76 research outputs found
Dataset of mRNA levels for dopaminergic receptors, adrenoceptors and tyrosine hydroxylase in lymphocytes from subjects with clinically isolated syndromes
No full textThis data article presents a dataset of mRNA levels for dopaminergic receptors, adrenoceptors and for tyrosine hydoxylase, the rate-limiting enzyme in the synthesis of catecholamines, in peripheral blood mononuclear cells as well as in CD4+ T effector and regulatory cells from subjects with clinically isolated syndromes (CIS), which is a first episode of neurological disturbance(s) suggestive of multiple sclerosis. CIS subjects are divided into two groups according to their eventual progression, after 12 months from CIS, to clinically established multiple sclerosis. The data reported are related to the article entitled "Dopaminergic receptors and adrenoceptors in circulating lymphocytes as putative biomarkers for the early onset and progression of multiple sclerosis" (M. Cosentino, M. Zaffaroni, M. Legnaro, R. Bombelli, L. Schembri, D. Baroncini, A. Bianchi, R. Clerici, M. Guidotti, P. Banfi, G. Bono, F. Marino, 2016
Global Public Goods, Global Commons, Fundamental Values and International Investment Law: the Responses of the New Generation of International Economic Law Agreements and Investment Arbitration Proceedings
No full textThe group of five articles forming this special section of Brill Open Law is a selection of the papers presented at the Workshop on “Global Public Goods, Global Commons, Fundamental Values: the Responses of International Economic Law,” organized by the Interest Group (ig) on International Economic Law (iel) of the European Society of International Law (esil) in Naples on September 6th, 2017. The mission of the esil iel ig is to promote research in the field of International Economic Law, endorsing exchange of views among young and experienced scholars, as well as supporting debate and discussion with practitioners, lawyers and officials from international organizations and national administrations working in the fields of international trade and investments and International Financial Law.
The articles appearing in this Section are all devoted to International Investment Law, the first work being the opening speech to the Naples Workshop by Professor Pavel Šturma on “Public Goods and International Investment Law: Do the New Generation of iias Better Protect Human Rights?”, while the subsequent four essays are all dedicated to the recent case-law developed in international arbitration proceedings dealing with the right to water and the right to human health.
Professor Šturma provides a synthetic effective reconstruction of the way in which International Investment Law now interacts with International Human Rights Law. Starting from the description of the situation in the first generation of Bilateral Investment Treaties (bits), establishing the rights of investors and the obligations of States, the author then goes on exposing the differences with human rights treaties, and analyzes the significant developments in relation to the new generation of investment treaties. The relevant clauses concerning the exceptions to investment protection, or the right to regulate of the host State, expressed by the new generation of International Investment Agreements (iias), such as the eu-Canada Comprehensive Economic Trade Agreement (ceta), the now-abandoned Transatlantic Trade and Investment Partnership (ttip), or the bit models of Norway, Canada, Austria, or the Czech Republic, are therefore considered, stressing their relevance to guide interpreters and arbitrators when having to combine investment protection with human rights. Due attention is then given to the role of private parties with reference to human rights, underlining the introduction of the concept of Corporate Social Responsibility (csr) in the new iias encouraging economic operators to conduct their business in compliance with the relevant international soft law codes inspired by the principle of sustainable development – requiring that economic development be constantly combined with environmental protection and social progress. The article also emphasizes the role that the principle of systemic integration in treaty interpretation, as codified in Article 31, para. 3(c) of the Vienna Convention on the Law of Treaties, may play when arbitrators have to combine human rights, environmental protection and bits, illustrating the relevance of the case-law of international investment disputes in order to strike a fair balance between non-economic considerations and investors’ rights.
