST ANNUAL MEETING OF THE British Medical Association". BMJ 2 (2759): 1282. 1913. doi:10.1136/bmj.2.2759.1282. 
26. ^ Akhavan, Omid; Ghaderi, Elham (2009). "Enhancement of antibacterial properties of Ag nanorods by electric field". Science and Technology of Advanced Materials 10: 015003. doi:10.1088/1468-6996/10/1/015003. 
27. ^ Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 1. U.S. National Academy of Sciences. 2004. p. 324. http://books.nap.edu/openbook.php?record_id=10942&page=324. 
28. ^ Solsona, Felipe; Juan Pablo Mendez (2003). "Water Disinfection" (PDF). World Health Organization. http://whqlibdoc.who.int/paho/2003/a85637.pdf. 
29. ^ Richmond, Caroline (2008-10-16). "Ron Rivera: Potter who developed a water filter that saved lives in the third world". The Guardian. http://www.guardian.co.uk/science/2008/oct/16/1. Retrieved 2009-05-16. 
30. ^ Corbett, Sara (December 24, 2008). "Solution in a Pot". New York Times. http://www.nytimes.com/2008/12/28/magazine/28rivera-t.html. Retrieved May 15, 2009. 
31. ^ Committee on Creation of Science-based Industries in Developing Countries, Development, Security, and Cooperation, Policy and Global Affairs, National Research Council of the National Academies, Nigerian Academy of Science. (2007). Mobilizing Science-Based Enterprises for Energy, Water, and Medicines in Nigeria. Washington, D.C: National Academies Press. p. 39. ISBN 0-309-11118-8. 
32. ^ "Drugs@FDA". Accessdata.fda.gov. http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/index.cfm?fuseaction=Search.DrugDetails. Retrieved 2010-07-10. 
33. ^ "MRSA, Mersa, Staph, Staff Infection, Treatment & Symptoms: MRSA Silver". Tahilla.typepad.com. 2005-11-09. http://tahilla.typepad.com/mrsawatch/wounds_silver/. Retrieved 2010-07-10. 
34. ^ Chopra, I. (2007). "The increasing use of silver-based products as antimicrobial agents: a useful development or a cause for concern?". Journal of Antimicrobial Chemotherapy 59 (4): 587–90. doi:10.1093/jac/dkm006. PMID 17307768. 
35. ^ Tian J, Wong KK, Ho CM et al. (January 2007). "Topical delivery of silver nanoparticles promotes wound healing". Chemmedchem 2 (1): 129–36. doi:10.1002/cmdc.200600171. PMID 17075952. 
36. ^ "Several Silver-Containing Wound Dressings: Abstract and Introduction". Medscape.com. 2006-03-23. http://www.medscape.com/viewarticle/525199. Retrieved 2010-07-10. 
37. ^ "Comparison of Two Silver Dressings for Wound Management in Pediatric Burns | WOUNDS". Woundsresearch.com. http://www.woundsresearch.com/content/comparison-two-silver-dressings-wound-management-pediatric-burns. Retrieved 2010-07-10. 
38. ^ Silver Antimicrobial Dressings in Wound Management: A Comparison of Antibacterial, Physical, and Chemical Characteristics ConvaTec Ltd, Flintshire, United Kingdom
39. ^ Lo SF, Hayter M, Chang CJ, Hu WY, Lee LL (2008). "A systematic review of silver-releasing dressings in the management of infected chronic wounds". Journal of clinical nursing 17 (15): 1973–85. doi:10.1111/j.1365-2702.2007.02264.x. PMID 18705778. 
40. ^ Vermeulen H, van Hattem JM, Storm-Versloot MN, Ubbink DT (2007). Vermeulen, Hester. ed. "Topical silver for treating infected wounds". Cochrane Database of Systematic Reviews (1): CD005486. doi:10.1002/14651858.CD005486.pub2. PMID 17253557. 
41. ^ ScienceDaily (May 21, 2008): Silver-coated Endotracheal Tube Dramatically Reduces Resistant Infections
42. ^ Silver-Coated Endotracheal Tube Reduces Risk for Ventilator-Associated Pneumonia, by News Author: Laurie Barclay, MD and CME Author: Penny Murata, MD - August 20 issue of the Journal of the American Medical Association.
