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Silver-induced lipid peroxidation in mice: interactions with selenium and nickel.

Lipid peroxidation in silver-treated mice was assayed by measuring the malondialdehyde (MDA) content of liver, kidney and brain tissue. After a single intraperitoneal injection of 20 mg/kg silver lactate, lipid peroxidation was significantly increased in the liver 3, 12 and 48 h after exposure whereas MDA levels in kidney and brain were not significantly affected. Pretreatment with 2 mg/kg sodium selenite i.p. for 2 days resulted in an increase in silver-induced lipid peroxidation in the liver. Liver from mice treated with 20 mg/kg silver lactate followed by an injection of 35 micrograms/kg nickel chloride had significantly higher contents of MDA than did livers from mice treated with either silver or nickel alone, suggesting a synergism between silver and other lipid peroxidation-inducing compounds.

Animals↗

Combined use of topical cyclosporin A and silver sulphadiazine on allografts infected with Pseudomonas in burned rats.

In this study, we investigated the effects of a combination of topical Cyclosporin A (CyA) and silver sulphadiazine on infected and normal skin allografts in burned and unburned rats. Buffalo (Buf) allografts on unburned Lewis (Lew) recipients survived 16.8 +/- 0.9 days after a 10-day course of topical CyA and silver sulphadiazine, as compared to 7.4 +/- 1.1 days for untreated allografts and 18.6 +/- 0.9 days for those receiving CyA only for 10 days. Allografts infected with Pseudomonas aeruginosa and placed on burned recipients survived significantly longer (13.7 +/- 1.1 days) when treated with silver sulphadiazine and topical CyA for 7 days compared to a similar group of animals treated with silver sulphadiazine alone (8.4 +/- 1.0 days). The mortality rate for burned, infected and allografted animals receiving no medication or topical CyA was 50 per cent compared with zero in animals treated with silver sulphadiazine only or combined silver sulphadiazine and topical CyA.

Administration, Topical↗

Effect of cerium nitrate-silver sulphadiazine on deep dermal burns: a histological hypothesis.

Although there are excellent clinical results from using cerium nitrate plus silver sulphadiazine in the treatment of deep dermal burns in our burn centre, its mechanism of action remains unexplained. We set up a prospective study to establish a hypothesis which could explain the formation of the typical leathery crust. Burns treated with cerium nitrate plus silver sulphadiazine and silver sulphadiazine alone were compared histologically and metallurgically. Application of cerium nitrate plus silver sulphadiazine on deep dermal burns caused superficial connective tissue calcification with few deep dermal changes. Cerium penetration was low and silver was never detected intradermally. The precipitation of cerium and pyrophosphate destroys the calcification inhibitory function of the latter, creates multiple calcification nuclei and leads to superficial dermal calcification. No calcium was detectable in biopsies from silver sulphadiazine-treated wounds. No major toxicological side-effects were seen during this study. The clinical results were favourable, as have been reported previously.

Adolescent↗

Effects of silver in isolated rat hepatocytes.

Addition of silver nitrate or silver lactate to freshly isolated hepatocytes caused dose-dependent loss of cell viability, measured by trypan blue exclusion, at concentrations within 30-70 microM. Silver cytotoxicity was accompanied by a decrease in hepatic thiol concentration and an increase in lipid peroxidation. Treatment of hepatocytes with the reduced glutathione (GSH)-depleting agent diethylmaleate markedly increased their vulnerability to silver toxicity whereas protective effects were produced by the thiol-reducing agent, dithiothreitol. Both alpha-tocopherol, which protected from the onset of silver-associated lipid peroxidation, and the iron chelator agent, deferoxamine failed to prevent loss of cell viability. These data suggest that perturbation of intracellular thiol homeostasis may play a critical role in the mechanism underlying silver-induced lethal damage to isolated rat hepatocytes.

Animals↗

Effect of silver-coated urinary catheters: efficacy, cost-effectiveness, and antimicrobial resistance.

