Blood clearance and tissue distribution of PEGylated and non-PEGylated gold nanorods after intravenous administration in rats\ud

Aims: To develop and determine the safety of gold nanorods, whose aspect ratios can be tuned to obtain plasmon peaks between 650 and 850 nm, as contrast enhancing agents for diagnostic and therapeutic applications. Materials & methods: In this study we compared the blood clearance and tissue distribution of cetyl trimethyl ammonium bromide (CTAB)-capped and polyethylene glycol (PEG)-coated gold nanorods after intravenous injection in the tail vein of rats. The gold content in blood and various organs was measured quantitatively with inductively coupled plasma mass spectrometry. Results & discussion: The CTAB-capped gold nanorods were almost immediately (<15 min) cleared from the blood circulation whereas the PEGylation of gold nanorods resulted in a prolonged blood circulation with a half-life time of 19 h and more wide spread tissue distribution. While for the CTAB-capped gold nanorods the tissue distribution was limited to liver, spleen and lung, the PEGylated gold nanorods also distributed to kidney, heart, thymus, brain and testes. PEGylation of the gold nanorods resulted in the spleen being the organ with the highest exposure, whereas for the non-PEGylated CTAB-capped gold nanorods the liver was the organ with the highest exposure, per gram of organ. Conclusion: The PEGylation of gold nanorods resulted in a prolongation of the blood clearance and the highest organ exposure in the spleen. In view of the time frame (up to 48 h) of the observed presence in blood circulation, PEGylated gold nanorods can be considered to be promising candidates for therapeutic and diagnostic imaging purpose

Structure and the Physico-Mechanical Properties of the Ceramic Coatings Obtained by the Cumulative -Detonation Device

Dense, with good adhesion to the substrate, hard, wear-resistant coatings from the powder of Al2O3 were obtained on the surface of the steel (STE255) by using the cumulative-detonation device. The results of investigations of the structure and physico-mechanical properties of the coatings by using scanning, optical microscopy, X-ray phase analysis, microhardness and tribological tests are presented. It was found that optimization of plasma spraying to helps reduce the porosity of coatings of Al2O3 less than 1 % and to increase the hardness of them to 1250 HV0.3. The tribological investigations have shown that the coatings of Al2O3 significantly increase the wear resistance of the sample STE255 and provide a low ability to wear out the coating. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/3546

Antenatal screening for HIV, hepatitis B and syphilis in the Netherlands is effective

Abstract Background A screening programme for pregnant women has been in place since the 1950s in the Netherlands. In 2004 universal HIV screening according to opting out was implemented. Here, we describe the evaluation of the effectiveness of antenatal screening in the Netherlands for 2006-2008 for HIV, hepatitis B virus (HBV) and syphilis in preventing mother-to-child transmission, by using various data sources. Methods The results of antenatal screening (2006-2008) were compared with data from pregnant women and newborns from other data sources. Results Each year, around 185,000 pregnant women were screened for HIV, HBV and syphilis. Refusal rates for the screening tests were low, and were highest (0.2%) for HIV. The estimated annual prevalence of HIV among pregnant women was 0.05%. Prior to the introduction of screening, 5-10 children were born with HIV annually After the introduction of screening in 2004, only 4 children were born with HIV (an average of 1 per year). Two of these mothers had become pregnant prior to 2004; the third mother was HIV negative at screening and probably became infected after screening; the fourth mother's background was unknown. Congenital syphilis was diagnosed in fewer than 5 newborns annually and 5 children were infected with HBV. In 3 of these, the mothers were HBeAg positive (a marker for high infectivity). We estimated that 5-10 HIV, 50-75 HBV and 10 syphilis cases in newborns had been prevented annually as a result of screening. Conclusions The screening programme was effective in detecting HIV, HBV and syphilis in pregnant women and in preventing transmission to the child. Since the introduction of the HIV screening the number of children born with HIV has fallen dramatically. Previous publication [Translation from: 'Prenatale screening op hiv, hepatitis B en syphilis in Nederland effectief', published in 'The Dutch Journal of Medicine ' (NTVG, in Dutch)]</p

The MARINA Risk Assessment Strategy: A Flexible Strategy for Efficient Information Collection and Risk Assessment of Nanomaterials

An engineered nanomaterial (ENM) may actually consist of a population of primary particles, aggregates and agglomerates of various sizes. Furthermore, their physico-chemical characteristics may change during the various life-cycle stages. It will probably not be feasible to test all varieties of all ENMs for possible health and environmental risks. There is therefore a need to further develop the approaches for risk assessment of ENMs. Within the EU FP7 project Managing Risks of Nanoparticles (MARINA) a two-phase risk assessment strategy has been developed. In Phase 1 (Problem framing) a base set of information is considered, relevant exposure scenarios (RESs) are identified and the scope for Phase 2 (Risk assessment) is established. The relevance of an RES is indicated by information on exposure, fate/kinetics and/or hazard; these three domains are included as separate pillars that contain specific tools. Phase 2 consists of an iterative process of risk characterization, identification of data needs and integrated collection and evaluation of data on the three domains, until sufficient information is obtained to conclude on possible risks in a RES. Only data are generated that are considered to be needed for the purpose of risk assessment. A fourth pillar, risk characterization, is defined and it contains risk assessment tools. This strategy describes a flexible and efficient approach for data collection and risk assessment which is essential to ensure safety of ENMs. Further developments are needed to provide guidance and make the MARINA Risk Assessment Strategy operational. Case studies will be needed to refine the strategy

