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As the use of engineered nanomaterials increases, so does the risk of them spreading to natural ecosystems. Hitherto, knowledge regarding the toxic properties of nanoparticles (NP’s) and their potential interactions with natural bio-organic molecules adsorbed to them, and thereby forming surface coronas, is limited. However, we show here that the toxic effect of NPs of tungsten carbide cobalt (WC–Co) and cobalt (Co) on the crustacean Daphnia magna is postponed in the presence of natural biological degradation products (eco-corona biomolecules). For Daphnia exposed to WC–Co NPs the survival time increased with 20–25% and for Co NPs with 30–47% after mixing the particles with a solution of eco-corona biomolecules before exposure. This suggests that an eco-corona, composed of biomolecules always present in natural ecosystems, reduces the toxic potency of both studied NPs. Further, the eco-coronas did not affect the particle uptake, suggesting that the reduction in toxicity was related to the particle-organism interaction after eco-corona formation. In a broader context, this implies that although the increasing use and production of NPs may constitute a novel, global environmental threat, the acute toxicity and long-term effects of some NPs will, at least under certain conditions, be reduced as they enter natural ecosystems.

Rigidification of the isobutyl side chain of drug-like AT2 receptor agonists and antagonists that are structurally related to the first reported selective AT2 receptor agonist 1 (C21) delivered bioactive indane derivatives., Rigidification of the isobutyl side chain of drug-like AT2 receptor agonists and antagonists that are structurally related to the first reported selective AT2 receptor agonist 1 (C21) delivered bioactive indane derivatives. Four enantiomer pairs were synthesized and the enantiomers were isolated in an optical purity >99%. The enantiomers 7a, 7b, 8a, 8b, 9a, 9b, 10a and 10b bind to the AT2 receptor with moderate (Ki = 54–223 nM) to high affinity (Ki = 2.2–7.0 nM). The enantiomer with positive optical rotation (+) exhibited the highest affinity at the receptor. The indane derivatives 7b and 10a are among the most potent AT2 receptor antagonists reported so far. As illustrated by the enantiomer pairs 7a/b and 10a/b, an alteration at the stereogenic center has a pronounced impact on the activation process of the AT2 receptor, and can convert agonists to antagonists and vice versa.

The quartz crystal microbalance (QCM) has been used to study how the interfacial layer of an ionic liquid dissolved in a polar oil at low weight percentages responds to changes in applied potential. The changes in surface composition at the QCM gold surface depend on both the magnitude and sign of the applied potential. The time-resolved response indicates that the relaxation kinetics are limited by the diffusion of ions in the interfacial region and not in the bulk, since there is no concentration dependence. The measured mass changes cannot be explained only in terms of simple ion exchange; the relative molecular volumes of the ions and the density changes in response to ion exclusion must be considered. The relaxation behavior of the potential between the electrodes upon disconnecting the applied potential is more complex than that observed for pure ionic liquids, but a measure of the surface charge can be extracted from the exponential decay when the rapid initial potential drop is accounted for. The adsorbed film at the gold surface consists predominantly of ionic liquid despite the low concentration, which is unsurprising given the surtactant-like structures of (some of) the ionic liquid ions. Changes in response to potential correspond to changes in the relative numbers of cations and anions, rather than a change in the oil composition. No evidence for an electric field induced change in viscosity is observed. This work shows conclusively that electric potentials can be used to control the surface composition, even in an oil-based system, and paves the way for other ion solvent studies.

The influence of surface adsorption of benzotriazole (BTAH) and of chloride ions (Cl-) on the kinetics of copper electrodeposition/dissolution in copper sulfate solutions and on copper deposit char ...

Welding fume particles are hazardous. Their toxicity likely depends on their composition and reactivity. This study aimed at exploring the role of sodium or other fluorides (NaF), which are intentionally added to flux-cored wire electrodes for stainless steel welding, on the solubility (in phosphate buffered saline) and toxicity of the generated welding fume particles. A multi-analytical particle characterization approach along with in-vitro cell assays was undertaken. The release of Cr(VI) and Mn from the particles was tested as a function of fluoride solution concentration. The welding fume particles containing NaF released significantly higher amounts of Cr(VI) compared with solid wire reference fumes, which was associated with increased cytotoxicity and genotoxicity in-vitro. No crystalline Na or potassium (K) containing chromates were observed. Cr(VI) was incorporated in an amorphous mixed oxide. Solution-added fluorides did not increase the solubility of Cr(VI), but contributed to a reduced Mn release from both solid and flux-cored wire fume particles and the reduction of Cr(VI) release from solid wire fume particles. Chemical speciation modeling suggested that metal fluoride complexes were not formed. The presence of NaF in the welding electrodes did not have any direct, but possibly an indirect, role in the Cr(VI) solubility of welding fumes.

Metal-based high-touch surfaces used for indoor applications such as doorknobs, light switches, handles and desks need to remain their antimicrobial properties even when tarnished or degraded. A novel laboratory methodology of relevance for indoor atmospheric conditions and fingerprint contact has therefore been elaborated for combined studies of both tarnishing/corrosion and antimicrobial properties of such high-touch surfaces. Cu metal was used as a benchmark material. The protocol includes pre-tarnishing/corrosion of the high touch surface for different time periods in a climatic chamber at repeated dry/wet conditions and artificial sweat deposition followed by the introduction of bacteria onto the surfaces via artificial sweat droplets. This methodology provides a more realistic and reproducible approach compared with other reported procedures to determine the antimicrobial efficiency of high-touch surfaces. It provides further a possibility to link the antimicrobial characteristics to physical and chemical properties such as surface composition, chemical reactivity, tarnishing/corrosion, surface roughness and surface wettability. The results elucidate that bacteria interactions as well as differences in extent of tarnishing can alter the physical properties (e.g. surface wettability, surface roughness) as well as the extent of metal release. The results clearly elucidate the importance to consider changes in chemical and physical properties of indoor hygiene surfaces when assessing their antimicrobial properties.

