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Hepatobiliary transport and organ distribution of silver in the rat as influenced by selenite.

Bile from rats injected with 110mAgNO3 (1 micromol/kg) were fractionated on Sephadex G-15 revealing binding of silver to one high molecular weight substance and one low molecular weight substance eluting corresponding to the void volume and glutathione (GSH) respectively. Fractionation of AgNO3 and GSH mixed in vitro gave rise to a polynuclear complex and a 1 : 1 complex of Ag+-GSH which both eluted corresponding to silver in bile. Depletion of GSH in the liver by diethylmaleate (3.9 mmol/kg) caused a parallel decrease in the biliary excretion of both silver and reduced GSH. These findings support the hypothesis that silver is excreted into bile by a GSH-dependent mechanism most likely using GSH as a carrier molecule. Selenite (1 micromol/kg) inhibited the biliary excretion of silver while AgNO3 (1 mumol/kg) did not influence the excretion of selenium into bile. Pretreatment with selenite (1 micromol/kg) also caused a retention of silver (AgNO3, 1 micromol/kg) in the blood, kidney and brain. The liver content of silver was decreased and the organ to plasma ratio of silver was unchanged for erythrocytes, but decreased for the brain, kidney and liver, respectively. The effects caused by selenite are attributed to the formation of Ag2Se complexes which are nearly water insoluble and probably unavailable for biliary excretion. Selenium metabolites (GSSeSG, GSSeH) which are excreted into bile are probably not available for complexing with Ag+.

Animals↗

Mechanism of prophylaxis by silver compounds against infection of burns.

To clarify tthe mechanism by which local application of silver compounds protects burns against infection, an ion-specific electrode was used to measùre the concentration of silver ions in solutions. By this method it was shown that in burn dressings silver ions were reduced to a very low level by precipitation as silver chloride. The antibacterial effect was found to depend on the availability of silver ions from solution in contact with precipitate. Between 10(-5) and 10(-6) molar silver nitrate solution in water was rapidly bactericidal. The minimal amount of silver nitrate causing inhibition of respiration of skin in tissue culture was about 25 times the minimal concentration of silver nitrate that inhibited growth of Pseudomonas aeruginosa.

Adsorption↗

Silver-resistant Enterobacteriaceae from hospital patients.

The inclusion of agar medium containing 0.5 mM AgNO3 in the hospital laboratory replicating system for routine antibiotic-susceptibility determinations resulted in identification of species of Enterobacteriaceae (Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Proteus mirabilis, and Citrobacter freundii) with silver resistance. Since the study began in October, 1975, 11 in-hospital patients receiving silver sulfadiazine for burn wound prophylaxis have yielded silver-resistant bacteria from their infected burns. During this treatment routine burn-site cultures from these patients yielded 230 isolates of Enterobacteriaceae, including 211 which were sulfonamide-resistant, 97 of which were also silver-resistant, and 38 of which were untested for silver resistance. Seven silver-resistant but sulfonamide-sensitive isolates were incidentally recovered from respiratory specimens from four nonburn patients with silver tracheostomy tubes, one silver-resistant sulfonamide-sensitive isolate was recovered from a small infected burn on the foot of an Emergency Room patient. Previous treatment of this burn was unknown. Representative AgNO3-resistant E. coli isolates from four patients were serologically untypable. Serotyping of representative isolates of K. pneumoniae showed a diversity of types except from two patients who had been in the same ward at the same time.

Burns↗

Determination of silver in blood, urine, and tissues of volunteers and burn patients.

