艾司西酞普兰添加治疗对帕金森病患者非运动症状的临床疗效

目的：考察普拉克索添加艾司西酞普兰治疗对帕金森病患者非运动症状的临床疗效。方法: 将60 例帕金森病患者按收治顺序单双号分为观察组和对照组,每组30 例。对照组采用口服盐酸普拉克索治疗,观察组则在口服盐酸普拉克索基础上添加艾司西酞普兰治疗,连续治疗8 周后,分别以帕金森病综合评分量表（UPDRS）、汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表(HAMA)、匹兹堡睡眠质指数(PQSI ) 和生活质量综合评定量表(GQOLI-74) 的评分为指标,对比考察2 组患者的综合症状、抑郁和焦虑症状、睡眠和生活质量等的变化。结果: 与治疗前相比,2 组患者治疗后,UPDRS 总分、运动检查以及精神、行为和情感评分均显著降低（P <0.05）,治疗并发症和日常生活评分无显著差异（P >0.05）,其中观察组患者的UPDRS 总分以及精神、行为和情感评分较对照组显著降低（P <0.05）,而2 组患者的治疗并发症、日常生活和运动检查评分无显著差异（P >0.05）;且2 组患者治疗后,HAMD、HAMA 和PQSI 评分均显著降低（P <0.05）,其中观察组患者的HAMD、HAMA 和PQSI 评分较对照组显著降低（P <0.05）,而2 组患者的GQOLI-74 评分均显著升高（P <0.05）,其中观察组患者GQOLI-74 评分显著高于对照组（P <0.05）。结论: 普拉克索添加艾司西酞普兰治疗可有效改善帕金森病患者抑郁、焦虑、睡眠障碍等非运动症状,从而提高患者生活质量,具有重要的临床意义。     

多巴丝肼联合普拉克索治疗帕金森病的临床疗效

目的:探讨多巴丝肼联合普拉克索治疗帕金森病的临床疗效。方法:以入院病历号为编号,根据随机数字表,将106名帕金森病患者随机分成分两组,每组53例。治疗过程中,给予多巴丝肼片治疗的患者记为对照组(53例);给予多巴丝肼联合普拉克索治疗的患者记为观察组(53例)。连续治疗12周,观察两组患者总疗效、UPDRS评分、HAMD评分及不良反应,探讨其临床治疗价值。结果:1观察组总有效率明显高于对照组总有效率,差异有统计学意义(P0.05)。2与治疗前相比,治疗后两组UPDRS各项评分均明显改善(P0.05),且观察组UPDRS各项评分明显优于对照组(P0.05)。3与治疗前相比,治疗后两组HAMD评分均明显改善(P0.05),且观察组HAMD评分明显优于对照组(P0.05)。结论:多巴丝肼联合普拉克索治疗帕金森病疗效确切,安全可靠,值得临床推广应用。     

盐酸普拉克索联合美多巴对老年帕金森病的临床疗效及对运动功能的影响

目的:研究盐酸普拉克索联合美多巴对老年帕金森病的临床疗效及对运动功能的影响。方法:选择2014年3月~2015年8月在我院进行诊治的老年帕金森病患者210例,随机分为观察组和对照组,对照组给予美多巴,观察组给予盐酸普拉克索联合美多巴,比较两组的临床疗效,治疗前后运动功能、生活质量的变化情况和不良反应的发生情况。结果:观察组的治疗有效率为85.71%,明显高于对照组的65.71%(P0.05);治疗12周后,观察组UPDRS评分与治疗前和对照组相比均明显降低(P0.05);治疗12周后,观察组生理、心理、独立性、社会关系和环境等方面的评分与治疗前和对照组相比均明显升高(P0.05);两组间恶心、呕吐、开关现象、精神症状等不良反应发生率相比无明显差异(P0.05)。结论:盐酸普拉克索联合美多巴对老年帕金森病疗效显著,能明显改善运动功能,且用药安全,值得推广应用。     

