Objective:This study is aimed to explore the effect of triazole fungicide tebuconazole(TEB)exposure on the oral absorption behavior of atenolol(AT),based on the homeostasis of bile acids(BAs).Methods:TEB was daily gav...Objective:This study is aimed to explore the effect of triazole fungicide tebuconazole(TEB)exposure on the oral absorption behavior of atenolol(AT),based on the homeostasis of bile acids(BAs).Methods:TEB was daily gavaged to rats with 3 mg/kg dose for 28 days to establish the TEB-exposure rat model.The amounts of glycocholic acid,glycochenodeoxycholic acid,taurocholic acid and taurine deoxycholic acid in the small intestine contents of normal and TEB-exposure rats were detected by LC-MS/MS.AT(10 mg/kg)were gavaged to the normal and TEB-exposure rats,and then blood were collected from orbital venous plexus at predetermined time-points.The concentration of AT in plasma was detected by LC-MS/MS,and the pharmacokinetic parameters were calculated by the DAS pharmacokinetic software.An intestinal circulation perfusion model was established in normal rats,and perfused with the perfusates containing the model drug of fluorescein and the BAs with the same compositions as the normal/TEB-exposure rats.After perfusion,the absorption and permeability of fluorescein in intestine were detected,as well as the oxidative stress status and ZO-1 expression level in the intestinal tissues.Results:Compared with normal rats,TEB-exposure increased the amounts of glycocholic acid,glycochenodeoxycholic acid,taurocholic acid and taurine deoxycholic acid in intestine significantly(P<0.001).In TEB-exposure rats,the maximum plasma concentration and area under the curve of AT were increased significantly than those of normal rats(P<0.05),and the peak time was significantly delayed(P<0.05).The TEB-induced BAs homeostasis perturbance increased intestinal permeability,and this effect was associated with the elevation of oxidative stress and the down-regulation of intercellular tight junction proteins in intestinal tissues.Conclusion:TEB-exposure can affect the oral absorption behavior of AT,which is probably related with the intestinal BAs homeostasis perturbance,thus it might affect the clinical efficacy and safety of this drug.展开更多
本文通过比较 7 T 场强下化学交换饱和转移(chemical exchange saturation transfer,CEST)成像技术不同量化方式在急性帕金森氏病小鼠模型研究中的应用效果,探讨了客观无创的帕金森氏病研究方案.使用 Bruker PharmaScan7 T小动物磁共振...本文通过比较 7 T 场强下化学交换饱和转移(chemical exchange saturation transfer,CEST)成像技术不同量化方式在急性帕金森氏病小鼠模型研究中的应用效果,探讨了客观无创的帕金森氏病研究方案.使用 Bruker PharmaScan7 T小动物磁共振成像(Magnetic Resonance Imaging,MRI)扫描仪,对经 1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)急性造模前及造模后第3、10天的小鼠黑质、皮层及海马进行扫描,计算弛豫时间 T1、T2、MTRasym(magnetization transfer ratio based on asymmetry analysis)、MTRrex(magnetization transfer ratio yielding Rex)、AREX(apparent exchange-dependent relaxation)及5池拟合后的胺峰面积 Areaamine、酰胺峰面积 Areaamide.结果显示仅黑质中融合了倒Z谱分析和5池洛仑兹拟合所得的量化指标 MTRrex、AREX及Areaamine在造模后显著减小,与黑质免疫组化结果一致,而 T1、T2以及基于Z谱非对称性分析的 MTRasym未见统计学差异,这表明此量化方式消除了直接饱和效应及磁化转移效应的影响,准确性上要优于Z谱非对称分析法,更能正确地提示帕金森氏病黑质的变化.展开更多
Objective:To compare the effects of different conservative managements on patients with adolescent idiopathic scoliosis (AIS). Method:One hundred and four AIS patients were recruited for this study. The patients were ...Objective:To compare the effects of different conservative managements on patients with adolescent idiopathic scoliosis (AIS). Method:One hundred and four AIS patients were recruited for this study. The patients were divided into 3 groups:exercise (E group), brace (B group) and combined rehabilitation treatment (brace treatment combined with exercise, CR group). Radiological parameter were used to assess AIS patients before and after treatment. The Chinese version of scoliosis research society-22(SRS-22) patient questionnaires were filled out by patients after treatment. The SRS-22 scores were compared among management groups. Result:The maximal Cobb angles were smaller in E group than in B group or CR group both before and af- ter treatment. The maximal Cobb angles were significantly smaller after treatment than before treatment in B group and CR group. Function/activity was better in E group than in B group or CR group. Self-image/appear- ance and satisfaction with management were better in E group and CR group than in B group. There was no significant difference among treatment groups in pain and mental health. Conclusion:Both brace and combined rehabilitation treatment can reduce the spinal curve of AIS patients. Both exercise and combined rehabilitation treatment have positive influence on self-image/appearance and satis- faction with management. We support preference of combined rehabilitation treatment above brace treatment.展开更多
基金supported by National Natural Science Foundation of China(81874348)Academic Support Program for Top Talents of Higher Education in Anhui Province(GXBJZD2022027)Science and Technology Innovation Project of Anhui Drug Administration(AHYJ-KJ-202110)。
文摘Objective:This study is aimed to explore the effect of triazole fungicide tebuconazole(TEB)exposure on the oral absorption behavior of atenolol(AT),based on the homeostasis of bile acids(BAs).Methods:TEB was daily gavaged to rats with 3 mg/kg dose for 28 days to establish the TEB-exposure rat model.The amounts of glycocholic acid,glycochenodeoxycholic acid,taurocholic acid and taurine deoxycholic acid in the small intestine contents of normal and TEB-exposure rats were detected by LC-MS/MS.AT(10 mg/kg)were gavaged to the normal and TEB-exposure rats,and then blood were collected from orbital venous plexus at predetermined time-points.The concentration of AT in plasma was detected by LC-MS/MS,and the pharmacokinetic parameters were calculated by the DAS pharmacokinetic software.An intestinal circulation perfusion model was established in normal rats,and perfused with the perfusates containing the model drug of fluorescein and the BAs with the same compositions as the normal/TEB-exposure rats.After perfusion,the absorption and permeability of fluorescein in intestine were detected,as well as the oxidative stress status and ZO-1 expression level in the intestinal tissues.Results:Compared with normal rats,TEB-exposure increased the amounts of glycocholic acid,glycochenodeoxycholic acid,taurocholic acid and taurine deoxycholic acid in intestine significantly(P<0.001).In TEB-exposure rats,the maximum plasma concentration and area under the curve of AT were increased significantly than those of normal rats(P<0.05),and the peak time was significantly delayed(P<0.05).The TEB-induced BAs homeostasis perturbance increased intestinal permeability,and this effect was associated with the elevation of oxidative stress and the down-regulation of intercellular tight junction proteins in intestinal tissues.Conclusion:TEB-exposure can affect the oral absorption behavior of AT,which is probably related with the intestinal BAs homeostasis perturbance,thus it might affect the clinical efficacy and safety of this drug.
基金the National Natural Science Foundation of China(61671228,61728107)
文摘本文通过比较 7 T 场强下化学交换饱和转移(chemical exchange saturation transfer,CEST)成像技术不同量化方式在急性帕金森氏病小鼠模型研究中的应用效果,探讨了客观无创的帕金森氏病研究方案.使用 Bruker PharmaScan7 T小动物磁共振成像(Magnetic Resonance Imaging,MRI)扫描仪,对经 1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)急性造模前及造模后第3、10天的小鼠黑质、皮层及海马进行扫描,计算弛豫时间 T1、T2、MTRasym(magnetization transfer ratio based on asymmetry analysis)、MTRrex(magnetization transfer ratio yielding Rex)、AREX(apparent exchange-dependent relaxation)及5池拟合后的胺峰面积 Areaamine、酰胺峰面积 Areaamide.结果显示仅黑质中融合了倒Z谱分析和5池洛仑兹拟合所得的量化指标 MTRrex、AREX及Areaamine在造模后显著减小,与黑质免疫组化结果一致,而 T1、T2以及基于Z谱非对称性分析的 MTRasym未见统计学差异,这表明此量化方式消除了直接饱和效应及磁化转移效应的影响,准确性上要优于Z谱非对称分析法,更能正确地提示帕金森氏病黑质的变化.
基金supported by the Science and Technology Committee of Shanghai Gran(t114119a2700)
文摘Objective:To compare the effects of different conservative managements on patients with adolescent idiopathic scoliosis (AIS). Method:One hundred and four AIS patients were recruited for this study. The patients were divided into 3 groups:exercise (E group), brace (B group) and combined rehabilitation treatment (brace treatment combined with exercise, CR group). Radiological parameter were used to assess AIS patients before and after treatment. The Chinese version of scoliosis research society-22(SRS-22) patient questionnaires were filled out by patients after treatment. The SRS-22 scores were compared among management groups. Result:The maximal Cobb angles were smaller in E group than in B group or CR group both before and af- ter treatment. The maximal Cobb angles were significantly smaller after treatment than before treatment in B group and CR group. Function/activity was better in E group than in B group or CR group. Self-image/appear- ance and satisfaction with management were better in E group and CR group than in B group. There was no significant difference among treatment groups in pain and mental health. Conclusion:Both brace and combined rehabilitation treatment can reduce the spinal curve of AIS patients. Both exercise and combined rehabilitation treatment have positive influence on self-image/appearance and satis- faction with management. We support preference of combined rehabilitation treatment above brace treatment.
