All that is silver is not toxic: silver ion and particle kinetics reveals the role of silver ion aging and dosimetry on the toxicity of silver nanoparticles.

BACKGROUND: When suspended in cell culture medium, nano-objects composed of soluble metals such as silver can dissolve resulting in ion formation, altered particle properties (e.g. mass, morphology, etc.), and modulated cellular dose. Cultured cells are exposed not just to nanoparticles but to a complex, dynamic mixture of altered nanoparticles, unbound ions, and ion-ligand complexes. Here, three different cell types (RAW 264.7 macrophages and bone marrow derived macrophages from wild-type C57BL/6 J mice and Scavenger Receptor A deficient (SR-A(-/-)) mice) were exposed to 20 and 110 nm silver nanoparticles, and RAW 264.7 cells were exposed to freshly mixed silver ions, aged silver ions (ions incubated in cell culture medium), and ions formed from nanoparticle dissolution. The In Vitro Sedimentation, Diffusion, Dissolution, and Dosimetry Model (ISD3) was used to predict dose metrics for each exposure scenario. RESULTS: Silver nanoparticles, freshly mixed ions, and ions from nanoparticle dissolution were toxic, while aged ions were not toxic. Macrophages from SR-A(-/-) mice did not take up 20 nm silver nanoparticles as well as wild-types but demonstrated no differences in silver levels after exposure to 110 nm nanoparticles. Dose response modeling with ISD3 predicted dose metrics suggest that amount of ions in cells and area under the curve (AUC) of ion amount in cells are the most predictive of cell viability after nanoparticle and combined nanoparticle/dissolution-formed-ions exposures, respectively. CONCLUSIONS: Results of this study suggest that the unbound silver cation is the ultimate toxicant, and ions formed extracellularly drive toxicity after exposure to nanoparticles. Applying computational modeling (ISD3) to better understand dose metrics for soluble nanoparticles allows for better interpretation of in vitro hazard assessments.

ISD3: a particokinetic model for predicting the combined effects of particle sedimentation, diffusion and dissolution on cellular dosimetry for in vitro systems.

BACKGROUND: The development of particokinetic models describing the delivery of insoluble or poorly soluble nanoparticles to cells in liquid cell culture systems has improved the basis for dose-response analysis, hazard ranking from high-throughput systems, and now allows for translation of exposures across in vitro and in vivo test systems. Complimentary particokinetic models that address processes controlling delivery of both particles and released ions to cells, and the influence of particle size changes from dissolution on particle delivery for cell-culture systems would help advance our understanding of the role of particles and ion dosimetry on cellular toxicology. We developed ISD3, an extension of our previously published model for insoluble particles, by deriving a specific formulation of the Population Balance Equation for soluble particles. RESULTS: ISD3 describes the time, concentration and particle size dependent dissolution of particles, their delivery to cells, and the delivery and uptake of ions to cells in in vitro liquid test systems. We applied the model to calculate the particle and ion dosimetry of nanosilver and silver ions in vitro after calibration of two empirical models, one for particle dissolution and one for ion uptake. Total media ion concentration, particle concentration and total cell-associated silver time-courses were well described by the model, across 2 concentrations of 20 and 110 nm particles. ISD3 was calibrated to dissolution data for 20 nm particles as a function of serum protein concentration, but successfully described the media and cell dosimetry time-course for both particles at all concentrations and time points. We also report the finding that protein content in media affects the initial rate of dissolution and the resulting near-steady state ion concentration in solution for the systems we have studied. CONCLUSIONS: By combining experiments and modeling, we were able to quantify the influence of proteins on silver particle solubility, determine the relative amounts of silver ions and particles in exposed cells, and demonstrate the influence of particle size changes resulting from dissolution on particle delivery to cells in culture. ISD3 is modular and can be adapted to new applications by replacing descriptions of dissolution, sedimentation and boundary conditions with those appropriate for particles other than silver.

The Impact of Initial Specimen Diversion Systems on Blood Culture Contamination.

Blood culture contamination is associated with increased antimicrobial use, length of stay, and hospital cost. To address this problem, blood culture diversion has been developed as an additional measure to reduce contamination to targeted goals. Three different versions were proposed, including an open technique and 2 commercially available devices. This study aims to review the existing literature and analyze evidence for these 3 techniques.

Response of the reactor performance and microbial community to a shift of ISDD process from micro-aerobic to anoxic condition.

Micro-aerobic condition has proven to be effective in enhancing sulfide oxidation to elemental sulfur (S0) during integrated simultaneous desulfurization and denitrification process (ISDD). In this study we investigated and compared the performance and microbial community of ISDD process operating under initially anoxic, then micro-aerobic and finally switch back to anoxic condition. For all the three tested scenarios, comparable bioreactor performance in terms of sulfate (95.0 ±â€¯4.4%, 90.6 ±â€¯3.8%, 89.8 ±â€¯3.5%) and nitrate (∼100%) removal was achieved. However, a shift of ISDD bioreactor from micro-aerobic to anoxic environment clearly increased the S0 production (30.6%), relative to that at initial anoxic condition (14.2%). Further anoxic bioreactor operation with different influent nitrate concentrations also obtained satisfactory performance particularly in terms of S0 production. Microbial community analysis results showed that functional microorganisms selectively enriched at micro-aerobic condition, particularly sulfide-oxidizing bacteria (SOB), could also function well and enhance S0 production when bioreactor switching from micro-aerobic to anoxic environment. We proposed that micro-aerobic strategy could function as a bio-selector and provide a new idea in functional microorganisms selectively enrichment for wastewater treatment.

Semi-analytical solution for the in-vitro sedimentation, diffusion and dosimetry model: surveying the impact of the Peclet number.

Reducing size of the particles to the nanoscale range gives them new physicochemical properties. Several experiments have shown cytotoxic effects for different kinds of engineered nanoparticles (ENP). In-vitro cell culture assays are widely utilized by researchers to evaluate cytotoxic effects of the ENPs. The present paper deals with the "In vitro Sedimentation, Diffusion and Dosimetry (ISDD)" model. This mathematical model uses an advection-diffusion equation with specific assumptions and coefficients to estimate the dose of the particles delivered to the cells monolayer in the culture medium. In the present work, utilizing the generalized integral transform technique (GITT), a semi-analytical solution is developed for the ISDD model. The parameters affecting the ISDD predictions are integrated into two dimensionless numbers, Pe and τ. The Pe number shows the ratio of the convective to the diffusive mass transport rates and τ is a dimensionless time parameter. The quality of the results for an extensive range of Pe and τ numbers is surveyed through application of the developed formula to two series of test cases. A comparison of the results with those obtained from numerical methods shows deviations in the numerical results at high Pe numbers. Applying the developed formula, ISDD predictions for a wide practical range of Pe and τ numbers are calculated and plotted in two- and three-dimensional plots. The curves and formula obtained in this study facilitate the achievement of ISDD predictions with higher accuracies and capabilities for verification of the results.