Preparation modification strategies for clinical treatment drugs of Parkinson's disease / 药学学报

Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.

Low serum uric acid levels and levodopa-induced dyskinesia in Parkinson's disease / Níveis séricos baixos de ácido úrico e discinesia induzida por levodopa na doença de Parkinson

Abstract Background Levodopa is the most used and effective medication for motor symptoms of Parkinson disease (PD), its long-term use is associated with the appearance of levodopa-induced dyskinesia (LID). Uric acid (UA) is believed to play an important neuroprotective role in PD. Objective To investigate if serum UA levels are related with the presence of LIDs in PD patients. Also, we investigated the associations among UA levels and clinical features of PD. Methods We enrolled 81 PD patients (dyskinesia = 48; no dyskinesia = 33) in the present study. A blood sample was collected to evaluate serum UA levels, clinical evaluation included the following instruments: Montreal Cognitive Assessment (MoCA), Beck Depression Inventory II (BDI-II), MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr (HY), and the sub-item 4.1 of MDS-UPDRS IV (score ≥ 1). Additional relevant clinical information was obtained by a clinical questionnaire. Results Serum UA levels were lower in the dyskinesia group when compared with the no dyskinesia group. The same result was found in the UA levels of both men and women. The multivariate analysis showed lower uric acid levels were significantly associated with having dyskinesia (odds ratio [OR] = 0.424; 95% confidence interval [CI]: 0.221-0.746; p= 0.005). Additional analysis verified that serum UA levels are inversely correlated with depressive symptoms, disease duration, MDS-UPDRS IV and time spent with dyskinesia. A positive correlation was found with age at onset of PD symptoms. Conclusions The present study provides a possible role of serum UA levels in LID present in PD patients.

Resumo Antecedentes A levodopa é a medicação mais utilizada e eficaz para os sintomas motores da doença de Parkinson (DP); seu uso a longo prazo está associado ao aparecimento de discinesia induzida por levodopa (LID). Acredita-se que o ácido úrico desempenhe um importante papel neuroprotetor na DP. Objetivo Investigar se os níveis séricos de AU estão relacionados com a presença de LID em pacientes com DP. Além disso, investigamos as associações entre os níveis de AU e as características clínicas da DP. Métodos Foram incluídos 81 pacientes com DP (discinesia = 48; sem discinesia = 33) no presente estudo. Uma amostra de sangue foi coletada para avaliar os níveis séricos de AU, a avaliação clínica incluiu os seguintes instrumentos: Avaliação Cognitiva de Montreal (MoCA), Inventário de Depressão de Beck (BDI-II), MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr (HY) e o subitem 4.1 da MDS-UPDRS IV (escore ≥ 1). Informações clínicas relevantes adicionais foram obtidas por meio de um questionário clínico. Resultados Os níveis séricos de AU foram menores no grupo com discinesia quando comparados ao grupo sem discinesia. O mesmo resultado foi encontrado nos níveis de AU de homens e mulheres. A análise multivariada mostrou que níveis mais baixos de ácido úrico foram significativamente associados a ter discinesia (odds ratio [OR] = 0,424; intervalo de confiança (IC) de 95%: 0,221-0,746; p= 0,005). Análises adicionais verificaram que os níveis séricos de AU estão inversamente correlacionados com sintomas depressivos, duração da doença, MDS-UPDRS IV e tempo gasto com discinesia. Uma correlação positiva foi encontrada com a idade de início dos sintomas da DP. Conclusões O presente estudo fornece um possível papel dos níveis séricos de AU na LID presente em pacientes com DP.

