In order to study neurotransmitter receptor regulation in the basal ganglia involved in the functional changes underlying levodopa-induced motor complications, quantitative autoradiography was used to observe receptor...In order to study neurotransmitter receptor regulation in the basal ganglia involved in the functional changes underlying levodopa-induced motor complications, quantitative autoradiography was used to observe receptor bindings of dopamine D1 and D2, N-methyl-D-aspartate （NMDA）, amino-3-hydroxy-5-methylisoxazole propionic acid （AMPA） and amino butyric acid （GABA） in the basal ganglia of rats that had unilateral nigrostriatal lesions and had been chronically treated with levodopa until motor complications developed. The rats were randomly assigned to three groups： normal, denervated and treatment-complicated groups. The results showed that response duration to levodopa became progressively shorter and abnormal involuntary movement （AIM） score was progressively increased during the course of levodopa treatment. Chronic treatment augmented D1 receptors more than denervation, and reduced D2 receptors that were also increased by dopamine denervation. Striatal NMDA receptors were substantially up-regulated in the treatment-complicated group. Levodopa treatment did not change receptors of nigral AMPA, pallidal GABA, and subthalamic GABA, which remained the same as that in denervation group. However, chronic treatment reversed the increase of nigral GABA receptors caused by the lesion. It was concluded that a shortening of response duration and AIM mimicked levodopa-induced motor complications of Parkinson＇s patients. These data suggested that up-regulation of dopamine D1 and NMDA receptors in the striatum leads to an imbalance of stimulation through the striatal output pathways, which is associated with levodopa-induced motor complications.展开更多
Objective: In the manuscript titled “Liquid subcutaneous Levodopa-Carbidopa ND0612 effects on motor symptoms in individuals with Parkinson’s Disease: A systematic review and meta-analysis”, the objective was to con...Objective: In the manuscript titled “Liquid subcutaneous Levodopa-Carbidopa ND0612 effects on motor symptoms in individuals with Parkinson’s Disease: A systematic review and meta-analysis”, the objective was to conduct a systematic review with meta-analysis to investigate the effects ND0612 24-hour dosing regimen has on motor symptoms in individuals with Parkinson’s Disease (PD). Introduction: ND0612 is a novel minimally invasive continuous subcutaneous delivery system of liquid Levodopa-Carbidopa being investigated for the treatment of PD in individuals experiencing motor symptoms. Methods: A systematic literature search was conducted in PubMed, Cochrane, and EBSCO databases to identify randomized controlled trials investigating the effects of ND0612 on motor symptoms in individuals with PD. Outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II and Part III scores. Methodological quality was assessed using the Cochrane Grading of Recommendations Assessment, Development, and Evaluation approach. Meta-analysis was performed using a random effects model with the DerSimonian and Laird method to estimate the effects of the ND0612 24-hour dosing regimen on UPDRS Part II and Part III scores. Results: Three studies were included in our review. There were statistically significant reductions in UPDRS Part II scores (mean difference (MD) −3.299;95% confidence interval (CI) −3.438, −3.159) and in UPDRS Part III scores (MD −12.695;95% CI −24.428, −0.962) in the ND0612 24-hour dosing regimen. Results were based on very low certainty of evidence. Conclusion: Based on very low certainty evidence, the ND0612 24-hour dosing regimen is effective at improving motor symptoms in individuals with PD. Our findings suggest that ND0612 is more effective at improving UPDRS Part II and Part III scores in individuals with PD than other pharmacological and non-pharmacological treatments, warranting further study.展开更多
