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  • 1
    Online Resource
    Online Resource
    Wiley ; 2007
    In:  Journal of Biomedical Materials Research Part A Vol. 83A, No. 2 ( 2007-11), p. 538-545
    In: Journal of Biomedical Materials Research Part A, Wiley, Vol. 83A, No. 2 ( 2007-11), p. 538-545
    Abstract: Two types of hydroxyethyl‐methacrylated dextran (dex‐HEMA) hydrogels differing in crosslink density were compared for local tissue responses and degradation characteristics in mice and rats. Implants (1 mm thick, rat: 10 mm diameter, mouse: 6 mm diameter) varying in degree of HEMA substitution (DS5 and DS13, meaning 5 or 13 HEMA groups per 100 glucose units of dextran) were subcutaneously implanted and tissue responses were evaluated at week 2, 6, and 13 after implantation. In the rat after 2 weeks a slight fibrous capsule was formed composed of macrophages and fibroblasts sometimes accompanied by a minimal infiltrate. Small fragments, surrounded by macrophages and giant cells indicated hydrogel degradation. After 13 weeks DS5 implants were resorbed while parts of the DS13 implants were still present. In the mouse a moderate to strong capsule formation was present at 2 weeks accompanied by inflammatory cells (macrophages and polymorphonuclear granulocytes) and debris. Draining lymph node activation was observed. Skin ulceration was present irrespective of the type of implant. Clear differences in the tissue responses between the rat and mouse were noted, as well as between implants of different degree of substitution. Mice showed a more pronounced early inflammatory response compared with rats, whereas the degradation was more complete in rats than in mice. The differences in histology between the hydrogels disappeared over time at 13 weeks after implantation and similar responses were noted for both types of hydrogels. Both in mice and rats the DS5 hydrogels showed a faster degradation rate than the DS13 hydrogels. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007
    Type of Medium: Online Resource
    ISSN: 1549-3296 , 1552-4965
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2007
    detail.hit.zdb_id: 1477192-5
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  • 2
    In: Small, Wiley, Vol. 19, No. 21 ( 2023-05)
    Abstract: Physiologically‐based kinetic (PBK) modeling is a valuable tool to understand the kinetics of nanoparticles (NPs) in vivo. However, estimating PBK parameters remains challenging and commonly requires animal studies. To develop predictive models to estimate PBK parameter values based on NP characteristics, a database containing PBK parameter values and corresponding NP characteristics is needed. As a first step toward this objective, this study estimates PBK parameters for gold NPs (AuNPs) and provides a comparison of two different NPs. Two animal experiments are conducted in which varying doses of AuNPs attached with polyethylene glycol (PEG) are administered intravenously to rats. The resulting Au concentrations are used to estimate PBK model parameters. The parameters are compared with PBK parameters previously estimated for poly(alkyl cyanoacrylate) NPs loaded with cabazitaxel and for LipImage 815. This study shows that a small initial database of PBK parameters collected for three NPs is already sufficient to formulate new hypotheses on NP characteristics that may be predictive of PBK parameter values. Further research should focus on developing a larger database and on developing quantitative models to predict PBK parameter values.
    Type of Medium: Online Resource
    ISSN: 1613-6810 , 1613-6829
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2168935-0
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  • 3
    In: Environmental and Molecular Mutagenesis, Wiley, Vol. 55, No. 6 ( 2014-07), p. 500-509
    Abstract: Titanium dioxide (TiO 2 ) nanomaterials (NMs) are widely used in a diversity of products including cosmetics, pharmaceuticals, food, and inks, despite uncertainties surrounding the potential health risks that they pose to humans and the environment. Previous studies on the genotoxicity of TiO 2 have reported discrepant or inconclusive findings in both in vitro and in vivo systems. This study explores the in vivo genotoxic potential of a well‐characterized uncoated TiO 2 NM with an average diameter of 22 nm (NM‐102, from JRC repository) using several genotoxicity endpoints in the LacZ plasmid‐based transgenic mouse model. Mice were exposed by intravenous injection to two daily doses of NM‐102: 10 and 15 mg/kg of body weight/day. Micronuclei were analyzed in peripheral blood reticulocytes 42 hr after the last treatment. DNA strand breaks (comet assay) and gene mutations were determined in the spleens and livers of the same animals 28 days after the last treatment. Histopathological and cytological analyses were also performed in liver samples. Genotoxic effects were not detected in mice exposed to the nanosized TiO 2 under the experimental conditions used, despite a moderate inflammatory response that was observed in the liver. Considering the biopersistence of TiO 2 in mouse liver and the moderate inflammatory response, the possibility of a secondary genotoxic effect at higher doses and in conditions that result in a stronger inflammatory response, for example, within a longer time window, should be investigated further. Environ. Mol. Mutagen. 55:500–509, 2014. © 2014 Wiley Periodicals, Inc.