Silver sulfadiazine cream (SSD) has been used successfully in the management of burn wound sepsis. Silver deposition has been found in the skin, gingiva, cornea, liver, and kidney of patients treated with this cream, causing argyria, ocular injury, leukopenia, and toxicity in kidney, liver, and neurologic tissues. Monitoring concentrations of silver in blood and urine of patients receiving this treatment has become necessary, but sensitive and suitable methods adaptable to a clinical laboratory are still needed. We have developed a flameless thermal atomic absorption spectrophotometric method to measure silver concentrations in blood, urine, and other tissues. The detection limit is 0.4 microgram/L; the within-run precisions (CV) are 5.16%, 3.83%, and 2.79% for concentrations of 5, 13.5, and 42 micrograms/L, respectively; and the between-run precisions are 4.3% and 3.2% for concentrations of 13.5 and 42 micrograms/L. The concentrations of silver in blood, urine, liver, and kidney of subjects without industrial or medicinal exposure are less than 2.3 micrograms/L, 2 micrograms/day, 0.05 microgram/g wet tissue, and 0.05 microgram/g wet tissue, respectively. In SSD cream-treated burn patients, plasma concentrations may be as great as 50 micrograms/L within 6 h of treatment and can reach a maximum of 310 micrograms/L. Silver in urine is detectable after one day of treatment and may reach a maximum of 400 micrograms/day. After absorption, silver was found to be deposited in various tissues. Tissue silver concentrations in one burn patient who died of renal failure after eight days of treatment were 970, 14, and 0.2 micrograms/g wet tissue in cornea, liver, and kidney, respectively.

Aged↗

A randomized crossover study of silver-coated urinary catheters in hospitalized patients.

BACKGROUND: Urinary tract infections (UTIs) account for 30% to 40% of nosocomial infections resulting in morbidity, mortality, and increased length of hospital stay. OBJECTIVE: To assess the efficacy of a silver-alloy, hydrogel-coated latex urinary catheter for the prevention of nosocomial catheter-associated UTIs. METHODS: A 12-month randomized crossover trial compared rates of nosocomial catheter-associated UTI in patients with silver-coated and uncoated catheters. A cost analysis was conducted. RESULTS: There were 343 infections among 27,878 patients (1.23 infections per 100 patients) during 114,368 patient-days (3.00 infections per 1000 patient-days). The relative risk of infection per 1000 patient-days was 0.79 (95% confidence interval, 0.63-0.99; P =.04) for study wards randomized to silver-coated catheters compared with those randomized to uncoated catheters. Infections occurred in 291 of 11,032 catheters used on study units (2.64 infections per 100 catheters). The relative risk of infection per 100 silver-coated catheters used on study wards compared with uncoated catheters was 0.68 (95% confidence interval, 0.54-0.86; P =.001). Fourteen catheter-associated UTIs (4.1%) were complicated by secondary bloodstream infection. One death appeared related to the secondary infection. Estimated hospital cost savings with the use of the silver-coated catheters ranged from $14,456 to $573,293. CONCLUSIONS: The risk of infection declined by 21% among study wards randomized to silver-coated catheters and by 32% among patients in whom silver-coated catheters were used on the wards. Use of the more expensive silver-coated catheter appeared to offer cost savings by preventing excess hospital costs from nosocomial UTI associated with catheter use. Arch Intern Med. 2000;160:3294-3298.

Adult↗

Silver acetate for smoking cessation.

BACKGROUND: Silver acetate produces an unpleasant taste when combined with cigarettes, thereby producing an aversive stimulus. It has been marketed in various forms with the aim of extinguishing the urge to smoke, by pairing the urge with an unpleasant stimulus. OBJECTIVES: The aim of this review was to determine the effectiveness of silver acetate products (gum, lozenge, spray) in promoting smoking cessation. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register. SELECTION CRITERIA: We included randomised trials of silver acetate for smoking cessation with reports of smoking status at least six months after the beginning of treatment. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of subjects, the dose and form of silver acetate, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measure was biochemically validated abstinence from smoking after at least six months follow-up in patients smoking at baseline. Subjects lost to follow-up were counted as continuing smokers. Where appropriate, we performed meta-analysis using a fixed effects model. MAIN RESULTS: Two studies provided long-term follow-up data on patients randomised to silver acetate or placebo. In one of these studies, there was a third arm, randomised to 2mg nicotine gum. The combined odds ratio for quitting for silver acetate vs placebo was 1.05 (95% confidence interval 0.63 to 1.73). REVIEWER'S CONCLUSIONS: Existing trials show little evidence for a specific effect of silver acetate in promoting smoking cessation. The confidence intervals for the ratio are quite wide. However, the upper limit of the confidence intervals for a positive effect equates to an absolute increase in the smoking cessation rate of about 4%. Any effect of this agent is therefore likely to be smaller than nicotine replacement therapy. The lack of effect of silver acetate may reflect poor compliance with a treatment whose rationale is to create an unpleasant stimulus.

