La paralysie obstétricale du plexus brachial (POPB) est une parésie d’un ou des membres supérieurs causée le plus souvent par un étirement excessif des racines nerveuses à la naissance. Les enfants sans récupération complète garderont des séquelles à vie, comprenant une diminution de force et des mouvements, des déformations osseuses, impactant leurs activités quotidiennes. L'atteinte de l’épaule est la principale cause de morbidité. Les muscles gléno-huméraux sont au coeur de la pathologie de l’épaule. L’IRM permet l’évaluation de l’atteinte des muscles de l’épaule. Les volumes musculaires, intéressants du fait de leur corrélation avec la force, peuvent être obtenus par différentes techniques de segmentation dont les propriétés métrologiques sont inégales. Chez l’enfant avec POPB, l’utilisation d’une technique de segmentation sur un grand nombre de coupes a montré une atrophie variable des muscles glénohuméraux menant à des déséquilibres musculaires dans les trois plans de l’espace. Des corrélations entre les volumes musculaires et la force, significatives mais plus faibles que chez les enfants à développement typique étaient retrouvées. Du fait de l’atteinte osseuse et musculaire, la mobilité de l’articulation gléno-humérale est limitée. Dans une étude utilisant l’analyse quantifiée du mouvement, cette limitation, majeure en rotation externe d’épaule ainsi que des compensations au niveau de l’ensemble du membre supérieur ont été objectivées. La performance du mouvement était bonne. A partir des résultats obtenus différents objectifs et cibles thérapeutiques sont discutés. La lutte contre le déséquilibre musculaire rotateurs internes-externes apparaît comme une priorité. / Obstetric Brachial Plexus Palsy (OBPP) is the paralysis of one or both upper limbs. It is most often caused by excessive traction on cervical nerve roots during a difficult birth. The children without incomplete recovery will have long-term impairment, including loss of active and passive mobility, loss of strength, bony deformities, activity limitation and participation restriction. The loss of shoulder function is the main cause of morbidity in this population.Glenohumeral muscles involvement is a key element of the pathology of the shoulder. MRI allows evaluation of the shoulder muscle involvement. Muscle volumes in particular, well correlated with muscle strength, can be modified by different segmentation techniques whose metrological properties are unequal.In children with OBPP, the use of a segmentation technique on a large number of slices has shown a variable atrophy of the gleno-humeral muscles leading to three-dimensional muscular imbalances.Correlations between muscle volumes and strength were significant but lower than in children with typical development.Because of the bone deformity and muscle involvement, the mobility of the glenohumeral joint is limited. In a study using 3D motion analysis of the movement, this limitation, which is large in external shoulder rotation, as well as compensations on the whole upper limb, were shown. The performance of the movement was good.From these results, different objectives and therapeutic targets are discussed. Internal-external rotator muscular imbalance correction appears as a priority.

La radiculopathie cervicale caudale a été identifiée comme cause de boiterie affectant le membre antérieur chez le cheval. Les affections dégénératives des articulations intervertébrales des processus articulaires entraînent un remodelage périarticulaire pouvant comprimer les racines du nerf spinal ou leur rameau ventral. Les objectifs de l’étude étaient de décrire la réalisation d’injections échoguidées périneurales du rameau ventral des nerfs spinaux cervicaux 7 et 8 (RV7 et RV8), d’évaluer sur des cadavres de chevaux par dissection la diffusion péri-nerveuse d’une solution colorée ainsi que de décrire chez des chevaux sains les signes cliniques associés à une anesthésie périneurale échoguidée du RV7 et RV8 individuellement. Dans l’étude post-mortem, 5 RV7 et 5 RV8 ont été visualisés échographiquement et colorés par une injection de 7 ou 14 ml de solution colorée. Une portion du tronc nerveux a été trouvée coloré pour chaque injection. La coloration était uniforme transversalement sur toute la largeur du nerf et couvrait une longueur supérieure à 2 cm pour 8 RV alors qu’une coloration de la moitié crâniale du RV sur une longueur de moins de 2 cm pour un RV7 et un RV8. L’étude sur cheval sain portait sur 4 chevaux sains sans image radiographique anormale de la colonne cervicale. Six RV7 et 8 RV8 ont été anesthésiés de la Lidocaïne 2% mélangés à du iohexol. Toutes les injections ont entraîné boiterie antérieure ipsilatérale de l’injection. Les boiteries les plus sévères correspondaient à une parésie du nerf suprascapulaire pour RV7 et à une