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Cysteine protects Na,K-ATPase and isolated human lymphocytes from silver toxicity.

Metal-binding proteins are important components of retroviruses such as human immunodeficiency virus (HIV). Therefore, metals could be used as antiviral agents. However, most metals are toxic for humans with the exception of silver which is toxic only to prokaryotic cells and viruses. In addition, HIV infection causes a decrease in body cysteine. We formed a complex of silver and cysteine, named silver-cysteine. Healthy human lymphocytes were incubated with silver-nitrate or silver-cysteine. Negligible cell survival was seen at 50 microM silver-nitrate. However, in presence of 1 mM cysteine, the viability remained unaffected up to 1 mM of silver. Further, silver inhibition of isolated Na,K-ATPase was easily reversed by cysteine. Thus, non-toxic silver-cysteine could be used as an anti-viral and cysteine-replenishing agent.

Animals↗

Inhibition of bacterial adhesion on PVC endotracheal tubes by RF-oxygen glow discharge, sodium hydroxide and silver nitrate treatments.

Medical-grade poly(vinyl chloride) (PVC) was chemically modified to study how the incorporation of monovalent silver influences Pseudomonas aeruginosa adhesion and colonization. The modification investigated consisted of a radio frequency-oxygen (RF-O(2)) glow discharge pre-functionalization, followed by a two-step wet-treatment in sodium hydroxide and silver nitrate solutions. X-ray photoelectron spectroscopy (XPS) analysis and contact angle measurements were used to investigate the chemical nature and surface wettability of the films following each step of the modification. XPS analysis proved that the RF-O(2) plasma pre-functionalization of native PVC reproducibly increased the amount of functional groups representative of PVC additives, including ether/alcohol, esters and carboxyl groups. More specifically, we demonstrated that the O-C=O groups representative of the phthalic ester and zinc carboxylate additives identified for native PVC increased by two-fold following the RF-O(2) plasma pre-functionalization step. Although RF-O(2) pre-functionalization did not have an effect on the silver content of the NaOH/AgNO(3) treated substrates, such a modification was necessary for biomaterial products that did not have reproducible surfaces amongst production lots. XPS analysis also demonstrated that saponification with sodium hydroxide (NaOH) of esters, like those of the phthalic ester additives of PVC is a simple, irreversible method of hydrolysis, which produced sodium carboxylate and sodium phthalate salts. Exposure of native PVC to NaOH resulted in an increased surface hydrophilicity (from ca 90 degrees to ca 60 degrees ) due to dechlorination. XPS analysis following further incubation in silver nitrate demonstrated that silver ions can be trapped when the sodium of sodium carboxylate is replaced by silver after performing a second treatment with a monovalent silver-containing solution. The creation of silver salt on native PVC resulted in an ultra-hydrophobic (>120 degrees ) surface. The chemical modifications using NaOH and AgNO(3) wet treatments completely inhibited bacterial adhesion of four strains of P. aeruginosa to both native and oxygen-pre-functionalized PVC, and efficiently prevented colonization over longer periods (72 h). Our results suggest that surface modifications that incorporate silver ions would be extremely effective at reducing bacterial colonization to medical devices.

Bacterial Adhesion↗

Silver-coated megaendoprostheses in a rabbit model--an analysis of the infection rate and toxicological side effects.

Deep infection of megaprostheses remains a serious complication in orthopedic tumor surgery. Despite the use of systemic and local antibiotic prophylaxis the reported infection rate is between 5% and 35%. Silver-coated medical devices proved their effectiveness in reducing infections. The objective of this study was to examine in vivo the antimicrobial efficacy and possible side-effects of a silver-coated megaprosthesis. In a first study, 30 rabbits (15 titanium versus 15 silver-coated Mutars-endoprostheses) were infected with Staphylococcus aureus. In a second study, toxicological side effects were analyzed in 10 rabbits with a silver-coated megaprosthesis. The silver group showed significantly (p<0.05) lower infection rates (7% versus 47%) in comparison with the titanium group. Measurements of the C-reactive-protein, neutrophilic leukocytes, rectal temperature and body weight showed significant (p<0.05) lower signs of inflammation in the silver group. The analysis of the silver concentration in blood (median 1.883ppb) and in organs (0.798-86.002ppb) showed elevated silver concentrations without pathologic changes in laboratory parameters and without histological changes of organs. In conclusion, the new silver-coated Mutars-megaprosthesis resulted in reduced infection rates without toxicological side effects, suggesting that this prosthesis might be a promising device in tumor surgery exhibiting antimicrobial activity.

