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1.
Pan Afr Med J ; 33: 229, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31692664

RESUMO

Introduction: Currently we have no precise data on the parkinsonian syndromes in Madagascar. This study aims to collect data on these diseases and to describe the frequency and the clinical profile of parkinsonian syndromes in our Department of Neurology. Methods: We conducted a retrospective and descriptive study in the Department of Neurology, in Befelatanana from January 2014 to June 2018. The demographic and clinical data of patients diagnosed as having a parkinsonian syndrome were collected. We assessed data rates and characteristics and then we compared patients with idiopathic Parkinson's disease and patients with other parkinsonian syndromes. Data were processed using R. software. Results: The study included 104 of 3528 patients, seen in our Department. Among the patients with parkinsonian syndrome, 67(64.42%) had idiopathic Parkinson's disease (PD) and 37 (35.47%) another parkinsonian syndrome. The average interval between the onset of the disease and the consultation or the hospitalization in the Department was 2.5 years. For MP, the median age at onset was 58.5 [23; 80] years, the median age at diagnosis was 62 [28; 83] years and the sex ratio were 1.97. The median Hoehn and Yahr score were 2.0. Tremor-dominant Parkinson's disease was found in 24 (35.42%) of cases, a mixed phenotype was found in 28 (41.71%) of cases while akineto-rigid Parkinson's disease was found in 15 (22.38%) of cases. The other parkinsonian syndromes ocuurred in 27 (72.97%) men, with a median age at onset of 57.5 [26; 83] years, a median age at diagnosis of 59.3 [26; 83] years. Etiologies were dominated by Multiple System Atrophy 17/37 (46.64%). Patients with other parkinsonian syndromes had several cognitive disorders (p=0,0306) and MPs were more sensitive to dopamine (p=0.006). Conclusion: The patients with idiopathic parkinsonian syndrome had features different from those of patients with parkinsonism. There was a diagnostic delay as in other developing countries.


Assuntos
Dopamina/administração & dosagem , Doença de Parkinson/epidemiologia , Transtornos Parkinsonianos/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Tardio , Dopamina/farmacologia , Dopaminérgicos/administração & dosagem , Dopaminérgicos/farmacologia , Feminino , Humanos , Madagáscar/epidemiologia , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , Transtornos Parkinsonianos/diagnóstico , Transtornos Parkinsonianos/fisiopatologia , Estudos Retrospectivos , Fatores de Tempo
2.
Adv Exp Med Biol ; 1175: 335-353, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583594

RESUMO

Microglia are the most abundant immune cells in the central nervous system (CNS), where they interact with neurons and exhibit a wide array of functions in physiological and pathological conditions. Physiologically, microglia mediate synaptic pruning and remodeling crucial for neural circuits and brain connectivity. In pathological conditions such as neurodegeneration in the Parkinson's disease (PD), microglia are activated, migrated to the injury site, and prone to engulf debris, sense pathology, and secrete possible pro- and anti-inflammatory factors. Microglia mediate responses such as inflammation and phagocytosis associated with neurodegeneration and are pivotal players in exacerbating or relieving disease progression. This chapter provides an overview on microglial function in the neurodegenerative disease-Parkinson's disease (PD). An overview on the pathology of PD will first be given, followed by discussion on receptors and signaling pathways involved in microglia-mediated inflammation and phagocytosis. Mechanism of how microglia contribute to PD by inflammation, phagocytosis of α-Synuclein (α-Syn), and interaction with PD genes will also be discussed.


Assuntos
Microglia/citologia , Doença de Parkinson/fisiopatologia , Humanos , Inflamação/fisiopatologia , Fagocitose , Transdução de Sinais , alfa-Sinucleína
3.
Nursing ; 49(11): 24-32, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31651771

RESUMO

Parkinson disease (PD) is a progressive, incurable disease caused by dopamine deficiency. This article provides an overview of this neurodegenerative disorder and offers information for optimal outcomes.