Hazard classification of metal alloys is today generally based on their bulk content, an approach that seldom reflects the extent of metal release for a given environment. Such information can instead be achieved via bioelution testing under simulated physiological conditions. The use of bioelution data instead of bulk contents would hence refine the current hazard classification of alloys and enable grouping. Bioelution data have been generated for nickel (Ni) and cobalt (Co) released from several stainless steel grades, one low-alloyed steel, and Ni and Co metals in synthetic sweat, saliva and gastric fluid, for exposure periods from 2 to 168 h. All stainless steel grades with bulk contents of 0.11–10 wt% Ni and 0.019–0.24 wt% Co released lower amounts of Ni (up to 400-fold) and Co (up to 300-fold) than did the low-alloyed steel (bulk content: 0.034% Ni, 0.015% Co). They further showed a relative bioaccessibility of Ni and Co considerably less than 1, while the opposite was the case for the low-alloyed steel. Surface oxide- and electrochemical corrosion investigations explained these findings in terms of the high passivity of the stainless steels related to the Cr(III)-rich surface oxide that readily adapted to the fluid acidity and chemistry.

The results of a recent meta-analysis aroused concern about an increased risk of death associated with the use of paclitaxel-coated angioplasty balloons and stents in lower-limb endovascular interventions for symptomatic peripheral artery disease.We conducted an unplanned interim analysis of data from a multicenter, randomized, open-label, registry-based clinical trial. At the time of the analysis, 2289 patients had been randomly assigned to treatment with drug-coated devices (the drug-coated-device group, 1149 patients) or treatment with uncoated devices (the uncoated-device group, 1140 patients). Randomization was stratified according to disease severity on the basis of whether patients had chronic limb-threatening ischemia (1480 patients) or intermittent claudication (809 patients). The single end point for this interim analysis was all-cause mortality.No patients were lost to follow-up. Paclitaxel was used as the coating agent for all the drug-coated devices. During a mean follow-up of 2.49 years, 574 patients died, including 293 patients (25.5%) in the drug-coated-device group and 281 patients (24.6%) in the uncoated-device group (hazard ratio, 1.06; 95% confidence interval, 0.92 to 1.22). At 1 year, all-cause mortality was 10.2% (117 patients) in the drug-coated-device group and 9.9% (113 patients) in the uncoated-device group. During the entire follow-up period, there was no significant difference in the incidence of death between the treatment groups among patients with chronic limb-threatening ischemia (33.4% [249 patients] in the drug-coated-device group and 33.1% [243 patients] in the uncoated-device group) or among those with intermittent claudication (10.9% [44 patients] and 9.4% [38 patients], respectively).In this randomized trial in which patients with peripheral artery disease received treatment with paclitaxel-coated or uncoated endovascular devices, the results of an unplanned interim analysis of all-cause mortality did not show a difference between the groups in the incidence of death during 1 to 4 years of follow-up. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT02051088.).

The neurotoxicity of hard metal-based nanoparticles (NPs) remains poorly understood. Here, we deployed the human neuroblastoma cell line SH-SY5Y differentiated or not into dopaminergic- and cholinergic-like neurons to study the impact of tungsten carbide (WC) NPs, WC NPs sintered with cobalt (Co), or Co NPs versus soluble CoCl2. Co NPs and Co salt triggered a dose-dependent cytotoxicity with an increase in cytosolic calcium, lipid peroxidation, and depletion of glutathione (GSH). Co NPs and Co salt also suppressed glutathione peroxidase 4 (GPX4) mRNA and protein expression. Co-exposed cells were rescued by N-acetylcysteine (NAC), a precursor of GSH, and partially by liproxstatin-1, an inhibitor of lipid peroxidation. Furthermore, in silico analyses predicted a significant correlation, based on similarities in gene expression profiles, between Co-containing NPs and Parkinson's disease, and changes in the expression of selected genes were validated by RT-PCR. Finally, experiments using primary human dopaminergic neurons demonstrated cytotoxicity and GSH depletion in response to Co NPs and CoCl2 with loss of axonal integrity. Overall, these data point to a marked neurotoxic potential of Co-based but not WC NPs and show that neuronal cell death may occur through a ferroptosis-like mechanism.

The use of silver nanoparticles (Ag NPs) in consumer products can result in diffuse environmental dispersion of both NPs and ionic silver. This study investigated the transformation of Ag NPs present in two consumer products (skin cream, mouth spray) in terms of release of Ag NPs and ionic silver and changes in particle size in artificial sweat and saliva solutions. Large differences in silver release were observed with the smaller sized Ag NPs in mouth spray releasing more silver compared with the Ag NPs of the skin cream. Substantial particle agglomeration took place in both artificial sweat and saliva, forming large-sized agglomerates (> 100 nm). The amount of dissolved silver in solution after 24 h was less than 10% of the total amount of Ag NPs for both products. The results show that the Ag NPs of these consumer products will largely remain as NPs even after 24 h of skin or saliva contact. The use of normalization by geometric surface area of the particles was tested as a way to compare dissolution for Ag NPs of different characteristics, including pristine, bare, as well as PVP-capped Ag NPs. Normalization of silver dissolution with the geometric surface area was shown promising, but more extensive studies are required to unambiguously conclude whether it is a way forward to enable grouping of the dissolution behavior of Ag NPs released from consumer products. Electronic supplementary material The online version of this article (10.1007/s11356-020-11241-w) contains supplementary material, which is available to authorized users.