43. ^ Loertzer H, Soukup J, Hamza A et al. (April 2006). "Use of catheters with the AgION antimicrobial system in kidney transplant recipients to reduce infection risk". Transplantation Proceedings 38 (3): 707–10. doi:10.1016/j.transproceed.2006.01.064. PMID 16647450. 
44. ^ "AGC Flat Glass Europe launches world's first antibacterial glass". 2007-09-04. http://www.agc-flatglass.eu/AGC+Flat+Glass+Europe/English/Homepage/News/Press+room/Press-Detail-Page/page.aspx/979?pressitemid=1031. 
45. ^ Cochrane Collaboration: Topical silver for preventing wound infection, 2009
46. ^ Fung MC, Weintraub M, Bowen DL (October 1995). "Colloidal silver proteins marketed as health supplements". JAMA 274 (15): 1196–7. doi:10.1001/jama.274.15.1196. PMID 7563503. 
47. ^ Newman M, Kolecki P (October 2001). "Argyria in the ED". Am J Emerg Med 19 (6): 525–6. doi:10.1053/ajem.2001.25773. PMID 11593479. 
48. ^ ^{a b c} "Over-the-counter drug products containing colloidal silver ingredients or silver salts. Department of Health and Human Services (HHS), Public Health Service (PHS), Food and Drug Administration (FDA). Final rule". Federal Register 64 (158): 44653–8. August 1999. PMID 10558603. 
49. ^ ^{a b} Okan D, Woo K, Sibbald RG (June 2007). "So what if you are blue? Oral colloidal silver and argyria are out: safe dressings are in". Adv Skin Wound Care 20 (6): 326–30. doi:10.1097/01.ASW.0000276415.91750.0f. PMID 17538258. "Colloidal silver suspensions are solutions of submicroscopic metallic silver particles suspended in a colloid base. These products deliver predominantly inactive metallic silver, not the antimicrobial ionized form." 
50. ^ Tien DC, Tseng KH, Liao CY, Tsung TT (October 2008). "Colloidal silver fabrication using the spark discharge system and its antimicrobial effect on Staphylococcus aureus". Medical Engineering & Physics 30 (8): 948–52. doi:10.1016/j.medengphy.2007.10.007. PMID 18069039. 
51. ^ van Hasselt P, Gashe BA, Ahmad J (April 2004). "Colloidal silver as an antimicrobial agent: fact or fiction?". Journal of Wound Care 13 (4): 154–5. PMID 15114827. http://www.internurse.com/cgi-bin/go.pl/library/article.cgi?uid=26606;article=JWC_13_4_154_155. 
52. ^ Kalouche H, Watson A, Routley D (August 2007). "Blue lunulae: argyria and hypercopprecaemia". Australas. J. Dermatol. 48 (3): 182–4. doi:10.1111/j.1440-0960.2007.00376.x. PMID 17680971. 
53. ^ Baker CD, Federico MJ, Accurso FJ (December 2007). "Case report: skin discoloration following administration of colloidal silver in cystic fibrosis". Curr. Opin. Pediatr. 19 (6): 733–5. doi:10.1097/MOP.0b013e3282f11fee. PMID 18025945. 
54. ^ Chang AL, Khosravi V, Egbert B (December 2006). "A case of argyria after colloidal silver ingestion". J. Cutan. Pathol. 33 (12): 809–11. doi:10.1111/j.1600-0560.2006.00557.x. PMID 17177941. 
55. ^ McKenna JK, Hull CM, Zone JJ (July 2003). "Argyria associated with colloidal silver supplementation". International Journal of Dermatology 42 (7): 549. doi:10.1046/j.1365-4362.2003.01899.x. PMID 12839605. 
56. ^ "Blue Man's Skin 'Lightening'". ninemsn staff. 2009-09-11. http://news.ninemsn.com.au/glance/861170/blue-mans-skin-lightening. Retrieved 2009-09-11. 
57. ^ ^{a b} Brandt D, Park B, Hoang M, Jacobe HT (August 2005). "Argyria secondary to ingestion of homemade silver solution". Journal of the American Academy of Dermatology 53 (2 Suppl 1): S105–7. doi:10.1016/j.jaad.2004.09.026. PMID 16021155. 