Distinct T cell responsiveness to different COVID-19 vaccines and cross-reactivity to SARS-CoV-2 variants with age and CMV status

Introduction: Accumulating evidence indicates the importance of T cell immunity in vaccination-induced protection against severe COVID-19 disease, especially against SARS-CoV-2 Variants-of-Concern (VOCs) that more readily escape from recognition by neutralizing antibodies. However, there is limited knowledge on the T cell responses across different age groups and the impact of CMV status after primary and booster vaccination with different vaccine combinations. Moreover, it remains unclear whether age has an effect on the ability of T cells to cross-react against VOCs. Methods: Therefore, we interrogated the Spike-specific T cell responses in healthy adults of the Dutch population across different ages, whom received different vaccine types for the primary series and/or booster vaccination, using IFNɣ ELISpot. Cells were stimulated with overlapping peptide pools of the ancestral Spike protein and different VOCs. Results: Robust Spike-specific T cell responses were detected in the vast majority of participants upon the primary vaccination series, regardless of the vaccine type (i.e. BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad26.COV2.S). Clearly, in the 70+ age group, responses were overall lower and showed more variation compared to younger age groups. Only in CMV-seropositive older adults (>70y) there was a significant inverse relation of age with T cell responses. Although T cell responses increased in all age groups after booster vaccination, Spike-specific T cell frequencies remained lower in the 70+ age group. Regardless of age or CMV status, primary mRNA-1273 vaccination followed by BNT162b2 booster vaccination showed limited booster effect compared to the BNT162b2/BNT162b2 or BNT162b2/mRNA-1273 primary-booster regimen. A modest reduction in cross-reactivity to the Alpha, Delta and Omicron BA.1, but not the Beta or Gamma variant, was observed after primary vaccination. Discussion: Together, this study shows that age, CMV status, but also the primary-booster vaccination regimen influence the height of the vaccination-induced Spike-specific T cell response, but did not impact the VOC cross-reactivity

Contribution of SARS-CoV-2 infection preceding COVID-19 mRNA vaccination to generation of cellular and humoral immune responses in children

Primary COVID-19 vaccination for children, 5-17 years of age, was offered in the Netherlands at a time when a substantial part of this population had already experienced a SARS-CoV-2 infection. While vaccination has been shown effective, underlying immune responses have not been extensively studied. We studied immune responsiveness to one and/or two doses of primary BNT162b2 mRNA vaccination and compared the humoral and cellular immune response in children with and without a preceding infection. Antibodies targeting the original SARS-CoV-2 Spike or Omicron Spike were measured by multiplex immunoassay. B-cell and T-cell responses were investigated using enzyme-linked immunosorbent spot (ELISpot) assays. The activation of CD4+ and CD8+ T cells was studied by flowcytometry. Primary vaccination induced both a humoral and cellular adaptive response in naive children. These responses were stronger in those with a history of infection prior to vaccination. A second vaccine dose did not further boost antibody levels in those who previously experienced an infection. Infection-induced responsiveness prior to vaccination was mainly detected in CD8+ T cells, while vaccine-induced T-cell responses were mostly by CD4+ T cells. Thus, SARS-CoV-2 infection prior to vaccination enhances adaptive cellular and humoral immune responses to primary COVID-19 vaccination in children. As most children are now expected to contract infection before the age of five, the impact of infection-induced immunity in children is of high relevance. Therefore, considering natural infection as a priming immunogen that enhances subsequent vaccine-responsiveness may help decision-making on the number and timing of vaccine doses

Distinct T cell responsiveness to different COVID-19 vaccines and cross-reactivity to SARS-CoV-2 variants with age and CMV status

