Aim and methods The study of three-dimensional quantitative structure-activity relationship （3D-QSAR） of DDPH and its derivatives has been performed using Apex-3D programme. Results The result indicates that substit...Aim and methods The study of three-dimensional quantitative structure-activity relationship （3D-QSAR） of DDPH and its derivatives has been performed using Apex-3D programme. Results The result indicates that substituents of para- and ortho-positions in phenyl ring of aryloxyalkylamine greatly influence the bioactivity. Conclusion The biophore model and 3D-QSAR equation help us not only further understand receptor-ligand interactions, but also design new compounds with better bioactivity.展开更多
AIM： To investigate whether microproteinuria could be used as an early and sensitive indicator to detect calcineurin inhibitor （CNI）-related nephrotoxicity after liver transplantation.METHODS： All liver transplant...AIM： To investigate whether microproteinuria could be used as an early and sensitive indicator to detect calcineurin inhibitor （CNI）-related nephrotoxicity after liver transplantation.METHODS： All liver transplant recipients with normal serum creatinine （SCr） and detectable microproteinuria at baseline were included in this study. The renal function was monitored by the blood clearance of 99mTc-diethylenetriaminepentaacetic acid every 6 mo. Microproteinuria, SCr and blood urea nitrogen （BUN） were measured at entry and at subsequent follow-up visits. The patients were divided into different groups according to the mean values of glomerular filtration rate （GFR） at the follow-up time points： Group 1, GFR decreased from baseline by 0%-10%; Group 2, GFR decreased from baseline by 11%-20%; Group 3, GFR decreased from baseline by 21%-40%; Group 4, GFR decreased from baseline by 〉 40% and/or SCr was increasing.RESULTS： A total of 143 patients were enrolled into this study （23 females and 120 males）. The mean follow-up was 32 mo （range 16-36 mo）. Downward trends in renal function over time were observed in the study groups. SCr and BUN increased significantly only in Group 4 patients （P 〈 0.001）. β2-microglobulin （β2m） and al-microglobulin （αlm） significantly increased with the subtle change of renal function in recipients who were exposed to CNI-based immunosuppression regimens. The reductions in GFR were closely correlated with elevated cclm （P = -0.728, P 〈 0.001） and β2m （r2 = -0.787, P 〈 0.001）.CONCLUSION： β2m and α1m could be useful as early and sensitive indicators of CNI-induced nephrotoxicity.展开更多
Objective： To explore the optimal dose of L-arginine to prevent acute high-dose （HD）-PDD nephrotoxicity. Methods： 128 cases using PDD with the dosage of 100 mg/m^2 within two days （D1, 2） in combination with L-a...Objective： To explore the optimal dose of L-arginine to prevent acute high-dose （HD）-PDD nephrotoxicity. Methods： 128 cases using PDD with the dosage of 100 mg/m^2 within two days （D1, 2） in combination with L-arginine were randomly divided into 3 groups of A, B and C. The dosages of L- arginine in the 3 groups were 5 g/（m^2·d）, 10 g/（m^2·d） and 15 g/（m^2·d）, respectively. Each patient received 2 cycles chemotherapy to form self control： 1 cycle combined with L-arginine, while 1 cycle chemotherapy alone, β2-MG in urine, BUN, Cr and uric acid in blood were detected just 24 h before and after using PDD. The changes of each index in the three groups were observed in the presence or absence, and the therapeutic effects were compared among the three groups. Results： There was no significant difference in BUN, Cr and uric acid in blood before and after chemotherapy in the presence or absence, showing these indexes could not be used as markers of early acute nephrotoxicity. Urine β2-MG values in the presence and absence were 0.9120±0.6618 vs 1.5167±0.7908 （P〈0.05）, 0.5404±0.5810 vs 1.4616±0.8120 （P〈0.01）, 0.4998±0.6210 vs 1.5210±0.7710 （P〈0.01） in the groups A, B and C respectively. The excellent effective rate and total effective rate in groups A, B and C were 40.9% and 59.1%, 68.2% and 90.9%, and 77.5% and 97.5%, respectively. There was significant difference in the excellent effective rate and total effective rate between groups A and B, but not between groups B and C. Conclusion： The optimal dose of L- arginine to prevent acute HD-PDD nephrotoxicity is 10 g/（m^2·d）. Increased dosage can＇t improve the effect accordingly.展开更多
In the present study, we aimed to investigate the optimal dosage regimens of piperacillin/tazobactam in patients with chronic kidney disease according to their different classes of renal function based on bacterial re...In the present study, we aimed to investigate the optimal dosage regimens of piperacillin/tazobactam in patients with chronic kidney disease according to their different classes of renal function based on bacterial resistance. A total of 2700 simulationswere applied based on a published population pharmacokinetic and pharmacodynamic model using nonlinear mixed effects modeling (NONMEM) software. Permissible optimal dosage regimens were defined as those associated with a less than 10% of patients whose probabilities of target attainment (PTA) were not attain target. For patients with mild to moderate renal injury, 4/0.5 g of piperacillin/tazobactam every 12 h in 30 min intermittent infusion could attain the target. If the MIC (minimum inhibitory concentration) for the pathogen was 8 mg/L or 16 mg/L, either an 8-h or 6-h dosing interval or extended 2–6 h infusion regimen had to be used to achieve the outcome of the therapy. Regarding MIC was up to above 32 mg/L, a high dose of piperacillin (12–24 g/d) in continuous infusion was the only approach that could achieve the effective target in patients with renal dysfunction. A low dose with extended 4–6 h infusion regimen was recommended for patients with severe renal injury. Our study identified permissible optimal piperacillin/tazobactam dosage regimens for patients with renal dysfunction with an MIC up to 64 mg/L. The findings of this study would be helpful for precise administration of piperacillin/tazobactam in clinical practice.展开更多
文摘Aim and methods The study of three-dimensional quantitative structure-activity relationship （3D-QSAR） of DDPH and its derivatives has been performed using Apex-3D programme. Results The result indicates that substituents of para- and ortho-positions in phenyl ring of aryloxyalkylamine greatly influence the bioactivity. Conclusion The biophore model and 3D-QSAR equation help us not only further understand receptor-ligand interactions, but also design new compounds with better bioactivity.