parésie radiale pour RV8. Cette étude a montré qu’il était possible de réaliser une injection périneurale des RV 7 et RV8 chez le cheval et que l’anesthésie tronculaire des deux racines provoque une atteinte motrice essentiellement de la fonction nerveuse. Ces résultats contribuent à mieux comprendre la symptomatologie des compressions nerveuses cervicales chez le cheval. / Caudal cervical radiculopathy has been identified as a cause of frontlimb lameness in horses. Degenerative conditions of articular process joint result in periarticular remodeling responsible for compression of spinal nerve roots or their ramus ventralis (RV). The objectives of the study were to describe how to perform perineural RV injection under ultrasonographic guidance, to evaluate on cadaver perineural RV staining after a dye solution injection, as well as describe clinical signs associated with a perineural ultranosonography-guided anesthesia of RV7 and RV8 respectively. In the post-mortem study, the RV of the spinal cervical nerves was visualized in all cadavers. Eight RV had a uniform transversal staining of the nerve trunk that covered longitudinally a distance greater than 2 cm. One C7 and one C8 RV showed incomplete transversal staining with a more concentrated color on its half cranial aspect and a longitudinal coverage of less than 2 cm. The in vivo study included 6 RV7 and 8 RV8 perineural injections of a local anesthetic agent, performed on 4 horses that had no abnormal finding on cervical radiographs. All anesthetic injections (lidocaine 2% and iohexol) resulted in modifications of the locomotion with variable degree of lameness on the ipsilateral frontlimb. Severe lameness was characteristic of a suprascapular paresis for RV7 and a radial paresis for RV8. Mild to moderate lameness on the ipsilateral frontlimb included decreased anterior phase of the stride, intern circumduction of the limb and sometimes stumbling for that same frontlimb. Signs of ataxia on the hindlimbs were encountered for 3 injections. This study showed that it is possible to perform perineural injections of RV7 and RV8 in horses and that perineural anesthesia of RV7 and RV8 results in motor dysfunction. These findings constitute a contribution to understanding clinical signs associated with cervical nerve compression in horses.

Methods of regional anaesthesia and regional postoperative analgesia are common in perioperative management of patients in traumatology-orthopaedics. One of most challenging fields of traumatology-orthopaedics is shoulder surgery. Shoulder surgery is associated with intense and long-lasting postoperative pain. It affects patients’ well-being, limits limb function and worsens results of surgical treatment. Determination of optimal methods for postoperative pain relief is very important in clinical practice. Several modern studies compared methods of systemic analgesia with continuous interscalene infusion of bupivacaine 0,15 - 0,25 % solution. Application of these concentrations of bupivacaine resulted in sufficient analgesia but profound motor blockade and anaesthetic toxicity were observed. There are few studies on interscalene infusions of small concentrations of bupivacaine. Data on effects of small doses of bupivacaine on intensity of motor blockade and adjuvant drugs on postoperative analgesia is lacking. AIM OF THE STUDY: to evaluate the quality of post-operative pain treatment after shoulder surgery using continuous perineural infusions of different concentrations (0.1% and 0.15%) of bupivacaine and bupicacaine (0.1%) in combination with adjuvant clonidine and effects on operated hand motor function. To assess clinical advisability of interscalene brachial plexus identification and catheterization using G. Meier’s technique. 159 patients scheduled for elective... [to full text]

La neurogenèse adulte permet la formation de nouveaux neurones dans les bulbes olfactifs de la souris. Les propriétés des cellules souches neurales situées dans la zone sous-ventriculaire (ZSV) et des précurseurs sont régulées par la niche contenant des cellules de support et une matrice extracellulaire (MEC). Des facteurs contenus dans le liquide cérébrospinal (LCS), produits par les plexus choroïdes (PC), contrôlent aussi la niche. L'homéoprotéine Otx2 est secrétée dans le LCS par les PC, et internalisée spécifiquement par certaines cellules du parenchyme cérébral. Otx2 est impliquée dans différentes étapes du développement du cerveau, dont celui des PC, et peut agir de manière non-cellulaire-autonome. Ma thèse vise à comprendre comment Otx2 régule les fonctions des PC et participe à la neurogenèse adulte. Grâce à des études génomiques d'un modèle murin knockdown (KD) d'Otx2 dans les PC adultes, nous avons montré que (i) les PC de différents ventricules présentent des profils