The enteric nervous system (ENS) is an incredibly complex neural network that is extensively integrated within the neuroimmunoendocrine system through countless signalling pathways that have yet to be fully characterized. In the last decade we have discovered that many more neurotransmitters are at work in the ENS than was originally thought. This opens up new avenues of research into physiological phenomena traditionally thought to be associated only with the central nervous system, such as NMDA receptor-induced excitotoxicity, and how these may influence immune interactions. In particular, the kynurenine pathway of the tryptophan catabolism produces many neuro-active and immuno-active constituents whose effects are unknown in the ENS but are of great consequence in many neurodegenerative disorders of the CNS. Our study hypothesized that co-culture of the enteric neurons with mast cells would increase neuronal survival through kynurenic acid production in quinolinic acid (QUIN)-induced excitotoxic conditions. This study developed a novel in vitro co-culture system of enteric neurons and glia grown from murine longitudinal muscle-myenteric plexus tissue and bone marrow-derived mast cells. In addition, a pipeline in image analysis software CellProfiler was designed and optimized in order to reduce human bias and error in subsequent immunocytochemical image analysis. Furthermore, we identified the genetic expression of subunits of the NMDA glutamate receptor in cultured enteric neurons via PCR, which suggests that these cultured neurons may be susceptible to excitotoxicity. PCR analysis of cultured mast cells seemed to indicate that our cultured mast cells do not express KAT-III, the enzyme needed to produce the neuroprotective KYNA. Overall, co-culture with mast cells seemed to decrease neuronal survival. This project developed a novel methodology for the in vivo study of mast cell-nerve interactions, and lays the groundwork for future studies in excitotoxicity in the ENS. / Thesis / Master of Science (MSc) / The enteric nervous system is a vast web of nerves and immune cells that innervates the gut and interacts with the central nervous system through the gut-brain axis. An important mediator in this system is the mast cell, a type of immune cell often involved in protective responses to venoms and allergens. Intriguingly, in normal physiological conditions these cells are in close contact with nerves in the periphery, despite their potential to release damaging constituents. While mast cells are well-known for inciting inflammation and releasing toxic granules, they can also synthesize and release potentially beneficial neuroactive compounds, such as neurotransmitters or growth factors. The aim of this study was to characterize mast cell-nerve interactions in neurotoxic conditions, to see if the proximity of mast cells to nerves might serve a neuroprotective purpose.

<p dir="ltr">A neurological disorder, hydrocephalus, has an estimated global pediatric prevalence of 380,000 new cases each year [<a href="#_ENREF_1" target="_blank">1</a>]. It is a family of diseases that can occur at any age when cerebrospinal fluid builds up within the ventricles of the brain. Thus, the only available treatments are surgical, invasive, and prone to complications. There is a global need for successful treatment strategies without brain surgery.</p><p><br></p><p dir="ltr">Choroid plexus epithelial cells (CPEC) are responsible for production of cerebrospinal fluid (CSF). Ependymal cells line the ventricles and play roles in CSF maintenance and waste clearance. Astrocytes perform various functions, one being blood-brain barrier (BBB) maintenance. Collectively these cells contribute to brain fluid/electrolyte regulation and barrier integrity. Increased glial fibrillary acidic protein (GFAP) fluorescence, a marker of activated astrocytes, appeared in hydrocephalic (<i>Tmem67</i>^-/-) animals by immunohistochemistry as early as postnatal day (P)10. The tight junction proteins expressed in choroid plexus (CP); claudin-1 (Cl-1) and zona occludin 1 (ZO-1) fluorescent intensity increased in P15 hydrocephalic animals compared to wildtype (<i>Tmem67</i>^+/+). These cells also contain aquaporins (AQP), aquaporin-1 (AQP1) and aquaporin-4 (AQP4), important in regulating CSF and interstitial fluid (ISF). Increased fluorescent intensity of AQP4 in the subventricular zone and increased AQP1 apical localization and protein amount in the CP was observed in hydrocephalic animals at postnatal day (P)15. Many of these may be targeted for the treatment of hydrocephalus. However, there is no consensus in pathological findings between models of hydrocephalus and these finding may not translate to common pharmacological targets.