    Type of Medium: Online Resource
    ISSN: 0893-6692 , 1098-2280
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2014
    detail.hit.zdb_id: 1497682-1
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  • 4
    In: WIREs Nanomedicine and Nanobiotechnology, Wiley, Vol. 12, No. 5 ( 2020-09)
    Abstract: Various nanomedicinal products (NMPs) have been reported to induce an adverse immune response, which may be related to their tendency to accumulate in or target cells of the immune system. Therefore, before their market authorization, NMPs should be thoroughly evaluated for their immunotoxic potential. Nonclinical regulatory immunotoxicity testing of nonbiological medicinal products, including NMPs, is currently performed by following the guideline S8 “Immunotoxicity Studies for Human Pharmaceuticals” of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). However, this guideline does not cover all the immunotoxicity endpoints reported for NMPs in the literature, such as complement activation related pseudo allergy, hypersensitivity and immunosuppression. In addition, ICH‐S8 does not provide any nanospecific testing considerations, which is important given their tendency to interfere with many commonly used toxicity assays. We therefore propose a nonclinical regulatory immunotoxicity assessment strategy, which considers the immunotoxicity endpoints currently missing in the ICH‐S8. We also list the known pitfalls related to the testing of NMPs and how to tackle them. Next to defining the relevant physicochemical and pharmacokinetic properties of the NMP and its intended use, the proposed strategy includes an in vitro assay battery addressing various relevant immunotoxicity endpoints. A weight of evidence evaluation of this information can be used to shape the type and design of further in vivo investigations. The final outcome of the immunotoxicity assessment can be included in the overall risk assessment of the NMP and provide alerts for relevant endpoints to address during clinical investigation. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine 〉 Regulatory and Policy Issues in Nanomedicine Toxicology and Regulatory Issues in Nanomedicine 〉 Toxicology of Nanomaterials
    Type of Medium: Online Resource
    ISSN: 1939-5116 , 1939-0041
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2483266-2
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  • 5
    In: Environmental Toxicology and Chemistry, Wiley, Vol. 34, No. 5 ( 2015-05), p. 1015-1022
    Abstract: Traditionally, administered mass is used to describe doses of conventional chemical substances in toxicity studies. For deriving toxic doses of nanomaterials, mass and chemical composition alone may not adequately describe the dose, because particles with the same chemical composition can have completely different toxic mass doses depending on properties such as particle size. Other dose metrics such as particle number, volume, or surface area have been suggested, but consensus is lacking. The discussion regarding the most adequate dose metric for nanomaterials clearly needs a systematic, unbiased approach to determine the most appropriate dose metric for nanomaterials. In the present study, the authors propose such an approach and apply it to results from in vitro and in vivo experiments with silver and silica nanomaterials. The proposed approach is shown to provide a convenient tool to systematically investigate and interpret dose metrics of nanomaterials. Recommendations for study designs aimed at investigating dose metrics are provided. Environ Toxicol Chem 2015;34:1015–1022. © 2015 SETAC
    Type of Medium: Online Resource
    ISSN: 0730-7268 , 1552-8618
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2027441-5
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  • 6
    In: Journal of Cellular and Molecular Medicine, Wiley, Vol. 13, No. 8b ( 2009-08-02), p. 2148-2157