The analysis by Pavel Šturma opens the door to the subsequent four articles. Professor Ursula Kriebaum, in her work on “The Right to Water Before Investment Tribunals,” provides a complete overview of the case-law developed in international investment arbitration proceedings with reference to the right to water. She presents the constantly rising relevance that the human right to water has been given by the Arbitral Tribunals while discussing the respect of the investors’ prerogatives enshrined in the various bits invoked by the claimants. Professor Kriebaum thus emphasizes that the Arbitrators never denied that they have an obligation to take into consideration human rights while interpreting bits. On the contrary, international awards concluded that national measures introduced in order to protect the environment against the pollution of water resources, and the termination of concessions as a consequence of inadequate performance of an investment contract on the part of the investor involved in water distribution services cannot be automatically considered as infringements of bits by the States benefitting from the foreign investments. Furthermore, Ursula Kriebaum stressed the highly relevant developments reached by the Arbitral Tribunal in the Urbaser case, where it was held in an obiter that investors have to abstain from acts which may violate the human right to water by endangering access to water.
The Urbaser case is at the center of the analysis by Dr Edward Guntrip and Dr Patrick Abel. In his work on “Private Actors, Public Goods and Responsibility for the Right to Water in International Investment Law: An Analysis of Urbaser v. Argentina,” Dr Guntrip considers how the Arbitral Tribunal allocated responsibility for compliance with the right to water between the host State and the foreign investor while being asked to settle the dispute over privatized water services in Greater Buenos Aires. The author underlined that the Arbitrators chose to follow the scheme defined by the un Committee on Economic, Social and Cultural Rights (cescr). Pursuant to that, human rights obligations in relation to economic, social and cultural rights, which include the right to water, have to be broken down into obligations to respect, protect and fulfil. Edward Guntrip criticizes the Tribunal’s decision to limit the duties of the investor to the obligation to respect only, i.e. not to interfere with the enjoyment of the right to water. In fact, such a limitation makes the human right to water vulnerable for the right holders trying to hold a foreign investor responsible. Dr Patrick Abel manifests further perplexities on the counterclaim raised by Argentina in relation to the existence of an international investor obligation under the human right to water, for the first time accepted as possible in international investment arbitration proceedings. While stressing the importance of the novelty of the Urbaser award -i.e. the possibility of holding investors accountable for a breach of an international human rights obligation- Patrick Abel highlights the flaws in the legal reasoning of the Tribunal, which he considers unclear in the way it perceives the integration of human rights obligations as a source of international law external to the relevant bit invoked in the investment arbitration.
Last but not least, Professor Pei-Kan Yang, in his article on “The Margin of Appreciation Debate over Novel Cigarette Packaging Regulations in Philipp Morris v. Uruguay,” explores the legal reasoning of the Arbitrators in the case brought by the famous tobacco multinational company against the Latin-American State. The majority of the Tribunal, applying the “margin of appreciation” doctrine as originally developed by the European Court of Human Rights (ECtHR), found that Uruguay’s tobacco legislation did not violate the Switzerland – Uruguay bit as the Latin-American State enjoyed a substantial degree of discretion in choosing the regulatory means to achieve its public health objectives among various options of effective measures. Pei-Kan Yang analyzes both the majority conclusions and the dissenting opinion by Gary Born, and identifies lacunae in each of the two approaches, suggesting an adjustment of the concept of the margin of appreciation in order to better accommodate the right to regulate of the host State for public health purposes and balance it against the investor’s private rights.
