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Implant-associated infections remain a major issue in orthopaedics and antimicrobial functionalization of the implant surface by antibiotics or other anti-infective agents have gained interest. The goal of this article is to identify antimicrobial coatings, for which clinical data are available and to review their clinical need, safety profile, and their efficacy to reduce infection rates. PubMed database of the National Library of Medicine was searched for clinical studies on antimicrobial coated implants for internal fracture fixation devices and endoprostheses for bone surgery, for which study design, level of evidence, biocompatibility, development of resistance, and effectiveness to reduce infection rates were analyzed. Four different coating technologies were identified: gentamicin poly(d, l-lactide) coating for tibia nails, one high (MUTARS®) and one low amount silver (Agluna) technology for tumor endoprostheses, and one povidone-iodine coating for titanium implants. There was a total of 9 published studies with 435 patients, of which 7 studies were case series (level IV evidence) and 2 studies were case control studies (level III evidence). All technologies were reported with good systemic and local biocompatibility, except the development of local argyria with blue to bluish grey skin discoloration after the use of silver MUTARS® megaendoprostheses. For the local use of gentamicin, there is contradictory data on the risk of emergence of gentamicin-resistance strains, a risk that does not seem to exist for silver and iodine based technologies. Regarding reduction of infection rates, one case control study showed a significant reduction of infection rates by Agluna silver coated tumor endoprostheses. Based on socio-economic data, there is a strong need for improvement of infection prevention and treatment strategies, including implant coatings, in fracture care, primary and revision arthroplasty, and bone tumor surgery. The reviewed gentamicin, silver Agluna, and povidone-iodine technologies have shown a good risk benefit ratio for patients. Further data from randomized control trials are desirable, although this will remain challenging in the context of infection prevention due to the required large sample size of such studies.

Silver is used as a water disinfectant in hospital settings as well as in purifiers for potable water. Although there are no strict regulations on the concentration of silver in water, adverse effects such as argyria and respiratory tract irritation have been correlated to excess silver consumption. Based on this, the levels of silver in water are recommended to be maintained below 100 ppb to ensure safety for human consumption. In this work, we present a silver sensor for use in aqueous media that utilizes bathocuproine, a silver selective chromophore, adsorbed onto few-layer graphene (FLG) flake networks for the chemiresistive detection of silver. Complexation of silver to bathocuproine modulates the conductivity of the FLG film, which can be probed by applying a small voltage bias. The decrease in resistance of the film correlates with the concentration of silver in solution between 3 ppb and 1 ppm. Exposing the sensor to a lower pH resets the sensor, allowing it to be reused and reset multiple times. This sensor demonstrates a new pathway to chemiresistive cation sensing using known selective complexing agents adsorbed onto graphitic thin films. This concept can be expanded to the detection of other relevant analytes in domestic, industrial and environmental water sources.

Silver is used in a wide range of products, and during their production and use, humans may be exposed through inhalation. Therefore, it is critical to know the concentration levels at which adverse effects may occur. In rodents, inhalation of silver nanoparticles has resulted in increased silver in the lungs, lymph nodes, liver, kidney, spleen, ovaries, and testes. Reported excretion pathways of pulmonary silver are urinary and faecal excretion. Acute effects in humans of the inhalation of silver include lung failure that involved increased heart rate and decreased arterial blood oxygen pressure. Argyria—a blue-grey discoloration of skin due to deposited silver—was observed after pulmonary exposure in 3 individuals; however, the presence of silver in the discolorations was not tested. Argyria after inhalation seems to be less likely than after oral or dermal exposure. Repeated inhalation findings in rodents have shown effects on lung function, pulmonary inflammation, bile duct hyperplasia, and genotoxicity. In our evaluation, the range of NOAEC values was 0.11–0.75 mg/m3. Silver in the ionic form is likely more toxic than in the nanoparticle form but that difference could reflect their different biokinetics. However, silver nanoparticles and ions have a similar pattern of toxicity, probably reflecting that the effect of silver nanoparticles is primarily mediated by released ions. Concerning genotoxicity studies, we evaluated silver to be positive based on studies in mammalian cells in vitro and in vivo when considering various exposure routes. Carcinogenicity data are absent; therefore, no conclusion can be provided on this endpoint.

