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1.
Artigo em Inglês | MEDLINE | ID: mdl-38442043

RESUMO

OBJECTIVE: A pathological tremor (PT) is an involuntary rhythmic movement of varying frequency and amplitude that affects voluntary motion, thus compromising individuals' independence. A comprehensive model incorporating PT's physiological and biomechanical aspects can enhance our understanding of the disorder and provide valuable insights for therapeutic approaches. This study aims to build a biomechanical model of pathological tremors using OpenSim's realistic musculoskeletal representation of the human wrist with two degrees of freedom. METHODS: We implemented a Matlab/OpenSim interface for a forward dynamics simulation, which allows for the modeling, simulation, and design of a physiological H∞ closed-loop control. This system replicates pathological tremors similar to those observed in patients when their arm is extended forward, the wrist is pronated, and the hand is subject to gravity forces. The model was individually tuned to five subjects (four Parkinson's disease patients and one diagnosed with essential tremor), each exhibiting distinct tremor characteristics measured by an inertial sensor and surface EMG electrodes. Simulation agreement with the experiments for EMGs, central frequency, joint angles, and angular velocities were evaluated by Jensen-Shannon divergence, histogram centroid error, and histogram intersection. RESULTS: The model emulated individual tremor statistical characteristics, including muscle activations, frequency, variability, and wrist kinematics, with greater accuracy for the four Parkinson's patients than the essential tremor. CONCLUSION: The proposed model replicated the main statistical features of subject-specific wrist tremor kinematics. SIGNIFICANCE: Our methodology may facilitate the design of patient-specific rehabilitation devices for tremor suppression, such as neural prostheses and electromechanical orthoses.


Assuntos
Discinesias , Tremor Essencial , Doença de Parkinson , Humanos , Tremor , Punho/fisiologia , Articulação do Punho , Fenômenos Biomecânicos
2.
Parkinsonism Relat Disord ; 116: 105847, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37844348

RESUMO

INTRODUCTION: Progressive Supranuclear Palsy (PSP) is a neurodegenerative tauopathy and, to date, the pathophysiological mechanisms in PSP that lead to Tau hyperphosphorylation and neurodegeneration are not clear. In some brain areas, Tau pathology in glial cells appears to precede Tau aggregation in neurons. The development of a model using astrocyte cell lines derived from patients has the potential to identify molecules and pathways that contribute to early events of neurodegeneration. We developed a model of induced pluripotent stem cells (iPSC)-derived astrocytes to investigate the pathophysiology of PSP, particularly early events that might contribute to Tau hyperphosphorylation, applying omics approach to detect differentially expressed genes, metabolites, and proteins, including those from the secretome. METHODS: Skin fibroblasts from PSP patients (without MAPT mutations) and controls were reprogrammed to iPSCs, further differentiated into neuroprogenitor cells (NPCs) and astrocytes. In the 5th passage, astrocytes were harvested for total RNA sequencing. Intracellular and secreted proteins were processed for proteomics experiments. Metabolomics profiling was obtained from supernatants only. RESULTS: We identified hundreds of differentially expressed genes. The main networks were related to cell cycle re-activation in PSP. Several proteins were found exclusively secreted by the PSP group. The cellular processes related to the cell cycle and mitotic proteins, TriC/CCT pathway, and redox signaling were enriched in the secretome of PSP. Moreover, we found distinct sets of metabolites between PSP and controls. CONCLUSION: Our iPSC-derived astrocyte model can provide distinct molecular signatures for PSP patients and it is useful to elucidate the initial stages of PSP pathogenesis.