The Dynamics of Dopamine D2 Receptor-Expressing Striatal Neurons and the Downstream Circuit Underlying L-Dopa-Induced Dyskinesia in Rats / 神经科学通报·英文版

L-dopa (l-3,4-dihydroxyphenylalanine)-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy for Parkinson's disease. The potential contribution of striatal D2 receptor (D2R)-positive neurons and downstream circuits in the pathophysiology of LID remains unclear. In this study, we investigated the role of striatal D2R+ neurons and downstream globus pallidus externa (GPe) neurons in a rat model of LID. Intrastriatal administration of raclopride, a D2R antagonist, significantly inhibited dyskinetic behavior, while intrastriatal administration of pramipexole, a D2-like receptor agonist, yielded aggravation of dyskinesia in LID rats. Fiber photometry revealed the overinhibition of striatal D2R+ neurons and hyperactivity of downstream GPe neurons during the dyskinetic phase of LID rats. In contrast, the striatal D2R+ neurons showed intermittent synchronized overactivity in the decay phase of dyskinesia. Consistent with the above findings, optogenetic activation of striatal D2R+ neurons or their projections in the GPe was adequate to suppress most of the dyskinetic behaviors of LID rats. Our data demonstrate that the aberrant activity of striatal D2R+ neurons and downstream GPe neurons is a decisive mechanism mediating dyskinetic symptoms in LID rats.

ZHUANG Lixing's Experience in Differentiating and Treating Levodopa-Induced Dyskinesia in Parkinson's Disease / 中医杂志

This paper summarized Professor ZHUANG Lixing's clinical experience in differentiating and treating levodopa-induced dyskinesia （LID） in Parkinson's disease. It is believed that the fundamental pathogenesis of LID lies in the disharmony or malnourishment of tendons and vessels. Based on the clinical manifestations， peak-dose LID is differentiated into two syndromes： syndrome of hyperactive liver yang causing wind and syndrome of deficiency of both liver and kidney. For the syndrome of hyperactive liver yang causing wind， the treatment focuses on calming the liver to stop the wind， and relaxing the tendons to stop tremors. The main prescription used is Zhengan Xifeng Decoction （镇肝熄风汤） with the addition of Shijueming （石决明） and Zhenzhumu （珍珠母）. For the syndrome of deficiency of both liver and kidney， the treatment focuses on nourishing the liver and kidneys， and replenishing yin to stop the wind. The main prescription used is Dabuyin Pills （大补阴丸） with modification. LID in the acoustic phase is differentiated into syndrome of phlegm-damp blocking middle jiao and syndrome of deficiency of both qi and yin. For the syndrome of phlegm-damp blocking middle jiao， the treatment focuses on dissipating phlegm and eliminating dampness， and nurturing tendons and vessels. Wendan Decoction （温胆汤） or Erchen Decoction （二陈汤） with modification is used. For the syndrome of deficiency of both qi and yin， the treatment focuses on replenishing qi and nourishing blood， and nurturing tendons and vessels. The main prescriptions used are Buzhong Yiqi Decoction （补中益气汤） or Bazhen Decoction （八珍汤） or Shenling Baizhu Powder （参苓白术散） with modification. Biphasic LID is differentiated as the Shaoyang pivot disadvantageousness， and the treatment focuses on harmonizing Shaoyang and regulating the pivot. The main prescription used is Xiaochaihu Decoction （小柴胡汤） with modification.

Effects of pramipexole combined with levodopa on cognitive and mitochondrial function of rats after global cerebral ischemia-reperfusion injury / 中国康复理论与实践