普拉克索联合补肾活血通络胶囊治疗老年帕金森病的临床疗效及对血清5-HT、BDNF、S-100β水平的影响

目的:分析普拉克索联合补肾活血通络胶囊治疗老年帕金森病的临床效果及对血清5-羟色胺(5-HT)、脑源性神经营养因子(BDNF)、S-100β水平的影响。方法:选择我院2014年12月~2016年12月收治的96例老年帕金森病患者,按随机数字表法分为对照组和研究组,每组48例。对照组采用普拉克索治疗,研究组基于对照组加以补肾活血通络胶囊治疗。观察并比较两组临床疗效指标统一帕金森病评分量表Ⅰ(unified parkinson’s disease rating scale,UPDRS)Ⅰ、UPDRSⅡ、UPDRSⅢ、UPDRSⅣ、总UPDRS,血清5-HT、BDNF、S-100β水平的变化及不良反应的发生情况。结果:治疗后,研究组总有效率为87.50%,显著高于对照组(64.58%,P<0.05)。两组治疗后的UPDRSⅠ、UPDRSⅡ、UPDRSⅢ、UPDRSⅣ、总UPDRS、血清S-100β水平均较治疗前显著下降,且研究组以上指标均明显低于对照组。两组治疗后的血清5-HT、BDNF水平均较治疗前明显上升,且研究组以上指标均明显高于对照组(P<0.05)。研究组不良反应发生率显著低于对照组(P<0.05)。结论:普拉克索联合补肾活血通络胶囊治疗治疗老年帕金森病的临床效果优于单用普拉克索,可能与其显著提高血清5-HT及BDNF表达并降低S-100β水平有关。     

阿托伐他汀钙对帕金森病细胞模型的保护作用及其临床意义

目的:评价阿托伐他汀钙对帕金森病细胞模型及帕金森病患者临床症状的影响。方法:首先使用MPP+处理SH-SY5Y细胞建立帕金森病细胞模型。观察阿托伐他汀钙在该模型中对Wnt通路以及细胞凋亡的影响。其次选取66例符合纳入标准的临床患者,其中33例服用多巴丝肼片和盐酸普拉克索(普通治疗组)。其余33例则因其他原因在使用多巴丝肼片和盐酸普拉克索治疗期间服用阿托伐他汀钙片(阿托伐他汀组)。观察两组患者的Hoehn-Yahr分级,UPDRS评分,以及不良反应的发生率。结果:在MPP+处理组,Wnt通路受到抑制且细胞发生凋亡,而阿托伐他汀钙预处理可缓解MPP+引起的Wnt通路的抑制和细胞凋亡,差异具有统计学意义(P0.05)。治疗8周后阿托伐他汀组的Hoehn-Yahr分级改善情况显著优于普通治疗组的改善情况,并且差异具有统计学意义(P0.05);治疗8周后普通治疗组的UPDRS评分高于阿托伐他汀组的评分,差异具有统计学意义(P0.05);阿托伐他汀组的不良反应发生率低于普通治疗组,但差异无统计学意义(P0.05)。结论:阿托伐他汀钙可通过Wnt通路保护MPP+引起的细胞凋亡并且在临床治疗中能较好的改善帕金森病患者的运动和非运动症状。     

普拉克索治疗帕金森病合并抑郁症的随机对照研究

目的:研究普拉克索治疗帕金森病合并抑郁症的临床效果。方法:选取2009年5月至2011年5月我院收治的帕金森病合并抑郁症的患者56例,随机分为对照组(给予舍曲林)和观察组(给予普拉克索),连续应用12周。对治疗前、治疗后第4、8、12周两组患者的抑郁情况及临床疗效进行分析。结果:两组治疗后,第4、8、12周末HAMD总分均较治疗前显著下降(P<0.05),到第12周末观察组HAMD总分显著低于对照组(P<0.05);第4、8、12周末CGI-SI评分均显著下降(P<0.05),观察组下降更为明显(P<0.05)。结论:普拉克索治疗帕金森病合并抑郁症效果显著,抗抑郁效应和抗运动症状效果优于舍曲林。     