Assuntos
Doença de Parkinson/enfermagem , Humanos , Diagnóstico de Enfermagem , Doença de Parkinson/fisiopatologia , Educação de Pacientes como Assunto
4.
Codas ; 31(6): e20180160, 2019.
Artigo em Português, Inglês | MEDLINE | ID: mdl-31618343

RESUMO

PURPOSE: To compare pharyngeal residues of different consistencies among groups of individuals with neurogenic oropharyngeal dysphagia. METHODS: In a cross-sectional study, a fiberoptic endoscopic evaluation was performed in 30 swallowing exams of individuals diagnosed with neurological disease and oropharyngeal dysphagia, regardless of the time or stage of the disease. The individuals were divided into three groups according to etiology: group I, 10 post-stroke, 8 male and 2 female, aged 51 to 80 years (average age: 67 years); group II, 10 individuals with amyotrophic lateral sclerosis, 5 male and 5 female, aged 39 to 78 years (average age: 57 years); group III, 10 examinations of individuals with Parkinson's disease, 5 male and 5 female aged 65-88 years (average age: 74 years). The Yale Pharyngeal Residue Severity Rating Scale was applied by two independent raters in a blind manner for the analysis of pharyngeal residues in valleculae and pyriform sinuses based on the first swallowing of 5 mL of pureed and thickened liquid. RESULTS: No statistically significant difference was observed among groups in the degree of pharyngeal residues of puree food or thickened liquid in the valleculae (p = 0.25/p = 0.18) or the pyriform sinuses (p = 1.41/0.49). CONCLUSION: The pharyngeal residue levels of pureed and thickened liquid were similar for the groups studied, with less severe levels being more frequent.


Assuntos
Esclerose Amiotrófica Lateral/complicações , Transtornos de Deglutição/fisiopatologia , Doença de Parkinson/complicações , Acidente Vascular Cerebral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Esclerose Amiotrófica Lateral/fisiopatologia , Estudos Transversais , Transtornos de Deglutição/diagnóstico por imagem , Transtornos de Deglutição/etiologia , Feminino , Humanos , Laringoscopia , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Índice de Gravidade de Doença , Acidente Vascular Cerebral/fisiopatologia , Gravação em Vídeo
5.
Adv Exp Med Biol ; 1158: 17-44, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31452133

RESUMO

Parkinson's disease (PD) is a multifactorial disorder whose etiology is not completely understood. Strong evidences suggest that mitochondrial impairment and altered mitochondrial disposal play a key role in the development of this pathology. Here we show this association in both genetic and sporadic forms of the disease. Moreover, we describe the mitochondrial dysfunctions in toxin-induced models of PD, thus highlighting the importance of environmental factors in the onset of this pathology. In particular, we focus our attention on mitochondrial dynamics, mitochondrial biogenesis, and mitophagy and explain how their impairment could have a negative impact on dopaminergic neurons function and survival. Lastly, we aim at clarifying the important role played by proteomics in this field of research, proteomics being a global and unbiased approach suitable to unravel alterations of the molecular pathways in multifactorial diseases.


Assuntos
Proteínas Mitocondriais , Doença de Parkinson , Neurônios Dopaminérgicos/patologia , Humanos , Mitocôndrias/metabolismo , Degradação Mitocondrial , Proteínas Mitocondriais/metabolismo , Doença de Parkinson/fisiopatologia
6.
J Clin Neurosci ; 68: 235-242, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31420273

RESUMO

This study used Voxel-based morphometry (VBM) and resting-state functional magnetic resonance imaging (rs-fMRI) to investigate changes in brain structure and networks functional connectivity, respectively. We tried to identify the potential biomarkers in Parkinson's disease (PD) progression. We recruited nine idiopathic PD patients and seven healthy control participants (HC group) who were age-matched to undergo T1-weighted images and rs-fMRI on 1.5 T. Brain structure differences were analyzed by VBM. Topological properties of networks functional connectivity were analyzed by graph theory. Thirty-two nodes of 8 networks and 133 nodes of interest then were identified with graph theory approaches. VBM examinations showed significant decreases of brain gray matter regions including the left temporal lobe, left middle temporal, middle temporal gyrus, parietal lobe, postcentral gyrus, left inferior parietal gyrus, medial frontal gyrus and supplement motor area in PD patients compared to the HC group. The 32 ROI of networks topological metrics measurement in PD demonstrated increases of global efficiency, cost, and degree in frontoparietal PPC (R) network, but decreases of local efficiency, clustering coefficient, and average path length in salience ACC, dorsal attention FEF (L), and salience aInsula (R) networks, respectively. All 165 ROI connectomes showed eight connections intensity changes, that decrease in OP r to frontoparietal PPC, putamen r to cereb11, and SFG l to Ver8 in PD. These results suggest that the graph theory and the network topological metrics measurement may be the potential biomarkers in PD to evaluate the disease progress and to monitor the therapeutic results.


