Disposition of intravenously or orally administered silver nanoparticles in pregnant rats and the effect on the biochemical profile in urine.

Few investigations have been conducted on the disposition and fate of silver nanoparticles (AgNP) in pregnancy. The distribution of a single dose of polyvinylpyrrolidone (PVP)-stabilized AgNP was investigated in pregnant rats. Two sizes of AgNP, 20 and 110 nm, and silver acetate (AgAc) were used to investigate the role of AgNP diameter and particle dissolution in tissue distribution, internal dose and persistence. Dams were administered AgNP or AgAc intravenously (i.v.) (1 mg kg-1 ) or by gavage (p.o.) (10 mg kg-1 ), or vehicle alone, on gestation day 18 and euthanized at 24 or 48 h post-exposure. The silver concentration in tissues was measured using inductively-coupled plasma mass spectrometry. The distribution of silver in dams was influenced by route of administration and AgNP size. The highest concentration of silver (µg Ag g-1 tissue) at 48 h was found in the spleen for i.v. administered AgNP, and in the lungs for AgAc. At 48 h after p.o. administration of AgNP, the highest concentration was measured in the cecum and large intestine, and for AgAc in the placenta. Silver was detected in placenta and fetuses for all groups. Markers of cardiovascular injury, oxidative stress marker, cytokines and chemokines were not significantly elevated in exposed dams compared to vehicle-dosed control. NMR metabolomics analysis of urine indicated that AgNP and AgAc exposure impact the carbohydrate, and amino acid metabolism. This study demonstrates that silver crosses the placenta and is transferred to the fetus regardless of the form of silver. Copyright © 2016 John Wiley & Sons, Ltd.

Assessment of Silver Levels in a Closed-Incision Negative Pressure Therapy Dressing: In Vitro and In Vivo Study.

Objective: In recent years, reticulated open-cell foam-based closed-incision negative pressure therapy (ROCF-ciNPT) has shown effectiveness in management of various postoperative incisions. These dressings consist of a skin interface layer that absorbs fluid from the skin surface and reduces the potential for microbial colonization within the dressing by means of ionic silver. This study examines the ability of silver to reduce the bioburden within the dressing as well as the localized effect due to potential silver mobility. Approach: Ability of silver to reduce bioburden within the ROCF-ciNPT dressing was assessed using Staphylococcus aureus, Pseudomonas aeruginosa, and Candida spp. Furthermore, silver mobility was assessed using an in vitro skin model to study the zone of inhibition along with released silver quantification. Using a porcine model, diffusion of silver into blood and tissue was studied using emission spectrometry and histology. Results: Microbial growth in the ROCF-ciNPT dressing was significantly reduced (∼2.7-4.9 log reduction) compared to a silver-free negative control. No zone of inhibition was observed for microbial colonies for up to 7 days with minimal localized silver release (<5.5 ppm release). In vivo studies demonstrated no measurable concentration (<0.2 µg/g) of silver in the blood, urine, feces, kidney, and liver tissue biopsy. Innovation: This study provides an important insight into silver concentration and mobility within the ROCF-ciNPT dressing, given emerging concerns associated with potential silver cytotoxicity. Conclusion: These results indicate the concentration of silver (0.019% silver by weight) in the ROCF-ciNPT dressings has been adequate to reduce bioburden within the skin interface layer, while severely limiting the amount of silver leaching out.

Fructose-coated Angstrom silver inhibits osteosarcoma growth and metastasis via promoting ROS-dependent apoptosis through the alteration of glucose metabolism by inhibiting PDK.

