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A discussion of silver as an antimicrobial agent: alleviating the confusion.

Within the last 3 to 5 years, many silver-based antimicrobial dressings have become available and more are on the way. However, sometimes dressing manufacturers and authors make claims and send messages that conflict with data and conclusions in the literature, creating confusion for clinicians. A literature review of six relevant and frequently discussed topics was conducted. Pre-clinical and clinical study data suggest that: a) bacterial resistance to silver may occur, b) silver dissociation is affected by the test medium used, c) bactericidal activity differences may be a function of the bacterial strain used for testing, d) higher rather than lower levels of silver may be needed because Ag+ binds to proteins and nucleic acids, e) rapid delivery of silver (ie, rate of kill) may be a positive factor when considering prevention of silver resistance and biofilm formation, and f) based on the vast majority of in vivo studies available, silver does not adversely effect viable cells; thus, is not cytototoxic. Continued research into the implications of the data is warranted.

Anti-Infective Agents, Local↗

Large-scale synthesis of single crystal silver nanowires by a sodium diphenylamine sulfonate reduction process.

Silver nanowires with high aspect ratios of up to more than 60 were synthesized on a large scale by the redox reaction between silver nitrate and sodium diphenylamine sulfonate at room temperature and in the absence of surfactant and hard-template and seed. When the molar ratio of reductant sodium diphenylamine sulfonate and silver nitrate < or =1, most products were all the nanowires. When the molar ratio increases to 2:1, silver nanowires and nanobelts were concomitantly formed. The redox product N, N'-diphenylbenzidinedisulfonate and sodium diphenylamine sulfonate all play an important role in the formation of silver nanostructures. The structure, morphology, and composition of the silver nanowires were characterized by the X-ray powder diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray energy dispersive microanalysis (EDX), and UV-Vis spectroscopy respectively. High-resolution transmission microscopy (HRTEM) and selected area electron diffraction (SAED) reveal the single-crystal nature of the silver nanowires.

Benzenesulfonates↗

Connective tissue responses to some heavy metals. III. Silver and dietary supplements of ascorbic acid. Histology and ultrastructure.

Silver-loaded ion exchange resin beads implanted into loose connective tissue of the rat pinna produced a local reaction. Initially the lesion comprised local necrosis and tissue disruption with predominantly small round cell infiltration. The subsequent organization was delayed and disordered. Fibroblasts developed grossly dilated cisternae of the rough endoplasmic reticulum. The matrix contained poorly orientated collagen fibrils of varying size and ground substance appeared condensed and granular. Distorted collagen fibrils were identified within membrane-bound vacuoles in the cytoplasm of both fibroblasts and macrophages. Abnormalities of the silver lesion were indicative of disordered collagen biosynthesis. Silver interfered with the biosynthesis and assembly of matrix components of the connective tissue. The reaction to silver beads in rats maintained on a diet heavily supplemented with ascorbic acid approached that of the control (sodium-loaded bead) with respect to the time scale, tissue reaction and tissue organization. The collagen matrix which formed was more organized and of greater density than that in the rat maintained on a normal diet. However, the repair tissue retained some of the morphological features of the legacy of silver toxicity, in particular delayed repair and dense intracellular fibrils within fibroblasts and macrophages. The excess of ascorbic acid partially ameliorated the effect of silver, possibly by compensating catabolysis of ascorbic acid caused by the presence of the released silver.

Animals↗

Colored silver-intensified gold technique for light microscopy.

The development of silver-intensified immunogold-labeled antibodies for light microscopy described by Fritz et al. (4) has been investigated. Principles and chemistries used in color photographic science have been applied to immunogold enhancement. In this technique, colloidal gold acts as the catalytic center for the reduction of silver ions to metallic silver with subsequent color development in the presence of hydroquinone. Silver ions and hydroquinone are adsorbed onto the surface of colloidal gold. The reduction of silver ions to metallic silver is further catalyzed by autometallography. The colored-SIG technique offers several advantages. It has sensitivity comparable to the silver-intensified gold (SIG) method and greater sensitivity than immunoenzymatic procedures, takes approximately one hour, results in one of three color reaction products (magenta, cyan, or yellow), and produces better contrast between the reaction products and the background (Figure 1). Thus, this method should prove useful in double- and even triple-staining procedures.

Gold↗

Scanning ion microscopy mapping of basement membrane elements and arterioles in the kidney after selenium-silver interaction.