Assuntos
Encéfalo/fisiopatologia , Interpretação de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Modelos Teóricos , Doença de Parkinson/fisiopatologia , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Conectoma/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Modelos Neurológicos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia
7.
Sheng Li Xue Bao ; 71(4): 547-554, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31440751

RESUMO

The aim of the present study was to reveal the role of cortical-striatum postsynaptic dopamine D2 receptor (D2R) in improving motor behavioral dysfunction in Parkinson's disease (PD) mice by exercise. C57/BL6 male adult mice were randomly divided into control, PD and PD plus exercise groups. The mice were injected with 6-OHDA in striatum to establish a unilateral injury PD model. The exercise intervention program was uniform speed running (16 m/min, 40 min/d, 5 d per week for 4 weeks). Autonomic activity of mice was tested by open field test. Cortical-striatum synaptic transmission efficiency was assessed by peak amplitude of field excitatory postsynaptic potential (fEPSP) recorded from in vitro brain slides. Meanwhile, the effects of D2R agonist on autonomic activity and cortical-striatal synaptic transmission were observed. The results showed that, compared with PD group, PD plus exercise group exhibited significantly increased autonomic motor distance and proportion of fast-moving (P < 0.05), as well as decreased maximum amplitude of fEPSP under increasing stimulation intensity (0.75-3.00 pA) (P < 0.05) and slope of stimulus-response curve. Compared with PD mice without D2R agonist, the movement distance and rapid movement ratio of PD mice treated with D2R agonist were increased significantly (P < 0.05), whereas fEPSP peak amplitude (P < 0.05) and the slope of stimulus-response curve were decreased. These results indicate that either early exercise intervention or D2R agonist treatment can inhibit the abnormal increase of cortical-striatum synaptic transmission and improve the autonomic motor ability in PD mice, suggesting that the cortical-striatum synaptic D2R may be an important molecular target for exercise to improve the autonomic motor ability of PD mice.


Assuntos
Corpo Estriado/fisiologia , Doença de Parkinson/terapia , Condicionamento Físico Animal , Receptores de Dopamina D2/fisiologia , Transmissão Sináptica , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxidopamina , Doença de Parkinson/fisiopatologia , Distribuição Aleatória , Receptores de Dopamina D2/agonistas
8.
Adv Exp Med Biol ; 1173: 45-66, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456205

RESUMO

The key molecular events that provoke Parkinson's disease (PD) are not fully understood. Iron deposit was found in the substantia nigra pars compacta (SNpc) of PD patients and animal models, where dopaminergic neurons degeneration occurred selectively. The mechanisms involved in disturbed iron metabolism remain unknown, however, considerable evidence indicates that iron transporters dysregulation, activation of L-type voltage-gated calcium channel (LTCC) and ATP-sensitive potassium (KATP) channels, as well as N-methyl-D-aspartate (NMDA) receptors (NMDARs) contribute to this process. There is emerging evidence on the structural links and functional modulations between iron and α-synuclein, and the key player in PD which aggregates in Lewy bodies. Iron is believed to modulate α-synuclein synthesis, post-translational modification, and aggregation. Furthermore, glia, especially activated astroglia and microglia, are involved in iron deposit in PD. Glial contributions were largely dependent on the factors they released, e.g., neurotrophic factors, pro-inflammatory factors, lactoferrin, and those undetermined. Therefore, iron chelation using iron chelators, the extracts from many natural foods with iron chelating properties, may be an effective therapy for prevention and treatment of the disease.


Assuntos
Ferro/metabolismo , Doença de Parkinson/fisiopatologia , alfa-Sinucleína/metabolismo , Animais , Canais de Cálcio Tipo L , Neurônios Dopaminérgicos/patologia , Humanos , Canais KATP , Receptores de N-Metil-D-Aspartato , Substância Negra/patologia
9.
Fortschr Neurol Psychiatr ; 87(8): 445-461, 2019 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-31430812

RESUMO

At least 300,000 people with idiopathic Parkinson's disease are living in Germany. Due to the demographic change the number of affected patients is expected to increase continuously. This article presents the evidence-based diagnostics and therapy of idiopathic Parkinson's disease. It provides an overview especially on new findings and developments in recent years.


