A doença de Parkinson (DP) caracteriza-se pela perda progressiva de neurônios dopaminérgicos da substância nigra, o que acarreta diversas disfunções motoras. Não há ainda tratamentos capazes de deter ou retardar a degeneração dos neurônios dopaminérgicos, e os medicamentos hoje empregados na clínica apenas amenizam os sintomas, sem alterar a progressão da DP. No presente estudo foi avaliada a atividade neuroprotetora do éster fenetil do ácido cafeico (CAPE), um componente abundante do própolis de abelhas, com atividade anti-inflamatória, antiviral, antioxidante e imunomodulatória. Estudos têm sugerido seus efeitos benéficos contra as doenças neurodegenerativas, incluindo a doença de Parkinson, e alguns mecanismos têm sido propostos; porém muitos dos estudos com CAPE foram feitos apenas em culturas celulares. Este é o primeiro estudo a demonstrar que a administração intraperitoneal do CAPE protege contra a perda neuronal dopaminérgica e a disfunção motora induzidas pela neurotoxina 6-OHDA em ratos, confirmando a capacidade do CAPE de atravessar a barreira hematoencefálica e exercer seus efeitos benéficos no sitema nervoso central (SNC). Adicionalmente foram empregados dois modelos in vitro para o delineamento de possíveis mecanismos de neuroproteção: (i) mitocôndrias isoladas de cérebro de ratos não tratados e (ii) células SH-SY5Y tratadas com 6-OHDA. Os achados in vivo e in vitro sugerem o envolvimento dos seguintes mecanismos: (i) atividade antioxidante (sequestro de ERO, neutralização de radicais livres e quelação de metais); (ii) atividade anti-inflamatória (inibição da ativação do NF-kB, TNF-?, IkK? e Ikk?); (iii) aumento da expressão da conexina 43; (iv) inibição da Transição de Permeabilidade Mitocondrial (TPM); (v) inibição da liberação de citocromo c e (vi) inibição da ativação da caspase-3, executora final da apoptose. Além disso, o estudo também demonstrou que, por si só, o CAPE não interfere nas funções mitocondriais, o que representa uma vantagem com relação a outros inibidores da TPM. Assim, de acordo com nossos achados, o CAPE é um agente neuroprotetor promissor e pode auxiliar em futuras estratégias terapêuticas para as doenças neurodegenerativas, bem como para o melhor entendimento dos mecanismos responsáveis pelo desenvolvimento dessas doenças. / Parkinson\'s disease (PD) is characterized by progressive loss of dopaminergic neurons in the substantia nigra, which causes various motor dysfunctions. There are no treatments able to delay or stop the degeneration of dopaminergic neurons and the therapy employed nowadays only alleviate the symptoms without altering the progression of PD. In the present study we evaluated the neuroprotective activity of caffeic acid phenethyl ester (CAPE), a compound abundant in honeybees\' propolis, with anti-inflammatory, antiviral, antioxidant and immunomodulatory activities. Its beneficial effects against neurodegenerative diseases, including Parkinson\'s disease, have been suggested and some mechanisms have been proposed; however, many of the studies with CAPE have been performed only in cell cultures. This is the first study to demonstrate that the intraperitoneal administration of CAPE protects against the dopaminergic neuronal loss and the motor dysfunction induced by the neurotoxin 6-OHDA in rats, confirming the ability of CAPE to cross the blood brain barrier and exert its beneficial effects on the central nervous system (CNS). Additionally two in vitro models were used to delineate the possible mechanisms of neuroprotection: (i) mitochondria isolated from the brain of non-treated rats and (ii) cells SH-SY5Y treated with 6-OHDA. The in vivo and in vitro findings suggest the involvement of the following mechanisms: (i) antioxidant activity (scavenger of ROS, free radicals neutralization and metal chelation); (ii) anti-inflammatory activity (inhibition of activation of NF-kB, TNF-?, IkK? and Ikk?); (iii) increased expression of connexin-43; (iv) Inhibition of Mitochondrial Permeability Transition (MPT); (v) inhibition of cytochrome c release (vi) inhibition of the activation of caspase-3, the final executioner of apoptosis. Furthermore, the study also showed that CAPE alone does not interfere with mitochondrial functions, which represents an advantage in relation to other inhibitors of MPT. Therefore, according to our findings, CAPE is a promising neuroprotective agent and may be useful for future therapeutic strategies for neurodegenerative diseases, as well as to better understand the mechanisms responsible for the development of these diseases.

