165 research outputs found

    A novel concept for the manufacture of individual sapphire-metallic hip joint endoprostheses.

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    At the present time, artificial joints made with metallic, ceramic, metal-polymeric or ceramicpolymeric friction pairs substituting for the natural biomechanic articulations "head of the hip joint-acetabulum" are widely used for endoprosthetic operations on hip joints. Experience gained in the course of more than 2000 operations has shown that along with the advantageous properties of modern endoprosthetic constructions made of metal, ceramics and polymers, they have certain drawbacks. Among them are insufficient biological inertness and susceptibility to excessive wear of the friction pair components. In addition, as a result of wear of the hinge friction pair, toxic and oncologically dangerous products of degradation accumulate in the different organs and tissues. This in turn results in severe complications and demands correspondingly complicated corrective intervention, often leading to worse disability than that which the original operation was designed to cure. The aim of the study reported here was the development and clinical validation of a highly effective and long-lived hip joint endoprosthesis with a sapphire head whose wear capacity is superior to all others. The endoprosthesis consists of a metallic pedicle, a dismountable articulation (metallic necklayer of supramolecular polyethylene-sapphire head) and an acetabular cup. The endoprostheses with the sapphire head proved themselves positively in clinical trials and are considered to be highly promising for future applications

    Genotoxic agents promote the nuclear accumulation of annexin A2: role of annexin A2 in mitigating DNA damage

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    Annexin A2 is an abundant cellular protein that is mainly localized in the cytoplasm and plasma membrane, however a small population has been found in the nucleus, suggesting a nuclear function for the protein. Annexin A2 possesses a nuclear export sequence (NES) and inhibition of the NES is sufficient to cause nuclear accumulation. Here we show that annexin A2 accumulates in the nucleus in response to genotoxic agents including gamma-radiation, UV radiation, etoposide and chromium VI and that this event is mediated by the nuclear export sequence of annexin A2. Nuclear accumulation of annexin A2 is blocked by the antioxidant agent N-acetyl cysteine (NAC) and stimulated by hydrogen peroxide (H2O2), suggesting that this is a reactive oxygen species dependent event. In response to genotoxic agents, cells depleted of annexin A2 show enhanced phospho-histone H2AX and p53 levels, increased numbers of p53-binding protein 1 nuclear foci and increased levels of nuclear 8-oxo-2'-deoxyguanine, suggesting that annexin A2 plays a role in protecting DNA from damage. This is the first report showing the nuclear translocation of annexin A2 in response to genotoxic agents and its role in mitigating DNA damage.Natural Sciences and Engineering Research Council of Canada (NSERC); European Union [PCOFUND-GA-2009-246542]; Foundation for Science and Technology of Portugal; Beatrice Hunter Cancer Research Institute; Terry Fox Foundationinfo:eu-repo/semantics/publishedVersio

    Association of Single Nucleotide Polymorphisms in the IL-18 Gene with Production of IL-18 Protein by Mononuclear Cells from Healthy Donors

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    IL-18 has proinflammatory effects and participates in both innate and adaptive cellular and humoral immunity. A number of SNPs that influence IL-18 production are found in the gene promoter region. We investigated the association of SNPs in the IL-18 promoter at −607 and −137 with the level of IL-18 protein production by PBMC from healthy donors from Southwestern Siberia. The genetic distribution of these SNPs in the promoter site was established by PCR. IL-18 protein production was determined by ELISA. Our results showed that PBMC from donors carrying allele 137C have lower levels of both spontaneous and LPS-stimulated IL-18 production. In contrast, PBMC from donors carrying allele 607A showed significant increases in spontaneous and stimulated IL-18 production compared to wild type. Our study suggests that the SNPs −607 and −137 in the promoter region of the IL-18 gene influence the level of IL-18 protein production by PBMC from healthy donors in Southwestern Siberia
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