Assuntos
Doença de Parkinson/diagnóstico , Doença de Parkinson/terapia , Alemanha/epidemiologia , Humanos , Doença de Parkinson/classificação , Doença de Parkinson/fisiopatologia
10.
Georgian Med News ; (291): 82-85, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31418736

RESUMO

Aim of the study - to assess the impact of physical therapy using musical elements, for Parkinson disease diagnosed people static and dynamic body balance thus psychological state. Research subjects were Parkinson disease diagnosed elderly people. Age 67-80 (67.5±12.5) years old, 9 men and 9 women, n=18. Research tools: Dynamic Gait Index (DGI) (Wrisley D., et al., 2003); Romberg's test - RT (Khasnis A, Gokula R.M, 2003); Burns Depression Checklist - BDC (Burns D., 2013). Microsoft Excel 2016, statistical significance level was set at p<0.05. BDC summarizing the research results, patients with PD tended to have less depression after the physical therapy with music elements sessions appliance. In terms of the DGI percentage decreased from 77.8% to 72.2% after physical therapy sessions. The evaluation of patients by RT, showed the positive results, compared in the beginning more than > 50 % of patients needed help or they could not complete the task. After classes - the percentage decreased. Patients static balance improved statistically significant.


Assuntos
Musicoterapia , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Modalidades de Fisioterapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Marcha , Humanos , Masculino , Equilíbrio Postural
11.
Pharm Res ; 36(9): 135, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31317279

RESUMO

PURPOSE: The aim of this work was to allow combination of information from recent and historical trials in Parkinson's Disease (PD) by developing bridging methodology between two versions of the clinical endpoint. METHODS: A previously developed Item Response Model (IRM), that described longitudinal changes in Movement Disorder Society (MDS) sponsored revision of Unified Parkinson's Disease Rating Scale (UPDRS) [MDS-UPDRS] data from the De Novo PD cohort in Parkinson's Progression Markers Initiative, was first adapted to describe baseline UPDRS data from two clinical trials, one in subjects with early PD and another in subjects with advanced PD. Assuming similar IRM structure, items of the UPDRS version were mapped to those in the MDS-UPDRS version. Subsequently, the longitudinal changes in the placebo arm of the advanced PD study were characterized. RESULTS: The parameters reflecting differences in the shared items between endpoints were successfully estimated, and the model diagnostics indicated that mapping was better for early PD subjects (closer to De Novo cohort) than for advanced PD subjects. Disease progression for placebo in advanced PD patients was relatively shallow. CONCLUSION: An IRM able to handle two variants of clinical PD endpoints was developed; it can improve the utilization of data from diverse sources and diverse disease populations.


Assuntos
Doença de Parkinson/classificação , Índice de Gravidade de Doença , Estudos de Coortes , Avaliação da Deficiência , Humanos , Modelos Teóricos , Doença de Parkinson/fisiopatologia , Placebos
12.
Rev Med Chil ; 147(4): 465-469, 2019 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-31344208

RESUMO

BACKGROUND: Multicomponent physical training in patients with Parkinson disease may improve their functional independence, especially in terms of gait speed and coordination. AIM: To assess the effects of an eight weeks multicomponent physical training program in patients with Parkinson disease. MATERIAL AND METHODS: Fourteen patients with Parkinson disease participated in a physical training program that lasted eight weeks. Three sessions lasting 60 minutes per week were carried out. Patients were assessed using the six minutes walk, timed up and go and the unipodal stance test. RESULTS: After the training period, significant improvements in the six minute walk test and timed up and go were observed. No significant changes were observed in the unipodal stance test. CONCLUSIONS: The eight weeks training program improved gait speed and functional status in these patients with Parkinson disease.


