目的探讨阿加曲班注射液联合法舒地尔治疗急性脑梗死(acute cerebral infarct,ACI)的临床效果及对美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分、巴氏(Barthel)指数评分的影响。方法选取106例AC...目的探讨阿加曲班注射液联合法舒地尔治疗急性脑梗死(acute cerebral infarct,ACI)的临床效果及对美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分、巴氏(Barthel)指数评分的影响。方法选取106例ACI患者,采用简单随机分组法将患者分为观察组和对照组,各53例。对照组患者采用法舒地尔注射液静脉滴注治疗,观察组在对照组治疗的基础上联合阿加曲班注射液静脉滴注治疗,均持续治疗2周。治疗后,比较2组ACI患者的临床疗效和治疗前后NIHSS评分、Barthel指数评分和血液流变学指标(红细胞聚集指数、血小板聚集指数、全血还原黏度、纤维蛋白原及血浆黏度)变化,比较2组ACI患者治疗期间不良反应发生情况。结果观察组ACI患者治疗有效率为90.57%,高于对照组的73.58%,组间比较差异有统计学意义(χ^(2)=5.194,P<0.05);治疗后,与对照组ACI患者比较,观察组NIHSS评分明显下降,Barthel指数评分则显著升高(t=9.601、7.687,P<0.05);与对照组相比,观察组治疗后ACI患者红细胞聚集指数、血小板聚集指数、全血还原黏度、纤维蛋白原和血浆黏度等血液流变学指标均明显降低(t=5.767、4.503、7.600、4.592、3.727,P<0.05);观察组ACI患者的不良反应发生率(20.75%)与对照组(13.21%)比较差异无统计学意义。结论阿加曲班注射液联合法舒地尔可显著提高ACI患者的临床效果,改善患者神经功能受损情况,提高日常生活能力,安全性高。展开更多
OBJECTIVE Alzheimer disease(AD)is a leading cause of dementia in elderly individuals and therapeutic options for AD are very limited.Over-activation of N-methyl-D-aspar⁃tate(NMDA)receptors,amyloidβ(Aβ)aggrega⁃tion,a...OBJECTIVE Alzheimer disease(AD)is a leading cause of dementia in elderly individuals and therapeutic options for AD are very limited.Over-activation of N-methyl-D-aspar⁃tate(NMDA)receptors,amyloidβ(Aβ)aggrega⁃tion,a decrease in cerebral blood flow(CBF),and downstream pathological events play impor⁃tant roles in the disease progression of AD.This study seeks to explore the efficacy and mecha⁃nism of action of MN-08,a novel memantine ni⁃trate,in established animal models of AD.METHODS MN-08′s effectiveness as a preventative and therapeutic agent was tested in 2-to 8-month-old APP/PS1 transgenic mice and 9-to 12-month-old 3×Tg-AD mice,respectively.The neuroprotective mechanism of MN-08 was tested in the glutamate cell model.The pharmacokinet⁃ics and safety of MN-08 in vivo were determined in normal rats and beagle dogs.For the behavioral test,Western blotting analysis,pathology,ELISA test and in vitro cell tests,investigators were blinded to the experimental grouping and drug treatment.RESULTS MN-08,a novel meman⁃tine nitrate,was found to inhibit Aβaccumulation,prevent neuronal and dendritic spine loss,and consequently attenuate cognitive deficits in 2-month-old APP/PS1 transgenic mice(for a 6-month preventative course)and in the 8-month-old triple-transgenic(3×Tg-AD)mice(for a 4-month therapeutic course).In vitro,MN-08 could bind to and antagonize NMDA receptors,inhibit the calcium influx,and reverse the dysregula⁃tions of ERK and PI3K/Akt/GSK3βpathway,sub⁃sequently preventing glutamate-induced neuro⁃nal loss.In addition,MN-08 had favorable phar⁃macokinetics,blood-brain barrier penetration,and safety profiles in rats and beagle dogs.CON⁃CLUSION The novel memantine nitrate MN-08 may be a useful therapeutic agent for AD.展开更多
文摘目的探讨阿加曲班注射液联合法舒地尔治疗急性脑梗死(acute cerebral infarct,ACI)的临床效果及对美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分、巴氏(Barthel)指数评分的影响。方法选取106例ACI患者,采用简单随机分组法将患者分为观察组和对照组,各53例。对照组患者采用法舒地尔注射液静脉滴注治疗,观察组在对照组治疗的基础上联合阿加曲班注射液静脉滴注治疗,均持续治疗2周。治疗后,比较2组ACI患者的临床疗效和治疗前后NIHSS评分、Barthel指数评分和血液流变学指标(红细胞聚集指数、血小板聚集指数、全血还原黏度、纤维蛋白原及血浆黏度)变化,比较2组ACI患者治疗期间不良反应发生情况。结果观察组ACI患者治疗有效率为90.57%,高于对照组的73.58%,组间比较差异有统计学意义(χ^(2)=5.194,P<0.05);治疗后,与对照组ACI患者比较,观察组NIHSS评分明显下降,Barthel指数评分则显著升高(t=9.601、7.687,P<0.05);与对照组相比,观察组治疗后ACI患者红细胞聚集指数、血小板聚集指数、全血还原黏度、纤维蛋白原和血浆黏度等血液流变学指标均明显降低(t=5.767、4.503、7.600、4.592、3.727,P<0.05);观察组ACI患者的不良反应发生率(20.75%)与对照组(13.21%)比较差异无统计学意义。结论阿加曲班注射液联合法舒地尔可显著提高ACI患者的临床效果,改善患者神经功能受损情况,提高日常生活能力,安全性高。
文摘OBJECTIVE Alzheimer disease(AD)is a leading cause of dementia in elderly individuals and therapeutic options for AD are very limited.Over-activation of N-methyl-D-aspar⁃tate(NMDA)receptors,amyloidβ(Aβ)aggrega⁃tion,a decrease in cerebral blood flow(CBF),and downstream pathological events play impor⁃tant roles in the disease progression of AD.This study seeks to explore the efficacy and mecha⁃nism of action of MN-08,a novel memantine ni⁃trate,in established animal models of AD.METHODS MN-08′s effectiveness as a preventative and therapeutic agent was tested in 2-to 8-month-old APP/PS1 transgenic mice and 9-to 12-month-old 3×Tg-AD mice,respectively.The neuroprotective mechanism of MN-08 was tested in the glutamate cell model.The pharmacokinet⁃ics and safety of MN-08 in vivo were determined in normal rats and beagle dogs.For the behavioral test,Western blotting analysis,pathology,ELISA test and in vitro cell tests,investigators were blinded to the experimental grouping and drug treatment.RESULTS MN-08,a novel meman⁃tine nitrate,was found to inhibit Aβaccumulation,prevent neuronal and dendritic spine loss,and consequently attenuate cognitive deficits in 2-month-old APP/PS1 transgenic mice(for a 6-month preventative course)and in the 8-month-old triple-transgenic(3×Tg-AD)mice(for a 4-month therapeutic course).In vitro,MN-08 could bind to and antagonize NMDA receptors,inhibit the calcium influx,and reverse the dysregula⁃tions of ERK and PI3K/Akt/GSK3βpathway,sub⁃sequently preventing glutamate-induced neuro⁃nal loss.In addition,MN-08 had favorable phar⁃macokinetics,blood-brain barrier penetration,and safety profiles in rats and beagle dogs.CON⁃CLUSION The novel memantine nitrate MN-08 may be a useful therapeutic agent for AD.
