Associação entre a capacidade funcional, transtorno do sono e nível de atividade física em indivíduos com doença de Parkinson durante o período de pandemia de covid-19: um estudo transversal / Association between functional capacity, sleep disorder and physical activity level in individuals with Parkinson's disease during the covid-19 pandemic period: a cross-sectional study

Resumo Objetivo Avaliar o nível de atividade física, considerando as condições sociodemográficas, clínicas e funcionais, de pessoas idosas com Doença de Parkinson (DP). Método Foi realizado um estudo transversal a partir dos seguintes dados: nível de atividade física (International Physical Activity Questionnaire versão curta - IPAQ curto), transtornos do sono, queixa cognitiva, tempo de doença, grau de dependência para realizar atividades básicas do dia a dia pela escala Schwab & England (S & E) de indivíduos idosos com DP atendidos em um serviço de saúde terciário, durante a pandemia da covid-19. Regressão de Poisson, teste U de Mann-Whitney e teste t de Student foram utilizados para análise estatística. Resultados A cada 10 pontos de elevação na escala de S & E, a razão de prevalência de ser ativo foi maior em 1,04 (IC 95% 1,01 - 1,08) e quem não referiu transtorno de sono teve razão de prevalência de 1,17 (IC95% 1,02-1,34) vez maior de ser ativo. Indivíduos com DP inativos eram mais velhos e tinham maior tempo de doença. Conclusão Ênfase deve ser dada a capacidade funcional e ao sono de indivíduos com DP para o manejo adequado do nível de AF em períodos de restrição social.

Abstract Objective To assess the level of exercise of older people with Parkinson's disease (PD), taking into account sociodemographic, clinical, and functional characteristics. Method A cross-sectional study was carried out based on the following data: level of physical activity (International Physical Activity Questionnaire short version - short IPAQ), sleep disorders, cognitive complaints, duration of illness, degree of dependence to perform basic daily activities through Schwab & England (S&E) scale of older individuals with PD treated at a tertiary health service during the covid-19 pandemic. Poisson regression, Mann-Whitney U test and Student's t test were used for statistical analysis. Results The prevalence ratio of being active increased by 1.04 (95% CI 1.01 - 1.08) for every 10 points of elevation on the S&E scale, whereas those who did not report sleep difficulties had a prevalence ratio of 1.17 (95% CI 1.02-1.34) times greater to be active. Inactive individuals with PD were older and had longer disease duration. Conclusion Emphasis should be given to the functional capacity and sleep of individuals with PD for the adequate management of the PA level in periods of social restriction.

Apomorphine in the treatment of Parkinson's disease: a review / O uso da apomorfina no tratamento da doença de Parkinson: revisão da literatura

ABSTRACT Optimizing idiopathic Parkinson's disease treatment is a challenging, multifaceted and continuous process with direct impact on patients' quality of life. The basic tenet of this task entails tailored therapy, allowing for optimal motor function with the fewest adverse effects. Apomorphine, a dopamine agonist used as rescue therapy for patients with motor fluctuations, with potential positive effects on nonmotor symptoms, is the only antiparkinsonian agent whose capacity to control motor symptoms is comparable to that of levodopa. Subcutaneous administration, either as an intermittent injection or as continuous infusion, appears to be the most effective and tolerable route. This review summarizes the historical background, structure, mechanism of action, indications, contraindications and side effects, compares apomorphine infusion therapy with other treatments, such as oral therapy, deep brain stimulation and continuous enteral infusion of levodopa/carbidopa gel, and gives practical instructions on how to initiate treatment.

