Role of cardiac β1-adrenergic and A1-adenosine receptors in severe arrhythmias related to Parkinson's disease

Abstract Aims Although reduced life expectancy in Parkinson's Disease (PD) patients has been related to severe cardiac arrhythmias due to autonomic dysfunctions, its molecular mechanisms remain unclear. To investigate the role of cardiac β1-Adrenergic (β1AR) and A1-Adenosine (A1R) receptors in these dysfunctions, the pharmacological effects of stimulation of cardiac β1AR (isoproterenol, ISO), in the absence and presence of cardiac β1AR (atenolol, AT) or A1R (1,3-dipropyl-8-cyclopentyl xanthine, DPCPX) blockade, on the arrhythmias induced by Ischemia/Reperfusion (CIR) in an animal PD model were studied. Methods PD was produced by dopaminergic lesions (confirmed by immunohistochemistry analysis) caused by the injection of 6-hydroxydopamine (6-OHDA, 6 μg) in rat striatum. CIR was produced by a surgical interruption for 10 min followed by reestablishment of blood circulation in the descendent left coronary artery. On the incidence of CIR-Induced Ventricular Arrhythmias (VA), Atrioventricular Block (AVB), and Lethality (LET), evaluated by Electrocardiogram (ECG) analysis, the effects of intravenous treatment with ISO, AT and DPCPX (before CIR) were studied. Results VA, AVB and LET incidences were significantly higher in 6-OHDA (83%, 92%, 100%, respectively) than in control rats (58%, 67% and 67%, respectively). ISO treatment significantly reduced these incidences in 6-OHDA (33%, 33% and 42%, respectively) and control rats (25%, 25%, 33%, respectively), indicating that stimulation of cardiac β1AR induced cardioprotection. This response was prevented by pretreatment with AT and DPCPX, confirming the involvement of cardiac β1AR and A1R. Conclusion Pharmacological modulation of cardiac β1AR and A1R could be a potential therapeutic strategy to reduce severe arrhythmias and increase life expectancy in PD patients.

Correlation analysis of mental resilience and quality of life in patients with Parkinson's disease / 中国实用护理杂志

Objective:To investigate the relationship between mental resilience and quality of life in patients with Parkinson ′s disease and provide basis for paying attention to the mental health of this group. Methods:A total of 190 in patients with Parkinson ′s disease (PD) were selected from April to July 2017 in the First Affiliated Hospital of Dalian Medical University. The general data questionnaire, Mental Resilience Scale and 39-Item Quality of Life (QOL) Questionnaires were used to investigate among the patients. Results:The mental resilience score of PD patients was 48.0 (29.8, 62.2) points and the quality of life score was 56.0 (27.8, 82.0) points. There was a significant negative correlation between mental resilience and quality of life score ( r value was -0.538, P<0.01). Multivariate linear regression analysis showed that with the increase of psychological elasticity score, the score of quality of life decreased ( b value was -0.002, P<0.001). Conclusions:The mental resilience and quality of life of PD patients are both at a low level, the improvement of mental resilience is beneficial to improve their quality of life.

Acortamiento de telómeros en enfermedades neurodegenerativas: implicaciones terapéuticas / Telomere attrition in neurodegenerative disorders: therapeutic implications

Introducción: Varias enfermedades neurodegenerativas están asociadas a la ocurrencia de acortamiento de los telómeros, y los convierten en biomarcadores y dianas terapéuticas potenciales. Objetivo: Reflejar la relevancia del acortamiento de los telómeros para enfermedades neurodegenerativas, y destacar sus implicaciones Material y métodos: Se realizó una revisión bibliográfica durante los meses de septiembre de 2019 a enero de 2020. Fueron consultadas bases de datos de referencia, con el uso de descriptores y operadores booleanos. La estrategia de búsqueda avanzada para la selección de los artículos fue empleada, teniendo en cuenta la calidad metodológica o validez de los estudios. Desarrollo: Fueron identificadas evidencias sólidas de asociación entre el acortamiento de los telómeros y las enfermedades de Alzheimer y Huntington, que sugieren un papel relevante de la biología de los telómeros en la fisiopatología de estas enfermedades. Las evidencias disponibles hasta el momento no permiten establecer la relevancia de la biología de los telómeros en la fisiopatología de la Enfermedad de Parkinson o de la esclerosis lateral amiotrófica. Se obtuvieron evidencias de la utilidad de terapias orientadas a la prevención del acortamiento de los telómeros para el tratamiento de enfermedades neurodegenerativas. Conclusiones: El acortamiento de los telómeros es de relevancia fisiopatológica y clínica para las enfermedades de Alzheimer y Huntington, mientras que existen evidencias insuficientes para establecer su importancia en la Enfermedad de Parkinson y la esclerosis lateral amiotrófica. El uso de estrategias para estimular la actividad de la telomerasa tiene potenciales aplicaciones terapéuticas en el contexto de enfermedades neurodegenerativas(AU)