</p><p><br></p><p dir="ltr">A transient receptor potential cation channel, subfamily vanilloid, member 4 (TRPV4) antagonist (RN1734) ameliorates hydrocephalus in a rat model of congenital hydrocephalus (<i>Tmem67</i> model). It was hypothesized that targeting this mechanosensitive ion channel may slow production of CSF by targeting the CP. However, hydrocephalus pathology can have various effects on the brain. Astrocytes were visualized using fluorescent immunohistochemistry of glial fibrillary acidic protein (GFAP) and RN1734 did not seem to change immunoreactivity to wildtype untreated levels. Increased immunoreactivity of TRPV4 and AQP1 was observed in CP of untreated and RN1734 treated <i>Tmem67</i>^-/- rats. AQP4 and TRPV4 immunoreactivity increased in the subventricular zone and periventricular white matter (WM) of hydrocephalic rats. With RN1734, TRPV4 immunoreactivity, but not AQP4, had similar immunoreactivity to wildtype untreated. Increased GFAP and AQP immunoreactivity may indicate residual inflammation in the <i>Tmem67</i>^-/- rats. More experiments must be done to further elucidate TRPV4’s role in hydrocephalus pathology.</p><p><br></p><p dir="ltr">Serum and glucocorticoid-regulated kinase 1 (SGK1) is a kinase implicated in cell volume regulation and CSF production. SI113, an SGK1 inhibitor, ameliorates hydrocephalus in the <i>Tmem67</i> rodent model. The goal of this study was to determine if SI113 could be used with a new solvent other than dimethyl sulfoxide (DMSO), which can have possible toxic effects. 1-methyl-2-pyrrolidinone (NMP) has high solubility and ability to cross the BBB. These studies showed that NMP as a solvent did not have adverse effects on body weight, however thus far, it has not ameliorated hydrocephalus significantly at the concentration used in this study. There is a possibility that the concentration in NMP that we used was not efficacious enough. CSF and blood plasma samples from animals treated with SI113 24 hours and 30 minutes before euthanasia will be used to investigate the concentration of SI113 that remains in the circulation and the amount that crosses the BBB and blood-cerebrospinal fluid (BCSFB) barriers. We hope that the results will inform dosage for our future studies. Future studies may also examine SI113 mechanism of action in hydrocephalus.</p><p><br></p><p dir="ltr">This thesis addresses hydrocephalus cell and molecular pathology in the <i>Tmem67</i> model and examines potential treatment strategies. Future directions include comparing models of hydrocephalus to find common treatment strategies in the hope to find pharmaceutical strategies to better manage human hydrocephalus.</p>

No description available.

Essai cinique randomisé / Objectifs : Démontrer la supériorité de l’analgésie périopératoire optimale par rapport aux traitements analgésiques usuels ou conventionnels pour diminuer l'intensité de la douleur aiguë postopératoire (DAPO), la fréquence d'apparition de la douleur chronique post chirurgicale (DCPC) et améliorer la qualité de vie des patients. Méthodes : Un essai clinique randomisé à double insu, sur 57 patients ayant subi une trapéziectomie à l'hôpital Notre-Dame du CHUM. Après avoir reçu une analgésie locorégionale via un cathéter du plexus brachial, le groupe expérimental a reçu une perfusion de bupivacaïne 0,5%, débutée dans la salle de réveil et poursuivie pendant 72 h en ambulatoire, grâce à une pompe à perfusion. Le groupe de contrôle a reçu une solution saline. Les deux groupes ont reçu du célécoxib durant cette même période. L'évolution du profil de la douleur, du fonctionnement de la main et de la qualité de vie des patients ont été saisis à l'aide de questionnaires et de tests fonctionnels