We do hope that the proposed set of articles may represent a welcome perspective of analysis of some recent developments concerning treaties and case-law in the field of International Investment Law. Enjoy the reading
Hydrocéphalie chronique de l’adulte : synthèse diagnostique, traitement chirurgical et suivi
No full textPhysiopathology of intracranial flows
No full textNombreuses pathologies encéphaliques peuvent être liées à des troubles de la circulation du liquide cérébrospinal (LCS) appelés troubles hydrodynamiques. L'objectif de notre étude était d'analyser la circulation du LCS dans un contexte pathologique et d'analyser ses interactions avec la circulation artérioveineuse. Les modèles pathologiques retenus étaient les hydrocéphalies pédiatriques et chroniques de l'adulte, les hypertensions intracrâniennes idiopathiques et les malformations de Chiari. L'hémodynamique et l'hydrodynamique étaient étudiées de manière non invasive par IRM en contraste de phase. Nous avons observé des altérations des écoulements de LCS dans l'ensemble de ces pathologies. Ces altérations hydrodynamiques étaient complémentaires de données d'IRM morphologiques. Des altérations associées de l'hémodynamique étaient retrouvées. L'analyse de l'hydrodynamique et de l'hémodynamique cérébrale permet d'apporter une analyse des mécanismes physiopathologiques de ces pathologiesMany encephalic pathology can be related to circulation disorders of the cerebrospinal fluid (LCS) called hydrodynamic disorders. The objective of our study was to analyze the circulation of LCS in a pathological context and to analyze its interactions with arteriovenous circulation. The pathological models selected were adult pediatric and chronic hydrocephalus, idiopathic intracranial hypertension and Chiari malformations. Hemodynamics and hydrodynamics were studied non-invasively by MRI in phase contrast. We have observed alterations in the flow of LCS in all of these pathologies. These hydrodynamic alterations were complementary to morphological MRI data. Associated alterations in hemodynamics were found. The analysis of hydrodynamics and cerebral hemodynamics makes it possible to provide an analysis of the pathophysiological mechanisms of these pathologie
Clinical and radiographic performance of indirect foraminal decompression with anterior retroperitoneal lumbar approach for interbody fusion (ALIF)
No full textStudy design: Retrospective study Background: Indirect decompression with ALIF allows the restoration of the disk and foraminal height with limited soft tissue damage. However, it does not offer a direct view of the neural structure and a direct intraoperative assessment of the results of the decompression is not possible. For this reason, ALIF is often accompanied by posterior, direct decompression. So far, there is no consensus on the effects of indirect decompression alone for L5-S1 foraminal stenosis. Objective: Evaluation of the clinical and mechanical performance of indirect decompression with anterior lumbar interbody fusion (ALIF) in L5-S1 foraminal stenosis. Methods: All patients who underwent ALIF at our institution and had a minimum follow-up of six months were assessed for inclusion. Radiographic parameters (anterior and posterior disc height, foraminal height and surface, L5-S1 angle, pelvic incidence, pelvic tilt and lumbar lordosis) and clinical data (Oswestry Disability Index - ODI and Numeric Rating Scale - NRS) before ALIF and at the last follow-up were compared. A regression analysis was performed to investigate the correlation between radiographic and clinical outcomes. Results: Thirty-four patients were available for the study (55.9% female, mean age 53.4 +/- 11.5 years), mean follow-up was 26.4 +/- 11.1 months. At the last follow-up, a significant increase in foraminal height (14.6 +/- 4.0 vs. 17.9 +/- 3.9 mm, p<0.001), posterior disc height (6.5 +/- 2 vs. 9.1 +/- 2 mm, p<0.001) was observed. ODI and NRS back and leg improved significantly. The NRS leg correlated with foraminal height (r=-0.45), foraminal surface (r=-0.36) and anterior (r=-0.41) and posterior disc height (r=-0.43). Conclusion: ALIF provided significant indirect foraminal decompression and improvement of radicular pain. The increase of foraminal height, surface, and posterior disc height is directly associated with radicular pain improvement. Level of evidence: IV Availability of data and material: The datasets used and/or analyzed in the present study are available from the corresponding author on reasonable request
A role for median eminence tanycytes in the transport of leptin from the periphery to the hypothalamus