    Abstract: Studies in cervical dysplasia have reported overexpression of the tumour suppressors p14 and p16 – and absence of p53 – in high‐risk human papilloma virus (HPV)‐ associated lesions. In skin carcinogenesis, the relation between these tumour suppressors and HPV remain unclear. We evaluated the expression of the tumour suppressors p14, p16 and p53 in pre‐malignant and malignant squamous skin tumours, and its relation with risk factors for skin carcinogenesis (HPV, immune status and sun exposure). We performed immunohistochemical stainings for p14, p16 and p53 on paraffin embedded material of 71 pre‐malignant squamous skin lesions and 34 squamous cell carcinomas, from 52 renal transplant recipients (RTRs) and 53 immunocompetent individuals. PCR‐based assays were used for detection and genotyping of β‐papilloma virus (β‐PV) types and mucosal HPV types. P14 expression was independent of the expression of p16 and p53, irrespective of immune status and skin site. In 49 of 105 specimens (46.6%), one or more β‐PV types were detected. We found no significant association between p14, p16 or p53 protein expression and overall presence of β‐PV, irrespective of immune status. There was a significant association between presence of β‐PV and lesions from sun‐exposed skin sites in the RTRs ( P = 0.002). We conclude that in skin carcinogenesis, relations between the herein studied tumour suppressors and HPV are different from what one would expect based on findings in cervical neoplasia. P14, p16 and p53 expressions are independent of immune status. Our data indicate that in immunosuppressed patients, β‐PV together with ultraviolet radiation act synergetic in promoting carcinogenesis.
    Type of Medium: Online Resource
    ISSN: 1582-1838 , 1582-4934
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2009
    detail.hit.zdb_id: 2076114-4
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  • 7
    In: The Plant Journal, Wiley, Vol. 80, No. 1 ( 2014-10), p. 136-148
    Abstract: We explored genetic variation by sequencing a selection of 84 tomato accessions and related wild species representative of the Lycopersicon , Arcanum , Eriopersicon and Neolycopersicon groups, which has yielded a huge amount of precious data on sequence diversity in the tomato clade. Three new reference genomes were reconstructed to support our comparative genome analyses. Comparative sequence alignment revealed group‐, species‐ and accession‐specific polymorphisms, explaining characteristic fruit traits and growth habits in the various cultivars. Using gene models from the annotated Heinz 1706 reference genome, we observed differences in the ratio between non‐synonymous and synonymous SNPs (dN/dS) in fruit diversification and plant growth genes compared to a random set of genes, indicating positive selection and differences in selection pressure between crop accessions and wild species. In wild species, the number of single‐nucleotide polymorphisms (SNPs) exceeds 10 million, i.e. 20‐fold higher than found in most of the crop accessions, indicating dramatic genetic erosion of crop and heirloom tomatoes. In addition, the highest levels of heterozygosity were found for allogamous self‐incompatible wild species, while facultative and autogamous self‐compatible species display a lower heterozygosity level. Using whole‐genome SNP information for maximum‐likelihood analysis, we achieved complete tree resolution, whereas maximum‐likelihood trees based on SNPs from ten fruit and growth genes show incomplete resolution for the crop accessions, partly due to the effect of heterozygous SNPs. Finally, results suggest that phylogenetic relationships are correlated with habitat, indicating the occurrence of geographical races within these groups, which is of practical importance for Solanum genome evolution studies.