Acetates↗

Preparation of antibacterial silver-doped silica glass microspheres.

Various types of inorganic substances doped with silver ions have been developed as antibacterial materials, and some have already been commercialized. Colorless and chemically durable materials that slowly release silver ions are, however, still need to be developed. The present authors have previously shown that when a silica glass doped with silver and aluminium ions is prepared using the sol-gel method, the resultant product is colorless, chemically durable, and slowly releases silver ions into water over a long period. The doped silica glass takes a form of microspheres <1 microm in diameter, it is easily mixed with organic polymers, and the mixture can be formed into a thin film or fine fibers, etc. We report on the preparation of silver doped silica glass microspheres having a diameter =1 microm, using the sol-gel method. Initially, tetraethoxysilane was partially prehydrolyzed by water in ethanol, and then aluminium triisopropoxide was added to the solution to form Si-O-Al bonds. Finally, an ammonia solution containing silver nitrate was added to form silica microspheres doped with silver ion together with aluminium ions. The results show monodispersed microspheres 0.4-0.6 microm in diameter were obtained with nominal compositions of Si/Al/Ag = 1/0.01-0.03/0.003-0.03, with a molar ratio of Al/Ag = 1-3.3. The microspheres were colorless, showed a high chemical durability, and slowly released silver ions into water at 37 degrees C. Microspheres with the composition Si/Al/Ag = 1/0.01/0.01 showed excellent antibacterial activity against Escherichia coli. The minimum inhibitory concentration (MIC) of the microspheres was 400, which is less than the MIC value (800) of commercial antibacterial materials.

Anti-Bacterial Agents↗

Effect of silver addition on the properties of nickel-titanium alloys for dental application.

Equiatomic and near-equiatomic nickel-titanium alloys exhibit a shape-memory effect and superelasticity. However, the properties of such alloys are extremely sensitive to the precise nickel-titanium ratio and the addition of alloying elements. High corrosion resistance is necessary for biomedical applications, especially orthodontic. The purpose of this study was to investigate the effect of silver addition to nickel-titanium alloys for dental and medical application. Arc melting, homogenization, hot rolling, and solution heat treatment were performed to prepare the nickel-titanium-silver (NiTi-Ag) specimens. The properties of the ternary NiTi-Ag alloys such as phase-transformation temperature, microstructure, microhardness, corrosion resistance, and cytotoxicity were investigated. The NiTi-Ag alloys showed low silver recovery rate for the cast alloy, due to silver's low evaporation temperature, and low silver solubility in nickel-titanium. Silver addition to nickel-titanium increased the transition temperature range to 100 degrees C and stabilized the martensitic phase (monoclinic structure) at room temperature, because the martensitic transformation starting temperature (Ms) was above room temperature. Martensitic and austenitic phases existed in X-ray diffraction patterns of solution-annealed NiTi-Ag alloys. The silver addition was considered to improve the corrosion resistance and form a stable passive film. Significantly, the mechanical properties of the silver-added alloys were dependent upon the amount of alloying addition. There was no toxicity in the NiTi-Ag alloys, as the response index showed none or mild levels.

Animals↗

Age-dependent variability of ribosomal RNA-gene activity in man as determined from frequencies of silver staining nucleolus organizing regions on metaphase chromosomes of lymphocytes and fibroblasts.

