美多芭联合恩他卡朋治疗对帕金森病患者血浆同型半胱氨酸水平的影响

目的探讨美多芭联合恩他卡朋治疗对帕金森病(PD)患者血浆同型半胱氨酸(Hcy)水平的影响。方法选取30名健康体检者作为对照组,20例未服用过左旋多巴(LD)制剂的PD患者为未服药组,63例美多芭治疗的PD患者为美多芭组,49例美多芭联合恩他卡朋治疗的PD患者为联合组。检测患者外周血中的LD稳态峰浓度并进行统一PD评分量表Ⅲ(UPDRSⅢ)的评分。检测所有研究对象的血浆Hcy水平。结果联合组患者LD血浆浓度明显高于美多芭组(P0.05)。美多芭组及联合组患者UPDRSⅢ评分均明显低于未服药组(均P0.05)。与对照组比较,未服药组、美多芭组及联合组患者血浆Hcy水平均明显升高(均P0.05);且美多芭组患者血浆Hcy水平明显高于未服药组及联合组(均P0.05)。结论美多芭联合恩他卡朋能显著降低PD患者血浆Hcy水平,对PD治疗有积极意义。     

恩他卡朋对帕金森病大鼠的疗效

目的:观察恩他卡朋与左旋多巴/苄丝肼(美多芭)联用对帕金森病大鼠的治疗作用。方法:6-羟多巴(6-OHDA)毁损内侧前脑束(MFB)建立SD大鼠PD模型。成模大鼠腹腔注射不同剂量的美多芭与恩他卡朋,观测大鼠旋转圈数和持续时间。结果:单用恩他卡朋不能诱导PD大鼠旋转。采用美多芭(6.25、12.5mg·kg-1)和不同剂量的恩他卡朋(10、5、0mg·kg-1)联用的PD大鼠,旋转圈数明显增加、旋转时间也明显延长;恩他卡朋的剂量越大,旋转运动的持续时间越长,但出现旋转反应高峰的时间向后推迟。结论:足量的恩他卡朋可以加强左旋多巴的疗效,半量的恩他卡朋疗效欠佳。     

恩他卡朋双多巴联合B族维生素治疗中晚期帕金森病临床分析

目的探讨恩他卡朋双多巴联合B族维生素对中晚期帕金森患者的临床疗效。方法收集中晚期帕金森病(PD)患者80例,将其随机分为美多芭组、美多芭+B族维生素组、达灵复组、达灵复+B族维生素组,治疗6个月后评估LD血药浓度、UPDRSⅢ评分、H-Y分级、PSQI、PDQ-39等指标。结果与治疗前相比,达灵复+B族维生素组能显著降低血浆Hcy水平以及PSQI、PDQ-39、UPDRSⅢ评分(P0.05),提高LD血药浓度(P0.05);与美多芭+B族维生素组相比,达灵复+B族维生素组可提高LD血药浓度(P0.05),降低血浆Hcy水平(P0.05)。结论达灵复联合B族维生素可提高中晚期PD患者LD血药浓度,降低血浆Hcy水平,改善临床症状和生活质量。     

恩他卡朋治疗帕金森病剂末现象的临床观察

目的探讨恩他卡朋对PD患者剂末现象影响。方法选择40例出现剂末现象的PD患者进行相关资料分析,根据不同治疗方案分为普拉克索组和恩他卡朋组,入选患者治疗8周,分析恩他卡朋对PD剂末现象的疗效。结果恩他卡朋组疗效(90%)高于普拉克索组(60%),UPDRSⅡ评分低于普拉克索组,关期时间短于普拉克索组;恩他卡朋组异动症时间(2.3±0.6)h,低于普拉克索组的(2.7±1.0)h,差异均有统计学意义(P0.05)。结论恩他卡朋能够延长患者开期时间,缩短关期时间,改善剂末现象开期运动症状。     

恩他卡朋治疗帕金森病的疗效观察

目的观察恩他卡朋辅助复方多巴制剂对帕金森病患者运动症状的影响。方法原发性帕金森病患者28例,均服用复方多巴制剂并在出现症状加重或运动波动时加用恩他卡朋。服药前、后定期行统一帕金森病评分量表(unified parkinson disease rating scale,UPDRS)Ⅱ与Ⅲ评分,观察其副作用,记录每剂复方多巴制剂的起效时间及药效维持时间。结果UPDRSⅡ与Ⅲ评分在服药前分别为15.1±5.1、22.2±8.1,服药1个月后(10.9±2.8;16.4±4.5)、服药3个月后(12.2±3.5;18.8±5.2)均降低(P<0.01)。服药后每剂药物起效时间不变,药效维持时间延长(1.3±0.6)h(P<0.05)。结论恩他卡朋可改善帕金森病患者的运动功能,副作用少,服用安全。     

