Le traumatisme crânien (TC) représente un des problèmes majeurs de santé publique, pour lequel à l’heure actuelle il n’existe aucun traitement. Le TC induit une neuro-inflammation délétère qui pourrait contribuer à l’apparition des lésions de la substance blanche (SB). Ces dernières sont à l’origine de lourdes conséquences neurologiques chez les patients victimes de TC. Néanmoins, très peu d’études se sont intéressées à ces lésions bien que plus sévères que les lésions de la substance grise. Ainsi une meilleure connaissance de leur évolution et des causes devient indispensable. L’hyperactivation de la poly(ADP ribose)polymérase (PARP) joue un rôle délétère dans les conséquences post-traumatiques, notamment sur la neuro-inflammation. Ainsi son inhibition pourrait être bénéfique le développement des lésions de la SB. Dans ce contexte, l’objectif de notre travail a été d’évaluer le rôle de la PARP dans les lésions de la SB dans un modèle expérimental de TC induit par impact cortical contrôlé chez la souris. Dans une première partie, nous avons étudié l’évolution de la démyélinisation dans le corps calleux, une structure riche en SB, entre 6 heures et 3 mois post-TC. Parallèlement, les évolutions de la lésion cérébrale, des déficits sensorimoteurs, de la neuro-inflammation et de l’œdème cérébral ont été étudiées. Le TC induit (1) une démyélinisation dès 7 jours et au moins jusqu’à 3 mois post-TC, précédée par (2) une lésion cérébrale entre 24 et 72 heures suivie par une cicatrisation, (3) une neuro-inflammation entre 6 heures et 7 jours et (4) un œdème cérébral entre 6 et 72 heures post-TC. De plus, le TC induit des déficits sensorimoteurs à 6 heures et 3 mois. Ces résultats montrent que ce modèle est adapté pour étudier les lésions de la SB post-TC, et que la neuro-inflammation et l’œdème cérébral pourrait être impliqués dans la démyélinisation. Dans une deuxième partie, nous avons étudié le rôle de la PARP dans les lésions de la SB suite à TC à l’aide de souris knockout (KO) et wild-type (WT) pour le gène de la PARP. Nous avons mis en évidence que les souris KO ne présentent pas de démyélinisation bilatérale du corps calleux après un TC par rapport aux souris WT à 7 jours post-TC, démontrant pour la première fois l’implication de cette enzyme dans les lésions de la SB consécutives à un TC. De plus, nous avons constaté que les souris KO non traumatisées présentent une diminution de myélinisation comparativement aux souris WT non traumatisées, suggérant un rôle de la PARP dans le processus physiologique de la myélinisation.En conclusion, l’ensemble de ce travail expérimental a permis (1) une meilleure caractérisation de la démyélinisation post-TC et des mécanismes potentiellement impliqués dans cette dernière, et (2) de démontrer pour la première fois le rôle délétère de la PARP dans la démyélinisation induite par un TC. Nos travaux suggèrent le potentiel de l’inhibition de la PARP comme stratégie thérapeutique pour la prévention des lésions de la SB post-traumatiques. / Traumatic brain injury (TBI) is a leading cause of death and disability for which there is no neuroprotective treatment up to date. It results in neuroinflammation that may participate in lasting motor and cognitive impairments accompanied by changes in white matter (WM) tracts. WM lesions, evidenced by demyelination, are associated with neurological disorders and in clinical studies are common consequences in patients with chronic TBI. Several studies suggest a contribution of an overactivation of the poly(ADP-ribose) polymerase (PARP) to the neuroinflammatory response which may lead to demyelination. The first part of this study was dedicated to a detailed in vivo assessment of the evolution over time of neurological disorders, cerebral lesion and edema, neuroinflammation and white matter injury induced by controlled cortical impact (CCI) between 6 hours and 12 weeks post-TBI. Notably in the corpus callosum, a significant demyelination starting at 7 days appeared to be a major consequence to post-traumatic neuroinflammation associated with motor dysfunctions. The second part of this study was dedicated to the evaluation of PARP’s role in WM lesions post-TBI, using PARP knockout (KO) mice. Our main findings reveal a diminished demyelination in the corpus callosum of TBI PARP KO as opposed to TBI PARP wildtype specimens. Hence, these data suggest for the first time PARP’s deleterious role in post-traumatic demyelination. In conclusion, taken together these data give an overall view of motor/sensorimotor deficits, neuroinflammation and demyelination in a CCI model of TBI that could help to validate pharmacological strategy for preventing post-traumatic WM injury. Notably, PARP’s inhibition seems to be a valid candidate as this enzyme participates in the establishment of a demyelinating process.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