BACKGROUND: Urinary tract infections (UTIs) are the most common nosocomial infection experienced by patients in United States hospitals and are responsible for significant morbidity and excess hospital costs. The purpose of this study was to determine the efficacy of a silver alloy, hydrogel-coated, urinary catheter in the prevention of catheter-associated UTI, to assess the cost effectiveness of the coated catheter, and to test for the emergence of silver-resistance in urinary microbial isolates. METHODS: A 2-year prospective surveillance study in 10 patient care units was conducted to determine the rate of catheter-associated UTI. Historic control data was utilized to assess the effect of the coated catheter. A cost-effectiveness analysis was conducted using a range of cost estimates. Silver susceptibility was determined for microbes responsible for catheter-associated UTI. RESULTS: Data were analyzed using a Poisson regression model. The rate of catheter-associated UTI fell from 6.13/1000 catheter-days during the period 1999-2000 to 2.62/1000 catheter-days during 2001-2002 ( P = .002). Calculated cost savings varied widely. Modest savings were achieved at the realistic lower cost estimates. No silver-resistant microbes were recovered in the susceptibility tests. CONCLUSIONS: The introduction of a silver alloy, hydrogel-coated urinary catheter was associated with a significant decline in nosocomial UTI and cost savings over the range of cost estimates. Silver-resistant urinary pathogens were not recovered from patients experiencing catheter-associated UTI during the study period.

Anti-Bacterial Agents↗

In vitro anti-tumour and cyto-selective effects of coumarin-3-carboxylic acid and three of its hydroxylated derivatives, along with their silver-based complexes, using human epithelial carcinoma cell lines.

The chemotherapeutic potential of coumarin-3-carboxylic acid (C-3-COOH) and a series of three hydroxylated coumarin-3-carboxylic acid ligands, namely 6-hydroxy-coumarin-3-carboxylic acid (6-OH-C-3-COOH), 7-hydroxy-coumarin-3-carboxylic acid (7-OH-C-3-COOH) and 8-hydroxy-coumarin-3-carboxylic acid (8-OH-C-3-COOH), along with their corresponding silver-based complexes, namely 6-hydroxycoumarin-3-carboxylatosilver (6-OH-C-COO-Ag), 7-hydroxycoumarin-3-carboxylatosilver (7-OH-C-COO-Ag) and 8-hydroxycoumarin-3-carboxylatosilver (8-OH-C-COO-Ag), was determined using two human-derived carcinoma (A-498 and Hep-G2), along with two non-carcinoma human-derived cell lines (CHANG and HK-2). All of the ligands and their silver complexes induced a concentration-dependent cytotoxic effect. Furthermore, hydroxylation of C-3-COOH and its subsequent complexation with silver led to the production of a series of compounds with dramatically enhanced cytotoxicity, with 6-OH-C-3-COO-Ag having the greatest activity. Additionally, all of the metal-based complexes were selectively cytotoxic to both carcinoma-derived cell lines, relative to normal renal and hepatic cells. In comparative studies with cisplatin, and based on the IC(50) values obtained with Hep-G2 cells, it appeared that the coumarin-silver complexes were between 2 and 5.5 times more cytotoxic than cisplatin. All of the coumarin-silver complexes inhibited DNA synthesis, which did not appear to be mediated through intercalation. Furthermore, results obtained from Ames tests showed that all of the test agents and their phase I metabolites were non-mutagenic. Taken together, these findings suggest that both hydroxylation particularly in the 6th position and complexation with silver, served to significantly augment the cytotoxic properties of C-3-COOH, to yield a compound which acts as a cyto-selective agent, as it is a significant killer of cancer, relative to normal cells. We suggest that this group of compounds may have a therapeutic role to play in the successful treatment and management of cancer in man.

Antineoplastic Agents↗

Effects of silver nanoparticles on the fluidity of bilayer in phospholipid liposome.

This paper describes the formation and characterization of liposome entrapping the silver nanoparticles in bilayer. Silver nanoparticles were entrapped in the bilayer of dipalmitoylphosphatidylcholine (DPPC) liposome, named as silver-loaded liposome. Specifically, above the gel to liquid-crystalline phase transition temperature of this lipid (i.e., 41 degrees C), it was observed that membrane fluidities of silver-loaded liposomes were increased, and fluorescence anisotropy values were reduced from 0.114 to 0.097. This might be due to the structural modifications and interactions between DPPC molecules and silver nanoparticles within the bilayer. It was also confirmed that silver nanoparticles were entrapped in hydrophobic region of lipid bilayer with transmission electron microscopy (TEM) and electron energy loss spectroscopy (EELS) measurements.

1,2-Dipalmitoylphosphatidylcholine↗

Fundamental considerations on the mechanisms of silver cementation onto zinc particles in the Merril-Crowe process.