Animals↗

Silver ion release from antimicrobial polyamide/silver composites.

Silver ion (Ag(+)) the versatile antimicrobial species was released in a steady and prolonged manner from a silver-filled polyamide composite system. Metallic silver powder having varying specific surface area (SSA) has been used as a resource of biocide in polyamide. Strong evidences are found showing the release of the antimicrobial species from the resulting composite upon soaking it in water due to the interaction of the diffused water molecules with the dispersed silver powder within the matrix. The Ag(+) release was observed as increasing with time and concentration of the silver powder and is found to be influenced by the SSA of the silver powder, changes in the physical state of the composite specimen as a result of the water diffusion and the composite morphology. It is observed that the Ag(+) release increases initially which is followed by a marginal increase between day 4 and 6. Composites containing higher amounts of silver (4 and 8 wt%) exhibit a further rise in Ag(+) release from the sixth day of storage in water. Composite containing silver particles with the lowest specific surface area (0.78 m(2)/g) showed highest Ag(+) release. SEM shows a finer dispersion of the silver powder (4 wt%) having lowest SSA. However particles with higher (1.16 and 2.5 m(2)/g) SSA possess an agglomerated morphology leading to lower Ag(+) release. The composites are found to release Ag(+) at a concentration level capable of rendering an antimicrobial efficacy.

Anti-Bacterial Agents↗

Extracellular biosynthesis of silver nanoparticles using the fungus Aspergillus fumigatus.

Development of reliable and eco-friendly process for synthesis of metallic nanoparticles is an important step in the filed of application of nanotechnology. One of the options to achieve this objective is to use natural processes such as use of biological systems. In this work we have investigated extracellular biosynthesis of silver nanoparticles using Aspergillus fumigatus. The synthesis process was quite fast and silver nanoparticles were formed within minutes of silver ion coming in contact with the cell filtrate. UV-visible spectrum of the aqueous medium containing silver ion showed a peak at 420 nm corresponding to the plasmon absorbance of silver nanoparticles. Transmission electron microscopy (TEM) micrograph showed formation of well-dispersed silver nanoparticles in the range of 5-25 nm. X-ray diffraction (XRD)-spectrum of the silver nanoparticles exhibited 2theta values corresponding to the silver nanocrystal. The process of reduction being extracellular and fast may lead to the development of an easy bioprocess for synthesis of silver nanoparticles.

Aspergillus fumigatus↗

Bacterial resistance to silver in wound care.

Ionic silver exhibits antimicrobial activity against a broad range of micro-organisms. As a consequence, silver is included in many commercially available healthcare products. The use of silver is increasing rapidly in the field of wound care, and a wide variety of silver-containing dressings are now commonplace (e.g. Hydrofiber dressing, polyurethane foams and gauzes). However, concerns associated with the overuse of silver and the consequent emergence of bacterial resistance are being raised. The current understanding of the biochemical and molecular basis behind silver resistance has been documented since 1998. Despite the sporadic evidence of bacterial resistance to silver, there have been very few studies undertaken and documented to ascertain its prevalence. The risks of antibacterial resistance developing from the use of biocides may well have been overstated. It is proposed that hygiene should be emphasized and targeted towards those applications that have demonstrable benefits in wound care. It is the purpose of this review to assess the likelihood of widespread resistance to silver and the potential for silver to induce cross-resistance to antibiotics, in light of its increasing usage within the healthcare setting.

