AIM:To investigate the neuroprotective potential of ciclosporin during acute liver failure. We evaluated the effect of intrathecally administered ciclosporin on intracranial pressure, brain water content and aquaporin...AIM:To investigate the neuroprotective potential of ciclosporin during acute liver failure. We evaluated the effect of intrathecally administered ciclosporin on intracranial pressure, brain water content and aquaporin-4 expression in a rat model with acute hyperammonaemia.METHODS:Twenty-four male Wistar rats with portacaval anastomosis were randomised into four groups receiving ciclosporin or vehicle and ammonia or saline infusion. Ciclosporin or vehicle was given intrathecally prior to the ammonia or saline infusion. The ammonia or saline infusion was given intravenously for 4 h,while intracranial pressure and arterial pressure was recorded. At the end of the experiment, cerebral cortex and cerebellar brain tissue was analysed for water and aquaporin-4 content.RESULTS:The following intracranial pressures were found at the end of the experiment:ammonia + ciclosporin:10.0±1.7 mmHg, ammonia + vehicle:6.8±1.0mmHg, saline + ciclosporin:3.1±0.5 mmHg, saline +vehicle:3.3 ± 0.6 mmHg. Ammonia infusion had a significant effect on intracranial pressure and brain water content, which both were higher in the groups receiving ammonia(P<0.001, two-way analysis of variance). Treatment with ciclosporin resulted in relevant tissue concentrations of ciclosporin(>0.2 micromolar)but did not reduce intracranial pressure after 4 h. Furthermore, ciclosporin did not attenuate the increase in cerebral water content, and did not affect aquaporin-4expression.CONCLUSION:Intrathecal administration of ciclosporin does not attenuate intracranial hypertension or brain oedema in rats with portacaval anastomosis and 4 h of ammonia infusion.展开更多
Background and Aims:Previous trials comparing cyclosporine and tacrolimus after liver transplantation(LT)showed conflicting results.Most used trough monitoring for cyclosporine(C0),leading to less accurate dosing than...Background and Aims:Previous trials comparing cyclosporine and tacrolimus after liver transplantation(LT)showed conflicting results.Most used trough monitoring for cyclosporine(C0),leading to less accurate dosing than with 2-h monitoring(C2).Only one larger trial compared C2 with tacrolimus based on trough level(T0)after LT,with similar treated biopsy-proven acute rejection(tBPAR)and graft loss,while a smaller trial had less tBPAR with C2 compared to T0.Therefore,it is still unclear which calcineurin inhibitor is preferred after LT.We aimed to demonstrate superior efficacy(tBPAR),tolerability,and safety of C2 or T0 after first LT.Methods:Patients after first LT were randomized to C2 or T0.tBPAR,patient-and graft survival,safety and tolerability were the main endpoints,with analysis by Fisher test,Kaplan-Meier survival analysis and log-rank test.Results:In intention-totreat analysis 84 patients on C2 and 85 on T0 were included.Cumulative incidence of tBPAR C2 vs.T0 was 17.7%vs.8.4%at 3 months(p=0.104),and 21.9%vs.9.7%at 6 and 12 months(p=0.049).One-year cumulative mortality C2 vs.T0 was 15.5%vs.5.9%(p=0.049)and graft loss 23.8%vs.9.4%(p=0.015).Serum triglyceride and LDL-cholesterol was lower with T0 than with C2.Incidence of diarrhea in T0 vs,C2 was 64%vs.31%(p≤0.001),with no other differences in safety and tolerability.Conclusions:In the first year after LT immunosuppression with T0 leads to less tBPAR and better patient-/re-transplant-free survival as compared to C2.展开更多