RESUMO A optimização do tratamento da doença de Parkinson idiopática se faz um desafio, pois tem impacto direto na qualidade de vida do paciente. O melhor esquema terapêutico é o que permite o melhor controle motor com os menores efeitos adversos, através de terapêutica individualizada. A apomorfina é o único medicamento antiparkinsoniano que pode ser comparável à potência da levodopa no controle dos sintomas motores. Trata-se de um agonista dopaminérgico empregado na terapia de resgate em pacientes com flutuações motoras e também contribui para a melhora de muitos sintomas não motores. A via subcutânea, com injeções intermitentes, ou com infusão contínua, parece ser a melhor opção pela eficácia e tolerabilidade. Essa revisão resume aspectos históricos, estrutura da molécula, mecanismo de ação, indicação, contra-indicação e efeitos colaterais, compara a terapia de infusão com apomorfina com outros tratamentos, como a terapia oral, estimulação cerebral profunda e infusão enteral contínua de levodopa/carbidopa gel, e fornece instruções práticas de como iniciar o tratamento.

Non-motor symptoms in Parkinson′s disease patients with different motor types / 中华全科医师杂志

One hundred ten patients with Parkinson′s disease(PD)and 110 age-matched healthy controls were enrolled in the study.The non-motor symptoms(NMS)were assessed with Non-motor symptoms of Parkinson′s disease questionnaire(PDNMSQ30).The PD patients were classified as gait abnormality posture type(PIGD, n=73)and tremor type(TD, n=37).The non-motor symptoms were compared between two groups.Results showed that the NMS in PD patients was higher than that in healthy controls[(35.2 ±3.0)vs.(6.0 ±2.0)symptoms, t=6.43, P=0.01].The NMS score of PIGD group was higher than that of TD group[(28.9 ±1.1)vs.(6.2 ±0.7)symptoms, t=2.73, P<0.01]; Mini-mental state examination(MMSE)and Montreal cognitive assessment scale(MoCA)scores of TD group were significantly higher than those of PIGD group(t=11.52,P<0.01; t=8.79,P<0.01).The results indicate that for PD patients with different motor types,their NMS are different,and PD patients with PIGD have more axial involvement,and more NMS.

Initial circulatory response to active standing in Parkinson's disease without typical orthostatic hypotension / Resposta circulatoria inicial apos ortostatismo ativo na doenca de Parkinson sem hipotensao ortostatica tipica

While the circulatory response to orthostatic stress has been already evaluated in Parkinson's disease patients without typical orthostatic hypotension (PD-TOH), there is an initial response to the upright position which is uniquely associated with active standing (AS). We sought to assess this response and to compare it to that seen in young healthy controls (YHC). Method In 10 PD-TOH patients (8 males, 60±7 years, Hoehn and Yahr ≤3) the changes in systolic blood pressure (SBP) and heart rate that occur in the first 30 seconds (sec) of standing were examined. Both parameters were non-invasively and continuously monitored using the volume-clamp method by Peñáz and the Physiocal criteria by Wesseling. The choice of sample points was prompted by the results of previous studies. These sample points were compared to those of 10 YHC (8 males, 32±8 years). Results The main finding of the present investigation was an increased time between the AS onset and SBP overshoot in PD-TOH group (24±4 vs. 19±3 sec; p<0.05). Conclusion This delay might reflect a prolonged latency in the baroreflex-mediated vascular resistance response, but more studies are needed to confirm this preliminary hypothesis. .

Apesar da resposta circulatória ao estresse ortostático já foi estudada em pacientes com doença de Parkinson sem hipotensão ortostática típica (PD-TOH), não há uma resposta inicial que é exclusivamente associada com o ortostase ativa (AS). Portanto, buscou-se avaliar esta resposta e compará-la à observada em jovens saudáveis (YHC). Método Em 10 PD-TOH pacientes (8 homens, 60±7 anos, Hoehn e Yahr ≤3) as mudanças na pressão arterial sistólica (PAS) e da frequência cardíaca que ocorrem nos primeiros 30 segundos (seg) de pé foram examinados. Ambos parâmetros foram monitorizados continuamente através do método Peňáz e os critérios de Wesseling. Os pontos de amostragem foram escolhidos com base em estudos anteriores. Estes pontos foram comparados com os de 10 YHC (32±8 anos). Resultados O principal achado deste estudo foi o aumento do tempo entre o início de AS e rebote sistólica no grupo PD-TOH (24±4 vs 19±3 seg, p<0,05). Conclusão Este atraso pode refletir uma latência prolongada na resposta da resistência vascular mediado pelo barorreflexo, mas outros estudos são necessários para confirmar esta hipótese preliminar. .