酪酸梭菌辅助根除幽门螺杆菌感染的Meta分析

目的系统评价酪酸梭菌辅助根除幽门螺杆菌(Helicobacter pylori,H.pylori)感染的疗效和安全性。方法计算机检索PubMed、CENTRAL(2016年7期)、CBM、CNKI、万方数据库、维普数据库,同时追溯纳入文献和相关综述的参考文献,收集关于酪酸梭菌辅助根除H.pylori感染的随机对照试验(RCT),检索时间均从建库至2016年7月30日。由两名评价员根据纳入排除标准筛选文献、提取资料、评价纳入研究的偏倚风险,采取RevMan 5.3进行Meta分析。结果最终纳入13个RCT,共1 372例患者(其中试验组742例,对照组630例)。Meta分析结果显示:与标准根除方案相比,酪酸梭菌辅助治疗组有利于提高H.pylori的根除率(RR=1.26,95%CI:1.18~1.34,P0.00001),并且降低总不良反应(RR=0.41,95%CI:0.32~0.52,P0.00001)、腹泻(RR=0.31,95%CI:0.16~0.58,P=0.0003)、味觉紊乱的发生率(RR=0.35,95%CI:0.17~0.73,P=0.005);然而,在腹胀、恶心的发生率上,酪酸梭菌辅助治疗组虽低于标准方案组,但差异无统计学意义。结论当前证据显示酪酸梭菌联合标准方案不仅可提高H.pylori的根除率,还能降低总不良反应、腹泻及味觉紊乱的发生。受纳入研究的质量和数量的限制,上述结论有待更多高质量的研究予以验证。     

坦度螺酮与艾司西酞普兰治疗帕金森病伴抑郁状态的疗效观察

目的观察坦度螺酮与艾司西酞普兰对帕金森病伴抑郁状态的作用及影响。方法将我院收治的帕金森病伴抑郁状态患者110例随机分为对照组和观察组各55例,对照组给予艾司西酞普兰治疗,观察组给予度螺酮治疗,并采用帕金森病综合评分表(UPDRS)和汉密尔顿抑郁量表(HAMD)为量化指标,比较两组患者治疗前及治疗后2、4、6周UPDRS、HAMD指标变化以及不良反应情况。结果两组患者的临床总有效率比较,差异无明显统计学意义(P0.05。治疗6周后,两组患者的UPDRS和HAMD评分与治疗前比较均下降(P0.05),且观察组的下降幅度优于对照组,差异有统计学意义(P0.05)。治疗过程中,两组患者均未出现严重不良反应。结论坦度螺酮的受体选择性高,能有效缓解帕金森病患者常见的情感症状(如抑郁状态)和明显改善帕金森病肌强直症状,且用药安全,是帕金森病伴抑郁状态患者有效抗抑郁剂。     

非索非那定治疗变应性鼻炎的随机对照试验的Meta分析

目的:评价非索非那定治疗变应性鼻炎的疗效及其安全性。方法:计算机检索SCI,Pubmed,Elsevier,Cochrane图书馆,知网,万方数据库,维普数据库中关于非索非那定治疗变应性鼻炎的随机对照试验,同时追索纳入文献的参考文献。检索年限均从建库检索到2013年12月。由两名评价员独立筛查文献,对纳入的文献进行质量评价并提取文献,对符合质量标准的随机对照试验(RCT)进行Meta分析,比较非索非那定组和安慰剂组鼻部症状评分、血清中白三烯浓度、生活质量评价、症状改善率和安全性评估。统计学分析采用RevMan5.2软件。结果:共纳入9个RCT。患者口服非索非那定片30 mg/d,120 mg/d,180 mg/d后可有效改善变应性鼻炎患者的症状,可降低患者鼻部症状评分、血清中白三烯浓度;有效提高生活质量,降低患者总的生活质量评分(P均0.05)。非索非那定不良反应的发生率与安慰剂组相似,不良反应发生率差异无统计学意义(P0.05)。结论:患者口服非索非那定片30mg/d,120 mg/d,180 mg/d后可以有效缓解患者的症状,改善患者的生活质量,且不良反应发生率与对照组相近。基于非索非那定较好的有效性和安全性,故可以广泛应用于临床,更加有效的缓解变应性鼻炎患者的症状。     