Anti-Infective Agents, Local↗

Silver enhancement of quantum dots resulting from (1) metabolism of toxic metals in animals and humans, (2) in vivo, in vitro and immersion created zinc-sulphur/zinc-selenium nanocrystals, (3) metal ions liberated from metal implants and particles.

Autometallographic (AMG) silver enhancement is a potent histochemical tool for tracing a variety of metal containing nanocrystals, e.g. pure gold and silver nanoclusters and quantum dots of silver, mercury, bismuth or zinc, with sulphur and/or selenium. These nanocrystals can be created in many different ways, e.g. (1) by manufacturing colloidal gold or silver particles, (2) by treating an organism in vivo with sulphide or selenide ions, (3) as the result of a metabolic decomposition of bismuth-, mercury- or silver-containing macromolecules in cell organelles, or (4) as the end product of histochemical processing of tissue sections. Such nano-sized AMG nanocrystals can then be silver-amplified several times of magnitude by being exposed to an AMG developer, i.e. a normal photographic developer enriched with silver ions. The present monograph attempts to provide a review of the autometallographic silver amplification techniques known today and their use in biology. After achieving a stronghold in histochemistry by Timm's introduction of the "silver-sulphide staining" in 1958, the AMG technique has evolved and expanded into several different areas of research, including immunocytochemistry, tracing of enzymes at LM and EM levels, blot staining, retrograde axonal tracing of zinc-enriched (ZEN) neurons, counterstaining of semithin sections, enhancement of histochemical reaction products, marking of phagocytotic cells, staining of myelin, tracing of gold ions released from gold implants, and visualization of capillaries. General technical comments, protocols for the current AMG methods and a summary of the most significant scientific results obtained by this wide variety of AMG histochemical approaches are included in the present article.

Animals↗

A large randomized clinical trial of a silver-impregnated urinary catheter: lack of efficacy and staphylococcal superinfection.

PURPOSE: The antibacterial activity of silver-containing compounds has recently been employed in constructing medical devices, such as vascular and urinary catheters, that may be effective in blocking infection. The present study was designed to evaluate the efficacy of a silver oxide-coated urinary catheter. PATIENTS AND METHODS: A total of 1,309 hospitalized patients who required placement of an indwelling urinary catheter for 24 hours or longer were randomly assigned to receive either a silicone catheter coated externally with 5% silver oxide or a standard silicone elastomer-coated latex catheter. Daily catheter-urine specimens were collected aseptically and catheter-care violations were monitored daily for the duration of the catheterization. RESULTS: Bacteriuria developed in 85 of 745 patients (11.4%) in the silver-coated catheter group and in 73 of 564 patients (12.9%) in the control group (P = 0.45). In women who did not receive antibiotics, the rates were 29.3% and 30.4%, respectively (P = 0.98). In men who did not receive antibiotics, the rate of bacteriuria was significantly higher with the silver-coated catheter (29.4% compared to 8.3%, respectively, P = 0.02). Staphylococcal species were isolated more often from the silver-coated catheter group than from the control group (25% versus 8% of all isolates, respectively, P = 0.002). CONCLUSIONS: This study, the largest ever reported evaluating any silver-impregnated device, has not only failed to demonstrate the efficacy of silver in prevention of catheter-associated bacteriuria, as suggested in prior studies, but it has also shown a significantly increased incidence of bacteriuria in male patients and a significantly increased occurrence of staphylococcal bacteriuria. These results suggest the need for caution and for similar large-scale trials before silver-containing compounds are widely used for preventing device-associated infections, both in vascular and urinary catheters.

Bacteriuria↗

Sensitivity of the spiny dogfish (Squalus acanthias) to waterborne silver exposure.