文摘AIM： To investigate whether microproteinuria could be used as an early and sensitive indicator to detect calcineurin inhibitor （CNI）-related nephrotoxicity after liver transplantation.METHODS： All liver transplant recipients with normal serum creatinine （SCr） and detectable microproteinuria at baseline were included in this study. The renal function was monitored by the blood clearance of 99mTc-diethylenetriaminepentaacetic acid every 6 mo. Microproteinuria, SCr and blood urea nitrogen （BUN） were measured at entry and at subsequent follow-up visits. The patients were divided into different groups according to the mean values of glomerular filtration rate （GFR） at the follow-up time points： Group 1, GFR decreased from baseline by 0%-10%; Group 2, GFR decreased from baseline by 11%-20%; Group 3, GFR decreased from baseline by 21%-40%; Group 4, GFR decreased from baseline by 〉 40% and/or SCr was increasing.RESULTS： A total of 143 patients were enrolled into this study （23 females and 120 males）. The mean follow-up was 32 mo （range 16-36 mo）. Downward trends in renal function over time were observed in the study groups. SCr and BUN increased significantly only in Group 4 patients （P 〈 0.001）. β2-microglobulin （β2m） and al-microglobulin （αlm） significantly increased with the subtle change of renal function in recipients who were exposed to CNI-based immunosuppression regimens. The reductions in GFR were closely correlated with elevated cclm （P = -0.728, P 〈 0.001） and β2m （r2 = -0.787, P 〈 0.001）.CONCLUSION： β2m and α1m could be useful as early and sensitive indicators of CNI-induced nephrotoxicity.
文摘Objective： To explore the optimal dose of L-arginine to prevent acute high-dose （HD）-PDD nephrotoxicity. Methods： 128 cases using PDD with the dosage of 100 mg/m^2 within two days （D1, 2） in combination with L-arginine were randomly divided into 3 groups of A, B and C. The dosages of L- arginine in the 3 groups were 5 g/（m^2·d）, 10 g/（m^2·d） and 15 g/（m^2·d）, respectively. Each patient received 2 cycles chemotherapy to form self control： 1 cycle combined with L-arginine, while 1 cycle chemotherapy alone, β2-MG in urine, BUN, Cr and uric acid in blood were detected just 24 h before and after using PDD. The changes of each index in the three groups were observed in the presence or absence, and the therapeutic effects were compared among the three groups. Results： There was no significant difference in BUN, Cr and uric acid in blood before and after chemotherapy in the presence or absence, showing these indexes could not be used as markers of early acute nephrotoxicity. Urine β2-MG values in the presence and absence were 0.9120±0.6618 vs 1.5167±0.7908 （P〈0.05）, 0.5404±0.5810 vs 1.4616±0.8120 （P〈0.01）, 0.4998±0.6210 vs 1.5210±0.7710 （P〈0.01） in the groups A, B and C respectively. The excellent effective rate and total effective rate in groups A, B and C were 40.9% and 59.1%, 68.2% and 90.9%, and 77.5% and 97.5%, respectively. There was significant difference in the excellent effective rate and total effective rate between groups A and B, but not between groups B and C. Conclusion： The optimal dose of L- arginine to prevent acute HD-PDD nephrotoxicity is 10 g/（m^2·d）. Increased dosage can＇t improve the effect accordingly.
基金Peking University Third Hospital research funding(Grant No.7476-01)
文摘In the present study, we aimed to investigate the optimal dosage regimens of piperacillin/tazobactam in patients with chronic kidney disease according to their different classes of renal function based on bacterial resistance. A total of 2700 simulationswere applied based on a published population pharmacokinetic and pharmacodynamic model using nonlinear mixed effects modeling (NONMEM) software. Permissible optimal dosage regimens were defined as those associated with a less than 10% of patients whose probabilities of target attainment (PTA) were not attain target. For patients with mild to moderate renal injury, 4/0.5 g of piperacillin/tazobactam every 12 h in 30 min intermittent infusion could attain the target. If the MIC (minimum inhibitory concentration) for the pathogen was 8 mg/L or 16 mg/L, either an 8-h or 6-h dosing interval or extended 2–6 h infusion regimen had to be used to achieve the outcome of the therapy. Regarding MIC was up to above 32 mg/L, a high dose of piperacillin (12–24 g/d) in continuous infusion was the only approach that could achieve the effective target in patients with renal dysfunction. A low dose with extended 4–6 h infusion regimen was recommended for patients with severe renal injury. Our study identified permissible optimal piperacillin/tazobactam dosage regimens for patients with renal dysfunction with an MIC up to 64 mg/L. The findings of this study would be helpful for precise administration of piperacillin/tazobactam in clinical practice.
