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<p><b>BACKGROUND</b>At present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone.</p><p><b>METHODS</b>This study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment.</p><p><b>RESULTS</b>At week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 μU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 μU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups.</p><p><b>CONCLUSIONS</b>Compared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated.</p><p><b>REGISTRATION NUMBER</b>ChiCTR-TRC-13003776.</p>
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glicemia , Proteína C-Reativa , Metabolismo , Diabetes Mellitus Tipo 2 , Sangue , Tratamento Farmacológico , Combinação de Medicamentos , Quimioterapia Combinada , Hipoglicemiantes , Usos Terapêuticos , Metformina , Usos Terapêuticos , Tiazóis , Usos TerapêuticosRESUMO
<p><b>OBJECTIVE</b>To investigate the autoimmune injuries of diabetic macrovascular disease (aorta) and the protective effects of immunosuppressive agent (cyclosporine A, CsA) on aortic injuries in streptozotocin (STZ)-induced diabetic rats.</p><p><b>METHODS</b>STZ-induced diabetic rats were assigned randomly to 6 groups which received low (BML or AML, 1 mgxkg(-1)xd(-1)), middle (BMM or AMM, 4 mgxkg(-1)xd(-1)) or high (BMH or AMH, 8 mgxkg(-1)xd(-1)) dose of CsA from 1 week before or after STZ for 8 weeks. Diabetic rats without any treatment, insulin-treated diabetic rats and normal rats were also monitored simultaneously and served as control groups. The pathologic abnormalities of the aorta were verified by HE, Masson staining and electronmicroscopy. The depositions of immunoglobulins (IgG, IgM and IgA) were determined by immunohistochemistry and immunofluorescence methods.</p><p><b>RESULTS</b>At the end of study, lymphocytes infiltration and collagen content (26 582 +/- 6901) were significantly higher in diabetic aorta than those in non-diabetic aorta (Collagen: 7482 +/- 3491, P < 0.01). The deposited IgG and IgA were also significantly increased in diabetic aorta compared with non-diabetic aorta (IgG: 11 789 +/- 2491 vs. 2518 +/- 1066, P < 0.01; IgA: 17 430 +/- 3159 vs. 1135 +/- 758, P < 0.01). These changes were not affected by insulin while CsA intervention significantly reduced aortic collagen content (BMH: 13 518 +/- 5440, P < 0.01 vs. STZ) and immunoglobulin deposition (BMH: IgG: 7584 +/- 4462; IgA: 6176 +/- 1900, all P < 0.01 vs. STZ). These immunoglobulin deposition changes were confirmed by results of immunofluorescence. Aortic collagen accumulation was positively correlated to aortic immunoglobulin deposition (IgG, r = 0.556, P < 0.01; IgA, r = 0.661, P < 0.01).</p><p><b>CONCLUSIONS</b>Our data suggest that the autoimmune injuries might be a promoting factor in the pathogenesis of the diabetic macrovascular disease which could lead to the development of macrovascular disease. Immunosuppressive agent, such as CsA, could inhibit the abnormal deposition of immunoglobulins and therefore, delay the development of diabetic macrovascular disease in this model.</p>
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Animais , Ratos , Aorta , Alergia e Imunologia , Patologia , Doenças da Aorta , Ciclosporina , Farmacologia , Diabetes Mellitus Experimental , Alergia e Imunologia , Patologia , Endotélio Vascular , Patologia , Imunossupressores , Farmacologia , Ratos Sprague-DawleyRESUMO
Objective To study the level of immunoglobulin and the prevalence of ANA in patients with Graves' diseases(GD).To explore the correlation between GD and other systemic autoimmune disorders.Methods Data of 145 patients with GD and 45 healthy subjects were collected.All cases were detected on the presence of ANA and the level of immunoglobulin,FT3,FT4,and thyroid specific antibodies.Results The presencerate of ANA and the level of IgG in patients with GD were higher than that in healthy controls [(28.28% vs 4.55%);(70.96?26.14 vs 60.41?11.01) mmol/L](P
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Complement system is an important constituent in immune system.Membrane attack complex (C5b-9)is the final ingredient in the complement activation.Recently,a few studies showed that C5b-9 deposition was found in the diabetics with chronic complications,indicating that complement activation might be involved in the pathogenesis of diabetic complications.Our aim is to summarize some newly published works and show a prelimimary work we did in this area.We hope that more attention should be paid to the role of autoimmune mechanism in diabetic complications.
