早期肠道菌群干预对帕金森病患者便秘症状及多巴丝肼疗效的影响

目的 探讨早期肠道菌群干预对帕金森病（PD）患者肠道便秘症状及多巴丝肼疗效的影响,为临床治疗提供参考。方法 纳入2015月1月至2017年10月我院神经内科初次诊断的PD患者114例,随机分为肠道菌群干预组（n=57）与对照组（n=57）,两组均予多巴丝肼片常规初始治疗,干预组在此基础上加用三联活菌制剂调理肠道菌群,采用便秘患者生活质量量表（PAC-QOL）等评估患者便秘症状及满意度,采用统一帕金森病评定量表（UPDRS-Ⅲ）等评估两组患者治疗前后的运动症状及心理状态。结果 1干预组较治疗前及较对照组的PAC-QOL,Bristol粪便性状量表（BSFS）评分改善显著,差异有统计学意义（P<0.05）;2两组患者较治疗前UPDRS-Ⅲ运动评分均有改善,差异有统计学意义（P<0.05）,干预组较对照组4周时UPDRS-Ⅲ评分有下降,差异有统计学意义（P<0.05）;3干预组较对照组治疗后医院焦虑量表（HAD-A）、医院抑郁量表（HAD-D）、匹兹堡睡眠质量指数（PSQI）评分均有下降,差异有统计学意义（P<0.05）。结论 早期肠道菌群干预能有效改善PD患者的便秘症状及焦虑睡眠等心理状态,可能有早期增强多巴丝肼制剂对运动症状的疗效,但远期影响仍有待研究。     

左旋多巴微囊漂浮片的处方优选

摘 要 目的： 优选左旋多巴微囊漂浮片的处方。方法: 高效液相色谱法测定左旋多巴与苄丝肼的含量,以漂浮片释放度得分为指标,采用正交试验优选左旋多巴微囊漂浮片的处方,并对其体外释药特性进行评价。结果: 建立的测定左旋多巴胃内漂浮片中左旋多巴与苄丝肼含量的高效液相色谱法,符合方法学要求。优化的微囊漂浮片处方组成为硬脂酸：主药：丙烯酸树脂：HPMC=2∶5∶2∶1,平均片重为550 mg。验证试验结果表明该微囊漂浮片具有漂浮、缓释、可分剂量使用等特性。结论: 优选出的复方左旋多巴微囊漂浮片处方合理,生产工艺稳定、可行。     

多巴丝肼联合普拉克索治疗帕金森综合征的效果观察

目的:观察多巴丝肼联合普拉克索治疗帕金森综合征的临床效果。方法:选取收治的40例帕金森综合征患者为研究对象,采用随机数字表法分为研究组和对照组,每组20例。对照组予多巴丝肼治疗,研究组在对照组基础上联合普拉克索治疗,比较两组治疗前后帕金森病评定量表(UPDRS)评分,临床疗效及治疗后运动功能。结果:治疗后,两组UPDRS评分均低于治疗前,且研究组低于对照组,差异均有统计学意义(P<0.05);研究组治疗总有效率为95.00%,高于对照组的60.00%,差异有统计学意义(P<0.05);研究组左手及右手1 min限时运动次数均多于对照组,差异有统计学意义(P<0.05);研究组10 m步行折返起立耗时及转弯耗时均短于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:多巴丝肼联合普拉克索治疗帕金森综合征,可有效改善患者的临床症状,改善预后。     

The role of 5-hydroxytryptophan (5-HTP) in the regulation of the sleep/wake cycle in parachlorophenylalanine (p-CPA) pretreated rat: a multiple approach study

Summary In the rat, the insomnia which follows the administration of parachlorophenylalanine (p-CPA), a serotonin synthesis inhibitor, is transiently reversed either by intra-cisternal injection of L-5-HTP or by an associated injection of 5-HTP and an L-aromatic-aciddecarboxylase inhibitor (benserazide). Histochemical, immunohistochemical and chemical investigations showed that 5-HTP administration does not lead to a detectable increase in cerebral 5-HT. These findings suggest that the restoration of sleep after p-CPA treatment could be mediated by the central action of 5-HTP.     