Frequencies of silver staining nucleolus organizing regions (NORs) have been determined in lymphocytes and fibroblasts from very young and from aged persons. Since silver staining of NORs is associated with activity of ribosomal RNA-genes, we used this approach to investigate a possible inactivation of these genes during aging. Our lymphocyte data are based on a study per age-group of 220 metaphases from 10 subjects. Although in both age-groups modal numbers of silver staining chromosomes per metaphase had similar ranges over the subjects, the frequency of metaphases containing the maximal number of staining chromosomes was in the old age-group (80--89 years) significantly lower than in the young age-group (less than 1 year old). In fibroblasts, of which 75 metaphases from 4 subjects were included per age-group, differences were more pronounced. Modal numbers of silver staining chromosomes were for the aged persons (69--83 years) lower than for the young children (less than 1 year old). Highly significant differences were observed between both groups in frequency of metaphases containing the maximal number of positively reacting acrocentric chromosomes and, more in general, in frequencies of silver staining D- and G-group chromosomes, the lower frequencies being found in the old age-group. We propose the term NOR-junctions as distinct from satellite associations for arrangements of acrocentric chromosomes which after silver staining are visibly connected at their NORs. The number of acrocentric chromosomes involved in lymphocyte NOR-junctions of aged people was significantly higher than the number of joined acrocentrics in young children. The frequency of these NOR-junctions themselves, irrespective of the number of chromsomes involved, was higher for aged persons than for young children, although this difference appeared to be statistically not significantly higher than in fibroblasts. Also based on qualitative observations from our study we discuss tcehnical and biological problems of our approach to study cell aging in vivo by means of silver staining of NORs. We conclude that in man, reflected by the difference in frequencies of silver staining NORs between young and aged persons, a rather extensive loss of ribosomal RNA-gene activity may occur during aging.

Aged↗

Germanium and silver resistance, accumulation, and toxicity in microorganisms.

Germanium is an inert metal with no known biological function in prokaryotic or eukaryotic organisms. Its toxicity is low compared to that of silver. Germanium is accumulated in certain bacterial strains by either energy-independent passive binding or an energy-dependent mechanism. Little is known about the molecular aspects of silver resistance, toxicity, and accumulation in bacterial strains. This is surprising because silver has been used as an antimicrobial agent in the medical field for centuries. It is likely that silver ions are excluded (resulting in decreased silver accumulation) from certain bacterial strains or immobilized intracellularly to prevent toxic effects from being exerted. These mechanisms of silver resistance have not been fully elucidated. This review examines the toxicity and accumulation of germanium and silver in selected microbial species. In addition, resistance mechanisms to these biologically nonessential metals is discussed, with more emphasis placed on silver-resistant bacteria due to the knowledge available.

Bacteria↗

Control of burn wound infections by pefloxacin and its silver derivative.

As might be anticipated, strains of Pseudomonas aeruginosa resistant to silver sulfadiazine have appeared. We have found an analogue of nalidixic acid (pefloxacin) which, along with its silver derivative, is highly effective against these resistant strains. In vitro the minimal inhibitory concentrations are 10 to 20 times lower than that of silver sulfadiazine against bacteria. In burned mice and rats infected with silver sulfadiazine resistant pseudomonas strains, mortality in groups receiving topical therapy with pefloxacin and silver pefloxacin is about 10 per cent compared to 80 per cent with silver sulfadiazine (100 per cent in untreated controls). There is little systemic absorption of pefloxacin and no absorption of silver from topical treatment. In addition, silver pefloxacin exhibits higher antifungal activity in vitro.

Administration, Topical↗

Evaluation of topical therapy with silver-kaolin (Argostop) in an experimental model of burn wound sepsis.

Burn wound therapy with silver-kaolin, a topical agent applied as an aerosol spray, was evaluated in male rats given a 20 per cent total body surface area, full thickness dorsal scald burn. Burn wounds treated with silver-kaolin healed at rates comparable to untreated wounds. No significant differences were noted in the numbers or types of organisms colonizing the wounds of treated and untreated rats at 5, 12 and 19 days post-burn. To evaluate the effectiveness of silver-kaolin in treating burn wound sepsis, rats were inoculated on the wound surface with 2.5 x 10(8) Pseudomonas aeruginosa. This inoculum resulted in 100 per cent mortality in untreated rats. Rats treated with silver-kaolin had a mortality rate of 71 per cent, compared to a 9 per cent mortality rate in rats treated with 1 per cent silver sulphadiazine. When silver-kaolin was applied to the wound prior to bacterial inoculation, the mortality rate was reduced to 6 per cent. When wounds were treated with kaolin alone and then inoculated with bacteria, the mortality rate was 50 per cent, indicating that part of the effectiveness of silver-kaolin appeared to be due to a barrier effect. These results indicate that silver-kaolin may be useful for preventive topical antimicrobial therapy of acute burns or after wound debridement or excision, but is not suitable for therapy of wounds previously colonized by microorganisms.