A literatura mostra um número substancial de trabalhos que descrevem a influência do treinamento físico sobre o remodelamento ventricular em pacientes no contexto do pós-infarto agudo do miocárdio (IAM). Entretanto, essas publicações têm apresentado resultados conflitantes. O presente estudo teve como objetivo avaliar os efeitos do treinamento físico aeróbico de moderada intensidade, realizado em pacientes pós-IAM, sobre o remodelamento ventricular, e sua correlação com a ativação neuro-humoral. Foram avaliados 14 pacientes, de ambos os gêneros, idade média de 55,1 ± 10,8 anos, acometidos por um único IAM de parede anterior, divididos em dois grupos: grupo treinado (GT) (n=07) e grupo controle (GC) (n=07). O período de seguimento para esse estudo foi de 12 semanas. Antes e após o período de seguimento, os pacientes realizaram exames laboratoriais, avaliação antropométrica, coleta da freqüência cardíaca (FC) de repouso, teste cardiopulmonar e ressonância magnética cardíaca. O GT realizou treinamento físico aeróbico supervisionado em esteira ergométrica, três vezes por semana, com intensidade definida pela FC atingida no limiar de anaerobiose ventilatório. A análise estatística foi realizada através do teste não paramétrico da Soma de Postos de Wilcoxon (análise intragrupo) e teste não paramétrico de Mann-Whitney (análise intergrupo), com nível de significância de 5%. Não houve alteração estatisticamente significante no peso, índice de massa corporal, perfil lipídico e glicemia de jejum pré e pós-intervenção tanto no GC quanto no GT. Houve redução estatisticamente significante da FC de repouso no GT, sem alteração no GC. Observou-se aumento estatisticamente significante do consumo de oxigênio no limiar de anaerobiose e no pico do esforço, bem como, no incremento do pulso de oxigênio apenas no GT. Houve redução estatisticamente significante do volume diastólico final, e tendência a significância no volume sistólico final do GC. Não se observou mudanças estatisticamente significantes nos volumes cavitários pré e pós-intervenção no GT. Não houve mudança estatisticamente significante na fração de ejeção tanto no GT quanto no GC. Houve redução estatisticamente significativa do fragmento N-terminal do proBNP na condição basal e no pico do esforço tanto no GT quanto no GC. Concluímos que o treinamento físico aeróbico, de moderada intensidade, propiciou um aumento da aptidão física e cardiorrespiratória, manutenção dos volumes cavitários e da função cardíaca, e comportamento satisfatório do status neuro-humoral no GT durante o período do estudo. / The literature shows a substantial number of studies describing the influence of physical training on ventricular remodeling in patients in the context of post-acute myocardial infarction (AMI). However, these publications have produced conflicting results. The present study was to evaluate the effects of aerobic physical training of moderate intensity, performed in patients after MI on ventricular remodeling, and its correlation with neurohumoral activation. We evaluated 14 patients of both genders, mean age 55.1 ± 10.8 years, affected by a single anterior wall AMI were divided into two groups: trained group (TG) (n = 07) and control group ( CG) (n = 07). The follow-up period for this study was 12 weeks. Before and after follow-up period, patients underwent laboratory tests, anthropometric measurements, collection of heart rate (HR) at rest, cardiopulmonary exercise testing and cardiac MRI. The TG performed supervised aerobic exercise training on a treadmill three times a week, with intensity defined by HR reached at ventilatory anaerobic threshold. Statistical analysis was performed using the nonparametric Wilcoxon Sum of stations (intragroup analysis) and nonparametric Mann-Whitney test (intergroup analysis), with a significance level of 5%. There was no statistically significant change in weight, body mass index, lipid profile and fasting glucose and post-intervention in both the CG and TG. There was a statistically significant reduction in resting HR in TG, no change in CG. There was a statistically significant increase in oxygen uptake in the anaerobic threshold and peak effort, as well as an increase in oxygen pulse only in the TG. There was a statistically significant reduction in end-diastolic volume, and a tendency to significance in end-systolic volume of the CG. There was no statistically significant changes in cavity volume before and after intervention in TG. There was no statistically significant change in ejection fraction in both the TG and GC. There was a statistically significant reduction of the N-terminal fragment of proBNP at baseline and at peak exercise in both the TG and CG. We conclude that aerobic exercise training of moderate intensity, provided an increase in cardiorespiratory fitness and, maintenance of the cavity volume and cardiac function, and satisfactory performance of the neuro-humoral status in TG during the study period.