Levodopa alone and in combination with a peripheral decarboxylase inhibitor benserazide (madopar®) in the treatment of Parkinson's disease

Summary A combination of levodopa and the extracerebrally acting decarboxylase inhibitor benserazide (ratio 4:1) (Madopar^®), was compared with levodopa alone in a controlled double-blind clinical multicenter trial on 94 patients with Parkinson's disease. During 4 months of therapy levodopa + benserazide proved superior to levodopa on several accounts. Nausea and vomiting occurred with statistically significant less severity and frequency. Clinical improvement expressed through improvement in Webster rating occurred sooner and was all together greater.The treatment schedules did not differ with regard to other side effects, in particular involuntary movements and reduction in supine blood pressure. Neither treatment seemed to influence liver function, renal function and hematological parameters.

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Zusammenfassung Levodopa in Kombination mit dem extracerebral wirkenden Dekarboxylasehemmer Benserazid (Dosisverhältnis 4:1) (Madopar^®) wurde mit Levodopa allein in einer kontrollierten, doppelblinden, klinischen Multizenterprüfung an 94 Patienten mit Morbus Parkinson verglichen. Während der viermonatigen Therapie zeigte sich in mehreren Beziehungen Levodopa + Benserazid dem Levodopa überlegen. Übelkeit und Erbrechen waren statistisch signifikant weniger schwerwiegend und traten seltener auf. Klinische Besserung, ausgedrückt durch Reduktion im Webster Rating, trat schneller ein und war im großen und ganzen höher.Andere Nebenerscheinungen, insbesondere unwillkürliche Bewegungen und Reduktion des Blutdruckes im Liegen, verteilen sich gleich über die beiden Gruppen. Bestimmungen von sowohl Leberfunktion und Nierenfunktion als auch hämatologischen Parametern ergaben keine signifikanten Änderungen.

     

Peripheral conversion of L-5-Hydroxytryptophan to serotonin induces drinking in rats

Female rats administered serotonin (0.25 to 4.0 mg/kg, s.c.) showed a dose-dependent increase in water intake. The dipsogenic response was nearly maximal when 2 mg/kg was administered s.c. and plateaued by 2 hr after treatment. l-5Hydroxytryptophan (5-HTP), the precursor of serotonin, is also a potent dipsogen which induces drinking by way of the renin-angiotensin system. The possibility that the dipsogenic activity of 5-HTP is dependent on decarboxylation to serotonin was the objective of these studies. Either benserazide (30 mg/kg. s.c.), a central and peripheral decarboxylase inhibitor, or carbidopa (6.5 mg/kg, s.c.), a peripheral decarboxylase inhibitor, was administered 15 min prior to the dipsogen. Both decarboxylase inhibitors attenuated the dipsogenic response to 5-HTP (25 mg/kg, s.c.) but not to serotonin (2 mg/kg, s.c.). The peripheral serotonergic receptor antagonist, methysergide (3 mg/kg, i.p.), blocked the dipsogenic responses to both 5-HTP (25 mg/kg, s.c.) and serotonin (2 mg/kg, s.c.). There was no interaction between 5-HTP (18 mg/kg, s.c.) and serotonin (1 mg/kg, s.c.) when administered simultaneously with respect to their dipsogenic effects. Thus, the drinking response accompanying administration of 5-HTP occurs following peripheral conversion to serotonin which, in turn, activates peripheral serotonergic receptors. The mechanism(s) by which activation of peripheral serotonergic receptors increases water intake is not known, but appears to involve release of renin from the kidney.     