Osteosarcoma is a common malignant bone cancer easily to metastasize. Much safer and more efficient strategies are still needed to suppress osteosarcoma growth and lung metastasis. We recently presented a pure physical method to fabricate Ångstrom-scale silver particles (AgÅPs) and determined the anti-tumor efficacy of fructose-coated AgÅPs (F-AgÅPs) against lung and pancreatic cancer. Our study utilized an optimized method to obtain smaller F-AgÅPs and aimed to assess whether F-AgÅPs can be used as an efficient and safe agent for osteosarcoma therapy. We also investigated whether the induction of apoptosis by altering glucose metabolic phenotype contributes to the F-AgÅPs-induced anti-osteosarcoma effects. Methods: A modified method was developed to prepare smaller F-AgÅPs. The anti-tumor, anti-metastatic and pro-survival efficacy of F-AgÅPs and their toxicities on healthy tissues were compared with that of cisplatin (a first-line chemotherapeutic drug for osteosarcoma therapy) in subcutaneous or orthotopic osteosarcoma-bearing nude mice. The pharmacokinetics, biodistribution and excretion of F-AgÅPs were evaluated by testing the levels of silver in serum, tissues, urine and feces of mice. A series of assays in vitro were conducted to assess whether the induction of apoptosis mediates the killing effects of F-AgÅPs on osteosarcoma cells and whether the alteration of glucose metabolic phenotype contributes to F-AgÅPs-induced apoptosis. Results: The newly obtained F-AgÅPs (9.38 ± 4.11 nm) had good stability in different biological media or aqueous solutions and were more effective than cisplatin in inhibiting tumor growth, improving survival, attenuating osteolysis and preventing lung metastasis in osteosarcoma-bearing nude mice after intravenous injection, but were well tolerated in normal tissues. One week after injection, about 68% of F-AgÅPs were excreted through feces. F-AgÅPs induced reactive oxygen species (ROS)-dependent apoptosis of osteosarcoma cells but not normal cells, owing to their ability to selectively shift glucose metabolism of osteosarcoma cells from glycolysis to mitochondrial oxidation by inhibiting pyruvate dehydrogenase kinase (PDK). Conclusion: Our study suggests the promising prospect of F-AgÅPs as a powerful selective anticancer agent for osteosarcoma therapy.

Initial experience with silver-impregnated polyurethane ventricular catheter for shunting of cerebrospinal fluid in patients with infected hydrocephalus.

OBJECTIVE: Infection is a major complication and risk factor of cerebrospinal fluid (CSF) shunting procedures. Recently, antibiotic-impregnated shunt systems have been developed in an attempt to prevent or reduce the CSF infection. The aim of this study was to determine the efficacy of silver-impregnated polyurethane ventricular catheter for shunting of CSF in patients with infected hydrocephalus. METHODS: Seven patients who had hydrocephalus with high protein level and positive CSF culture underwent implantation of ventriculoperitoneal shunt with silver-impregnated polyurethane ventricular catheter. All of them experienced shunt failure previously due to infection. The Silverline ventricular catheter, which was connected to the Miethke gravity-assisted valve system and peritoneal catheter, was used in all patients. The mean follow-up period after operation was 14 months. Cerebrospinal fluid samples from the reservoir of the shunts were obtained at the end of the third month after operation in all patients. RESULTS: The CSF protein level of the patients was reduced significantly, and the CSF culture became negative after shunt placement with silver-impregnated polyurethane ventricular catheters. The mean CSF silver (Ag) level was 0.51 ng/ml [parts per billion (ppb)], and blood Ag level was 3.65 ng/ml (ppb) at the first month after operation. No shunt obstruction or infection was observed in the follow-up period. CONCLUSION: Silver-impregnated polyurethane ventricular catheters appear to be safe and well tolerated in patients who sustained infected hydrocephalus. Preliminary results suggest a complete improvement of infection. Longer follow-up and large number of patients are needed to more accurately assess the efficacy of these catheters.

Possibilities of single particle-ICP-MS for determining/characterizing titanium dioxide and silver nanoparticles in human urine.