The effects of selenium and silver salts was studied by scanning ionic microscopy during experimental argyria mapping of the different basement membrane elements. The ionic microscope (IMS 4F) was equipped with a high resolution spectrometer giving high spatial resolution on the image obtained. After long-term treatment with silver salt alone, silver and sulphur deposits were observed in the membranes. After administration of selenium and silver salt, it was possible to map nitrogen, sulphur, selenium and silver to the glomerular basement membrane as well as to the wall of the kidney arterioles. In the latter, sulphur, selenium and silver were localized only in the elastic laminae of the walls. This process of precipitation of silver deposits in the membrane can be interpreted as process of selenium "detoxification" of the organism.

Animals↗

Biocompatibility of silver-modified polyester for antimicrobial protection of prosthetic valves.

BACKGROUND AND AIMS OF THE STUDY: The biocompatibility of a silver-coated polyethylene terephthlate (PET, polyester) fabric for the inhibition of prosthetic valve endocarditis (PVE) associated with mechanical heart valves (MHVs) was assessed. The infrequency of PVE is outweighed by mortality rates commonly exceeding 50%. These high mortality rates have been attributed to the poor effect of antibiotic therapy on colonized valves and infected myocardial tissue. Silver has been used as an antimicrobial for centuries due to its general effectiveness and relative lack of toxicity. Our previous work has shown PET polyester fabric coated with metallic silver by an ion beam-assisted deposition (IBAD) process to: (i) be effective in vitro in the inhibition of microbial attachment and colonization; (ii) be tightly adherent and low leaching; and (iii) promote tissue ingrowth and the organization of tissue pannus in a short-duration (five weeks) sheep mitral mechanical heart valve model. METHODS: This paper addresses additional biocompatibility assessment consisting of a cell compatibility assay in which serum extracts of silver-coated fabric were exposed to fibroblasts for 48 hours, after which cell viability and function were measured. The amount of silver in the extract was measured using elemental analysis techniques. RESULTS: No signs of toxicity were seen in the cells until the extract concentration reached 1200 p.p.m. Ten-week duration mechanical valve replacement studies in sheep with uncoated or coated polyester sewing cuffs showed comparable tissue ingrowth and mature pannus with a suggestion of a thinner pannus on the silver-coated fabric. Additional antimicrobial testing confirmed the effectiveness of this coating in inhibiting colonization of polyester fabric. CONCLUSIONS: These current results, together with the earlier data, suggest that IBAD silver coating on polyester facilitates healing and may provide protection against PVE.

Animals↗

Controlling Legionella in hospital water systems: experience with the superheat-and-flush method and copper-silver ionization.

OBJECTIVE: To evaluate the effect of copper-silver ionization on Legionella colonization and nosocomial legionnaires' disease and to compare the efficacy of metal ions versus the superheat-and-flush method of disinfection. DESIGN: Prospective determination over a 36-month period of copper and silver ion concentrations in the recirculating hot-water system, Legionella colonization of the hospital water distribution system, and cases of nosocomial legionnaires' disease. Retrospective comparison of results with the previous 13 years, during which the superheat-and-flush method was used. SETTING: The Pittsburgh Veterans' Affairs Health Care System (University Drive Division) acute-care hospital. INTERVENTION: Three copper-silver ionization systems were installed on the hot-water distribution system in November 1994. RESULTS: The average number of cases of legionnaires' disease per year and the percentage of distal sites positive for Legionella pneumophila for the superheat-and-flush method versus the copper-silver ionization method was six cases with 15% positivity versus two cases with 4% positivity, respectively. The reduction in Legionella colonization after copper-silver ionization was significant (P<.05) compared to the superheat and flush. Mean copper and silver ion concentrations (mg/L) were 0.29 and 0.054 from hot-water tanks, and 0.17 and 0.04 from distal outlets, respectively. CONCLUSIONS: We conclude that a properly maintained and monitored copper-silver ionization system was more effective than the superheat-and-flush method for reducing the recovery of Legionella from the hospital water distribution system.

Copper↗

Induction of lesions of selenium-vitamin E deficiency in pigs fed silver.