美金刚联合普拉克索治疗帕金森患者临床疗效及对CysC、Hcy水平影响

目的:探究美金刚联合普拉克索在治疗帕金森患者中的临床疗效,并就治疗对患者胱抑素C(cystatin C,CysC)以及血同型半胱氨酸(homocysteine,Hcy)水平的影响。方法:选择2018年1月至2020年1月于我院接受治疗的98例帕金森患者,随机数字表法均分为两组(每组各49例),对照组单纯接受美金刚治疗,研究组在对照组基础上加用普拉克索进行治疗,对比两组治疗有效率,治疗前后CysC、Hcy水平,以及治疗前后简易智能精神状态检查量表(mini mental state examination,MMSE)以及帕金森病评定量表III(parkinson comprehensive rating scale,UPDRS III)评分,最后对两组患者治疗中不良反应发生率进行统计对比。结果:(1)研究组患者治疗有效率明显高于对照组患者(P0.05);(2)治疗前两组患者CysC、Hcy水平对比差异不具有统计学意义(P0.05),治疗后研究组患者CysC、Hcy水平低于对照组(P0.05);(3)治疗前两组患者MMSE及UPDRS III量表评分对比差异不具有统计学意义(P0.05),治疗后研究组患者MMSE得分高于对照组,UPDRS III量表评分低于对照组(P0.05);(4)两组治疗不良反应诸如胃肠道反应、嗜睡、体位性低血压等对比无差异(P0.05)。结论:美金刚联合普拉克索对帕金森具有较好的治疗效果,能够显著改善患者认知及运动功能,降低CysC、Hcy水平,同时治疗安全性较高。     

Pramipexole Reduces Reactive Oxygen Species Production In Vivo and In Vitro and Inhibits the Mitochondrial Permeability Transition Produced by the Parkinsonian Neurotoxin Methylpyridinium Ion

Abstract: Sporadic Parkinson's disease is associated with a defect in the activity of complex I of the mitochondrial electron transport chain. This electron transport chain defect is transmitted through mitochondrial DNA, and when expressed in host cells leads to increased oxygen free radical production, increased antioxidant enzyme activities, and increased susceptibility to programmed cell death. Pramipexole, a chemically novel dopamine agonist used for the treatment of Parkinson's disease symptoms, possesses antioxidant activity and is neuroprotective toward substantia nigral dopamine neurons in hypoxic-ischemic and methamphetamine models. We found that pramipexole reduced the levels of oxygen radicals produced by methylpyridinium ion (MPP⁺) both when incubated with SH-SY5Y cells and when perfused into rat striatum. Pramipexole also exhibited a concentration-dependent inhibition of opening of the mitochondrial transition pore induced by calcium and phosphate or MPP⁺. These results suggest that pramipexole may be neuroprotective in Parkinson's disease by attenuating intracellular processes such as oxygen radical generation and the mitochondrial transition pore opening, which are associated with programmed cell death.     

Blood-brain barrier transport of pramipexole, a dopamine D2 agonist

The blood-brain barrier (BBB) transport of pramipexole, a potent dopamine receptor agonist with high efficacy for Parkinson's disease, was mainly characterized using immortalized rat brain capillary endothelial cells (RBEC)1 as an in vitro BBB model. [(14)C]Pramipexole uptake by RBEC1 was dependent on temperature and pH, but not sodium ion concentration or membrane potential. The uptake was inhibited by several organic cations including pyrilamine. Mutual inhibition was observed between pramipexole and pyrilamine. In addition, [(14)C]pramipexole uptake was stimulated by preloading unlabeled pramipexole. RT-PCR analysis for organic cation transporters (rOCT1-3, rOCTN1-2) in RBEC1 was performed. The mRNA level of rOCTN2 was the highest, followed by rOCTN1, while expression of rOCT1, rOCT2 and rOCT3 was negligible. The brain uptake of [(14)C]pramipexole, which was measured by the in situ rat brain perfusion technique, was significantly inhibited by unlabeled pramipexole. These results suggest that pramipexole is, at least in part, transported across the BBB by an organic cation-sensitive transporter. The pramipexole transport in RBEC1 was pH-dependent, but sodium- and membrane potential-independent.     

