Homocysteine levels after acute levodopa intake in patients with Parkinson's disease

Levodopa (L ‐dopa) administered with a dopadecarboxylase inhibitor (DDI) increases homocysteine plasma levels. This may support the onset of atherosclerosis‐related disorders and neuropsychiatric complications in patients with Parkinson's disease (PD). This homocysteine elevation is considered as long‐term effect of chronic L ‐dopa/DDI treatment. Little is known about the acute effects of L ‐dopa/DDI intake on homocysteine generation. The objective of this trial was to investigate the relations between L ‐dopa and homocysteine after acute L ‐dopa/DDI administration in PD patients with different L ‐dopa metabolism. Thirty PD patients were divided into groups with superior (I) and less (II) L ‐dopa absorption after standardized intake of 125 mg L ‐dopa/benserazide with determination of L ‐dopa, 3‐O‐methyl‐dopa (3‐OMD) and homocysteine in plasma at baseline, 30, 60, and 90 minutes. There was a homocysteine increase in Group I (F = 5; P = 0.005) and a moderate decrease in Group II (F = 4.27; P = 0.01). A rise of 3‐OMD (F = 10.51; P < 0.0001) appeared in Group I, but not in Group II (F = 0.91; P = 0.44), accordingly L ‐dopa accumulation was better in Group I than in Group II. Thus, in conclusion, L ‐dopa metabolism is an important component for homocysteine elevation after one time L ‐dopa/DDI administration in PD patients. © 2009 Movement Disorder Society     

神经节苷脂GM1在帕金森氏病症状波动治疗中的应用

目的探讨神经节苷脂GM1治疗帕金森氏病(PD)的疗效和安全性。方法对33例长期服用左旋多巴等治疗帕金森氏病药物后出现症状波动的患者,加用神经节苷脂GM1100mg/d,静脉滴注,每日1次,疗程4周。分别在GM1治疗后2、3、4周对患者进行帕金森病统一评分量表(UPDRS)运动评分及日常生活活动能力(ADL)评分,并观察治疗期间药物的毒副作用。结果33例PD患者在GM1治疗后2、3、4周UPDRS运动评分分别为(23.5±8.9)、(22.8±8.3)和(22.5±9.1),与治疗前(36.7±10.2)比较,均有非常显著性差异(P<0.01);ADL评分分别为(21.4±10.9)、(20.3±9.5)和(20.6±10.2),与治疗前(30.5±12.1)比较,亦均有非常显著性差异(P<0.01)。但治疗2、3、4周的UPDRS运动评分或ADL评分两两比较,无显著性差异(P>0.05)。治疗期间没有观察到明显的毒副作用。结论对长期服用左旋多巴出现症状波动或疗效减退的PD患者,加用GM1治疗,能在一定程度上改善患者的运动功能和日常生活能力。     

急性阶梯式左旋多巴试验受试者工作特征曲线在帕金森病诊断中的应用

目的建立急性阶梯式左旋多巴试验,观察原发性帕金森病和非帕金森病帕金森综合征患者急性多巴反应性受试者工作特征（ROC）曲线,以期选择适当的运功改善程度指标临界值诊断原发性帕金森病。方法对帕金森病患者102例和非帕金森病帕金森综合征患者49例进行不同剂量水平的急性左旋多巴试验,以统一帕金森病评分量表（UPDRS）运动部分评分为指标,比较两组患者在不同左旋多巴/苄丝肼剂量水平服药后UPDRS运动部分评分平均最大改善率的差异,建立急性左旋多巴试验的ROC曲线,计算不同临界值下的诊断敏感度和特异度。结果在左旋多巴/苄丝肼150/37.5mg、200/50mg、300/75mg剂量均有临界值可到达80%以上的敏感度和特异度。临界值设定在300/75mg剂量水平的28.5%时可达到97.1%的敏感度;临界值设定在150/37.5mg剂量水平的22.5%可达到93.2%的特异度。结论通过阶梯式急性左旋多巴试验方法可以有效量化帕金森病患者的多巴反应性。选择一定的UPDRS运动评分最大改善率为临界值可使该试验在帕金森病诊断中达到较高的敏感度和特异度。     