Le traumatisme crânien (TC) représente un des problèmes majeurs de santé publique, pour lequel à l’heure actuelle il n’existe aucun traitement. Le TC induit une neuro-inflammation délétère qui pourrait contribuer à l’apparition des lésions de la substance blanche (SB). Ces dernières sont à l’origine de lourdes conséquences neurologiques chez les patients victimes de TC. Néanmoins, très peu d’études se sont intéressées à ces lésions bien que plus sévères que les lésions de la substance grise. Ainsi une meilleure connaissance de leur évolution et des causes devient indispensable. L’hyperactivation de la poly(ADP ribose)polymérase (PARP) joue un rôle délétère dans les conséquences post-traumatiques, notamment sur la neuro-inflammation. Ainsi son inhibition pourrait être bénéfique le développement des lésions de la SB. Dans ce contexte, l’objectif de notre travail a été d’évaluer le rôle de la PARP dans les lésions de la SB dans un modèle expérimental de TC induit par impact cortical contrôlé chez la souris. Dans une première partie, nous avons étudié l’évolution de la démyélinisation dans le corps calleux, une structure riche en SB, entre 6 heures et 3 mois post-TC. Parallèlement, les évolutions de la lésion cérébrale, des déficits sensorimoteurs, de la neuro-inflammation et de l’œdème cérébral ont été étudiées. Le TC induit (1) une démyélinisation dès 7 jours et au moins jusqu’à 3 mois post-TC, précédée par (2) une lésion cérébrale entre 24 et 72 heures suivie par une cicatrisation, (3) une neuro-inflammation entre 6 heures et 7 jours et (4) un œdème cérébral entre 6 et 72 heures post-TC. De plus, le TC induit des déficits sensorimoteurs à 6 heures et 3 mois. Ces résultats montrent que ce modèle est adapté pour étudier les lésions de la SB post-TC, et que la neuro-inflammation et l’œdème cérébral pourrait être impliqués dans la démyélinisation. Dans une deuxième partie, nous avons étudié le rôle de la PARP dans les lésions de la SB suite à TC à l’aide de souris knockout (KO) et wild-type (WT) pour le gène de la PARP. Nous avons mis en évidence que les souris KO ne présentent pas de démyélinisation bilatérale du corps calleux après un TC par rapport aux souris WT à 7 jours post-TC, démontrant pour la première fois l’implication de cette enzyme dans les lésions de la SB consécutives à un TC. De plus, nous avons constaté que les souris KO non traumatisées présentent une diminution de myélinisation comparativement aux souris WT non traumatisées, suggérant un rôle de la PARP dans le processus physiologique de la myélinisation.En conclusion, l’ensemble de ce travail expérimental a permis (1) une meilleure caractérisation de la démyélinisation post-TC et des mécanismes potentiellement impliqués dans cette dernière, et (2) de démontrer pour la première fois le rôle délétère de la PARP dans la démyélinisation induite par un TC. Nos travaux suggèrent le potentiel de l’inhibition de la PARP comme stratégie thérapeutique pour la prévention des lésions de la SB post-traumatiques. / Traumatic brain injury (TBI) is a leading cause of death and disability for which there is no neuroprotective treatment up to date. It results in neuroinflammation that may participate in lasting motor and cognitive impairments accompanied by changes in white matter (WM) tracts. WM lesions, evidenced by demyelination, are associated with neurological disorders and in clinical studies are common consequences in patients with chronic TBI. Several studies suggest a contribution of an overactivation of the poly(ADP-ribose) polymerase (PARP) to the neuroinflammatory response which may lead to demyelination. The first part of this study was dedicated to a detailed in vivo assessment of the evolution over time of neurological disorders, cerebral lesion and edema, neuroinflammation and white matter injury induced by controlled cortical impact (CCI) between 6 hours and 12 weeks post-TBI. Notably in the corpus callosum, a significant demyelination starting at 7 days appeared to be a major consequence to post-traumatic neuroinflammation associated with motor dysfunctions. The second part of this study was dedicated to the evaluation of PARP’s role in WM lesions post-TBI, using PARP knockout (KO) mice. Our main findings reveal a diminished demyelination in the corpus callosum of TBI PARP KO as opposed to TBI PARP wildtype specimens. Hence, these data suggest for the first time PARP’s deleterious role in post-traumatic demyelination. In conclusion, taken together these data give an overall view of motor/sensorimotor deficits, neuroinflammation and demyelination in a CCI model of TBI that could help to validate pharmacological strategy for preventing post-traumatic WM injury. Notably, PARP’s inhibition seems to be a valid candidate as this enzyme participates in the establishment of a demyelinating process.