Low specificity and sensitivity of smell identification testing for the diagnosis of Parkinsons disease / Baixa sensibilidade e especificidade do teste de identificacao de odores para o diagnostico da doenca de Parkinson

Objective: The aim of this study is to determine if the University of Pennsylvania’s Smell Identification Test (UPSIT) is an accurate diagnostic tool for olfactory dysfunction in Parkinson’s disease (PD). Method: We included 138 non-demented PD subjects and 175 control subjects matched by gender. Smell identification was tested using UPSIT. Results: The mean number of UPSIT items correctly identified by controls was 27.52±5.88; the mean score for PD subjects was 19.66±6.08 (p=<0.001). UPSIT sensitivity was 79.7% with a specificity of 68.5% using a cut-off score of ≤25. The overall accuracy for the diagnosis of PD was of 75.3%. Conclusion: UPSIT accuracy and specificity were lower than what has been previously reported. Our data demonstrates that 17.5% of items of the UPSIT were not well identified by healthy controls. Further research of the identification of a truly cross-cultural test is warranted. .

Objetivo: O objetivo deste estudo é determinar se o University of Pennsylvania Smell Identification Test (UPSIT) é uma ferramenta diagnóstica útil para a caracterizar disfunção olfativa na doença de Parkinson (DP). Método: Foram incluídos 138 indivíduos não dementes assuntos PD e 175 indivíduos controle pareados por sexo. Identificação cheiro foi testada usando UPSIT. Resultados: O número médio de itens UPSIT corretamente identificados pelos controles foi de 27,52±5,88; para sujeitos com DP foi de 19,66±6,08 (p=<0,001). A sensibilidade do UPSIT foi de 79,7%, com especificidade de 68,5%, utilizando um ponto de corte de ≤25. A exatidão global para o diagnóstico de DP foi de 75,3%. Conclusão: A precisão e a especificidade do UPSIT foram menores do que o que foi relatado anteriormente. Nossos dados demonstram que 17,5% dos itens da UPSIT não foram adequadamente identificados pelos controles saudáveis. São necessárias outras pesquisas para a identificação de um teste verdadeiramente cross-cultural nessa área. .

Prosody and levodopa in Parkinsons disease / Prosodia e levodopa na doenca de Parkinson

Objective Research is scarce regarding the use of prosodic parameters in the expression of attitudes in Parkinson’s disease (PD). The purpose of this study was to evaluate the parameters used in prosodic expression of attitudes in individuals with idiopathic PD and the effect of levodopa on these parameters. Method We studied the use of levodopa in 10 individuals with idiopathic PD during the “off” and “on” periods, and 10 individuals without neurological abnormalities. Results PD patients showed lower frequency measurements and longer duration measurements. The levodopa caused reduction in the duration parameter. Conclusion PD patients use prosody to express their attitudes in the same way as controls in both off and on periods. However, when attitudes are not taken into account, levodopa is effective in improving the duration parameter. .

Objetivo A literatura é omissa quando questionada sobre o emprego dos parâmetros prosódicos na expressão das atitudes em parkinsonianos. O objetivo do presente estudo foi avaliar os parâmetros prosódicos empregados na expressão de atitudes em indivíduos com doença de Parkinson (DP) idiopática e a interferência da levodopa sobre esses parâmetros. Método Foram estudados 10 indivíduos com DP idiopática, em uso de levodopa, nos períodos off e on e 10 indivíduos sem alterações neurológicas. Resultados A DP faz com que os parkinsonianos apresentem menores medidas de frequência e maiores medidas de duração. A levodopa provocou redução no parâmetro duração. Conclusão A DP não faz com que o sujeito use sua prosódia para expressar as atitudes de forma diferente do grupo controle, em ambos os períodos, off e on. No entanto, quando não são levadas em consideração as atitudes, observamos que a levodopa foi eficiente em melhorar o parâmetro de duração. .