OBJECTIVE: The current use of nanoparticles in personal care and cosmetics, food safety, agriculture, medicine and pharmacy has led to a growing concern on the toxicity of these emerging materials to humans and also to the environment. Nanoparticles assessment (determination and size distribution) is a challenge mainly due to limitations of the current analytical instrumentation, but also because nanoparticles in foodstuff and environmental samples are usually found at low concentrations. The scenario is even more critical when dealing with clinical samples, mainly when trying to assess nanoparticles at basal levels in complex samples such as blood and urine. The aim of this paper is to find data regarding the presence of nanoparticles at basal levels in urine human samples. METHODS: The use of single particle - inductively couple plasma - mass spectrometry (sp-ICP-MS) has been explored to determine and characterize silver and titanium dioxide nanoparticles in human urine. Urine samples were directly diluted (1:5 to 1:10) with 1%(v/v) glycerol before sp-ICP-MS measurements, and efforts were made for validating the over-all procedure. RESULTS: The limit of detection and quantification for Ag NPs were 5.72 × 103 and 1.91 × 104 Ag NPs mL-1, respectively; whereas, values for TiO2 NP concentrations were 4.31 × 103 and 1.44 × 104 TiO2 NPs mL-1. The limit of detection in size after applying several methods (3σ/5σ criteria) was found to be within the 8-9 nm for Ag NPs, and from 15 to 18 nm for TiO2 NPs. Within-batch precision for Ag NP concentration was 15% (11% for mean size of nanoparticle distributions). Repeatability for TiO2 NPs was 25% (TiO2 NP concentration) and 9% (TiO2 NP mean size). Good analytical recovery rates were found for spiked experiments with Ag NP standards of 40 and 60 nm (values within the 104-106% range), and also for TiO2 NPs of 50 and 100 nm (96-98%). Finally, basal levels of Ag NPs and TiO2 NPs, as well as total Ag and Ti concentrations, in human urine were assessed. Low Ag and Ag NP concentrations were found. Ag NPs exhibited mean sizes of approximately 16-17 nm. Total Ti levels, however, were higher than total Ag concentration, and TiO2 NP concentrations within the 1.56 × 104-2.80 × 104 NPs mL-1 range were measured (TiO2 NP mean sizes were from 76 to 98 nm).

Visual and colorimetric detection of p-aminophenol in environmental water and human urine samples based on anisotropic growth of Ag nanoshells on Au nanorods.

A simple, sensitive, selective and high-resolution colorimetric method has been developed for the detection of p-aminophenol in environmental water and human urine samples. In the presence of p-aminophenol, silver ions are reduced to silver atoms and subsequently Ag nanoshells anisotropically grow on the surface of Au nanorods to generate orange slice-like Au@Ag core-shell nanocrystals, thereby resulting in the blue-shift of longitudinal surface plasmon resonance band of Au nanorods accompanying a sharp-contrast multicolor change. Using Au@Ag core-shell nanocrystals as the transducer, sub-micromolar p-aminophenol can be detected by the colorimetric method and 10 µmol L(-1) p-aminophenol can be visual readout by the naked eyes. Furthermore, a simple, cheap, portable test kit is constructed for the visual assay of urinary p-aminophenol without complicated sample pretreatment and sophisticated instruments. The proposed colorimetric method has the potential for the rapid and on-site analyses of p-aminophenol in environmental water and human urine samples.

Pilot study on the identification of silver in skin layers and urine after dermal exposure to a functionalized textile.

Silver (Ag) is increasingly used in consumer products like functionalized textiles and medical devices owing to its strong antimicrobial activity which is largely assigned to Ag ions released after oxidation of metallic Ag. To increase generation of Ag ions, in various products Ag is often present as nanoparticles. Ideally, Ag ions would remain on the surface of the skin to combat the bacteria and the uptake of Ag into the body should be limited. However, the Ag ions might penetrate across the skin into the body leading to adverse health effects. Data on in vivo uptake of Ag due to dermal exposure are scarce partly caused by the lack of suitable analytical approaches for the determination of Ag in biological matrices, but strongly needed to enable risk assessment of skin exposure to (nano) Ag containing products. With the developed approach, the presence of Ag in a functionalized textile is confirmed by using scanning electron microscopy (SEM). After in vivo dermal exposure to Ag containing textile material under ׳׳in use׳׳ exposure scenarios, the outermost layers of the skin (Stratum Corneum, SC) were sampled by using adhesive tapes with a size of 3.8cm(2). Different leaching and dissolution procedures of Ag from biological samples prior analysis by inductively coupled plasma mass spectrometry (ICPMS) have been evaluated. The developed method results in a limit of detection (LOD) of 2ng Ag per removed SC layer. The method allows the measurement of the Ag concentrations at different depths of the SC enabling the deduction of the percutaneous penetration kinetics. Due to the possible bio distribution within the whole body, an indirect exposure matrix (urine) was studied too. The detection power of the method permits measuring the ultra-trace concentrations of Ag in urine before and after dermal exposure; LOD is 0.010µg Ag/L urine.

Percutaneous penetration of silver from a silver containing garment in healthy volunteers and patients with atopic dermatitis.

