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Ecole doctorale Innovation Thérapeutique : du Fondamental à l'Appliqué (Châtenay-Malabry, Haut-de-Seine / 2000-2015)

Overview
Works: 232 works in 261 publications in 1 language and 291 library holdings
Roles: Other, Degree grantor
Publication Timeline
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Most widely held works by Haut-de-Seine / 2000-2015) Ecole doctorale Innovation Thérapeutique : du Fondamental à l'Appliqué (Châtenay-Malabry
Application du procédé de prilling pour la préparation de micro-réseaux à base de chitosane by Leticia Martinez( Book )

2 editions published in 2004 in French and held by 4 WorldCat member libraries worldwide

Le chitosane est un polymère naturel, biodégradable et biocompatible. Les hydrogels pH- sensibles à base de chitosane sont des systèmes prometteurs pour la réalisation de formes pharmaceutiques à libération contrôlée. Dans le même temps, les formes divisées apparaissent comme étant particulièrement adaptées aux exigences pharmaceutiques et industrielles en termes de qualité, de sécurité et d'optimisation de procédés. Dans ce travail, nous préparons des micro réseaux semi-interpénétrés chitosane/poly(oxyéthylène) par un procédé de prilling. La caractérisation physico-chimique des systèmes divisés obtenus, ou prills, révèle des particules sphériques de taille calibrée et de distribution granulométrique étroite. La structure des micro réseaux est appréhendée à travers l'étude de la réticulation du chitosane. Les micro réseaux présentent un gonflement très important en milieu acide. Ces propriétés peuvent être appliquées à la formulation de principes actifs destinés à la voie orale
Synthèse pseudo-biomimétique d'acétogénines d'Annonaceae : application à la préparation des cis- et trans-solamines by Julie Defretin( )

2 editions published in 2002 in French and held by 3 WorldCat member libraries worldwide

Synthèse et évaluation biologique d'inhibiteurs de la dimérisation de la protéase du VIH-1 by Naïma Merabet-Bouraoui( Book )

2 editions published in 2004 in French and held by 3 WorldCat member libraries worldwide

New "molecular tongs" based on naphthalene and quinoline scaffolds linked to two peptidic strands were synthesized. They were designed to prevent dimerization of RN -1 protease, at the antiparallelj3- sheet structure level involving N- and C-termini of each monomer. Seventeen new molecular tongs were synthesized with dipeptidic or tripeptidic strands. These molecules were assayed on HIV-1 protease following Zhang kinetic techniques. Twelve molecules were shown as pure dimerization inhibitors, mostly in submicromolar range. Dimerization inhibition was ascertained using ANS fluorescence and gel filtration experiments which showed the dissociation of HIV-1 protease dimeric form in presence of synthesized molecular tongs
Nanoparticules métalliques fonctionnalisées pour le traitement spécifique des tumeurs solides by Fabio Sonvico( Book )

2 editions published in 2004 in French and held by 3 WorldCat member libraries worldwide

The aim of the present Ph.D. thesis has been the investigation of the use of metallic nanoparticles for targeted physic treatment of solid tumors In the first section of the thesis has been presented the set-up of an in vitro model suitable for he study of folate targeted carriers. Then, the application of this model to the study of a new bioconjugate b-cyclodextrin / folic acid has been described. Finally two types of metallic nanoparticles functionalised with folic acid have been investigated. Gold nanoparticles produced have not shown the expected specificity of targeting and some problems related to their surface modification with folic acid to their stability in biologic media have been evidenced. On the contrary folate targeted iron oxide superparamagnetic nanoparticles (g-Fe2O3, maghemite) have been characterized and their specific targeting have been clearly demonstrated
Développement d'un adsorbant synthétique pour un procédé d'épuration plasmatique destiné au traitement de patients hémophiles A sensibilisés by Hélène-Céline Huguet( Book )

2 editions published in 2004 in French and held by 3 WorldCat member libraries worldwide

The occurrence of anti-factor VIII (FVIII) allo-antibodies is a severe complication of the treatment of haemophilia A patients, leading to the inhibition of transfused FVIII activity. The selective elimination of these inhibitory antibodies using immunoadsorption device employing purely synthetic adsorbers, is of interest in the treatment strategy of haemophilia A patients with inhibitors. Adsorbers consisting of polystyrene-based beads substituted with sulphonate and L-tyrosyl methylester groups, which mimic par of epitope of FVIII recognized by inhibitors, exhibit selective binding capacities towards anti-FVIII antibodies. These adsorbers were investigated as regards to their adsorption capacity by simulating a therapeutic immunoadsorption in order to reproduce condition to be encountered in clinical setting. The final aim of these studies was to define an innovative medical device for the management of haemophilia A patients with inhibitors
Synthèse d'hétérocycles azotés quinoléiques et quinazoliniques à visée antileishmanienne by Jöel Dade( Book )