Nickel (Ni) and cobalt (Co) release from chromium-alloy powders (different stainless steels and a nickel-based Inconel alloy) compared with Ni and Co metal powders was investigated at simulated human exposure scenarios (ingestion, skin contact, and inhalation) between 2 and 168 h. All investigated powders consisted of particles sized within the respirable range. The powder particles and their surface reactivity were studied by means of nitrogen adsorption and electrochemical, spectroscopic (X-ray photoelectron spectroscopy and atomic absorption spectroscopy), light scattering, and microscopic techniques. The release of both Ni and Co was highest in the acidic and complexing fluids simulating the gastric environment and an inhalation scenario of small powders (artificial lysosomal fluid). Relatively high corrosion resistance and lower levels of released Ni and Co were observed in all fluids for all alloy powders compared with the corresponding pure metals. The extent of released metals was low for powders with a passive surface oxide. This study strongly emphasizes the importance of considering alloying effects in toxicological classification and/or regulation of Ni and Co in alloys and metals., Graphical Abstract

Background Genotoxicity is an important toxicological endpoint due to the link to diseases such as cancer. Therefore, an increased understanding regarding genotoxicity and underlying mechanisms is needed for assessing the risk with exposure to nanoparticles (NPs). The aim of this study was to perform an in-depth investigation regarding the genotoxicity of well-characterized Ni and NiO NPs in human bronchial epithelial BEAS-2B cells and to discern possible mechanisms. Comparisons were made with NiCl2 in order to elucidate effects of ionic Ni. Methods BEAS-2B cells were exposed to Ni and NiO NPs, as well as NiCl2, and uptake and cellular dose were investigated by transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS). The NPs were characterized in terms of surface composition (X-ray photoelectron spectroscopy), agglomeration (photon cross correlation spectroscopy) and nickel release in cell medium (ICP-MS). Cell death (necrosis/apoptosis) was investigated by Annexin V-FITC/PI staining and genotoxicity by cytokinesis-block micronucleus (cytome) assay (OECD 487), chromosomal aberration (OECD 473) and comet assay. The involvement of intracellular reactive oxygen species (ROS) and calcium was explored using the fluorescent probes, DCFH-DA and Fluo-4. Results NPs were efficiently taken up by the BEAS-2B cells. In contrast, no or minor uptake was observed for ionic Ni from NiCl2. Despite differences in uptake, all exposures (NiO, Ni NPs and NiCl2) caused chromosomal damage. Furthermore, NiO NPs were most potent in causing DNA strand breaks and generating intracellular ROS. An increase in intracellular calcium was observed and modulation of intracellular calcium by using inhibitors and chelators clearly prevented the chromosomal damage. Chelation of iron also protected against induced damage, particularly for NiO and NiCl2. Conclusions This study has revealed chromosomal damage by Ni and NiO NPs as well as Ni ionic species and provides novel evidence for a calcium-dependent mechanism of cyto- and genotoxicity. Electronic supplementary material The online version of this article (10.1186/s12989-018-0268-y) contains supplementary material, which is available to authorized users.

The interplay between atmospheric corrosion and antimicrobial efficiency of bare Cu and Cu5Zn5Al1Sn was studied upon exposures simulating high-touch surface conditions. The survival of the bacteria Bacillus subtilis during surface contact with Cu and Cu5Zn5Al1Sn was examined under different degrees of surface oxidation, tarnishing, wettability and copper ion release. Depending on surface conditions complete bacteria inhibition was obtained within 4 min on Cu and within 6–10 min on Cu5Zn5Al1Sn. The antibacterial efficiency increases slightly with copper release rate and is governed by complex interactions between the corroded metal surface, bacteria and extracellular polymeric substances produced by the bacteria.

Adsorption of thiols with cationic or anionic terminal group on gold has been studied from mixed solutions of 11-Amino-1-undecanethiol (AUT) and 3-Mercaptopropionic acid (MPA) using Quartz Crystal Microbalance with Dissipation (QCM-D), X-ray Photoelectron Spectroscopy (XPS), atomic force microscopy (AFM) and contact angles. The goal is to probe the nature of such layers, and the additivity or otherwise of the pH responsiveness, with a view to evaluate their suitability as smart materials. For each of the two pure (unmixed) cases, ordered molecular monolayers are formed with sulfur binding to gold and the alkane chain pointing out from the surface as expected. Adsorption from the thiol mixtures, however, leads to a more complex behaviour. The surface concentration of thiols from the mixtures, as determined by QCM-D, is considerably lower than for the pure cases and it reaches a minimum at a 3:1 MPA/AUT relative concentration in the solution. The XPS results confirm a reduction in adsorbed amount in mixtures with the lowest overall intensity for the 3:1 ratio. Monolayers formed from mixtures display a wettability which is much lower and less pH sensitive. Collectively these results confirm that for adsorption from mixed systems, the configuration is completely different. Complex formation in the mixed solutions leads to the adsorption of molecules parallel to the surface in an axially in-plane configuration. This parallel layer of thiols is mechanically relatively robust to nano-shaving based on AFM measurements. These results will have a significant impact on the design of biomimetic surface coatings particularly when mixtures of oppositely charged molecules are present on the surface, as is commonly the case in biological, proteinaceous surfaces (e.g. hair and skin).