Assuntos
Terapia por Exercício/métodos , Marcha/fisiologia , Doença de Parkinson/fisiopatologia , Doença de Parkinson/reabilitação , Condicionamento Físico Humano/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica/fisiologia , Valores de Referência , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento , Teste de Caminhada
13.
Nature ; 571(7766): 565-569, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31316206

RESUMO

Parkinson's disease is a neurodegenerative disorder with motor symptoms linked to the loss of dopaminergic neurons in the substantia nigra compacta. Although the mechanisms that trigger the loss of dopaminergic neurons are unclear, mitochondrial dysfunction and inflammation are thought to have key roles1,2. An early-onset form of Parkinson's disease is associated with mutations in the PINK1 kinase and PRKN ubiquitin ligase genes3. PINK1 and Parkin (encoded by PRKN) are involved in the clearance of damaged mitochondria in cultured cells4, but recent evidence obtained using knockout and knockin mouse models have led to contradictory results regarding the contributions of PINK1 and Parkin to mitophagy in vivo5-8. It has previously been shown that PINK1 and Parkin have a key role in adaptive immunity by repressing presentation of mitochondrial antigens9, which suggests that autoimmune mechanisms participate in the aetiology of Parkinson's disease. Here we show that intestinal infection with Gram-negative bacteria in Pink1-/- mice engages mitochondrial antigen presentation and autoimmune mechanisms that elicit the establishment of cytotoxic mitochondria-specific CD8+ T cells in the periphery and in the brain. Notably, these mice show a sharp decrease in the density of dopaminergic axonal varicosities in the striatum and are affected by motor impairment that is reversed after treatment with L-DOPA. These data support the idea that PINK1 is a repressor of the immune system, and provide a pathophysiological model in which intestinal infection acts as a triggering event in Parkinson's disease, which highlights the relevance of the gut-brain axis in the disease10.


Assuntos
Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/fisiopatologia , Intestinos/microbiologia , Doença de Parkinson/genética , Doença de Parkinson/microbiologia , Proteínas Quinases/deficiência , Proteínas Quinases/genética , Animais , Apresentação do Antígeno/imunologia , Autoantígenos/imunologia , Axônios/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Citrobacter rodentium/imunologia , Citrobacter rodentium/patogenicidade , Modelos Animais de Doenças , Neurônios Dopaminérgicos/imunologia , Neurônios Dopaminérgicos/patologia , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/patologia , Feminino , Intestinos/imunologia , Intestinos/patologia , Levodopa/uso terapêutico , Masculino , Camundongos , Mitocôndrias/imunologia , Mitocôndrias/patologia , Neostriado/imunologia , Neostriado/microbiologia , Neostriado/patologia , Neostriado/fisiopatologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Proteínas Quinases/imunologia , Ubiquitina-Proteína Ligases/deficiência , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/imunologia
14.
NeuroRehabilitation ; 44(4): 569-577, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31256088

RESUMO

BACKGROUND: Randomized clinical trials (RCTs) used the Nintendo Wii (NW) in the treatment of Parkinson Disease, however, no meta-analysis was developed to determine the effects in these patients. OBJECTIVE: To analyze RCTs that investigated the effects of NW versus traditional physiotherapy on balance rehabilitation and quality of life of patients with PD. METHODS: Electronic research was conducted between December 2018 and January 2019 in the MEDLINE, PEDro, CENTRAL, LILACS and SciELO databases. The methodological quality was evaluated by the PEDro scale and the completeness of the description of the interventions by the TIDieR checklist. Weighted mean differences (WMD) and 95% confidence interval (CI) were calculated. RESULTS: Five studies were included and presented an average of 5.4 (1.5) on the PEDro scale and 6.7 (1.4) on the TIDieR. Compared to traditional physiotherapy, combined NW and traditional physiotherapy resulted in improvement in balance WMD 1.24 (95% CI: CI: 0.2 to 2.3 N = 72) and quality of life WMD- 8.9 (95% CI: -15.2 to -2.6 N = 56). CONCLUSION: combined NW and traditional physiotherapy was more effective on balance rehabilitation and quality of life of patients with PD, but the values demonstrated a poor methodological quality and a low level of completeness of the intervention descriptions.


Assuntos
Terapia por Exercício/métodos , Terapia por Exercício/psicologia , Doença de Parkinson/psicologia , Doença de Parkinson/reabilitação , Equilíbrio Postural/fisiologia , Jogos de Vídeo/psicologia , Humanos , Doença de Parkinson/fisiopatologia , Qualidade de Vida/psicologia , Resultado do Tratamento
15.
NeuroRehabilitation ; 44(4): 579-586, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31256094