Introduction: Several neurodegenerative disorders are associated with telomere attrition, turning telomeres into potential biomarkers and potential therapeutic targets. Objective: To assess the relevance of telomere attrition for neurodegenerative disorders, highlighting its therapeutic implications. Material and methods: A literature review was carried out from September 2019 to January 2020. Several databases were searched by using descriptors and Boolean operators. Advanced search strategy was used for the selection of articles, taking into account the methodological quality and validity of the studies. Results: Strong evidence for an association between telomere attrition and Alzheimer and Huntington diseases was obtained, suggesting a potential importance of telomere biology in the physiopathology of these diseases. Current evidence does not allow establishing the relevance of telomere attrition in the physiopathology of Parkinson´s disease or Amyotrophic Lateral Sclerosis. Evidence was obtained for the usefulness of therapies for the prevention of telomere attrition in the treatment of neurodegenerative disorders. Conclusions: Telomere attrition has physiopathological and clinical relevance in Alzheimer´s and Huntington´s diseases, though current evidence is not enough to establish its role in Parkinson's disease and Amyotrophic Lateral Sclerosis. Strategies that enhance telomerase activity have therapeutic potential in the context of neurodegenerative disorders(AU)

Malnutrition and Associated Motor and Non-motor Factors in People with Parkinson's Disease

Background: People with Parkinson’s disease (PwP) are at higher risk of developing malnutrition. Several factors have been suggested to be involved including motor symptoms, non-motor symptoms, and treatment-related complications. Objective: The objective of the study was to analyze the combined effect of motor, non-motor, and pharmacological factors in the risk of malnutrition in PwP. Methods: Eighty-seven consecutive PwP were included in the study. Clinical data and pharmacological treatment were collected. Nutritional status was assessed using the Mini-Nutritional Assessment (MNA) questionnaire. Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Non-motor Symptoms Scale (NMSS), Hamilton Depression Rating Scale HAM-D, and Montreal Cognitive Assessment were applied. Results: Thirty (34.4%) PwP were at risk of malnutrition and seven had malnutrition (8%). Abnormal nutritional status was associated with lower education, higher MDS-UPDRS Parts I, II, and III and total scores, and higher scores in the NMSS domain of sleep disorders and fatigue. MDS-UPDRS motor score remained as a determinant of abnormal nutritional status, defined as MNA <23.5, with an odds ratio 1.1 (95% confidence interval 1.01-1.10, p = 0.02). Conclusion: The main factor associated with nutritional status was severity of the motor symptoms as assessed by the MDS-UPDRS Part III. Non-motor symptoms and treatment-related complications were not associated with malnutrition. (REV INVEST CLIN. 2020;72(5):293-9)

Role of sirt3 in molecular mechanism of melatonin protecting dopaminergic neurons in Parkinson' s disease / 中国药理学通报