The physiological effects of waterborne silver exposure (added as AgNO(3)) on spiny dogfish, Squalus acanthias, were evaluated at 30, 200 and 685 microg silver per l in 30 per thousand seawater. These concentrations cover the toxic range observed for freshwater teleosts, where silver is extremely toxic, to seawater teleosts which tolerate higher silver concentrations. However, these levels are considerably higher than those that occur in the normal environment. At 685 microg l(-1), dogfish died within 24 h. Causes of death were respiratory as well as osmoregulatory failure. Arterial P(a)O(2) rapidly declined below 20 Torr, and blood acidosis (both respiratory and metabolic) occurred. Urea excretion increased dramatically and plasma urea dropped from 340 to 225 mM. There were pronounced increases in plasma Na(+), Cl(-), and Mg(2+), indicative of ionoregulatory failure due to increased diffusive permeability as well as inhibited NaCl excretion. At 200 microg l(-1), fish died between 24 and 72 h of silver exposure. The same physiological events occurred with a small time delay. At 30 microg l(-1), effects were much less severe, although slight mortality (12.5%) still occurred. Respiratory alkalosis occurred, together with moderate elevations in plasma Na(+) and Cl(-) levels. Silver accumulated to the highest concentrations on gills, with only low levels in the intestine, in accord with the virtual absence of drinking. Na(+)/K(+)-ATP-ase activities of gill and rectal gland tissue were impaired at the highest silver concentration. Normal gill function was impaired due to swelling and fusion of lamellae, lamellar aneurism and lifting of the lamellar epithelium. Our results clearly indicate that this elasmobranch is much more sensitive (about 10-fold) to silver than marine teleosts, with silver's toxic action exerted on the gill rather than on the intestine, in contrast to the latter.

Animals↗

A comparison of silver ion to streptavidin coated microplates.

Direct comparisons are made between covalently linked streptavidin and silver ion coated microplates. Both coatings can immobilize biotinylated molecules. Silver ion coated microplate wells can immobilize 1.8 times higher amounts of biotin labeled horseradish peroxidase. The quantitation range and capacity for the capture of horseradish peroxidase using biotin labeled horseradish peroxidase are also greater for silver ion coated microplates. Approximately twice as many anti-horseradish peroxidase antibodies can be immobilized per well using silver ion coated microplates. Higher capacities are presumed to be due to the smaller footprint of silver ions as compared to streptavidin. A direct comparison between the two coatings for a beta-galactosidase ELISA showed that while the silver ion coated microplates gave higher readings, the streptavidin coated microplates exhibited smaller well-to-well variation. However, higher well to well variation for the silver microplates is attributed to the high density of anti-beta-galactosidase antibodies on the microplates and the weak binding of clone GAL-13 to beta-galactosidase, rather than the silver coating. These studies suggest silver ion coated microplates are a desirable alternative to streptavidin plates for quantitative immunoassays.

Antibodies, Monoclonal↗

Theoretical consideration on preparing silver particle films by adsorbing nanoparticles from bulk colloids to an air-water interface.

In our previous paper, a method for preparing enormous surface-enhanced Raman scattering (SERS) active substrates through the aggregation of silver particles trapped at an air-water interface was reported. Here, further efforts were devoted to investigate the origin of assembling silver particle films by adsorbing nanoparticles from bulk colloids to the air-water interface. It was revealed that it is thermodynamically favorable for a colloidal particle in bulk colloids to adsorb to the air-water interface; however, a finite sorption barrier between it and the nearby particles usually restrains the adsorption process. When an electrolyte such as KCl, which is commonly used as an activating agent for additional SERS enhancement, was added into silver colloids, it largely reduced the sorption barrier. Thus, silver nanoparticles can break through the sorption barrier, pop up, and be trapped at the air-water interface. The trapped silver particles are more inclined to aggregate at the interface than those in bulk colloids due to the increase of van der Waals forces and the reduction of electrostatic forces. The morphology of the as-prepared silver particle films was characterized by scanning electron microscope, and their SERS activity was tested using NaSCN as a probe molecule. The surface enhancement of the silver particle films is about 1-2 orders of magnitude higher compared with that of silver colloids, because most of the silver particles in the films are in the aggregation form that provides enormous SERS enhancement. Furthermore, the stability of such type of films is much better that of colloid solutions.

Adsorption↗

Phase 1 evaluation of a local delivery device releasing silver ions in periodontal pockets: safety, pharmacokinetics and bioavailability.