左旋多巴联合恩他卡朋治疗帕金森病疗效观察

目的研究左旋多巴联合恩他卡朋治疗帕金森病(PD)的疗效及对炎症因子、氧化应激指标水平的影响。方法选取132例PD患者为研究对象,随机数字表法分成治疗组和对照组各66例。治疗组给予左旋多巴联合恩他卡朋治疗,对照组给予左旋多巴治疗。3个月后采用帕金森统一评分量表(UPDRS)比较2组临床疗效,记录其治疗前后血清炎症因子[白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)]、血浆氧化应激指标[超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、丙二醛(MDA)水平变化情况。结果 2组治疗后UPDRS评分和IL-1β、IL-6、MDA水平均较治疗前显著降低(P0.05),SOD、GSH水平则较治疗前显著升高(P0.05),且治疗组变化幅度大于对照组(P0.05);治疗组总有效率优于对照组(P0.05)。结论左旋多巴联合恩他卡朋方案对PD患者体内炎症因子和氧化应激指标水平有一定调节作用,疗效确切,于病情转归有利。     

美多芭对帕金森病患者抗氧化效应的研究

目的探讨左旋多巴血药浓度与帕金森病(PD)患者治疗效果的相关性。方法选择81例临床确诊为原发性PD的患者,其中68例为服用美多芭的患者(给药组),13例为未服用药物的患者(未给药组),对比美多芭治疗后外周血中左旋多巴的水平及统一PD评分量表(UPDRSⅢ)的评分;检测患者血浆谷胱甘肽(GSH)、GSH过氧化物酶(GSH-Px、活性氧(ROS)水平,并与健康者(对照组)比较。结果给药组左旋多巴血药浓度为(2.189±1.065)μg/ml,给药组服药前后UPDRSⅢ的评分均显著低于对照组(P0.05~0.01)。与未给药组相比,给药组血浆中的GSH、GSH-PX水平明显上升(均P0.05)。给药组中对机体氧化损伤影响较大的为患病病程。结论美多芭能通过清除自由基显著改善PD患者的症状。     

美多芭联合tDCS治疗PD的疗效及对UPDRS评分的影响分析

目的探讨美多芭联合经颅直流电刺激(t DCS)治疗帕金森(PD)的疗效及对PD综合评分量表(UPDRS)评分的影响。方法将本院2016年3月至2017年3月期间收治的94例PD患者根据随机数字法分为试验组和对照组,试验组给予美多芭联合t DCS治疗,对照组给予美多芭治疗,分别于治疗前、治疗后7d及1个月对UPDRS评分、治疗效果以及不良反应等进行综合评价。结果治疗1个月后,试验组患者的治疗总有效率为82.98%显著高于对照组的72.34%,组间比较差异有统计学意义(P0.05)。对照组失眠2例,便秘2例,头晕3例,体位性低血压2例,不良反应发生率为23.40%。试验组失眠4例,便秘1例,头晕5例,体位性低血压1例,不良反应发生率为19.15%,两组的不良反应发生率(P0.05);治疗7d及1个月后,试验组UPDRSⅠ、Ⅱ、Ⅲ及总的评分均低于对照组,组间差异有统计学意义(P0.05)。结论对PD患者采用美多芭联合t DCS治疗方案,能显著改善患者的UPDRS评分,且该法具有较高的临床安全性,今后可能成为有潜力的PD治疗方法。     

恩他卡朋添加治疗症状波动的帕金森病的自身对照临床研究

目的:探讨添加恩他卡朋治疗帕金森病患者剂末现象的疗效及安全性。方法:17例伴有剂末现象的帕金森病患者进行添加服用恩他卡朋前后对照。根据患者日记记录的“开”“关”时间、UPDRSⅡ/Ⅲ评分、左旋多巴每天剂量来综合评估。结果:12周观察显示恩他卡朋添加治疗帕金森病剂末现象能够显著延长“开”时间、缩短“关”时间、降低UPDRSⅡ/Ⅲ评分,没有发现严重不良事件及实验室的异常改变。结论:帕金森病伴有剂末现象患者添加恩他卡朋治疗有效、安全。     

