Tissue distribution and acute toxicity of silver after single intravenous administration in mice: nano-specific and size-dependent effects

Background: Silver nanoparticles (AgNPs) are an important class of nanomaterials used as antimicrobial agents for a wide range of medical and industrial applications. However toxicity of AgNPs and impact of their physicochemical characteristics in in vivo models still need to be comprehensively characterized. The aim of this study was to investigate the effect of size and coating on tissue distribution and toxicity of AgNPs after intravenous administration in mice, and compare the results with those obtained after silver acetate administration. Methods: Male CD-1(ICR) mice were intravenously injected with AgNPs of different sizes (10 nm, 40 nm, 100 nm), citrate-or polyvinylpyrrolidone-coated, at a single dose of 10 mg/kg bw. An equivalent dose of silver ions was administered as silver acetate. Mice were euthanized 24 h after the treatment, and silver quantification by ICP-MS and histopathology were performed on spleen, liver, lungs, kidneys, brain, and blood. Results: For all particle sizes, regardless of their coating, the highest silver concentrations were found in the spleen and liver, followed by lung, kidney, and brain. Silver concentrations were significantly higher in the spleen, lung, kidney, brain, and blood of mice treated with 10 nm AgNPs than those treated with larger particles. Relevant toxic effects (midzonal hepatocellular necrosis, gall bladder hemorrhage) were found in mice treated with 10 nm AgNPs, while in mice treated with 40 nm and 100 nm AgNPs lesions were milder or negligible, respectively. In mice treated with silver acetate, silver concentrations were significantly lower in the spleen and lung, and higher in the kidney than in mice treated with 10 nm AgNPs, and a different target organ of toxicity was identified (kidney). Conclusions: Administration of the smallest (10 nm) nanoparticles resulted in enhanced silver tissue distribution and overt hepatobiliary toxicity compared to larger ones (40 and 100 nm), while coating had no relevant impact. Distinct patterns of tissue distribution and toxicity were observed after silver acetate administration. It is concluded that if AgNPs become systemically available, they behave differently from ionic silver, exerting distinct and size-dependent effects, strictly related to the nanoparticulate form

De-risking strategy: Longevity spread buy-in

The paper proposes a demographic de-risking strategy for a pension provider, to deal with the future uncertainty in longevity over a long time horizon. The innovative idea of a longevity spread buy-in is presented. The formulae for calculating the buy-in premium are proposed in the case of pension plans. The proposal directly impacts the pension provider’s risk management systems and hence can be an important part of the overall approach to risk management. The numerical results, developed under specified stochastic hypotheses for the dynamics of the underlying financial and demographic processes, show how the proposal of the paper can be practically implemented

Cost-effectiveness analysis of personalised versus standard dosimetry for selective internal radiation therapy with TheraSphere in patients with hepatocellular carcinoma

Aims: To perform a cost-effectiveness analysis (CEA) comparing personalised dosimetry with standard dosimetry in the context of selective internal radiation therapy (SIRT) with TheraSphere for the management of adult patients with locally advanced hepatocellular carcinoma (HCC) from the Italian Healthcare Service perspective. Materials and methods: A partition survival model was developed to project costs and the quality-adjusted life years (QALYs) over a lifetime horizon. Clinical inputs were retrieved from a published randomised controlled trial. Health resource utilisation inputs were extracted from the questionnaires administered to clinicians in three oncology centres in Italy, respectively. Cost parameters were based on Italian official tariffs. Results: Over a lifetime horizon, the model estimated the average QALYs of 1.292 and 0.578, respectively, for patients undergoing personalised and standard dosimetry approaches. The estimated mean costs per patient were €23,487 and €19,877, respectively. The incremental cost-utility ratio (ICUR) of personalised versus standard dosimetry approaches was €5,056/QALY. Conclusions: Personalised dosimetry may be considered a cost-effective option compared to standard dosimetry for patients undergoing SIRT for HCC in Italy. These findings provide evidence for clinicians and payers on the value of personalised dosimetry as a treatment option for patients with HCC