d'expression différents (ii) le KD d'Otx2 modifie l'expression de gènes impliqués dans des fonctions importantes des PC (iii) la dérégulation de certains gènes après KD est spécifique d'un type de PC. Une étude protéomique suggère (iv) qu'Otx2 pourrait être impliquée à d'autres niveaux que la régulation transcriptionnelle. L'étude de la neurogenèse adulte dans des modèles murins KD d'Otx2 nous a permis de montrer que (i) l'expression d'Otx2 dans les PC régule la neurogenèse adulte (ii) Otx2 transfère dans les astrocytes de la ZSV (iii) le transfert d'Otx2 est suffisant pour réguler la neurogenèse (iv) le KD d'Otx2 dans les PC modifie l'expression de protéines de la MEC secrétées par les astrocytes. / Adult neurogenesis in mice involves neural stem cells in the subventricular zone (SVZ) whose progenitors integrate into the olfactory bulbs. The neurogenic niche, which contains supporting cells and extracellular matrix (ECM), regulates the properties (proliferation, migration and differentiation) of progenitor cells. This niche is influenced by factors from cerebrospinal fluid (CSF), which is produced by the choroid plexus (CP) in the brain ventricles. The Otx2 homeoprotein transcription factor is secreted into CSF by CP, and taken up by a specific subset of cells within the brain parenchyma. Otx2 is involved in various stages of brain development, including CP development, and has non-cell autonomous functions. The aim of my thesis is to understand how Otx2 regulates adult CP function and participates in adult SVZ neurogenesis. Through genomic studies, we investigated the consequence of Otx2 knockdown (KD) in adult CP and found: (i) adult CP from different ventricles exhibit different expression profiles; (ii) Otx2 KD alters the expression of genes with important CP functions; and (iii) deregulation of certain genes after Otx2 KD can be CP specific. Through proteomics studies, we found that (iv) adult Otx2 could be involved in functions beyond transcriptional regulation, such as RNA processing.To evaluate the role of Otx2 in SVZ neurogenesis, we also used Otx2 KD mouse models. We found that: (i) the expression of Otx2 in CP regulates adult neurogenesis; (ii) Otx2 transfers to astrocytes of the SVZ; (iii) Otx2 transfer is sufficient to regulate adult neurogenesis; and (iv) Otx2 KD in CP alters the expression of ECM proteins secreted by astrocytes in the neurogenic niche.

The most frequent sequelae following an obstetric brachial plexus lesion without complete functional recovery concern the impaired shoulder rotation movements and the associated structural changes of the growing glenohumeral joint. <p>This pathology is often unrecognized and may lead to a limitation in active movements, a pathologic and less efficient motion pattern in the affected limb, and the development of a severely incongruent and dysplastic glenohumeral joint prone to further arthrosis.<p><p>Hypothesis<p><p>Glenohumeral dysplasia after obstetric brachial plexus lesion has multiple etiologies: A hypothetic obstetric trauma may precede the motor imbalance, due to the initial palsy and prevalent recovery of the medial rotators of the shoulder.<p>The correction of the muscular imbalance, by neurotization of the lateral rotators (supra- and infraspinatus muscle) using a local nerve transfer or by a later muscle transfer surgery, improves function, seems to prevent the development of joint dysplasia and limits the articular deformities once they are present. <p>The early (peripartal) glenohumeral subluxation must be recognized and treated immediately to prevent the development of a severe joint contracture and dysplasia.<p> <p>Material and methods<p><p>Two retrospective and one prospective study evaluate how surgery may correct the muscular imbalance.<p>In a first series of 65 children, we analyse the recovery of the supra- and infraspinatus muscle after a nerve transfer onto the suprascapular nerve.<p>In a second retrospective analysis on 114 children, we study the outcome after secondary surgery (anterior joint release, modified Hoffer muscle transfer) dedicated to improve active and passive lateral rotation of the shoulder.<p>A prospective study of 50 magnetic resonance (MRI) scans of the glenohumeral joint describes the articular deformities.<p>Finally, 10 children presenting a very early glenohumeral subluxation have undergone a closed orthopaedic reposition and plaster immobilisation and were followed for a minimum of 2 years.<p><p>Results<p><p>In the first group, neurotization of the suprascapular nerve has been performed either by a dorsal or a ventral approach at a mean age of 14 months. The mean follow up is of 3 years and the improvement in aLR(ABD) is 68°and only 25°in aLR(ADD). None of these children with improved active lateral rotation of the shoulder developed clinical signs of a glenohumeral dysplasia within the follow up period.