ObjectiveTo investigate the effects of dopamine receptor agonist pramipexole and levodopa on emotion and cognition, and mitochondrial membrane potential of rats after global cerebral ischemia-reperfusion injury. MethodsA total of 80 male Sprague-Dawley rats were divided into sham group (n = 20), model group (n = 20), pramipexole group (n = 20) and combined group (n = 20). The latter three groups were used to prepare the model of global cerebral ischemia-reperfusion injury with Pulsinelli's four-vessel occlusion. The pramipexole group was intraperitoneally injected pramipexole 0.5 mg/kg once a day, while the combined group was injected levodopa 50 mg/kg and pramipexole 0.5 mg/kg, for 14 days. Five rats in each group were tested with open field test three, seven and 14 days after modeling; five were tested with Y-maze test seven and 14 days after modeling; five were detected mitochondrial membrane potential three, seven and 14 days after modeling; and five were observed under Nissl's staining14 days after modeling. ResultsCompared with the model group, the number of entries into the central zone (P < 0.05), total distance travelled (P < 0.05) and average velocity (P < 0.05) in the open field test increased in the pramipexole and combined groups seven and 14 days after modeling, duration spent in the central zone increased in the pramipexole and combined groups seven days after modeling (P < 0.05); the rate of spontaneous alternation of Y-maze test increased in the pramipexole and combined groups 14 days after modeling (P < 0.05); mitochondrial membrane potential in hippocampus increased in the pramipexole and combined groups seven and 14 days after modeling (P < 0.05), and it was less in the pramipexole group than in the combined group 14 days after modeling (P < 0.05); and the number of surviving neurons in the hippocampal CA1 increased in the pramipexole and combined groups 14 days after modeling (P < 0.05). ConclusionPramipexole may improve emotion and cognition of rats after global cerebral ischemia-reperfusion injury, and it may be helpful for restoring mitochondrial membrane potential as combining with levodopa.

How I treat Parkinson's disease / Como eu trato a doença de Parkinson

ABSTRACT Background: Parkinson's disease (PD) is a complex neurodegenerative condition. Treatment strategies through all stages of disease progression could affect quality of life and influence the development of future complications, making it crucial for the clinician to be on top of the literature. Objective: This paper reviews the current treatment of PD, from early to advanced stages. Methods: A literature review was conducted focusing on the treatment of PD, in the different stages of progression. Results: Every individual with a new diagnosis of PD should be encouraged to start exercising regularly. In the early stage, treatment should focus on using the lowest dose of levodopa or combination therapy that provides maximum functional capacity, and does not increase the risk of complications, such as peak dose dyskinesias and impulse control disorders. At the moderate and advanced stages, motor fluctuations and complications of treatment dominate the picture, making quality of life one important issue. Rehabilitation programs can improve motor symptoms and should be offered to all patients at any stage of disease progression. Conclusion: Many factors need to be considered when deciding on the best treatment strategy for PD, such as disease progression, presence of risk factors for motor and behavioral complications, potential side effects from dopaminergic therapy and phenotypical variabilities. Treatment should focus on functional capacity and quality of life throughout the whole disease course.

RESUMO Antecedentes: A doença de Parkinson (DP) é uma doença neurodegenerativa complexa. As estratégias de tratamento ao longo de todos os estágios da evolução podem influenciar a qualidade de vida e o desenvolvimento de futuras complicações e, portanto, devem ser devidamente conhecidas pelos médicos que assistem o paciente. Objetivo: Neste artigo são revistos os tratamentos atuais para a DP, desde o estágio inicial até os estágios avançados. Métodos: Uma revisão da literatura foi realizada com enfoque em diferentes estágios da doença. Resultados: Todos os pacientes que recebem o diagnóstico de DP devem ser orientados a praticar atividades físicas regularmente. Em fase inicial do tratamento a estratégia consiste em usar doses mínimas de levodopa ou terapias combinadas que propiciem máxima capacidade funcional, que não aumentem o risco de complicações motoras, tais como discinesias induzidas por levodopa, ou não motoras, como transtornos do controle do impulso. Em estágio moderado ou avançado da doença, complicações como flutuações motoras e discinesias tornam-se relevantes e devem ser manejadas adequadamente. Programas de reabilitação devem ser oferecidos para os pacientes em todos os estágios da DP. Conclusões: Vários fatores devem ser considerados ao se escolher a melhor estratégia para o tratamento da DP. Entre eles destacam-se: fatores de risco para o desenvolvimento de complicações motoras e comportamentais, potenciais efeitos colaterais da terapia dopaminérgica e variabilidade fenotípica. O objetivo das estratégias de tratamento ao longo de toda a evolução da doença é a melhoria da capacidade funcional e da qualidade de vida dos pacientes.