2 editions published in 2004 in French and held by 3 WorldCat member libraries worldwide

This thesis consists in the synthesis of nitrogen heterocyclic compounds derived from quinolines and quinazolines. These compounds are structurally analogues to natural quinolines, the chimanines, having antileishmanial activity. During this work we have prepared about a hundred quinolinic and quinazolinic compounds and we have evaluated their activity against Leishmania donovani donovani and Leishmania amazonensis strains. Biological evaluation against Plasmodium falciparum is currently carry out. We also studied the reactivity of quinazolines substituted at the 2 position by an epoxy group towards nucleophilic reagents such as organolithium, Grignard reagents and amino compounds
Régulation des mécanismes d'autophagie par les herpesviridae : l'exemple du cytomégalovirus humain by Magali Chaumorcel( )

2 editions published in 2010 in French and held by 3 WorldCat member libraries worldwide

Bien qu'asymptomatique chez les sujets sains, le cytomégalovirus (CMV) est responsable d'infections opportunistes graves chez les patients immunodéprimés. L'autophagie est un mécanisme de dégradation du matériel cytoplasmique permettant le maintien de l'homéostasie. Il s'agit aussi d'un mécanisme de défense contre les microorganismes en modulant l'immunité. Certains virus contrecarrent cette autophagie. Dans une première partie, nous avons montré que le CMV inhibe l'autophagie dès 24h d'infection dans les fibroblastes. Dans un second temps, nous avons recherché les mécanismes impliqués dans cette inhibition. Le CMV est capable d'activer mTOR, un régulateur négatif de l'autophagie. Nous avons ensuite étudié le rôle du complexe Beclin-1/Bcl-2 au cours de l'infection et observé une surexpression et une phosphorylation de Bcl-2, mais qui ne sont pas impliquées dans cette inhibition. Du côté des protéines virales, nous montrons que la protéine précoce TRS1 est capable d'inhiber l'autophagie
Développement de nouvelles nanoparticules cœur (polyester) - couronne (polysaccharide) by Caroline Lemarchand( Book )

2 editions published in 2004 in French and held by 3 WorldCat member libraries worldwide

The aim of this work was to develop a new type of core-shell nanoparticles from a family of novel amphiphilic copolymers, based on dextran grafted with poly(epsilon caprolactone). The nanoparticles were prepared by an original method of interfacial migration and solvent evaporation. Firstly, the mechanism of formation was investigated studying the abilities of copolymers to stabilize the intermediate emulsion and to form nanoparticles with controlled size, without the need of additional surfactant. Then, the nanoparticle structure was investigated in order to demonstrate the presence of dextran coating. This coating was deeply examined using different complementary methods such as specific enzymatic degradation of dextran shell, electronic microscopy, electronic paramagnetic resonance. Finally, the ability of the dextran coating to modify the interactions with biological media was studied by plasma proteins adsorption, complement activation, phagocytosis by macrophage-like cells line
Étude chimique et biologique des neurotoxines d'Annona muricata L. (Annonaceae) pouvant être impliquées dans la survenue des parkinsonismes atypiques en Guadeloupe by Pierre Champy( Book )

2 editions published in 2004 in French and held by 3 WorldCat member libraries worldwide

In Guadeloupe (French West Indies), the proportion of parkinsonian patients with atypical syndromes is abnormaly high. An epidemiological study linked the occurence of these parkinsonian syndromes with the consumption, for alimentary and medicinal purpose, of plants of the Annonaceae family. We contributed to the evaluation of the putative neurotoxicity of Annona muricata L., the most consumed in guadeloupe. A bioguided fractionation of the leaves led to the identification of two classes of potential neurotoxines: isoquinoline alkaloids and annonaceous acetogenins. A qualitative an quantitative study (using MALDI-TOF MS) of these metabolites consumed in real-life situations was conducted. A biological study of annonacin, the major acetogenin of the tree, was conducted in vitro and in vivo. In rats this molecule induces, by sub-chronic intravenous infusion, a widespread neurodegeneration predominating in the basal ganglia nuclei and in the mesencephalon. These data reinforce the ætiological hypothesis, emphasize the contribution of acetogenins, and indicate that these molecules are mostly brought through alimentation
Implication des gènes des SREBP et de la SCAP dans le déterminisme génétique de l'athérosclérose ; Etude de la régulation du trafic intracellulaire du cholestérol by Peggy Robinet( Book )