During the past three or four months, May to July 1918, there has been a great pandemic of so-called influenza which, starting in Spain, has spread over the whole of Europe and even other parts of the world. It has caused considerable wastage in our own Army and those of our Allies and has, therefore, been the object of much study amongst the medical services.

No description available.

Les études sur les procédés de soudage et sur la fiabilité des structures assemblées apparaissent actuellement comme un domaine de recherche actif, ouvert et complexe, car elles nécessitent de combiner de nombreuses connaissances dans différents domaines de la physique, de la mécanique et des procédés. La distribution des contraintes résiduelles joue un rôle important dans la vie des structures en favorisant la rupture par fatigue ou par fissuration. Ainsi, une meilleure compréhension des contraintes résiduelles évite l'utilisation de facteurs de sécurité plus élevés et, par conséquent permet de mieux optimiser le cycle de vie des structures soudées. A travers ce travail de thèse, nous nous sommes intéressés au soudage par laser d'un acier dual phase DP600, soudé en configuration par recouvrement, dont l'application est l'utilisation dans le domaine automobile. Cette thèse présente deux volets : un volet expérimental et un volet numérique.L'étude expérimentale nous a permis d'une part d'appréhender les conséquences métallurgiques et mécaniques du procédé laser sur l'acier DP600 et d'autre part d'utiliser et de valider les résultats numériques des modèles développés. L'étude numérique a eu pour objectif de prédire l'histoire thermique, métallurgique et l'évolution des caractéristiques mécaniques des tôles soudées par faisceau laser. Nous avons développé, sur un code de calcul par élémentsfinis Abaqus, trois modèles numériques. Le modèle thermomécanique, nous a permis de simuler la distribution spatio-temporelle de la température. Dans ce cas, le chargement appliqué est dépendant des paramètres du procédé etdes caractéristiques du faisceau laser et est associé à des conditions aux limites. Pour le modèle mécanique, nous avonsconsidéré un comportement élasto-plastique avec un chargement thermique transitoire, résultat du modèle thermique.Le deuxième modèle thermo-métallurgique nous a permis de simuler les phénomènes d'austénisation pendant la phase de chauffage (modèle de Waeckel) et de prendre en compte les fractions volumiques des phases martensitiques générées par les transformations de phases austénite-martensite lors du refroidissement (modèle de Koistinen-Marburger). Enfin, dans la dernière partie de simulation, nous avons réalisé le couplage thermo-metallo-mécanique. Les résultats obtenus dans la partie précédente, ont été implémentés dans deux modèles mécaniques : le modèle mécanique classique et le modèle mécanique avec prise en compte de la déformation liée aux effets de dilatation métallurgique. Cet effet a été intégré à travers le coefficient de dilatation thermique des phases ferritiques et martensitiques et des fractions volumiques obtenues à partir du modèle thermo-métallurgique. Les résultats ont montré que la répartition des contraintes résiduelles dans la zone de fusion et dans la zone affectée thermiquement sous l'effet de la déformation thermo-métallurgique donne des valeurs supérieures à celles estimées par le modèle élasto-plastique classique.