The use of colloidal silver-containing products as dietary supplements, immune boosters and surface disinfectants has increased in recent years which has elevated the potential for human exposure to silver nanoparticles particles and ions. Product mislabeling and long-term use of these products may put consumers at risk for adverse health outcomes including argyria. This study assessed several physical and chemical characteristics of five commercial products as well as their cytotoxicity using a rat intestinal epithelial cell (IEC-6) model. Concentrations of silver were determined for both the soluble and particulate fractions of the products. Primary particle size distribution and elemental composition were determined by transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS), respectively. Hydrodynamic diameters were measured using nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS). The effect of gastrointestinal (GI) simulation on the colloidal silver products was determined using two systems. First, physical and chemical changes of the silver nanoparticles in these products was assessed after exposure to Synthetic Stomach Fluid (SSF) resulting in particle agglomeration, and the appearance of AgCl on the surfaces and between particles. IEC-6 cells were exposed for 24 h to dilutions of the products and assessed for cell viability. The products were also treated with a three-stage simulated GI system (stomach and intestinal fluids) prior to exposure of the IEC-6 cells to the isolated silver nanoparticles. Cell viability was affected by each of the consumer products. Based on the silver nitrate and commercial silver nanoparticle dose response, the cytotoxicity for each of the colloidal silver products was attributed to the particulate silver, soluble silver or non-silver matrix constituents.

Medical and non-medical uses of silver are increasing. While the health benefits of silver therapy are widely claimed, few studies address the possible side effects of resistance, allergy, or skin discoloration. In this manuscript, a review of silver absorption, mechanism of action, allergy, microbial resistance and skin changes is presented. The ideal silver-delivery system is unknown. Most studies of side effects are animal or laboratory studies, which may not correlate with human experience. There is little correlation between serum silver levels, end-organ deposition and cytotoxic effects. The multiple mechanisms of antimicrobial action make true resistance unlikely. In microbes, genotypic resistance does not necessarily confer phenotypic resistance. Most cases of argyria occur from occupational exposure or from ingestion of colloidal silver rather than from topical application. Although toxicity, resistance and chronic skin changes are a theoretic concern, the lack of reported side effects despite widespread silver use is reassuring.

Dental amalgam restorations release mercury and silver which is absorbed and distributed in the body. Animal studies have shown that both elements may interfere with the host by activation of the immune system in genetically susceptible strains at exposure levels relevant to those from dental amalgam restorations. The aim of this study was to test the hypothesis of no change over time in concentrations of a number of immune mediators in serum after removal of all dental amalgam restorations in patients with health complaints attributed to their amalgam restorations and compare with a healthy reference group. Twenty patients previously examined at a specialty unit for health complaints attributed to dental materials were included in a clinical trial and had all amalgam restorations replaced with other dental restorative materials. Serum samples were collected before amalgam removal and 3 and 12 months after the removal was finished. Twenty blood donors matched for age and gender were used as comparison group. A fluorescent bead-based (Luminex) immunoassay kit was used to measure cytokines, chemokines and growth factors in serum. At baseline, the patient group had slightly higher values for GM-CSF, IL-6, IL-2R, IFN-alpha, IL-7, and IL-12p40/p70 compared with the reference group. After amalgam removal a decrease towards the median value of the reference group was found for GM-CSF, IL-8, and IL-7. In conclusion, removal of all dental amalgam restorations and replacement with other dental restorative materials was associated with decreased concentrations of Th1-type proinflammatory markers in serum.

Objective: All dental cast alloys release metal ions into the oral environment which have the potential to interact with the oral tissues. Amount and type of metal elements released are varying and not directly related to the composition of the alloy. The aim of the present literature survey was to describe the interactions of dental cast alloys with living tissues and to relate them to clinically adverse local reactions of the oral tissues. Results: Interactions of dental cast alloys with the oral tissues take place by different mechanisms; e.g. bacterial adherence promotion, toxic and subtoxic effects and allergy. Whereas bacterial adhesion promotion may be counteracted by adequate oral hygiene measures, the other mechanisms may lead to clinically adverse local reactions due to the metal present. However, the number of cases, where such a relation can be safely diagnosed, is small. Safe ground is felt with proven allergies. The comparatively high allergy rate towards nickel should be the impetus to replace those alloys whenever there is a suitable alternative. Medical and dental impairments as well as general medication may lead to symptoms allegedly attributed to metal restorations. Conclusions and Significance: Patients relating oral symptoms to metal restorations should be subjected to a thorough dental and general medical examination in order to exclude non-material related diseases being the cause for their complaints/symptoms. These cases are a challenge for the collaboration between the medical and dental professions.

