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Clinical and Experimental Nephrology - The number of patients aged ≥ 75 years and who need renal replacement therapy is steadily increasing. The study aimed to determine...  相似文献   
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Dendritic cells (DCs) polarize naive CD4(+) T cells to either T helper 1 (Th1) or Th2 cells. We examined the role of glycogen synthase kinase 3 (GSK3) activity during DC development from murine bone marrow (BM) cells. DCs were generated by culturing lineage-marker-negative BM cells with granulocyte-macrophage colony-stimulating factor in the presence or absence of a specific inhibitor of GSK3 (Gi), SB415286, for 6 days. DCs generated in the presence (GiDC) or absence (control DC) of SB415286 similarly exhibited a conventional DC phenotype (CD11b(+) B220(-) CD8(-)). These DCs were mixed with allogeneic CD4(+) T cells and the ability to polarize Th1 or Th2 cells was evaluated. The GiDCs exhibited markedly impaired function to induce Th2 polarization compared to control DCs. In contrast, the ability of GiDCs to generate Th1 cells was slightly higher than that of control DCs. CD86 expression and CD40-mediated interleukin-6 production were completely diminished in GiDCs, which might be associated with the impaired ability of the GiDCs to induce Th2 differentiation. These results suggest that the GSK3 activity during DC development is essential for the establishment of the DC function to induce Th2, but not Th1, differentiation.  相似文献   
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Excessive nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS) aggravates acute lung injury (ALI) by producing peroxynitrite. We previously showed by immunostaining that the expression of iNOS was suppressed by inhalation of N(G)-nitro-L-arginine methyl ester in mice with Candida-induced ALI. This study tested the hypothesis that a novel iNOS inhibitor suppresses not only iNOS expression, but also iNOS messenger RNA (mRNA) production by interrupting a positive feedback loop at the time of NO production in Candida-induced ALI. Mice were pretreated by inhalation of saline or ONO-1714, a selective iNOS inhibitor, and were given an intravenous injection of Candida albicans to induce ALI. After inhalation of 1 mM aerosolized ONO-1714, the nitrite-nitrate concentration in bronchoalveolar lavage fluid (BALF) at 24 h was significantly lower than that after inhalation of saline. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels and neutrophils in BALF were decreased by inhalation of ONO-1714. Inhalation of ONO-1714 markedly suppressed nitrotyrosine production and inhibited the expression of iNOS mRNA as well as proteins in the lung. Survival was prolonged by inhalation of ONO-1714. We conclude that pretreatment with inhaled ONO-1714 suppresses the production of peroxinitrite and decreases oxidative stress associated with peroxinitrite in Candida-induced ALI.  相似文献   
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BackgroundThere is a conflict in the treatment of distal radius fractures in elderly patients, because fracture reduction does not appear to be as strongly associated with functional outcomes as in younger patients. The purpose of this study was to evaluate radiographic findings of acceptable reduction without leading to wrist dysfunction and poor outcomes.MethodsFifty-two active and healthy elderly patients with conservatively managed distal radius fractures were included in the study. They consisted of 7 men and 45 women, all 60 years or older. Radiographic assessment included volar tilt, radial inclination and ulnar variance, and outcome evaluation included the Mayo wrist score and DASH score. As a control group, the preoperative radiographic and clinical outcomes were examined as well for 19 patients older than 60 with malunion, for whom corrective osteotomy was performed because of wrist dysfunction. The radiographic parameters and clinical outcomes were compared between the two groups in a statistical manner. Correlation coefficients of the radiographic parameters with Mayo wrist score and DASH score were analyzed by multiple regression.ResultsVolar tilt (mean —1.2°) and ulnar variance (mean 2.5 mm), as well as Mayo wrist score (mean 80.0 points) and DASH score (mean 8.6 points) in the objective group were significantly superior to those in the control group when comparing radiographic parameters and clinical outcomes. There was no significant difference between the two groups in regard to RI (mean 14.9°). Multiple regression analysis revealed that volar tilt and ulnar variance were significantly correlated with the clinical outcomes in the objective.ConclusionThe parameters of volar tilt and ulnar variance had a significant correlation with clinical outcomes. Clinical outcomes significantly worsened when those parameters exceeded a tolerable range. In elderly patients, it is important to determine an appropriate therapeutic modality for a distal radius fracture when considering the acceptable parameters for alignment.  相似文献   
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The purpose of this study was to evaluate the clinical and radiographic treatment effects of percutaneous autologous concentrated bone marrow grafting in nonunion cases and to evaluate the effectiveness of this grafting procedure. We enrolled 17 cases those had atrophic changes due to continuous nonunion for over 9 months after injury and had undergone low-intensity pulsed ultrasound treatment for more than 3 months. The site of nonunion was the femur in 10 cases, the tibia in 5 cases, the humerus in 1 case, and the ulna in 1 case. They underwent percutaneous autologous concentrated bone marrow grafting and continued low-intensity pulsed ultrasound stimulation treatment after grafting. Patients were evaluated using the visual analogue scale for pain at immediately before the procedure, 3, 6, and 12 months after grafting. Plain radiographs of the affected site were taken and evaluated about the healing of the nonunion site at each clinical evaluation. As quantitative assessment, CT scans were undertaken before the procedure and 6 months after grafting. The visual analogue scale pain score was reduced consistently after grafting in all patients. About the healing at the nonunion site, 11 and 13 cases of bone union were observed at 6 and 12 months after grafting. The mean volume of callus formation based on CT images was 4,147 (262–27,392) mm3 total between grafting and 6 months. Percutaneous autologous concentrated bone marrow grafting is an effective procedure for the treatment of patients with nonunion.  相似文献   
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