IntroductionAccumulating evidence indicates the importance of T cell immunity in vaccination-induced protection against severe COVID-19 disease, especially against SARS-CoV-2 Variants-of-Concern (VOCs) that more readily escape from recognition by neutralizing antibodies. However, there is limited knowledge on the T cell responses across different age groups and the impact of CMV status after primary and booster vaccination with different vaccine combinations. Moreover, it remains unclear whether age has an effect on the ability of T cells to cross-react against VOCs.MethodsTherefore, we interrogated the Spike-specific T cell responses in healthy adults of the Dutch population across different ages, whom received different vaccine types for the primary series and/or booster vaccination, using IFNɣ ELISpot. Cells were stimulated with overlapping peptide pools of the ancestral Spike protein and different VOCs.ResultsRobust Spike-specific T cell responses were detected in the vast majority of participants upon the primary vaccination series, regardless of the vaccine type (i.e. BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad26.COV2.S). Clearly, in the 70+ age group, responses were overall lower and showed more variation compared to younger age groups. Only in CMV-seropositive older adults (&gt;70y) there was a significant inverse relation of age with T cell responses. Although T cell responses increased in all age groups after booster vaccination, Spike-specific T cell frequencies remained lower in the 70+ age group. Regardless of age or CMV status, primary mRNA-1273 vaccination followed by BNT162b2 booster vaccination showed limited booster effect compared to the BNT162b2/BNT162b2 or BNT162b2/mRNA-1273 primary-booster regimen. A modest reduction in cross-reactivity to the Alpha, Delta and Omicron BA.1, but not the Beta or Gamma variant, was observed after primary vaccination.DiscussionTogether, this study shows that age, CMV status, but also the primary-booster vaccination regimen influence the height of the vaccination-induced Spike-specific T cell response, but did not impact the VOC cross-reactivity

Overview of potential adverse health effects of oral exposure to nanocellulose.

Nanocellulose is an emerging material for which several food-related applications are foreseen, for example, novel food, functional food, food additive or in food contact materials. Nanocellulose materials can display a range of possible shapes (fibers, crystals), sizes and surface modifications. For food-related applications in the EU, information on the safety of substances must be assessed. The present review summarizes the current knowledge on (possible) adverse health effects of nanocellulose upon oral exposure, keeping EU regulatory aspects in mind. The overview indicates that toxicity data, especially from in vivo studies, are limited and outcomes are not unambiguous. The hazard assessment is further complicated by: the diversity in morphologies and surface modifications, lack of standard reference materials, limited knowledge about intestinal fate and absorption, analytical difficulties in biological matrices, dispersion issues, the possible presence of impurities and interferences within biological assays. Two subchronic in vivo toxicity studies show no indications of toxicity for two specific nanocellulose materials, even at high doses. However, these studies may have missed certain early or nano-specific toxic effects, such as inflammation potential, for which other, subacute studies provide some indications. Most in vitro studies show no cytotoxicity; however, several indicate that effects on oxidative stress and inflammatory responses depend on differences in size or surface treatments. Further, too few studies assessed genotoxicity of nanocelluloses. Therefore, immunotoxicity, oxidative stress and genotoxicity require further attention, as do absorption and effects on nutrient uptake. Recommendations for future research facilitating the safety assessment and safe-by-design of nanocellulose in food-related applications are provided

Issues currently complicating the risk assessment of synthetic amorphous silica (SAS) nanoparticles after oral exposure.

Synthetic amorphous silica (SAS) is applied in food products as food additive E 551. It consists of constituent amorphous silicon dioxide (SiO2) nanoparticles that form aggregates and agglomerates. We reviewed recent oral toxicity studies with SAS. Some of those report tissue concentrations of silicon (Si). The results of those studies were compared with recently determined tissue concentrations of Si (and Si-particles) in human postmortem tissues. We noticed inconsistent results of the various toxicity studies regarding toxicity and reported tissue concentrations, which hamper the risk assessment of SAS. A broad range of Si concentrations is reported in control animals in toxicity studies. The Si concentrations found in human postmortem tissues fall within this range. On the other hand, the mean concentration found in human liver is higher than the reported concentrations causing liver effects in some animal toxicity studies after oral exposure to SAS. Also higher liver concentrations are observed in other, negative animal studies. Those inconsistencies could be caused by the presence of other Si-containing chemical substances or particles (which potentially also includes background SAS) and/or different sample preparation and analytical techniques that were used. Other factors which could explain the inconsistencies in outcome between the toxicity studies are the distinct SAS used and different dosing regimes, such as way of administration (dietary, via drinking water, oral gavage), dispersion of SAS and dose. More research is needed to address these issues and to perform a proper risk assessment for SAS in food. The current review will help to progress research on the toxicity of SAS and the associated risk assessment

Rangeland management effects on soil properties in the savanna biome, South Africa: A case study along grazing gradients in communal and commercial farms

Although the savanna biome of South Africa is a major resource for rangeland management, little is known about how differences in rangeland management systems affect soil properties in such biomes. Near to Kuruman, commercial farms have practiced rotational grazing for decades. In communal areas of former homeland Bophuthatswana, similar strategies were used prior to 1994. Nowadays, a continuous grazing system is common. We hypothesized that these changes in management affected soil properties. To test this, we sampled soils at communal and commercial land along a gradient with increasing distance to water points. The results revealed that communal systems with continuous grazing showed enlarged spatial gradients. The soils were depleted in most nutrients close to the water relative to those of commercial systems. In contrast, as the distance to the water increased, the nutrient stocks of these communal systems were higher. Changes in soil nutrient stocks were related to a zone of increased bush encroachment (up to 25%). Specific analyses (phosphorus fractions, particulate organic carbon, δ13C) confirmed that the soils of the communal grazing systems benefited from the shift of grass-dominated to bush-dominated system with woody Acacia vegetation, while the rangeland degraded in the sense that it lost palatable grass species