Four weanling swine fed for 4 weeks a commercial ration adequate in selenium and vitamin E, but supplemented with 0.5% silver acetate, developed lesions typical of selenium-vitamin E deficiency. Clinically, the pigs fed this high level of silver had anorexia, diarrhea, and growth depression; 3 of 4 pigs died. At necropsy, hepatic lesions of hepatosis dietetica were present in 4 of 4 silver-fed pigs, and 1 of 4 pigs had cardiac and skeletal muscle lesions characteristic of selenium-vitamin E deficiency. Development of lesions and mortality was prevented in 2 pigs fed the silver diet supplemented with alpha-tocopherol (100 IU/kg of diet), but not in 2 pigs fed the ration supplemented with selenium as selenite (1 ppm). Four pigs fed a lower dose level of silver (0.2% silver acetate) for 6 weeks failed to develop clinical or pathologic features of selenium-vitamin E deficiency. However, hepatic selenium content was significantly increased in pigs fed the silver-supplemented ration.

Animals↗

Silver-resistant mutants of Escherichia coli display active efflux of Ag+ and are deficient in porins.

Silver-resistant mutants were selected by stepwise exposure of silver-susceptible clinical strains of Escherichia coli, two of which did not contain any plasmids, to either silver nitrate or silver sulfadiazine. These mutants showed complete cross-resistance to both compounds. They showed low-level cross-resistance to cephalosporins and HgCl2 but not to other heavy metals. The Ag-resistant mutants had decreased outer membrane (OM) permeability to cephalosporins, and all five resistant mutants tested were deficient in major porins, either OmpF or OmpF plus OmpC. However, the well-studied OmpF- and/or OmpC-deficient mutants of laboratory strains K-12 and B/r were not resistant to either silver compound. Resistant strains accumulated up to fourfold less (110m)AgNO3 than the parental strains. The treatment of cells with carbonyl cyanide m-chlorophenylhydrazone increased Ag accumulation in Ag-susceptible and -resistant strains, suggesting that even the wild-type Ag-susceptible strains had an endogenous Ag efflux activity, which occurred at higher levels in Ag-resistant mutants. The addition of glucose as an energy source to starved cells activated the efflux of Ag. The results suggest that active efflux, presumably coded by a chromosomal gene(s), may play a major role in silver resistance, which is likely to be enhanced synergistically by decreases in OM permeability.

Adenosine Triphosphate↗

The mitochondrial tricarboxylate carrier: unexpected increased activity in starved silver eels.

The tricarboxylate carrier was purified to homogeneity from liver mitochondria of European eel at the silver and the yellow stage and functionally reconstituted into liposomes. Unexpectedly, the molecular activity of the tricarboxylate carrier obtained from silver eel was about twofold higher than that of the same protein from yellow eel, although eels at the silver stage stop feeding. Parallel changes were found in the activities of the lipogenic enzymes in silver eels. This suggests a functional coordination between all these proteins sequentially involved in hepatic lipogenesis. Cardiolipin added to proteoliposomes strongly stimulated the activity of the purified tricarboxylate carrier from yellow eels, whereas it slightly reduced the activity of the same protein from silver eels. The higher activity of the tricarboxylate carrier from silver eels could therefore be ascribed, at least in part, to a different composition of the lipid domain surrounding the carrier protein, possibly in response to the hormonal alterations accompanying metamorphosis from yellow to silver stage.

Acetyl-CoA Carboxylase↗

Characterization of Silver-Containing Pitch-Based Activated Carbon Fibers.

Silver-containingpitch-based activated carbon fibers (ACFs) were prepared by activation with steam. Silver particles acted as catalyst by accelerating activation rate and increasing micropore size. Scanning electron microscopy (SEM) was used to investigate the surface morphology and behavior of silver particles in carbon fibers during activation. SEM images of the silver-containing fibers at about 70% burn-off were similar to those of nonactivated carbon fibers. Characterization of the ACFs studied was performed by using nitrogen adsorption isotherms, pore size distributions, silver content data, and adsorption capacities of iodine and methylene blue. Nitrogen adsorption isotherms and specific surface areas for the silver-containing ACFs were similar to those measured on the pure ACFs, i.e., ACFs to which silver had not been added. Also, adsorption capacities of iodine and methylene blue measured from liquid solutions were similar to those of the pure ACFs. However, the average micropore size of ACFs increased with increasing burn-off. Copyright 1999 Academic Press.

Journal Article↗

Age-related changes in sulfide-silver stainable fibres in the rat cerebral cortex.