en préopératoire et pendant six mois de suivi. Les résultats ont été analysés à l'aide du modèle linéaire général. Une différence de 2 au niveau de l'intensité de la douleur, mesurée par l'échelle visuelle analogique (EVA : 0-10), a été considérée statistiquement significative. Résultats : Notre méthode a abouti à une diminution significative de l'intensité de la DAPO et de la douleur chronique (DC) par rapport à la méthode conventionnelle. Les activités générales, la qualité du sommeil et la concentration des patients étaient significativement meilleures chez le groupe qui a reçu la nouvelle méthode. De plus, dans ce groupe il y avait deux fois moins des patients qui ont continué à souffrir de DC que le groupe de contrôle. Conclusion : Dans la chirurgie de la main, une couverture analgésique périopératoire est essentielle pour réduire l’intensité de la DAPO, la fréquence de la DCPC et pour améliorer la qualité de vie des patients. Mots-clés : essai clinique, douleur chronique, chirurgie, main, analgésie préventive, plexus brachial. / Objectives: Demonstrate the superiority of Optimal Perioperative Analgesia compared to Usual Analgesic Treatment to reduce the intensity of Acute Postoperative Pain (APOP), the frequency of occurrence of Chronic Post Surgical Pain (CPSP) and improve patients’ quality of life. Methods: A double-blinded randomized clinical trial conducted in Notre-Dame Hospital on 57 patients who underwent a trapeziectomy. After locoregional analgesia via a catheter in the brachial plexus, the experimental group received an infusion of bupivacaine 0.5%, which started in the recovery room and continued for 72 h as an outpatient through an infusion pump. Meanwhile, the control group received a saline solution. Both groups took celecoxib during the same period. The evolution of pain profile, hand function and patients’ quality of life have been obtained using questionnaires and functional tests in the preoperative period and through months of follow-up. Results were analyzed using General Linear Model. A difference of 2 in the intensity of pain, measured by Visual Analogue Scale (VAS: 0-10), was considered statistically significant. Results: This method resulted in a significant decrease in the intensity of APOP and Chronic Pain (CP) compared to usual treatment. General activities, quality of sleep and patients’ concentration were better in the experimental group. Moreover, two times less patients continued to suffer from the CP than in the placebo group. Conclusion: In hand surgery, a perioperative analgesic coverage is necessary to reduce the APOP intensity, the CPSP frequency and to improve patients’ quality of life. Keywords: clinical trial, chronic pain, surgery, hand, preemptive analgesia, brachial plexus.

No description available.

Objectifs : Démontrer la supériorité de l’analgésie périopératoire optimale par rapport aux traitements analgésiques usuels ou conventionnels pour diminuer l'intensité de la douleur aiguë postopératoire (DAPO), la fréquence d'apparition de la douleur chronique post chirurgicale (DCPC) et améliorer la qualité de vie des patients. Méthodes : Un essai clinique randomisé à double insu, sur 57 patients ayant subi une trapéziectomie à l'hôpital Notre-Dame du CHUM. Après avoir reçu une analgésie locorégionale via un cathéter du plexus brachial, le groupe expérimental a reçu une perfusion de bupivacaïne 0,5%, débutée dans la salle de réveil et poursuivie pendant 72 h en ambulatoire, grâce à une pompe à perfusion. Le groupe de contrôle a reçu une solution saline. Les deux groupes ont reçu du célécoxib durant cette même période. L'évolution du profil de la douleur, du fonctionnement de la main et de la qualité de vie des patients ont été saisis à l'aide de questionnaires et de tests fonctionnels en préopératoire et pendant six mois de suivi. Les résultats ont été analysés à l'aide du modèle linéaire général. Une différence de 2 au niveau de l'intensité de la douleur, mesurée par l'échelle visuelle analogique (EVA : 0-10), a été considérée statistiquement significative. Résultats : Notre méthode a abouti à une diminution significative de l'intensité de la DAPO et de la douleur chronique (DC) par rapport à la méthode conventionnelle. Les