Silver (Ag) nanoparticles are commonly used in consumer products due to their antimicrobial properties. Here we studied the impact of Ag nanoparticles on immune responses by using cell lines of monocyte/macrophage and lung epithelial cell origin, respectively. Short-term experiments (24 h) showed that Ag nanoparticles reduced the lipopolysaccharide (LPS)-induced secretion of pro-inflammatory cytokines in THP-1 cells under serum-free conditions. ICP-MS analysis revealed that cellular uptake of Ag was higher under these conditions. Long-term exposure (up to 6 weeks) of BEAS-2B cells to Ag nanoparticles also suppressed pro-inflammatory cytokine production following a brief challenge with LPS. Experiments using reporter cells revealed that Ag nanoparticles as well as AgNO3 inhibited LPS-triggered Toll-like receptor (TLR) signaling. Furthermore, RNA-sequencing of BEAS-2B cells indicated that Ag nanoparticles affected TLR signaling pathways. In conclusion, Ag nanoparticles reduced the secretion of pro-inflammatory cytokines in response to LPS, likely as a result of the release of silver ions leading to an interference with TLR signaling. This could have implications for the use of Ag nanoparticles as antibacterial agents. Further in vivo studies are warranted to study this.

Millions of people in the world perform welding as their primary occupation resulting in exposure to metal-containing nanoparticles in the fumes generated. Even though health effects including airway diseases are well-known, there is currently a lack of studies investigating how different welding set-ups and conditions affect the toxicity of generated nanoparticles of the welding fume. The aim of this study was to investigate the toxicity of nine types of welding fume particles generated via active gas shielded metal arc welding (GMAW) of chromium-containing stainless steel under different conditions and, furthermore, to correlate the toxicity to the particle characteristics. Toxicological endpoints investigated were generation of reactive oxygen species (ROS), cytotoxicity, genotoxicity and activation of ToxTracker reporter cell lines. The results clearly underline that the choice of filler material has a large influence on the toxic potential. Fume particles generated by welding with the tested flux-cored wire (FCW) were found to be more cytotoxic compared to particles generated by welding with solid wire or metal-cored wire (MCW). FCW fume particles were also the most potent in causing ROS and DNA damage and they furthermore activated reporters related to DNA double- strand breaks and p53 signaling. Interestingly, the FCW fume particles were the most soluble in PBS, releasing more chromium in the hexavalent form and manganese compared to the other fumes. These results emphasize the importance of solubility of different metal constituents of the fume particles, rather than the total metal content, for their acute toxic potential.

Rigidification of the isobutyl side chain of drug-like AT(2) receptor agonists and antagonists that are structurally related to the first reported selective AT(2) receptor agonist 1 (C21) delivered bioactive indane derivatives. Four enantiomer pairs were synthesized and the enantiomers were isolated in an optical purity >99%. The enantiomers 7a, 7b, 8a, 8b, 9a, 9b, 10a and 10b bind to the AT(2) receptor with moderate (K-i = 54-223 nM) to high affinity (K-i = 2.2-7.0 nM). The enantiomer with positive optical rotation (+) exhibited the highest affinity at the receptor. The indane derivatives 7b and 10a are among the most potent AT(2) receptor antagonists reported so far. As illustrated by the enantiomer pairs 7a/b and 10a/b, an alteration at the stereogenic center has a pronounced impact on the activation process of the AT(2) receptor, and can convert agonists to antagonists and vice versa.

Copper foil electrodeposition has been explored using a pure titanium rotating disk electrode (RDE) in acidic electrolytes containing gelatin and/or chloride ions under different convection conditi ...

A new technical guideline has been implemented by the Council of Europe (CoE) to ensure the stability and safety of food contact articles of metals and alloys, using 5 g/L citric acid (pH 2.4) and ...

Copper nanoparticles (Cu NPs) are increasingly used in various biologically relevant applications and products, e.g., due to their antimicrobial and catalytic properties. This inevitably demands for an improved understanding on their interactions and potential toxic effects on humans. The aim of this study was to investigate the corrosion of copper nanoparticles in various biological media and to elucidate the speciation of released copper in solution. Furthermore, reactive oxygen species (ROS) generation and lung cell (A549 type II) membrane damage induced by Cu NPs in the various media were studied. The used biological media of different complexity are of relevance for nanotoxicological studies: Dulbecco’s modified eagle medium (DMEM), DMEM+ (includes fetal bovine serum), phosphate buffered saline (PBS), and PBS+histidine. The results show that both copper release and corrosion are enhanced in DMEM+, DMEM, and PBS+histidine compared with PBS alone. Speciation results show that essentially no free copper ions are present in the released fraction of Cu NPs in neither DMEM+, DMEM nor histidine, while labile Cu complexes form in PBS. The Cu NPs were substantially more membrane reactive in PBS compared to the other media and the NPs caused larger effects compared to the same mass of Cu ions. Similarly, the Cu NPs caused much more ROS generation compared to the released fraction only. Taken together, the results suggest that membrane damage and ROS formation are stronger induced by Cu NPs and by free or labile Cu ions/complexes compared with Cu bound to biomolecules.

Agonists of the angiotensin II receptor type 2 (AT2), a G-protein coupled receptor, promote tissue protective effects in cardiovascular and renal diseases, while antagonists reduce neuropathic pain. We here report detailed molecular models that explain the AT2 receptor selectivity of our recent series of non-peptide ligands. In addition, minor structural changes of these ligands that provoke different functional activity are rationalized at a molecular level, and related to the selectivity for the different receptor conformations. These findings should pave the way to structure based drug discovery of AT2 receptor ligands.