Human data on dermal absorption of silver under "in use" scenario are scarce which hampers health risk assessment. The main objective of the present study was to determine percutaneous penetration of silver after dermal exposure to silver containing garment in healthy individuals and atopic dermatitis (AD) patients. Next to assess pro-inflammatory effect of silver in the skin. Healthy subjects (n=15) and patients with AD (n=15) wore a sleeve containing 3.6% (w/w) silver on their lower arms for 8h during 5 consecutive days. The percutaneous penetration parameters were deduced from the silver concentration-depth profiles in the stratum corneum (SC) collected by adhesive tapes. Furthermore, silver was measured in urine samples collected before and after exposure. Inflammatory response was assessed by measuring IL-1α and IL-1RA in the exposed and non-exposed skin sites. Dermal flux of silver in healthy subjects and AD patients was respectively 0.23 and 0.20 ng/cm(2)/h. The urine silver concentrations showed no increase after exposure. Furthermore, exposure to silver did not lead to the changes in the profiles of IL-1α and IL-1RA. Dermal absorption of silver under "real life scenario" was lower than the current reference dose. Furthermore, dermal exposure did not lead to altered expression of inflammatory IL-1 cytokines in the skin.

Human exposure to mercury and silver released from dental amalgam restorations.

In 35 healthy individuals, the number of amalgam surfaces was related to the emission rate of mercury into the oral cavity and to the excretion rate of mercury by urine. Oral emission ranged up to 125 micrograms Hg/24 h, and urinary excretions ranged from 0.4 to 19 micrograms Hg/24 h. In 10 cases, urinary and fecal excretions of mercury and silver were also measured. Fecal excretions ranged from 1 to 190 micrograms Hg/24 h and from 4 to 97 micrograms Ag/24 h. Except for urinary silver excretion, a high interplay between the variables was exhibited. The worst-case individual showed a fecal mercury excretion amounting to 100 times the mean intake of total Hg from a normal Swedish diet. With regard to a Swedish middle-age individual, the systemic uptake of mercury from amalgam was, on average, predicted to be 12 micrograms Hg/24 h.

[Determination of Ag ions in water, urine and blood]. / Dosage des ions Ag+ dans l'eau, les urines et le sang.

Developments in polarography techniques over the last thirty years have enabled us to register outstanding increases in sensitivity: the order of concentration studies has evolved from 10(-3) g ions/1 to 10(-10) g ions/1. Pulse polarography with anodic stripping voltammetry is therefore particulary suitable for the determination of numerous metals which are to be found in extremely low concentration in biological samples which may be of limited volume e.g. blood. Our objects has been to describe and to apply in the case of silver a determination technique which would be sufficently sensitive, precise, practical and rapid for it to be easily used by biologists and toxicologists. A fortiori, this method may be applied in hydrology to the determination of these metals in water.

[Increased serum and urinary levels of silver during treatment with topical silver sulfadiazine]. / Elévation des taux sériques et urinaires d'argent au cours d'un traitement topique par sulfadiazine argentique (Flammazine(R)).

BACKGROUND: Argyria, induced by prolonged absorption, is often of professional or medical origin. We report two cases of per cutaneous intoxication with topical silver sulfadiazine. CASE REPORTS: A 64 year-old hypertensive, diabetic woman presented bilateral venous ulcers on the legs. She had applied 100 g of silver sulfadiazine 1 p. 100 cream per week for the past 18 months. Silver concentration in blood high: 38 microgram/l (N<0.5) and led to renal dysfunction, without ocular or hepatic abnormality. A 19 year-old woman was treated with topical silver sulfadiazine for thermic cutaneous burns on legs. Renal and hepatic function was normal but silver concentration in blood was high at 440 microgram/l (N<0) with urinary excretion of silver at 12 microgram/l (N=0). DISCUSSION: Silver, from prolonged and excessive use of topical silver sulfadiazine, deposits in large amounts throughout the body: skin, labial mucosa, gingiva, kidney, liver and cornea. Monitoring concentration of silver in blood and/or urine is necessary, especially in patients treated with silver sulfadiazine cream for cutaneous burns. Indeed, silver is rapidly absorbed through the burn wound. It provokes hepatic, renal and neurologic tissue toxicity. Renal and hepatic function tests are not correlated with serum silver levels. CONCLUSION: The potential for silver toxicity is a direct consequence of applying silver sulfadiazine to extensive burn wounds. Hence monitoring concentrations of silver in blood and/or urine of patients receiving this treatment is recommended.

Simultaneous ionization and analysis of 84 anabolic androgenic steroids in human urine using liquid chromatography-silver ion coordination ionspray/triple-quadrupole mass spectrometry.

