Narcolepsy: current treatment options and future approaches

The management of narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1) Two tendencies characterize the conventional treatment of narcolepsy. Modafinil has replaced methylphenidate and amphetamine as the first-line treatment of excessive daytime sleepiness (EDS) and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of modafinil, but on no direct comparison of modafinil versus traditional stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new antidepressants tend to replace tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2) The conventional treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good efficacy and is active on all symptoms of narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3) A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy

GÖÇ VE YAŞAM

Uluslararası Bakalorya Programı, A1 dersi Türk Dili ve Edebiyatı alanında ele alınan bu tezde, Orhan Kemal'in Gurbet Kuşları adlı yapıtında göç olgusu nedenleri ve sonuçlarıyla beraber incelenmiştir. Göç olgusuyla değişen toplumsal yapı, ekonomik ve kültürel farklılıklar çerçevesinde değerlendirilmiştir. Bu tezin amacı, göç olgusunun toplumsal yapıda alt sınıf ve üst sınıflardaki bireyler üzerindeki etkilerini ortaya koymaktır. Üç ana bölümden oluşan tezin ilk bölümünde yapıta adını veren Gurbet Kuşları kavramı üzerinde durulmuştur. Köylülerin aidiyetsizliği ve uyum sorunu bu bölümde aktarılmıştır. Tezin ikinci bölümünde ise köylülerin köyden kente göç sürecinde yaşadıkları kadın ve erkek figürler üzerinden neden ve sonuçlarıyla işlenmiştir. Tezin üçüncü bölümünde şehirliler başlığı altından genel olarak şehirde – İstanbul – yaşayan insanların göç sürecinde köylülerle yaşadıkları uyumsuzluk ve çatışmalara yer verilmektedir. Çalışmada göç sürecinde şehre yerleşen figürlerin şehirlilerle aralarındaki ekonomik ve kültürel farklılıkların sınıflar arasında geçişe olanak tanımadığı sonucuna varılmıştır

Etude critique de la somnolence chez le sujet atteint de la maladie de Parkinson

MONTPELLIER-BU Pharmacie (341722105) / SudocSudocFranceF

Aspects génétiques et familiaux de la narcolepsie

MONTPELLIER-BU Médecine (341722104) / SudocMONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Evaluation de la somnolence, de la fatigue, et des fonctions cognitives dans les troubles respiratoires légers survenant au cours du sommeil

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUP (751062107) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

\u3ci\u3eSleep: Physiology, Investigations and Medicine\u3c/i\u3e

Chapter 40: Circadian rhythm sleep disorders related to an abnormal escape of the sleep-wake cycle, co-authored by Jonathan Bruce Santo, UNO faculty member. Sleep medicine is a recent discipline but its field of knowledge is already extensive. This results from the progress made in understanding sleep-wake mechanisms, the development of reliable means of investigation, and advances in our knowledge of the nosology of the disorders of sleep and wakefulness. This volume comprises five sections: the first looks at the semiotics of normal sleep in adults and children, sleep mechanisms and the major physiological functions and mental activity during sleep. The second section is a review of the different means of investigating sleep and wakefulness and the methods of analysis currently available. The third section deals with the disorders of sleep and wakefulness, insomnias, hypersomnias, circadian rhythm sleep disorders and parasomnias. The fourth section describes a number of medical disorders which are either sleep-related or simply exacerbated by sleep: snoring, chronic obstructive lung diseases, restless legs syndrome or periodic limb movement disorder, sleep epilepsies, etc. The final section encompasses disorders which are not sleep-dependent but to which sleep investigations may add further insight, such as mood disorders, certain neurological pathologies, dysautonomias, and again, epilepsy. The appendix contains questionnaires, indexes, and assessment scales designed to assist the clinician in evaluating the different disorders. The present edition, written in English is a complete revision of the two preceding French editions. It represents the work of European and North and South American specialists.https://digitalcommons.unomaha.edu/facultybooks/1093/thumbnail.jp

Maintenance of handedness polymorphism in humans: A frequency-dependent selection model

International audienceFrequency-dependent selection is an important process in the maintenance of genetic variation in fitness. In humans, it has been proposed that the polymorphism of handedness is maintained by negative frequency-dependent selection, through a strategic advantage of left-handers in fighting interactions. Using simple mathematical models, we explore: 1°) whether it is possible to predict the range of left-handedness frequencies observed in human populations by the frequency and the violence of fighting interactions; 2°) the consequences of the sex differences in the probability of transmission of hand preference to offspring. We show that a wide range of values of the frequency of lefthanders can be obtained with realistic changes of the parameters values. Our models reinforce the idea that negative frequency dependence may have played a role in maintaining left-handedness in human populations, and provide further support for the importance of fighting interactions in the evolution of hand preference. Moreover, they suggest an explanation for the occurrence of left-handedness among women in this context, namely an indirect selective advantage through their male offspring