The present study was designed to assess the age-dependent changes in sulfide-silver stainable fibres in frontal, parietal and occipital cortex areas of the rat cerebral cortex. Male Sprague-Dawley rats of 2 months (young), 12 months (adult) and 24 months (aged) were used. Sulfide-silver stainable fibres, which represent predominantly zinc-containing associational fibres arising from local cortical interneurons, were visualized using the neo-Timm histochemical technique. The density of sulfide-silver stainable fibres within the neuropil of laminae I-III (upper zone) and of lamina V (lower zone) of the different cerebral cortex areas was assessed microdensitometrically. In the frontal and parietal cortices the density of sulfide-silver stainable fibres was higher in adult and in aged than in young rats both in the upper and in the lower zones. No significant differences were noticeable in the density of sulfide-silver stainable fibres between adult and old rats. In the occipital cortex the density of sulfide-silver stainable fibres was similar in young or adult rats. but was remarkably increased in old animals. The possibility that the increase in the density of sulfide-silver stainable fibres represents a compensatory mechanism in the cerebral cortex area showing the most consistent nerve cell loss is discussed.

Journal Article↗

Phase transfer of oleic acid capped Ni(core)Ag(shell) nanoparticles assisted by the flexibility of oleic acid on the surface of silver.

The phase transfer protocols in vogue for the oleic acid capped silver nanoparticles, viz., salt-induced precipitation and redispersion or phosphoric acid-induced method, are examined and compared thoroughly. A comprehensive evaluation with respect to the mechanistic aspects involved is made and the merits and demerits of the different procedures are delineated. It is found that the salt-induced precipitation and redispersion is more versatile in that the precipitate can actually be redispersed in both aqueous and organic media. However, in terms of mechanism both the routes seem to be very similar wherein the orientational change of oleic acid on the silver surface in the two different environments-organic and aqueous-plays a crucial role in the adaptability of the system to the different environments. Subsequently, this change of orientation of oleic acid on silver surface in aqueous and organic media has been utilized to phase transfer Ni-based nanoparticulate systems. The nascent oleic acid-capped Ni nanoparticles, which were synthesized by a foam-based protocol, were dispersible in water but not in nonpolar organic media such as cyclohexane or toluene. Then, just by coating a thin shell of silver on them we could achieve complete phase transfer of the Ni(core)Ag(shell) from aqueous to organic media following similar procedures used for oleic acid-capped silver nanoparticles. Here, the phase transfer seems to be facilitated by the orientational flexibility of oleic acid on the silver surface as opposed to other metal surfaces as evidenced from the infrared and thermogravimetric analyses of oleic acid-capped Ni and Ni(core)Ag(shell) nanoparticles. This orientation-assisted phase transfer method could be generalized and can be adapted to other systems where, if the nascent nanoparticles cannot be phase transferred as is, they can be coated by a silver shell and oleic acid making them suitable for dispersion in both aqueous and organic media.

Journal Article↗

Influence of dentinal adhesives and a prefabricated post on fracture resistance of silver amalgam cores.

PURPOSE: Failures of silver amalgam cores for endodontically treated teeth have been attributed to the use of posts. The use of adhesive agents has been reported to improve the strength of silver amalgam restorations. The purpose of this study was to test the effects of two adhesive agents on the fracture resistance of silver amalgam cores with and without a post. MATERIAL AND METHODS: Sixty mandibular molars were restored with the use of silver amalgam, with or without one of the adhesive agents and/or a tapered prefabricated post. A universal testing machine, with a constant load rate of 0.5 mm/minute, was used to determine the force in kilograms at failure. RESULTS: The use of either adhesive agent with silver amalgam significantly increased the force at failure, and neither adhesive agent was significantly better than the other. Silver amalgam with a post and without an adhesive agent had the least resistance to fracture. CONCLUSIONS: The results indicated that endodontically treated mandibular molars restored with silver amalgam are more resistant to fracture when an adhesive agent is used.

Analysis of Variance↗

New riches in carbaporphyrin chemistry: silver and gold organometallic complexes of benzocarbaporphyrins.