Assuntos
Células-Tronco Pluripotentes Induzidas , Paralisia Supranuclear Progressiva , Tauopatias , Humanos , Paralisia Supranuclear Progressiva/diagnóstico , Astrócitos/metabolismo , Proteínas tau/genética , Tauopatias/patologia , Neurônios/metabolismo
3.
Mov Disord ; 38(9): 1625-1635, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37469269

RESUMO

BACKGROUND: Sex differences in Parkinson's disease (PD) risk are well-known. However, the role of sex chromosomes in the development and progression of PD is still unclear. OBJECTIVE: The objective of this study was to perform the first X-chromosome-wide association study for PD risk in a Latin American cohort. METHODS: We used data from three admixed cohorts: (1) Latin American Research consortium on the Genetics of Parkinson's Disease (n = 1504) as discover cohort, and (2) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (3) Bambui Aging cohort (n = 1442) as replication cohorts. We also developed an X-chromosome framework specifically designed for admixed populations. RESULTS: We identified eight linkage disequilibrium regions associated with PD. We replicated one of these regions (top variant rs525496; discovery odds ratio [95% confidence interval]: 0.60 [0.478-0.77], P = 3.13 × 10-5 replication odds ratio: 0.60 [0.37-0.98], P = 0.04). rs5525496 is associated with multiple expression quantitative trait loci in brain and non-brain tissues, including RAB9B, H2BFM, TSMB15B, and GLRA4, but colocalization analysis suggests that rs5525496 may not mediate risk by expression of these genes. We also replicated a previous X-chromosome-wide association study finding (rs28602900), showing that this variant is associated with PD in non-European populations. CONCLUSIONS: Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Cromossomos Humanos X , Doença de Parkinson , Feminino , Humanos , Masculino , Estudo de Associação Genômica Ampla , Hispânico ou Latino , América Latina , Doença de Parkinson/genética , Fatores Sexuais , Cromossomos Humanos X/genética , Desequilíbrio de Ligação/genética
4.
medRxiv ; 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36778409

RESUMO

Sex differences in Parkinson Disease (PD) risk are well-known. However, it is still unclear the role of sex chromosomes in the development and progression of PD. We performed the first X-chromosome Wide Association Study (XWAS) for PD risk in Latin American individuals. We used data from three admixed cohorts: (i) Latin American Research consortium on the GEnetics of Parkinson's Disease (n=1,504) as discover cohort and (ii) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (iii) Bambui Aging cohort (n= 1,442) as replication cohorts. After developing a X-chromosome framework specifically designed for admixed populations, we identified eight linkage disequilibrium regions associated with PD. We fully replicated one of these regions (top variant rs525496; discovery OR [95%CI]: 0.60 [0.478 - 0.77], p = 3.13 × 10 -5 ; replication OR: 0.60 [0.37-0.98], p = 0.04). rs525496 is an expression quantitative trait loci for several genes expressed in brain tissues, including RAB9B, H2BFM, TSMB15B and GLRA4 . We also replicated a previous XWAS finding (rs28602900), showing that this variant is associated with PD in non-European populations. Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies.

5.
Parkinsonism Relat Disord ; 102: 7-15, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35917738

RESUMO

BACKGROUND: Large-scale Parkinson's disease (PD) genome-wide association studies (GWAS) have, until recently, only been conducted on subjects with European-ancestry. Consequently, polygenic risk scores (PRS) constructed using PD GWAS data are likely to be less predictive when applied to non-European cohorts. METHODS: Using GWAS data from the largest study to date, we constructed a PD PRS for a Latino PD cohort (1497 subjects from LARGE-PD) and tested it for association with PD status and age at onset. We validated the PRS performance by testing it in an independent Latino cohort (448 subjects) and by repeating the analysis in LARGE-PD with the addition of 440 external Peruvian controls. We also tested SNCA haplotypes for association with PD risk in LARGE-PD and a European-ancestry PD cohort. RESULTS: The GWAS-significant PD PRS had an area under the receiver-operator curve (AUC) of 0.668 (95% CI: 0.640-0.695) in LARGE-PD. The inclusion of external Peruvian controls mitigated this result, dropping the AUC 0.632 (95% CI: 0.607-0.657). At the SNCA locus, haplotypes differ by ancestry. Ancestry-specific SNCA haplotypes were associated with PD status in both LARGE-PD and the European-ancestry cohort (p-value < 0.05). These haplotypes both include the rs356182 G-allele, but only share 14% of their variants overall. CONCLUSION: The PD PRS has potential for PD risk prediction in Latinos, but variability caused by admixture patterns and bias in a European-ancestry PD PRS data limits its utility. The inclusion of diverse subjects can help elucidate PD risk loci and improve risk prediction in non-European cohorts.