Distonías primarias respondedoras a levodopa (DRD): búsqueda sistemática en Latinoamérica / Dopa-responsive dystonia (DRD): systematic search in Latin America

RESUMEN Las distonías que responden a levodopa (DRD, siglas en inglés) abarcan un grupo de distonías primarias, causadas por deficiencias enzimáticas en la vía metabólica de las aminas y, por definición, comparten como característica principal su respuesta favorable y sostenida a levodopa. Existen hasta seis genes asociados a DRD, siendo el gen GCH1 el más frecuentemente involucrado. La presentación típica de esta entidad se caracteriza por su aparición en la niñez, distonía de inicio en miembros inferiores con fluctuación diurna, leve parkinsonismo y respuesta clara a dosis bajas de levodopa. Se incluye una búsqueda sistemática de la literatura con casos de DRD publicados en Latinoamérica.

SUMMARY Dopa-responsive dystonia (DRD) encompasses a heterogenous group of primary dystonias, caused by enzymatic deficiencies across the amines pathway and, by definition, show as their main characteristic a favorable and sustained response to levodopa. There are up to 6 genes associated with DRD, including pathogenic variants of the GCH1 gene as the most frequently involved. The typical presentation of DRD is characterized by start in childhood, lower limb-onset dystonia with daytime fluctuation, mild parkinsonism, and a sustained response to low doses of levodopa. A systematic literature search on DRD reported cases in Latin America is presented.

Experience with the Rehabilitation of Patients with Parkinson's Disease Using Levodopa-Carbidopa Intestinal Gel（LCIG）Treatment for Their Return to Work / The Japanese Journal of Rehabilitation Medicine

Patients with Parkinson's disease (PD) experience difficulties with activities of daily living (ADLs) at workplace and in their social life depending on the extent of disease progression. Because of their disabilities, patients with PD are forced into early retirement compared to other people of their age group. We present our experience with the rehabilitation of three patients with PD using levodopa-carbidopa intestinal gel (LCIG) treatment for their return to work. The rehabilitation program comprised the following three modules：1) evaluating the patients' ability to walk indoor for a short time；2) assessing their standing and sitting positions to enable them to more easily handle a device；and 3) improving their upper limb function, including skilled movements, for operating a device in emergency. Finally, all three patients exhibited improvements in the Timed Up and Go test results and device operation. Two of the patients returned to their former workplace within 10 months of LCIG treatment initiation and the remaining patient found new employment 1 year after treatment commencement.In conclusion, establishing a rational support system that involves rehabilitation programs and information sharing across multiple occupations is essential for the return to work of patients with PD receiving LCIG treatment.

Experience with the Rehabilitation of Patients with Parkinson's Disease Using Levodopa-Carbidopa Intestinal Gel（LCIG）Treatment for Their Return to Work / The Japanese Journal of Rehabilitation Medicine

Patients with Parkinson's disease (PD) experience difficulties with activities of daily living (ADLs) at workplace and in their social life depending on the extent of disease progression. Because of their disabilities, patients with PD are forced into early retirement compared to other people of their age group. We present our experience with the rehabilitation of three patients with PD using levodopa-carbidopa intestinal gel (LCIG) treatment for their return to work. The rehabilitation program comprised the following three modules：1) evaluating the patients' ability to walk indoor for a short time；2) assessing their standing and sitting positions to enable them to more easily handle a device；and 3) improving their upper limb function, including skilled movements, for operating a device in emergency. Finally, all three patients exhibited improvements in the Timed Up and Go test results and device operation. Two of the patients returned to their former workplace within 10 months of LCIG treatment initiation and the remaining patient found new employment 1 year after treatment commencement.In conclusion, establishing a rational support system that involves rehabilitation programs and information sharing across multiple occupations is essential for the return to work of patients with PD receiving LCIG treatment.