A new local delivery device (LDD) capable of releasing silver in periodontal pockets has been developed and tested pre-clinically. Silver has potent antimicrobial effects on Gram-negative periodontal pathogens with a mean in vitro minimum bactericidal concentration (MBC) < or =0.5 microg/ml. This phase 1 study assessed the safety, pharmacokinetics and bioavailability of silver ions delivered intracrevicularly with a resorbable LDD (PocketGuard) in a group of 9 volunteers affected with periodontitis. In each subject, a PLGA/PEG LDD loaded with 12% silver nitrate (w/w) was inserted in each of 4 selected pockets > or =5 mm. Serum, gingival fluid and subgingival plaque samples were evaluated before and at various time points after LDD placement for 21 days. At each time point, the concentration of silver in gingival crevicular fluid (GCF) was quantified with an Inductively Coupled Plasma-Mass Spectrometer. Subgingival plaque samples were processed for evaluation of total anaerobic and aerobic counts (CFU/ml). The maximum mean silver concentration in GCF was 1,493 +/- 709 microg/ml (range 589-2,245). It decayed exponentially with a half-life of 7.1 +/- 6.1 days (2.7-20.4). Average silver concentrations in excess of 10 microg/ml were detected in each patient for 14 days after LDD placement with the average concentration for all patients in excess of 25 microg/mL at day 21. Total anaerobic counts decreased an average of 1.7 +/- 1.9 x 10(6) CFU/ml (p= 0.0078) from baseline to day 7, indicating that the silver was biologically active. A mild increase in cervical root discoloration was observed at day 21:0.25 +/- 0.31 stain index units. Discoloration that did not resolve spontaneously could be removed at the end of the study with polishing. No systemic effects were observed. It is concluded that local silver concentrations above the MBC in serum were maintained for at least 21 days. A specific microbiologic effect was also observed.

Absorbable Implants↗

Selective precipitation separation and inductively coupled plasma mass spectrometric determination of trace metal impurities in high purity silver.

A simple and rapid method for the determination of some trace element impurities in high purity silver, combining the isolation of analytes from the silver matrix with selective precipitation followed by ICP-MS determination was developed. On the basis of an extreme difference in the solubilities of the chlorides of silver and the other accompanying trace elements, silver can be separated completely through the addition of hydrochloric acid. The sample of silver was at first dissolved in 7 M nitric acid followed by addition of hydrochloric acid to remove the silver matrix by formation of a silver chloride precipitate, while leaving the trace element impurities in the solution, which was subsequently analysed by ICP-MS. Eleven elements (Al, Au, Cd, Co, Cu, Fe, Mg, Mn, Ni, Pb and Sn) were determined with good accuracy and precision. The limits of detection (based on the 3 sigma criterion) of these elements were 10(-1)-10(-3) ng g-1. The proposed method was successfully applied to the determination of metal impurities in high-purity silver samples (EM9465 and EM 9343) and validated by the analysis of NIST SRM 8171 (Fine Silver FS 14).

Chemical Precipitation↗

Xenobiotic metal-induced autoimmunity: mercury and silver differentially induce antinucleolar autoantibody production in susceptible H-2s, H-2q and H-2f mice.