O exercício aeróbico é recomendado para indivíduos pré-hipertensos como prevenção da hipertensão arterial. Uma única sessão de exercício aeróbico promove hipotensão pósexercício. Estudos prévios com normotensos observaram menor hipotensão pós-exercício pela manhã do que ao final da tarde, porém, estes estudos não incluíram uma situação controle (sem exercício) e avaliaram apenas alguns determinantes hemodinâmicos desse fenômeno. Dessa forma, o objetivo deste estudo foi analisar e comparar a resposta da pressão arterial (PA) e seus determinantes hemodinâmicos e mecanismos autonômicos após uma sessão de exercício aeróbico realizado pela manhã (9:00 h) e ao final do dia (18:30 h), relacionando os resultados obtidos com os efeitos deste exercício em alguns marcadores neuro-hormonais do ritmo circadiano. Para tanto, 16 homens pré-hipertensos participaram de 4 sessões experimentais conduzidas em ordem aleatória: duas pela manhã e duas ao final do dia. Em cada fase do dia, foram realizadas uma sessão controle (repouso) e outra de exercício (cicloergômetro, 45 min, 50% VO2pico). A PA clínica, o débito cardíaco (DC), a resistência vascular periférica (RVP), o volume sistólico (VS), a frequência cardíaca (FC), a modulação autonômica cardíaca e vasomotora, a sensibilidade barorreflexa, o fluxo sanguíneo muscular, a capacidade vasodilatadora e as concentrações plasmáticas de noradrenalina e adrenalina foram medidos antes e após a intervenção em cada sessão. Além disso, a PA ambulatorial de 24 horas foi medida após as sessões e a concentração do metabólito da melatonina 6- sulfatoximelatonina produzida durante a noite anterior e posterior a cada sessão foi dosada. Os dados foram analisados pela ANOVA de 2 ou 3 fatores repetidos bem como pelo teste t ou teste de wilcoxon pareado e as associações foram calculadas pelas correlações de Pearson e Spearman. Foi aceito como significante P0,05. O exercício promoveu maior redução da PA sistólica pela manhã do que ao final do dia (-7±3 vs -3±4 mmHg, P<0,05), enquanto que a PA diastólica diminuiu de forma semelhante nestas duas fases do dia (-3±3 vs -3±3 mmHg, respectivamente). O DC diminuiu e a RVP tendeu a aumentar pós-exercício pela manhã, enquanto que estas variáveis não se modificaram pós-exercício ao final do dia (-460±771ml/min e +2,0±3,8 mmHg.min/l; +148±633ml/min e -1,4±2,8 mmHg.min/l, respectivamente). O VS diminuiu similarmente pós-exercício em ambas as fases do dia (- 12±15 vs. -9±10 ml, P<0,05), enquanto que a FC aumentou mais ao final do dia (+7±5 vs. +10±5 bpm, P<0,05). Isto ocorreu, devido ao exercício promover aumento do balanço simpatovagal (BF/AF) somente ao final do dia (+1,5±1,6, P<0,05), enquanto que a modulação vasomotora (BFPAS) pós-exercício diminuiu apenas pela manhã (-0,5±0,9 mmHg2, P<0,05). A sensibilidade barorreflexa espontânea, avaliada pelo do ganho médio de sequências positivas e negativas (SBR±) diminuiu pós-exercício nas duas fases do dia. O exercício não teve nenhum efeito sobre o fluxo sanguíneo e a capacidade vasodilatadora do braço, mas aumentou a capacidade vasodilatadora da perna apenas quando o exercício foi realizado ao final do dia (+116±172 ua, P<0,05). Nas medidas ambulatoriais, o exercício realizado ao final do dia reduziu a PA de sono e no período entre a 5 e 7ª hora pós-exercício. O exercício não teve nenhum efeito sobre os níveis de noradrenalina, adrenalina e 6-sulfatoximelatonina. Dessa forma, não houve correlações consistentes entre o efeito do exercício nos níveis hormonais e nas variáveis hemodinâmicas, autonômicas e ambulatoriais em nenhuma das fases do dia. Em conclusão, em pré-hipertensos, uma única sessão de exercício aeróbico reduz a PA pósexercício tanto quando o exercício é realizado pela manhã quanto ao final do dia, mas o maior efeito hipotensor é observado quando o exercício é realizado pela manhã para a PA sistólica. Este maior efeito hipotensor sistólico se deve à queda do DC pela manhã, que ocorre devido à diminuição do volume sistólico e menor aumento da FC pós-exercício nesta fase do dia, o que é provocado pelo menor aumento do balanço simpatovagal e se acompanha de menor aumento na capacidade vasodilatadora da musculatura ativa nesta fase do dia. O efeito hipotensor do exercício, no entanto, ao final do dia se reflete em redução da PA de sono pósexercício. Os efeitos do exercício aeróbico, realizado em diferentes fases do dia, sobre a PA clínica e ambulatorial e seus mecanismos hemodinâmicos, autonômicas e vasculares não se relacionam aos efeitos deste exercício sobre as catecolaminas e a produção de melatonina / Aerobic exercise is recommended for prehypertensive individuals to prevent hypertension development. An aerobic exercise bout promotes post-exercise hypotension, and previous studies with normotensive individuals reported that post-exercise hypotension is lower when exercise is conducted in the morning than in the evening. However, these studies have not included a control situation (without exercise) and only evaluated some hemodynamic determinants of this phenomenon. Thus, the aim of this study was to analyze and to compare blood pressure (BP) responses and their hemodynamic determinants and autonomic mechanisms after an aerobic exercise performed in the morning (9:00a.m) and the evening 6:30p.m), associating these results with the effects of this exercise in some neurohormonal markers of circadian rhythms. For this, 16 