Simultaneous quantitation of levodopa and 3-O-methyldopa in human plasma by HPLC-ESI-MS/MS: application for a pharmacokinetic study with a levodopa/benserazide formulation

A sensitive and simple method was developed for the quantitation of levodopa and its metabolite 3-O-methyldopa, in human plasma, after oral administration of tablet formulations containing levodopa (200 mg) and benserazide (50 mg). The analytes were extracted by a protein precipitation procedure, using carbidopa as an internal standard. A mobile phase consisting of 0.2% formic acid and acetonitrile (94:6, v/v) was used and chromatographic separation was achieved using ACE C₁₈ column (50 mm × 4.6 mm i.d.; 5 μm particle size). Selected reaction monitoring was performed using the fragmentation transitions m/z 198 → m/z 107, m/z 212 → m/z 166 and m/z 227 → m/z 181 for levodopa, 3-O-methyldopa and carbidopa, respectively. Calibration curves were constructed over the range 50.0-6000.0 ng/mL for levodopa and 25.0-4000.0 ng/mL for 3-O-methyldopa. The method shown to be specific, precise, accurate and provided recovery rates higher than 85% for all analytes. No matrix effect was detected in the samples. The validated method was applied in a pharmacokinetic study with a levodopa/benserazide tablet formulation in healthy volunteers.     

Renal response to amino acid infusion in rats: effect of dopamine receptor antagonists and benserazide

Previously, we have found that feeding is a dominant factor controlling urinary dopamine excretion (U_DA) in conscious rats (Mühlbauer and Osswald 1992). Since the renal response to feeding is also characterized by an increase in glomerular filtration rate (GFR), we wanted to investigate in a first step whether the feeding-induced elevations of GFR and U_DA could be causally related phenomena. Therefore, we studied the influence of dopamine synthesis and dopamine receptor blockade on the renal response to amino acid infusion (AA) in thiopental anesthetized rats. AA infusion (n = 7) increased GFR by 33±7% (P<0.001) and U_DA by 87±19% (P<0.001). In the presence of benserazide (BZD, n = 5), an inhibitor of dopamine synthesis, infused i.v. at a dose of 30 g/min/kg, U_DA was suppressed to values below detection limit and the AA-induced GFR increase was abolished. Continuous intravenous infusion of the DA₁ receptor antagonist SCH 23390 (SCH, n = 7) in a dose of 4.0 g/kg/min did not prevent the AA-induced increase in GFR (33±3%, P<0.001) and U_DA (97±12%, P< 0.001). In contrast, S-sulpiride (SUL), a specific DA₂ receptor antagonist, infused continuously i.v. in a dose of 5 g/kg/min, completely abolished the AA-induced GFR increase, while U_DA was increased 1.6-fold (P<0.01). Like BZD, both dopamine receptor antagonists did not affect renal sodium excretion substantially.Our results suggest, that endogenous dopamine could act as a mediator in the renal response to amino acid infusion in the rat, most likely by activation of DA₂ receptors. Correspondence to:B. Mühlbauer at the above address     

普拉克索联合左旋多巴／苄丝肼治疗晚期帕金森病的疗效观察

目的 评估盐酸普拉克索联合左旋多巴/苄丝肼治疗晚期帕金森病的临床疗效.方法 50例患者随机分为治疗组25例、对照组25例.对照组给予左旋多巴/苄丝肼片和安慰剂,疗程16周;治疗组给予盐酸普拉克索片、左旋多巴/苄丝肼片,疗程16周.观察两组临床疗效.结果 与对照组比较,治疗组帕金森病评定量表评分显著下降,临床疗效明显提高（P＜0.05）,治疗组显效率（84.0%）高于对照组（36.0%）（χ^2=10.08,P＜0.01）.结论 盐酸普拉克索联合左旋多巴/苄丝肼治疗晚期帕金森病效果满意,值得推广应用.     

针刺阳经穴为主治疗帕金森病疗效观察

目的观察针刺阳经穴为主治疗帕金森病的临床疗效。方法将57例帕金森病患者随机分为治疗组30例和对照组27例。治疗组采用针刺阳经穴为主配合口服多巴丝肼片治疗,对照组采用单纯口服多巴丝肼片治疗。治疗1个月后比较两组临床疗效。结果治疗组总有效率为93.3%、对照组为66.7%,两组比较差异具有统计学意义(P0.05)。结论针刺阳经穴为主配合服用多巴丝肼片是一种治疗帕金森病的有效方法。