Xenobiotic-metals such as mercury (Hg) and silver (Ag) induce an H-2 linked antinucleolar autoantibody (ANolA) production in susceptible mice. The mechanism for induction of ANolA synthesis is not well understood. However, it has been suggested that both metals interact with nucleolar proteins and reveal cryptic self-peptides to nontolerant autoreactive T cells, which in turn stimulate specific autoreactive B cells. In this study, we considered this suggestion and asked if mercury and silver display, if not identical, similar cryptic self-peptides, they would induce comparable ANolA responses in H-2 susceptible mice. We analysed the development of ANolA production in mercury- and/or silver-treated mice of H-2s, H-2q and H-2f genotypes. We found that while mercury stimulated ANolA synthesis in all strains tested, silver induced ANolA responses of lower magnitudes in only H-2s and H-2q mice, but not in H-2f mice. Resistance to silver in H-2f mice was independent of the dosage/time-period of silver-treatment and non-H-2 genes. Further studies showed that F1 hybrid crosses between silver-susceptible A.SW (H-2s) and -resistant A.CA (H-2f) mice were resistant to silver, but not mercury with regard to ANolA production. Additionally, the magnitudes of mercury-induced ANolA responses in the F1 hybrids were lower than those of their parental strains. The above differential ANolA responses to mercury and silver can be explained by various factors, including the different display of nucleolar cryptic peptides by these xenobiotics, determinant capture and coexistence of different MHC molecules. Our findings also suggest that the ability of a xenobiotic metal merely to create cryptic self-peptides may not be sufficient for the induction of an ANolA response.

Animals↗

Persistent silver disinfectant for the environmental control of pathogenic bacteria.

BACKGROUND: Contaminated surfaces can act as a reservoir for pathogenic microorganisms and potentially exacerbate the risk of infection. Surface disinfection and decontamination provide temporary amelioration against bacterial colonization. Disinfected surfaces eventually become contaminated, thus, mitigating the benefit of the initial disinfection. It is hypothesized that to improve on the current state of the art, a disinfectant should not only immediately disinfect a surface but also provide persistent antimicrobial action after the product has been applied. We describe here a silver-based disinfectant technology designed to provide long-lasting sanitization and disinfection to treated surfaces as evaluated on hard surfaces after repeated environmental insults. METHODS: A comparative evaluation of 6 disinfectant formulations for residual antimicrobial activity after water rinsing was performed. Log reduction of bacterial populations on disinfectant-treated substrates were measured after 30 minutes to 8 hours of exposure and compared with an untreated control. In a similar study, the residual antimicrobial activity of a silver disinfectant was evaluated against antibiotic- and biocide-resistant bacteria also after water rinsing. Further, residual antimicrobial activity of the silver disinfectant was measured after 5 cycles of rinsing, abrasion, and contamination against representative household and nosocomial pathogens (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Enterobacter aerogenes, Enterococcus faecium, or Salmonella choleraesuis) after 10-minute exposure times. RESULTS: In the comparative assay, only the silver disinfectant and a persistent quaternary ammonium compound disinfectant demonstrated significant residual activity (> or =3.0 log(10) reduction to control) against S aureus whereas only the silver disinfectant demonstrated activity against Pseudomonas. No residual activity (< or = 0.5 log reduction to untreated control) was observed for the other disinfectant products. The silver-based disinfectant also showed significant and equivalent efficacy against antibiotic- and silver-resistant bacteria. In addition, the silver disinfectant was able to achieve significant residual activity in 10 minutes against all organisms tested after 1, 3, and 5 cycles of water rinse, abrasion, and microbial contamination. CONCLUSIONS: The findings show the ability of a new silver-based disinfectant to reduce bacterial populations that contact treated surfaces within minutes, highlight the potential to interrupt cross-contamination from environmental surfaces, and reduce the risk of infection within the home and health care settings.

Bacteria↗

Water chloride provides partial protection during chronic exposure to waterborne silver in rainbow trout (Oncorhynchus mykiss) embryos and larvae.