Studies on the Merrill-Crowe process as applied to silver recovery have shown that one half of the used zinc powder is wasted in water reduction at high cyanide concentrations, while the other half reduces silver ions from the cyanide solution. However, the cementation mechanisms as an electrochemical process taking place on the zinc surface do not explain the split of the electric current resulting from the anodic dissolution of zinc into two equal values. This study demonstrates that the mechanism for silver precipitation at high and low cyanide concentrations differs considerably. At low cyanide concentrations cementation is essentially an electrochemically-controlled process following a shrinking-core behavior. At high cyanide concentrations, the process seems not to be electrochemically controlled. The areas for zinc dissolution and silver deposition are not connected by an electrical-conducting medium and reduction of silver-cyano complex ions takes place by hydrogen adsorbed onto silver growing outward from the cementing zinc particles. The results are based on scanning electron microscopy of solids recovered from cementations in stirred reactors and in situ observations by optical microscopy of the cementation process on the edge of thin zinc disks in cyanide solutions.

Adsorption↗

Surface-enhanced Raman scattering of a series of n-hydroxybenzoic acids (n = P, M and O) on the silver nano-particles.

Surface-enhanced Raman scattering (SERS) spectra of a series of n-hydroxybenzoic acids (n-HBA, n = P, M and O) adsorbed on the silver nano-particles were studied, respectively, in the silver colloidal solution and on the dried silver-coated filter paper. On the same substrate, the different molecules' SERS spectra were different, while on the different substrates the same molecules' SERS spectra were also different. Significant changes were found in the SERS spectra of PHBA molecules adsorbed on the two substrates, and the changes found in MHBA's spectra on two substrates were next to PHBA's, while almost no changes were found in the spectra of OHBA molecules. Moreover, it was found, on the filter paper, that the SERS spectra of the same molecules would change with the coverage density of the silver nano-particles. The analyses showed that the origins of these changes were the different adsorption behavior of molecules adsorbed on the silver nano-particles. Because in these three molecules the relative positions of the carboxyls and hydroxyls on the benzenes are different, the adsorption behaviors of these three molecules adsorbed on the silver surfaces are also different. The experimental results suggest that the surface characteristic of the substrate and the surface configuration of the adsorbate could exert a great influence on the adsorption behavior of the adsorbates on the substrates.

Adsorption↗

Roughened silver electrodes for use in metal-enhanced fluorescence.

Roughened silver electrodes are widely used for surface-enhanced Raman scattering (SERS). We tested roughened silver electrodes for metal-enhanced fluorescence. Constant current between two silver electrodes in pure water resulted in the growth of fractal-like structures on the cathode. This electrode was coated with a monolayer of human serum albumin (HSA) protein that had been labeled with a fluorescent dye, indocyanine green (ICG). The fluorescence intensity of ICG-HSA on the roughened electrode increased by approximately 50-fold relative to the unroughened electrode, which was essentially non-fluorescent and increased typically two-fold as compared to the silver anode. No fractal-like structures were observed on the anode. Lifetime measurements showed that at least part of the increased intensity was due to an increased radiative decay rate of ICG. In our opinion, the use of in situ generated roughened silver electrodes will find multifarious applications in analytical chemistry, such as in fluorescence based assays, in an analogous manner to the now widespread use of SERS. To the best of our knowledge this is the first report of roughened silver electrodes for metal-enhanced fluorescence.

Electrodes↗

Antibacterial activity of silver ions implanted in SiO2 filler on oral streptococci.

OBJECTIVE: To evaluate the role of silver ions in composite resin dental materials, an in vivo investigation was conducted into the antibacterial effect of SiO2 filler implanted with silver ions on oral streptococci. METHODS. SiO2 filler samples (0.1g) were implanted with silver ions. The effect of the filler with silver ions (Ag+ filler) was tested on oral streptococci bacteria. These bacterial strains had been isolated predominantly from composite resin surfaces. The organisms tested were anaerobically cultured in 5 mL Trypticase Soy Broth containing 0.5 per cent yeast extract at 37 degrees C for 10-12 h. Each bacterial strain was adjusted to a concentration of 1 x 10(6) cells per mL with reduced transport fluid (RTF). Ag+ filler was immersed in 1 mL of RTF and anaerobically incubated 2, 6 and 12 h to study the antibacterial effect. The survival of bacteria was then estimated by culturing on TSBY agar plates. A plate with approximately 100 discrete colonies was chosen from the serial agar cultures, and the number of colonies was counted at each sampling time. RESULTS: The Ag+ filler showed significantly more antibacterial activity than the control filler without silver ions. SIGNIFICANCE: These results indicate that the antibacterial effect found in this study was due to the silver ions released by the Ag+ filler and that it may be useful to add this filler to composite resin dental materials for secondary caries protection.

Anti-Infective Agents, Local↗

Silver coated materials for external fixation devices: in vitro biocompatibility and genotoxicity.