Pramipexole protects against apoptotic cell death by non-dopaminergic mechanisms

We have investigated the ability of pramipexole, a dopamine agonist used in the symptomatic treatment of Parkinson's disease (PD), to protect against cell death induced by 1-methyl-4-phenylpyridinium (MPP+) and rotenone in dopaminergic and non-dopaminergic cells. Pre-incubation with either the active (-)- or inactive (+)-enantiomer forms of pramipexole (10 microm) decreased cell death in response to MPP+ and rotenone in dopaminergic SHSY-5Y cells and in non-dopaminergic JK cells. The protective effect was not prevented by dopamine receptor blockade using sulpiride or clozapine. Protection occurred at concentrations at which pramipexole did not demonstrate antioxidant activity, as shown by the failure to maintain aconitase activity. However, pramipexole reduced caspase-3 activation, decreased the release of cytochrome c and prevented the fall in the mitochondrial membrane potential induced by MPP+ and rotenone. This suggests that pramipexole has anti-apoptotic actions. The results extend the evidence for the neuroprotective effects of pramipexole and indicate that this is not dependent on dopamine receptor occupation or antioxidant activity. Further evaluation is required to determine whether the neuroprotective action of pramipexole is translated to a disease-modifying effect in PD patients.     

Pramipexole protects against MPTP toxicity in non-human primates

The neurotoxin MPTP induces nigral dopaminergic cell death in primates and produces a partial model of Parkinson's disease (PD). Pramipexole is a D2/D3 dopamine receptor agonist used in the symptomatic treatment of PD, and which also protects neuronal cells against dopaminergic toxins in vitro. We now demonstrate that pramipexole partially prevents MPTP toxicity in vivo in a primate species. Common marmosets were repeatedly treated with pramipexole either before, coincidentally with, or after low-dose MPTP treatment designed to induce a partial lesion of the substantia nigra. Animals pretreated with pramipexole had a significantly greater number of surviving tyrosine hydroxylase (TH) positive neurones in the pars compacta of the substantia nigra. Pramipexole pretreatment also prevented degeneration of striatal dopamine terminals. Treatment with pramipexole concurrently with MPTP or following MPTP did not prevent TH-positive cell loss. Pramipexole pretreatment appears to induce adaptive changes that protect against dopaminergic cell loss in primates.     

Neuroprotection by pramipexole against dopamine- and levodopa-induced cytotoxicity

Pramipexole, a novel non-ergoline dopamine (DA) agonist, has been applied successfully for treatment of Parkinson's disease (PD). We report here that pramipexole can protect dopaminergic cell line Mes23.5 against dopamine- and levodopa-induced cytotoxicity possibly through a mechanism related to antioxidant activity. In the MES 23.5 cultures, DA and L-DOPA induce a dose- and time-dependent cytotoxicity, as determined by tetrazolium salt and trypan blue assays. Furthermore, an in situ terminal deoxynucleotidyl transferase assay demonstrates that DA-induced cell death is apoptotic. Pretreatment with pramipexole in a concentration range (4-100 microM) significantly attenuates DA- or L-DOPA-induced cytotoxicity and apoptosis, an action which is not blocked by D3 antagonist U-99194 A or D2 antagonist raclopride. Pramipexole also protects MES 23.5 cells from hydrogen peroxide-induced cytotoxicity in a dose-dependent manner. In cell-free system, pramipexole can effectively inhibit the formation of melanin, an end product resulting from DA or L-DOPA oxidation. These results indicate that pramipexole exerts its neuroprotective effect possibly through a mechanism, which is independent of DA receptors but related to antioxidation or scavenging of free radicals (e.g. hydrogen peroxide). As a direct DA agonist and potentially neuroprotective agent, pramipexole remains attractive in the treatment of PD.     