RESUMO

BACKGROUND: Gait function is known to be impaired by Parkinson's disease (PD). The effect of exercise to improve gait has been widely examined, often with special intervention. However, in clinical settings, physiotherapy rarely consists only of gait training. OBJECTIVE: To examine whether versatile physiotherapy intervention conducted in accordance with European Physiotherapy Guideline for Parkinson's Disease (EPGPD) is sufficient to increase gait speed (GS). METHODS: Participants (24) with idiopathic PD were randomly enrolled into intervention (IG) and control groups (CG) (n = 12, 7 females and 5 males in each group). Sixteen one-hour therapy sessions (twice per week) were conducted for IG. Each session focused on core areas recommended in EPGPD. Participants were assessed twice with 10 weeks between assessments. GS was calculated based on a gait test of Short Physical Performance Battery. Dominant side hip flexion and abduction range of motion (HFLEX & HABD) were measured and Freezing of Gait questionnaire (FOG) was administered. RESULTS: Versatile intervention in groups resulted in increase of GS (ES -0.9 [CI{0.1}-{0.4}] m/s) and HFLEX (ES-0.6 [CI{5.9}-{16.6°}]. FOG was reduced (ES -0.41 [CI {-2.8}{-5.5}]). Re-evaluation HABD differed between groups and indicated large ES (r = -0.5). CONCLUSIONS: Versatile physiotherapy is sufficient to improve GS, range of motion and reduce FOG.


Assuntos
Transtornos Neurológicos da Marcha/terapia , Doença de Parkinson/terapia , Modalidades de Fisioterapia , Velocidade de Caminhada/fisiologia , Idoso , Exercício/fisiologia , Terapia por Exercício/métodos , Feminino , Marcha/fisiologia , Transtornos Neurológicos da Marcha/epidemiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Doença de Parkinson/fisiopatologia , Distribuição Aleatória , Inquéritos e Questionários
17.
BMC Neurol ; 19(1): 113, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164098

RESUMO

BACKGROUND AND AIM: Toxic oligomeric α-synuclein (αS; O-αS) has been suggested to play a central role in the pathogenesis of Lewy body diseases such as Parkinson's disease (PD). Cerebrospinal fluid (CSF) levels of αS, O-αS, total and phosphorylated tau, and amyloid ß 1-42 (Aß1-42) are thought to reflect the pathophysiology or clinical symptoms in PD. In this study, we examined correlations of the CSF levels of these proteins with the clinical symptoms, and with each other in drug-naïve patients with PD. METHODS: Twenty-seven drug-naïve patients with PD were included. Motor and cognitive functions were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), and Neurobehavioral Cognitive Status Examination (COGNISTAT). CSF levels of total αS, O-αS, Aß1-42, total tau and tau phosphorylated at threonine 181 (P-tau181p) were measured. CSF levels of these proteins were compared with clinical assessments from the UPDRS, MoCA and COGNISTAT using Spearman correlation analysis. Spearman correlation coefficients among CSF protein levels were also evaluated. RESULTS: CSF levels of αS were negatively correlated with UPDRS part III (motor score) (p < 0.05) and bradykinesia (p < 0.01), and positively correlated with COGNISTAT subtest of judgement (p < 0.01) and CSF levels of Aß1-42 (p < 0.001), total tau (p < 0.001) and P-tau181p (p < 0.01). Lower CSF levels of Aß1-42, total tau and P-tau181p were significantly related to worsening of some motor and/or cognitive functions. The CSF level of O-αS showed no correlation with any motor and cognitive assessments or with CSF levels of the other proteins. CONCLUSION: CSF levels of αS are correlated with some clinical symptoms and CSF levels of other pathogenic proteins in drug-naïve PD patients. These correlations suggest a central role for interaction and aggregation of αS with Aß1-42, tau, and phosphorylated tau in the pathogenesis of PD. Although O-αS has been shown to have neurotoxic effects, CSF levels do not reflect clinical symptoms or levels of other proteins in cross-sectional assessment.


