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Migraine is a chronic neurovascular disease that affects about 15% of the population and is characterized by recurrent episodes of unilateral throbbing headaches with associated symptoms such as nausea, vomiting, photophobia and phonophobia. For many patients, available pharmacological options do not meet their expectations, because of lake of efficacy, side effects for because they have contraindications. Lately, proof-of-concept clinical trials show that the blockade of CGRP receptors, a neuropeptide that is found in 50% of trigeminovascular neurones, can significantly decrease many migraine symptoms without inducing any vasoconstriction and that these molcules are beeing very well tolerated, even in patients with cardiovascular dieases. This leads to the development of many other molecules. None of them did pass the phase 2 of clinical trials but the Telcagepant. This molecule has been shown to be very efficient and well tolerated in the acute treatment of migraine. However, its development has been stopped because of hepatotoxicity concerns have been found out in trials about prophylactic use, but not in its acute use, maintaining absence of pharmacological options for the acute treatment of migraine for migrainers who also suffer from cardiovascular diseases. More recently, antibodies against CGRP or its receptors have been developped for the prophylactic management of migraine and seem to be very promising. The promising nature of all these molecules in the treatment of acute migraine attacks or in its prophylaxis will be discussed. La migraine est un désordre neuro-vasculaire présent chez environ 15% de la population et se manifeste par des épisodes récurrents de céphalées lancinantes hémilatérales associées à de nombreux autres symptômes, tels que nausées, vomissements, photophobie et/ou phonophobie. Pour de nombreux patients, les options pharmacologiques disponibles actuellement sur le marché pour le traitement de leurs crises de migraine ne répondent pas à leurs attentes, par manque d’efficacité, à cause d’effets secondaires mal supportés, ou car ceux-ci leur sont contre-indiqués. Dernièrement, des études « preuve de concept » ont montré que le blocage des récepteurs du CGRP, un neuropeptide présent dans 50% des neurones du système trigémino-vasculaire, diminuait significativement de nombreux symptômes de la crise de migraine sans induire de vasoconstriction et était très bien toléré, y compris chez les patients présentant des pathologies cardiovasculaires, ce qui a mené au développement de plusieurs petites molécules. De ces nombreuses petites molécules étant allées jusqu’en phase II, seul le Telcagepant a été testé en étude clinique de phase III. Celui-ci s’est avéré efficace et très bien toléré dans le traitement de crise de la migraine. Son développement a malheureusement été interrompu par la firme à cause de la détection d’une hépatotoxicité en usage quotidien dans un but prophylactique, maintenant l’absence d’options pharmacologiques de traitement de la migraine aiguë pour les patients migraineux et souffrant de pathologies cardiovasculaires. Plus récemment, des anticorps ciblant le CGRP ou les récepteurs du CGRP sont entrés en développement dans le traitement prophylactique de la migraine et s’avèrent très prometteurs. L’intérêt de toutes ces molécules et leur potentiel dans la prise en charge aiguë ou prophylactique de la migraine sera discuté dans ce mémoire.

Receptors, Calcitonin Gene-Related Peptide --- Migraine Disorders

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Le diabète de type 2 est une maladie non auto-immune d'évolution progressive. Bien qu'il existe une prédisposition génétique, de nombreux facteurs environnementaux (excès pondéral, ...) sont incriminés dans son développement.La prévalence du diabète de type 2, étroitement corrélée à celle de !'obésité, est en constante augmentation à un point tel que !'OMS la qualifie de pandémie.Caractérisée par une hyperglycémie chronique, cette pathologie engendre à terme de nombreuses complications micro et macro-vasculaires., Au vu de ces conséquences chroniques et des prévisions inquiétantes des sociétés scientifiques, ce type de diabète représente un problème majeur de santé publique.Le GLP-1, hormone sécrétée par l'intestin en réponse à un repas, agit principalement en stimulant l'insulinosécrétion, ralentissant la vitesse de vidange gastrique et augmentant la sensation de satiété. Cette hormone est déficitaire chez le patient diabétique et constitue, de ce fait, une stratégie thérapeutique intéressante. En Belgique, l'adjonction d'analogues du GLP-1 se situe après échec du traitement en bithérapie, en association avec de la metformine et des sulfamidés ou des glitazones.Les études s'accordent pour dire que les analogues du GLP-1 contribuent à l'amélioration du contrôle glycémique, de la tension artérielle et du profil lipidique donnant tout son sens à ce mémoire.Ce travail consiste à évaluer les effets à moyen et long terme des analogues du GLP-1 sur le diabète de type 2. L'analyse rétrospective des dossiers des patients mis sous ces molécules entre 2008 et 2016, permettra de déterminer les facteurs prédictifs de réponse au traitement et la durée de contrôle de la maladie.