    Type of Medium: Online Resource
    ISSN: 0960-7412 , 1365-313X
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2014
    detail.hit.zdb_id: 2020961-7
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  • 8
    In: Transfusion, Wiley, Vol. 59, No. 8 ( 2019-08), p. 2575-2583
    Abstract: In the Netherlands, needle‐related events (NREs) including tattoos, piercings, and acupuncture are a reason for temporary blood donor deferral. This study aims to evaluate whether donors with recent NREs had a higher risk of transfusion‐transmissible infections (TTIs) compared to donors without recent NREs. STUDY DESIGN AND METHODS Data from 2006 through 2015 on all blood donation attempts in the Netherlands were collected. Multivariate regression models (for repeated measurements) were used to assess the associations between recent NREs and the acquisition of TTIs. Posttest counseling data were used to determine the most likely risk factor in TTI‐positive new and repeat donors. RESULTS Recent NREs were documented in 97,518 out of 9,266,036 (1.1%) donation attempts; 14,097 (14.5%) NREs resulted in NRE‐based donor deferral. Recent NREs reported pre‐donation were not associated with an increased risk for TTIs. A total of 29 out of 287 TTI‐positive donors (11 repeat donors, 18 new donors) reported a recent NRE pre‐ and/or post‐donation. Recent NREs, all needle‐stick injuries, were the likely route of transmission in 12 out of 287 (4.2%) of TTI‐positive donors. The donor health questionnaire (DHQ) identified only 1 out of 12 TTI‐linked NREs. Non‐return after NRE deferral, any deferral, or no deferral was 24, 15, and 5%, respectively. DISCUSSION Recent tattoos, body piercings, or acupuncture were not associated with an increased risk for TTIs in Dutch donors. Given the lower return rates of donors following a temporary NRE‐based deferral, we advocate ending blood donor deferral policies for acupuncture, tattooing, and body piercings, but not needle‐stick injuries, in countries where these practices can be considered safe.
    Type of Medium: Online Resource
    ISSN: 0041-1132 , 1537-2995
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2018415-3
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  • 9
    In: FEBS Letters, Wiley, Vol. 431, No. 1 ( 1998-07-10), p. 75-79
    Abstract: Leader peptidase is an integral membrane protein of E. coli and it catalyses the removal of most signal peptides from translocated precursor proteins. In this study it is shown that when the transmembrane anchors are removed in vivo, the remaining catalytic domain can bind to inner and outer membranes of E. coli . Furthermore, the purified catalytic domain binds to inner membrane vesicles and vesicles composed of purified inner membrane lipids with comparable efficiency. It is shown that the interaction is caused by penetration of a part of the catalytic domain between the lipids. Penetration is mediated by phosphatidylethanolamine, the most abundant lipid in E. coli , and does not seem to depend on electrostatic interactions. A hydrophobic segment around the catalytically important residue serine 90 is required for the interaction with membranes.
    Type of Medium: Online Resource
    ISSN: 0014-5793 , 1873-3468
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 1998
    detail.hit.zdb_id: 1460391-3
    SSG: 12
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  • 10
    In: Transfusion, Wiley, Vol. 58, No. 3 ( 2018-03), p. 692-700
    Abstract: Deferral for low hemoglobin (Hb) increases the likelihood that donors do not return for future donations. Zinc protoporphyrin (ZPP) has been described as a sensitive marker of iron‐deficient erythropoiesis, before Hb decreases. It is a relatively cheap, rapid, and easy‐to‐perform measurement in a drop of whole blood. To assess the utility of ZPP measurement in donor management we examined whether ZPP and Hb levels among first‐time donors differ from repeat donors. We further explored whether ZPP increases over subsequent donations at a donor population level and whether increasing ZPP levels coincide with decreasing Hb levels and donor deferral. STUDY DESIGN AND METHODS We included first‐time (n = 4983) and repeat (n = 3533) whole blood donors from the ZPP and Iron in the Netherlands Cohort (ZINC) study. ZPP and Hb were measured at each subsequent donation during a 4‐year period after inclusion in the study. RESULTS Median ZPP levels were higher in repeat than in first‐time donors. In first‐time donors, especially women, ZPP levels were increased with a corresponding decline in Hb levels over subsequent donations. ZPP levels were increased among first‐time donors deferred for low Hb. CONCLUSION Our results suggest that adding ZPP to Hb measurements in the daily blood collection setting, especially for first‐time donors and first‐time female donors may add to the identification of a donor subpopulation with low functional iron stores.
    Type of Medium: Online Resource
    ISSN: 0041-1132 , 1537-2995
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2018415-3
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