prehypertensive men underwent 4 experimental sessions conducted in random order: two in the morning and two in the evening. At each time of day, one control (rest) and one exercise (cycle ergometer, 45 min, 50% of VO2peak) sessions were performed. Clinic BP, cardiac output (CO), systemic vascular resistance (SVR), stroke volume (SV), heart rate (HR), cardiac autonomic modulation, vasomotor modulation, baroreflex sensitivity, muscle blood flow, vasodilation and plasma concentrations of norepinephrine and epinephrine were measured before and after the intervention in each session. In addition, ambulatory BP was measured for 24 hours after the experimental sessions and the concentration of melatonin metabolite 6-sulfatoxymelatonin produced during the sleep before and after each session was assessed. Data were analyzed by 2 or 3-way ANOVA for repeated measures as well as by paired t test or Wilcoxon test, and the associations between variables were calculated by Pearson and Spearman correlations. P 0.05 was accepted as significant. Exercise produced a greater systolic BP reduction in the morning than the evening (-7 ± 3 -3 ± 4 mmHg, P<0.05), while the diastolic blood pressure decreased similarly in both times of day (-3±3 vs -3±3 mmHg, respectively, P<0.05). CO decreased and SVR tended to increased after exercise in the morning, while these variables did not change after exercise in the evening (-460 ± 771ml/min and +2.0 ± 3.8 mmHg.min/l; +148 633ml/min ± 2.8 and -1.4 ± mmHg.min/l , respectively). VS decreased similarly after exercise in both times of day (-12 ± 15 vs -9 ± 10 ml, P<0.05), while the HR increased more in the evening (+7 ± 5 vs +10 ± 5 bpm, P<0.05). This occurred because exercise increased sympathovagal balance only in the evening (+1.5 ± 1.6, P<0.05), whereas vasomotor modulation decreased only after exercise performed in the morning (-0.5 ± 0.9 mmHg2, P<0.05). Spontaneous baroreflex sensitivity, measured by the average gain of positive and negative sequences (± SBR) decreased after the exercise in both times of day. The exercise did not affect arm blood flow and vasodilatory capacity, but increased leg vasodilation when exercise was performed in the evening (+116 ± 172 au, P<0.05). In regard to ambulatory measures, the exercise performed in the evening reduced asleep BP and BP measured 5-7hr post-exercise. The exercise did not have any effect in the norepinephrine, epinephrine and 6- sulphatoxymelatonin. Thus, there was not consistent correlation between the effect of exercise in hormone levels and in hemodynamic, autonomic and ambulatory responses. In conclusion, in prehypertensives, a single bout of aerobic exercise reduces post-exercise BP regardless if the exercise is performed in the morning or in the evening, however a greater hypotensive effect is observed in the morning for systolic BP. This greater systolic hypotensive effect is due to the decrease in CO in the morning, related to a decrease in SV and a lower increase in HR after the exercise performed in the morning, which is caused by a lower increase in sympathovagal balance and is accompanied by a smaller increase in active muscles vasodilatory capacity in the morning. The hypotensive effect of evening exercise leads to a reduction in asleep BP. The effects of exercise, performed at different times of day, on postexercise clinic and ambulatory BP as well in its hemodynamic, autonomic and vascular determinants are not related to the effects of this exercise in catecholamines and melatonin production

Made available in DSpace on 2016-08-10T10:55:33Z (GMT). No. of bitstreams: 1 Luciana Martins Soares.pdf: 6149797 bytes, checksum: 7b62e95f2fb71974c5c913ff0947646d (MD5) Previous issue date: 2007-01-30 / The aim of this work was to evaluate the application of a protocol of ambulatorial intervention, based in the Bobath neuro-developmental concept, associate or not it domiciliary intervention and/or use of positive reinforcement in twelve children with cerebral palsy level I, III and IV of the GMFCS (System of classification of the gross motor function). They had been used, the GMFM (Measure of gross motor function) and the postural evaluation, for evaluation of the children. The study it occurred in a period of six weeks. The final result showed that had positive answer the application of the protocol of ambulatorial intervention it independently of the type of association. The association of the protocol with the domiciliary intervention showed was better. Already the results of the association of the positive reinforcement to the interventions had not been conclusive. / O objetivo desse trabalho foi avaliar a aplicação de um protocolo de intervenção ambulatorial, baseado no conceito neuroevolutivo Bobath, associado ou não a intervenção domiciliar e/ou uso de reforço positivo em doze crianças com paralisia cerebral nível I, III e IV do GMFCS (Sistema de classificação da função motora grossa). Foram utilizados, o GMFM (Medida de função motora grossa) e a avaliação postural, para avaliação das crianças. O estudo ocorreu num período de seis semanas. O resultado final mostrou que houve uma resposta positiva na aplicação do protocolo de intervenção ambulatorial independentemente do tipo de associação. A associação do protocolo com a intervenção domiciliar mostrou o melhor resultado. Já os resultados da associação do reforço positivo às intervenções não foram conclusivos.