Aim To investigate the role of SIRT3 in the molecular mechanism of melatonin protecting do-paminergic neurons in Parkinson' s disease ( PD). Methods Forty-eight mice were randomly divided into control group, model group and treatment group. The mice in treatment group received intraperitoneal injection of melatonin (10 mg • kg"1) and MPTP (30 mg • kg ~1). The mice in model group only received intraperitoneal injection of MPTP (30 mg • kg~1 ) , and the mice in control group received the same a-mount of normal saline. Melatonin was administered continuously for 14 days. The expressions of TH and lba-1 in substantia nigra were analyzed by immunohis-tochemistry. The levels of oxidative stress ( ROS, MDA, SOD) and inflammatory factors (TNF-a, IL-lp) in the midbrain were measured by ELISA. SIRT3 mRNA level was analyzed by qRT-PCR, and protein expression level was detected by immunocytochemistry assay and Western blot. Results Compared to control group, the TH expression decreased and Iba-1 expression increased in the substantia nigra, the oxidative stress and inflammatory injury in the midbrain were significantly enhanced, the SIRT3 mRNA and protein levels in the substantia nigra obviously declined, the SOD2 protein expression was also dramatically reduced, and the iNOS protein expression was elevated in model group; the differences between the groups were all statistically significant ( P < 0. 05 ). After treatment with melatonin, the TH expression increased, Iba-1 expression decreased, oxidative stress and inflammatory injury markedly decreased, SIRT3 mRNA and protein levels were elevated, SOD2 protein expression was up-regulated, and iNOS protein expression was down-regulated in treatment group. Compared to model group, the differences were all statistically significant ( P < 0.05). Conclusions Melatonin can counteract the damage of dopaminergic neurons by up-regulating the expression of SIRT3 in PD animal model. Its mechanisms of action are related to inhibiting microglia activation, and alleviating oxidative stress and inflammation injury.

Toxina botulínica para tratamento da sialorreia nos pacientes com doença de Parkinson / Botulinum toxin for treatment of sialorrhea in patients with Parkinson's disease

A sialorreia/ptialismo é um sintoma não motor frequente da doença de Parkinson, que pode causar impacto na saúde e na qualidade de vida dos pacientes. O sintoma decorre da combinação da disfagia com disautonomia e, muitas vezes, também do efeito adverso de drogas frequentemente utilizadas no tratamento de sintomas da doença, como por exemplo, os antipsicóticos atípicos e os inibidores da acetilcolinesterase. Diversas opções terapêuticas são utilizadas na prática clínica para controle da sialorreia, dentre elas, drogas anticolinérgicas ou antagonistas dos receptores adrenérgicos, injeção de toxina botulínica, cirurgia, radioterapia e terapias comportamentais e fonoaudiológicas. Este trabalho faz uma revisão das propostas terapêuticas até o presente momento para controlar a secreção de saliva dos pacientes com doença de Parkinson. A injeção de toxina botulínica nas glândulas salivares guiada por ultrassom é a opção com mais evidência de eficácia e segurança, de acordo com os últimos estudos.

Sialorrhea is a frequent nonmotor symptom in Parkinson´s disease (PD) that influences the patients' health and quality of life. The symptom arises from a combination of difficulty in swallowing saliva, autonomic dysfunction or as a side effect of frequent used drugs to control symptoms of the disease, as for example, atypical antipsychotics and acetylcholinesterase inhibitors. In clinical practice, different therapeutic approaches are used to control sialorrhea, such as anticholinergic or beta adrenergic antagonistic drugs, botulinum toxin injection, surgery, radiotherapy, behavioral psychotherapy and speech therapy. This paper reviews the therapeutic options available until now to control the loss of saliva from PD patient. Botulinum toxin injection in the salivary glands guided by ultrasound shows the best efficacy and security profile, according to the last published data.

Ritmo samba como estimulação auditiva rítmica e desempenho da marcha na doença de Parkinson / Samba rhythm for rhy thmic hearing stimulation and gait performance in Parkinson´s disease

A estimulação auditiva rítmica tem sido utilizada para amenizar as disfunções motoras na doença de Parkinson, no entanto não são evidentes as alterações que a música popular brasileira causa nos parâmetros espaço-temporais e desempenho funcional da marcha. O objetivo do estudo foi analisar o gênero musical samba durante a marcha de pacientes com doença de Parkinson em situações de dupla tarefa. Estudo de caráter transversal, descritivo e exploratório; cinco indivíduos atenderam aos critérios propostos e realizaram o Timed Up and Go Test nas situações sem música e música popular brasileira (samba) sensibilizadas com tarefas cognitivas e motoras para análise da marcha. Análise estatística descritiva e inferencial com teste de Fridman e post-hoc de Wilcoxon pareado (nível de significância de 5%). Evidenciou-se que o samba associado a uma tarefa motora reduziu a velocidade (p=0,01) e o comprimento de passos (p=0,04) quando comparados à condição de teste sem música. Ouvir música proporcionou maiores demandas atencionais, resultando na adoção de estratégias para diminuir as exigências de equilíbrio postural como a redução do comprimento do passo e velocidade e desta forma diminuir o risco de quedas em situações de duplas tarefas enquanto escuta música.