No full textLe noyau arqué hypothalamique (ARH) est un composant majeur des circuits neuronaux qui régulent la balance énergétique. Cependant les mécanismes d’entrée des hormones périphériques dans l’ARH sont peu connus. L’ARH est adjacent à l’éminence médiane (ME), où des cellules épendymales hautement spécialisées appelées tanycytes son tprésentes. Les corps cellulaires des tanycytes bordent le troisième ventricule et leurs prolongements basaux contactent le plexus de capillaires fenêtrés de la ME. Récemment, il a été proposé que les tanycytes joueraient un rôle dans la régulation de la barrière sang hypothalamus métabolique. Leur localisation privilégiée à l’interface entre le sang et le cerveau suggère que ces cellules pourraient être la cible directe de nombreux signaux hormonaux périphériques, incluant l’hormone adipocytaire qu’est la leptine. La compréhension des mécanismes régissant le transport de la leptine est fondamentale car cela apporterait de nouvelles pistes pour la détermination des mécanismes cellulaires impliqués dans la résistance à la leptine accompagnant l’obésité.Le but de ce travail de thèse était de déterminer si les tanycytes de la ME pouvaient être responsable du transport de la leptine vers l’hypothalamus et dans ce cas, si ils pouvaient être impliqués dans les mécanismes de résistance à la leptine associée à l’obésité.Dans un premier temps, nous avons étudié le transport de la leptine vers l’hypothalamus à travers diverses approches. Les expériences de western-blots ont révélé que la leptine injectée en périphérie est retrouvée de manière séquentielle dans la ME puis dans le MBH, de plus le délai d’activation du récepteur à la leptine suit la même séquence. Par ailleurs, nous avons observé que la leptine s’accumule dans la ME n’atteignant pas l’hypothalamus chez les souris obèses (modèles db/db et DIO) qui ont perdu la capacité à activer le récepteur à la leptine. L’utilisation de leptine fluorescente a permis de démontrer que la leptine est internalisée de manière polarisée dans les tanycytes de la ME,l’internalisation a lieu au niveau des prolongements qui contactent les capillaires fenêtrés puis la leptine est transportée vers le pôle apical. De plus, nous avons démontré par immunohistochimie que ces tanycytes constituent le premier type cellulaire de la ME à répondre à une injection prériphérique de leptine par l’activation de P-STAT3.L’administration d’un antagoniste de la leptine a permis de mettre en évidence que l’internalisation de la leptine dans les tanycytes est dépendante de l’activation du récepteur à la leptine.L’utilisation d’un modèle in vitro, les cultures primaires de tanycytes, constitue un outil permettant l’étude détaillée des mécanismes responsables du transport de la leptine. Les expériences menées sur ces cultures ont confirmé les résultats obtenus in vivo et montrent que la libération de la leptine par les tanycytes, étape du transport qui est bloquée chez les souris obèses, est sous la dépendance de l’activation de la voie de signalisation ERK. L’utilisation d’un agent pharmacologique capable d’activer la voie de signalisation ERK dans les tanycytes permet de restaurer le transport de la leptine de la ME vers le MBH chez les souris obèses.En définitive, ces résultats apportent d’importantes informations sur la compréhension du transport central de la leptine et pourraient aider à expliquer les mécanismes responsables de la résistance à la leptine associée à l’obésité.The arcuate nucleus of the hypothalamus (ARH) is a critical component of the neural circuits that regulate energy balance. However, little is known about how peripheral signals reach the ARH to mediate their central effects. The ARH is adjacent to the median eminence (ME), where highly specialized ependymal cells called tanycytes are found. The cell bodies of tanycytes are lining the floor of the third ventricle and their end-feet are contacting the rich capillary plexus with fenestrated endothelium of the ME. Tanycytes have recently been proposed to play a role in blood-hypothalamus barrier regulation. Their privileged location at the interface between the blood and the brain suggests that these cells might be direct target for a variety of peripheral signals, including the adipocyte-derived hormone leptin. The understanding of leptin transport mechanisms is fundamental as it may provide new insights into cellular processes involved in leptin resistance linked to obesity.The aim of this work was to determine wether tanycytes of the median eminence could be responsible for leptin entry in the hypothalamus and in this case if they could be involved in the mechanisms responsible for obesity-associated leptin resistance.We first investigated leptin uptake