activités générales, la qualité du sommeil et la concentration des patients étaient significativement meilleures chez le groupe qui a reçu la nouvelle méthode. De plus, dans ce groupe il y avait deux fois moins des patients qui ont continué à souffrir de DC que le groupe de contrôle. Conclusion : Dans la chirurgie de la main, une couverture analgésique périopératoire est essentielle pour réduire l’intensité de la DAPO, la fréquence de la DCPC et pour améliorer la qualité de vie des patients. Mots-clés : essai clinique, douleur chronique, chirurgie, main, analgésie préventive, plexus brachial. / Objectives: Demonstrate the superiority of Optimal Perioperative Analgesia compared to Usual Analgesic Treatment to reduce the intensity of Acute Postoperative Pain (APOP), the frequency of occurrence of Chronic Post Surgical Pain (CPSP) and improve patients’ quality of life. Methods: A double-blinded randomized clinical trial conducted in Notre-Dame Hospital on 57 patients who underwent a trapeziectomy. After locoregional analgesia via a catheter in the brachial plexus, the experimental group received an infusion of bupivacaine 0.5%, which started in the recovery room and continued for 72 h as an outpatient through an infusion pump. Meanwhile, the control group received a saline solution. Both groups took celecoxib during the same period. The evolution of pain profile, hand function and patients’ quality of life have been obtained using questionnaires and functional tests in the preoperative period and through months of follow-up. Results were analyzed using General Linear Model. A difference of 2 in the intensity of pain, measured by Visual Analogue Scale (VAS: 0-10), was considered statistically significant. Results: This method resulted in a significant decrease in the intensity of APOP and Chronic Pain (CP) compared to usual treatment. General activities, quality of sleep and patients’ concentration were better in the experimental group. Moreover, two times less patients continued to suffer from the CP than in the placebo group. Conclusion: In hand surgery, a perioperative analgesic coverage is necessary to reduce the APOP intensity, the CPSP frequency and to improve patients’ quality of life. Keywords: clinical trial, chronic pain, surgery, hand, preemptive analgesia, brachial plexus. / Essai cinique randomisé

IntroductionL’anatomie nerveuse pelvienne est imprécise dans la littérature. ObjectifsReprésenter en 3D l’innervation autonome du pelvis. Démontrer la capacité de l’IRM voir cette innervation.Matériels et méthodesDes coupes ont été faites sur le bassin de fœtus et d’adultes, puis traitées par des colorations et immunomarquages. Les lames ont été numérisées et reconstruites en 3D.Nous avons effectué une confrontation anatomo-radiologique entre des images d’IRM et de dissection.RésultatsNous avons pu décrire l’innervation autonome du pelvis et faire une cartographie des neuromédiateurs. Nous avons également pu suggérer des plans d’épargne nerveuse lors de la chirurgie. Les acquisitions IRM ont permis une visualisation de l’innervation de façon précise avec une bonne concordance.ConclusionCe travail permet une meilleure description de l’innervation pelvienne et des plans chirurgicaux à emprunter en chirurgie pelvienne. L’IRM permet bien de visualiser l’innervation pelvienne. / Introduction :Pelvis nervous anatomy is imprecise in literature. Objectives:1-To describe and represent in 3D pelvic autonomic innervation. 2-To demonstrate the capacity of MRI to visualize pelvic autonomous innervation.Materiel/patients and methods:Serial histological sections were made from foetuses and adults. Sections were treated with conventional and immunostainings. Sections were digitalized and reconstructed in 3D. An anatomo-radiological comparison was made between MRI images and dissection. Results:Our study enabled to localize the pelvic autonomous innervation and to realize a complete neuro-mediators cartography.MRI acquisition allowed an good visualization of the autonomous innervation, with a good correlation with dissection.Conclusion and perspectives:This study enabled a better understanding of pelvic nervous anatomy and physiology. It also demonstrated that this anatomy is visible on MRI.