Effect of medication withdrawal on pain in Parkinson's disease patients - an observational study based on a sample of patients without antiparkinsonian medications

SUMMARY OBJECTIVES: To assess the effect of withdrawal of the antiparkinsonian drug regimen administration on patients with PD and its relation to pain. METHODS: The sample included 22 men and 12 women who were candidates for neurosurgery to control motor signs and symptoms treated with L-dopa as a drug, alone or in combination with others (Cholinergic Antagonists; Dopamine Agents). All of them were examined at two different moments, with and without medication, and analyzed for painful symptoms. The Hoehn and Yahr scale was used for functional staging of the disease. Pain intensity was assessed by using the numerical verbal scale. RESULTS: The mean pain intensity among those on medication {2.17±0.39 (SE)} was significantly lower than in the abstinence group {4.2±0.59 (SE), p=0.006, Wilcoxon}, which corresponded to the increase in the total functional staging score from 93 to 111, respectively. CONCLUSION: The interruption of the administration of specific medications in patients with Parkinson's disease caused, or increased the intensity of, painful discomfort correlated with the intensity of functional impairment. This effect was also observed in women, but it was statistically relevant only for men. The results suggest that pain may be a "red flag" that points to the need for a therapeutic drug review when its presence or worsening is detected.

The influencing factors and prevention progress of motor complications of Parkinson's disease / 预防医学

Abstract@#Long-term use of levodopa in the treatment of Parkinson's disease can cause motor complications, which seriously impair the patients'motor function, reduce the quality of life, and aggravate the functional disability. Since there has been no effective treatment for motor complications, clarifying the influencing factors and prevention methods are conducive to reducing the risk of incidence and improving the quality of life of the patients. This paper summarizes the types and mechanism of motor complications of Parkinson's disease, the influencing factors ( levodopa dose, onset age, Helicobacter pylori infection and high protein diet ) and preventive measures ( psychological intervention, low protein diet, rehabilitation exercise and drugs ), so as to provide reference for the prevention and control of the disease.

Blood pressure and its association with antiparkinsonian medications in patients with Parkinson′s disease / 中华神经科杂志

Parkinson′s disease (PD) is the second most common neurodegenerative disease following Alzheimer′s disease. The non-motor symptoms of PD have attracted increasing attention. The occurrence of abnormal blood pressure is related to many factors, including aging, PD related autonomic nerve dysfunction, and drugs for PD treatment,including levodopa, dopamine receptor agonists. Abnormal blood pressure severely limits the clinical use of anti-PD drugs. In order to better understand the relationship between anti-PD drugs and blood pressure in patients with PD. This article summarizes the manifestations of abnormal blood pressure, and analyzes the correlation between anti-PD drugs and blood pressure, summarizes the possible mechanisms of how anti-PD drugs affects the blood pressure in PD.

Distonia Responsiva à Levodopa: Síndrome de Segawa ­ Relato de Caso / Dopa-Responsive Dystonia: Segawa disease - Case Report

Iniciada geralmente na infância e adolescência, a doença de Segawa é um tipo de distonia progressiva responsiva à Levodopa causada por uma mutação genética no braço longo do cromossomo 14. Os sintomas pioram ao longo do dia e com o envelhecer, entretanto tornam-se estáveis por volta da quarta década de vida. Descrita em 1971, é uma doença rara e frequentemente subdiagnosticada ou diagnosticada erroneamente. O objetivo deste estudo é descrever a síndrome cuja distonia é o principal sintoma e trazer atenção para o tratamento, que geralmente evidencia-se boa resposta a Levodopa. No presente relato de caso há a história de uma paciente encaminhada a um ambulatório de neurologia, de 20 anos e do sexo feminino, com distonia de membros inferiores e tremor de membros superiores, com piora progressiva dos sintomas desde os 6 anos de idade. O tratamento foi iniciado, havendo boa resposta, porém com necessidade de aumento da dose ao longo dos anos devido à progressão dos sintomas. Portanto, apesar de ser de origem no sistema nervoso central, a remissão dos sintomas é mantida com o tratamento preconizado, trazendo excelente qualidade de vida ao paciente.