Assuntos
Estudo de Associação Genômica Ampla , Doença de Parkinson , Predisposição Genética para Doença/genética , Haplótipos , Hispânico ou Latino/genética , Humanos , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , alfa-Sinucleína/genética
6.
Front Aging Neurosci ; 14: 900029, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35645779

RESUMO

Background: Medication adherence is a crucial component in the management of patients with chronic diseases needing a long-term pharmacotherapy. Parkinson's disease (PD) is a chronic, degenerative disease with complex drug treatment that poses challenging barriers to patient adherence. The adoption of best practices of scale development can contribute to generate solid concepts and, in the long run, a more stable knowledge base on the underlying constructs of medication adherence in PD measured by the items of the first scale to be created for this purpose. Purpose: To present the development process and clinimetric testing plan of the Parkinson's Disease Medication Adherence Scale (PD-MAS). Method: We adopted a hybrid approach plan based on the United States Food and Drug Administration and Benson and Clark Guide that will create a patient-reported outcome instrument. We presented an overview of consecutive and interrelated steps, containing a concise description of each one. International research centers from Brazil and United States were initially involved in the planning and implementation of the methodological steps of this study. Results: We developed a four-phase multimethod approach for the conceptualization and the clinimetric testing plan of the PD-MAS. First, we describe the development process of the conceptual framework of the PD-MAS underpinning the scale construct; second, we formalized the development process of the first version of the PD-MAS from the generation of item pools to the content validation and pre-testing; third, we established the steps for the first pilot testing and revision; fourth, we describe the steps plan for the first pilot testing and revision, to finally describe its clinimetric testing plan and validation. Conclusion: The overview presentation of the development phases and the clinimetric testing plan of the PD-MAS demonstrate the feasibility of creating an instrument to measure the multidimensional and multifactorial components of the medication adherence process in people with PD.

7.
Front Genet ; 12: 671079, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630506

RESUMO

In adulthood, the ability to digest lactose, the main sugar present in milk of mammals, is a phenotype (lactase persistence) observed in historically herder populations, mainly Northern Europeans, Eastern Africans, and Middle Eastern nomads. As the -13910∗T allele in the MCM6 gene is the most well-characterized allele responsible for the lactase persistence phenotype, the -13910C > T (rs4988235) polymorphism is commonly evaluated in lactase persistence studies. Lactase non-persistent adults may develop symptoms of lactose intolerance when consuming dairy products. In the Americas, there is no evidence of the consumption of these products until the arrival of Europeans. However, several American countries' dietary guidelines recommend consuming dairy for adequate human nutrition and health promotion. Considering the extensive use of dairy and the complex ancestry of Pan-American admixed populations, we studied the distribution of -13910C > T lactase persistence genotypes and its flanking haplotypes of European origin in 7,428 individuals from several Pan-American admixed populations. We found that the -13910∗T allele frequency in Pan-American admixed populations is directly correlated with allele frequency of the European sources. Moreover, we did not observe any overrepresentation of European haplotypes in the -13910C > T flanking region, suggesting no selective pressure after admixture in the Americas. Finally, considering the dominant effect of the -13910∗T allele, our results indicate that Pan-American admixed populations are likely to have higher frequency of lactose intolerance, suggesting that general dietary guidelines deserve further evaluation across the continent.