When using biosensors, analyte biomolecules of several different concentrations are percolated over a chip with immobilized ligand molecules that form complexes with analytes. However, in many cases of biological interest, e.g., in antibody interactions, complex formation steady-state is not reached. The data measured are so-called sensorgram, one for each analyte concentration, with total complex concentration vs time. Here we present a new four-step strategy for more reliable processing of this complex kinetic binding data and compare it with the standard global fitting procedure. In our strategy, we first calculate a dissociation graph to reveal if there are any heterogeneous interactions. Thereafter, a new numerical algorithm, AIDA, is used to get the number of different complex formation reactions for each analyte concentration level. This information is then used to estimate the corresponding complex formation rate constants by fitting to the measured sensorgram one by one. Finally, all estimated rate constants are plotted and clustered, where each cluster represents a complex formation. Synthetic and experimental data obtained from three different QCM biosensor experimental systems having fast (close to steady-state), moderate, and slow kinetics (far from steady-state) were evaluated using the four-step strategy and standard global fitting. The new strategy allowed us to more reliably estimate the number of different complex formations, especially for cases of complex and slow dissociation kinetics. Moreover, the new strategy proved to be more robust as it enables one to handle system drift, i.e., data from biosensor chips that deteriorate over time.

An increasing use of cobalt (Co)-based nanoparticles (NPs) in different applications and exposures at occupational settings triggers the need for toxicity assessment. Improved understanding regarding the physiochemical characteristics of Co metal NPs and different oxides in combination with assessment of toxicity and mechanisms may facilitate decisions for grouping during risk assessment. The aim of this study was to gain mechanistic insights in the correlation between NP reactivity and toxicity of three different Co-based NPs (Co, CoO, and Co3O4) by using various tools for characterization, traditional toxicity assays, as well as six reporter cell lines (ToxTracker) for rapid detection of signaling pathways of relevance for carcinogenicity. The results showed cellular uptake of all NPs in lung cells and induction of DNA strand breaks and oxidative damage (comet assay) by Co and CoO NPs. In-depth studies on the ROS generation showed high reactivity of Co, lower for CoO, and no reactivity of Co3O4 NPs. The reactivity depended on the corrosion and transformation/dissolution properties of the particles and the media highlighting the role of the surface oxide and metal speciation as also confirmed by in silico modeling. By using ToxTracker, Co NPs were shown to be highly cytotoxic and induced reporters related to oxidative stress (Nrf2 signaling) and DNA strand breaks. Similar effects were observed for CoO NPs but at higher concentrations, whereas the Co3O4 NPs were inactive at all concentrations tested. In conclusion, our study suggests that Co and CoO NPs, but not Co3O4, may be grouped together for risk assessment.

Knowledge of how metal releases from the stainless steels used in food processing applications and cooking utensils is essential within the framework of human health risk assessment. A new European ...

Cobalt chromium molybdenum alloys (CoCr-Mo) are commonly used as articulating components in joint prostheses. In this tribocorrosive environment, wear debris and metal ionic species are released and interact with proteins, possibly resulting in protein aggregation. This study aimed to investigate whether this could have an eff ect on the friction coefficient in a typical material couple, namely CoCrMo-onpolyethylene. It was confirmed that both Co(II) and Cr(III) ions, and their combination, at concentrations relevant for the metal release situation, resulted in protein aggregation and its concomitant precipitation, which increased the friction coeffi cient. Future studies should identify the clinical importance of these findings.

Background Approximately 1–3% of the adult population in Europe is allergic to chromium (Cr). A new restriction in REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) based on the ISO 17075 standard has recently been adopted in the EU to limit Cr(VI) in consumer and occupational leather products. Objectives The aim of this study was to critically assess key experimental parameters in this standard on the release of Cr(III) and Cr(VI) and their relevance for skin exposure. Material and methods Four differently tanned, unfinished, leather samples were systematically investigated for their release of Cr(III) and Cr(VI) in relation to surface area, key exposure parameters, temperature, ultraviolet irradiation, and time. Results Although the total release of Cr was largely unaffected by all investigated parameters, except exposure duration and temperature, the Cr oxidation state was highly dynamic, with reduced amounts of released Cr(VI) with time, owing to the simultaneous release of reducing agents from the leather. Significantly more Cr(III) than Cr(VI) was released from the Cr-tanned leather for all conditions tested, and it continued to be released in artificial sweat up to at least 1 week of exposure. Conclusions Several parameters were identified that influenced the outcome of the ISO 17075 test.

Background: Correlations between CRP and serum lipids are weak, and there are conflicting and incomplete results in the literature. The aim of the present study was to clarify the strength and independence of relationships between CRP and serum lipids in outpatients. Methods: Inclusion criteria were outpatients where all the following analyses were requested in clinical routine: high sensitivity CRP, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, ApoB, ApoA-1 and Lp(a). Data for patients meeting the above criteria during a period of six years (2004-2010) were copied from Aleris Medilab’s Laboratory Information System to the software Statistica. Basic statistics and correlations were calculated for 2771 patients. In patients with two (n = 959) or more sampling times changes over time were calculated. The study was a quality assurance project without access to patient files. Results: Median age was 59 years and median serum CRP concentration was 1.5 mg/L. The strongest correlations (Spearman R) were seen between CRP and triglycerides (0.25), ApoB/ApoA-1 ratio (0.21) and HDL-cholesterol (−0.18). Stepwise regression analysis showed that ApoB, total cholesterol, log triglycerides and log Lp(a) together explained 8% of the variation in log CRP. Unfavourable time trends for CRP and triglycerides counteracted a significant decrease in LDL-cholesterol and total cholesterol. Conclusion: In a large cohort of outpatients CRP showed stronger correlation with triglycerides and ApoB/ApoA-1 ratio than with LDL-cholesterol and Lp(a). LDL-cholesterol concentrations changed favorably over time whereas CRP and triglycerides did not.