Assuntos
Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Doença de Parkinson/líquido cefalorraquidiano , alfa-Sinucleína/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia
18.
Life Sci ; 231: 116581, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31220524

RESUMO

AIMS: The aims of this study were to investigate the effect of colonic electrical stimulation (CES) on delayed colonic transit in Parkinson's disease (PD) model induced by rotenone and its possible mechanisms. MAIN METHODS: Sprague-Dawley male rats were implanted with a pair of electrodes on the serosa at the proximal colon and rotenone was subcutaneously injected for 6 weeks to induce the PD model. Behavior activity, stool volume and open-field test were recorded during the injection. Colonic propulsion rate was measured 6 weeks after rotenone injection. Colon samples of all rats were collected for the measurement of phosphorylated alpha-synuclein, choline acetyltransferase (CHAT), neuronal nitric oxide synthase (nNOS), and tyrosine hydroxylase (TH). The protocols of control rats were the same as the PD rats except that no electrodes were implanted and no rotenone was injected. KEY FINDINGS: (1) Rotenone-induced PD rats demonstrated weight loss, significant decrease of the dopaminergic neurons in substantia nigra, and impairment of colon movement. (2) CES significantly accelerated the delayed colonic transmit (91.67 ±â€¯5.58% vs 51.33 ±â€¯4.18%), superior to Macrogol-4000. (3) CES significantly upregulated the expression of CHAT, nNOS and TH protein in colon of PD rats. (4) In colon of PD rats, the phosphorylated alpha-synuclein was significantly upregulated, but CES had no significant effect on phosphorylated alpha-synuclein. SIGNIFICANCE: Our data show that CES can normalize the delayed colonic transit and this normalization may attribute to affecting enteric excitatory and inhibitory neurons.


Assuntos
Colo/metabolismo , Sistema Nervoso Entérico/efeitos dos fármacos , Doença de Parkinson/fisiopatologia , Animais , Colina O-Acetiltransferase/metabolismo , Colo/fisiopatologia , Constipação Intestinal/fisiopatologia , Modelos Animais de Doenças , Estimulação Elétrica , Motilidade Gastrointestinal/efeitos dos fármacos , Intestino Delgado/metabolismo , Masculino , Neurônios/efeitos dos fármacos , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Ratos , Ratos Sprague-Dawley , Rotenona/metabolismo , Rotenona/farmacologia , Substância Negra/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/metabolismo , alfa-Sinucleína/metabolismo
19.
Nervenarzt ; 90(8): 767-772, 2019 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-31243506

RESUMO

Over the last two decades important achievements in research of Parkinson's disease led to the identification of specific pathways as well as histopathological fingerprints underlying the pathophysiology of the disease. This knowledge represents the basis for targeted disease-modifying treatment strategies. These treatment options target specific molecular defects in the causal chain or focus on the pathological α­synuclein species and their propagation. This article highlights the most relevant treatment approaches that are currently being addressed in preliminary clinical trials.


Assuntos
Doença de Parkinson , Medicina de Precisão , Ensaios Clínicos como Assunto , Humanos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , alfa-Sinucleína/química , alfa-Sinucleína/metabolismo
20.
Clin Nucl Med ; 44(9): 707-713, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31205154

RESUMO

OBJECTIVE: Nonmotor symptoms (NMS) are critical players in the patients' quality of life in Parkinson disease (PD). Vesicular monoamine transporter type 2 (VMAT2) has been reported owing to a role in affecting dopamine neurons in the striatum. Therefore, this study set out to characterize the relationship between VMAT2 distribution in the striatum in relation to the NMS in PD. METHODS: Totally, 21 age-matched normal controls and 37 patients with PD in the moderate stages were included, followed by examination using F-DTBZ (F-AV133) PET/CT. The specific uptake ratio (SUR) of each striatal subregion was then determined with the occipital cortex as the reference background region. The overall NMSs of each individual patient were evaluated. Finally, the role of the striatal SURs in the clinical symptom scores were evaluated through the application of a Spearman correlation analysis as well as a multivariable stepwise regression analysis. RESULTS: Patients with PD, particularly those at a more advanced stage, exhibited a more pronounced reduction in SURs in the bilateral putamen and caudate nucleus (P < 0.05, vs healthy controls). Meanwhile, patients at more advanced PD stages were found to have significantly worse scores in NMS except cognitive function. The Spearman correlation analysis demonstrated that NMS scores, with the exception of cognition scores, were correlated with striatal SURs (P < 0.05). CONCLUSION: The key findings of the study identified a correlation between decreased striatal VMAT2 with a broad spectrum of NMS in patients with PD, highlighting the association between diminished dopamine supply and the development of NMS in PD.


Assuntos
Neostriado/metabolismo , Doença de Parkinson/metabolismo , Proteínas Vesiculares de Transporte de Monoamina/metabolismo , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Qualidade de Vida
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