<p><p>Among the 114 children operated between 6 months and 44 years with a shoulder release, 74 had an isolated release procedure, 40 an associated tendon transfer or a suprascapular neurotization. The mean improvement in passive lateral rotation with the arm adducted (pLR (ADD)) was 60°. Active lateral rotation was possible in 63 % of children who underwent an isolated joint release.<p>The Hoffer muscle transfer was performed in 29 children and improved the aLR (ABD) by 60° (mean postoperative follow-up of 30 months). No signs of severe glenohumeral dysplasia developed in these children later on.<p><p>The prospective study of 50 consecutive MRI scans in children presenting at the consultation with a rotatory imbalance of their shoulder, as a sequel from obstetric brachial plexus palsy (Bahm et al. 2007) shows 37 congruent joints, 10 dorsal subluxations, 2 dorsal luxations and one complete dislocation associated with the formation of an independent neoglenoid. The humeral head was deformed in 12 cases; the glenoid in 34 children (flat in 23, biconcave 7 times, convex 3 times).<p><p>The follow up of 2 years in 10 children who underwent an immediate closed reposition shows evidence of joint congruence with a limited (30°) pLR (ADD), definitely lower than after a surgical release.<p><p>Conclusion<p><p>Some osteo-articular deformities secondary to neuromuscular diseases are well described ;those following an obstetric brachial plexus lesion are insufficiently recognized. Their etiology is unclear.<p>At the level of the shoulder joint, these sequels might be very important.<p>Our neuroorthopaedic hypothesis concerning a multifactorial etiology and treatment strategy raises the need of an early and precise screening of the deforming forces to render normal biomechanics and function.<p>The surgical strategy includes the reconstruction of the responsible motor nerve and the improvement of the passive and active range of motion of the shoulder in lateral rotation<p>It seems to be efficient to limit the progression to severe glenohumeral dysplasia and further arthrosis.<p> / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

The aim of the study was to examine adolescents’ experiences of having brachial plexus birth palsy, which is impaired arm function due to a birth injury. Psychosocial focal points were how the adolescent’s experience their lives concerning studies, spare time activities and relationships, experiences of limitations in comparison to their peers, and how they experience health care. Eight adolescents who had surgery of the injury were interviewed. Through qualitative phenomenological analysis the following meaning units were identified: ‘Me and others’; ‘Professional medical contacts and experiences’; and ‘Adjustment and strategies to solutions and obstacles’ with essences ‘Disabled or have a disability’; ‘Then and now’ and ‘Lack of references’. The result showed that the adolescents did not identify themselves as disabled, and did not focus on their arm, but wished for improved physical function. They had good support from health care, although wanted more follow-ups and more aimed information. They had adjusted well to their injury, but did not have any comparisons as they had their injury since birth. Understanding the experiences adolescents with BPBP have is essential for advancing the care of these individuals. Further research is necessary regarding the experience people with this injury have. / Syftet med studien var att studera ungdomars erfarenheter av att leva med en plexusskada, det vill säga nedsatt armfunktion på grund av en förlossningsskada, ur ett psykosocialt perspektiv med fokus på hur ungdomarna upplever sina liv beträffande studier, fritid och relationer, upplevelser av begränsningar i jämförelse med generationskamrater på grund av skadan, samt erfarenheter av sjukvården. Åtta ungdomar som opererats för skadan intervjuades. Genom kvalitativ fenomenologisk analys kunde följande meningsbärande enheter urskiljas: ’Jag och andra’; ’Professionella kontakter och erfarenheter’ och ’Anpassningar och strategier till lösningar och hinder’ där ’Funktionshindrad eller ha funktionshinder’; ’Då och nu’ samt ’Brist på referenser’ var gemensamma samtalsämnen. Resultatet visade att ungdomarna inte betraktade sig som handikappade, de fokuserade inte på sin arm i sin vardag, och önskade klara av mer fysiska aktiviteter. De upplevde gott stöd från sjukvården, men önskade uppföljningar och mer riktad information. De hade anpassat sig till skadan, men upplevde att de inte kunde jämföra med andra eftersom de haft skadan sedan födseln. Att kunna förstå ungdomars erfarenheter av att leva med en plexusskada, är nödvändigt för att förbättra vården och bemötandet för dessa individer.