To ensure the safety of metals and alloys intended for food contact, a new European test protocol (CoE protocol) using citric acid as a food simulant was published in 2013. This study investigated the influence of citric acid and exposure conditions on the metal release from an austenitic manganese stainless steel (AISI 201). Exposures in 5g/L citric acid resulted in significantly lower metal releases compared with specific release limits set by the CoE protocol. 5g/L (0.3vol%) citric acid was more aggressive than 3vol% acetic acid (Italian protocol) due to higher metal complexation. Studies on abraded surfaces revealed that most metals were released during the first 0.5h of exposure due to surface passivation. Surface abrasion, increased temperature (40–100°C), increased surface area to solution volume ratio (0.25–2cm2/mL) and increased citric acid concentration (0–21g/L) all resulted in increased released metal quantities.

Welding fume of stainless steels is potentially health hazardous. The aim of this study was to investigate the manganese (Mn) and chromium (Cr) speciation of welding fume particles and their extent of metal release relevant for an inhalation scenario, as a function of particle size, welding method (manual metal arc welding, metal arc welding using an active shielding gas), different electrodes (solid wires and flux-cored wires) and shielding gases, and base alloy (austenitic AISI 304L and duplex stainless steel LDX2101). Metal release investigations were performed in phosphate buffered saline (PBS), pH 7.3, 37°, 24h. The particles were characterized by means of microscopic, spectroscopic, and electroanalytical methods. Cr was predominantly released from particles of the welding fume when exposed in PBS [3-96% of the total amount of Cr, of which up to 70% as Cr(VI)], followed by Mn, nickel, and iron. Duplex stainless steel welded with a flux-cored wire generated a welding fume that released most Cr(VI). Nano-sized particles released a significantly higher amount of nickel compared with micron-sized particle fractions. The welding fume did not contain any solitary known chromate compounds, but multi-elemental highly oxidized oxide(s) (iron, Cr, and Mn, possibly bismuth and silicon).

The zeta potential (ZP) is a parameter commonly used to characterize metal nanoparticles (NPs) in solution. Such determinations are for example performed in nanotoxicology since the ZP influences e.g. the interaction between cells and different biomolecules. Four case studies on different metal NPs (Cu and Zn NPs, and citrate capped Ag NPs) are presented in this study in order to provide guidance on how to accurately interpret and report ZP data. Solutions of high ionic strength (150 mM NaCl) induce a higher extent of particle agglomeration (elucidated with Ag NPs) when compared with conditions in 10 mM NaCl, which further complicates the prediction of the ZP due to e.g. sedimentation and broadening of the zeta potential distribution. The particle size is seldom included specifically in the standard ways of determining ZP (Hückel and Smoluchowski approximations). However corrections are possible when considering approximations of the Henry function. This was seen to improve the analysis of NPs, since there are cases when both the Hückel and the Smulochowski approximations are invalid. In biomolecule-containing cell media (BEGM), the signal from e.g. proteins may interfere with the measured ZP of the NPs. The intensity distribution of the ZP of both the blank solution and the solution containing NPs should hence be presented in addition to the mean value. Due to an increased ionic strength for dissolving of metal NPs (exemplified by Zn NPs), the released metal ions must be considered when interpreting the zeta potential measurements. In this work the effect was however negligible, as the particle size was several hundred nm, conditions that made the Smoluchowski approximation valid despite an increased ionic strength. However, at low ionic strengths (mM range) and small-sized NPs (tens of nm), the effect of released metal ions can influence the choice of model for determining the zeta potential. Sonication of particle dispersions influences not only the extent of metal release but also the outermost surface oxide composition, which often results in an increased ZP. Surface compositional changes were illustrated for sonicated and non-sonicated Cu NPs. In all, it can be concluded that accurate measurements and interpretations are possible in most cases by collecting and reporting complementary data on characteristics such as particle size, ZP distributions, blank sample information, and particle oxide composition.

This paper presents an in-depth characterisation study of the patina formed on a copper tile taken from the roof of Queen Anne's Summer Palace in Prague after > 300 years of exposure to the action of the atmosphere. A wide variety of techniques have been used, including metallographic and chemical analysis (electrogravimetry, AAS, XRF) of the copper matrix, and spectroscopic and microscopic investigations (GIXRD, FTIR, TEM/EDS and SEM/EDS) to determine the composition and structure of the patina. The major conclusions of the study are: (a) the base copper contains abundant inclusions mainly of rosiaite (PbSbO); (b) the patina is formed by an inner sublayer of cuprite (CuO) and an outer sublayer of brochantite [CuSO(OH)] and antlerite [CuSO(OH)] and traces of azurite [Cu(CO)(OH)]; and (c) the brochantite/antlerite crystals are randomly doped with Fe and C.