Rhythmic hearing stimuli have been employed to attenuate motor dysfunctions in Parkinson´s disease. However, changes that may be caused in space-time parameters and functional performance of gait brought about by Brazilian popular music are not always evident. Current analysis deals with the musical genre samba during gait of patients suffering from Parkinson´s disease in a twotask situation. Current transversal, descriptive and exploratory study comprised five agents who fulfilled criteria and undertook the Timed Up and Go Test in situations without music and with Brazilian popular music (samba) through cognitive and motor tasks for gait analysis. Descriptive and inferential statistical analysis with Friedman´s test and with paired Wilcoxon post-hoc test (at 5% significance) evidenced that samba associated with a motor task reduced the speed (p=0.01) and gait length (p=0.04) when compared to test conditions without any music. Listening to music demanded more attention and resulted in the use of strategies to decrease demands of posture balance, such as reduction in gait length and speed. Decrease in falling risks in a twotask situation while listening to music may occur.

Impacto da estimulação cerebral profunda na qualidade de vida e humor em pacientes com doença de Parkinson / Impact of deep brain stimulation on quality of life and mood in patients with Parkinson's disease

A doença de Parkinson (DP) é uma doença neurodegenerativa deri¬vada de uma redução da produção de dopamina. O seu tratamento é basicamente por medidas farmacológicas. No entanto, nos está¬dios avançados da doença, especialmente devido às flutuações do motor, o tratamento farmacológico por si só não é completamente bem-sucedido. Assim, surge a possibilidade de benefícios ao pacien¬te pela técnica de estimulação cerebral profunda (DBS). O objetivo deste estudo foi analisar o impacto do DBS palidal ou subtalâmica sobre a qualidade de vida desses pacientes (QoL). Para tanto, em¬pregaram-se duas escalas, comparando os resultados pré e pós-ope¬ratórios: o Inventário de Depressão de Beck - BDI (avalia o aspecto emocional dos pacientes) e o PDQ-39 (avalia os aspectos motores e as relações sociais). Podemos observar que a avaliação do BDI apon¬tou para uma melhora média de 9,5% e os escores do PDQ-39 me¬lhoraram 10,28%. Há evidências que pacientes submetidos à técnica de DBS subalâmicos ou paliativos mostraram uma QoL de melhoria importante, assim, o DBS surge como um adjuvante na luta contra a doença de Parkinson. (AU)

Parkinson's disease (PD) is a neurodegenerative disorder derived from a reduction of dopamine production. The treatment of PD is basically by pharmacological measures. However, in the advanced stages of the disease, especially due to motor fluctuations, phar¬macological treatment by itself is not completely successful. At that moment, the possibility of the patient´s benefits by the technique of deep brain stimulation (DBS) comes up. The aim of this study was to analyze the impact of pallidal or subthalamic DBS on PD patients' quality of life (QoL). To do so, two scales were employed, comparing the pre and post-operative results: Beck Depression Inventory - BDI (evaluates the patients' emotional aspect) and PDQ-39 (evaluates mo¬tor aspects and social relations). We could observe that BDI evalua¬tion pointed to an average improvement of 9.5% and PDQ-39 scores improved 10.28%. We can conclude that patients who have undergo¬ne the technique of subthalamic or pallidal DBS showed an important improvement QoL. DBS comes up as an adjuvant in the fight against Parkinson's disease. (AU)

The protective effects of cordycepin on MPTP-induced dopaminergic neuron damage in mice and its mechanism / 中国药理学通报