Os objetivos desta pesquisa consistiram em contribuir para o projeto das órteses, realizar a análise cinemática do movimento de flexão/extensão do cotovelo, além de avaliar qualitativamente a independência na execução de atividades de vida diária e o ganho neurológico decorrente de um período de 6 meses de estimulação elétrica neuro-muscular (EENM). Participaram desta pesquisa oito tetraplégicos e um sujeito saudável. As órteses foram projetadas e os primeiros protótipos desenvolvidos. As avaliações cinemáticas foram realizadas durante dez tentativas do movimento de flexão/extensão do cotovelo em diferentes atividades. As avaliações qualitativas foram realizadas com os Protocolos ASIA e FIM. As órteses mostraram eficácia e funcionalidade. A avaliação cinemática mostrou que durante os movimentos com EENM houve repetibilidade, mudança no tipo de onda (de pico para retangular) e aumento do tempo de execução da atividade, comparado ao movimento voluntário. Com preensão de objeto e adição de cargas, houve alteração no padrão cinemático do movimento para a maioria dos pacientes, que indica insegurança em relação a preensão, fraqueza muscular, bem como, perturbação e incoordenação do movimento; em outros casos, houve aumento da amplitude de onda e predominância do tipo em rampa durante a EENM, o que possivelmente indica ação sinergista. Os resultados dos protocolos ASIA e FIM mostraram ganho neurológico e aumento no índice de independência funcional, para a maioria dos pacientes, decorrentes dos efeitos terapêuticos da EENM / The objectives of this research consisted of contributing for the orthosis project, to asses the knematics of the elbow flexion and extension, besides the qualitative evaluations of the independence to perform activities of daily living and neurological improvements due to a period of six months of neuromuscular electrical stimulation (NMES). Eight tetraplegics and one healthy subject participated in this study. The orthosis was projected and the first prototypes were developed. The kinematic assessment consisted of ten trials of elbow flexion and extension in different activities. The qualitative evaluations were accomplished with the ASIA and FIM Protocols. The orthosis showed effectiveness and functionality. The kinematics analysis showed that during movements with NMES there was repeatability, change in the wave form (peak to rectangular) and increase in time of performed trials, compared to the voluntary movement. With prehension of object and addition of loads, there was alteration in the kinematics pattern of the movement for most of the patients, which indicates insecurity during the prehension, muscular weakness, as well as perturbation and movement incoordination. On the others cases, there were higher wave amplitudes and wave forms mostly in ramp during NMES, which possibly indicates synergist action. The results of the ASIA e FIM Protocols showed neurological improvements and also in the index of functional independence for most of the patients due to the therapeutic effects of NMES

O complexo da esclerose tuberosa (TSC) é um transtorno clínico, com expressividade variável, caracterizado por hamartomas que podem ocorrer em diferentes órgãos. Tem herança autossômica dominante e é devido a mutações em um de dois genes supressores de tumor, TSC1 ou TSC2. Estes codificam para as proteínas hamartina e tuberina, respectivamente, que se associam formando um complexo macromolecular que regula funções como proliferação, diferenciação, crescimento e migração celular. As lesões cerebrais podem ser muito graves em pacientes com TSC e caracterizam-se por nódulos subependimários (SEN), astrocitomas subependimários de células gigantes (SEGA), tuberosidades corticais e heterotopias neuronais, podendo relacionar-se clinicamente à epilepsia refratária à terapia medicamentosa, deficiência intelectual, desordens do comportamento e hidrocefalia. O potencial de crescimento de SEGA até os 21 anos de idade dos pacientes exige acompanhamento periódico por exame de imagem e condutas clínicas ou cirúrgicas, conforme indicação médica. As lesões subependimárias têm sido explicadas por déficits de controle da proliferação, crescimento e diferenciação de precursores neuro-gliais na zona subventricular telencefálica. Embora a capacidade da tuberina em inibir a proliferação celular pela repressão do alvo da rapamicina em mamíferos (mTOR) esteja bem documentada, outros aspectos celulares do desenvolvimento de SEGA ainda não foram examinados. Assim, é importante estabelecer um sistema in vitro para o estudo de células da zona subventricular e testá-lo na análise das proteínas hamartina e tuberina. Neste sentido, o cultivo de neuroesferas em suspensão é muito apropriado. Neste estudo, buscamos relacionar a expressão e distribuição subcelular da hamartina e tuberina à capacidade proliferativa e de diferenciação das células de neuroesferas cultivadas in vitro a partir da dissociação da vesícula telencefálica de embriões de ratos normais. Analisamos a expressão e distribuição subcelular da hamartina e tuberina por imunofluorescência indireta em células entre a primeira e a quarta passagens das neuroesferas, sincronizadas nas fases G1 ou S do ciclo celular e após a reentrada no ciclo celular, através da incorporação de 5-bromo-2\'-desoxiuridina (BrdU) e imunofluorescência com anticorpo anti-BrdU. Em geral, células de neuroesferas apresentaram baixa colocalização