Neuropsychological and quality of life assessment in patients with Parkinsons disease submitted to bilateral deep brain stimulation in the subthalamic nucleus / Avaliação neuropsicológica e da qualidade de vida em pacientes com doença de parkinson submetidos à estimulação cerebral profunda bilateral nos núcleos subtalâmicos

Deep brain stimulation (DBS) has been widely used to control motor symptoms and improve quality of life inpatients with Parkinsons disease (PD). Recently, DBS in the subthalamic nucleus (STN) has become the preferred targetfor patients with mixed motor symptoms. Despite resultant motor and quality of life improvements, the procedure has beenassociated with cognitive decline, mainly in language skills, and also with psychiatric symptoms. Objective: To evaluatethe influence of DBS in the STN on cognition, mood and quality of life. Methods: We studied 20 patients with PD submittedto DBS in the STN from May 2008 to June 2012 with an extensive battery of cognitive tests including memory, language,praxis, executive functions and attention assessments; the Parkinsons Disease Quality of Life Questionnaire (PDQ-39); and the Hospital Anxiety and Depression Scale (HAD), were applied both before and after the surgery. Data was analyze dusing SPSS version 17.0 and results compared using the paired Students test. Results: A total of 20 patients with preand post-operative assessments were included. A statistically significant improvement was found in total score and onsubscales of mobility, activities of daily living and emotional well-being from the PDQ-39 (P=0.009, 0.025, 0.001 and0.034, respectively). No significant difference was found on the cognitive battery or mood scale. Conclusion: DBS in theSNT improved quality of life in PD with no negative impact on cognitive skills and mood.

Estimulação cerebral profunda tem sido utilizada para controle das alterações motoras e melhorar qualidade devida dos pacientes com Doença de Parkinson (DP). Mais recentemente, DBS em núcleo subtalâmico (STN) tem sido o alvopreferencialmente escolhido para sintomas mistos. Apesar da melhora motora e da qualidade de vida, o procedimento temsido associado com declínio cognitivo, principalmente na linguagem e distúrbios psiquiátricos. Objetivo: Avaliar a influênciado DBS em NST na cognição, humor e qualidade de vida. Métodos: Nós estudamos 20 pacientes submetidos a DBS emNST no período de Maio de 2008 a Junho de 2012, por meio de uma extensa avaliação neuropsicológica incluindo testesde memória, linguagem, praxia, funções executivas, funções atencionais, Parkinsons Disease Quality of Life Questionnaire(PDQ-39) e Escala Hospitalar de depressão e ansiedade (HAD) na fase pré e pós-operatória. Nós analisamos os dadosusando o SPSS versão 17.0 e os resultados foram comparados através do teste pareado t-Student. Resultados: Houvemelhora estatisticamente significativa no escore total e nas dimensões de mobilidade, atividades de vida diária e bem estaremocional do PDQ-39 (P=0,009, 0,025, 0,001 e 0,034, respectivamente). Diferenças significativas não foram encontradasna bateria cognitiva e nem na escala de humor. Conclusão: DBS em SNT melhorou a qualidade de vida nos pacientes com DP sem trazer impacto negativo nas funções cognitivas e humor.

Vascular Parkinsonism and cognitive impairment: literature review, Brazilian studies and case vignettes / Parkinsonismo vascular e disfunção cognitiva: revisão da literatura e estudo de casos brasileiros

Vascular Parkinsonism (VP) is a form of secondary Parkinsonism resulting from cerebrovascular disease. Estimates of the frequency of VP vary greatly worldwide; 3% to 6% of all cases of Parkinsonism are found to have avascular etiology. In a Brazilian community-based study on Parkinsonism, 15.1% of all cases were classified as VP, thethird most common form, with a prevalence of 1.1% in an elderly cohort. Another Brazilian survey found a prevalence of 2.3% of VP in the elderly. VP is usually the result of conventional vascular risk factors, particularly hypertension, leading tostrategic infarcts of subcortical gray matter nuclei, diffuse white matter ischaemic lesions and less commonly, large vessel infarcts. Patients with VP tend to be older and present with gait difficulties, symmetrical predominant lower-body involvement, poor levodopa responsiveness, postural instability, falls, cognitive impairment and dementia, corticospinal findings, urinary incontinence and pseudobulbar palsy. This article intends to provide physicians with an insight on the practical issues of VP, a disease potentially confounded with vascular dementia, idiopathic Parkinsons disease, dementia with Lewy bodies andother secondary causes of Parkinsonism.