With symptoms starting in childhood and teenage years, the Segawa disease is a type of progressive dystonia responsive to levodopa, caused by a genetic change located on the long arm of chromosome 14. The symptoms worsen as the day goes by and as the patient gets older, becoming stable around the fourth decade of life. Initially described in 1971, it is a rare condition and under-diagnosis or misdiagnosis are frequent. The objetive of this study is to describe the syndrome in which dystonia is the main symptom and highlight its treatment, generally showing positive response to levodopa. In the present report, the patient referred to a neurology ambulatory was 20 years old, female, with lower limbs dystonia, as well as tremor affecting upper limbs, and manifestations worsening from 6 years of age. Treatment was started, with good response, even though higher dosages in the subsequent years were necessary due to the progression of symptoms. Thus, besides being originated in the central nervous system, the remission of symptoms is kept with the proposed treatment with excellent quality of life.

Diagnostic prediction model for levodopa-induced dyskinesia in Parkinson's disease / Modelo de predição diagnóstica para discinesias induzidas por levodopa na doença de Parkinson

Abstract Background: There are currently no methods to predict the development of levodopa-induced dyskinesia (LID), a frequent complication of Parkinson's disease (PD) treatment. Clinical predictors and single nucleotide polymorphisms (SNP) have been associated to LID in PD. Objective: To investigate the association of clinical and genetic variables with LID and to develop a diagnostic prediction model for LID in PD. Methods: We studied 430 PD patients using levodopa. The presence of LID was defined as an MDS-UPDRS Part IV score ≥1 on item 4.1. We tested the association between specific clinical variables and seven SNPs and the development of LID, using logistic regression models. Results: Regarding clinical variables, age of PD onset, disease duration, initial motor symptom and use of dopaminergic agonists were associated to LID. Only CC genotype of ADORA2A rs2298383 SNP was associated to LID after adjustment. We developed two diagnostic prediction models with reasonable accuracy, but we suggest that the clinical prediction model be used. This prediction model has an area under the curve of 0.817 (95% confidence interval [95%CI] 0.77‒0.85) and no significant lack of fit (Hosmer-Lemeshow goodness-of-fit test p=0.61). Conclusion: Predicted probability of LID can be estimated with reasonable accuracy using a diagnostic clinical prediction model which combines age of PD onset, disease duration, initial motor symptom and use of dopaminergic agonists.

Resumo Introdução: No momento, não há métodos para se predizer o desenvolvimento de discinesias induzidas por levodopa (DIL), uma frequente complicação do tratamento da doença de Parkinson (DP). Preditores clínicos e polimorfismos de nucleotídeo único (SNP) têm sido associados às DIL na DP. Objetivo: Investigar a associação entre variáveis clínicas e genéticas com as DIL e desenvolver um modelo de predição diagnóstica de DIL na DP. Métodos: Foram avaliados 430 pacientes com DP em uso de levodopa. A presença de DIL foi definida como escore ≥1 no item 4.1 da MDS-UPDRS Parte IV. Nós testamos a associação entre variáveis clínicas específicas e sete SNPs com o desenvolvimento de DIL, usando modelos de regressão logística. Resultados: Em relação às variáveis clínicas, idade de início da doença, duração da doença, sintomas motores iniciais e uso de agonistas dopaminérgicos estiveram associados às DIL. Apenas o genótipo CC do SNP rs2298383 no gene ADORA2A esteve associado com DIL após o ajuste. Nós desenvolvemos dois modelos preditivos diagnósticos com acurácia razoável, mas sugerimos o uso do modelo preditivo clínico. Esse modelo de predição tem uma área sob a curva de 0,817 (intervalo de confiança de 95% [IC95%] 0,77‒0,85) e sem perda significativa de ajuste (teste de qualidade de ajuste de Hosmer-Lemeshow p=0,61). Conclusão: A probabilidade prevista de DIL pode ser estimada, com acurácia razoável, por meio do uso de um modelo preditivo diagnóstico clínico, que combina a idade de início da doença, duração da doença, sintomas motores iniciais e uso de agonistas dopaminérgicos.

