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OBJECTIVES: To determine the causal association between genetically predicted obesity and the risk of hip osteoarthritis. METHODS: We performed two-sample Mendelian randomization (MR) analysis to analyze the association between body mass index (BMI) and hip osteoarthritis using pooled-level genome-wide association study (GWAS) data. The inverse variance weighted (IVW), MRâEgger, and weighted median methods were used to estimate the causal association. In addition, we applied the MR Steiger filtering method, MR robust adjusted profile score (MR.RAPS) methods, and the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test to examine and address potential horizontal pleiotropy. RESULTS: We found a causal relationship between genetically predicted BMI and the risk of hip osteoarthritis by the IVW method [OR = 1.45, 95% confidence interval (CI) = 1.04-2.00, P = 0.02]. In the sensitivity analysis, the results of the MRâEgger and weighted median methods revealed similar estimations but with a wide CI with lower precision. The funnel plot, MR-Egger intercept, and MR-PRESSO all indicated the absence of a directional pleiotropic effect. In addition, no heterogeneity was observed in the present analysis. Therefore, the result of IVW is most suitable and reliable for the present MR analysis. CONCLUSION: There is a causal relationship between obesity and a higher risk of hip osteoarthritis, suggesting that weight management may be an intervention for the prevention and management of hip osteoarthritis. LEVEL OF EVIDENCE: Bioinformatics, Basic science.
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Estudio de Asociación del Genoma Completo , Osteoartritis de la Cadera , Humanos , Osteoartritis de la Cadera/genética , Índice de Masa Corporal , Nonoxinol , Obesidad/complicaciones , Obesidad/genética , Polimorfismo de Nucleótido SimpleRESUMEN
OBJECTIVE: To evaluate the combined effect of topical rapamycin (RAPA) eye drop in nanometer vector and poly (lactic acid) (PLA) wafers of cyclosporine A (CsA) in the prevention of acute allograft rejection after rabbit corneal transplantation. Methods It was an experimental study. RAPA was incorporated into the nanometer particles and CsA was incorporated into PLA wafers. A was syngeneic control whose both donor and recipient are New Zealand rabbit. Gray donor corneas were implanted into the 102 recipients of New Zealand albino rabbits with corneal neovascularization who were randomly divided into B, C, D, E, F, G 6 groups to receive the different types of therapy: B was no therapy control; C was eye drop of nanometer vector but no RAPA twice a day, 28 days; D was PLA wafers in the anterior chamber of rabbit eyes but no drugs; E was 0.5% RAPA eye drop of nanometer vector twice a day, 28 days; F was PLA wafers of CsA in the anterior chamber of rabbit eyes; G was PLA wafers of CsA in the anterior chamber of rabbit eyes and 0.5% RAPA eye drop of nanometer vector eye drop twice a day for 28 days together. Postoperative evaluation included slit-lamp biomicroscopy, histopathology and immunohistology, Cytokines related with neovascularization and immunosuppression in the corneal tissue by RT-PCR. The graft survival was assessed by One-Way ANOVA and q test. RESULTS: Corneal allograft survival time: A (100.00 +/- 0.00), B (8.44 +/- 1.24), C (8.89 +/- 2.57), D (8.56 +/- 2.30), E (43.11 +/- 5.58), F (43.67 +/- 9.54), G (72.00 +/- 15.34) d. Group G led to a statistically significant prolongation of transplant survival and was superior than group E and F which was a statistical prolongation compared with group B, C and D (qGE = 11.42, qGF = 11.24, qEB = 13.64, qEC = 13.38, qED = 13.46, qFB = 13.82, qFC = 13.56, qFD = 13.64; P < 0.01). Immunohistopathologically, the grafts were subjected to an immune response contained a dense infiltrate of neutrophils, CD4+ and CD8+ T lymphocytes in the group B, C and D. This cellular infiltrate was a significant reduction in group E,F,G. RT-PCR showed that the gene expression of IL-2 was inhibited earlier (3 days) in group F, G and VEGF gene expression being suppressed later (14 days) in group E, G. CONCLUSIONS: Combined therapy with topical application of RAPA eye drop of nanometer vector and CsA PLA wafers can significantly prolong the survival of allograft at high-risk. Moreover, topical combined treatment of them is more effective, lower dosage, less side-effects and cheaper than the treatment with topical individual immunosuppressive drug.
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Ciclosporina/uso terapéutico , Rechazo de Injerto/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Sirolimus/uso terapéutico , Animales , Trasplante de Córnea , Sistemas de Liberación de Medicamentos , Ácido Láctico/uso terapéutico , Nanopartículas/uso terapéutico , Poliésteres , Polímeros/uso terapéutico , ConejosRESUMEN
OBJECTIVE: To study the biocompatibility of F-heparin surface modified intraocular lenses (IOLs) by observing cellular reaction on the surface of IOLs implanted into the rhesus monkeys' eyes. METHODS: Ten monkeys (20 eyes) were classified into two groups. PMMA IOLs and F-heparin modified IOLs were respectively implanted into 10 monkeys' eyes. The IOLs were examined with computer image analysis, light microscope (LM) and scanning electron microscope (SEM) at postoperative 180 and 360 days. RESULTS: A few of adhered cells were on the surface of the central part of the IOL and more on the border of the IOL optics. The giant cells deposited on the surface occupied the largest area and the number of the macrophages was the greatest. The cells deposited on the surface of the IOLs in the F-heparin modified group were less than that in the non-modified group. In the modified group, there was fine granular proteinaceous membrane on the surface of the IOLs, but in the non-modified group there was fibrinous reticular proteinaceous membrane. CONCLUSION: The biocompatibility of the F-heparin surface modified IOLs is better than that of non-modified PMMA IOLs.
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Adhesión Celular/efectos de los fármacos , Flúor/farmacología , Heparina/farmacología , Lentes Intraoculares , Animales , Adhesión Celular/fisiología , Materiales Biocompatibles Revestidos/farmacología , Células Gigantes/fisiología , Implantación de Lentes Intraoculares/métodos , Macaca mulatta , Macrófagos/fisiología , Propiedades de SuperficieRESUMEN
PURPOSE: To evaluate biocompatibility of Carbon (C) and Titanum (T) surface modified Polymethyl-methacrylate (PMMA) Intraocular Lens (IOLs) in pseudophakic rabbit model. METHODS: Extracapsule Cataract Extraction (ECCE) and IOLs implantation were performed in Japanese albino rabbit eyes. The white cell concentration from the aqueous humor in the eyes was counted within 3 months post operation. The inflammatory cells in the eyes were noted and graded by slit lamp using a semiquantitive scale up to 1-year post operation. The rabbit eyes were inspected under light microscopy, where pathology of the eyes was caracterized. RESULTS: The white cell concentration in the aqueous humor was significantly attenuated in C and T IOL-implanted eyes compared with PMMA IOL-implanted eyes 1 week post operation. The exudate levels in the anterior ocular chamber and the posterior synechias were significant lower in T IOL-implanted eyes than in PMMA IOL-implanted eyes 1 week and 2 weeks after surgery. The exudate levels in the anterior chambers and the posterior synechias were not significantly different in C IOL-implanted versus PMMA IOL-implanted eyes. CONCLUSIONS: This in vivo study provides evidence of effectiveness of Carbon and Titanium IOLs in improving the biocompatibility of PMMA IOLs.