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The (GCT)o polymorphism of the MICA gene was investigated in 100 patients with latent autoimmune diabetes in adult (LADA) and 145 healthy controls by PCR and denaturing polyacrylamide gel electrophoresis.The A5.1 allele was present at a significantly higher frequency in LADA group (0.340) than that in control group (0.183) (P
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The polymorphism of (AT) repeat within the 3' untranslated region in exon 3 of CTLA-4 gene was evaluated by PCR-SSCP in 139 patients with Graves' disease (GD) and 110 normal subjects in Tianjin. The gene frequency of 106 bp in patients with GD was significantly increased than that in the control group (RR =1.992,P
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<p><b>OBJECTIVE</b>To detect the changes in the expression of apoptosis signals: Fas, FasL and NF-kappa B in the process of osteoclast-like cell (OLC) apoptosis effected by sodium fluoride.</p><p><b>METHODS</b>After co-culture of osteoclast-like cells with 0, 5, 10 and 15 mg/L sodium fluoride, Fas, FasL and NF-kappa B antibody expressions were detected by immune-histochemistry.</p><p><b>RESULTS</b>The expression of Fas and FasL increased with the concentration of the sodium fluoride, however the expression of NF-kappa B decreased with the concentration of sodium fluoride.</p><p><b>CONCLUSION</b>In the process of OLC apoptosis induced by sodium fluoride, the expression of Fas and FasL increased, and that of NF-kappa B decreased with the concentration of sodium fluoride respectively, and the changes of the expression present a dose-dependent pattern.</p>
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Animais , Feminino , Camundongos , Apoptose , Proteína Ligante Fas , Fluoretos , Farmacologia , Ligantes , Glicoproteínas de Membrana , Metabolismo , Camundongos Endogâmicos C57BL , NF-kappa B , Metabolismo , Osteoclastos , Biologia Celular , Metabolismo , Receptor fas , MetabolismoRESUMO
<p><b>OBJECTIVE</b>To clarify the effects of nylestriol on microarchitecture and interleukin-6 (IL-6) mRNA expression in tibial bone in ovariectomized rats.</p><p><b>METHODS</b>30 female rats were randomly allocated into 3 groups: sham, OVX and nylestriol-treated group. Nylestriol-treated group were ovariectomized, then fed with nylestriol for 3 months and the bone mineral density (BMD) was measured in lumbar vertebra by dual energy x-ray absorptiometry. After sacrifice of the animal, bone histomorphometric parameters were measured to study the changes in bone microarchitecture, and RT-PCR was performed to detect the expression of IL-6 mRNA in bone tissue.</p><p><b>RESULTS</b>BMD was significantly reduced, while IL-6 mRNA level elevated in the OVX group compared with the sham group. Static histomorphometric data showed that the trabecular bone volume, mean trabecular plate thickness and density were reduced while the mean trabecular plate space elevated remarkably in the OVX group in comparison with that in the sham group. As for dynamic parameters, trabecular osteoid surface, tetracyclin labeled surface and bone turnover rate were increased while osteoid maturation rate decreased significantly in the OVX group compared with the sham group. BMD, IL-6 mRNA expression and bone histomorphometric parameters were improved in nylestriol-treated rats.</p><p><b>CONCLUSION</b>Nylestriol plays an important role in maintaining bone volume and improving bone microarchitecture by markedly inhibiting bone turnover and bone resorption, which might be to some degree attributed to reduced IL-6 expression.</p>
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Animais , Feminino , Ratos , Remodelação Óssea , Reabsorção Óssea , Congêneres do Estradiol , Farmacologia , Usos Terapêuticos , Interleucina-6 , Genética , Osteoporose , Tratamento Farmacológico , Patologia , Ovariectomia , Quinestrol , Farmacologia , Usos Terapêuticos , RNA Mensageiro , Genética , Distribuição Aleatória , Ratos Wistar , Tíbia , PatologiaRESUMO
The depositions of immunoglobulins on the retina of diabetic rat were studied with immunohistochemistry,immunofluorecence and computer analysing system.In comparison with control group, depositions of IgG,IgA and IgM on the retina of diabetic rat induced by streptozotocin were significantly increased (all P<0.05 ).So the immunoglobulin depositions may contribute to the pathogenesis of diabetic retinopathy.
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<p><b>OBJECTIVE</b>To investigate the distribution of tetracycline-arginine-glycine-aspartate-tyrosine (T-RGDY) in mice and its effect on bone.</p><p><b>METHODS</b>125-labeled T-RGDY was studied for its distribution in mice and for its effects on bone by histomorphometry in ovariectomized rats.</p><p><b>RESULTS</b>The 125I-labeled T-RGDY was more concentrated in the osteoporotic bone than in the normal bone. Compared with ovariectomy group, the morphologic index such as trabecular bone volume/total tissue volume (TBV/TTV), TBV/sponge bone volume (SBV), and mean trabecular plate thickness (MTPT) in T-RGDY group significantly increased (P < 0.05). As compared with sham operation group, MTPT significantly increased in T-RGDY group (P < 0.05), while TBV/SBV and mean trabecular plate density significantly decreased (P < 0.05), and TBV/TYV and mean trabecular plate spacing were almost the same as those in sham operation group (P > 0.05).</p><p><b>CONCLUSION</b>T-RGDY may concentrate in bone tissue to a certain degree, which is closely related with the status of bone remodeling. T-RGDY may inhibit the bone loss caused by ovariectomy.</p>