Flat lesions of the eyelids are in most cases related to precancerous skin lesions or malignant tumors of the eyelids. Rarely, the following diagnoses can be established: alkaptonuria, Addison disease, argyrosis, or toxicity to systemic medications.

Argyria is grayish black discoloration of skin or mucous membrane caused by silver deposition; it may be localized or diffuse. Diffuse argyria occurs as a result of elevated silver levels in blood, whereas localized argyria occurs when there is direct deposition from an external source. Exposure to silver was common in the last century; however, in the present times, argyria is an uncommon entity because of the restrictive use of silver-containing medicines and decreased industrial exposure. Occupational exposure is common among silversmiths [1], mineworkers, photographic film laboratory workers, and individuals involved in the electroplating industry. Cases after prolonged use of silver salts for wound dressing, acupuncture needles, silver earrings [2], eyedrops containing silver, and irrigation of urethral or nasal mucous membranes with silver-containing solutions have been reported. Argyria has also been seen among patients undergoing dental procedures, such as silver amalgam tattooing. 2. Case presentation A 66-year-old man had nasal blockage and intermittent drainage from both nares for many years. The drainage was watery and persistent even after being treated with multiple medications. Nasal examination revealed bilateral bluish black pigmentation of mucosa in the superior-anterior portion of the nasal septum. There was no other area of pigmentation either on the skin or elsewhere. The patient’s history is significant for stroke, myocardial infarction, and hypertension. He worked as a supervisor in the chemical sensitizing paper unit of a photographic film–producing company before retiring in 1992 and was exposed to a large number of chemicals, including silver nitrate. In 2004, a computed tomographic scan of the patient’s paranasal sinuses showed minimal mucosal thickening in the left maxillary sinus. A small biopsy specimen of the pigmented nasal mucosa was taken under local anesthesia and sent for routine histopathologic analysis. Subsequently, analysis using scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy (EDS) was also performed.

Dry silver sulfadiazine (AgSD) is not light sensitive but shows a greenish-blue r.t. photoluminescence at λmax = 482 nm which is suggested to originate from an IL triplet. In the presence of water AgSD undergoes a partial hydrolysis with the formation of free sulfadiazine (HSD) which has been previously shown to be photoreactive. Moreover, irradiation of an aqueous suspension of AgSD leads also to the photoreduction of Ag+ to elemental silver. This photolysis might explain the origin of argyria which can occur when AgSD in contact with human skin is exposed to sun light

Silver sulfadiazine cream is a topical antibacterial agent that combines the antibacterial effects of both silver and sulfadiazine. Its reported cutaneous side effects include hypersensitivity reactions, allergic contact dermatitis, erythema multiforme, and systemic argyria. We report the case of a patient who had localized argyria develop in a scar after the use of silver sulfadiazine cream. In this case, the silver sulfadiazine cream was applied to and argyria developed within a postsurgical wound and area of severe contact dermatitis.

A case of localized argyria with chrysiasis caused by implanted acupuncture needles in a 41-year-old Japanese woman was studied by electron microscopy and x-ray microanalysis. Large amounts of silver granules with selenium and sulfur were detected around eccrine secretory cells in much greater amounts than around ductal cells. Many granules were also observed along the outer edge of the basement membrane but never within cells or intercellular spaces. The granules were also present around blood vessels, lymphatics and nerve fibers, and in elastic fibers. Small numbers of gold fragments were also seen, mostly within macrophages. These results suggest that silver deposits extracellularly as selenide and sulfide, whereas free gold is found intracellularly.

A mesangiopathic glomerulonephritis with prominent mesangial immunoglobulin deposits was induced in mice by single or multiple intraperitoneal injections of bovine serum albumin. The silver-labelled basement membrane in mice which had ingested 6mM silver nitrate in drinking water proved a useful marker indetermining that the immune deposits were on the intracapillary aspect of the basement membrane.

