Objective: To evaluate the antioxidant, immunomodulatory and anti-inflammatory activities of pyrrolidine dithiocarbamate and saxagliptin in rats with thioacetamide-induced ulcerative colitis. Methods: Animals were ora...Objective: To evaluate the antioxidant, immunomodulatory and anti-inflammatory activities of pyrrolidine dithiocarbamate and saxagliptin in rats with thioacetamide-induced ulcerative colitis. Methods: Animals were orally administered with a vehicle, sulfasalazine(500 mg/kg), pyrrolidine dithiocarbamate(100 mg/kg), and saxagliptin(10 mg/kg) for two weeks. Ulcerative colitis was induced by a single intrarectal instillation of thioacetamide on day 8. Colon samples were collected to assess mitogen-activated protein kinase(MAPK), phosphorylated extracellular signal-regulated kinase(ERK), c AMP response element-binding protein(CREB), interleukin-12(IL-12), caspase-3, β-defensin, inducible nitric oxide synthase(i NOS) and glucagon like peptide-1(GLP-1). Moreover, histopathological examination was performed. Results: Rats treated with thioacetamide caused increases in colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin, i NOS, as well as decreases in body weight and GLP-1. In addition, distortion of colonic structure was found by histopathological examination. Pyrrolidine dithiocarbamate and saxagliptin mitigated colitis severity by improving body weight decrease and GLP-1, and reducing colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin and i NOS. Conclusions: Pyrrolidine dithiocarbamate and saxagliptin are efficient against thioacetamide induced colitis through improving inflammatory and oxidative changes.展开更多
针对增材制造过程中形成的缺陷会对工件造成不可逆的影响,分析了冷金属过渡(Cold metal transfer,CMT)增材制造过程的焊接电流信号和焊接电压信号,提出了一种基于时间序列算法的CMT增材制造缺陷在线监测方法。设置不同的焊接工况,收集...针对增材制造过程中形成的缺陷会对工件造成不可逆的影响,分析了冷金属过渡(Cold metal transfer,CMT)增材制造过程的焊接电流信号和焊接电压信号,提出了一种基于时间序列算法的CMT增材制造缺陷在线监测方法。设置不同的焊接工况,收集良好组和缺陷组的原始焊接电流和焊接电压信号,使用SAX(Symbolic aggregate approximation)算法对数据进行预处理。使用随机森林模型对数值型数据再分类,达到实时监测的效果;同时为突出SAX算法的优越性,设置对比试验组,将原始的焊接电流数据直接放入随机森林模型进行分类。结果表明,原始焊接电流组的测试集准确率为80%,SAX算法数据预处理组的测试集准确率为96%。展开更多
A simple, specific, sensitive, precise and accurate reverse phase high performance liquid chromatographic method (RP-HPLC) was developed for the simultaneous analysis of Metformin and Saxagliptin in active pharmaceuti...A simple, specific, sensitive, precise and accurate reverse phase high performance liquid chromatographic method (RP-HPLC) was developed for the simultaneous analysis of Metformin and Saxagliptin in active pharmaceutical ingredients (APIs) as well as in marketed tablet (combination) dosage forms. The method was achieved on Enable C18 G (250 × 4.6 mm;5 μm particle size) column using 0.05 M KH2PO4 buffer (pH 4.5):Methanol:Acetonitrile (60:20:20 %v/v) as a mobile phase at a flow rate of 0.6 mL/min and by employing UV detection at 220 nm wavelength. The retention time of Metformin and Saxagliptin were found to be 4.38 min and 6.92 min, respectively. The method was validated as per ICH guidelines. The limit of detection (LOD) and limit of quantification (LOQ) of Metformin were found to be 0.112 μg/mL and 0.373 μg/mL, respectively, while those of Saxagliptin were found to be 0.029 μg/mL and 0.096 μg/mL, respectively. The method was found to be rapid, sensitive, linear, specific, accurate, precise and economic for the quality control and stability assays of Metformin and Saxagliptin in marketed tablet dosage forms.展开更多