58. ^ Stepien KM, Morris R, Brown S, Taylor A, Morgan L (September 2009). "Unintentional silver intoxication following self-medication: an unusual case of corticobasal degeneration". Ann. Clin. Biochem. 46 (Pt 6): 520–2. doi:10.1258/acb.2009.009082. PMID 19729504. 
59. ^ Pamela L. Drake, M.P.H., National Institute for Occupational Health and Safety; Edmund Pribitkin, M.D., Thomas Jefferson University; and Wendy Weber, N.D., Ph.D., M.P.H., NCCAM (July 2009). Colloidal Silver Products. U.S. Department of Health and Human Services. http://nccam.nih.gov/health/silver/D209.pdf 
60. ^ Mirsattari SM, Hammond RR, Sharpe MD, Leung FY, Young GB (April 2004). "Myoclonic status epilepticus following repeated oral ingestion of colloidal silver". Neurology 62 (8): 1408–10. PMID 15111684. http://www.neurology.org/cgi/pmidlookup?view=long&pmid=15111684. 
61. ^ Rhee, DY, Chang, SE, Lee, MW, et al. Treatment of argyria after colloidal silver ingestion using Q-switched 1,064-nm Nd: YAG laser. Dermatol Surg 2008 July 24 [Epub ahead of print]
62. ^ Geyer O, Rothkoff L, Lazar M (December 1989). "Clearing of corneal argyrosis by YAG laser". The British Journal of Ophthalmology 73 (12): 1009–10. doi:10.1136/bjo.73.12.1009. PMC 1041957. PMID 2611183. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1041957. 
63. ^ "Science Links Japan | Generalized Argyria: A Therapeutic Trial with Q-switched Alexandrite Laser Irradiation". Sciencelinks.jp. 2009-03-18. http://sciencelinks.jp/j-east/display.php?id=000020032303A0734435. Retrieved 2010-07-10. 
64. ^ "ToxFAQs™: Silver". Atsdr.cdc.gov. 2010-07-19. http://www.atsdr.cdc.gov/tfacts146.html. Retrieved 2010-12-04. 
65. ^ Gaul LE, Staud AH (1935). "Seventy cases of generalized argyrosis following organic and colloidal silver medication, including a biospectrometric analysis of ten cases". JAMA 104 (16): 1387–90. doi:10.1001/jama.1935.02760160011004 (inactive 2009-12-07). http://jama.ama-assn.org/cgi/content/summary/104/16/1387. 
66. ^ Bryant BL (1940). "Argyria resulting from intranasal medication: a clinical and experimental study". Archives of Otolaryngology 31 (1): 127–39. doi:10.1001/archotol.1940.00660010128013 (inactive 2009-12-07). http://archotol.ama-assn.org/cgi/content/summary/31/1/127. 
67. ^ "Colloidal Silver Not Approved". U.S. Food and Drug Administration. 2007-02-12. http://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm127976.htm. Retrieved 2008-09-22. 
68. ^ "FDA Warning Letter". U.S. Food and Drug Administration. 2001-03-13. http://www.fda.gov/cder/warn/cyber/2001/Cyber097.pdf. Retrieved 2008-09-22. 
69. ^ "Regulation of colloidal silver and related products". Australian Therapeutic Goods Administration. 2005-11-09. http://www.tga.gov.au/docs/html/csilver.htm. Retrieved 2008-09-22. 
70. ^ ICON backgrounder: Environmental Impacts of Nanosilver, 2008

External links

• Colloidal Silver information from the National Center for Complementary and Alternative Medicine
• Final Rule on Colloidal Silver Drug Products - U.S. Food and Drug Administration
• "Complementary/Integrative Medicine Therapies: Colloidal Silver". M. D. Anderson Cancer Center. http://google.com/search?q=cache:jzq3x02xQhEJ:www.mdanderson.org/departments/cimer/display.cfm%3Fid%3Dca255d3c-2ca8-46ed-a19011aa9f45cd23%26method%3Ddisplayfull%26pn%3D5ac57a83-0f8d-4a3f-b743a0cdf23f193c+colloidal+silver+site:www.mdanderson.org&cd=1&hl=en&ct=clnk&gl=us. 
• "About Herbs: Colloidal Silver". Memorial Sloan-Kettering Cancer Center. http://www.mskcc.org/mskcc/html/69189.cfm.