目的基于时间序列的分析方法,探讨差分整合移动平均自回归模型(autoregressive integrated moving average model,ARIMA)预测集采药品环孢素口服制剂用量的可行性,为科学预测集采药品报量提供参考。方法应用R语言和SPSS对2018年1月—202...目的基于时间序列的分析方法,探讨差分整合移动平均自回归模型(autoregressive integrated moving average model,ARIMA)预测集采药品环孢素口服制剂用量的可行性,为科学预测集采药品报量提供参考。方法应用R语言和SPSS对2018年1月—2021年12月环孢素口服制剂用量的用药数据建立最优的ARIMA模型,经模型参数识别、校验后,对数据进行拟合,并验证拟合效果。结果环孢素口服制剂用量拟合效果最佳的模型为ARIMA(0,1,1)(0,1,0)[12]。2022年预测值与实际值的相对误差为3.13%,证明模型拟合效果很好。结论ARIMA模型能够很好地拟合和预测环孢素口服制剂用量在时间序列上的变化趋势,可为集采的科学报量提供一定的参考。展开更多
文摘AIM:To investigate the neuroprotective potential of ciclosporin during acute liver failure. We evaluated the effect of intrathecally administered ciclosporin on intracranial pressure, brain water content and aquaporin-4 expression in a rat model with acute hyperammonaemia.METHODS:Twenty-four male Wistar rats with portacaval anastomosis were randomised into four groups receiving ciclosporin or vehicle and ammonia or saline infusion. Ciclosporin or vehicle was given intrathecally prior to the ammonia or saline infusion. The ammonia or saline infusion was given intravenously for 4 h,while intracranial pressure and arterial pressure was recorded. At the end of the experiment, cerebral cortex and cerebellar brain tissue was analysed for water and aquaporin-4 content.RESULTS:The following intracranial pressures were found at the end of the experiment:ammonia + ciclosporin:10.0±1.7 mmHg, ammonia + vehicle:6.8±1.0mmHg, saline + ciclosporin:3.1±0.5 mmHg, saline +vehicle:3.3 ± 0.6 mmHg. Ammonia infusion had a significant effect on intracranial pressure and brain water content, which both were higher in the groups receiving ammonia(P<0.001, two-way analysis of variance). Treatment with ciclosporin resulted in relevant tissue concentrations of ciclosporin(>0.2 micromolar)but did not reduce intracranial pressure after 4 h. Furthermore, ciclosporin did not attenuate the increase in cerebral water content, and did not affect aquaporin-4expression.CONCLUSION:Intrathecal administration of ciclosporin does not attenuate intracranial hypertension or brain oedema in rats with portacaval anastomosis and 4 h of ammonia infusion.
基金This study was funded by Novartis Pharma,producer of Neoral ciclosporin.
文摘Background and Aims:Previous trials comparing cyclosporine and tacrolimus after liver transplantation(LT)showed conflicting results.Most used trough monitoring for cyclosporine(C0),leading to less accurate dosing than with 2-h monitoring(C2).Only one larger trial compared C2 with tacrolimus based on trough level(T0)after LT,with similar treated biopsy-proven acute rejection(tBPAR)and graft loss,while a smaller trial had less tBPAR with C2 compared to T0.Therefore,it is still unclear which calcineurin inhibitor is preferred after LT.We aimed to demonstrate superior efficacy(tBPAR),tolerability,and safety of C2 or T0 after first LT.Methods:Patients after first LT were randomized to C2 or T0.tBPAR,patient-and graft survival,safety and tolerability were the main endpoints,with analysis by Fisher test,Kaplan-Meier survival analysis and log-rank test.Results:In intention-totreat analysis 84 patients on C2 and 85 on T0 were included.Cumulative incidence of tBPAR C2 vs.T0 was 17.7%vs.8.4%at 3 months(p=0.104),and 21.9%vs.9.7%at 6 and 12 months(p=0.049).One-year cumulative mortality C2 vs.T0 was 15.5%vs.5.9%(p=0.049)and graft loss 23.8%vs.9.4%(p=0.015).Serum triglyceride and LDL-cholesterol was lower with T0 than with C2.Incidence of diarrhea in T0 vs,C2 was 64%vs.31%(p≤0.001),with no other differences in safety and tolerability.Conclusions:In the first year after LT immunosuppression with T0 leads to less tBPAR and better patient-/re-transplant-free survival as compared to C2.
文摘目的基于时间序列的分析方法,探讨差分整合移动平均自回归模型(autoregressive integrated moving average model,ARIMA)预测集采药品环孢素口服制剂用量的可行性,为科学预测集采药品报量提供参考。方法应用R语言和SPSS对2018年1月—2021年12月环孢素口服制剂用量的用药数据建立最优的ARIMA模型,经模型参数识别、校验后,对数据进行拟合,并验证拟合效果。结果环孢素口服制剂用量拟合效果最佳的模型为ARIMA(0,1,1)(0,1,0)[12]。2022年预测值与实际值的相对误差为3.13%,证明模型拟合效果很好。结论ARIMA模型能够很好地拟合和预测环孢素口服制剂用量在时间序列上的变化趋势,可为集采的科学报量提供一定的参考。