Parkinsonismo vascular (VP) é a forma secundária da síndrome parkinsoniana resultante de doença cerebrovascular. Há grande variação das estimativas de frequência em estudos mundiais, sendo que em média 3% a 6% de todos os casos de parkinsonismo têm a etiologia vascular. Em um estudo brasileiro de base comunitária sobre parkinsonismo, 15,1% de todos os casos foram classificados como VP, que foi a terceira causa mais comum, com uma prevalência de 1,1% em uma coorte de idosos. Outro estudo brasileiro encontrou uma prevalência de 2,3% de VP também em idosos. VP usualmente resulta de fatores de risco vasculares como a hipertensão, levando a infartos estratégicos nos núcleos da base, lesões isquêmicas difusas da substância branca subcortical e menos comumente, infartos de grandes vasos. Os pacientes com VP geralmente são mais idosos e apresentam dificuldades para a marcha, envolvimento simétrico predominante em membros inferiores, resposta pobre à terapêutica com levodopa, instabilidade postural e quedas, comprometimento cognitivo e demência, sinais de acometimento cortico espinhal, incontinência urinária e paralisia pseudobulbar. Este artigo apresenta algumas informações práticas sobre o VP, uma condição neurológica potencialmente confundida com demência vascular, doença de Parkinson idiopática, demência com corpos de Lewy e com outras causas de parkinsonismo.

Cognitive assessment instruments in Parkinsons disease patients under going deep brain stimulation / Intrumentos de avaliação cognitiva em indivíduos com doença de parkinson submetidos à estimulação cerebral profunda

Deep Brain Stimulation (DBS) is a widely used surgical technique in individuals with Parkinsons disease (PD) thatcan lead to significant reductions in motor symptoms. Objectives: To determine, from publications, the most commonly usedinstruments for cognitive evaluation of individuals with PD undergoing DBS. Methods: A systematic review of the databases:PubMed, Medline, EBECS, Scielo and LILACS was conducted, using the descriptors Deep Brain Stimulation, VerbalFluency, Parkinson Disease, Executive Function, Cognition and Cognitive Assessment in combination. Results: TheVerbal Fluency test was found to be the most used instrument for this investigation in the studies, followed by the BostonNaming Test. References to the Stroop Test, Trail Making Test, and Reys Auditory Verbal Learning Test were also found.Conclusions: The validation of instruments for this population is needed as is the use of batteries offering greater specificityand sensitivity for the detection of cognitive impairment .

A Estimulação Cerebral Profunda (ECP) tem sido uma técnica cirúrgica bastante utilizada devido à reduçãosignificativa dos sintomas motores. Objetivos: Verificar, a partir das publicações, quais os instrumentos mais utilizados paraavaliação cognitiva em pacientes com DP submetidos à ECP. Métodos: Foi realizado uma revisão sistemática nas basesde dados PubMed, Medline, EBECS, Scielo e LILACS utilizando os descritores Deep Brain Stimulation, Verbal Fluency, Parkinson Disease, Executive Function, Cognition e Cognitive Assessment de forma combinada. Resultados: O teste deFluência Verbal o instrumento mais utilizado para esta investigação nos estudos encontrados, seguido pelo Teste de Nomeaçãode Boston. Foram também encontradas referências aos testes Teste de Stroop, Teste das Trilhas, Teste de AprendizadoAuditivo Verbal de Rey. Conclusões: A validação de instrumentos para esta população se faz necessária bem como autilização de baterias com mais especificidade e sensibilidade para detecção das alterações cognitivas nesta população.Palavras-chave: doença de Parkinson, cognição, estimulação cerebral profunda.

