帕金森病与QTc间期的关系

目的：观察帕金森病（PD）与QTc间期的关系。方法：分析了37例PD患者及37例健康对照组的QTc间期,并比较PD病病情与QTc间期的关系,结果：PD组QTc间期明显超过对照组（P＝0．001）,PD病情的轻重可影响QTc间期。结论：对QTc间期的监测有助于发现PD患者自主神经功能障碍,同时可作了为解病情轻重的一个参考指标。     

Genetics of Parkinson Disease

Summary: Parkinson disease (PD) is the second most common neurodegenerative disorder. Recent studies have consistently demonstrated that in some families, disease is attributable to a mutation in a single gene. To date, genetic analyses have detected linkage to six chromosomal regions and have identified three causative genes: PARK1 (alpha-synuclein), PARK2 (parkin), and PARK7 (DJ-1). In addition, mutations in several other genes have been implicated in familial PD. Identification of the mutations in these genes has led to the recognition that the ubiquitin-proteasome system is an important pathway that may be disrupted in PD. Studies are ongoing to identify additional genes that may contribute to PD susceptibility, particularly in late-onset families without a clear pattern of disease inheritance. With the identification of mutations in particular genes and the likely role of additional genes that are important in PD risk-susceptibility, appropriate protocols must be developed so that accurate and informative genetic counseling can be offered to families in which one or more members has PD. Further diagnostic testing should be delayed until more is learned about the frequency, penetrance, and risk assessment of certain gene mutations. Important lessons can be learned from the implementation of counseling protocols for other neurodegenerative disorders, such as Huntington disease and Alzheimer disease.     

One-Year Open-Label Study of Entacapone in Patients with Advanced Parkinson Disease

Background and purpose

A carboxy-O-methyl transferase inhibitor entacapone has been introduced as an adjuvant drug for Parkinson disease (PD) patients. Although clinical trials reported beneficial role of entacapone, a long-term trial over 3 years failed to show significant effect. The goals of this study were to evaluate the clinical benefit and the efficacy of entacapone in an open clinical practice.

Methods

After the completion of a double-blind placebo-controlled entacapone study, 149 patients from 4 centers were included. Antiparkinsonian medications were optimized by the judgment of the neurologists in charge. The clinical global impression (CGI) scale was obtained at 6 months and 1 year after the initiation of entacapone treatment.

Results

Of the 149 patients, 117 patients chose to try entacapone in an open-label fashion. Sixty-nine (59%) patients completed the 1-year trial. Twenty-nine patients discontinued entacpaone before 6 months, and 19 between 6 months and 1 year during trial. Twelve patients out of 48 patients discontinued entacapone because of its poor efficacy. The CGI scale was 3.9 (±1.5) at the beginning of the trial, 4.3 (±1.1) at 6 month, and 3.8 (±1.3) at 1 year, respectively. The CGI scale of those who discontinued between 6 month and 1 year was 3.4 (±1.7), which was worse, but insignificantly, than that of the continuer.

Conclusions

The dropout at 1 year of our study was very high at 41%. Even though entacapone is indicated for advanced PD patients with motor fluctuation, the fluctuators commonly have dyskinesia and mental symptoms, which can become more troublesome with entacapone. In the patients with advanced PD, the clinical efficacy and side effects should be carefully considered in a long-term use of entacapone.     

一种帕金森病大鼠模型的建立及评价

目的探讨应用6-羟基多巴胺（6-OHDA）毁损大鼠黑质致密部制作偏侧帕金森病（PD）模型的方法和应用价值。方法采用立体定向微量注射6-OHDA于大鼠黑质致密部,观察经阿朴吗啡诱导后大鼠的行为及黑质多巴胺能神经元形态学变化。结果部分大鼠注射后即出现行动迟缓、少动、竖毛、躬身、尾部强直、肢体震颤、嗅探和易激惹等异常行为。术后4周时,共33只大鼠经阿朴吗啡诱导后在30min（P〈0．01）的平均旋转圈数〉7r／min,达到成功模型的标准,模型成功率为82．5％（33／40）。免疫组化观察发现模型组大鼠注射侧黑质区多巴胺能神经元较对侧和对照组注射侧区明显减少（P〈0．01）。结论利用6-OHDA毁损大鼠黑质致密部可以较快建立稳定的PD大鼠模型,方法简便实用,动物死亡率低,模型成功率高。     

Classical Parkinson disease versus Parkinson complex – Reflections against staging and in favour of heterogeneity

Pathological studies have prompted the idea that Parkinson disease (PD) is a multisystem disorder, which starts far away from the nigrostriatal dopamine system and it goes through a long pre-clinical period. Evidence from epidemiological research, functional imaging, olfaction and sleep studies provides support to this hypothesis. Accordingly, PD is seen as an homogeneous disease which sequentially affects different neural structures leading to a well-defined clinical picture. This concept, recently named PD complex, has deep theoretical and practical implications which raise some concerns. This report shows the concept of classical PD as opposed to PD complex. Although the relevance of the central argument concerning the PD complex concept is admitted, it needs to be fully proved before premature conclusions are drawn. In contrast, the notion of classical and clinically significant PD can explain many of the well-characterized pathological and clinical features of the disease and it gives support to the idea that the magic word in PD is variability.     