2 editions published in 2005 in French and held by 3 WorldCat member libraries worldwide

L'athérosclérose, par ses complications telles que les cardiopathies ischémiques et les accidents vasculaires cérébraux, constitue l'une des premières causes de mortalité dans le monde. Ainsi, comprendre les mécanismes mis en jeu dans cette pathologie apparaît comme un enjeu majeur de santé publique. Dans cette optique, notre travail a suivi deux approches. La première, plus appliquée, a cherché à identifier de nouveaux variants génétiques des SREBP (Sterol Regulatory Element Binding Protein) et de la SCAP (SREBP Clivage Activating Protein) puis à étudier leur impact sur les profils lipidique et clinique de sujets hypercholestérolémiques. Nous avons ainsi pu mettre en évidence que certains polymorphismes des gènes étudiés sont associés aux variations de la glycémie à jeun, de l'index de masse corporelle, des paramètres lipidiques et de l'épaisseur intima-média ; ces associations étant observées dans les analyses génotypiques et/ou haplotypiques réalisées pour ce travail. Dans un second temps, par une approche plus fondamentale, nous avons voulu caractériser les mécanismes moléculaires engagés dans le transport intracellulaire du cholestérol et leurs implications dans le maintien de l'homéostasie cellulaire du cholestérol. Nous avons montré l'importance du transport vésiculaire dépendant de la dynamine dans le trafic intracellulaire du cholestérol et, par conséquent, dans la régulation de l'expression des gènes sensibles aux stérols. En conclusion, notre étude a permis de caractériser de nouveaux gènes candidats dans le déterminisme génétique de l'athérosclérose et d'identifier la dynamine comme un acteur de la régulation du transport intracellulaire de cholestérol. Ces résultats permettent d'envisager des perspectives expérimentales mais également diagnostiques (détermination polymorphique des sujets à haut risque cardiovasculaire) et thérapeutiques (identification de nouvelles cibles pharmacologiques pour les traitement de l'athérosclérose)
Formulation de liposomes d'interleukine-2 conventionnels ou à temps de circulation prolongé et spécifiques des cellules du système immunitaire by Yann Pellequer( Book )

2 editions published in 2003 in French and held by 3 WorldCat member libraries worldwide

The key role played by the cytokine Interleukin-2 (IL-2) in the immune response gives it great potential for the treatment of cancers and HW infection. However, the short haif-life ofIL-2 after intravenous administration means that large doses have to be given leading to serious side-effects. We have formulated liposomes containing IL-2 as one strategy for reducing these side-effects. We first developed a method based on the intrinsic fluorescence of IL-2 to measure its association with liposomes. The effect of the preparation conditions of liposomes on the biological activity of IL-2 and the nature of the lipid-protein interactions were studied. The ultimate aim of this work was to formulate long-circulating liposomes which were specifically targeted to cells of the immune system. This carrier system could increase the circulating haif-life of the protein and release it in the vicinity of the target cells, thus increasing its efficacy
Validation des hydrolases du peptidoglycane comme nouvelles cibles thérapeutiques contre l'infection à Helicobacter pylori by Mathilde Bonis( )

2 editions published in 2010 in French and held by 3 WorldCat member libraries worldwide

L'infection à Helicobacter pylori touche près de 50 % de la population mondiale, et peut être associée à des pathologies sérieuses. De plus, l'émergence de résistances bactériennes ne cesse d'accroître le taux d'échec thérapeutique, justifiant pleinement la recherche de nouvelles stratégies thérapeutiques. Dans ce sens, ce travail de thèse a eu pour objet de rechercher de nouvelles cibles thérapeutiques contre H. pylori, via la caractérisation d'acteurs du métabolisme du peptidoglycane et de leur rôle dans la virulence bactérienne. Ainsi, nos travaux ont permis d'une part, la caractérisation d'une nouvelle peptidase bifonctionnelle du PG, HdpA, impliquée dans la virulence de H. pylori, via la régulation de sa forme bâtonnet, et d'autre part, la mise en évidence de l'action inhibitrice de la bulgécine sur la transglycosylase lytique Slt, engendrant une altération de la mobilité de H. pylori, ainsi qu'une forte réduction de sa croissance par action synergique avec l'amoxicilline
Administration pulmonaire d'immunoglobulines dans le cadre de la prophylaxie des infections respiratoires du combattant : étude chez la souris infectée par influenza A de l'intérêt de formulations liposomales by Christelle Dreffier( Book )