帕金森病患者运动皮质兴奋性的经颅磁刺激研究

目的:本研究拟应用低频重复性经颅磁刺激(rTMS)分别刺激帕金森病(PD)患者M1手代表区(M1Hand)及运动前区(PMC),探讨不同干预手段对运动皮质兴奋性的影响,以及M1与PMC间的联系。方法:对18名确诊PD患者先后进行4种不同干预,即口服美多芭、低频rTMS刺激M1Hand(0.5Hz,100%静息阈值,共1600次脉冲)、低频rTMS刺激PMC(0.5Hz,100%静息阈值,共1600次脉冲)以及假刺激。于每次干预前后各进行临床评价并测定运动诱发电位(MEP)相关指标。结果:①口服美多芭后UPDRSⅢ(P=0.001)以及其中有关僵直(P=0.001)、运动迟缓(P<0.001)的评分均较服药前显著改善。三种不同磁刺激干预产生结果不同,M1Hand组UPDRSⅢ减低(P=0.015),僵直(P=0.010)、运动迟缓(P=0.004)亦有所改善;PMC组UPDRSⅢ较干预前减低(P=0.046),僵直评分亦减低,但无显著性意义(P=0.163);②口服美多芭1h后MEP120减低(P=0.002),CSP延长(P=0.006);M1Hand组MEP120无著变,而CSP延长(P=0.015);PMC组MEP120减低(P=0.004),而CSP无著变;假刺激组则均无显著性改变。结论:低频rTMS对不同脑区产生的效应不同:刺激M1可使CSP延长;而刺激PMC可使MEP波幅减低。     

普拉克索添加治疗帕金森病临床随机对照研究

目的 评价新型多巴胺受体激动剂普拉克索联合美多巴与单用美多巴治疗帕金森病(PD)患者的疗效及安全性. 方法 采用随机对照开放式研究,将70例PD患者按照随机数字表法分为普拉克索+美多巴组和美多巴组,每组各35例.治疗12周后判断其疗效及安全性.疗效判定的主要指标为统一PD评定量表第Ⅲ部分(UPDRSⅢ)的运动检查总评分相对患者基线的变化和第Ⅱ部分(UPDRS Ⅱ)的日常生活活动能力总评分相对患者基线的变化;次要指标为第Ⅰ部分(UPDRS Ⅰ)的精神、行为和情感总评分相对患者基线的变化和第Ⅳ部分(UPDRS Ⅳ)的治疗并发症总评分相对患者基线的变化和美多巴药物每日剂量相对基线的变化.安全性指标依据药物的不良反应来判定. 结果 普拉克索+美多巴组患者UPDRS Ⅲ总评分均值与基线相比下降了11.40分,高于美多巴组(9.26分),比较差异有统计学意义(P<0.05);UPDRS Ⅱ总评分均值与基线相比下降了4.57分,高于美多巴组(4.50分),比较差异无统计学意义(P<0.05);UPDRS Ⅰ总评分均值与基线相比下降了0.66分,低于美多巴组(1.14分),差异无统计学意义(P0.05);UPDRS Ⅳ总评分均值与基线相比下降了0.22分,美多巴组则升高了0.06分,差异有统计学意义(P<0.05).与基线相比,治疗后12周普拉克索+美多巴组美多巴的日用量下降了163.57 mg/d,美多巴组升高了8.57 mg/d,差异有统计学意义(P<0.05).普拉克索+美多巴组在治疗后12周发生疗效减退、症状波动、异动症的例数均低于美多巴组,差异有统计学意义(P<0.05).美多巴组出现了明显的疗效减退、症状波动、异动症,而普拉克索+美多巴组无明显的上述症状,但有2例出现突然入睡发作、1例嗜睡、1例直立性低血压. 结论 普拉克索+美多巴组在改善PD运动功能方面优于美多巴组,在日常活动,精神、行为和情绪方面疗效相似.同时服用普拉克索可以明显减少美多巴的用量及其治疗后所引起的并发症(疗效减退、症状波动及异动症)的发生率.普拉克索可引起突然入睡发作、嗜睡、直立性低血压等副作用.     