Research progress of 6-18F fluoro-L-dopa PET/CT imaging / 中华核医学与分子影像杂志

6-[18F]fluoro-L-dopa (18F-DOPA) is a levodopa analogue.18F-DOPA PET/CT imaging is considered as an ideal tool in the diagnosis and evaluation of Parkinson's disease,brain tumors,pheochromocytoma/paraganglioma,neuroblastoma,gastrointestinal carcinoid,medullary thyroid cancer and congenital hyperinsulinemia.This paper reviews the synthesis,mechanism of localization,imaging procedures,clinical indications and research advances of 18F-DOPA.

Systematic review and screening of basic Chinese herbs for traditional Chinese medicine compounds combined with levodopa medicine in treatment of Parkinson's disease / 中国中药杂志

To systematically evaluate the efficacy of traditional Chinese medicine(TCM) compounds combined with levodopa medicine in the treatment of Parkinson's disease(PD), and screen basic herbs to provide certain evidence-based medical proof and program for better guidance on clinical drug use. Six databases were searched to screen out the randomized controlled trial on the TCM compounds combined with levodopa medicine in the treatment of PD. Literature quality of the included studies was evaluated by improved Jadad rating scale, and the Meta-analysis was performed by RevMan 5.3 software. After the data of the basic TCM compounds involved were sorted out, the strong association rules were found by using Apriori algorithm of SPSS Modeler 18.0 software, and then the basic herbs for the treatment of PD could be picked out. A total of 20 studies were eventually included, involving 1 784 patients. Ten studies were of high-quality literature, Jadad score≥4 points. Meta-analysis showed that efficacy of TCM combined with levodopa medicine was better than levodopa medicine alone in lowering Unified Parkinson's Disease Rating Scale(UPDRS) score: UPDRS Ⅰ(MD=-0.43, 95%CI[-0.62,-0.24], P<0.000 1), UPDRS Ⅱ(MD=-2.72, 95%CI[-3.24,-2.21], P<0.000 01), UPDRS Ⅲ(MD =-1.97, 95%CI[-2.69,-1.25], P<0.000 01), UPDRS Ⅳ(MD=-0.28, 95%CI[-0.46,-0.11], P=0.002). And the improvement in UPDRS score reduction rate of TCM combined with levodopa medicine was better than that in levodopa medicine alone: effective rate(OR=4.81, 95%CI[3.50, 6.62], P<0.000 01). Data mining results showed that the basic prescription for treating PD consisted of Paeoniae Radix Alba-Rehmanniae Radix Praeparata-Gastrodiae Rhizoma in general. According to each part of UPDRS, the basic prescription for treating mentation, behavior and mood(UPDRS Ⅰ) consists of Paeoniae Radix Alba-Rehmanniae Radix Praeparata-Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, Among which Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle might have unique efficacy. The basic prescriptions for treating UPDRS Ⅱ and UPDRS Ⅲ consisted of Paeoniae Radix Alba-Rehmanniae Radix Praeparata, or Chuanxiong Rhizoma-Angelicae Sinensis Radix(two drug combinations). However, in the treatment of UPDRS Ⅳ, the drugs were scattered. But due to the limitations in the quantity and quality of clinical studies, the results obtained still need further research and clinical confirmation of its efficacy.

Effect of daidzein on Parkinson disease induced by reserpine in rats

Parkinson disease is a neurodegenerative disorder characterised by the cardinal symptoms of stiffness, resting tremor, slowness (bradykinesia) and reduction of movement (hypokinesia). Involvement of oxidative damage has been reported in the pathophysiology of Parkinson disease and its related complications. The purpose of this study was to examine the effect of daidzein to quench the free radicals produced as a result of the increased oxidative stress in Parkinson disease.Parkinson disease is induced by administration of reserpine (5 mg/kg/day, i.p) for 5 consecutive days. The symptoms of PD such as tremors, akinesia and rigidity were evaluated. The effect was evaluated by assessing various behavioral parameters (grip strength and locomotor activity), biochemical parameters (lipid peroxidation, and reduced glutathione), as well as histopathological parameters in brain tissue. Daidzein (an antioxidant) was administered at the dose of 50 and 100 mg/kg, p.o. once daily for 5 days. Reserpine significantly causes tremor, rigidity, akinesia and oxidative damage which were reversed by daily administration of daidzein when compared toreserpine group. There was a significant histological improvement in the neuronal degeneration in brain tissue with daidzein. So, the results indicated the protective effect of daidzein against PD.

