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1.
Stanislav Bondarenko Volodymyr Filipenko Michael Karpinsky Olena Karpinska Gennadiy Ivanov Valentyna Maltseva Ahmed Amine Badnaoui Ran Schwarzkopf 《World journal of orthopedics》2021,12(4):214-222
BACKGROUNDToday, biological fixation of uncemented press-fit acetabular components plays an important role in total hip arthroplasty. Long-term stable fixation of these implants depends on the osseointegration of the acetabular cup bone tissue into the acetabular cup implant, and their ability to withstand functional loads.AIMTo compare the strength of bone-implant osseointegration of four types of porous metal implants in normal and osteoporotic bone in rabbits.METHODSThe study was performed in 50 female California rabbits divided into non-ovariectomized (non-OVX) and ovariectomized groups (OVX) at 6 mo of age. Rabbits were sacrificed 8 wk after the implantation of four biomaterials [TTM, CONCELOC, Zimmer Biomet''s Trabecular Metal (TANTALUM), and ATLANT] in a 5-mm diameter defect created in the left femur. A biomechanical evaluation of the femur was carried out by testing implant breakout force. The force was gradually increased until complete detachment of the implant from the bone occurred.RESULTSThe breakout force needed for implant detachment was significantly higher in the non-OVX group, compared with the OVX group for all implants (TANTALUM, 194.7 ± 6.1 N vs 181.3 ± 2.8 N; P = 0.005; CONCELOC, 190.8 ± 3.6 N vs 180.9 ± 6.6 N; P = 0.019; TTM, 186.3 ± 1.8 N vs 172.0 N ± 11.0 N; P = 0.043; and ATLANT, 104.9 ± 7.0 N vs 78.9 N ± 4.5 N; P = 0.001). In the OVX group, The breakout forces in TANTALUM, TTM, and CONCELOC did not differ significantly (P = 0.066). The breakout force for ATLANT in the OVX group was lower by a factor of 2.3 compared with TANTALUM and CONCELOC, and by 2.2 compared with TTM (P = 0.001). In the non-OVX group, the breakout force for ATLANT was significantly different from all other implants, with a reduction in fixation strength by a factor of 1.9 (P = 0.001).CONCLUSIONTANTALUM, TTM, and CONCELOC had equal bone-implant osseointegration in healthy and in osteoporotic bone. ATLANT had significantly decreased osseointegration (P = 0.001) in healthy and in osteoporotic bone. 相似文献
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Birgit Bjerre H?yer Cecilia H?st Ramlau-Hansen Martine Vrijheid Damaskini Valvi Henning Sloth Pedersen Valentyna Zviezdai Bo A.G. J?nsson Christian H. Lindh Jens Peter Bonde Gunnar Toft 《Environmental health perspectives》2015,123(8):841-846
Background
In some animal studies, perfluorinated alkyl substances are suggested to induce weight gain. Human epidemiological studies investigating these associations are sparse.Objective
We examined pregnancy serum concentrations of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) and the prevalence of offspring overweight (> 1 SD) and waist-to-height ratio (WHtR) > 0.5 at 5–9 years of age.Methods
Sera from 1,022 pregnant women enrolled in the INUENDO cohort (2002–2004) from Greenland and Kharkiv (Ukraine) were analyzed for PFOA and PFOS using liquid chromatography–tandem mass spectrometry. Relative risks (RR) of being overweight and having WHtR > 0.5 in relation to continuous and categorized (tertiles) PFOA and PFOS were calculated at follow-up (2010–2012) using generalized linear models.Results
Pooled PFOA median (range) was 1.3 (0.2–5.1) and PFOS median (range) was 10.8 (0.8–73.0) ng/mL. For each natural logarithm-unit (ln-unit) increase of pregnancy PFOA, the adjusted RR of offspring overweight was 1.11 [95% confidence interval (CI): 0.82, 1.53] in Greenlandic children. In Ukrainian children, the adjusted RR of offspring overweight was 1.02 (95% CI: 0.72, 1.44) for each ln-unit increase of pregnancy PFOA. Prenatal exposure to PFOS was not associated with overweight in country-specific or pooled analysis. The adjusted RR of having WHtR > 0.5 for each ln-unit increase of prenatal exposure to PFOA was 1.30 (95% CI: 0.97, 1.74) in the pooled analysis. For 1–ln-unit increase of prenatal exposure to PFOS, the adjusted RR of having a WHtR > 0.5 was 1.38 (95% CI: 1.05, 1.82) in the pooled analysis.Conclusions
The results indicate that prenatal PFOA and PFOS exposures may be associated with child waist-to-height ratio > 0.5. Prenatal PFOA and PFOS exposures were not associated with overweight.Citation
Høyer BB, Ramlau-Hansen CH, Vrijheid M, Valvi D, Pedersen HS, Zviezdai V, Jönsson BA, Lindh CH, Bonde JP, Toft G. 2015. Anthropometry in 5- to 9-year-old Greenlandic and Ukrainian children in relation to prenatal exposure to perfluorinated alkyl substances. Environ Health Perspect 123:841–846; http://dx.doi.org/10.1289/ehp.1408881 相似文献3.