Retrospective Studies --- Diabetes Mellitus, Type 2 --- Glucagon-Like Peptide 1 --- Anthropometry

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This volume focuses on various aspects of interleukin-27 (IL-27), especially its potential for clinical applications. The authors discuss the downstream signaling from the IL-27 receptor and its molecular targets in immune cells including Th1, Th2, Th17, Treg, Tr1, Tfh, B cells, DCs and macrophages. The inhibition of Th17 cells by IL-27 is vital for the maintenance of the feto-maternal tolerance and the prevention of lupus, multiple sclerosis, autoimmune uveitis, immune thrombocytopenia and atherosclerosis. However, the same inhibitory capabilities compromise the immune response to bacterial pathogens, and IL-27 is a pathogenic factor in sepsis and tuberculosis. Also covered are the conflicting reports on the role of IL-27 in rheumatoid arthritis, the effect of IL-27 on epithelia, which seems to play a role in asthma, psoriasis and inflammatory bowel diseases, and the direct cytotoxic and anti-vascular effects of IL-27, which make it a promising agent for the treatment of cancer. Accordingly, this volume will be of interest to researchers and clinicians alike.

Medicine. --- Immunology. --- Cytokines. --- Growth factors. --- Biomedicine. --- Cytokines and Growth Factors. --- Interleukins. --- Growth factors --- Lymphocytes --- Cellular immunity --- Immune response --- Immunobiology --- Life sciences --- Serology --- Regulation --- Cell growth factors --- Cellular growth factors --- Growth peptides --- Growth promoting substances --- Growth substances --- Peptide growth factors --- Peptide regulatory factors --- Polypeptide growth factors --- Cytokines --- Peptides

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This book describes the diverse roles that growth factors and cytokines play in skeletal muscle. The extracellular environment has profound effects on the biology of skeletal muscle. The soluble portion of this environment includes a rich milieu of growth factors and cytokines which have been shown to regulate virtually all facets of the response of skeletal muscle to external stimuli, whether it be exercise induced metabolic shifts, remodeling in response to trauma or loading of the ongoing pathology associated with neuromuscular disease. The chapters included in this work illustrate growth factors that directly affect skeletal muscle cells and those which influence non-muscle cells that contribute to the biology of skeletal muscle as a whole tissue. The current state of the art, with the advent of systems biology, allows for the delineation of signaling networks which are regulated by suites of growth factors. This is in stark contrast to early more traditional studies, which only examined the effects of isolated growth factors on the activity of skeletal muscle precursor cells in tissue culture. The work presented in this volume ranges from reviewing and analyzing the roles of individual growth factors in detail, to the complex interplay of multiple soluble factors in the control of muscle functional, and dysfunctional states. The material covered in this volume will particularly suit readers from a range of research fields spanning general muscle biology and physiology, and those working on diseases and conditions affecting skeletal muscle both directly and indirectly.

Microbiology & Immunology --- Biology --- Health & Biological Sciences --- Muscles --- Musculoskeletal system. --- Muscle cells. --- Regeneration. --- Myocytes --- Locomotor system --- Musculo-skeletal system --- Skeletomuscular system --- Cells --- Cytokines. --- Human physiology. --- Biochemistry. --- Cytokines and Growth Factors. --- Human Physiology. --- Medical Biochemistry. --- Human biology --- Medical sciences --- Physiology --- Human body --- Cellular immunity --- Immune response --- Biological chemistry --- Chemical composition of organisms --- Organisms --- Physiological chemistry --- Chemistry --- Regulation --- Composition --- Muscle, Skeletal. --- Intercellular Signaling Peptides and Proteins. --- Growth Factors --- Paracrine Peptide Factors --- Paracrine Protein Factors --- Peptide Factors, Paracrine --- Paracrine Communication --- Peptide Hormones --- Anterior Tibial Muscle --- Gastrocnemius Muscle --- Muscle, Voluntary --- Plantaris Muscle --- Skeletal Muscle --- Soleus Muscle --- Muscle, Anterior Tibial --- Muscle, Gastrocnemius --- Muscle, Plantaris --- Muscle, Soleus --- Muscles, Skeletal --- Muscles, Voluntary --- Skeletal Muscles --- Tibial Muscle, Anterior --- Voluntary Muscle --- Voluntary Muscles --- Growth factors. --- Medical biochemistry. --- Medical biochemistry --- Pathobiochemistry --- Pathological biochemistry --- Biochemistry --- Pathology --- Cell growth factors --- Cellular growth factors --- Growth peptides --- Growth promoting substances --- Growth substances --- Peptide growth factors --- Peptide regulatory factors --- Polypeptide growth factors --- Cytokines --- Peptides

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This fully updated and extended second edition provides a comprehensive overview on the basic concepts of the rapidly developing field of osteoimmunology and also offers in-depth insights into the molecular mechanisms of bone diseases. Clinical data is presented and put into context with the latest research findings. This second edition in addition discusses the latest topics in transplantation immunology. The book addresses scientists and physicians working in immunology, pathophysiology and osteology.

Medicine. --- Human physiology. --- Immunology. --- Rheumatology. --- Cytokines. --- Growth factors. --- Biomedicine. --- Human Physiology. --- Cytokines and Growth Factors. --- Bones --- Diseases --- Osteology --- Musculoskeletal system --- Bone --- Skeleton --- Cellular immunity --- Immune response --- Internal medicine --- Connective tissues --- Joints --- Human biology --- Medical sciences --- Physiology --- Human body --- Immunobiology --- Life sciences --- Serology --- Regulation --- Cell growth factors --- Cellular growth factors --- Growth peptides --- Growth promoting substances --- Growth substances --- Peptide growth factors --- Peptide regulatory factors --- Polypeptide growth factors --- Cytokines --- Peptides