Aim To observe the protective effects of cordycepin ( Cor) on dopaminergic neurons in 1-meth-yl-4-phenyl-1 , 2 , 3 , 6-tetrahydropyridine ( MPTP )-in-duced mouse model of Parkinson's disease ( PD) and to explore its mechanism. Methods C57BL/6 mice were administered with MPTP to establish the PD mod-el. Mice in Cor groups were pretreated with Cor (2.5,5.0 and 10.0 mg·kg-1 ) by intragastric administra-tion, respectively. The motor functions of the mice were observed in the open-field test, rotarod test and pole test. The content of DA, the numbers of TH-im-munoreactive cells and apoptotic cells were measured respectively by HPLC-ECD, immunohistochemistry staining and TUNEL staining. The expression of apop-tosis related proteins and MAPK signaling pathway-re-lated proteins ( p38 , p-p38 , ERK1/2 , p-ERK1/2 JNK1/2 and p-JNK1/2 ) were determined by Western blot. Results Cor could significantly improve the mo-tor dysfunction in PD mice. The contents of DA, DOPAC and HVA in the striatum remarkably increased after administration of Cor in MPTP-induced mice. Mo-reover, Cor could obviously reduce both the loss of TH-immunoreactive neurons and the numbers of TUNEL-positive cells in substantia nigra pars compacta ( SNpc) of PD mice. The protein expressions of Bax and cleaved caspase-3 were markedly down-regulated,whereas those of Bcl-2 and the ration of Bcl-2/Bax were significantly up-regulated by Cor pre-treatment followed by MPTP treatment. Furthermore, the protein expressions of p-p38 , p-ERK1/2 and p-JNK1/2 signif-icantly decreased in substantia nigra in Cor groups. Conclusions The results suggest that Cor can protect DA neurons against MPTP-induced injury by inhibiting apoptosis, which may be closely relevant to the inhibi-tion of MAPK signaling pathways.

Research progress on animal models of Parkinson's disease / 中国比较医学杂志

Parkinson's disease(PD)is a progressive neurodegenerative disorder, with an etiology that is now considered to be due to interaction between genetic and environmental factors. Typical PD features include loss of dopaminergic neurons in the nigrostriatal region, with typical motor traits of PD associated with dopamine deficiency. Animal models have contributed to determining PD etiology and pathogenesis,as well as testing new therapeutic schedules and novel drug research. Rodents, tree shrews, primates, and other animal models of PD have been established by different method. These models each have their own advantages and limitations, showing different clinical features and pathological mechanisms to those in humans. Therefore, the appropriate model for scientific research must be carefully considered. This article reviews the main neurotoxic and transgenic models of PD.

Novedoso profármaco derivado de la lilolidina con actividad dopaminérgica central / Novel prodrug derivative from lilolidine with central dopaminergic activity

La desregulación de la neurotransmisión dopaminérgica central ha sido relacionada con enfermedades neurodegenerativas, tales como la enfermedad de Parkinson y la Corea de Huntington. En las últimas décadas son muchos los compuestos con actividad dopaminérgica central que se han diseñado, sintetizado y evaluado farmacológicamente y, a pesar de estos esfuerzos, no se ha logrado obtener un fármaco efectivo capaz de mejorar o curar estas patologías. Con el fin de contribuir en esta búsqueda primordial, en el presente trabajo se describe el diseño, la síntesis y la evaluación farmacológica del derivado de la lilolidina, clorhidrato de 6-(2-aminoindanil)-N-(2,4,5,6-tetrahidro-1H-pirrolo[3,2,1-ij]quinolina) 4 (MAIL), con el propósito de restablecer la homeostasis de la transmisión dopaminérgica en la enfermedad de Parkinson y/o la Corea de Huntington. Para ello, se utilizaron las diferentes estrategias nigroesclásicas y heterocíclicas enmarcadas en la síntesis orgánica a través de una ruta convergente. Asimismo, se realizó la evaluación farmacológica preliminar, al determinar el comportamiento estereotipado en ratas Sprague-Dawley cuando les fue administrado el derivado de la lilolidina, por las vías ICV (intracerebroventricular) e IE (intraestriatal). Los resultados obtenidos del compuesto 4 mostraron una acción central como agonista, a través de mecanismos dopaminérgicos.