Friesen DE Barakat KH Semenchenko V Perez-Pineiro R Fenske BW Mane J Wishart DS Tuszynski JA 《Chemical biology & drug design》2012,79(5):639-652
Recent studies have shown an overexpression of γ-tubulin in human glioblastomas and glioblastoma cell lines. As the 2-year survival rate for glioblastoma is very poor, potential benefit exists for discovering novel chemotherapeutic agents that can inhibit γ-tubulin, which is known to form a ring complex that acts as a microtubule nucleation center. We present experimental evidence that colchicine and combretastatin A-4 bind to γ-tubulin, which are to our knowledge the first drug-like compounds known to interact with γ-tubulin. Molecular dynamics simulations and docking studies were used to analyze the hypothesized γ-tubulin binding domain of these compounds. The suitability of the potential binding modes was evaluated and suggests the subsequent rational design of novel targeted inhibitors of γ-tubulin. 相似文献
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Jonathan Y. Mane Valentyna Semenchenko Rolando Perez‐Pineiro Philip Winter David Wishart Jack A. Tuszynski 《Chemical biology & drug design》2013,82(1):60-70
The binding free energies on human tubulin of selected colchicine and thiocolchicine compounds were determined. Two methods were used for the determination of binding free energies: one is based on theoretical prediction simulating the dissociation of the compound from tubulin using a series of molecular dynamics simulations, and the other method involves a series of experiments that measured the affinity of the compound on a synthetically expressed and purified tubulin protein using a spectrofluorometric technique. 相似文献
5.
Grad LI Guest WC Yanai A Pokrishevsky E O'Neill MA Gibbs E Semenchenko V Yousefi M Wishart DS Plotkin SS Cashman NR 《Proceedings of the National Academy of Sciences of the United States of America》2011,108(39):16398-16403
Human wild-type superoxide dismutase-1 (wtSOD1) is known to coaggregate with mutant SOD1 in familial amyotrophic lateral sclerosis (FALS), in double transgenic models of FALS, and in cell culture systems, but the structural determinants of this process are unclear. Here we molecularly dissect the effects of intracellular and cell-free obligately misfolded SOD1 mutant proteins on natively structured wild-type SOD1. Expression of the enzymatically inactive, natural familial ALS SOD1 mutations G127X and G85R in human mesenchymal and neural cell lines induces misfolding of wild-type natively structured SOD1, as indicated by: acquisition of immunoreactivity with SOD1 misfolding-specific monoclonal antibodies; markedly enhanced protease sensitivity suggestive of structural loosening; and nonnative disulfide-linked oligomer and multimer formation. Expression of G127X and G85R in mouse cell lines did not induce misfolding of murine wtSOD1, and a species restriction element for human wtSOD1 conversion was mapped to a region of sequence divergence in loop II and β-strand 3 of the SOD1 β-barrel (residues 24-36), then further refined surprisingly to a single tryptophan residue at codon 32 (W32) in human SOD1. Time course experiments enabled by W32 restriction revealed that G127X and misfolded wtSOD1 can induce misfolding of cell-endogenous wtSOD1. Finally, aggregated recombinant G127X is capable of inducing misfolding and protease sensitivity of recombinant human wtSOD1 in a cell-free system containing reducing and chelating agents; cell-free wtSOD1 conversion was also restricted by W32. These observations demonstrate that misfolded SOD1 can induce misfolding of natively structured wtSOD1 in a physiological intracellular milieu, consistent with a direct protein-protein interaction. 相似文献
6.