Neurólises de plexos simpáticos têm sido utilizadas no tratamento da dor oncológica, mostrando ser um recurso terapêutico bastante eficaz e seguro. Alguns estudos apontam a utilização da neurólise de plexos simpáticos em estágios iniciais da doença por prevenir a dor e melhorar a qualidade de vida, contrariando a OMS que preconiza o uso de métodos invasivos em última instância. Em estudo prospectivo, randomizado e controlado, neurólise de plexos simpáticos realizada em estágios diferentes do tratamento da dor oncológica foi comparada com o tratamento farmacológico. Foram selecionados 60 pacientes com câncer abdominal ou pélvico e alocados em três grupos. No grupo I (precoce) os pacientes estavam em uso de AINEs e opióides fracos ou fortes (dose inferior a 90mg/dia de morfina) e reportavam dor (VAS &#61619; 4) quando foram submetidos a neurólise plexo celíaco (NPC), neurólise do plexo hipogástrico superior (NPHS) ou neurólise plexo simpático lombar (NPSL) de acordo com o sítio de dor. No grupo II (tardio) a neurólise foi realizada quando a utilização de AINEs e morfina foram iguais ou superiores a 90mg/dia de morfina e VAS>4. No grupo III (controle) os pacientes fizeram uso somente de medicação analgésica. Os pacientes foram observados durante 8 semanas e avaliados quanto à intensidade da dor (VAS), consumo de opióides e qualidade de vida. Imediatamente após as neurólises e durante todo o tempo de observação, os pacientes dos grupos precoce e tardio apresentaram redução da intensidade da dor e do consumo de opióides, além disso melhora da qualidade de vida quando comparados com o grupo controle. Não houve diferenças entre os grupos precoce e tardio nestes aspectos. Efeitos adversos correlacionados com o uso de opióide, como náuseas e/ou vômitos, perda do apetite e constipação foram significativamente maiores no grupo controle. Complicações relacionadas às neurólises, tais como hipotensão e diarréia, foram transitórias e não deferiram significativamente do grupo controle. Não foram encontradas complicações sérias em nenhum dos grupos experimentais. A neurólise de plexos simpáticos foi efetiva na redução da intensidade da dor e do consumo de analgésicos e dos efeitos adversos relacionados com a administração de drogas, e na melhora da qualidade de vida dos pacientes. Embora não havendo diferenças entre os grupos precoce e tardio, os resultados apontam a necessidade de utilizar esta técnica como recurso não somente em fase terminal da doença. / Neurolytic sympathetic plexus blocks (NSPB) have been used as a quite effective and safe therapeutic resource for the treatment of cancer pain. Studies point to the use of NSPB in the early phases of the disease to prevent pain and to improve the life quality, contradicting WHO that extols the use of invasive methods ultimately. We compared the use of neurolytic plexus block in two different phases of the treatment of oncology pain with the pharmacological therapy. In prospective study, randomized and controlled, sixty patients with abdominal or pelvic oncology pain were allocated to tree groups. In group I (early block) the patients using NSAID and weak opioid or oral morphine at a dose of less than 90 mg/day and reporting pain (VAS &#61619; 4) were submitted to a neurolytic celiac plexus block (NCPB), superior hypogastric plexus block (SHPB) or lumbar sympathetic ganglionic chain (LSGCB), in accordance to the site of pain. In group 2 (late block) the patients were submitted neurolysis when using NSAID and oral morphine at a dose equals to or more than 90 mg/day and VAS &#61619; 4. In group 3 (control), patients were treated with pharmacological therapy only. The patients were observed for 8 weeks and appraised for the intensity of the pain (VAS), opioid consumption and quality of live. The patients of groups I and II had reduction of the intensity of the pain, opioid consumption and get better quality of live immediately after to the neurolytic and during the whole time of observation when compared with the group control. There were no significant differences between groups I and II with these aspects. Adverse effects correlated with the use of opioids, as nauseas and/or vomits, loss of the appetite and constipation were significantly larger in the group control. Neurolysis related complications such as hypotension and diarrhea, were transitory and statistically similar to these found in the control group. They were not found serious complications. The neurolysis of sympathetic plexus was shown to be effective to reduce the intensity of pain, analgesic consumption and adverse effects related to the use of opioids, and in the improvement of the quality of life. The results point to the usefulness of indicating neurolytic procedure for the management of cancer pain not only in terminal phase of the disease.