左旋多巴微囊制备工艺的研究

目的以乙基纤维素为囊材,优选左旋多巴微囊的制备工艺。方法以微囊的包封率及载药量为评价指标,采用正交实验优选左旋多巴微囊液中干燥法制备工艺条件,并对制备的微囊进行质量检查。结果优选出的制备工艺为:囊材与药量比例为0.6∶1.4,油水相比例为105∶30,PVP量为0.2g,验证实验表明,优化工艺所制左旋多巴微囊的平均载药量为54.94%,平均包封率为89.2%。质量检查结果表明,微囊外观圆整且无粘连现象,大部分微囊的粒径分布在300～600μm范围内。优选出的左旋多巴微囊在体外具有明显的缓释效果。结论采用液中干燥法制备左旋多巴微囊,工艺稳定可靠,操作简便,工艺条件合理、可行。     

Norepinephrine and cardiovascular responses to maximal exercise in Parkinson's disease on and off medication

The aim of this experiment is to understand how Parkinson's disease (PD) medication affects the autonomic responses of individuals during an acute exercise stress test. Fourteen people with PD and fifteen healthy individuals age‐matched between 50 and 80 years performed a modified Bruce protocol. Subjects with PD performed the test once off medication (PD‐off) and then 1 week later on medication (PD‐on). Heart rate (HR), blood pressure (BP), VO₂, and norepinephrine (NE) levels were taken at rest and at peak exercise. At peak exercise HR, BP, and NE values for the PD‐on and PD‐off group were all significantly lower than healthy controls, regardless of whether subjects were on their medication. Autonomic abnormalities during exercise in this population appear to be disease manifested and not impactedby medications used to treat PD. We can assume, both on and off medication, this population will show markedly lower BP, HR, and NE responses. © 2009 Movement Disorder Society     

Prevalence and treatment strategies of dyskinesia in patients with Parkinson’s disease

Summary A study into the prevalence and treatment of dyskinesia in Parkinson’s disease (PD) patients was performed with 380 PD specialists’ completed interviews relating to PD and retrospectively completed 1900 patient record forms for patients with dyskinesia. Physicians reported, that 34% of their PD patients experience dyskinesia, 57% of dyskinetic PD patients were affected by moderately-to-completely disabling dyskinesia. Treatment of dyskinesia was looked upon as not satisfactory, fractionating of levodopa dose was used as first choice therapeutic option of dyskinesia.     

Levodopa "drug holiday" with amantadine infusions as a treatment of complications in Parkinson's disease.

The loss of beneficial effect of levodopa due to progression of the disease and alteration of receptor sensitivity makes the treatment of the advanced stadium of Parkinson's disease (PD) very difficult. In the past "drug holidays" was used in attempt to resensitize dopamine receptors in the striatum to make the treatment easier. However possible serious complications like neuroleptical malignant-like syndrome discouraged the use of this procedure. Intravenous administration of amantadine, another antiparkinsonian medication during "drug holidays," procedure could be a solution for this problem. We studied 12 patients with PD suffering from complication of the therapy. Daily dose of Levodopa used as monotherapy before amantadine infusions ranged between 700 and 2,000 mg. Levodopa was discontinued for 3 days and during that time amantadine sulfate intravenous was administrated. After "drug holidays" levodopa in the same dose as before treatment was resumed. An assessment of the parkinsonian condition was performed with Unified Parkinson's Disease Rating Scale before "drug holidays" 2 days after and 1, 2, 3, 4, 5, 6 months later. The follow-up study demonstrated a significant improvement both in the motor condition and complication of therapy. The improvement after therapy was maintained up to 4 month. The levodopa "drug holidays" with amantadine infusion is a valuable option in the therapy of advanced stages of PD.     

左旋多巴治疗帕金森病发生剂末现象的相关因素

目的 探讨左旋多巴治疗帕金森病发生剂末现象的相关因素。方法 收集帕金森病患者临床资料,通过统计学分析对比分析剂末现象发生的相关因素。结果 剂末现象的发生与性别、年龄、教育年限、体重、毒药物接触史、吸烟史、饮酒史、高蛋白饮食、脑血管病史无关（P>0.05）。发生剂末现象的患者发病年龄早,病程长,左旋多巴起始、终点剂量高,左旋多巴用药时间长,疾病进展阶段（H&Y分期）高,统一帕金森病评分量表第三部分（UPDRSⅢ）评分高,汉密尔顿焦虑评分（HAMA）评分高（P<0.05）。其中发病年龄、左旋多巴起始剂量、H&Y分期、焦虑是发生剂末现象的独立影响因素（P<0.05）;独立预测因素分别为H&Y分期、HAMA评分、发病年龄、左旋多巴起始剂量（P<0.05）。H&Y分期具有较好的敏感度和特异度（80.9%）。随治疗时间的增长,中晚期患者剂末现象发生风险高（P<0.05）。结论 多种因素影响左旋多巴临床治疗中发生剂末现象。