Administration, Topical↗

The mechanism of corrosion of palladium-silver binary alloys in artificial saliva.

Palladium dental casting alloys are alternatives to gold alloys. The aim of this study was to determine the electrochemical behaviour and the corrosion mechanism of binary silver-palladium alloys. Seven binary silver-palladium alloys and pure palladium and silver were tested in a model saliva solution. Electrochemical tests included corrosion potential, polarization resistance, and potentiodynamic polarization measurements. The corrosion products, which may be theoretically formed, were determined by thermodynamic calculation. The behaviour of silver and silver-rich alloys was dominated by the preferential formation of a thiocyanate surface layer, which controlled the free corrosion potential. Palladium dissolved in the form of a thiocyanate complex, but the surface became passivated by either palladium oxide or solid palladium thiocyanate layer, the thermodynamic calculations indicating preference for the oxide. Palladium-rich alloys showed evidence of silver depletion of the surface, resulting in behaviour similar to palladium. Examination of binary silver-palladium alloys has made possible determination of the role of the components of the alloys and model saliva in the corrosion behaviour. The findings are applicable to the more complex commercial dental alloys containing silver and palladium as major components.

Biocompatible Materials↗

Separation, preconcentration and determination of silver ion from water samples using silica gel modified with 2,4,6-trimorpholino-1,3,5-triazin.

A new modified silica gel using 2,4,6-trimorpholino-1,3,5-triazin was used for separation, preconcentration and determination of silver ion in natural water by atomic absorption spectrometry (AAS). This new bonded silica gel was used as an effective sorbent for the solid-phase extraction (SPE) of silver ion from aqueous solutions. Experimental conditions for effective adsorption of trace levels of silver ion were optimized with respect to different experimental parameters in column process. Common coexisting ions did not interfere with the separation and determination of silver at pH 3.5 so that silver ion completely adsorbed on the column. The preconcentration factor is 130 (1 mL elution volume for a 130 mL sample volume). The relative standard deviation (R.S.D.) under optimum conditions is 3.03% (n=5). The accuracy of the method was estimated by using spring and tap water samples that were spiked with different amounts of silver ion. The adsorption isotherm of silver ion was obtained. The capacity of the sorbent at optimum conditions has been found to be 384 microg of silver per gram of sorbent.

Adsorption↗

Biomimetic synthesis silver crystallite by peptide AYSSGAPPMPPF immobilized on PET film in vitro.

AG3 (AYSSGAPPMPPF) is an inorganic-binding peptide that specifically and selectively binds to silver demonstrated by phage display library according to the Stone group. In our experiment, synthesized silver-binding peptide AG3 was immobilized on the surface of protonated poly(ethylene terephthalate) (PET) film which was prepared for biomimetic synthesis silver particles in vitro. Silver crystallites formatted on the surface of AG3-PET film showed various shapes and was 1-4 microm in size. In addition to hexagonal and triangular crystallite, a silver crystallite presents a cubical shape that has seldom been reported in the literatures so far. With comparison of the control and silver nitrate salt, the surface energy of the silver particles on AG3-PET film surface XPS analysis suggested that Ag+ was being reduced to Ag0 in the reaction. Moreover, CD spectrum revealed that the secondary structure of AG3 peptide in solution had a little change before and after binding silver.

Amino Acid Sequence↗

An in vitro biotic ligand model (BLM) for silver binding to cultured gill epithelia of freshwater rainbow trout (Oncorhynchus mykiss).