Avaliação da geração de palavras, em indivíduos com doença de parkinson, através de ressonância magnética funcional / Word generation in parkinson's disease a functional magnetic resonance study

As alterações cognitivas na doença de Parkinson (DP) têm sido mais estudadas nos últimos anos, porém alterações de linguagem, embora detectadas clinicamente, permanecem pouco exploradas. Neste estudo, avalia-se a capacidade de pacientes com DP de gerar palavras, durante paradigma de ressonância magnética funcional (RMf), comparandose com voluntários sadios. MÉTODOS: Neste estudo, foram incluídos 17 pacientes com doença de Parkinson, em seguimento no ambulatório de Distúrbios do Movimento do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo e 20 voluntários normais, pareados quanto à idade e escolaridade. Todos foram submetidos à avaliação neurológica e neuropsicológica. Cada indivíduo realizou dois exames de RMf, sendo utilizado o paradigma de geração de palavras, constando de 70 letras cada, durante os quais dados comportamentais foram coletados. As imagens foram analisadas com testes não paramétricos e mapas de correlação entre os resultados de RMf e dados comportamentais (percentagem de acertos) foram construídos. RESULTADOS: Os grupos apresentavam perfis neuropsicológicos semelhantes, com diferenças somente em testes que envolviam velocidade motora. Nos indivíduos com DP, observou-se ativação das regiões frontal dorsolateral esquerda, giro do cíngulo anterior, área motora suplementar esquerda e do cerebelo à direita durante a geração de palavras, à semelhança do grupo controle. Na comparação entre grupos, notou-se maior resposta hemodinâmica nos pacientes com DP, em relação aos controles, em áreas do córtex frontal dorsolateral esquerdo. Observouse, ainda, no grupo com DP, menor atividade na porção anterior do cíngulo e área motora suplementar esquerda. Na análise comportamental, incluindo a classificação dos erros, não houve diferenças entre os grupos. Para explicar esses resultados, especula-se que as diferenças nas áreas subcorticais possam estar relacionadas com o aumento da atividade no córtex frontal...

Cognitive disturbances have been studied in patients with Parkinson´s disease (PD) in the last years but language dysfunction, although observed in clinical practice, are just now being explored. In this study, we investigate PD patients ability to generate words using a functional magnetic resonance (fRMI) paradigm and compare these areas with healthy volunteers. We selected 17 PD patients from the Movement Disorders Clinics of Hospital das Clinicas, Universidade de São Paulo and 20 healthy volunteers, matched for age and years of formal education. Both groups were evaluated from neurological and neurophsychological perspective and showed similar profiles, with differences only in tests that involved motor speed. Each subject was scanned twice using an overt-speech block design fRMI paradigm with visual presentation of 70 stimuli during which behavioral data were collected. Images were analyzed using a non-parametric approach, and correlation maps between fRMI results and behavioral data (percentage of correct responses) were produced. PD patients showed activity on the left dorsolateral frontal cortex, anterior cingulate gyrus, motor supplementary areas and right cerebellum during the word generation paradigm, similar to the healthy volunteers group. PD patients had increased hemodynamic response in the left dorsolateral frontal cortex and a reduction was found at anterior cingulated gyrus and motor supplementary area compared to healthy volunteers. Behavioral analyses (including error classification) did not show any differences between groups. We speculate that the difference found in subcortical areas may be related to the increment observed in the frontal dorsolateral cortex, since degeneration of mesolimbic dopaminergic pathways is described in PD associated with dysfunction on basal ganglia circuitry, especially involving the cingulated and dorsolateral loop...

The Predictable Clinical Factors for the Levodopa Responsiveness of Resting Tremor in Patients with Parkinson's Disease