The most significant complication in external fixation is pin tract infection causally related to the highly adaptive ability of bacteria to colonise the surfaces of "inert" biomaterials or of adjacent damaged tissue cells. The hypothesis that coating a pin with a silver-containing compound will decrease bacterial colonisation and/or pin tract infection has been confirmed in other studies in vitro and in vivo experiments. In this work, biocompatibility of silver-coated orthopaedic external fixation pins was compared with stainless steel controls in an in vitro study. Human peripheral blood lymphocytes were used to assess the possible genotoxic effect of silver, studying the frequency of sister-chromatid exchanges and micronuclei while fibroblasts (NIH 3T3) and osteoblast-like cells were used for cytotoxicity and cytocompatibility studies. These studies have shown that silver is neither genotoxic nor cytotoxic as compared to stainless steel, a material in wide use as a metal implant. At 4 days cells cultured on the silver-coated material evidenced good cell spreading and a higher cell count with respect to the uncoated material. It appears that the addition of silver onto implantable medical devices could be beneficial when specific biological properties, such as antibacterial behaviour, are required. Based on these and the previous bacterial studies it seems like the toxicity towards bacteria was quite a bit greater than that towards the human cells.

3T3 Cells↗

Evaluation of the silver iontophoretic catheter in an animal model.

Silver iontophoretic catheters (SIC) were shown to be highly efficacious in preventing catheter infections in vitro and in a rabbit model (J. Infect. Dis. 173 (1996) 495). Furthermore, we sought to determine the safety and durability of SIC prior to use in humans. A total of 30 New Zealand white rabbits (3-4 kg) were randomly assigned to one of three groups whereby SIC or Arrow Guard (AG) catheters were tunneled and inserted in the jugular vein. All animals were followed for 2-12 weeks after catheter implantation. Blood was collected from each rabbit for assessment of toxicity and determination of silver levels. The electrical current generated by each SIC was measured once daily. At the end of the follow-up period, tissue samples were collected from the skin surrounding the catheter, the lungs, spleen, and liver. Microscopically, none of the tissues examined from any of the animals showed evidence of silver deposits, silver toxicity, thermal or electrical injury. The silver levels in the animals that received the SIC ranged from 0.1 to 2.23 microg/l with a mean of 0.62 (+/-0.44 SD). In conclusion SIC were safe with normal serum silver levels and were not associated with any local or systemic toxicity.

Animals↗

Antibacterial silver-containing silica glass prepared by sol-gel method.

Recently, various inorganic antibacterial materials containing silver have been developed and some of them are in commercial use. Colorless and more chemically durable materials which slowly release the silver ion for a long period are, however, desirable to be developed for medical applications such as composite resin for dental restoration. In the present study, Si(OC2H5)4, Al(NO3)3 x 9H2O, AgNO3, HNO3, C2H5OH and H2O solutions with various Al/Ag atomic ratios under a constant Si/Ag atomic ratio of 1/0.023 were kept at 40 degrees C for gelation and drying. Thus obtained gels were pulverized into fine powders with average particle size of approximately 10 microm and then heat-treated at 900-1000 degrees C for 2 h. For the composition Al/Ag = 0, a yellow-colored glass was formed, since the silver existed in the form of metallic colloids in the glass. However, for the compositions Al/Ag > or = 1, colorless glasses were successfully obtained, since the silver existed in the form of Ag+ ions in the glasses. For the composition Al/Ag = 0, the silver ions got released rapidly into the water, whereas, for the compositions Al/Ag > or = 1, they gradually got released into the water at a controlled rate. A composite of the obtained powders with Al/Ag atomic ratio of 1 with Bis-GMA/TEGDMA in 70:30 weight ratio showed excellent antibacterial property. The sol-gel derived silica glass powders containing silver with compositions Al/Ag > or = 1 are believed to be useful as an antibacterial material for medical applications such as filler of composite resin for dental restoration.

Aluminum Compounds↗

Acute and chronic physiological effects of silver exposure in three marine teleosts.