entre hamartina e tuberina in vitro. A expressão da tuberina foi elevada em basicamente todas as células das esferas e fases do ciclo celular; ao contrário, a hamartina apresentou-se principalmente nas células da periferia das esferas. A colocalização entre hamartina e tuberina foi observada em células mais periféricas das esferas, sobretudo no citoplasma e, em G1, no núcleo celular. A proteína rheb, que conhecidamente interage diretamente com a tuberina, apresentou distribuição subcelular muito semelhante à desta. Ao carenciamento das células visando à parada do ciclo celular na transição G1/S, tuberina distribuiu-se ao núcleo celular em quase todas as células avaliadas e, de forma menos frequente, a hamartina também. À reentrada no ciclo celular pelo reacréscimo dos fatores de crescimento, avaliaram-se células com incorporação de BrdU ao seu núcleo celular, após 72 e 96 horas. Nestas, tuberina mostrou-se novamente no citoplasma de forma preponderante e hamartina manteve-se citoplasmática, em geral subjacente à membrana plasmática, em níveis mais baixos. Os grupos cujas células reciclaram por 72 ou 96 horas diferiram quanto ao aumento significativo da expressão da hamartina em células proliferativas no último. À diferenciação neuronal, aumentaram-se os níveis de expressão de hamartina observáveis à imunofluorescência indireta, tornando-se equivalentes àqueles da tuberina. Concluímos que as células de neuroesferas cultivadas em suspensão apresentam-se como um sistema apropriado ao estudo da distribuição das proteínas hamartina e tuberina e sua relação com o ciclo celular / The tuberous sclerosis complex (TSC) is a clinical disorder with variable expressivity, characterized by hamartomas that can occur in different organs. It has autosomal dominant inheritance and is due to mutations in one of two tumor suppressor genes, TSC1 or TSC2. These encode for the proteins hamartin and tuberin, respectively, which are associated in a macromolecular complex which functions as a regulator of cell proliferation, differentiation, growth and migration. TSC brain lesions may be severe and are characterized by subependymal nodules (SEN), subependymal giant cell astrocytomas (SEGA), neuronal heterotopias and cortical tubers, and may be clinically related to refractory epilepsy, intellectual disability, behavioral disorders and hydrocephaly. The growth potential of SEGA up to 21 years of age in TSC patients requires regular monitoring by imaging. Clinical and surgical interventions may be medically indicated. Subependymal lesions have been explained by deficient control of proliferation, growth and differentiation of neuro-glial progenitors from the telencephalic subventricular zone. While tuberin ability to inhibit cell proliferation by repressing the mammalian target of rapamycin (mTOR) has been well documented, other cell aspects of SEGA development have not been thoroughly examined. Therefore, it is important to establish conditions for an in vitro system to study the cells from the subventricular zone and to test its suitability for the study of the TSC proteins. In this regard, the neurosphere suspension culture is very appropriate. We evaluated the expression and subcellular distribution of hamartin and tuberin in relation to the proliferation and differentiation capability of neurosphere cells derived in vitro from the dissociation of the telencephalic vesicle of normal E14 rat embryos. These analyses were performed by indirect immunofluorescence in cells from first through fourth passages of neurospheres, synchronized in G1 or S phases of the cell cycle, and after reentry into the cell cycle by the addition of 5-brome-2\'-desoxyuridine (BrdU) and immunolabeling with anti-BrdU antibody. In general, neurosphere cells presented low colocalization between hamartin and tuberin in vitro. Tuberin expression was relatively high in basically all neurosphere cells and cell cycle phases, whereas hamartin distributed mainly to cells from the periphery of the spheres. In these cells, hamartin and tuberin colocalization was evident mostly in the cytoplasm and, in G1, also in the cell nucleus. Rheb, which is known to interact directly with tuberin, had subcellular distribution very similar to tuberin. Cell starvation indicating cell cycle arrest at G1/S redistributed tuberin to the cell nucleus in virtually all cells examined, what was accompanied by nuclear location of hamartin in a small subset of cells. When cells were allowed to reenter cell cycle by adding growth factors, we evaluated BrdU-labeled nuclei 72 and 96 hours later. In the two groups, tuberin was shown to move back to the cytoplasm as well as hamartin, which apparently maintained its lower expression levels distribution underneath the plasma membrane. Group of cells that recycled for 96 hours had significantly more expression of hamartin than those cells that cycled for only 72 hours. After neuronal differentiation, hamartin expression levels observed by immunofluorescence were similar to those of tuberin. We conclude that neurosphere cells cultured in suspension showed to be an appropriate cell system to study hamartin and tuberin distribution in respect to the cell cycle