帕金森病患者线粒体功能缺陷的研究

目的　探讨帕金森病 (PD)患者线粒体功能缺陷类型及其基因突变基础。方法　用溴化乙啶抑制人食管癌细胞系的线粒体DNA复制 ,制备出无线粒体DNA细胞系。将 2 0例PD患者组及2 0名正常对照组血小板与之融合 ,用选择性培养液挑选出融合细胞 ,大量培养后用极谱法测定线粒体酶复合体活性及抗氰呼吸。结果　以苹果酸和谷氨酸为底物时患者组 ( 1.2 5± 0 .0 8)明显低于正常对照组 ( 1.75± 0 .0 8) ,降低 2 8.6% ;以琥珀酸、维生素C和TMPD为底物时患者组与正常对照组差别无统计学意义。这些结果表明 ,线粒体酶复合体II～Ⅴ活性正常 ,以苹果酸和谷氨酸为底物的氧耗率的降低来源于酶复合体I活性受损。由于融合细胞核背景一致 ,其线粒体功能仅受mtDNA影响 ,因此本试验发现的患者酶复合体I缺陷来源于mtDNA的突变。抗氰呼吸PD患者组平均为 ( 8.76±0 .2 5 ) % ,正常对照组平均为 ( 6.2 0± 0 .10 ) % ,差异有显著意义 (P <0 .0 5 )。结论　PD患者线粒体酶复合体I活性降低 ,来源于线粒体DNA突变 ,可能导致自由基增多 ,在PD神经元变性中起重要作用。     

雌激素对帕金森病保护作用的实验研究

目的探讨雌激素对帕金森病是否具有保护作用.方法利用免疫组化染色(ABC)法计数酪氨酸羟化酶(TH)的阳性细胞数,用TUNEL法观察每视野下凋亡细胞的数目,比较各组的差异.结果正常雌性小鼠造模(A)组比去势后造模(B)组中只给予生理盐水(B1)组、造模后去势(C)组中只给予生理盐水(C1)组的TH阳性细胞数目多,凋亡细胞数目少(P＜0.05);B1组与C1组差异无显著性(P＞0.05);B2组(B组中给予雌激素组)比B1组及C2组(C组中给予雌激素组)比C1组TH阳性细胞多,凋亡细胞数目少(P＜0.05).结论雌激素对帕金森病具有保护作用和损伤修复作用,且与凋亡有关.     

帕金森病患外红外周血T淋巴细胞亚群及红细胞免疫研究

目的：观察帕金森病（PD）外周血T淋巴细胞亚群及红细胞免疫功能,方法：应用直接免疫荧光染色法和免疫酵母菌花环法分别测定20例PD患者外周血T淋巴细胞亚群和红细胞免疫功能,并对其中10例服用L－多巴前后进行比较,结果：病例组CD2、CD4、CD8水平较对照组明显降低,而RBC－ICR水平增高。治疗前后比较结果表明,服药后CD3、CD8水平升高,RBC－ICR水平降低,结论：PD存在T细胞免疫功能下及循环中免疫复合物增多,应用多巴胺制剂可改善PD的免疫学异常,提示PD的免疫功能异常与体内多巴胺递质改变密切相关。     

环境和职业危险因素与帕金森病

近年来帕金森病(PD)的发病率日益增多。PD发病的危险因素受人注意。本文就与化合物1-甲基-4-苯基-丙氧哌啶结构相似的造成PD的可能毒物,以及PD发病机制作一简单介绍。详细介绍工业职业和环境因素如铅、锰污染等重金属导致PD的危险因素,以引起人们的注意。     

分期双侧多靶点毁损治疗帕金森病

目的 探讨分期双侧多靶点毁损治疗帕金森病的疗效和适应证。方法 应用MR解剖定位及电极刺激靶点调整定位,对26例帕金森病患者实施分期双侧多靶点毁损治疗,两次手术平均间隔时间9个月。一侧单靶点毁损21例,一侧双靶点毁损24例,手术前后采用UPDRS、Hoehn和Yahr计分评价手术疗效。结果 本组随访期内均有显著疗效。其中行动迟缓改善87.0％(21/23),肢体僵硬改善90.9％(10/11),震颤消失86.7％(13/15),UPDRS改善80.8％(21/26),Hoehn和Yahr分级为0～Ⅰ级。手术后6例发生不同程度的语言障碍,其中1例随访至今未完全恢复,2例有轻度障碍,其余在短期内均恢复。结论 分期双侧多靶点毁损术是治疗帕金森病的有效方法,靶点精确定位是提高手术疗效,降低手术并发症的关键。     

蛋白酶体抑制诱导的PC12细胞帕金森病模型

目的探讨蛋白酶体抑制剂对PC12细胞的作用以及用该药物制作帕金森病(PD)模型的可能性。方法用不同浓度蛋白酶体抑制剂PSI作用于PC12细胞24、48、72 h后,以MTT法检测细胞活性,荧光染色检测凋亡细胞百分率,HE染色观察细胞形态变化,透射电镜观察细胞超微结构变化。结果不同浓度PSI作用于PC12细胞24 h时,细胞存活率无变化;作用48~72 h时,1~20μmol/L PSI使细胞存活率分别降至47.03%~58.98%和19.58%~34.72%;凋亡细胞由1.15%升至5.27%。HE染色显示经PSI处理的PC12细胞胞浆内有嗜酸性包涵体出现,透射电镜下细胞呈凋亡的超微结构特点。结论PC12细胞蛋白酶体受抑模拟了PD的两大病理特点,蛋白酶体功能异常可能是PD的发病因素之一,短期抑制PC12细胞的蛋白酶体功能可作为PD的细胞模型。