Este projeto, analisou a distribuição dos neurônios nos plexos mioentérico (PM) e submucoso (PS) imunorreativos aos receptores P2X2 (ir) e P2X7 (ir), calbindina (Calb-ir), calretinina (Calr-ir), colina acetil transferase (ChAT-ir) e ao óxido nítrico sintase (NOS-ir) do colo distal de ratos submetidos à desnutrição a renutrição protéica. Utilizaram-se colos distais de ratos nutridos (N42), desnutridos (D42) e renutridos (RN42). Os resultados do plexo PM, demonstraram que 100% dos neurônios Calb-ir, Calr-ir, ChAT-ir e NOS-ir, expressavam os receptores P2X2-ir e P2X7-ir nos três grupos. A densidade neuronal no PM, demonstrou um aumento de 20% a 97% dos neurônios receptores P2X2-7-ir, Calr-ir, ChAT-ir e NOS-ir e no PS foi de 29% a 75%, ambos D42 e recuperação no RN42. O perfil neuronal P2X7-ir, Calb-ir, Calr-ir e ChAT-ir do PM demonstrou diminuição de 28% a 40% e no PS os neurônios P2X2-7-ir, Calb-ir e ChAT-ir de 19% a 47% no D42. Concluí-se que, a desnutrição afeta os neurônios entéricos havendo recuperação na renutrição, podendo influenciar nas funções gastrintestinais. / The aim of the work was to analyze the distal colon myenteric (MN) and submucous (SN) neurons immunoreactive for P2X2-7 receptors, calbindin (Calb-ir), calretinin (Calr-ir), choline acetyltransferase (ChAT) and nitric oxide synthase (NOS) of the animals submitted to undernutrition and refeeding proteic. Distal colon was used from nourished (N42), undernourished (D42) and refeeding (RN42) rats. The results have shown 100% coexpression of the myenteric and submucous Calb-ir, Calr-ir, ChAt-ir e NOS-ir neurons with P2X2-7-ir receptors. The MN density have shown increase of the 20% and 97% of the P2X2-7-ir, Calr-ir, ChAT-ir e NOS-ir neurons of the D42 group, and the SN have been increased 29% a 75% in the D42 group. In the MN neuronal profile have shown decrease P2X7-ir, Calb-ir, Calr-ir and ChAT-ir neurons of the 28% to 40% and in the PS P2X2-7-ir, Calb-ir and ChAT-ir of the 19% a 47% neurons in the D42 group. I concluded that, the undernutrition affects the enteric neurons and there was recuperation in the refeeding, this can influence the gastrintestinal functions.

L’ion calcium est un second messager qui intervient dans de nombreux processuscellulaires dont la prolifération, la différenciation et l’apoptose. Ainsi, l’homéostasiecalcique constitue un point central de régulation de la signalisation cellulaire. En effet, laconcentration calcique cytosolique de calcium subit des oscillations, qui suivant leuramplitude ou leur fréquence, vont être capables d’activer spécifiquement certains facteursde transcription. La régulation de ces oscillations implique entre autres les ATPases de typeSERCA (Sarco/Endoplasmic Reticulum Calcium ATPase) qui accumulent le calcium dansle réticulum endoplasmique. L’objectif de ce travail de thèse a été l’étude des SERCAs aucours de la différenciation lymphocytaire B et dans l’épithélium du plexus choroïde ; ceci,afin de mieux comprendre le profil d’expression de ces pompes et les mécanismes derégulation impliqués.Au cours de la différenciation de lignées de leucémie aiguë lymphoblastique (LAL) nousavons observé que l’expression de l’isoforme SERCA2 restait stable ou augmentaitlégèrement alors que celle de l’isoforme SERCA3 était toujours fortement induite, pouvantatteindre des niveaux observés dans les cellules lymphoïdes matures. Nous avons égalementobservé que l’inhibition de l’activité des SERCAs altère la différenciation cellulaire qui estdépendante de la voie des PKC. Ces données indiquent que SERCA3 pourrait être utiliséecomme marqueur de la différenciation lymphocytaire B. Une régulation de l’expression desSERCAs a également été mise en évidence au cours de la différenciation de l’épithélium duplexus choroïde normal ou tumoral. SERCA3 est fortement exprimée dans l’épithéliumnormal, mais on retrouve une baisse ou une perte de son expression dans l’épithéliumtumoral, cette baisse est corrélée à la perte de la différenciation selon le grade des tumeurs.L’étude de l’expression des SERCAs dans les cellules primaires du plexus choroïde traitépar des agents cyto-différenciateurs (acides gras