Submitted by Luciclea Silva (luci@ufpa.br) on 2018-10-01T14:39:49Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Previsaodistorcaoharmonica.pdf: 4236129 bytes, checksum: bb47a1edb3151361639a5867d6c2c545 (MD5) / Approved for entry into archive by Luciclea Silva (luci@ufpa.br) on 2018-10-01T14:40:33Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Previsaodistorcaoharmonica.pdf: 4236129 bytes, checksum: bb47a1edb3151361639a5867d6c2c545 (MD5) / Made available in DSpace on 2018-10-01T14:40:33Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Previsaodistorcaoharmonica.pdf: 4236129 bytes, checksum: bb47a1edb3151361639a5867d6c2c545 (MD5) Previous issue date: 2018-07-11 / Este trabalho apresenta uma modelagem para DHTv%, DHTi% e harmônicos individuais utilizando previsões de um sistema ANFIS que aprende com dados medidos e prevê o comportamento da rede para valores futuros. Estas previsões podem ajudar a atender as normas nacionais de DHTv% estipuladas pela Agência Nacional de Energia Elétrica (ANEEL) através dos Procedimentos de Distribuição (PRODIST), como as normas internacionais de DHTi%., desta forma se antecipando às normas que atualmente são recomendativas, mas em um futuro próximo serão punitivas. A modelagem é realizada por meio de um sistema Neuro-Fuzzy denominado ANFIS, o qual utiliza rede neural para aprender o comportamento do sistema e ajuste dos parâmetros e regra Fuzzy para a determinação dos valores de saída do sistema levando em consideração o aprendizado da rede Neural. A grande vantagem desta ferramenta é o poder de se modelar padrões utilizando uma previsão de estado harmônico das cargas conectadas na baixa tensão, o que ajuda na criação de pseudomedidas para as redes de distribuição, onde é difícil e oneroso a obtenção de medições reais. Entre as aplicações práticas para esta ferramenta pode-se destacar a utilização dos valores previstos em substituição a valores anômalos medidos, a utilização em medidores de energia para prever e evitar a ultrapassagem dos valores de Distorção Harmônico estipulados em norma e a utilização como base para a previsão de harmônicas individuais, que podem ser utilizadas em estudos de fluxo de carga harmônicos. / This work presents a modeling for THDv%, THDi% and individual harmonics using predictions from an ANFIS system that learns with measured data and predicts the behavior of the network for future values. These forecasts can help meet national THDv% standards stipulated by the Agência Nacional de Energia Elétrica (ANEEL) through Distribution Procedures (PRODIST), such as THDi% international standards, thus anticipating the currently recommended standards, but in the near future will be punitive. The modeling is performed by means of a Neuro-Fuzzy system called ANFIS, which uses neural network to learn the behavior of the system and adjustment of the parameters and Fuzzy rule for the determination of the system output values taking into account the learning of the Neural network. The great advantage of this tool is the power of modeling standards using a prediction of the harmonic state of the connected loads in the low voltage, which helps in the creation of pseudomedidas for the distribution networks, where it is difficult and costly to obtain real measurements. Among the practical applications for this tool is the use of the predicted values instead of measured anomalous values, the use in energy meters to predict and avoid exceeding the values of Harmonic Distortion stipulated in standard and the use as a basis for the prediction of individual harmonics that can be used in harmonic load flow studies.

In recent years, response analysis of complex structures under impact loads has attracted a great deal of attention. For example, a collision or an accident that produces impact loads that exceed the design load can cause severe damage on the structural components. Although the AASHTO specification is used for impact-resistant bridge design, it has many limitations. The AASHTO specification does not incorporate complex and uncertain factors. Thus, a well-designed structure that can survive a collision under specific conditions in one region may be severely damaged if it were impacted by a different vessel, or if it were located elsewhere with different in-situ conditions. With these limitations in mind, we propose different solutions that use smart control technology to mitigate impact hazard on structures. However, it is challenging to develop an accurate mathematical model of the integrated structure-smart control systems. The reason is due to the complicated nonlinear behavior of the integrated nonlinear systems and uncertainties of high impact forces. In this context, novel algorithms are developed for identification, control and monitoring of nonlinear responses of smart structures under high impact forces. To evaluate the proposed approaches, a smart aluminum and two smart reinforced concrete beam structures were designed, manufactured, and tested in the High Impact Engineering Laboratory of Civil and Environmental Engineering at WPI. High-speed impact force and structural responses such as strain, deflection and acceleration were measured in the experimental tests. It has been demonstrated from the analytical and experimental study that: 1) the proposed system identification model predicts nonlinear behavior of smart structures under a variety of high impact forces, 2) the developed structural health monitoring algorithm is effective in identifying damage in time-varying nonlinear dynamic systems under ambient excitations, and 3) the proposed controller is effective in mitigating high impact responses of the smart structures.