8.
Ann Neurol ; 90(3): 353-365, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34227697

RESUMO

OBJECTIVE: This work was undertaken in order to identify Parkinson's disease (PD) risk variants in a Latino cohort, to describe the overlap in the genetic architecture of PD in Latinos compared to European-ancestry subjects, and to increase the diversity in PD genome-wide association (GWAS) data. METHODS: We genotyped and imputed 1,497 PD cases and controls recruited from nine clinical sites across South America. We performed a GWAS using logistic mixed models; variants with a p-value <1 × 10-5 were tested in a replication cohort of 1,234 self-reported Latino PD cases and 439,522 Latino controls from 23andMe, Inc. We also performed an admixture mapping analysis where local ancestry blocks were tested for association with PD status. RESULTS: One locus, SNCA, achieved genome-wide significance (p-value <5 × 10-8 ); rs356182 achieved genome-wide significance in both the discovery and the replication cohorts (discovery, G allele: 1.58 OR, 95% CI 1.35-1.86, p-value 2.48 × 10-8 ; 23andMe, G allele: 1.26 OR, 95% CI 1.16-1.37, p-value 4.55 × 10-8 ). In our admixture mapping analysis, a locus on chromosome 14, containing the gene STXBP6, achieved significance in a joint test of ancestries and in the Native American single-ancestry test (p-value <5 × 10-5 ). A second locus on chromosome 6, containing the gene RPS6KA2, achieved significance in the African single-ancestry test (p-value <5 × 10-5 ). INTERPRETATION: This study demonstrated the importance of the SNCA locus for the etiology of PD in Latinos. By leveraging the demographic history of our cohort via admixture mapping, we identified two potential PD risk loci that merit further study. ANN NEUROL 2021;90:353-365.


Assuntos
Loci Gênicos/genética , Variação Genética/genética , Estudo de Associação Genômica Ampla/métodos , Hispânico ou Latino/genética , Doença de Parkinson/etnologia , Doença de Parkinson/genética , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Polimorfismo de Nucleotídeo Único/genética , América do Sul/etnologia
9.
Neurorehabil Neural Repair ; 35(8): 729-737, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34047233

RESUMO

BACKGROUND: Functional imaging studies have associated dystonia with abnormal activation in motor and sensory brain regions. Commonly used techniques such as functional magnetic resonance imaging impose physical constraints, limiting the experimental paradigms. Functional near-infrared spectroscopy (fNIRS) offers a new noninvasive possibility for investigating cortical areas and the neural correlates of complex motor behaviors in unconstrained settings. METHODS: We compared the cortical brain activation of patients with focal upper-limb dystonia and controls during the writing task under naturalistic conditions using fNIRS. The primary motor cortex (M1), the primary somatosensory cortex (S1), and the supplementary motor area were chosen as regions of interest (ROIs) to assess differences in changes in both oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb) between groups. RESULTS: Group average activation maps revealed an expected pattern of contralateral recruitment of motor and somatosensory cortices in the control group and a more bilateral pattern of activation in the dystonia group. Between-group comparisons focused on specific ROIs revealed an increased activation of the contralateral M1 and S1 cortices and also of the ipsilateral M1 cortex in patients. CONCLUSIONS: Overactivity of contralateral M1 and S1 in dystonia suggest a reduced specificity of the task-related cortical areas, whereas ipsilateral activation possibly indicates a primary disorder of the motor cortex or an endophenotypic pattern. To our knowledge, this is the first study using fNIRS to assess cortical activity in dystonia during the writing task under natural settings, outlining the potential of this technique for monitoring sensory and motor retraining in dystonia rehabilitation.


Assuntos
Distonia/diagnóstico por imagem , Escrita Manual , Córtex Motor/diagnóstico por imagem , Adulto , Mapeamento Encefálico , Distonia/fisiopatologia , Feminino , Neuroimagem Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/fisiopatologia , Espectroscopia de Luz Próxima ao Infravermelho
10.
Am J Phys Med Rehabil ; 100(4): 359-366, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33727518