帕金森病血抗氧化酶活性的研究

本文报道６７例帕金森病（ＰＤ）患者血超氧化物歧化酶（ＳＯＤ）．谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ），过氧化氢酶（ＣＡＴ）活性及脂质过氧化物（ＬＰＯ）量的测定结果。ＰＤ病人ＳＯＤ和ＧＳＨ－Ｐｘ活性高于正常对照组，但ＳＯＤ，ＧＳＨ－Ｐｘ和ＣＡＴ的活性及ＬＰＯ量与病程长短无明显关系，也与是否服用美多巴无关。研究结果提示，抗氧化酶活性的改变可能与ＰＤ病因有关。     

同型半胱氨酸在帕金森病患者血浆中的变化及临床意义

目的对比研究同型半胱氨酸(homocystein,Hcy)在帕金森病(Parkinson’s disease,PD)和脑梗死患者血浆中的变化,探讨其临床意义。方法检测PD、脑梗死患者及对照组血浆Hcy水平,检测PD、脑梗死患者及对照组血浆叶酸和维生素B_(12)水平。对PD患者血浆Hcy水平与叶酸及维生素B_(12)水平进行相关性分析,对血浆Hcy水平与PD严重程度、病程、临床类型、情绪、认知功能及是否服用美多芭进行相关性分析。结果 (1)PD组、脑梗死组及对照组血浆Hcy水平分别为20±11μmol/L、16±7μmol/L及11±2μmol/L,PD组和脑梗死组血浆Hcy水平均高于对照组,差异有统计学意义(P0.05或0.01),PD组血浆Hcy水平明显高于脑梗死组(P0.01);(2)PD组血浆叶酸和维生素B_(12)水平分别为6±5μg/L和514±345ng/L。PD组血浆叶酸和Hcy水平呈明显负相关(r=-0.453,P0.01);血浆维生素B_(12)和Hcy水平无明显相关性(r=-0.268,P0.05)。(3)按照Hoehn-Yahr分期对PD严重程度进行分组,轻、中、重度PD组血浆Hcy水平分别为16±8μmol/L、21±9μmol/L和35±3μmol/L,三组之间差异有统计学意义(P0.05);(4)血浆Hcy水平与病程、临床类型、情绪、认知功能及是否服用美多芭无关。结论 PD组和脑梗死组血浆Hcy水平明显增高,PD组Hcy水平与疾病严重程度密切相关,PD组血浆叶酸和Hcy水平呈明显负相关。     

A comparison of the effects of controlled-release levodopa (Madopar CR) with conventional levodopa in late Parkinson''s disease.

In this multicentre study a controlled-release formulation of levodopa and the decarboxylase inhibitor benserazide (Madopar CR) was evaluated in patients with Parkinson's disease exhibiting dose-related fluctuations in motor performance in response to conventional levodopa preparations. The effect of Madopar CR, with or without conventional levodopa/benserazide, on the proportion of time spent "on", "off" or "intermediate" was compared with that of previous conventional levodopa/decarboxylase inhibitor therapy. Evaluation of the two periods of optimum therapy was based on both patient diary data and investigator opinion. Forty seven patients completed the study but full patient diaries were available for only 37. The mean optimum total daily dosage of conventional Madopar was 820 mg taken in a mean of 6.4 doses, compared with a mean optimum daily dosage of combined Madopar CR and conventional Madopar of 1088 mg, taken in a mean of 5.2 doses. Conventional Madopar was taken in addition to Madopar CR in all but eight patients. Madopar CR was felt to be advantageous in 83% and disadvantageous in 11% of patients completing the study. Considering the 37 patients for whom diary data were available, Madopar CR therapy resulted in an increase in the mean time spent "on" (p = 0.016) and a decrease in the mean time spent "off" (p = 0.029) compared with conventional Madopar alone. Individually 25 out of 37 had an increase in "on" time and 19 out of 37 experienced a decrease in "off" time. Thus Madopar CR was found to be beneficial in a significant proportion of patients experiencing fluctuations in response to conventional levodopa.     