Introduction: Parmi les structures anatomiques impliquées dans les fonctions génitales et urinaires, l’innervation autonome et somatique du rétro-péritoine, du pelvis et du périnée a un rôle contrôle déterminant. Cette innervation reste incomplètement systématisée et elle apparaît vulnérable lors d’interventions chirurgicales ou au cours de maladies neurologiques. Classiquement, deux voies nerveuses se situent de part et d’autre du muscle élévateur de l’anus (MEA) : la voie autonome est supra-lévatorienne ; la voie somatique est infra-lévatorienne. Les nerfs autonomes viennent du plexus hypogastrique supérieur (PHS) (fibres sympathiques) qui se divise en deux nerfs hypogastriques (NHs) s’engageant dans le pelvis. Les NHs reçoivent des nerfs splanchniques pelviens (fibres parasympathiques) qui forment le plexus hypogastrique inférieur (PHI). Les voies somatiques proviennent des nerfs pudendaux. Ces notions établies par la dissection conventionnelle peuvent aujourd’hui être complétées par l’analyse de marqueurs nerveux en Dissection Anatomique Assisté par Ordinateur (DAAO). Celle-ci est susceptible de préciser les connaissances anatomiques et d’éclairer la compréhension des dysfonctions génito-urinaires.Objectifs: L’objectif était de décrire le système nerveux autonome rétro-péritonéal et pelvi-périnéal dans ses aspects morphologiques (origine, topographie, trajet, rapports) et fonctionnels (nature des fibres, terminaisons viscérales) pour mettre en perspective les implications potentielles dans les dysfonctions génito-urinaires.Matériel et méthodes: Des coupes histologiques sériées de 5 µm d’épaisseur ont été effectuées dans les régions lombaire et pelvienne de onze fœtus humains âgés de 14 à 31 semaines de gestation, et au niveau pénien chez cinq sujets anatomiques adultes masculins. Pour chaque niveau de coupe, des lames ont été colorées puis traitées en immunohistochimie pour détecter : l’ensemble des fibres nerveuses (anticorps anti-protéine S100), les fibres nerveuses somatiques (anti-PMP 22), les fibres autonomes adrénergiques (anti-TH), les fibres autonomes cholinergiques (anti-VAChT), les fibres autonomes nitrergiques (anti-nNOS), et les fibres musculaires lisses (anti-actine lisse). Les coupes ont ensuite été numérisées par un scanner de haute résolution optique et les images ont été reconstruites en 3D avec le logiciel Winsurf®.Résultats: Au niveau rétro-péritonéal, le PHS est formé de fibres adrénergiques, cholinergiques et nitrergiques. Ses fibres proviennent à la fois du plexus mésentérique inférieur, des ganglions sympathiques voisins et des nerfs splanchniques lombaires. Au niveau pelvien, le PHI se systématise en : une portion supérieure recevant ses fibres du PHS et innervant détrusor, uretères et vésicales séminales ; une portion inférieure recevant ses fibres des nerfs splanchniques pelviens et innervant trigone, prostate et corps érectiles. La jonction uretéro-vésicale est une zone richement innervée par des fibres adrénergiques, cholinergiques et nitrergiques provenant du PHI et des NHs. En outre, le PHI fournit un contingent nerveux autonome au MEA par voie supra-lévatorienne, tandis que le nerf pudendal (NP) lui fournit un contingent somatique par voie infra-lévatorienne. Au niveau pénien, la composante autonome prédomine dans les 2 tiers proximaux quand, en distalité, l’innervation est presque exclusivement somatique. Trois niveaux de communication entre les voies autonome et somatique ont été observés : pré- trans- et post-lévatorien.Conclusion: L’intrication des voies autonomes et somatiques rétropéritonéo-pelvi-périnéales, la diversité de leurs origines, leurs communications et répartition depuis les plexus jusqu’aux viscères s’établissent par DAAO. Ces voies méritent d’être au mieux préservées au cours d’interventions chirurgicales ou instrumentales. Elles représentent de potentielles voies de modulation, de plasticité ou de régénération à explorer. / Introduction: The autonomous and somatic innervations of the retro-peritoneum, the pelvis and the perineum have a determining control role among the anatomical structures involved in the genital and urinary functions. The innervations remain incompletely systematized and appear vulnerable during surgical procedures or during neurological diseases. Normally, two nerve pathways are located on both side of levator ani muscle (LAM): the autonomic pathway is supra-levatorian and the somatic pathway is infra-Levatorian. The autonomic nerves come from the superior hypogastric plexus (SHP) (sympathetic fibers) which divides into two hypogastric nerves (HNs) engaging in the pelvis. The HNs receive pelvic splanchnic nerves (parasympathetic fibers) which form the inferior hypogastric plexus (IHP). The somatic pathways come from the pudendal nerves. These notions which are established by conventional dissection can now be supplemented by the analysis of nerve markers in computer-assisted anatomic dissection (CAAD). This is likely to clarify anatomical knowledge and illuminate the understanding of genitourinary dysfunction.Objectives: The objective of this study was to describe the retro peritoneal and pelvic -perineal autonomic nervous system, its morphological (origin, topography, path and relationships) and functional (nature of fibers, visceral endings) aspects and to put into perspective the potential implications on genitourinary dysfunction.Materials and methods: Serial histological sections of 5 μm of thickness were performed in the lumbar and pelvic