BACKGROUND: The pathophysiology of resting tremor in Parkinsons disease (PD) remains unclear. Dopaminergic treatment provides variable effects on resting tremor in PD. We aimed to evaluate the predictable clinical factors for the levodopa responsiveness of resting tremor in patients with PD. METHODS: Eighty-five PD patients with prominent resting tremor who visited Asan Medical Center between June 2004 and June 2005 were included. The prominent resting tremor was defined as tremor scoring more than 3 in at least one limb in the Unified Parkinsons Disease Rating Scale (UPDRS). Subjects were divided into the responsive group (RG) or non-responsive group (NRG) according to the responsiveness of resting tremor to dopaminergic treatment. Responsiveness was defined as a minimum 2 points reduction of UPDRS score for the resting tremor after dopaminergic treatment for more than 3 months. RESULTS: Among the 85 patients, there were 35 men and 50 women ages 34-87 years (mean age, 67 years). Thirty-six patients (42.4%) were grouped into RG and 49 (57.6%) into NRG. Mean age of RG was significantly younger than that of NRG. RG showed significantly higher initial UPDRS part III subtotal score (p=0.015) and more severe Hoehn & Yahr stage (p=0.010) than those of NRG. UPDRS subscores for rigidity (p=0.012), bradykinesia (p=0.021) and postural impairment (p=0.018) were correlated with the responsiveness of dopaminergic treatment. CONCLUSIONS: Resting tremor in PD patients more favorably responded to dopaminergic treatment when it presented in combination with bradykinesia and rigidity suggesting dopaminergic role in the genesis of resting tremor in those PD patients.

New light on neuronal ATP-sensitive potassium channels / 中国药理学通报

ATP sensitive potassium (K ATP ) channels widely expressed in many tissue and cell types including neurons are heteromultimers of sulfonylurea receptor (SUR) and inward rectifier K + channel (Kir6) subunits associated with 1∶1 stoichiometry as a tetramer (SUR/Kir6) 4. The activity of K ATP channels is modulated by intracellular ATP concentrations. Neuronal K ATP channels are involved in the mediation of glucose sensing and metabolic stress. Under physiological condition, they also possess important pathophysiological functions in acute brain ischemic and chronic neurodegenerative diseases.

Regulation of dopamine and glutamate release by metabotropic glutamate receptors in the basal ganglia motor circuit:implications for treatment of parkinsons disease / 中国药理学通报

Metabotropic glutamate receptors (mGluRs) are a family of G protein coupled receptors linked to modulation of ion channel functions and multiple second messengers. These receptors are widely distributed throughout the basal ganglia (BG). Studies have demonstrated that these mGluRs subtypes located at various synapses in BG could modulate the release of dopamine and glutamate which correlates with brain area,the subtype selectivity and concentration of the ligands. Metab otropic glutamate receptors have been proposed as potentially new therapeutic targets for Parkinsons disease by providing a method of pharmacologically regulating neurotransmission in the BG.

The protective effects of polysaccharide from spirulina platensis on dopaminergic neurons of MPTP-induced Parkinsons disease model in mice / 中国药理学通报

Aim The present study is designed to elucidate the protective effect of Polysaccharide from Spirulina Platensis(PSP) on dopaminergic neurons of MPTP-induced Parkinsons disease model in C57BL mice.Methods C57BL mice were divided into 5 groups:control group,MPTP group,PSP 200 mg?kg-1 plus MPTP group,PSP 400 mg?kg-1 plus MPTP group,and PSP 800 mg?kg-1 plus MPTP group.Immunohistochemistry assay,RT-PCR,and HPLC-ECD were used to detect the immunoreactivity of tyrosine hydroxylase(TH) and dopamine transporters(DAT),the expression of TH mRNA and DAT mRNA in substantia nigra(SN),the content of dopamine(DA) and its metabolites,i.e.3,4-dihydroxyphenyl acetic acid(DOPAC) and homovanilic acid(HVA) in striatum(Str).Results The result showed that,compared with control group,the TH and DAT immunoreactive stain in MPTP group was significantly decreased(P

A novel therapy for PD-adenosine A_ (2A) receptor antagonist / 中国药理学通报

Adenosine A_ 2A receptors are selectively localized in basal ganglia and can affect the locomotor activity. Epidemiological and laboratory data have suggested that A_ 2A blockade may confer neuroprotection against the underlying dopaminergic neuron degeneration. A_ 2A receptor antagonist may ameliorate the symptom of Parkinsons disease (PD) and block the disease progress. Thus, the data suggested that A_ 2A receptor antagonist might be effective as a novel therapy for the management of PD.