Le secret partagé est une exception légale au secret professionnel, permettant à ceux qui prennent en charge le patient d'échanger des informations le concernant, sans être sanctionnés du fait de cette révélation d'informations protégées. Si les soignants depuis toujours communiquent au sujet du patient dans son intérêt, il n'y en a pas moins un équilibre à trouver entre l'échange d'informations nécessaire à la pratique médicale, et le respect de la vie privée qu'un partage trop large peu compromettre. Or, l'émergence de l'outil informatique, multipliant les possibilités de partage de données de santé, remet en cause un équilibre fondé sur des mécanismes traditionnels de protection de l'intimité de la personne. Le traitement de données de santé partagées doit alors s'analyser au regard des règles du secret partagé, des règles de la législation "Informatique et Libertés", mais également au jour d'un foisonnement vertigineux de normes relatives à la mise en oeuvre de dossiers spécifiques comme le Dossier médical personnel, le Dossier pharmaceutique ou l'Historique des remboursements. La mise en relief systématique de la place du consentement de la personne concernée conduit au constat de l'impérative inscription à la Constitution du droit de la personne à la protection de ses données de santé partagées. / The medical professional secret is a legal exception to the professional secret; it allows a patient's caregivers to exchange health information that is relevant to that patient's care without being punished for revealing confidential information. That caregivers discuss patient's health information with other medical professional involved in that patient's care is to the benefit of the patient. Nonetheless, there is a fine balance to be struck between a "need to know" professional exchange of information, which is essential to care of the patient, and a broad exchange of information, which may ultimately comprise the confidentiality of the patient's private life. The emergence of an electronic tool, which multiplies the potential possibilities for data exchange, further disrupts this balance. Consequently, the manipulation of this shared health information must be subject to the medical professional secret, the "Informatique et Libertés" legislation, and all of the numerous norms and standards as defined by the French national electronic medical record (DMP), the pharmaceutical medical record (Dossier pharmaceutique), or the reimbursement repository (Historique des remboursements). As the patient's health information is increasingly shared between health care providers - through means such as the DMP or DP - the patient's right and ability to control the access to his/her health information have to become more and more important. A study regarding the importance of obtaining the patient's consent lead to the following proposal: to inscribe in the French Constitution the patient's right to confidentiality regarding health information.

This study aimed to review the specialized literature on respiratory, postural and vocal manifestations, associated to stages in Parkinson´s Disease and its possible interrelations, as well as, aging in phonation. Method: Some researches were carried based in articles in some databases: Lilacs, Bireme, PubMed, MedLine, Scielo and Google Schoolar, besides books, theses, dissertations and the Internet. Results: senescence is a physiological process to all human beings, generating anatomical and functional changes, especially at the age of 60, as muscular atrophy, calcification of the laryngeal cartilage, and reduction in respiratory capacity, reflecting on the voice through changes in pitch, instability, decrease in the maximum phonation time and restriction of vocal intensity. Parkinson´s Disease causes a series of functional alterations, e.g., rigidity, shaking, bradikinesia, reduction in the respiratory muscular strength, in maximum phonation time and vocal intensity, as well as postural changes. Its repercussions occur simultaneously, due to the muscle chains, body posture, respiratory and, consequently, phonation. Postural deviations, as the head forward positioning, shoulder protrusion and chest hyperciphosis are common in aging and PD and contribute to vocal disturbances through biomechanic disadvantages, especially in the cervical-scapular segment. Associated to postural alterations, is the decreasing in the respiratory muscular strength, causing the chest to expand less, reduction in the lungs volume and capacity, interfering in vocal production. There is a tendency for these disturbances to occur more frequently and with more gravity according to the stage in which the parkinsonian is. Conclusion: Based in the premisse that the human movement and its disorders, as well as the comunication disturbances, from aging and neurological diseases are interrelated by means of complex neural and muscle-skeleton nets, it becomes essential for a better understanding of the integration of physiotherapy and speech therapy, in order to have a complementarity, aiming the Parksonian's well-being. / Este estudo objetivou realizar uma revisão de literatura sobre as manifestações respiratórias, posturais e vocais, associadas aos estágios da Doença de Parkinson e suas possíveis inter-relações, bem como, o envelhecimento na fonação. Método: Realizaram-se buscas a partir de publicações nas bases de dados Lilacs, Bireme, PubMed, MedLine, Scielo e Google Schoolar, tendo sido utilizados também livros, teses, dissertações e Internet. Resultados: a senescência é um processo fisiológico a todos os seres humanos, gerando modificações anátomo-funcionais, especialmente a partir dos 60 anos, como atrofia muscular, calcificação das cartilagens laríngeas, e redução na capacidade respiratória, refletindo-se na voz através de alterações no pitch, instabilidade, decréscimo dos tempos máximos de fonação e restrição à intensidade vocal. A Doença de Parkinson ocasiona uma série de alterações funcionais, por exemplo, rigidez, tremor, bradicinesia, redução na força muscular respiratória, nos tempos máximos de fonação e na intensidade vocal, bem como alterações posturais. Suas repercussões ocorrem simultaneamente, devido às cadeias musculares, na postura corporal, na respiração e, conseqüentemente, na fonação. Desvios posturais, como anteriorização da cabeça, protrusão de ombros e hipercifose torácica são comuns no envelhecimento e na DP e contribuem para os distúrbios vocais, por meio de desvantagens biomecânicas, especialmente no segmento cérvico-escapular. Associado às alterações posturais, ocorre o decréscimo na força muscular respiratória que propicia menor expansibilidade da caixa torácica, redução nos volumes e capacidades pulmonares, interferindo na produção vocal. Há uma tendência de que esses distúrbios ocorram com maior freqüência e gravidade de acordo com o estágio em que o parkinsoniano se encontra. Conclusão: Baseado na premissa de que o movimento humano e suas desordens, assim como os distúrbios da comunicação advindos tanto do envelhecimento quanto de doenças neurológicas apresentam-se inter-relacionados por meio de complexas redes neurais e músculoesqueléticas, torna-se essencial uma melhor compreensão da fisioterapia e da fonoaudiologia acerca dessas interações, a fim de que haja complementaridade, visando ao bem-estar do indivíduo.