"Reconstructed" gill epithelia on filter supports were grown in primary culture from dispersed gill cells of freshwater rainbow trout (Oncorhynchus mykiss). This preparation contains both pavement cells and chloride cells, and after 7-9 days in culture, permits exposure of the apical surface to true freshwater while maintaining blood-like culture media on the basolateral surface, and exhibits a stable transepithelial resistance (TER) and transepithelial potential (TEP) under these conditions. These epithelia were used to develop a possible in vitro version of the biotic ligand model (BLM) for silver; the in vivo BLM uses short-term gill binding of the metal to predict acute silver toxicity as a function of freshwater chemistry. Radio-labeled silver ((110m)Ag as AgNO(3)) was placed on the apical side (freshwater), and the appearance of (110m)Ag in the epithelia (binding) and in the basolateral media (flux) over 3 h were monitored. Silver binding (greater than the approximate range 0-100 mug l(-1)) and silver flux were concentration-dependent with a 50% saturation point (apparent K(d)) value of about 10 mug l(-1) or 10(-7) M, very close to the 96-h LC50 in vivo in the same water chemistry. There were no adverse effects of silver on TER, TEP, or Na(+), K(+)-ATPase activity, though the latter declined over longer exposures, as in vivo. Silver flux over 3 h was small (<20%) relative to binding, and was insensitive to water chemistry. However, silver binding was decreased by elevations in freshwater Na(+) and dissolved organic carbon (humic acid) concentrations, increased by elevations in freshwater Cl(-) and reductions in pH, and insensitive to elevations in Ca(2+). With the exception of the pH response, these effects were qualitatively and quantitatively similar to in vivo BLM responses. The results suggest that an in vitro BLM approach may provide a simple and cost-effective way for evaluating the protective effects of site-specific waters.

Animals↗

Feasibility of the silver-UV process for drinking water disinfection.

A synergistic effect between cationic silver and UV radiation (silver-UV disinfection) has been observed that can appreciably enhance inactivation of viruses. The purpose of this work was to assess the feasibility of this technique for drinking water disinfection and evaluate the effects of selected impurities, found in fresh water, and common parameters on inactivation of the coliphage MS-2 with the silver-UV process. Turbidity (kaolin), calcium hardness, carbonate alkalinity, and pH did not significantly degrade inactivation. Inactivation was reduced in the presence of chloride, at concentrations greater than 30 mg/L, and in water samples with UV-254 absorbance values greater than ca. 0.1 cm(-1). Inactivation of MS-2 with silver-UV disinfection was also reduced at high phosphate concentrations (above ca. 5 mM). Silver-UV inactivation of MS-2 increased with increases in temperature between 10 and 20 degrees C. Silver-UV inactivation of MS-2 was increased by greater than 1-log over UV alone, in two untreated fresh water sources, which indicates that silver-UV may be a viable treatment technology. An assessment of operation and management costs suggests that an increase in inactivation of MS-2 with silver-UV disinfection could be economically beneficial.

Chlorides↗

Increased resonance energy transfer between fluorophores bound to DNA in proximity to metallic silver particles.

We examined the effects of metallic silver particles on resonance energy transfer (RET) between fluorophores covalently bound to DNA. A coumarin donor and a Cy3 acceptor were positioned at opposite ends of a 23-bp double helical DNA oligomer. In the absence of silver particles the extent of RET is near 9%, consistent with a Forster distance R(0) near 50 A and a donor to acceptor distance near 75 A. The transfer efficiency increased when the solution of AMCA-DNA-Cy3 was placed between two quartz plates coated with silver island films to near 64%, as determined by both steady-state and time-resolved measurements. The apparent R(0) in the presence of silver island films increases to about 110 A. These values of the transfer efficiency and R(0) represent weighted averages for donor-acceptor pairs near and distant from the metallic surfaces, so that the values at an optimal distance are likely to be larger. The increased energy transfer is observed only between two sandwiched silvered slides. When we replaced one silvered slide with a quartz plate the effect vanished. Also, the increased energy transfer was not observed for silvered slides separated more than a few micrometers. These results suggest the use of metal-enhanced RET in PCR, hybridization, and other DNA assays, and the possibility of controlling energy transfer by the distance between silver surfaces.

Base Sequence↗