This study evaluated the physiological effects of waterborne silver (added as AgNO(3)) on seawater fish, using acute (48-72 h) high level exposures (250-650 microg/l Ag) on tidepool sculpins (Oligocottus maculosus), and chronic (up to 21 day) low level exposures (1.5-50 microg/l Ag) on tidepool sculpins, plainfin midshipmen (Porichthys notatus), and rainbow trout (Oncorhynchus mykiss). Sculpins were tested at different salinities. Acclimation to lower salinity (18 vs 30 ppt) led to altered physiology, with higher ammonia excretion (J(Amm)), lower oxygen consumption, and lower branchial and intestinal Na(+)/K(+)-ATPase activities, but no difference in drinking rate. Short-term exposure to high silver levels tended to stimulate M(O(2)), J(Amm), and drinking rate. However, long-term exposure to low levels of silver depressed both J(Amm) and M(O(2)), and also led to decreased drinking rates. Both inhibition and stimulation of Na(+)/K(+)-ATPase activity occurred, dependent upon length and concentration of exposure, salinity (18 vs 30 ppt), tissue (gill vs intestine), and fish species (sculpin vs midshipmen vs rainbow trout). While the effects were variable, due to differing balances between inhibitory and compensatory responses, chronic silver exposure significantly altered Na(+)/K(+)-ATPase activity levels in almost all tests. In total, these findings reinforce the view that intestinal osmoregulatory function (drinking, Na(+)/K(+)-ATPase activity) is an important site of toxic impact for waterborne silver, that gill Na(+)/K(+)-ATPase activity is also a site of impact, and that chronic exposures at silver concentrations (1.5, 14.5 microg/l Ag) close to current or proposed water quality guidelines (albeit much higher than normal environmental levels), exert a variety of sublethal effects on marine teleosts.

Ammonia↗

Modified pyrogallol-initiated immunogold-silver enhancement technique applicable to prokaryotes.

A modified immunogold-silver enhancement technique that was designed to reduce the nonspecific granular background staining, particularly for application on prokaryotic organisms, is reported. Aerial oxidation of pyrogallol contained in the commercial silver enhancer solution was effectively controlled during storage and in the reaction mixture. A combination of strategies such as storing the reagent under argon, modifying it using 0.5% (w/v) anhydrous sodium sulfite, reducing the concentration of silver ions in the reaction mixture and limiting the length of the silver enhancement reaction considerably reduced the granular background staining. The modified technique was demonstrated on the bacterium Xanthomonas campestris pv. malvacearum (Smith) Dye. A 7-min silver enhancement step produced little background staining, while optimal silver intensification of the bacterium pre-treated with the immunogold label was achieved.

Artifacts↗

The rate of re-epithelialization across meshed skin grafts is increased with exposure to silver.

UNLABELLED: The objective in this study was to determine whether exposure to pure silver increases the rate of re-epithelialization across a partial thickness wound. A meshed skin graft, placed on an excised burn wound was used as a healing model. METHODS: The rate of meshed skin graft epithelial closure on an exposed burn using a moist healing environment was shown. A moistened silver delivery system (Acticoat) was compared with a standard xeroform and eight ply gauze dressing continually moistened with a 0.01% neomycin and polymyxin solution (NP). Twenty burn patients with deep burns of over 15% of TBS were excised and grafted with 2:1 meshed grafts. One graft area was treated with the antibiotic solution and another with the silver delivery. The meshed graft was performed within 3 days of injury. RESULTS: No infections were noted and quantitative swab cultures gave less than 10(2) bacteria in all cases at wound closure. At day 7, re-epithelialization was complete with silver and 55% closed with NP solution. Wound closure was complete in the NP solution group at day 10. Silver increased re-epithelialization rate by over 40%, a significant increase. Graft take was over 95% in both groups. CONCLUSION: Silver released in a moist wound surface environment significantly increases the rate of re-epithelialization compared to a standard antibiotic solution.

Adult↗

A new silver sulfadiazine water soluble gel.

Silver sulfadiazine is the most commonly used topical antibacterial agent for the treatment of burn wounds. It has many clinical advantages, including a broad spectrum of antimicrobial activity, low toxicity, and minimal pain on application. The current formulation of silver sulfadiazine contains a lipid soluble carrier, polypropylene glycol, that has certain disadvantages, including pseudo-eschar formation and the need for twice daily application. The purpose of this investigation was to describe a new formulation of silver sulfadiazine in a water soluble gel, poloxamer 188. The antibacterial activity of this new gel has been compared to that of the commercially available silver sulfadiazine cream by in vitro and in vivo testing. The results of the in vitro antibacterial testing of these two different agents demonstrated the superiority of the new gel formulation. In experimental wounds, the antibacterial activity of the gel and the commercially available silver sulfadiazine cream were not significantly different when applied once a day. The antibacterial activity of the gel when applied once a day was comparable to that encountered by twice daily applications of the silver sulfadiazine cream by experimental wounds. The major advantage of this gel was its ease of application and removal that is attributed to its water solubility.

Administration, Topical↗