into the hypothalamus through several approaches in vivo. Western-blot experiments revealed that peripherally injected leptin is sequentially found in ME and later in MBH, moreover the timing of the leptin receptor activation appears to follow the same sequence. In contrast, we observed that leptin failed to reach the hypothalamus and was seen to accumulate in the ME in obese mice (db/db and DIO models) that has lost the capacity of activating LepRb signaling pathways in the ME. The use of fluorescent leptin demonstrated that leptin is internalized in ΜΕ tanycytes in a polarized manner, leptin is uptaken at the level of the basal processes contacting fenestrated capillaries and transported toward the apical pole. In addition, we showed that these tanycytes are the first cell type in the median eminence to respond to peripheral leptin injection through the activation of P-STAT3 detected by immunohistochemistry. The use of a leptin antagonist showed the dependence of leptin receptor(s) activation for leptin internalization in tanycytes. Then, the use of tanycyte primary cultures as an in vitro model system allowed us to study leptin transport mechanisms more in detail. Experiments performed on cultured tanycytes confirmed our in vivo findings and showed that the release of leptin from tanycytes, which is blocked in obese mice, depends on the activation of the X signaling pathway. The use of a pharmacological compound able to activate the X signaling pathway in tanycytes can rescue leptin transport from ME to MBH in obese mice. Altogether this data may provide valuable information in the understanding of central leptin transport and may help to explain mechanism underlying obesity-associated leptin resistance
Étude fonctionnelle de l'hypothalamus humain en IRM haute résolution (modifications induites par la prise alimentaire)
No full textLILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF
Lésions spinales intracanalaires dans la neurofibromatose de type 2
No full textLILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF
Study of the hypothalamic communication with the periphery in humans : effects on brain metabolic activity and on the control of energy homeostasis
No full textLe comportement alimentaire et l’homéostasie énergétique dépendent de l’intégrationhypothalamique de signaux périphériques de différentes natures : métaboliques, hormonales.Ce dialogue continu entre la périphérie et le cerveau est indispensable pour le maintien del’homéostat énergétique et permet ainsi une adéquation entre apports et dépenses caloriques.Malgré ce système finement régulé, des variations significatives de poids peuvent survenir eton observe alors un déséquilibre de la balance énergétique. L’origine de ce désordre estcomplexe, multifactorielle, avec une composante comportementale expliquant le trouble desconduites alimentaires. L’implication de l’hypothalamus dans ces pathologies est peu étudiéeet notamment sa communication avec la périphérie. En effet les mécanismes de transport dessignaux hormonaux au travers de l’éminence médiane, véritable porte d’entrée du cerveau,sont défaillants chez le sujet obèse. Le rôle des tanycytes dans le transport de ces signaux dontla leptine est aujourd’hui bien démontrée. Ces cellules gliales spécialisées forment un pontentre les vaisseaux sanguins et le système nerveux central et contrôlent l’accès des hormonespériphériques. Or des données récentes montrent qu’une voie de transport au sein destanycytes est défaillante, pouvant être à l’origine d’une résistance au passage de ces signaux,et mener à un éventuel trouble du comportement alimentaire, de l’anorexie à l’obésité.Au cours de ma thèse j’ai d’abord examiné comment évoluait in vivo l’activation de certainesrégions hypothalamiques impliquées dans la régulation de la prise alimentaire en réponse à lafaim chez une population de patientes souffrant d’anorexie mentale de type restrictif ou chezdes patientes maigres constitutionnelles grâce à des techniques d’IRM métaboliques. Nousavons pu mettre en évidence une inversion de la réponse glutamatergique à la prisealimentaire chez la patiente anorexique associée à un seuil basal plus élevé que les témoinsdans la condition de jeûne alors même que l’activation de neurones glutamatergiques dans lenoyau arqué hypothalamique et l’aire hypothalamique latérale, deux régions indispensables àla régulation de la prise alimentaire, provoque une perte d’appétit chez la souris nourrie adlibitum. De plus nous avons pu montrer que le nombre de fibres nerveuses passant à travers lenoyau arqué hypothalamique était considérablement réduit chez la patiente anorexique etmince constitutive reflétant un caractère