Kari L Walker Olga Kirillova Suzanne E Gillespie David Hsiao Valentyna Pishchalenko Akshatha Kalsanka Pai Jon E Puro Robert Plumley Rustam Kudyakov Weiming Hu Art Allisany MaryAnn McBurnie Stephen E Kurtz Brian L Hazlehurst 《J Am Med Inform Assoc》2014,21(6):1129-1135
Comparative effectiveness research (CER) studies involving multiple institutions with diverse electronic health records (EHRs) depend on high quality data. To ensure uniformity of data derived from different EHR systems and implementations, the CER Hub informatics platform developed a quality assurance (QA) process using tools and data formats available through the CER Hub. The QA process, implemented here in a study of smoking cessation services in primary care, used the ‘emrAdapter’ tool programmed with a set of quality checks to query large samples of primary care encounter records extracted in accord with the CER Hub common data framework. The tool, deployed to each study site, generated error reports indicating data problems to be fixed locally and aggregate data sharable with the central site for quality review. Across the CER Hub network of six health systems, data completeness and correctness issues were prevalent in the first iteration and were considerably improved after three iterations of the QA process. A common issue encountered was incomplete mapping of local EHR data values to those defined by the common data framework. A highly automated and distributed QA process helped to ensure the correctness and completeness of patient care data extracted from EHRs for a multi-institution CER study in smoking cessation. 相似文献
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Monika Z. Kaczmarek Ryan J. Holland Stephen A. Lavanier Jami A. Troxler Valentyna I. Fesenkova Charlotte A. Hanson Joan L. Cmarik Joseph E. Saavedra Larry K. Keefer Sandra K. Ruscetti 《Leukemia research》2014
The nitric oxide (NO) prodrug JS-K, a promising anti-cancer agent, consists of a diazeniumdiolate group necessary for the release of NO as well as an arylating ring. In this study, we research the mechanism by which JS-K kills a murine erythroleukemia cell line and determine the roles of NO and arylation in the process. Our studies indicate that JS-K inhibits the PI 3-kinase/Akt and MAP kinase pathways. This correlates with the activation of the tumor suppressor FoxO3a and increased expression of various caspases, leading to apoptosis. The arylating capability of JS-K appears to be sufficient for inducing these biological effects. Overall, these data suggest that JS-K kills tumor cells by arylating and inactivating signaling molecules that block the activation of a tumor suppressor. 相似文献
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Serebrovskaya TV Nikolsky IS Nikolska VV Mallet RT Ishchuk VA 《High altitude medicine & biology》2011,12(3):243-252
This study tested the hypothesis that intermittent hypoxia treatment (IHT) modulates circulating hematopoietic stem and progenitor cells (HSPC) and augments humoral and cellular components of innate immunity in young, healthy men. Ten subjects (group 1: age 31±4?yr) were studied before and at 1 and 7 days after a 14-day IHT program consisting of four 5-min bouts/day of breathing 10% O2, lowering arterial O2 saturation to 84% to 85%, with intervening 5-min room-air exposures. Five more subjects (group 2: age 29±5?yr) were studied during 1 IHT session. Immunofluorescence detected HSPCs as CD45+CD34+ cells in peripheral blood. Phagocytic and bactericidal activities of neutrophils, circulating immunoglobulins (IgM, IgG, IgA), immune complexes, complement, and cytokines (erythropoietin, TNF-α, IL-4, IFN-γ) were measured. In group 1, the HSPC count fell 27% below pre-IHT baseline 1 week after completing IHT, without altering erythrocyte and reticulocyte counts. The IHT program also activated complement, increased circulating platelets, augmented phagocytic and bactericidal activities of neutrophils, sharply lowered circulating TNF-α and IL-4 by >90% and ~75%, respectively, and increased IFN-γ, particularly 1 week after IHT. During acute IHT (group 2), HSPC increased by 51% after the second hypoxia bout and by 19% after the fourth bout, and total leukocyte, neutrophil, monocyte, and lymphocyte counts also increased; but these effects subsided by 30?min post-IHT. Collectively, these results demonstrate that IHT enhances innate immunity by mobilizing HSPC, activating neutrophils, and increasing circulating complement and immunoglobulins. These findings support the potential for eventual application of IHT for immunotherapy. 相似文献