regions of eleven human fetuses aged 14 to 31 weeks of gestation and at the penile level in five male adult anatomical subjects. For each level, slides were stained and then treated in immunohistochemistry to detect: general nerve fibers (anti-protein S100), somatic nerve fibers (anti-peripheral myelin protein 22), autonomic adrenergic fibers (anti-tyrosine hydroxylase), autonomic cholinergic fibers (anti-VAChT), autonomic nitrergic fibers (anti-nNOS), and smooth muscle fibers (anti-actin). The slides were then digitized by a high-resolution optical scanner and the images were reconstructed in 3D using the Winsurf® software.Results: At the retroperitoneal level, the SHP is composed of adrenergic, cholinergic and nitrergic fibers. Its fibers come from inferior mesenteric plexus, the adjacent ganglions and the lumbar splanchnic nerves. At the pelvic level, the IHP is systematized into: a superior portion receiving its fibers of the SHP and innervating detrusor, ureters and seminal vesicles, a inferior portion receiving its fibers from the pelvic splanchnic nerves and innervating trigone of bladder, prostate and erectile bodies. The ureterovesical junction is an area richly innervated by adrenergic, cholinergic and nitrergic fibers from the IHP and the HNs. In addition, the IHP provides an autonomic nervous to the LAM via the supra-levatorian route, while the pudendal nerve provides a infra-levatorian somatic nervous. At the penile level, the autonomic component predominately innervates in the proximal two thirds where, in distal third, the innervation is almost exclusively somatic. Three levels of communications between the autonomic and somatic pathways were observed: pre- trans- and post-levatorian.Conclusions: The interaction of the autonomic and somatic retroperitoneo-pelvic-perineal pathways, the diversity of their origins, their communications and distribution from the plexus to the viscera are established by CAAD. These pathways deserve to be best preserved during surgical or instrumental procedures. They represent potential pathways of modulation, plasticity or regeneration to be explored in future studies.

La paralysie obstétricale du plexus brachial (POPB) est une paralysie du membre supérieur qui survient à la naissance et peut entraîner une déformation de l'articulation et un fonctionnement anormal de l'épaule. Bien que le traitement de la POPB tente de restaurer la fonction de l'épaule, la pathomécanique sous-jacente n'est pas encore clairement comprise. Les modèles computationnels sont efficaces pour fournir de telles informations, mais il n'existe aucun modèle d'articulation de l'épaule pédiatrique pour comprendre la POPB. Ainsi, ce travail de recherche a pour but de construire un framework combinant les avancées dans les domaines de la modélisation statistique de forme (MSF) et de la modélisation musculo-squelettique multi-corps (MCM). Due à l’insuffisance des données dans la cohorte pédiatrique, ce cadre a été mis en place pour l'articulation de l'épaule adulte. Pour cela, la précision de la MSF a été illustrée en prédisant 1) la forme de l'omoplate pré-morbide, et 2) les régions d'insertion musculaire sur l'omoplate et l'humérus. Cette méthode a ensuite été intégrée aux modèles MCM pour l'épaule adulte pour souligner l’importance des modèles spécifique-patient pour l’usage clinique. Pour le second objectif de cette thèse, j'ai développé un modèle MCM pédiatrique du complexe articulaire de l'épaule en utilisant le logiciel OpenSim. Grâce aux approches de cinématique et dynamique inverse, le modèle a permis de déterminer les différences de dynamique articulaires entre le côté sain et le côté pathologique. Les travaux futurs seront axés sur l’extension du travail réalisé pour la population pédiatrique afin de comprendre la pathomécanique de POPB. / Obstetrician Brachial Plexus Palsy (OBPP) is a common birth injury in children leading to shoulder joint deformity and abnormal function. While the management of OBPP disorder focuses on restoring the shoulder joint function, the underlying pathomechanics is not clearly understood yet. Computational models are effective to provide such insights, however, there is no pediatric shoulder joint model to understand the OBPP disorder. Thus, the global aim of this research work was to build a computational framework combining the advances in statistical shape modeling (SSM) and multi-body musculoskeletal modeling (MSKM) domains. Due to a lack of sufficient data in the pediatric cohort, I first developed the framework for adult shoulder joint. For this, I illustrated the accuracy of SSM in predicting 1) missing part of the scapula, and 2) muscle insertion regions on scapula and humerus bones. This method was then integrated with adult shoulder MSKMs to show the differences between generic and subject specific constructs. For the second aim of this thesis, I developed a pediatric MSKM of the shoulder joint complex using OpenSim software. Pediatric MSKM represented scapulothoracic, sternoclavicular, acromioclavicular, and glenohumeral joints with 13 degrees of freedom, and actuated by 52 musculotendon actuators representing 14 shoulder muscles. Using inverse kinematics and inverse dynamics approaches, the model was used to determine the differences in joint kinematics, and joint dynamics between healthy and unhealthy side of a single OBPP subject. Future work is focused on completing the framework on pediatric population and understanding the pathomechanics of OBPP.