Central dopaminergic neurotransmission deregulation has been related with neurodegenerative sicknesses, like Parkinson’s disease and Huntington’s Chorea. During the last decades, many compounds with dopaminergic activity have been designed, synthesized and pharmacologically evaluated, but despite all these efforts, an effective drug able to improve or cure these pathologies has not been achieved. With the purpose to contribute in this essential search, this work describes the design, synthesis and pharmacological evaluation of the lilolidine derivative, 6-(2-aminoindanyl)-N-(2,4,5,6-tetrahydro-1H-pyrrolo[3,2,1-ij]quinoline hydrochloride) 4 (MAIL), with the purpose of restoring the homeostasis of dopaminergic transmission in Parkinson’s disease and/or Huntington’s Chorea. To perform that, different organic synthesis classic and heterocyclic strategies were employed through a convergent route. Also, a preliminar pharmacological evaluation was done, where the stereotyped behavior of Sprague-Dawley rats was studied after the ICV (intracerebroventricular) and IE (intrastriatum) administration of the lilodine derivative. The results obtained of compound 4 showed a central dopaminergic agonist activity through dopaminergic mechanisms.

Síntomas no motores en pacientes con enfermedad de Parkinson / Non motor symptoms in patients with Parkinson´s disease

Se realizó un estudio prospectivo de 44 pacientes con enfermedad de Parkinson, atendidos en la consulta de Trastornos del Movimiento del Hospital Provincial Docente Clinicoquirúrgico Saturnino Lora Torres de Santiago de Cuba, desde agosto de 2013 hasta julio de 2015, con vistas a determinar la frecuencia de aparición de síntomas no motores. Entre los más frecuentes figuraron los siguientes: depresión (72,7 por ciento), nicturia (68,2 por ciento), ansiedad (54,6 por ciento), síndrome de piernas inquietas (50,0 por ciento), estreñimiento (47,7 por ciento) e insomnio (40,9 por ciento), por citar algunos. Cabe destacar que 95,5 por ciento de los afectados presentó algún síntoma y el promedio por paciente fue de 7,45, con menor aparición durante el primer año de la enfermedad

A prospective study of 44 patients with Parkinson´s disease assisted in the service for movement disorders of Saturnino Lora Torres Teaching Clinical Surgical Provincial Hospital in Santiago de Cuba, was carried out from August, 2013 to July, 2015, aimed at determining the emergence frequency of non motors symptoms. Among the most frequent symptoms there were: depression (72.7 percent), nicturia (68.2 percent), anxiety (54.6 percent), restless legs syndrome (50.0 percent), constipation (47.7 percent) and insomnia (40.9 percent), just to mention some of them. It is necessary to highlight that 95.5 percent of the affected patients presented some symptom and the average for patient was 7.45, with less emergence during the first year of the disease

Estimulación de la médula espinal: una nueva estrategia terapéutica para restaurar la función motora / Spinal cord stimulation: a new therapeutic strategy to restore motor function

La estimulación de la Médula Espinal (EME) es una técnica de neuromodulación que ha mostrado ser efectiva en el manejo de los trastornos motores propios de enfermedades tan devastadoras como la Enfermedad de Parkinson (EP) y las lesiones de la médula espinal. Considerando que ambas patologías cuentan con opciones terapéuticas limitadas, la EME se podría posicionar como una técnica prometedora. Los mecanismos por los cuales operaría la estimulación difieren en ambos casos, generando cambios en la circuitería espinal local en el caso de las lesiones medulares, y cambios supraespinales, en el caso de la EP. En esta revisión se busca analizar los efectos de la EME en ambas enfermedades, tanto en modelos animales como en pacientes, hacer una breve descripción de los mecanismos y aludir a los desafíos futuros propuestos para ambos casos. (AU)

Spinal cord stimulation (SCS) is a neurophysiological technique that has shown to be effective in modulating motor dysfunction associated with devastating diseases such as: Parkinson's disease (PD) and spinal cord injuries. Considering that both pathologies have limited treatment options, SCS could be considered as a potential useful technique. The mechanism by which stimulation operates differs in both cases, generating changes in local circuits in the case of spinal cord injuries and supraspinal changes in PD. This review aims to analyze the effects of EES on both diseases, focusing in the results observed in animal models and patients, give a brief description of the mechanisms behind and postulate the future challenges proposed for SCS in both pathologies.(AU)