RESUMO

OBJECTIVE: The aim of the study was to verify the effect of a virtual rehabilitation protocol for patients with Parkinson disease, primarily assessing striatal dopamine transporters and secondarily motor symptoms and quality of life. DESIGN: Nineteen patients with Parkinson disease underwent an 8-wk virtual rehabilitation protocol using XBOX 360S. Evaluation of dopamine transporters was performed by single-photon emission computed tomography using TRODAT-1 as the radioligand. Participants were clinically assessed using the Unified Parkinson Disease Rating Scale to quantify motor symptoms. Moreover, the Parkinson Disease Questionnaire and Short-Form Health Status Survey were used to assess quality of life and the Berg Balance Scale to assess balance. RESULTS: Regarding our primary outcome, dopamine transporter was significantly increased in the putamen contralateral to the clinically most affected body side (P = 0.034) considering preintervention and postintervention measurements. Furthermore, we observed significant improvement in Unified Parkinson Disease Rating Scale (10-point reduction, P = 0.001), Parkinson Disease Questionnaire (11.3-point reduction, P = 0.001), Short-Form Health Status Survey ("Functional capacity," P = 0.001; "Pain," P = 0.006; and "Mental Health" domains, P < 0.001), and Berg Balance Scale (5-point increase, P = 0.015). CONCLUSIONS: In our group of Parkinson disease patients, this virtual rehabilitation protocol enabled a dopamine transporter increase in the region of the putamen contralateral to the clinically most affected body side. Moreover, motor signs and quality of life were significantly improved.


Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Terapia por Exercício/métodos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/reabilitação , Telerreabilitação/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Qualidade de Vida , Inquéritos e Questionários , Tomografia Computadorizada de Emissão de Fóton Único , Jogos de Vídeo
11.
Mov Disord ; 36(2): 434-441, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33150996

RESUMO

BACKGROUND: Parkinson's disease is the second most common neurodegenerative disorder and affects people from all ethnic backgrounds, yet little is known about the genetics of Parkinson's disease in non-European populations. In addition, the overall identification of copy number variants at a genome-wide level has been understudied in Parkinson's patients. The objective of this study was to understand the genome-wide burden of copy number variants in Latinos and its association with Parkinson's disease. METHODS: We used genome-wide genotyping data from 747 Parkinson's disease patients and 632 controls from the Latin American Research Consortium on the Genetics of Parkinson's disease. RESULTS: Genome-wide copy number burden analysis showed that patients were significantly enriched for copy number variants overlapping known Parkinson's disease genes compared with controls (odds ratio, 3.97; 95%CI, 1.69-10.5; P = 0.018). PRKN showed the strongest copy number burden, with 20 copy number variant carriers. These patients presented an earlier age of disease onset compared with patients with other copy number variants (median age at onset, 31 vs 57 years, respectively; P = 7.46 × 10-7 ). CONCLUSIONS: We found that although overall genome-wide copy number variant burden was not significantly different, Parkinson's disease patients were significantly enriched with copy number variants affecting known Parkinson's disease genes. We also identified that of 250 patients with early-onset disease, 5.6% carried a copy number variant on PRKN in our cohort. Our study is the first to analyze genome-wide copy number variant association in Latino Parkinson's disease patients and provides insights about this complex disease in this understudied population. © 2020 International Parkinson and Movement Disorder Society.


Assuntos
Doença de Parkinson , Idade de Início , Variações do Número de Cópias de DNA/genética , Estudo de Associação Genômica Ampla , Hispânico ou Latino/genética , Humanos , América Latina , Pessoa de Meia-Idade , Doença de Parkinson/genética
12.
PeerJ ; 8: e8552, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32095367

RESUMO

BACKGROUND: Parkinson's disease (PD) leads to several changes in motor control, many of them related to informational or cognitive overload. The aim of this study was to investigate the influence of knowledge and intention on the postural control performance and on the coupling between visual information and body sway in people with and without PD standing upright. METHODS: Participants were 21 people with PD (62.1 ± 7.2 years), stages 1 and 2 (Hoehn & Yahr scale), under dopaminergic medication, and 21 people in the control group (62.3 ± 7.1 years). Participants stood upright inside a moving room, performing seven trials of 60 s. In the first trial, the room remained motionless. In the others, the room oscillated at 0.2 Hz in the anterior-posterior direction: in the first block of three trials, the participants were not informed about the visual manipulation; in the second block of three trials, participants were informed about the room movement and asked to resist the visual influence. An OPTOTRAK system recorded the moving room displacement and the participants' sway. The variables mean sway amplitude (MSA), coherence and gain were calculated. RESULTS: With no visual manipulation, no difference occurred between groups for MSA. Under visual manipulation conditions, people with PD presented higher MSA than control, and both groups reduced the sway magnitude in the resisting condition. Control group reduced sway magnitude by 6.1%, while PD group reduced by 11.5%. No difference was found between groups and between conditions for the coupling strength (coherence). For the coupling structure (gain), there was no group difference, but both groups showed reduced gain in the resisting condition. Control group reduced gain by 12.0%, while PD group reduced by 9.3%. CONCLUSIONS: People with PD, under visual manipulation, were more influenced than controls, but they presented the same coupling structure between visual information and body sway as controls. People in early stages of PD are able to intentionally alter the influence of visual information.