Jean-Claude Daumas, géographe

Marié Michel, Dreyfus Jacques, Billiard Isabelle. Jean-Claude Daumas, géographe. In: Les Annales de la recherche urbaine, N°25, 1985. Villes des tiers et quart mondes. pp. 3-7

Biosynthèse des isoprénoïdes (Synthèses d'analogues du 1-désoxy-D-xylulose 5-phosphate,inhibiteurs potentiels de la voie du méthylérythritol phosphate)

Les isoprénoïdes sont des produits naturels présents chez tous les organismes vivants qui peuvent être synthétisés selon deux voies de biosynthèse différentes: la voie du mévalonate et la voie du méthylérythritol 4-phosphate (MEP). Les enzymes de la voie du MEP présentes chez de nombreux microorganismes mais absentes chez les animaux, représentent des cibles potentielles pour le développement de nouveaux médicaments contre les maladies causées par des bactéries pathogènes ou par des parasites. Dans cet objectif, l'élaboration d'inhibiteurs potentiels de cette voie a été envisagée. La désoxyxylulose réducto-isomèrase (DXR), une enzyme de la voie du MEP, a été choisie comme cible et des analogues de son substrat, le désoxyxylulose 5-phosphate, (DXP), ont été préparés puis leurs caractéristiques biochimiques (substrat, inhibiteur) ont été déterminées. La première partie de ce travail consiste en la mise au point d'une synthèse simple et efficace du DXP qui a été appliquée à la préparation de DXP marqué au deutérium, de son analogue non phosphorylé, le DX, et de DX marqué au deutérium. Ces composés ont été utilisés dans le cadre de collaborations. Dans une deuxième partie, la synthèse d'analogues phosphonates et fluorés du DXP est réalisée selon deux approches: une approche à partir de chirons et une approche par synthèse asymétrique. Les chirons utilisés sont des dérivés du L-tartrate. L'approche par synthèse asymétrique utilisée met en jeu une aldolisation asymétrique enzymatique. Au cours de ce travail une nouvelle méthode de synthèse d'un précurseur de la dihydroxyacétone phosphate (DHAP), substrat spécifique des aldolases, a été mise au point. L'activité biologique des analogues du DXP synthétisés a ensuite été évaluée in vitro sur la DXR et in vivo sur des souches d'E. coli. Nous avons pu montrer que l'analogue phosphonate du DXP est substrat de la DXR et que les autres composés synthétisés se comportent comme des inhibiteurs.Isoprenoids are natural compounds present in all living organism and can be synthesised via two different biosyntheses: the mevalonate pathway or the methylerytritol phosphate pathway (MEP). The enzymes involved in the MEP pathway are present in many microorganisms but absent in animal cells and therefore are potential targets for the design of new drugs acting on the diseases cause by pathogenic bacteria or parasites. In this purpose, the elaboration of potential inhibitors of this pathway has been considered. The deoxyxylulose 5-phosphate reducto-isomerase (DXR), one of the enzymes of the MEP pathway, has been chosen as a target. The synthesis of analogues of deoxuxylulose phosphate (DXP), the natural substrate of the DXR has been developed and their biochemical properties (substrate, inhibitor) have been determined. The first part of this work is the elaboration of a practical and efficient synthesis of DXP. This relevant synthesis allowed the preparation of deuterium labelled DXP, and its non phosphorylated analogue, DX, with a possible deuterium labelling at C-5. All these compounds were used for investigations on the MEP pathway. In a second part, phosphonate and fluorinated analogues of DXP have been synthesised via two different approaches: one from chirons and the other one from asymmetric synthesis. Compounds derived from the L-tartrate ester were used as chirons for the synthesis of the analogues of DXP. Such compounds were prepared by using biocatalysts: the aldolases, allowing an asymmetric aldolisation reaction. Due to the specific substrate of aldolases, the dihydroxyacetone phosphate (DHAP), a short and efficient synthesis of a precursor of DHAP, has been developed. The biological activity of the synthesised compounds was then determined in vitro on the DXR and in vivo on E. coli. We found that the phosphonate analogue of DXP is substrate of DXR and that the other analogues are inhibitors.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF