This study explored the effects of cucurbitacin E （CUE）, a bioactive compound from Cucurbitaceae, on the metabolism/ pharmacokinetic of tolbutamide, a model CYP2C9/11 probe substrate, and hepatic CYP2C11 expression ...This study explored the effects of cucurbitacin E （CUE）, a bioactive compound from Cucurbitaceae, on the metabolism/ pharmacokinetic of tolbutamide, a model CYP2C9/11 probe substrate, and hepatic CYP2C11 expression in rats. Liquid chro- matography-（tandem） mass spectrometry （LC-MS/MS） assay was used to detect tolbutamide as well as 4-hydroxytolbutamide, and then successfully applied to the pharmacokinetic study of tolbutamide in rats. The effect of CuE on CYP2C11 expression was determined by western blot. CuE （1.25-100μmol· L-1） competitively inhibited tolbutamide 4-hydroxylation （CYP2C11） activity only in concentration-dependent manner with a Ki value of 55.5 μmol L-1 in vitro. In whole animal studies, no signifi- cant difference in metabolism/pharmacokinetic of tolbutamide was found for the single pretreatment groups. In contrast, mul- tiple pretreatments of CuE （200 μg kg-1 d-1, 3 d, i.p.） significantly decreased tolbutamide clearance （CL） by 25% and pro- longed plasma half-time （T1/2） by 37%. Moreover, CuE treatment （50-200 pg kg-l d-1, i.p.） for 3 d did not affect CYP2C11 expression. These findings demonstrated that CuE competitively inhibited the metabolism of CYP2C11 substrates but had no effect on rat CYP2C11 expression. This study may provide a useful reference for the reasonable and safe use of herbal or nat- ural products containing CuE to avoid unnecessary drug-drug interactions.展开更多
The nonlinear propagation of dust acoustic waves is investigated in four-component plasmas consisting of positively charged dust grains, trapped ions, nonthermal electrons, and photoelectron due to ultraviolet irradia...The nonlinear propagation of dust acoustic waves is investigated in four-component plasmas consisting of positively charged dust grains, trapped ions, nonthermal electrons, and photoelectron due to ultraviolet irradiation.We use generalized viscoelastic hydrodynamic model for strongly coupled dust grain. In the weak nonlinearity limit, a modified Kadomstev–Petviashvili（KP） equation and a modified KP-Burger equation, which have a damping term coming from nonadiabatic charge variation, have been derived in the kinetic regime and hydrodynamic regime, respectively. With the increasing of UV photon flux, the hydrodynamic regime changes to kinetic regime. The approximate analytical line soliton and shock solutions are investigated in the kinetic regime and hydrodynamic regime, respectively.展开更多
To make clear the precise hemodynamic mechanism underlying the anti-atherogenesis benefit of enhanced external couterpulsation(EECP) treatment, and to investigate the proper role of some important hemodynamic factors ...To make clear the precise hemodynamic mechanism underlying the anti-atherogenesis benefit of enhanced external couterpulsation(EECP) treatment, and to investigate the proper role of some important hemodynamic factors during the atherosclerotic progress, a comprehensive study combining long-term animal experiment and numerical solving was conducted in this paper. An experimentally induced hypercholesterolemic porcine model was developed and the chronic EECP intervention was subjected. Basic hemodynamic measurement was performed in vivo, as well as the arterial endothelial samples were extracted for physiological examination. Meanwhile, a numerical model was introduced to solve the complex hemodynamic factors such as WSS and OSI. The results show that EECP treatment resulted in significant increase of the instant levels of arterial WSS, blood pressure, and OSI. During EECP treatment, the instant OSI level of the common carotid arteries over cardiac cycles raised to a mean value of 8.58 ×10-2±2.13 ×10-2. Meanwhile, the chronic intervention of EECP treatment significantly reduced the atherosclerotic lesions in abdominal aortas and the endothelial cellular adherence. The present study suggests that the unique blood flow pattern induced by EECP treatment and the augmentation of WSS level in cardiac cycles may be the most important hemodynamic mechanism that contribute to its anti-atherogenesis effect. And as one of the indices that cause great concern in current hemodynamic study, OSI may not play a key role during the initiation of atherosclerosis.展开更多
基金supported by the National Natural Science Foundation of China (81301908)the Science and Technology Commission of Shanghai Municipality (13ZR1412600, 14DZ2270100)
文摘This study explored the effects of cucurbitacin E （CUE）, a bioactive compound from Cucurbitaceae, on the metabolism/ pharmacokinetic of tolbutamide, a model CYP2C9/11 probe substrate, and hepatic CYP2C11 expression in rats. Liquid chro- matography-（tandem） mass spectrometry （LC-MS/MS） assay was used to detect tolbutamide as well as 4-hydroxytolbutamide, and then successfully applied to the pharmacokinetic study of tolbutamide in rats. The effect of CuE on CYP2C11 expression was determined by western blot. CuE （1.25-100μmol· L-1） competitively inhibited tolbutamide 4-hydroxylation （CYP2C11） activity only in concentration-dependent manner with a Ki value of 55.5 μmol L-1 in vitro. In whole animal studies, no signifi- cant difference in metabolism/pharmacokinetic of tolbutamide was found for the single pretreatment groups. In contrast, mul- tiple pretreatments of CuE （200 μg kg-1 d-1, 3 d, i.p.） significantly decreased tolbutamide clearance （CL） by 25% and pro- longed plasma half-time （T1/2） by 37%. Moreover, CuE treatment （50-200 pg kg-l d-1, i.p.） for 3 d did not affect CYP2C11 expression. These findings demonstrated that CuE competitively inhibited the metabolism of CYP2C11 substrates but had no effect on rat CYP2C11 expression. This study may provide a useful reference for the reasonable and safe use of herbal or nat- ural products containing CuE to avoid unnecessary drug-drug interactions.
基金Supported by National Natural Science Foundation of China under Grant No.11104012 the Fundamental Research Funds for the Central Universities under Grant Nos.FRF-TP-09-019A and FRF-BR-11-031B
文摘The nonlinear propagation of dust acoustic waves is investigated in four-component plasmas consisting of positively charged dust grains, trapped ions, nonthermal electrons, and photoelectron due to ultraviolet irradiation.We use generalized viscoelastic hydrodynamic model for strongly coupled dust grain. In the weak nonlinearity limit, a modified Kadomstev–Petviashvili（KP） equation and a modified KP-Burger equation, which have a damping term coming from nonadiabatic charge variation, have been derived in the kinetic regime and hydrodynamic regime, respectively. With the increasing of UV photon flux, the hydrodynamic regime changes to kinetic regime. The approximate analytical line soliton and shock solutions are investigated in the kinetic regime and hydrodynamic regime, respectively.
基金Key Clinical Project from the Ministry of Healthgrant number:25400+1 种基金National Natural Science Foundation of Chinagrant number:81170272
文摘To make clear the precise hemodynamic mechanism underlying the anti-atherogenesis benefit of enhanced external couterpulsation(EECP) treatment, and to investigate the proper role of some important hemodynamic factors during the atherosclerotic progress, a comprehensive study combining long-term animal experiment and numerical solving was conducted in this paper. An experimentally induced hypercholesterolemic porcine model was developed and the chronic EECP intervention was subjected. Basic hemodynamic measurement was performed in vivo, as well as the arterial endothelial samples were extracted for physiological examination. Meanwhile, a numerical model was introduced to solve the complex hemodynamic factors such as WSS and OSI. The results show that EECP treatment resulted in significant increase of the instant levels of arterial WSS, blood pressure, and OSI. During EECP treatment, the instant OSI level of the common carotid arteries over cardiac cycles raised to a mean value of 8.58 ×10-2±2.13 ×10-2. Meanwhile, the chronic intervention of EECP treatment significantly reduced the atherosclerotic lesions in abdominal aortas and the endothelial cellular adherence. The present study suggests that the unique blood flow pattern induced by EECP treatment and the augmentation of WSS level in cardiac cycles may be the most important hemodynamic mechanism that contribute to its anti-atherogenesis effect. And as one of the indices that cause great concern in current hemodynamic study, OSI may not play a key role during the initiation of atherosclerosis.