8-Propyl-6H-[1,3]dioxolo[4,5-g]chromen-6-one: A new coumarin with monoamine oxidase B inhibitory activity and possible anti-parkinsonian effects

Parkinson's disease is a common neurodegenerative disorder. In this study, the monoamine oxidase inhibitory activity and potential anti-parkinsonian effects of 8-propyl-6H-[1,3]dioxolo[4,5-g]chromen-6-one (FCS303), a new synthetic coumarin, were evaluated. To do this, we used the reserpine model of Parkinson's disease, an assay of levodopa/carbidopa potentiation, the catalepsy model of haloperidol, and an in vitro assay against monoamine oxidase (MAO) activity. Additionally, lipid peroxidation and protein carbonyl group quantification was performed in mice brain homogenates previously treated with haloperidol. FCS303 inhibited monoamine oxidase B (MAO-B) with an IC50 of 5.46 ± 0.36 µM; however, there was no effect on monoamine oxidase A (MAO-A). The oral administration of FCS303 led to a significant reversal of hypokinesia in the reserpine model (at 24 h, doses of 100 and 200 mg/kg) and in the levodopa/carbidopa potentiation assay (at 2 and 24 h, dose of 200 mg/kg). In addition, FCS303 (100 mg/kg) showed anti-cataleptic activity against haloperidol. FCS303 (50 mg/kg) significantly decreased lipid peroxidation and protein carbonyl quantification. These results suggest that FCS303 could present anti-parkinsonian activity related to MAO-B inhibitory activity.

Research progress of 6-18Ffluoro-L-dopa PET/CT imaging / 中华核医学与分子影像杂志

6-[18F]fluoro-L-dopa (18F-DOPA) is a levodopa analogue. 18F-DOPA PET/CT imaging is considered as an ideal tool in the diagnosis and evaluation of Parkinson′s disease, brain tumors, pheochromocytoma/paraganglioma, neuroblastoma, gastrointestinal carcinoid, medullary thyroid cancer and congenital hyperinsulinemia. This paper reviews the synthesis, mechanism of localization, imaging procedures, clinical indications and research advances of 18F-DOPA.

Tai Chi versus routine exercise in patients with early- or mild-stage Parkinson's disease: a retrospective cohort analysis

Parkinson's disease cannot be cured but symptoms can be improved by making use of physical therapy. The objective of the study was to compare the effect of routine exercises and Tai Chi on physical and clinical performance in elderly people suffering from Parkinson's disease. Data from interviews, physical and clinical performance, and levodopa consumption of 500 patients with confirmed Parkinson's disease (severity level I to III) were collected and analyzed. Participants who received 80 min/day Tai Chi 3 times/week for 2 months were included in the Tai Chi (TC) group (n=250) and those who received 90 min/day routine exercise 3 times/week for 2 months were included in routine exercise (RE) group (n=250). Timed up-and-go, 50-foot speed walk, and functional reach were improved by Tai Chi and routine exercise (P<0.05 for all) but intensities of Tai Chi for improvement of such parameters was higher than routine exercise. Incidence of falls was decreased by both physical therapies (P<0.05 for all) but more for the TC group (P<0.0001, q=38.512). In the TC group, at the end of follow-up, 22 (9%) patients were successful in withdrawal of levodopa treatment. Also, the dose of levodopa was decreased in patients of the TC group who had to continue levodopa. Tai Chi had the potential to slow down the progression of symptoms of Parkinson's disease and delayed the introduction of levodopa (level of evidence: III).