Rational Drug Use Analysis of Parkinson's Disease with the First Time Attack of Epilepsy / 中国药师

Objective:To bring to doctors' attention to the first time attack of epilepsy in the patients with Parkinson' s disease, enhance the rational drug use and reduce the occurrence of adverse reactions in clinics. Methods: A Parkinson patient with the first time attack of epilepsy was synthetically analyzed on the mechanism of disease, therapy regimen and pharmaceutical care. Results:It was difficult to distinguish the symptom of epilepsy during the treatment of Parkinson' s disease from that of L-dopa induced dyskinesia, therefore, the suitable treatment was difficult to perform. Moreover, antiepileptic drug valproic acid could aggravate Parkinson syn-drome imperceptibly, which was easy to be ignored in clinics. Conclusion:L-dopa induced dyskinesia should try to avoid during the treatment of Parkinson, and should distinguish from the first time attack of epilepsy in order to choose proper antiepileptic drugs.

Effect of TRPC6 knock-out on the mouse neuroinflammation induced by MPTP / 中国比较医学杂志

Objective To measure the level of microglia TRPC6 in mouse MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced neuroinflammation model and investigate its role in cytokine production and dopaminergic neuron damages. Methods Microglia were sorted by magnetic beads labeled with CD11b antibody and the level of TRPC6 in MPTP-induced neuroinflammation models was measured by western blotting. The proliferation of microglia and damages of dopaminergic neurons induced by MPTP were analyzed by immunofluorescence in CD11b-TRPC6 -/ - mice. Meanwhile, the expression of cryαB and cytokines in microglia was measured by western blotting and real-time quantitative PCR, respectively. Results The level of microglia TRPC6 in MPTP-induced neuroinflammation model was up-regulated. The expression of cryαB was increased and the cytokine level was down-regulated in the microglia in MPTP-injected CD11b-TRPC6 -/ - mice. Moreover, the dopaminergic neuron survival was improved in the MPTP-induced neuroinflammation model after TRPC6 knock-out in the microglia. Conclusions The expression of TRPC6 in microglia is up-regulated after MPTP injection, while in CD11b-TRPC6 -/ - mice the MPTP-induced cytokine expression is reduced, contributing to the improvement of dopaminergic neuron survival.

Determination of salsolinol N-methyltransferase activity in 6-OHDA-lesioned rats / 中国比较医学杂志

Objective The aim of this study was to establish a rat model of Parkinson''s disease ( PD) by using 6-hydroxydopamine (6-OHDA) and detect the salsolinol N-methyltransferase ( SNMT) activity in peripheral lymphocytes of PD rats for the development of a biomarker for early diagnosis of PD. Methods Rat model of PD was established by unilateral double-pointed injection of 6-OHDA into the striatum and was verified by behavior observation. An analytical method was developed based on multiple reaction monitoring with HPLC-ESI-QQQ to determine the SNMT activity in peripheral lymphocytes. Results Seven of 18 rats injected with 6-OHDA showed steadily apomorphine-induced rotation ( >7 r/min) . The success rate was 38. 9%. A sensitive and stable quantitative method with internal standard added was created, based on multiple reaction monitoring mode to analyze SNMT activity. The limit of detection ( LOD) and limit of quantitation ( LQD) of N-methyl-salsolinol, which is the product of Salsolinol catalyzed by SNMT, were 49 pmol/L and 98 pmol/L, respectively. The precisions of intra-day and inter-day assays both were below 6. 0%. SNMT activity of peripheral lymphocytes in the 6-OHDA-lesioned rats was significantly increased [43. 37 ±9. 49 pmol/(h·mg)NMSal] in comparison with that in the normal group [2. 16 ±5. 82 pmol/(h·mg)NMSal] and the sham-operated group [0. 58 ±2. 32 pmol/(h· mg)NMSal](P< 0. 01, n=5). There was no significant difference between the normal group and sham-operated group (P< 0. 05, n =5). Conclusions Our results indicate that SNMT activity may reflect the changes in the course of Parkison''s disease and may become a potential clinical biomarker in diagnosis of this disease.