Dread Disease and Cause-Specific Mortality: Exploring New Forms of Insured Loans

The relevance of critical illness coverage and life insurance in cause-specific mortality conditions is increasing in many industrialized countries. Specific conditions on the illness and on death event, providing cheapest premiums for the insureds and lower obligations for the insurers, constitute interesting products in an insurance market looking to offer appealing products. On the other hand, the systematic improvement in longevity gives rise to a market with agents getting increasingly older, and the insurer pays attention to this trend. There are financial contracts joined with insurance coverage, and this particularly happens in the case of the so-called insured loan. Insured loans are financial contracts often proposed together with a term life insurance in order to cover the lender and the heirs against the borrower’s death event within the loan duration. This paper explores new insurance products that, linked to an insured loan, are founded on specific illness hypotheses and/or cause-specific mortality. The aim is to value how much the insurance costs lighten with respect to the traditional term insurance. The authors project cause-specific mortality rates and specific diagnosis rates, in this last case overcoming the discontinuities in the data. The new contractual schemes are priced. Numerical applications also show, with several graphs, the rates projection procedure and plenty of tables report the premiums in the new proposed contractual forms. The complete amortization schedule closes the work

New challenges in pension industry: proposals of personal pension products

Insurance policies with profit participation are generally characterized by some contract peculiarities as the guarantee of a minimum rate of return and annual bonus based on return on investment. Within this framework, we propose a contract scheme of life annuities with participation level depending on the period financial resul

Real Estate Pension Schemes: Modeling and Perspectives

The paper is focused on a contractual scheme where an immediate life annuity is obtained by paying a single premium in the form of real estate rights (RERs). Such contract is framed within the varied macrocosm of personal pension products, that proves to be an increasingly attractive and scientifically stimulating tool in the economic and social context in which we currently find ourselves. The basic structure requires the lender to pay the borrower/homeowner a life annuity against a part or the totality of the future liquidation value of his home at the time of his death. In this work we will explore some characteristics of the product, paying attention to the risk sources which impact on it

Real estate pension schemes: modeling and perspectives

The paper is focused on a contractual scheme where an immediate life annuity is obtained by paying a single premium in the form of real estate rights (RERs). Such contract is framed within the varied macrocosm of personal pension products, that proves to be an increasingly attractive and scientifically stimulating tool in the economic and social context in which we currently find ourselves. The basic structure requires the lender to pay the borrower/homeowner a life annuity against a part or the totality of the future liquidation value of his home at the time of his death. In this work we will explore some characteristics of the product, paying attention to the risk sources which impact on it

Determination of total silicon and SiO2 particles using an ICP-MS based analytical platform for toxicokinetic studies of synthetic amorphous silica

Synthetic amorphous silica (SAS), manufactured in pyrogenic or precipitated form, is a nanomaterial with a widespread use as food additive (E 551). Oral exposure to SAS results from its use in food and dietary supplements, pharmaceuticals and toothpaste. Recent evidence suggests that oral exposure to SAS may pose health risks and highlights the need to address the toxic potential of SAS as affected by the physicochemical characteristics of the different forms of SAS. For this aim, investigating SAS toxicokinetics is of crucial importance and an analytical strategy for such an undertaking is presented. The minimization of silicon background in tissues, control of contamination (including silicon release from equipment), high-throughput sample treatment, elimination of spectral interferences affecting inductively coupled plasma mass spectrometry (ICP-MS) silicon detection, and development of analytical quality control tools are the cornerstones of this strategy. A validated method combining sample digestion with silicon determination by reaction cell ICP-MS is presented. Silica particles are converted to soluble silicon by microwave dissolution with mixtures of HNO3, H2O2 and hydrofluoric acid (HF), whereas interference-free ICP-MS detection of total silicon is achieved by ion-molecule chemistry with limits of detection (LoDs) in the range 0.2–0.5 µg Si g−1 for most tissues. Deposition of particulate SiO2 in tissues is assessed by single particle ICP-MS105Nanotechnology in Agriculture and Food IndustryThis work arises from the NANOGENOTOX Joint Action which has received funding from the European Union, in the framework of the Health Programme. The NANOGENOTOX Joint Action was co-funded by the Executive Agency for Health and Consumers (Grant Agreement 2009 21 01). This publication reflects only the authors’ views and the Executive Agency for Health and Consumers (now CHAFEA) is not liable for any use that may be made of the information contained therei