Metal ion coordination ionspray (M(+) CIS) ionization is a powerful technique to enhance ionization efficiency and sensitivity. In this study, we developed and validated an analytical method for simultaneous ionization and analysis of 84 anabolic androgenic steroids (65 exogenous and 19 endogenous) using liquid chromatography-silver ion coordination ionspray/triple-quadrupole mass spectrometry (LC-Ag(+) CIS/MS/MS). The concentrations of silver ions and organic solvents have been optimized to increase the amount of silver ion coordinated complexes. A combination of 25 µM of silver ions and methanol showed the best sensitivity. The validation results showed the intra- (0.8-9.2%) and inter-day (2.5-14.9%) precisions, limits of detection (0.0005-5.0 ng/mL), and matrix effect (71.8-100.3%) for the screening analysis. No significant ion suppression was observed. In addition, this method was successfully applied to analysis of positive samples from suspected abusers and useful for the detection of the trace levels of anabolic steroids in human urine samples.

Serum kinetics, distribution and excretion of silver in rabbits following 28 days after a single intravenous injection of silver nanoparticles.

Serum kinetics, tissue distribution, and excretion of citrate-coated silver nanoparticles (AgNPs) were investigated in rabbits (n = 4) up to 28 days after a single intravenous injection. Following a single injection of AgNPs, the AUC(last) was reported to be 3.65 ± 0.68 µg·day/ml in 5 mg/kg-treated group and 0.90 ± 0.16 µg·day/ml in 0.5 mg/kg-treated group, respectively. The accumulation of silver was observed in all the tested organs including liver, kidney, spleen, lung, brain, testis, and thymus at 1 day, 7 day, and 28 day of measurement. The liver and spleen seemed to be the major targets because of high accumulation of silver. Excretion via feces and urine was also monitored during the entire experimental period. Unexpectedly, much more excretion of silver occurred via feces than through urine after an intravenous injection, which suggests biliary excretion of AgNPs. General toxicity was analyzed and histopathological changes were also evaluated.

A health surveillance case study on workers who manufacture silver nanomaterials.

The levels of exposure and internal doses of nanomaterials are becoming more and more important for estimating the health effects resulting from exposure to nanomaterials. Health surveillance can be used as an indicator of whether exposure is occurring, rather than in determining if levels of exposure are safe. We have conducted a health surveillance study in a workplace which manufactures silver nanomaterials, including the assessment of personal exposure levels to silver nanoparticles, a walk-through evaluation of the manufacturing process and the collection of blood and urine samples from the exposed workers. Two male workers who had worked for 7 years in the business of manufacturing silver nanomaterial were exposed to silver concentrations of 0.35 and 1.35 µg/m(3). The blood and urine levels of silver were 0.034 and 0.0135 µg/dl for blood and 0.043 µg/dl and not detected level for urine. The blood chemistry and haematology data were determined to be within a normal range. Taken together, the health surveillance indicated that the nanomaterial manufacturing workers were exposed to a much lower concentration of silver dust or soluble silver threshold limit values and showed no significant findings on their health status.

Colloidal silver ingestion with copper and caeruloplasmin deficiency.

The copper concentration in serum can be affected by the presence of other trace elements such as silver. Low serum copper may result in decreased caeruloplasmin synthesis. We report the case of a 59-year-old woman, who was admitted to hospital with acute psychosis and who had been ingesting chronically, colloidal silver.

[Conditions affecting renal excretion of silver by humans. Studies on metabolism of trace elements. VIII]. / Renale Ausscheidungsbedingungen von Silber beim Menschen. Untersuchungen über den Stoffwechsel von Spurenelementen, VIII. Mitteilung

The renal excretion of silver was investigated in adult experimental persons of both sexes with normal or variously decreased kidney functions. Silver was measured by emission spectrum analysis. With an indifferent urinary flow of 4.71 plus or minus 2.5 (mean value with standard deviation) ml/min, the mean Ag-excretion was 0.653 plus or minus 0.432 ng/min for a standard 1.73 m2 body surface area. An apparent small increase in the Ag-excretion with increased rate of urine flow could not be statistically confirmed. The widely different Ag-excretion between individuals showed no dependence on the state of diuresis, or on kidney haemodynamic factors down to a decreased inulin clearance of less than 40 ml/min, and a decrease of the PAH clearance to values less than 200 ml/min.