Clinical Research Progress in Traditional Chinese Medicines Combined with Dopa Preparations in the Treatment of Parkinson' s Disease / 中国药师

Dopa preparations are currently first choice for the clinical treatment of Parkinson' s disease. With the application time extension and the dose increase of dopa preparations, the therapeutic effect is smaller and smaller, while the side effects are more and more significant, which have become the main problems affecting their clinical application. The current researches showed that the combination of traditional Chinese medicines and dopa preparations can improve the efficacy, decrease the dose of western medicines, reduce the adverse effects and so on. The paper reviewed the progress in the combination of dopa preparations and traditional Chinese medicines in the treatment of Parkinson' s disease in recent ten years.

Pimavanserin:a New Drug for the Treatment of Psychosis Associated with Parkinson' s Disease / 中国药师

Pimavanserin is a selective 5-HT2A receptor inverse agonist approved by FDA on April 29, 2016, and it is the first drug for the treatment of hallucinations and delusions associated with Parkinson' s disease. Pimavanserin is with high safety, good toleration and promising clinical efficiency, which is a timely option to resolve the drug shortage in clinic treatment. This paper summarized its pharmacodynamics, pharmacokinetics, clinical studies, adverse reactions and drug interactions.

A realidade virtual por meio do tapete de videodança melhora a marcha de pacientes com doença de Parkinson / Virtual reality for video dance pad means better patient running with Parkinson disease

Intervenções com realidade virtual apresentam efeitos positivos em várias habilidades físicas em pacientes com doença de Parkinson (DP). O objetivo foi verificar a efetividade do treinamento de curto prazo baseado em realidade virtual por um tapete de videodança no desempenho da marcha em pacientes com doença de Parkinson. Foram avaliados quatro pacientes pela Escala Hoehn e Yahr, Escala Unificada de Avaliação da Doença de Parkinson (UPDRS), Miniexa-me do Estado Mental, Avaliação Cognitiva Montreal, Escala de Berg e Escala de Atividade de Parkinson. Para avaliar o treinamento, foi realizado o teste de caminhada dos 10 metros antes (A1), após 1 hora de repouso (A2) e após o treino (A3) em seis situações diferentes. Realizou-se intervenção com o tapete de videodança, com uma sessão única de 1 hora. Análise estatística: ANOVA de medidas repetidas, post-hoc de Tukey, para análise das variáveis espaçotemporais da marcha nos três momentos de avaliação e teste de McNemar para investigar diferenças na proporção de acertos nos dois alvos ao longo do trajeto (nível de significância 5%). Resultados evidenciaram redução do tempo para percorrer o trajeto e aumento da cadência na A3 em relação às avaliações iniciais (p < 0,05). Redução do número de erros de colocação do pé no alvo na A3 (p < 0,05). A intervenção foi efetiva principalmente em reduzir o tempo para percorrer o per-curso e corrigir erros de colocação do pé no alvo.

The aim was to verify the effectiveness of short-term training based on virtual reality by video-dance carpetin gait performance in patients with Parkinson's disease (PD). Evaluated four patients with idiopathic PD assessed by Hoehn and Yahr scale, Unified Parkinson's Disease Rating Scale (UPDRS), Mini-Mental Status Examination, Cognitive Assessment Montreal, Berg Scale and Parkinson's Activity Scale. To check the effect of the training, patients held the 10 metres walk test before (A1), after resting one hour (A2) and after training (A3) in six different situations. Held with  the  video-dance mat, with a single session of 1 hour. Statistics analysis: ANOVA for repeated measures and post-hoc Tukey to analyse the spatio-temporal parameters of the gait in three moments of evaluation and for McNemar's test to investigate differences in the proportion of hits in two targets arranged along the path (significance level 5%). Results showed reduction of time to traverse, increase of cadence in A3, regarding to initial assessments (p < 0.05). There has been a reduction in the number of mistakes of placing the foot on target at A3 (p < 0.05). The proposed intervention was effective primarily in reducing the time to traverse the route and correct mistakes of placing the foot on the target.