Made available in DSpace on 2016-08-03T16:31:06Z (GMT). No. of bitstreams: 1 ABSTRACT.pdf: 21657 bytes, checksum: 63b3100346fe80ab65a8ea2cd6b5eb9e (MD5) Previous issue date: 2005-03-16 / This current study aims at verifying the dental angulation and the tipping at the end of an orthodontic treatment in cases treated with fixed appliance and the MBT prescription, and comparing them to the values found by Andrews for a natural normal occlusion. Thirty pairs of final cast models of thirty patients with average age between 13 and 23 years of age were used. As a requirement, these patients should not have undergone any kind of orthopedic intervention, they should not have used intermaxillary elastics, presented dento-alveolar compensation or being treated with extraction. In order to measure the mesiodistal angulation and the buccolingual tipping, a device manufactured in a previous research study aiming at taken these measurements was used. According to the methodology applied and to the results achieved, it can be concluded that the angulation of the dental crowns, for both upper and lower arches, presented positive values. As for the inclination of the dental crowns, in both dental arches, positive values were found for the central and the lateral teeth, whereas, canines, premolars, incisors, and first molars presented negative values. Individual variations were found in both measurements. Comparing the results achieved in this research study to the ones found by Andrews, statistical differences were verified for the majority of teeth, in both measurements taken in the study. / O presente trabalho tem o objetivo de verificar as angulações e as inclinações dentárias obtidas no final do tratamento ortodôntico, em casos tratados com aparelho ortodôntico fixo e prescrição MBT e compará-las com os valores encontrados por Andrews para a oclusão normal natural. Foram utilizados 30 pares de modelos de gesso finais, de 30 pacientes, tratados, na faixa etária de 13 a 23 anos. Como pré-requisitos, estes pacientes não deveriam ter sido submetidos a qualquer tipo de intervenção ortopédica, uso de elásticos intermaxilares, compensações dento-alveolares e tratamentos realizados com extração. Para a mensuração da angulação mésio-distal e da inclinação vestíbulo-lingual utilizou-se um dispositivo, desenvolvido em pesquisa anterior, capaz de realizar tais medições. De acordo com a metodologia empregada e diante dos resultados obtidos, pôde-se concluir que as angulações das coroas dentárias tanto superiores quanto inferiores apresentaram valores positivos. Quanto às inclinações das coroas dentárias, em ambos os arcos dentários, foram encontrados valores positivos para os incisivos centrais e laterais, ao passo que caninos, pré-molares e primeiros molares apresentaram valore s negativos. Variações individuais estiveram presentes nas duas mensurações realizadas. Ao comparar nossos resultados com os de Andrews, obtivemos diferenças estatisticamente significantes para a maioria dos dentes, em ambas as medidas efetuadas.

Le modèle induit par injectionunilatérale intrahippocampique d’acide kaïniquechez la souris présente de grandes analogiesavec l’épilepsie mésio-temporale (EMT) chezl’homme caractérisée par la périoded’épileptogénèse et par une sclérosehippocampique (SH) typique.De récents travaux ex vivo ont révélé l’existencede processus neuroinflammatoires au niveau dela SH chez des patients épileptiques et dans desmodèles animaux. La protéine translocatrice de18kDa (TSPO), la plus étudiée actuellement aumoyen de différents traceurs, est considéréecomme une cible de référence pour visualiser etquantifier la neuroinflammation.Ma thèse a donc eu pour objectif de déterminerl’évolution de l’expression de TSPO au cours dela constitution de la SH à l’aide de laTomographie par émission de positons (TEP) au18F-DPA-714 dans une étude longitudinale chezce modèle d’EMT, et à identifier son origine àpartir d’analyses d’immunohistofluorescence.Nous avons démontré la faisabilité de la TEPpour suivre in vivo le processus inflammatoiremême dans de petites structures cérébrales à lafois par la mesure locale du pourcentaged’activité injectée et par l’estimation du volumede distribution.Le signal maximum a été observé durantl’épileptogénèse et correspondait aux microgliesactivées puis il diminuait mais persistait lorsquela SH était bien établie, et était alorsprincipalement lié aux astrocytes activés.Nos principaux résultats ont permis d’identifierles phases pendant lesquelles de nouvellesstratégies thérapeutiques ciblant