The NH-N-NH-N core of the porphyrin system represents one of the best studied and most versatile platforms for coordination chemistry. However, the replacement of one or more of the interior nitrogens with carbon atoms would be expected to diminish the ability of these systems to form metallo derivatives considerably. Despite this expectation, carbaporphyrinoid systems have been shown to form stable organometallic derivatives. Although azuliporphyrins and benziporphyrins act as dianionic ligands, benzocarbaporphyrins are trianionic ligands. Treatment of five different meso unsubstituted benzocarbaporphyrins and two different meso tetraarylbenzocarbaporphyrins with excess silver(I) acetate afforded 65-97% yields of the corresponding silver(III) organometallic derivatives. The insertion of silver metal was confirmed by mass spectrometry and X-ray crystallography. The UV-vis spectra showed a strong Soret band at wavelengths between 437 and 451 nm, together with a series of Q-type bands at longer wavelengths. The new metallo carbaporphyrins demonstrate the presence of a strong diatropic ring current in their proton NMR spectra, and carbon-13 NMR spectroscopy indicates that the derivatives retain a plane of symmetry. The reaction of meso tetraaryl carbaporphyrins with gold(III) acetate afforded the related gold(III) complexes, and these also showed strongly porphyrin-like aromatic characteristics. The UV-vis spectra for the gold complexes again showed a strong Soret band between 437-439 nm, but a secondary band near 400 nm is somewhat intensified for the gold species compared to the spectra for the related silver(III) meso tetrasubstituted carbaporphyrins. The ring currents observed for the gold(III) complexes by proton NMR spectroscopy were comparable to those of the silver(III) derivatives, implying that both series have similar macrocyclic conformations. Cyclic voltammetry was performed on two different carbaporphyrins, their silver(III) derivatives, and a gold(III) complex. The silver complexes display a reversible cathodic wave that is assigned to the Ag(III/II) couple. However, the gold porphyrinoid gave a value for the reductive wave that could be due to a gold(III/II) couple or a ligand-based process.

Journal Article↗

Formation of water-soluble pincer silver(I)-carbene complexes: a novel antimicrobial agent.

Silver(I)-2,6-bis(ethanolimidazolemethyl)pyridine hydroxide (4a) and silver(I)-2,6-bis(propanolimidazolemethyl)pyridine hydroxide (4b) are water-soluble silver(I)-carbene complexes that were synthesized in high yield by reacting silver(I) oxide with N-substituted pincer ligands 3 (a = 2,6-bis(ethanolimidazoliummethyl)pyridine diiodide, b = 2,6-bis(propanolimidazoliummethylpyridine)pyridine dibromide). The X-ray crystal structure of 4a is a one-dimensional linear polymer, whereas the mass spectroscopy confirms a monomer in the gas phase. A change in the anion of 4a from a hydroxide to a hexafluorophosphate formed a silver(I)-carbene complex 4c that is dimeric in structure and insoluble in water. The bactericidal activities of the water-soluble silver(I)-carbene complexes were found to be improved over that of silver nitrate.

Anti-Bacterial Agents↗

A novel procedure for pre-embedding double immunogold-silver labeling at the ultrastructural level.

Pre-embedding double immunogold-silver labeling using two ultrasmall gold conjugates has not been attempted previously because a means of distinguishing labels by conjugates of identical sizes was lacking. This study investigated the feasibility of creating a particle size segregation between two ultrasmall gold conjugates through sequential immunogold incubations and silver enhancements. Two primary antibodies, mouse anti-synaptophysin and rabbit anti-glial fibrillary acidic protein (GFAP), were used in the model system. Differentiation of the double labeling was achieved by incubating with one ultrasmall gold conjugate, followed by silver enhancement, and then incubating with the second ultrasmall gold conjugate, followed by additional silver enhancement. This resulted in two groups of silver-enhanced particles: smaller particles enhanced once and larger particles enhanced twice. Electron microscopic examination revealed two readily distinguished populations of gold-silver particles within the appropriate structures, with very little size overlap. The quality of the ultrastructure permitted identification of most subcellular organelles. This procedure provides for the first time a pre-embedding immunogold-silver labeling protocol that allows the precise subcellular co-localization of multiple antigens.

Animals↗

Infrared absorption enhancement of C60 by overlaying thin silver island films.

Normal-incidence infrared absorption has been observed for silver overlaid C(60) thin films formed on surface-oxidized Si(111) substrates as a function of the silver or C(60) film thickness. The absorption spectra exhibit bands at 1429 and 1180 cm(-1) due, respectively, to the infrared active T(lu) (4) and T(lu) (3) modes of C(60) in multi-layers. Additionally, two bands appear at 1442 and 1370 cm(-1). The former band is caused by activation of the infrared inactive (Raman active) A(g) (2) mode via electron transfer from the silver to adsorbed C(60), and the latter is assigned to the T(1u) (4) mode red-shifted by the charge transfer. These bands are all enhanced in intensity dependent either upon the silver or C(60) thickness, i.e., the largest absorption enhancement is obtained for 25-monolayers-thick silver and 12-nm-thick C(60). Under atomic force microprobe inspection, the average size and height of the islands in the overlaid 25-monolayers-thick silver change with underlying C(60) film thickness. The influence of the C(60) film structure upon the silver film and in turn the absorption intensity is strongly suggested.

Journal Article↗