A doença de Parkinson (DP) caracteriza-se pela perda progressiva de neurônios dopaminérgicos da substância nigra, o que acarreta diversas disfunções motoras. Não há ainda tratamentos capazes de deter ou retardar a degeneração dos neurônios dopaminérgicos, e os medicamentos hoje empregados na clínica apenas amenizam os sintomas, sem alterar a progressão da DP. No presente estudo foi avaliada a atividade neuroprotetora do éster fenetil do ácido cafeico (CAPE), um componente abundante do própolis de abelhas, com atividade anti-inflamatória, antiviral, antioxidante e imunomodulatória. Estudos têm sugerido seus efeitos benéficos contra as doenças neurodegenerativas, incluindo a doença de Parkinson, e alguns mecanismos têm sido propostos; porém muitos dos estudos com CAPE foram feitos apenas em culturas celulares. Este é o primeiro estudo a demonstrar que a administração intraperitoneal do CAPE protege contra a perda neuronal dopaminérgica e a disfunção motora induzidas pela neurotoxina 6-OHDA em ratos, confirmando a capacidade do CAPE de atravessar a barreira hematoencefálica e exercer seus efeitos benéficos no sitema nervoso central (SNC). Adicionalmente foram empregados dois modelos in vitro para o delineamento de possíveis mecanismos de neuroproteção: (i) mitocôndrias isoladas de cérebro de ratos não tratados e (ii) células SH-SY5Y tratadas com 6-OHDA. Os achados in vivo e in vitro sugerem o envolvimento dos seguintes mecanismos: (i) atividade antioxidante (sequestro de ERO, neutralização de radicais livres e quelação de metais); (ii) atividade anti-inflamatória (inibição da ativação do NF-kB, TNF-?, IkK? e Ikk?); (iii) aumento da expressão da conexina 43; (iv) inibição da Transição de Permeabilidade Mitocondrial (TPM); (v) inibição da liberação de citocromo c e (vi) inibição da ativação da caspase-3, executora final da apoptose. Além disso, o estudo também demonstrou que, por si só, o CAPE não interfere nas funções mitocondriais, o que representa uma vantagem com relação a outros inibidores da TPM. Assim, de acordo com nossos achados, o CAPE é um agente neuroprotetor promissor e pode auxiliar em futuras estratégias terapêuticas para as doenças neurodegenerativas, bem como para o melhor entendimento dos mecanismos responsáveis pelo desenvolvimento dessas doenças. / Parkinson\'s disease (PD) is characterized by progressive loss of dopaminergic neurons in the substantia nigra, which causes various motor dysfunctions. There are no treatments able to delay or stop the degeneration of dopaminergic neurons and the therapy employed nowadays only alleviate the symptoms without altering the progression of PD. In the present study we evaluated the neuroprotective activity of caffeic acid phenethyl ester (CAPE), a compound abundant in honeybees\' propolis, with anti-inflammatory, antiviral, antioxidant and immunomodulatory activities. Its beneficial effects against neurodegenerative diseases, including Parkinson\'s disease, have been suggested and some mechanisms have been proposed; however, many of the studies with CAPE have been performed only in cell cultures. This is the first study to demonstrate that the intraperitoneal administration of CAPE protects against the dopaminergic neuronal loss and the motor dysfunction induced by the neurotoxin 6-OHDA in rats, confirming the ability of CAPE to cross the blood brain barrier and exert its beneficial effects on the central nervous system (CNS). Additionally two in vitro models were used to delineate the possible mechanisms of neuroprotection: (i) mitochondria isolated from the brain of non-treated rats and (ii) cells SH-SY5Y treated with 6-OHDA. The in vivo and in vitro findings suggest the involvement of the following mechanisms: (i) antioxidant activity (scavenger of ROS, free radicals neutralization and metal chelation); (ii) anti-inflammatory activity (inhibition of activation of NF-kB, TNF-?, IkK? and Ikk?); (iii) increased expression of connexin-43; (iv) Inhibition of Mitochondrial Permeability Transition (MPT); (v) inhibition of cytochrome c release (vi) inhibition of the activation of caspase-3, the final executioner of apoptosis. Furthermore, the study also showed that CAPE alone does not interfere with mitochondrial functions, which represents an advantage in relation to other inhibitors of MPT. Therefore, according to our findings, CAPE is a promising neuroprotective agent and may be useful for future therapeutic strategies for neurodegenerative diseases, as well as to better understand the mechanisms responsible for the development of these diseases.