à chaîne courte), montre que ladifférenciation est associée à une surexpression de SERCA3. SERCA3 peut donc égalementêtre un marqueur de la différenciation de l’épithélium du plexus choroïde.L’ensemble de ce travail a montré que la différenciation cellulaire est associée à la régulationde protéines impliquées dans la régulation de l’homéostasie calcique : les SERCAs. On peutainsi proposer SERCA3 comme un nouveau marqueur phénotypique utile pour l’analyse dela différenciation du plexus choroïde normale et néoplasique, ainsi que pour celle de ladifférenciation lymphoïde pré-B leucémique. / Cellular calcium is involved in a multitude of biological processes including thecontrol of cell proliferation, differentiation and programmed cell death, and constitutestherefore a keconcentration calcique cytosolique de calcium subit des oscillations, qui suivant leuramplitude ou leur fréquence, vont être capables d’activer spécifiquement certains facteursde transcription. La régulation de ces oscillations implique entre autres les ATPases de typeSERCA (Sarco/Endoplasmic Reticulum Calcium ATPase) qui accumulent le calcium dansle réticulum endoplasmique. L’objectif de ce travail de thèse a été l’étude des SERCAs aucours de la différenciation lymphocytaire B et dans l’épithélium du plexus choroïde ; ceci,afin de mieux comprendre le profil d’expression de ces pompes et les mécanismes derégulation impliqués.Au cours de la différenciation de lignées de leucémie aiguë lymphoblastique (LAL) nousavons observé que l’expression de l’isoforme SERCA2 restait stable ou augmentaitlégèrement alors que celle de l’isoforme SERCA3 était toujours fortement induite, pouvantatteindre des niveaux observés dans les cellules lymphoïdes matures. Nous avons égalementobservé que l’inhibition de l’activité des SERCAs altère la différenciation cellulaire qui estdépendante de la voie des PKC. Ces données indiquent que SERCA3 pourrait être utiliséey element in cell signaling. Calcium levels vary in a dynamic mannerdepending on the state of activation of the cell, and can display oscillations the amplitudeand frequency of which can convey specific signals to various transcription factors.Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes) accumulate calciumfrom the cytosol into the endoplasmic reticulum (ER). By modulating the spatiotemporalcharacteristics of calcium signals and oscillations, SERCA pumps constitute an importantand unique point of control of calcium-dependent cell activation. In this work weinvestigated SERCA expression during early B lymphoid differentiation and in normal,tumoral and hyperplastic choroid plexus epithelial cells.We have shown that SERCA3 expression is markedly increased during thepharmacologically induced differentiation of immature B acute lymphoblastic leukemiacells, whereas the expression of the simultaneously expressed SERCA2 isoform is notmodified significantly. SERCA3 expression during this differentiation process can reachlevels observed in mature B lymphoid cells, and is dependent on the activation of proteinkinase C. Moreover, the direct pharmacological inhibition of SERCA-dependent calciumtransport interferes with the differentiation process.Our investigations on the choroid plexus show, that whereas SERCA3 is highly expressedin normal choroid plexus epithelium, expression is strongly decreased in benign choroidplexus tumors and is lost in carcinoma, whereas expression is retained in hyperplasia. Inaddition, treatment of primary normal choroid plexus epithelial cells by short chain fattyacid-type cell differentiation-inducing agents in vitro leads to the induction of SERCA3expression.Our observations when taken together indicate that ER calcium homeostasis is remodeledduring the differentiation of immature B lymphoid cells and in the choroid plexus due to theinduction of SERCA3 expression. We show that a cross-talk exists between SERCA functionand the control of differentiation in B cells, that SERCA3 constitutes a new phenotypicmarker for the study of early B cell differentiation, and that the lack of SERCA3 expressionmay be useful for the identification of choroid plexus tumors.