A simple, specific, accurate and precise high performance thin layer chromatographic method (HPTLC) was developed for the quantitative analysis of Saxagliptin in active pharmaceutical ingredients (APIs) and pharmaceut...A simple, specific, accurate and precise high performance thin layer chromatographic method (HPTLC) was developed for the quantitative analysis of Saxagliptin in active pharmaceutical ingredients (APIs) and pharmaceutical dosage forms. The method was achieved using silica gel aluminum plate 60 F254 (10 × 10 cm) as stationary phase and Methanol:Chloroform (6:4 v/v) as mobile phase. The developed plate was scanned densitometrically using UV 222 nm wavelength. The Rf value of Saxagliptin was found to be 0.50 ± 0.02. The developed method was validated according to ICH guidelines. Limit of detection (LOD) and limit of quantification (LOQ) of Saxagliptin by this method were found as 7.96 ng/spot and 26.54 ng/spot, respectively. The method was found to be sensitive, specific, linear, accurate, precise and robust for the quantitative analysis of Saxagliptin in both APIs and marketed tablet formulation.展开更多
Introduction: Good glycaemic control without causing excessive hypoglycaemia reduced the risk of macrovascular and microvascular complications in type 2 DM patients on regular haemodialysis (HD). The objectives of thi...Introduction: Good glycaemic control without causing excessive hypoglycaemia reduced the risk of macrovascular and microvascular complications in type 2 DM patients on regular haemodialysis (HD). The objectives of this study were to assess the efficacy and safety of add-on saxagliptin to insulin therapy in blood sugar control compared to insulin therapy alone in diabetic patients undergoing HD. Design and Methods: In this prospective open-labelled randomized controlled trial, HD patients with type 2 DM and on stable insulin therapy with HbA1c 7% - 13% were randomized to receive add-on saxagliptin 2.5 mg once daily to insulin therapy or insulin therapy only for 12 weeks. Results: 24 patients were randomized into each arm equally. Baseline and week-12 serum HbA1c, fructosamine, fasting blood glucose (FBS) and mean self monitoring blood glucose (SMBG) were comparable in the groups. Reduction of HbA1c and mean SMBG were significant in both groups. There was a significant drop in fructosamine levels (p = 0.004) and trend of lower FBS (p = 0.097) in add-on saxagliptin group but not in insulin alone group. The incidence of hypoglycaemia was the same in both groups. Conclusion: Add-on saxagliptin to insulin is comparable to insulin therapy alone in blood sugar control in regular HD patients and is safe and generally well tolerated. Add-on saxagliptin group may have more persistent and less fluctuation of glucose control compared to insulin only group.展开更多
文摘Objective: To evaluate the antioxidant, immunomodulatory and anti-inflammatory activities of pyrrolidine dithiocarbamate and saxagliptin in rats with thioacetamide-induced ulcerative colitis. Methods: Animals were orally administered with a vehicle, sulfasalazine(500 mg/kg), pyrrolidine dithiocarbamate(100 mg/kg), and saxagliptin(10 mg/kg) for two weeks. Ulcerative colitis was induced by a single intrarectal instillation of thioacetamide on day 8. Colon samples were collected to assess mitogen-activated protein kinase(MAPK), phosphorylated extracellular signal-regulated kinase(ERK), c AMP response element-binding protein(CREB), interleukin-12(IL-12), caspase-3, β-defensin, inducible nitric oxide synthase(i NOS) and glucagon like peptide-1(GLP-1). Moreover, histopathological examination was performed. Results: Rats treated with thioacetamide caused increases in colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin, i NOS, as well as decreases in body weight and GLP-1. In addition, distortion of colonic structure was found by histopathological examination. Pyrrolidine dithiocarbamate and saxagliptin mitigated colitis severity by improving body weight decrease and GLP-1, and reducing colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin and i NOS. Conclusions: Pyrrolidine dithiocarbamate and saxagliptin are efficient against thioacetamide induced colitis through improving inflammatory and oxidative changes.