O objetivo deste estudo foi analisar os efeitos da suplementação com ácido ascórbico (AA) sobre os aspectos morfológicos do plexo mioentérico de camundongos mdx jovens. Foram utilizados camundongos mdx e controles C57BL/10 machos divididos em seis grupos (n=5): GC30 (Grupo controle com 30 dias de idade); GC60 (Grupo controle com 60 dias de idade); GCS60 (Grupo controle suplementado com ácido ascórbico, com 60 dias de idade); GD30 (Grupo distrófico com 30 dias de idade); GD60 (Grupo distrófico com 60 dias de idade) e GDS60 (Grupo distrófico suplementado com AA, com 60 dias de idade). Após a eutanásia, os segmentos orais do jejuno (SOJ) foram coletados e submetidos a técnicas histoquimicas de evidenciação neuronal: NADH-diaforase, NADPH-diaforase e AChE. Os resultados demonstraram um aumento significativo do peso corporal para os animais distróficos (grupos GD30 e GD60) quando comparados aos seus respectivos controles (grupos GC30 e GC60). A análise quantitativa demonstrou que os animais do grupo GD60 possui área total do intestino delgado significativamente maior que os animais do grupo GC60; Não houve diferenças significativas entre os grupos GCS60 e GDS60. Em todos os grupos de animais com 60 dias, exceto para a densidade de neurônios nitrérgicos que se apresentou maior no grupo GCS60, todos os demais parâmetros (densidade e área do perfil neuronal) foram semelhantes entre os grupos, tanto controle (GC60 e GCS60) como distrófico (GD60 E GDS60), nas duas metodologias de coloração utilizadas (NADH-d e NADPH-d). A análise qualitativa demonstrou que componentes do plexo mioentérico dos animais distróficos suplementados com AA (GDS60) evidenciados positivos a NADPH-d e AChE apresentaram manutenção dos aspectos normais do plexo mioentérico quando comparados aos animais do grupo GD60. / The aim of this study was assessment of the effects of ascorbic acid (AA) supplementation on morphoquantitative aspects of myenteric plexus of jejunum young mdx mice. Dystrophic mdx and control C57BL/10 animals were used and divided in six groups (n = 5): GC30 (control group with 30 days of age); GC60 (control group with 60 days of age); GCS60 (control group supplemented with ascorbic acid, 60 days of age); GD30 (dystrophic group 30 days of age); GD60 (dystrophic group 60 days of age) and GDS60 (dystrophic group supplemented with AA, 60 days of age). After euthanasia, the oral segments of the jejunum (SOJ) were collected and submitted to the histochemical techniques of neuronal evidencing: NADH-diaphorase, NADPHdiaphorase and AChE. The results showed a significant increase of weight in dystrophic mice (groups GD30, GD60 and GDS60) compared to its controls (groups GC30, GC60 and GCS60). The quantitative analysis showed that the GD60 group had a significantly higher small intestine total area than the GC60; no differences significant between GCS60 and GDS60 groups. All groups of animals with 60 days of age, except for the density of nitrergic neurons showed higher in GCS60 group, in all other parameters (the neuronal density and neuronal profile area) were similar between groups, controls (GC60 and GCS60) and dystrophic (GD60 e GDS60), for techniques of the NADH-d e NADPH-d.Morphological analysis of the components of myenteric plexus of dystrophic animals supplemented with AA (group GDS60) and evidenced by the techniques of NADPH-d and AChE, showed repair of the myenteric plexus aspects compared to animals of group no supplemented (GD60).