The present paper provides a description of the ultrastructural localization of silver deposits in eyes of adult rats exposed to silver either perorally or intraperitoneally. Silver was found in lysosomes of most cell types, an exception being the neural retina. Extracellularly, silver was present in vascular basal laminae and in connection with connective tissue fibers. Systemic silver intoxication was found to result in a rapid and long-lasting deposition of the metal in the eye.

Several categories of chemical and pharmacologic agents can cause alterations in cutaneous pigmentation, although the mechanisms differ and in several instances may be unknown. Fixed drug eruptions appear to have alteration of the basement membrane zone with incontinence of epidermal pigment as the mechanism of hyperpigmentation. Heavy metals produce increased pigmentation in part from deposition of metal particles and in part from an increase in epidermal melanin production. The antimalarials may bind to melanin. The phenothiazines and minocycline produce pigmentation from deposition of the drug. The mechanism, site, and nature of the pigment occurring with antineoplastic agents is not well understood, but the location is most likely predominantly epidermal. Clofazimine (Lamprene) alteration in pigmentation appears to result from deposition of the drug in subcutaneous fat.

The use of amalgam as a restorative material in dentistry is axiomatic. Its use in endodontics as a retrofilling material is well documented. Studies dealing with the biocompatibility of amalgam indicate that it is well tolerated in soft tissue 14 and cell cultures, s Some authors 6 have suggested that amalgam may even be less irritating than gutta-percha. Silver amalgam is presently the preferred material in endodontic surgery that requires a retrograde filling. The use of zinc-containing alloy has been challenged by.Omnell 7 because it was believed to have resulted in the formation of a zinc-carbonate precipitate in association with a root canal containing a post. The zinc-carbonate combination was believed to have been responsible for the eventual failure of the case reported in the literature. However, other authors 811 have shown little if no difference between zinccontaining and zinc-free amalgam. Although not as popular today as in the past, two root canal sealers (Kerr and AH-26) contain precipitated silver for increased radiopacity. In 1960, Orban and Wentz 12 reported localized argyria after obturation using root canal cement that contained silver. Localized argyria has also been repoted by KirchoW 3 after surgical endodontic treatment in teeth containing silver cones. On occasion, we have seen soft tissue argyria in teeth that have undergone root resection, which were obturated with guttapercha using a silver-containing sealer. The following case report describes an intraosseous discoloration strongly suggestive of argyria. It was associated with chronic periapical inflammation in an endodontically treated tooth. The root canal sealer was suspected of being the causative factor.

Argyria or chronic silver poisoning, once a fairly common condition, has now become a rare disease for reasons set forth in the body of this paper. Afflicted persons present an appearance of such startling singularity that in a pronounced case the diagnosis is unmistakable. The silver permeates the entire body and is deposited in all organs and tissues in the form of minute granules without producing the usual foreign body reactions. Argyria has not yet been mentioned in the gynecologic literature of the world because all published records deal only with men or children. A fortuitous chance gave the author the opportunity to remove the uterus in a woman with a very pronounced argyria and to add his histologic studies of this organ to the chapter on chronic silver poisoning.

Presented are a case report and discussion of a pigmented lesion of the gingiva, localized argyria, which can arise after endodontic treatment combined with apical surgery. Included are a pathologist's report and comments and a suggestion for prevention of this unesthetic lesion.

Argyria of the uterus and tube is of relatively little clinical importance in itself. However, in the connective tissue of the cutis only a definite amount of silver can be stored, otherwise general argyria may a.ppear. By any former application of silver the deposits mav be close to this threshhold. Then the additional absorption of a relat&ly small amount of silver may lead to discoloration of the skin. In cases of otherwise unaccountable argyria in women, t,he possibility of absorption from a silver pessary should be kept, in mind.

Systemic argyria can result from the ingestion of silver salts or silver protein colloids. A case of systemic argyria that has persisted for 16 years secondary to chewing of photographic film is reviewed.

A case of argyria secondary to chronic use of nose drops containing silver iodide is presented. The patient was initially referred to a cardiovascular surgeon for surgical correction of possible cyanotic heart disease. A brief review of the history and literature of argyria is presented. Since the pigmentary changes of argyria cannot be reversed once they have occurred, a plea is made to eliminate the exogenous use of silver-containing medications and to reduce exposure to the sun in those patients already affected in order to reduce the degree of pigmentation. It behooves physicians to become cognizant of the existence of argyria in the differential diagnosis of cyanosis of unknown origin.