文摘针对增材制造过程中形成的缺陷会对工件造成不可逆的影响,分析了冷金属过渡(Cold metal transfer,CMT)增材制造过程的焊接电流信号和焊接电压信号,提出了一种基于时间序列算法的CMT增材制造缺陷在线监测方法。设置不同的焊接工况,收集良好组和缺陷组的原始焊接电流和焊接电压信号,使用SAX(Symbolic aggregate approximation)算法对数据进行预处理。使用随机森林模型对数值型数据再分类,达到实时监测的效果;同时为突出SAX算法的优越性,设置对比试验组,将原始的焊接电流数据直接放入随机森林模型进行分类。结果表明,原始焊接电流组的测试集准确率为80%,SAX算法数据预处理组的测试集准确率为96%。
文摘A simple, specific, sensitive, precise and accurate reverse phase high performance liquid chromatographic method (RP-HPLC) was developed for the simultaneous analysis of Metformin and Saxagliptin in active pharmaceutical ingredients (APIs) as well as in marketed tablet (combination) dosage forms. The method was achieved on Enable C18 G (250 × 4.6 mm;5 μm particle size) column using 0.05 M KH2PO4 buffer (pH 4.5):Methanol:Acetonitrile (60:20:20 %v/v) as a mobile phase at a flow rate of 0.6 mL/min and by employing UV detection at 220 nm wavelength. The retention time of Metformin and Saxagliptin were found to be 4.38 min and 6.92 min, respectively. The method was validated as per ICH guidelines. The limit of detection (LOD) and limit of quantification (LOQ) of Metformin were found to be 0.112 μg/mL and 0.373 μg/mL, respectively, while those of Saxagliptin were found to be 0.029 μg/mL and 0.096 μg/mL, respectively. The method was found to be rapid, sensitive, linear, specific, accurate, precise and economic for the quality control and stability assays of Metformin and Saxagliptin in marketed tablet dosage forms.
文摘A simple, specific, accurate and precise high performance thin layer chromatographic method (HPTLC) was developed for the quantitative analysis of Saxagliptin in active pharmaceutical ingredients (APIs) and pharmaceutical dosage forms. The method was achieved using silica gel aluminum plate 60 F254 (10 × 10 cm) as stationary phase and Methanol:Chloroform (6:4 v/v) as mobile phase. The developed plate was scanned densitometrically using UV 222 nm wavelength. The Rf value of Saxagliptin was found to be 0.50 ± 0.02. The developed method was validated according to ICH guidelines. Limit of detection (LOD) and limit of quantification (LOQ) of Saxagliptin by this method were found as 7.96 ng/spot and 26.54 ng/spot, respectively. The method was found to be sensitive, specific, linear, accurate, precise and robust for the quantitative analysis of Saxagliptin in both APIs and marketed tablet formulation.
文摘Introduction: Good glycaemic control without causing excessive hypoglycaemia reduced the risk of macrovascular and microvascular complications in type 2 DM patients on regular haemodialysis (HD). The objectives of this study were to assess the efficacy and safety of add-on saxagliptin to insulin therapy in blood sugar control compared to insulin therapy alone in diabetic patients undergoing HD. Design and Methods: In this prospective open-labelled randomized controlled trial, HD patients with type 2 DM and on stable insulin therapy with HbA1c 7% - 13% were randomized to receive add-on saxagliptin 2.5 mg once daily to insulin therapy or insulin therapy only for 12 weeks. Results: 24 patients were randomized into each arm equally. Baseline and week-12 serum HbA1c, fructosamine, fasting blood glucose (FBS) and mean self monitoring blood glucose (SMBG) were comparable in the groups. Reduction of HbA1c and mean SMBG were significant in both groups. There was a significant drop in fructosamine levels (p = 0.004) and trend of lower FBS (p = 0.097) in add-on saxagliptin group but not in insulin alone group. The incidence of hypoglycaemia was the same in both groups. Conclusion: Add-on saxagliptin to insulin is comparable to insulin therapy alone in blood sugar control in regular HD patients and is safe and generally well tolerated. Add-on saxagliptin group may have more persistent and less fluctuation of glucose control compared to insulin only group.