différentescomposants de la neuroinflammationmériteraient d’être étudiés. / The model induced by unilateralinjection of kainic acid is considered as the bestreliable model for the mesial temporal lobeepilepsy (MTLE) and reproduces theepileptogenesis and the typical hippocampalsclerosis (HS).Recent ex vivo studies have revealed theexistence of neuroinflammation in the HS ofepileptic patients and animal models. The18kDa translocator protein (TSPO), which iscurrently the most widely studied with variousradiotracers, is considered as a reference targetto visualize and quantify theneuroinflammation.In that context, my thesis focused ondetermining the evolution of TSPO during theconstitution of HS using 18F-DPA-714positrons emission tomography (PET) in alongitudinal study in this mouse model, and toidentify its origin fromimmunohistofluorescence analysis.We demonstrated the feasibility of PET tomonitor in vivo the inflammatory process evenin small cerebral structures both by the localmeasurement of the percent injected dose or bythe measurement of the volume of distribution.The peak signal was found during theepileptogenesis and corresponded to activatedmicroglia, and then this signal decreased butpersisted after the HS was well established, andmainly originated from activated astrocytesduring this period.Our main results allowed us to identifydifferent phases during which potential antiepileptictreatment targeting differentcomponents of neuroinflammation could beinvestigated.

Les travaux de cette thèse ont pour but de mettre en œuvre des outils de modélisation et de simulation numériques de mécanismes sous-tendant l’activité neuronale, afin de promouvoir la découverte de médicaments pour le traitement des maladies du système nerveux. Les modèles développés s’inscrivent à différentes échelles : 1) les modèles dits « élémentaires » permettent de simuler la dynamique des récepteurs, des canaux ioniques, et les réactions biochimiques des voies de signalisation intracellulaires ; 2) les modèles de neurones permettent d’étudier l’activité électrophysiologique de ces cellules ; et 3) les modèles de microcircuits permettent de comprendre les propriétés émergentes de ces systèmes complexes, tout en conservant les mécanismes élémentaires qui sont les cibles des molécules pharmaceutiques. À partir d’une synthèse bibliographique des éléments de neurobiologie nécessaires, et d’une présentation des outils mathématiques et informatiques mis en œuvre, le manuscrit décrit les différents modèles développés ainsi que leur processus de validation, allant du récepteur de neurotransmetteur au microcircuit. D’autre part, ces développements ont été appliqués à trois études visant à comprendre : 1) la modulation pharmacologique de la potentialisation à long terme (LTP) dans les synapses glutamatergiques de l’hippocampe, 2) les mécanismes de l'hyperexcitabilité neuronale dans l'épilepsie mésio-temporale (MTLE) à partir de résultats expérimentaux in vitro et in vivo, et 3) la modulation cholinergique de l'activité hippocampique, en particulier du rythme thêta associé à la voie septo-hippocampique. / The work of this thesis aims to apply modeling and simulation techniques to mechanisms underlying neuronal activity, in order to promote drug discovery for the treatment of nervous system diseases. The models are developed and integrated at different scales: 1) the so-called "elementary models" permit to simulate dynamics of receptors, ion channels and biochemical reactions in intracellular signaling pathways; 2) models at the neuronal level allow to study the electrophysiological activity of these cells; and 3) microcircuits models help to understand the emergent properties of these complex systems, while maintaining the basic mechanisms that are the targets of pharmaceutical molecules. After a bibliographic synthesis of necessary elements of neurobiology, and an outline of the implemented mathematical and computational tools, the manuscript describes the developed models, as well as their validation process, ranging from the neurotransmitter receptor to the microcircuit. Moreover, these developments have been applied to three studies aiming to understand: 1) pharmacological modulation of the long-term potentiation (LTP) of glutamatergic synapses in the hippocampus, 2) mechanisms of neuronal hyperexcitability in the mesial temporal lobe epilepsy (MTLE), based on in vitro and in vivo experimental results, and 3) cholinergic modulation of hippocampal activity, particularly the theta rhythm associated with septo-hippocampal pathway.