Silver is increasingly used in antimicrobial coatings of biomedical devices and implants to hinder infections. As proteins have been shown to largely influence the extent of released metals from various metal surfaces at biological conditions, silver may also be influenced in the same way. The aim of this study is to relate the structure of adsorbed lysozyme (LSZ) to the release of silver from metallic silver surfaces. Simultaneous adsorption measurements were performed in real time on the same surface using combined ellipsometry and quartz crystal microbalance with dissipation monitoring measurements to provide a more comprehensive understanding on the adsorption kinetics and the layer structures. The concentration of LSZ in 0.15 M NaNO3 solution (pH 7, 25 °C) influences the structure of the adsorbed layer. Monolayer coverage is obtained at concentrations ≤0.1 g/L, while a bilayer structure with a rigid inner layer and a relatively loosely adsorbed outer layer is formed at 1 g/L. The inner layer of LSZ is assumed to bind firmly to silver via disulfide bridges, which makes it irreversibly adsorbed with respect to dilution. The amount of released silver is further influenced by the structure of the LSZ layer. At low LSZ concentrations (≤0.1 g/L) the amount of released silver is not significantly different compared with non-protein-containing NaNO3 solutions; however, noticeable reduction was observed at higher concentrations (1 g/L). This reduction in silver release has several possible explanations, including (i) surface complexation between LSZ and silver ions that may result in the incorporation of silver in the irreversible adsorbed layer and, hence, reduce the amount of released silver into solution, and (ii) net charge reversal at the protein/solution interface to slightly positive surface potentials. Any release of silver will therefore exhibit an electrostatic repulsion during transportation through the protein layer results in a reduced amount of silver in solution.

This work describes the chemical, mechanical and antibacterial properties of a novel silver nanocluster/silica composite coating, obtained by sputtering, on textiles for use in nuclear bacteriological and chemical (NBC) protection suites and for aerospace applications. The properties of the coated textiles were analyzed in terms of surface morphology, silver concentration and silver release in artificial sweat and synthetic tap water, respectively. No release of silver nanoparticles was observed at given conditions. The water repellency, permeability, flammability and mechanical resistance of the textiles before and after sputtering demonstrated that the textile properties were not negatively affected by the coating. The antibacterial effect was evaluated at different experimental conditions using a standard bacterial strain of Staphylococcus aureus and compared with the behavior of uncoated textiles. The coating process conferred all textiles a good antibacterial activity. Optimal deposition conditions were elaborated to obtain sufficient antibacterial action without altering the aesthetical appearance of the textiles. The antibacterial coating retained its antibacterial activity after one cycle in a washing machine only for the Nylon based textile. QC 20141205 NASLA

Saralasin and sarile, extensively studied over the past 40 years as angiotensin II (Ang II) receptor blockers, induce neurite outgrowth in a NG108-15 cell assay to a similar extent as the endogenous Ang II. In their undifferentiated state, these cells express mainly the AT2 receptor. The neurite outgrowth was inhibited by preincubation with the AT2 receptor selective antagonist PD 123,319, which suggests that the observed outgrowth was mediated by the AT2 receptor. Neither saralasin nor sarile reduced the neurite outgrowth induced by Ang II proving that the two octapeptides do not act as antagonists at the AT2 receptor and may be considered as AT2 receptor agonists.

The mechanism of corrosion product flaking on bare copper sheet and three copper-based alloys in chloride rich environments has been explored through field and laboratory exposures. The tendency for flaking is much more pronounced on Cu and Cu–4wt%Sn than on Cu–15wt%Zn and Cu–5wt%Al–5wt%Zn. This difference is explained by the initial formation of zinc and zinc–aluminum hydroxycarbonates on Cu15Zn and Cu5Al5Zn, which delays the formation of CuCl, a precursor of Cu2(OH)3Cl. As a result, the observed volume expansion during transformation of CuCl to Cu2(OH)3Cl, and concomitant corrosion product flaking, is less severe on Cu15Zn and Cu5Al5Zn than on Cu and Cu4Sn.

Selective laser melting (SLM) is increasingly used for the fabrication of customized dental components made of metal alloys such as CoCrMo. The main aim of the present study is to elucidate the influence of the non-equilibrium microstructure obtained by SLM on corrosion susceptibility and extent of metal release (measure of biocompatibility).A multi-analytical approach has been employed by combining microscopic and bulk compositional tools with electrochemical techniques and chemical analyses of metals in biologically relevant fluids for three differently SLM fabricated CoCrMo alloys and one cast CoCrMo alloy used for comparison.Rapid cooling and strong temperature gradients during laser melting resulted in the formation of a fine cellular structure with cell boundaries enriched in Mo (Co depleted), and suppression of carbide precipitation and formation of a martensitic ɛ (hcp) phase at the surface. These features were shown to decrease the corrosion and metal release susceptibility of the SLM alloys compared with the cast alloy. Unique textures formed in the pattern of the melting pools of the three different laser melted CoCrMo alloys predominantly explain observed small, though significant, differences. The susceptibility for corrosion and metal release increased with an increased number (area) of laser melt pool boundaries.This study shows that integrative and interdisciplinary studies of microstructural characteristics, corrosion, and metal release are essential to assess and consider during the design and fabrication of CoCrMo dental components of optimal biocompatibility. The reason is that the extent of metal release from CoCrMo is dependent on fabrication procedures.