Growing evidence has highlighted that angiotensin-converting enzyme(ACE)-inhibitors(ACEi)/AT1 receptor blockers(ARBs)may influence the complex interplay between dopamine and the renin-angiotensin system in the nigrost...Growing evidence has highlighted that angiotensin-converting enzyme(ACE)-inhibitors(ACEi)/AT1 receptor blockers(ARBs)may influence the complex interplay between dopamine and the renin-angiotensin system in the nigrostriatal pathway,thus affecting the development of levodopa-induced dyskinesia in Parkinson’s disease(PD).In the present study,we analyzed whether the use of this class of medication was associated with a reduced occurrence of levodopa-induced dyskinesia,using electronically-stored information of idiopathic PD patients enrolled at Novara University Hospital“Maggiore della Carità”.We conducted a retrospective case-control study identifying PD patients with dyskinesias(PwD;n=47)as cases.For each PwD we selected a non-dyskinetic control(NoD),nearly perfectly matched according to sex,Unified Parkinson’s Disease Rating Scale(UPDRS)part III score,and duration of antiparkinsonian treatment.Binary logistic regression was used to evaluate whether dyskinesias were associated with ACEi/ARBs use.Ninety-four PD patients were included,aged 72.18±9 years,with an average disease duration of 10.20±4.8 years and 9.04±4.9 years of antiparkinsonian treatment.The mean UPDRS part III score was 18.87±7.6 and the median HY stage was 2.In the NoD group,25(53.2%)were users and 22(46.8%)non-users of ACEi/ARBs.Conversely,in the PwD group,11(23.4%)were users and 36 non-users(76.6%)of this drug class(Pearson chi-square=8.824,P=0.003).Concerning general medication,there were no other statistically significant differences between groups.After controlling for tremor dominant phenotype,levodopa equivalent daily dose,HY 3-4,and disease duration,ACEi/ARBs use was a significant predictor of a lower occurrence of dyskinesia(OR=0.226,95%CI:0.080-0.636,P=0.005).Therefore,our study suggests that ACEi/ARBs may reduce levodopa-induced dyskinesia occurrence and,thanks to good tolerability and easy management,represent a feasible choice when dealing with the treatment of hypertension in PD patients.The study was approved by the Ethics Committee of Novara University Hospital“Maggiore della Carità”(CE 65/16)on July 27,2016.展开更多
目的探讨黄芪桂枝五物汤加味联合中频脉冲电刺激治疗糖尿病合并脑卒中偏瘫的临床疗效。方法选取2019年4月—2022年3月河北北方学院附属第一医院康复科及内分泌科老年糖尿病合并脑卒中偏瘫患者120例,依据随机表分为对照组60例和治疗组60...目的探讨黄芪桂枝五物汤加味联合中频脉冲电刺激治疗糖尿病合并脑卒中偏瘫的临床疗效。方法选取2019年4月—2022年3月河北北方学院附属第一医院康复科及内分泌科老年糖尿病合并脑卒中偏瘫患者120例,依据随机表分为对照组60例和治疗组60例,对照组给予中频脉冲电刺激加常规康复运动疗法,治疗组在对照组基础上给予黄芪桂枝五物汤加味治疗,比较两组患者治疗前后血糖水平、运动神经电生理指标[运动诱发电位潜伏期(motor evoked potentials,MEP)、中枢运动传导时间(central motor conduction time,CMCT)]、运动功能[Fugl-Meyer运动功能评分(Fugl-Meyer Assessment,FMA)]、生活质量及神经功能相关评分[脑卒中专用生活质量量表(Stroke Specific Quality of Life Scale,SS-QOL)、改良Barthel指数(modified Barthel Index,MBI)、美国国立卫生研究所卒中评分量表(National Institutes of Health Stroke Scale,NIHSS)、临床神经功能缺损评分(China Stroke Scale,CSS)量表、抑郁自评量表(Self-Rating Depression Scale,SDS)]。结果(1)血糖水平:治疗12周后,治疗组和对照组空腹血糖和餐后血糖均有所下降,降血糖效果明显;与对照组比较,治疗组血糖水平下降幅度更大(P<0.05)。(2)运动神经电生理指标:两组各项指标(MEP、CMCT)较治疗前均明显降低(P<0.05),且治疗组与对照组比较,治疗组降低幅度更大(P<0.05)。(3)上肢、下肢FMA评分:治疗12周后,对照组和治疗组评分均有明显升高,且治疗组分值提升显著高于对照组(P<0.05)。(4)生活质量评分:治疗后,对照组和治疗组各项评分(SS-QOL、MBI)均明显高于治疗前,且治疗组得分上升幅度显著优于对照组(P<0.05)。(5)神经功能评分:治疗后,两组各项评分(NIHSS、CSS、SDS)均有明显降低(P<0.05),且治疗组比对照组各项评分降低幅度更为显著(P<0.05)。结论黄芪桂枝五物汤加味联合中频脉冲电刺激可有效治疗糖尿病合并脑卒中偏瘫患者的运动功能,有利于改善生活质量,值得临床推广。展开更多
目的:观察基于危害分析及关键控制点(hazard analysis and critical control point,HACCP)原则的集束化护理在高血压脑出血患者中的应用效果。方法:选取2019年3月至2021年10月于首都医科大学附属北京友谊医院诊治的132例高血压脑出血患...目的:观察基于危害分析及关键控制点(hazard analysis and critical control point,HACCP)原则的集束化护理在高血压脑出血患者中的应用效果。方法:选取2019年3月至2021年10月于首都医科大学附属北京友谊医院诊治的132例高血压脑出血患者为研究对象。按照随机数字表法,分为研究组与对照组,每组66例。对照组给予常规护理,研究组给予基于HACCP原则的集束化护理。出院前,比较2组护理前后舒张压、收缩压、Fugl-Meyer运动功能评定量表(Fugl-Meyer Assessment Scale,FMAS)评分及并发症发生率。结果:护理前,2组患者的舒张压、收缩压相比,差异均无统计学意义(均P>0.05);护理后,2组患者的舒张压、收缩压明显降低,且研究组明显低于对照组,差异均有统计学意义(均P<0.05)。护理前,2组患者的FMAS评分相比,差异无统计学意义(P>0.05);护理后,2组FMAS评分明显升高,且研究组明显高于对照组,差异有统计学意义(P<0.05)。研究组患者的并发症发生率为12.12%,明显低于对照组的31.82%,差异有统计学意义(P<0.05)。结论:基于HACCP原则的集束化护理应用于高血压脑出血患者中可有效改善血压状况及运动功能,同时能降低并发症发生率,值得应用推广。展开更多
基金supported by a grant from the National Natural Science Foundation of China (No.30770753)
文摘In order to study neurotransmitter receptor regulation in the basal ganglia involved in the functional changes underlying levodopa-induced motor complications, quantitative autoradiography was used to observe receptor bindings of dopamine D1 and D2, N-methyl-D-aspartate （NMDA）, amino-3-hydroxy-5-methylisoxazole propionic acid （AMPA） and amino butyric acid （GABA） in the basal ganglia of rats that had unilateral nigrostriatal lesions and had been chronically treated with levodopa until motor complications developed. The rats were randomly assigned to three groups： normal, denervated and treatment-complicated groups. The results showed that response duration to levodopa became progressively shorter and abnormal involuntary movement （AIM） score was progressively increased during the course of levodopa treatment. Chronic treatment augmented D1 receptors more than denervation, and reduced D2 receptors that were also increased by dopamine denervation. Striatal NMDA receptors were substantially up-regulated in the treatment-complicated group. Levodopa treatment did not change receptors of nigral AMPA, pallidal GABA, and subthalamic GABA, which remained the same as that in denervation group. However, chronic treatment reversed the increase of nigral GABA receptors caused by the lesion. It was concluded that a shortening of response duration and AIM mimicked levodopa-induced motor complications of Parkinson＇s patients. These data suggested that up-regulation of dopamine D1 and NMDA receptors in the striatum leads to an imbalance of stimulation through the striatal output pathways, which is associated with levodopa-induced motor complications.
文摘Objective: In the manuscript titled “Liquid subcutaneous Levodopa-Carbidopa ND0612 effects on motor symptoms in individuals with Parkinson’s Disease: A systematic review and meta-analysis”, the objective was to conduct a systematic review with meta-analysis to investigate the effects ND0612 24-hour dosing regimen has on motor symptoms in individuals with Parkinson’s Disease (PD). Introduction: ND0612 is a novel minimally invasive continuous subcutaneous delivery system of liquid Levodopa-Carbidopa being investigated for the treatment of PD in individuals experiencing motor symptoms. Methods: A systematic literature search was conducted in PubMed, Cochrane, and EBSCO databases to identify randomized controlled trials investigating the effects of ND0612 on motor symptoms in individuals with PD. Outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II and Part III scores. Methodological quality was assessed using the Cochrane Grading of Recommendations Assessment, Development, and Evaluation approach. Meta-analysis was performed using a random effects model with the DerSimonian and Laird method to estimate the effects of the ND0612 24-hour dosing regimen on UPDRS Part II and Part III scores. Results: Three studies were included in our review. There were statistically significant reductions in UPDRS Part II scores (mean difference (MD) −3.299;95% confidence interval (CI) −3.438, −3.159) and in UPDRS Part III scores (MD −12.695;95% CI −24.428, −0.962) in the ND0612 24-hour dosing regimen. Results were based on very low certainty of evidence. Conclusion: Based on very low certainty evidence, the ND0612 24-hour dosing regimen is effective at improving motor symptoms in individuals with PD. Our findings suggest that ND0612 is more effective at improving UPDRS Part II and Part III scores in individuals with PD than other pharmacological and non-pharmacological treatments, warranting further study.