Binding of pramipexole to extrastriatal dopamine D2/D3 receptors in the human brain: a positron emission tomography study using 11C-FLB 457

The purpose of this study was to determine the binding sites of pramipexole in extrastriatal dopaminergic regions because its antidepressive effects have been speculated to occur by activating the dopamine D(2) receptor subfamily in extrastriatal areas. Dynamic positron emission tomography (PET) scanning using (11)C-FLB 457 for quantification of D(2)/D(3) receptor subtype was performed on 15 healthy volunteers. Each subject underwent two PET scans before and after receiving a single dose of pramipexole (0, 0.125, or 0.25 mg). The study demonstrated that pramipexole significantly binds to D(2)/D(3) receptors in the prefrontal cortex, amygdala, and medial and lateral thalamus at a dose of 0.25 mg. These regions have been indicated to have some relation to depression and may be part of the target sites where pramipexole exerts its antidepressive effects.     

个性化心理护理对帕金森病伴抑郁状态患者的影响

目的探讨个性化心理护理对帕金森病患者伴抑郁状态的影响。方法选择我院神经内科收治的帕金森病伴抑郁状态患者100例作为研究对象,随机分成对照组和观察组各50例。对照组按帕金森病常规药物治疗和护理,观察组在此基础上给予个性化心理护理,观察两组患者4周后汉密尔顿抑郁量表(HAMD)评定情况。结果通过个性化心理护理后,观察组患者的抑郁发生率明显低于对照组,差异有统计学意义(P0.01)。结论个性化心理护理可显著改善帕金森病患者的抑郁症状,提高患者的生活质量。     

Neuroprotective effect of the antiparkinsonian drug pramipexole against nigrostriatal dopaminergic degeneration in rotenone-treated mice

Pramipexole, an agonist for dopamine (DA) D2/D3-receptors, has been used to treat both early and advanced Parkinson's disease (PD). In this study, we examined the effect of pramipexole on DA neurons in a PD model of C57BL/6 mice, which were treated with rotenone (30 mg/kg, p.o.) daily for 28 days. Pramipexole (1 mg/kg, i.p.) was injected daily 30 min before each oral administration of rotenone. Chronic oral administration of rotenone caused a loss of DA neurons in the substantia nigra pars compacta (SNpc), motor deficits and the up-regulation of α-synuclein immunoreactivity in some surviving DA neurons. Pramipexole inhibited rotenone-induced DA neuronal death and motor deficits, and reduced immunoreactivity for α-synuclein. In addition, pramipexole inhibited the in vitro oligomerization of human wild-type α-synuclein by H₂O₂ plus cytochrome c. To examine the neuroprotective effect of pramipexole against oxidative stress, we used a DJ-1-knockdown SH-SY5Y cell line and electron spin resonance (ESR) spectrometry. Simultaneous treatment with H₂O₂ and pramipexole resulted in the significant protection of DJ-1-knockdown cells against cell death in a concentration-dependent manner. A high concentration of pramipexole directly scavenged hydroxyl radical (OH) generated from H₂O₂ and Fe²⁺. Furthermore, pramipexole increased Bcl-2 immunoreactivity in DA neurons in the SNpc. These results suggest that pramipexole may protect DA neurons against exposure to rotenone by chronic oral administration, and this effect is mediated by multiple functions including scavenging of OH and induction of Bcl-2 protein.     

Dopamine agonist increases risk taking but blunts reward-related brain activity

The use of D2/D3 dopaminergic agonists in Parkinson's disease (PD) may lead to pathological gambling. In a placebo-controlled double-blind study in healthy volunteers, we observed riskier choices in a lottery task after administration of the D3 receptor-preferring agonist pramipexole thus mimicking risk-taking behavior in PD. Moreover, we demonstrate decreased activation in the rostral basal ganglia and midbrain, key structures of the reward system, following unexpected high gains and therefore propose that pathological gambling in PD results from the need to seek higher rewards to overcome the blunted response in this system.