Neurólises de plexos simpáticos têm sido utilizadas no tratamento da dor oncológica, mostrando ser um recurso terapêutico bastante eficaz e seguro. Alguns estudos apontam a utilização da neurólise de plexos simpáticos em estágios iniciais da doença por prevenir a dor e melhorar a qualidade de vida, contrariando a OMS que preconiza o uso de métodos invasivos em última instância. Em estudo prospectivo, randomizado e controlado, neurólise de plexos simpáticos realizada em estágios diferentes do tratamento da dor oncológica foi comparada com o tratamento farmacológico. Foram selecionados 60 pacientes com câncer abdominal ou pélvico e alocados em três grupos. No grupo I (precoce) os pacientes estavam em uso de AINEs e opióides fracos ou fortes (dose inferior a 90mg/dia de morfina) e reportavam dor (VAS &#61619; 4) quando foram submetidos a neurólise plexo celíaco (NPC), neurólise do plexo hipogástrico superior (NPHS) ou neurólise plexo simpático lombar (NPSL) de acordo com o sítio de dor. No grupo II (tardio) a neurólise foi realizada quando a utilização de AINEs e morfina foram iguais ou superiores a 90mg/dia de morfina e VAS>4. No grupo III (controle) os pacientes fizeram uso somente de medicação analgésica. Os pacientes foram observados durante 8 semanas e avaliados quanto à intensidade da dor (VAS), consumo de opióides e qualidade de vida. Imediatamente após as neurólises e durante todo o tempo de observação, os pacientes dos grupos precoce e tardio apresentaram redução da intensidade da dor e do consumo de opióides, além disso melhora da qualidade de vida quando comparados com o grupo controle. Não houve diferenças entre os grupos precoce e tardio nestes aspectos. Efeitos adversos correlacionados com o uso de opióide, como náuseas e/ou vômitos, perda do apetite e constipação foram significativamente maiores no grupo controle. Complicações relacionadas às neurólises, tais como hipotensão e diarréia, foram transitórias e não deferiram significativamente do grupo controle. Não foram encontradas complicações sérias em nenhum dos grupos experimentais. A neurólise de plexos simpáticos foi efetiva na redução da intensidade da dor e do consumo de analgésicos e dos efeitos adversos relacionados com a administração de drogas, e na melhora da qualidade de vida dos pacientes. Embora não havendo diferenças entre os grupos precoce e tardio, os resultados apontam a necessidade de utilizar esta técnica como recurso não somente em fase terminal da doença. / Neurolytic sympathetic plexus blocks (NSPB) have been used as a quite effective and safe therapeutic resource for the treatment of cancer pain. Studies point to the use of NSPB in the early phases of the disease to prevent pain and to improve the life quality, contradicting WHO that extols the use of invasive methods ultimately. We compared the use of neurolytic plexus block in two different phases of the treatment of oncology pain with the pharmacological therapy. In prospective study, randomized and controlled, sixty patients with abdominal or pelvic oncology pain were allocated to tree groups. In group I (early block) the patients using NSAID and weak opioid or oral morphine at a dose of less than 90 mg/day and reporting pain (VAS &#61619; 4) were submitted to a neurolytic celiac plexus block (NCPB), superior hypogastric plexus block (SHPB) or lumbar sympathetic ganglionic chain (LSGCB), in accordance to the site of pain. In group 2 (late block) the patients were submitted neurolysis when using NSAID and oral morphine at a dose equals to or more than 90 mg/day and VAS &#61619; 4. In group 3 (control), patients were treated with pharmacological therapy only. The patients were observed for 8 weeks and appraised for the intensity of the pain (VAS), opioid consumption and quality of live. The patients of groups I and II had reduction of the intensity of the pain, opioid consumption and get better quality of live immediately after to the neurolytic and during the whole time of observation when compared with the group control. There were no significant differences between groups I and II with these aspects. Adverse effects correlated with the use of opioids, as nauseas and/or vomits, loss of the appetite and constipation were significantly larger in the group control. Neurolysis related complications such as hypotension and diarrhea, were transitory and statistically similar to these found in the control group. They were not found serious complications. The neurolysis of sympathetic plexus was shown to be effective to reduce the intensity of pain, analgesic consumption and adverse effects related to the use of opioids, and in the improvement of the quality of life. The results point to the usefulness of indicating neurolytic procedure for the management of cancer pain not only in terminal phase of the disease.