spécifique au phénotype de la maigreur, ce noyauétant considéré comme le chef d’orchestre de la régulation homéostatique. A l’inverse, l’airehypothalamique latérale contient plus de fibres nerveuses chez les patientes anorexiques.Enfin des analyses de volumétrie ont permis de constater des variations dans l’ultrastructurehypothalamiques, variations corrélées au poids des sujets.Ensuite, en miroir de l’anorexie, nous avons souhaité mieux comprendre le phénomène derésistance hormonale à la leptine du sujet obèse. Pour cela j’ai conçu une étude ayant pourobjectif de mettre en évidence à la fois des modifications d’imagerie comme dans l’anorexiemais également neuro-hormonales, de métabolisme, et de comportement alimentaire chez lesujet obèse, à l’issue d’un traitement par metformine. Ce traitement améliore en effet lepassage de la leptine dans les tanycytes de l’hypothalamus médio-basal dans un modèle desouris obèses. Les recrutements pour cette seconde étude sont en cours.L’ensemble de ces données démontrent pour la première fois des anomalies structurelles etfonctionnelles de l’ultrastructure hypothalamique in vivo chez la patiente anorexique mentale,avec nous l’espérons, la mise en évidence future de ces anomalies chez le sujet obèse afin depermettre une meilleure compréhension du mécanisme de leptinorésistance chez ces patients.Eating behavior and energy homeostasis depend on the hypothalamic integration of peripheralsignals of different natures, metabolic and hormonal. This continuous dialogue between theperiphery and the brain is essential for maintaining the energy homeostasis and thus allows abalance between caloric intake and energy expenditure. Despite this regulated system,significant variations in weight can occur and there is then an imbalance in the energybalance. The origin of this disorder is complex, multifactorial, with a behavioral componentexplaining the eating disorder. The implication of the hypothalamus in these pathologies islittle studied and in particular its communication with the periphery. In fact, the mechanismsfor hormonal transport through the median eminence, the real gateway to the brain, are faultyin the obese subject. The role of tanycytes in the transport of these signals, like leptin, is nowwell demonstrated. These specialized glial cells form a bridge between the blood vessels andthe central nervous system and control the access of peripheral hormones. However, recentdata show that a transport route within the tanycytes is faulty, which can be the source ofresistance to the passage of these signals, and lead to a possible eating disorder, from anorexiato obesity.During my thesis, I first examined how the activation of certain hypothalamic regionsinvolved in the regulation of food intake in response to hunger evolved in a population ofpatients suffering from restrictive anorexia nervosa or in lean constitutional patients usingmetabolic MRI techniques. We were able to demonstrate that the glutamatergic tonus wasaltered in the anorexic patient even though the activation of glutamatergic neurons in thehypothalamic arcuate nucleus and the lateral hypothalamic area, two regions essential for theregulation of food intake, causes a loss of appetite in mice fed ad libitum. In addition, wewere able to show that the number of nerve fibers passing through the hypothalamic arcuatenucleus was considerably reduced in the anorexic patient, this nucleus being considered as theleader of homeostatic regulation. Conversely, the lateral hypothalamic area contains muchless nerve fibers in thin constitutive and anorexic patients reflecting a character specific to theleanness phenotype. Finally, volume analyzes revealed variations in the hypothalamicultrastructure, variations correlated with the weight of the subjects.Then, mirroring anorexia, we wanted to better understand the phenomenon of hormonalresistance to leptin in the obese subject. For this I designed a study with the aim ofhighlighting both changes in imaging as in anorexia nervosa, but also neuro-hormonal,metabolism, and eating behavior in the obese subject, in the resulting from metformintreatment. This treatment improves the passage of leptin through the tanycytes of the midbasalhypothalamus in an obese mouse model. Recruitment for this second study is underway.All of these data demonstrate for the first time structural and functional anomalies of thehypothalamic ultrastructure in vivo in the anorexic mental patient, with hopefully the futuredemonstration of these anomalies in the obese subject in order to allow a better understandingof the mechanism of leptin resistance in these patients
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