13.
Mov Disord ; 34(11): 1722-1727, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31483534

RESUMO

BACKGROUND: In patients with Parkinson's disease, stimulation above the subthalamic nucleus (STN) may engage the pallidofugal fibers and directly suppress dyskinesia. OBJECTIVES: The objective of this study was to evaluate the effect of interleaving stimulation through a dorsal deep brain stimulation contact above the STN in a cohort of PD patients and to define the volume of tissue activated with antidyskinesia effects. METHODS: We analyzed the Core Assessment Program for Surgical Interventional Therapies dyskinesia scale, Unified Parkinson's Disease Rating Scale parts III and IV, and other endpoints in 20 patients with interleaving stimulation for management of dyskinesia. Individual models of volume of tissue activated and heat maps were used to identify stimulation sites with antidyskinesia effects. RESULTS: The Core Assessment Program for Surgical Interventional Therapies dyskinesia score in the on medication phase improved 70.9 ± 20.6% from baseline with noninterleaved settings (P < 0.003). With interleaved settings, dyskinesia improved 82.0 ± 27.3% from baseline (P < 0.001) and 61.6 ± 39.3% from the noninterleaved phase (P = 0.006). The heat map showed a concentration of volume of tissue activated dorsally to the STN during the interleaved setting with an antidyskinesia effect. CONCLUSION: Interleaved deep brain stimulation using the dorsal contacts can directly suppress dyskinesia, probably because of the involvement of the pallidofugal tract, allowing more conservative medication reduction. © 2019 International Parkinson and Movement Disorder Society.


Assuntos
Estimulação Encefálica Profunda , Discinesias/terapia , Doença de Parkinson/terapia , Núcleo Subtalâmico/cirurgia , Estimulação Encefálica Profunda/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
14.
Sci Rep ; 9(1): 8965, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31222185

RESUMO

After Alzheimer, Parkinson disease (PD) is the most frequently occurring progressive, degenerative neurological disease. It affects both sympathetic and parasympathetic nervous systems in a variable fashion. Cardiovascular symptoms are present in almost all stages of PD and narrower heart rate variability is the earliest sign. Administration of Levodopa to PD patients has proven to provide some degree of neurological protection. This drug, however, causes side effects including nausea and vomiting, lessened by the administration of domperidone. Autopsies in PD patients led some researchers to suggest the involvement of the ventricular arrhythmia induced by domperidone. The aim of the present study was to determine the impact of the adjusted human maximal dose of domperidone, on cardiological features of Wistar rats. domperidone was administered to both 6-hydroxydopamine Parkinsonism models and regular Wistar rats. Quantitative analysis of ranges of heart beat variation showed significant abnormal distribution in both groups receiving domperidone as compared with respective sham counterparts. However, qualitative analysis of Poincaré plots showed that 6-hydroxydopamine Parkinsonism models receiving domperidone had the narrowest full range of heart beat and the worst distribution heart beat ranges as compared with all study groups corroborating with previous suggestion that domperidone administration to PD patients is likely to play a role in sudden unexpected death in this group of patients.


Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Domperidona/farmacologia , Antagonistas de Dopamina/farmacologia , Oxidopamina/efeitos adversos , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/complicações , Animais , Comportamento Animal , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Modelos Animais de Doenças , Domperidona/administração & dosagem , Domperidona/efeitos adversos , Antagonistas de Dopamina/administração & dosagem , Antagonistas de Dopamina/efeitos adversos , Eletrocardiografia , Frequência Cardíaca , Humanos , Imuno-Histoquímica , Masculino , Ratos
19.
NPJ Parkinsons Dis ; 3: 19, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28649619

RESUMO

Mutations in Leucine-Rich Repeat Kinase 2 (LRRK2), primarily located in codons G2019 and R1441, represent the most common genetic cause of Parkinson's disease in European-derived populations. However, little is known about the frequency of these mutations in Latin American populations. In addition, a prior study suggested that a LRRK2 polymorphism (p.Q1111H) specific to Latino and Amerindian populations might be a risk factor for Parkinson's disease, but this finding requires replication. We screened 1734 Parkinson's disease patients and 1097 controls enrolled in the Latin American Research Consortium on the Genetics of Parkinson's disease (LARGE-PD), which includes sites in Argentina, Brazil, Colombia, Ecuador, Peru, and Uruguay. Genotypes were determined by TaqMan assay (p.G2019S and p.Q1111H) or by sequencing of exon 31 (p.R1441C/G/H/S). Admixture proportion was determined using a panel of 29 ancestry informative markers. We identified a total of 29 Parkinson's disease patients (1.7%) who carried p.G2019S and the frequency ranged from 0.2% in Peru to 4.2% in Uruguay. Only two Parkinson's disease patients carried p.R1441G and one patient carried p.R1441C. There was no significant difference in the frequency of p.Q1111H in patients (3.8%) compared to controls (3.1%; OR 1.02, p = 0.873). The frequency of LRRK2-p.G2019S varied greatly between different Latin American countries and was directly correlated with the amount of European ancestry observed. p.R1441G is rare in Latin America despite the large genetic contribution made by settlers from Spain, where the mutation is relatively common.

20.
Eur J Phys Rehabil Med ; 53(2): 173-183, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27879959

RESUMO

BACKGROUND: Evidences have shown that physiotherapy programs may improve the balance of individuals with Parkinson's disease (PD), although it is not clear which specific exercise program is better. AIM: The aim of this study was to compare the effectiveness of balance versus resistance training on postural control measures in PD patients. DESIGN: Randomized controlled trial. SETTING: The study was conducted in a physiotherapy outpatient clinic of a university hospital. POPULATION: A total of 40 PD participants were randomly divided into two groups: balance training (BT) and resistance training (RT). METHODS: The BT group focused on balance training, functional independence and gait while the RT group performed resistance exercises emphasizing the lower limbs and trunk, both supervised by trained physiotherapists. Therapy sessions were held twice a week (at 60 minutes), totaling 24 sessions. The primary outcome was evaluated by force platform with center of pressure sway measures in different balance conditions and the secondary outcome was evaluated by Balance Evaluation Systems Test (BESTest) scale to determine the effects of the intervention on postural control. RESULTS: Significant improvement of postural control (pre vs. post 15.1 vs. 9.6 cm2) was only reported in favor of BT group (d=1.17) for one-legged stand condition on force platform. The standardized mean difference between groups was significantly (P<0.02), with 36% of improvement for BT vs. 0.07% for RT on this condition. Significant improvement (P<0.05) was also observed in favor of BT (in mean 3.2%) for balance gains in some BESTest scores, when compared to RT group (-0.98%). CONCLUSIONS: Postural control in Parkinson's disease is improved when training by a directional and specific balance program than a resistance training program. CLINICAL REHABILITATION IMPACT: Balance training is superior to resistance training in regard to improving postural control of individuals with PD. Gold standard instruments (high in cost and difficult to access) were used to assess balance, as well as scales with clinical applicability (low cost, easily acceptable, applicable and valid), which can guide the management of physiotherapists both in their decision-making and in clinical practice.


Assuntos
Marcha/fisiologia , Doença de Parkinson/reabilitação , Equilíbrio Postural/fisiologia , Treinamento de Força/métodos , Idoso , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Doença de Parkinson/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento
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