Chronic subcutaneous injection of rotenone produces rodent Parkinsonian models / 中国药理学通报

Aim To establish a rat model of Parkinsons disease by chronic subcutaneous injection of low-dose rotenone.Methods Lewis rats were randomly divided into two groups: vehicle-treated group and rotenone-treated group.Rotenone(1.0 mg?kg~(-1)?d~(-1)) was subcutaneously injected at 08:00 and 20:00 for 30 days with drug holidays every 7 days.Following 30 days of rotenone administration,neuronal loss in the substantia nigra(SN) was determined with tyrosine hydroxylase(TH) immunohistochemistry and Nissl staining.Aggregation of ?-synuclein in SN neurons was observed with a laser cofocal microscopy.Result Three rotenone-treated rats showed resting tremor.The number of TH-positive neurons in SN significantly reduced(P

Molecular Pathway in parkinsons disease: An update on progress / 中国药理学通报

Parkinsons disease(PD) is characterized by a selective lo ss of dopaminergic neurons in the substantia nigra pars compacta. The etiology of PD is still not full y understood. Molecular pathways such as oxidative stress, mitochondrial dysfunc tion and impairment in the ubiquitinproteasomal system, are involved in the proc ess of the dopaminergic neuronal cell death and the progress of PD. The explorat ion and elucidation of these molecular pathways will provide new potential targe ts for the drug therapy of PD.

Iptakalim hydrochloride enhances glutamate uptake activity in synaptosomes from rat models of Parkinsons disease / 中国药理学通报

AIM To study the relationship between the activity of glutamate transporters and Parkinson's disease (PD), examine whether a novel ATP sensitive potassium (K ATP) channel opener Iptakalim (Ipt) hydrochloride enhances glutamate uptake activity, and to investigate its mechanisms. METHODS Rats were stereotaxically injected with 6 hydroxydopamine (6 OHDA) in SNpc. The synaptosomes from normal and PD rats were isolated, and [ 3H] glutamate uptake in synaptosomes was measured by using liquid scintillation counting. RESULTS [ 3H] glutamate uptake by synaptosomes from striatum and cerebral cortex of PD rats decreased and the redution was recovered by administration with Ipt (10, 50, 100 ?mol?L -1 ). The protective effect of Ipt was blocked by co adiministration with glibenclamide (20 ?mol?L -1 ), an inhibitor of sulphonylurea receptors. CONCLUSION Our results demonstrate for the first time the protective role of K ATP channel in glutamate uptake of synaptosomes and conceptually support the view that Ipt may have potential and feasibility in therapy for PD.

Effects of echinacoside on protein expression from substantia nigra and striatal tissue in mouse MPTP model of Parkinsons disease by using 2-dimensional electrophoresis analysis / 中国药理学通报

Aim To study the effect of echinacoside on behavior and proteins expression from substantia nigra and striatal tissue in MPTP mouse model of Parkinsons disease(PD)and discover the mechanism of its potential dopaminergic neuroprotective effect in the protein level.Methods The mouse model of PD was induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)and the behavioral analysis of C57BL/6 mice was performed by using spontaneous movement and rotarod test.A proteomic approach based on 2-dimensional electrophoresis(2-DE),mass spectrometry(MS)and figure analysis was used to evaluate the effect of echinacoside on the behavior and the protein expression in substantia nigra and striatal tissue in C57BL/6 mice after MPTP administration.Results ① Compared with control,MPTP lesion significantly reduced the number of spontaneous movement and latent period of mice on the rotating rod(both P

Matrix metalloproteinases and nervous diseases / 中国药理学通报

Matrix metalloproteinases (MMPs) are a family of Zn~ 2+ -dependent endopeptidases targeting extracellular matrix (ECM) compounds as well as a number of other proteins. Their proteolytic activity acts as an effector mechanism of tissue remodeling in physiologic and pathologic conditions, and as modulator of inflammation. Recently, it has been reported that MMPs play an important role in nervous diseases including cerebral ischemia, Alzheimers disease,multiple sclerosis and Parkinson′s disease.