文摘Growing evidence has highlighted that angiotensin-converting enzyme(ACE)-inhibitors(ACEi)/AT1 receptor blockers(ARBs)may influence the complex interplay between dopamine and the renin-angiotensin system in the nigrostriatal pathway,thus affecting the development of levodopa-induced dyskinesia in Parkinson’s disease(PD).In the present study,we analyzed whether the use of this class of medication was associated with a reduced occurrence of levodopa-induced dyskinesia,using electronically-stored information of idiopathic PD patients enrolled at Novara University Hospital“Maggiore della Carità”.We conducted a retrospective case-control study identifying PD patients with dyskinesias(PwD;n=47)as cases.For each PwD we selected a non-dyskinetic control(NoD),nearly perfectly matched according to sex,Unified Parkinson’s Disease Rating Scale(UPDRS)part III score,and duration of antiparkinsonian treatment.Binary logistic regression was used to evaluate whether dyskinesias were associated with ACEi/ARBs use.Ninety-four PD patients were included,aged 72.18±9 years,with an average disease duration of 10.20±4.8 years and 9.04±4.9 years of antiparkinsonian treatment.The mean UPDRS part III score was 18.87±7.6 and the median HY stage was 2.In the NoD group,25(53.2%)were users and 22(46.8%)non-users of ACEi/ARBs.Conversely,in the PwD group,11(23.4%)were users and 36 non-users(76.6%)of this drug class(Pearson chi-square=8.824,P=0.003).Concerning general medication,there were no other statistically significant differences between groups.After controlling for tremor dominant phenotype,levodopa equivalent daily dose,HY 3-4,and disease duration,ACEi/ARBs use was a significant predictor of a lower occurrence of dyskinesia(OR=0.226,95%CI:0.080-0.636,P=0.005).Therefore,our study suggests that ACEi/ARBs may reduce levodopa-induced dyskinesia occurrence and,thanks to good tolerability and easy management,represent a feasible choice when dealing with the treatment of hypertension in PD patients.The study was approved by the Ethics Committee of Novara University Hospital“Maggiore della Carità”(CE 65/16)on July 27,2016.
文摘目的探讨黄芪桂枝五物汤加味联合中频脉冲电刺激治疗糖尿病合并脑卒中偏瘫的临床疗效。方法选取2019年4月—2022年3月河北北方学院附属第一医院康复科及内分泌科老年糖尿病合并脑卒中偏瘫患者120例,依据随机表分为对照组60例和治疗组60例,对照组给予中频脉冲电刺激加常规康复运动疗法,治疗组在对照组基础上给予黄芪桂枝五物汤加味治疗,比较两组患者治疗前后血糖水平、运动神经电生理指标[运动诱发电位潜伏期(motor evoked potentials,MEP)、中枢运动传导时间(central motor conduction time,CMCT)]、运动功能[Fugl-Meyer运动功能评分(Fugl-Meyer Assessment,FMA)]、生活质量及神经功能相关评分[脑卒中专用生活质量量表(Stroke Specific Quality of Life Scale,SS-QOL)、改良Barthel指数(modified Barthel Index,MBI)、美国国立卫生研究所卒中评分量表(National Institutes of Health Stroke Scale,NIHSS)、临床神经功能缺损评分(China Stroke Scale,CSS)量表、抑郁自评量表(Self-Rating Depression Scale,SDS)]。结果(1)血糖水平:治疗12周后,治疗组和对照组空腹血糖和餐后血糖均有所下降,降血糖效果明显;与对照组比较,治疗组血糖水平下降幅度更大(P<0.05)。(2)运动神经电生理指标:两组各项指标(MEP、CMCT)较治疗前均明显降低(P<0.05),且治疗组与对照组比较,治疗组降低幅度更大(P<0.05)。(3)上肢、下肢FMA评分:治疗12周后,对照组和治疗组评分均有明显升高,且治疗组分值提升显著高于对照组(P<0.05)。(4)生活质量评分:治疗后,对照组和治疗组各项评分(SS-QOL、MBI)均明显高于治疗前,且治疗组得分上升幅度显著优于对照组(P<0.05)。(5)神经功能评分:治疗后,两组各项评分(NIHSS、CSS、SDS)均有明显降低(P<0.05),且治疗组比对照组各项评分降低幅度更为显著(P<0.05)。结论黄芪桂枝五物汤加味联合中频脉冲电刺激可有效治疗糖尿病合并脑卒中偏瘫患者的运动功能,有利于改善生活质量,值得临床推广。
文摘目的:观察基于危害分析及关键控制点(hazard analysis and critical control point,HACCP)原则的集束化护理在高血压脑出血患者中的应用效果。方法:选取2019年3月至2021年10月于首都医科大学附属北京友谊医院诊治的132例高血压脑出血患者为研究对象。按照随机数字表法,分为研究组与对照组,每组66例。对照组给予常规护理,研究组给予基于HACCP原则的集束化护理。出院前,比较2组护理前后舒张压、收缩压、Fugl-Meyer运动功能评定量表(Fugl-Meyer Assessment Scale,FMAS)评分及并发症发生率。结果:护理前,2组患者的舒张压、收缩压相比,差异均无统计学意义(均P>0.05);护理后,2组患者的舒张压、收缩压明显降低,且研究组明显低于对照组,差异均有统计学意义(均P<0.05)。护理前,2组患者的FMAS评分相比,差异无统计学意义(P>0.05);护理后,2组FMAS评分明显升高,且研究组明显高于对照组,差异有统计学意义(P<0.05)。研究组患者的并发症发生率为12.12%,明显低于对照组的31.82%,差异有统计学意义(P<0.05)。结论:基于HACCP原则的集束化护理应用于高血压脑出血患者中可有效改善血压状况及运动功能,同时能降低并发症发生率,值得应用推广。