Bare copper sheet and three commercial Cu-based alloys, Cu15Zn, Cu4Sn and Cu5Al5Zn, have been exposed to four test sites in Brest, France, with strongly varying chloride deposition rates. The corrosion rates of all four materials decrease continuously with distance from the coast, i.e. with decreasing chloride load, and in the following order: Cu4Sn>Cu sheet>Cu15Zn>Cu5Al5Zn. The patina on all materials was composed of two main layers, Cu2O as the inner layer and Cu2(OH)3Cl as the outer layer, and with a discontinuous presence of CuCl in between. Additional minor patina constituents are SnO2 (Cu4Sn), Zn5(OH)6(CO3)2 (Cu15Zn and Cu5Al5Zn) and Zn6Al2(OH)16CO3·4H2O/Zn2Al(OH)6Cl·2H2O/Zn5Cl2(OH)8·H2O and Al2O3 (Cu5Al5Zn). The observed Zn- and Zn/Al-containing corrosion products might be important factors for the lower sensitivity of Cu15Zn and Cu5Al5Zn against chloride-induced atmospheric corrosion compared with Cu sheet and Cu4Sn.Decreasing corrosion rates with exposure time were observed for all materials and chloride loads and attributed to an improved adherence with time of the outer patina to the underlying inner oxide. Flaking of the outer patina layer was mainly observed on Cu4Sn and Cu sheet and associated with the gradual transformation of CuCl to Cu2(OH)3Cl of larger volume. After three years only Cu5Al5Zn remains lustrous because of a patina compared with the other materials that appeared brownish–reddish.Significantly lower release rates of metals compared with corresponding corrosion rates were observed for all materials. Very similar release rates of copper from all four materials were observed during the fifth year of marine exposure due to an outer surface patina that with time revealed similar constituents and solubility properties.

The objective of this study was to investigate the extent of released Co, Cr(III), Cr(VI), and Mo from a biomedical high-carbon CoCrMo alloy exposed in phosphate-buffered saline (PBS), without and with the addition of 10 µM H2 O2 (PBS + H2 O2 ), and 10 g L(-1) bovine serum albumin (PBS + BSA) for time periods up to 28 days. Comparative studies were made on AISI 316L for the longest time period. No Cr(VI) release was observed for any of the alloys in either PBS or PBS + H2 O2 at open-circuit potential (no applied potential). However, at applied potentials (0.7 V vs. Ag/AgCl), Cr was primarily released as Cr(VI). Co was preferentially released from the CoCrMo alloy at no applied potential. As a consequence, Cr was enriched in the utmost surface oxide reducing the extent of metal release over time. This passivation effect was accelerated in PBS + H2 O2 . As previously reported for 316L, BSA may also enhance metal release from CoCrMo. However, this was not possible to verify due to the precipitation of metal-protein complexes with reduced metal concentrations in solution as a consequence. This was particularly important for Co-BSA complexes after sufficient time and resulted in an underestimation of metals in solution.

There is currently a need to develop and test in vitro systems for predicting the toxicity of nanoparticles. One challenge is to determine the actual cellular dose of nanoparticles after exposure.In this study, human epithelial lung cells (A549) were exposed to airborne Cu particles at the air-liquid interface (ALI). The cellular dose was determined for two different particle sizes at different deposition conditions, including constant and pulsed Cu aerosol flow.Airborne polydisperse particles with a geometric mean diameter (GMD) of 180 nm [geometric standard deviation (GSD) 1.5, concentration 10(5) particles/mL] deposited at the ALI yielded a cellular dose of 0.4-2.6 μg/cm(2) at pulsed flow and 1.6-7.6 μg/cm(2) at constant flow. Smaller polydisperse particles in the nanoregime (GMD 80 nm, GSD 1.5, concentration 10(7) particles/mL) resulted in a lower cellular dose of 0.01-0.05 μg/cm(2) at pulsed flow, whereas no deposition was observed at constant flow. Exposure experiments with and without cells showed that the Cu particles were partly dissolved upon deposition on cells and in contact with medium.Different cellular doses were obtained for the different Cu particle sizes (generated with different methods). Furthermore, the cellular doses were affected by the flow conditions in the cell exposure system and the solubility of Cu. The cellular doses of Cu presented here are the amount of Cu that remained on the cells after completion of an experiment. As Cu particles were partly dissolved, Cu (a nonnegligible contribution) was, in addition, present and analyzed in the nourishing medium present beneath the cells. This study presents cellular doses induced by Cu particles and demonstrates difficulties with deposition of nanoparticles at the ALI and of partially soluble particles.

New insights are presented on the speciation of surface oxide phases on fine inert gas atomised (GA

Differences in surface oxide characteristics and extent of nickel release have been investigated in two thoroughly characterized micron-sized (mainly

There is increasing evidence that angiotensin II (Ang II), through binding to the type 2 (AT(2)) receptor may have beneficial effects in various physiological and pathological situations. However, specific action presumably mediated by the angiotensin AT(2) receptor has been hampered by the absence of appropriate selective ligands. The aim of this study was to compare the biological properties of two related and selective drug-like nonpeptide AT(2) ligands, namely an agonist called M024 (also known as Compound 21) and a new ligand, presumably an antagonist, C38/M132, (originally called C38). Properties of the compounds were investigated in NG108-15 cells expressing angiotensin AT(2) receptor and known to develop neurite outgrowth upon Ang II stimulation. NG108-15 cells stimulated for three days with C21/M024 (0.1 or 100nM) exhibited the same neurite outgrowth as cells stimulated with Ang II (100nM) while co-incubation of Ang II or C21/M024 with C38/M132 (10 or 100nM) inhibited their effects, similarly to the angiotensin AT(2) receptor antagonist, PD123319 (10μM). As Ang II, C21/M024 induced a Rap1-dependent activation of p42/p44(mapk) whereas preincubation of cells with C38/M132 inhibited p42/p44(mapk) and Rap1 activation induced by Ang II. Three-day treatment with C21/M024 or Ang II decreased cell number in culture, an effect that was rescued by preincubation with C38/M132. Taken together, these results indicate that the nonpeptide ligand C21/M024 is a potent angiotensin AT(2) receptor agonist while C38/M132 acts as an antagonist. These selective nonpeptide angiotensin AT(2) ligands may represent unique and long-awaited tools for the pursuit of in vivo studies.