No description available.

No description available.

With the desire to lighten the frame while keeping or increasing the strength, Advanced High-Strength Steels (AHSS) have been developed for use in the automotive industry. AHSS meet many vehicle functional requirements because of their excellent strength and acceptable ductility. But joining AHSS is a challenge, because weldability is lower than that of mild steels. Friction stir spot welding (FSSW) is a solid state joining process that can provide a solution to the weldability issues in AHSS, but FSSW has not been studied in great detail for this application. In this work, Si3N4 tools were used for FSSW experiments on DP 980 steel with 1.2mm thickness. Joint strength was measured by lap shear tension testing, while thermocouples were used for the temperature measurements. A finite element model was developed in order to predict material flow and temperatures associated with FSSW. Since a 3D model of the process is very time consuming, a novel 2D model was developed for this study. An updated Lagrangian scheme was employed to predict the flow of sheet material, subjected to the boundary conditions of the fixed backing plate and descending rotating tool. Heat generation by friction was computed by including the rotational velocity component from the tool in the thermal boundary conditions. Material flow was calculated from a velocity field while an isotropic, viscoplastic Norton-Hoff law was used to compute the material flow stress as a function of temperature, strain and strain rate. Shear stress at the tool/sheet interface was computed using the viscoplastic friction law. The model predicted welding temperatures to within 4% of the experiments. The welding loads were significantly over predicted. Comparison with a 3D model of FSSW showed that frictional heating and the proportion of total heat generated by friction were similar. The position of the joint interface was reasonably well predicted compared to experiment.