Rainbow trout embryos and larvae were continuously exposed (at 12.5 degrees C) to waterborne silver in a flow-through setup, from fertilization to swim-up, at nominal silver concentrations of 0, 0.1, or 1.0 microg/L total silver (as AgNO(3)) at three different water Cl(-) levels (30, 300, and 3,000 microM, added as KCl). Exposures were conducted in synthetic soft water (hardness 20 mg CaCO(3)/L generated from reconstituted reverse osmosis freshwater). Continuous exposure to 1.0 microg/L total silver for 58 d at 30 microM water Cl(-) resulted in a pronounced ionoregulatory disturbance (as indicated by a reduction in whole body Na(+),K(+)-ATPase activity, unidirectional Na(+) uptake [Jin Na(+)], and whole body Na(+) and Cl(-) levels) and a reduction in extractable protein and wet weight. Thus, the mechanism of chronic silver toxicity appears to be similar to that observed during acute silver exposure in juvenile and adult fish, specifically an ionoregulatory disturbance. Higher water Cl(-) levels (300 and 3,000 microM Cl(-)) offered some degree of protection from the ionoregulatory disturbance, with only minor protective effects in terms of mortality. The protective effects of water Cl(-) on the toxicity of silver (as AgNO(3)) appear to be far less during chronic than during acute exposure. Mortality and larval Na(+) concentration, Jin Na(+), and Na(+),K(+)-ATPase activity all appear to be correlated with silver body burden and calculated water Ag(+) during chronic silver exposure. Thus, there appears to be potential to model chronic toxicity but not simply by recalibration of an acute model. A chronic model must be based on real chronic data because the protective effects of various ligands appear to be quantitatively very different from those in the acute situation.

Adenosine Triphosphatases↗

Anomaly and correlation of killing in the therapeutic properties of silver (I) chelation with glutamic and tartaric acids.

OBJECTIVES: To investigate whether silver chelates or silver ions are more effective as therapeutic agents, and to examine their mode of action so that safer and stable compounds that have a broad spectrum of therapeutic activities can be developed. METHODS: Efficacy was investigated against Pseudomonas aeruginosa (ATCC 15442) by determining MIC via a broth macrodilution procedure using NCCLS methods for antibiotic susceptibility testing. RESULTS: It was found that the responsible agent for silver therapeutic properties is the silver chelates rather than silver ions, contradicting previous findings, and the efficacy profiles mimic that of free silver ions present in solution. CONCLUSIONS: Silver therapeutic activities seem to be more effective as complexes-an intracellular package-rather than free silver ions, demonstrating that the effect of silver is linked to cells' DNA unwinding, and not respiratory or membrane functionality as was traditionally recognized.

Bacteria↗

Topical nanocrystalline silver cream suppresses inflammatory cytokines and induces apoptosis of inflammatory cells in a murine model of allergic contact dermatitis.

BACKGROUND: Nanocrystalline silver has both antimicrobial and anti-inflammatory properties. However, the exact mechanisms underlying these activities are not known. OBJECTIVES: The objectives of this study were to assess the anti-inflammatory effects of nanocrystalline silver using a murine model of allergic contact dermatitis, compare the effects with those of tacrolimus and a high potency steroid, and to relate the effects to modulation of pro-inflammatory cytokines and apoptosis of inflammatory cells. METHODS: Dermatitis was induced on the ears of BALB/c mice using dinitrofluorobenzene. Topical treatment, including vehicles, 1% nanocrystalline silver cream, tacrolimus ointment and a high potency steroid, was applied once a day for 4 days. Ear swelling was measured and the erythema was evaluated daily. After 4 days of treatment the mice were killed and samples from the ears were collected for histological and immunohistochemical examination, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labelling (TUNEL) staining and extraction of total RNA for reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Significant reductions of ear swelling, erythema and histopathological inflammation in mice ears were observed after 4 days of treatment with 1% nanocrystalline silver cream, tacrolimus ointment or a high potency steroid with no significant difference among them. Both RT-PCR and immunohistochemical staining of sections from ear biopsies demonstrated that nanocrystalline silver, tacrolimus and steroid significantly suppressed the expression of tumour necrosis factor (TNF)-alpha and interleukin (IL)-12. TUNEL staining demonstrated a significant increase in the numbers of apoptotic cells in material from the group treated with nanocrystalline silver when compared with that from groups treated with vehicle, tacrolimus or steroid. CONCLUSIONS: This study demonstrates that nanocrystalline silver inhibits allergic contact dermatitis in mice, similar to steroid and tacrolimus. Nanocrystalline silver suppresses the expression of TNF-alpha and IL-12 and induces apoptosis of inflammatory cells; mechanisms by which nanocrystalline silver may exert its anti-inflammatory effects.

Animals↗