Growth hormone and prolactin stimulation by Madopar in Parkinson's disease

Madopar, a combination of levodopa with benserazide, induced an inconsistent rise in plasma growth hormone in unmedicated patients with Parkinson's disease and in controls, and a greater growth hormone rise in Parkinsonian subjects on chronic Madopar therapy. In subjects on chronic therapy with levodopa and carbidopa (Sinemet), the growth hormone releasing effect of Madopar was blunted. Madopar increased plasma prolactin (PRL) in controls, unmedicated patients and patients on Madopar therapy while in patients on Sinemet therapy the PRL-releasing effect of Madopar was strikingly reduced. Since these data were interpreted as due to a defective dopamine tone in the hypothalamus of Parkinsonian subjects on Madopar but not Sinemet therapy, a direct dopamine receptor agonist, lisuride was administered. Lisuride, however, elicited a blunted growth hormone response both in patients on Madopar and Sinemet therapy, without revealing a state of supersensitivity of dopamine receptors for growth hormone control in Parkinsonian subjects on Madopar therapy. No difference was present in the PRL-lowering effect of lisuride in the different experimental groups. These findings suggest that: (1) hypothalamic dopamine function is impaired in Parkinsonian subjects on Madopar therapy, preserved in unmedicated patients and enhanced in patients on Sinemet therapy; (2) the endocrine effects observed in Parkinsonian subjects on chronic Madopar therapy may be due to some penetration of benserazide across the blood brain barrier in the region of the hypothalamus; (3) since Madopar and Sinemet are in essence equally effective antiparkinsonian remedies, penetration of benserazide does not occur across the blood brain barrier surrounding the nigrostriatal system.     

美多芭对帕金森病患者血小板中五羟色胺含量的影响与抑郁症状

目的分析口服美多芭治疗帕金森病运动障碍时对体内五羟色胺(5-HT)含量变化与抑郁症状产生的影响。方法观察本院就诊的帕金森病患者35例口服美多芭1年后患者血小板5-HT含量的变化,同时给患者汉密尔顿抑郁量表(HAMD)评分,观察治疗前后患者精神症状改变。结果美多芭治疗1年后患者血小板中5-HT含量明显降低,HAMD评分结果较治疗前明显增高。结论美多芭治疗PD运动障碍症状的同时能导致体内的5-HT含量降低,这可能会加重患者的抑郁症状。     

Bromocriptine alone or associated with L-dopa plus benserazide in Parkinson''s disease.

Twenty-six patients affected by Parkinson's disease were treated with a 2-Br-alpha-ergocriptine (CB 154): 14 cases were given CB 154 alone, and 12 were given CB 154 along with L-dopa plus benserazide (Madopar). Both CB 154 and combined therapy (CB 154+Madopar) induced a significant improvement in total disability score, tremor, rigidity, akinesia, self-sufficiency, and some motor performance tests (dynamic tests). No significant difference was found between results obtained with CB 154 therapy and with Madopar treatment, while the improvement induced by combined therapy (CB 154+Madopar) was significantly higher than that obtained by Madopar alone. The averse reactions caused by CB 154 alone or associated with Madopar are similar to those observed during other dopaminergic treatment. CB 154 alone or combined with Madopar appears to be a useful advance in the management of Parkinson's disease.     

Sustained-release Madopar HBS® compared with standard Madopar® in the long-term treatment of de novo parkinsonian patients

In this Danish-Norwegian randomized double-blind parallel-group multicentre study, we compared the therapeutic response of slow-release Madopar HBS® to standard Madopar® in 134 de novo patients with idiopathic Parkinson's disease during a 5-year period. The drugs were dosed according to the individual need of the patients. The Webster, NUDS, UPDRS and Hoehn & Yahr scales were used for evaluation of symptoms. Addition of a morning dose of standard Madopar 62.5 mg was allowed after 6 months. Bromocriptine could be administered but not Selegiline. Sixty-five patients got Madopar HBS and 69 standard Madopar. Surprisingly, no differences were found as to the mean daily levodopa dose, the mean number of daily doses or the use of and doses of bromocriptine. Unexpectedly, we found a trend towards a more frequent use of a morning dose of standard Madopar in the group treated with the standard formulation. No differences were observed in the occurrence of motor fluctuations or dyskinesia, the incidence of which was relatively low. Sustained-release Madopar (HBS) thus proved to be as effective as standard Madopar in the long-term treatment of de novo parkinsonian patients, but the drug showed no advantage in postponing or reducing the long-term levodopa treatment problems.     

The clinical efficacy of oral levodopa methyl ester solution in reversing afternoon "off" periods in Parkinson's disease

We compared the efficacy of a single dose of an oral solution of levodopa methyl ester (ME) to that of standard levodopa, in the form of a single dose of Madopar, in reversing afternoon "off" periods in 12 patients with Parkinson's disease (PD). The highly soluble ME solution led to a significantly more rapid reversal of "off" periods. This preparation may therefore convey a clinical advantage in patients experiencing motor fluctuations whilst taking multiple daily dosages of levodopa, particularly in those with long or highly variable latency to the next "on" period.