2 editions published in 2004 in French and held by 3 WorldCat member libraries worldwide

Pulmonary administration of immunoglobulins is efficient against respiratory infections and can be used in urgent prevention situation, but is of short effect. The aim of this work was to determine how liposomal formulations would be able to prolong the prophylactic efficiency of Ig. Physico-chemical studies allowed to characterize Ig / liposomes interactions and showed that IgG adsorption onto liposomes was not saturable and induced vesicle destabilization above a threshold Ig / lipid ratio, probably in relation with the preferential adsorption of Ig aggregates. In vivo studies in mice infected by Influenza A and receiving IVIG formulations by endotracheal nebulization showed a lower efficiency of the liposome associated Ig than the free Ig one, likely due to an enhanced macrophagic clearance of the liposomes presenting Ig aggregates on their surface
Les ß-lactamases chromosomiques de Klebsiella oxytoca : marqueurs de la résistance aux ß-lactamines et de l'évolution de l'espèce by Sophie A Granier( Book )

2 editions published in 2004 in French and held by 3 WorldCat member libraries worldwide

From clinical isolates, collected from 1984 to 2000, we have characterized (i) new variants within each of the two groups (OXY-1 and OXY-2) of the chromosomal KOXY b-lactamase of K. oxytoca and (ii) two genetic groups (oxy-1 and oxy-2) in the K. oxytoca taxon recognizable by four independent molecular markers (the types of blaOXY gene, 16S rDNA and rpoB gene sequences, and ERIC-1R profiles). This study has shown , for the first time, that the evolution of the chromosomal bla gene can reflect species evolution. A second study allowed us to find a K. oxytoca strain representative of a third genetic group (oxy-3) and a phylogenitically distant variant within the genetic group oxy-1. These findings were primarily based on the ERIC-1R profiles and the blaOXY gene sequence. By two other studies, we demonstrated that the KOXY b-lactamase of the reference strain SC 10,436 belongs to the group OXY-2 and the co-amoxiclav resistance observed in a K. oxytoca isolate was due to TEM-30 (IRT-2)
Etude de la microflore digestive au cours de la maladie de Crohn par une approche moléculaire ciblant les ARNr 16S by Philippe Seksik( Book )

2 editions published in 2004 in French and held by 3 WorldCat member libraries worldwide

The cause of Crohn's Disease (CD), a focal inflammatory bowel disease, remains unknown. Several lines of evidence support the role of the microflora in its pathogenesis. We have studied fecal and mucosa-associated microflora during CD using culure-independant techniques: quantitative dot-blot hybridization for the composition in phylogenetic groups, temporal temperature gradient gel electrophoresis for comparison of the bacterial biodiversity and molecular inventory technique for the dominant species distribution. Our results are consistent with an increase in Enterobateria, a decrease in Bifidobacteria and the finding of unusual dominant species in fecal samples of CD compared with controls. Mucosa-associated microflora differed from fecal microflora and appeared stable from ileum to rectum in a same individual irrespective of his clinical status (CD or controls). During active CD, microflora associated with mucosal ulcerations was similar to microflora. associated with adjacent non ulcerated mucosa
Conception et synthèse de dendrimères poly(arylpropargyléther) (pape) comme vecteurs potentiels de principes actifs by Nathalie L'Hermite( Book )

2 editions published in 2004 in French and held by 3 WorldCat member libraries worldwide

La vectorisation d'un principe actif permet de maîtriser son transport et sa distribution jusqu'à sa cible cellulaire dans le but notamment d'améliorer les traitements et de diminuer les effets indésirables. Les dendrimères sont des macromolécules isomoléculaires, obtenues par la réaction d'un cœur plurifonctionnalisé avec des dendrons (Voie convergente). Leurs caractéristiques principales (forme globulaire, cavités, fonctions terminales à la surface,) leur offrent des perspectives intéressantes dans le cadre de la vectorisation. Nous avons proposé la synthèse convergente de dendrimères PAPE (poly(arylpropargyléther)), dont le motif itératif arylpropargyléther composant les dendrons est introduit par une séquence réactionnelle de trois étapes (addition-1,2, réaction de Williamson, et couplage de Sonogashira). Dans un premier temps, nous avons synthétisé des dendrons de première et seconde génération iodés, à partir desquels sont introduits, par une réaction de Sonogashira, des alcools de longueur de chaîne différente. Les dendrons ainsi obtenus ont conduit aux dendrimères de liaison cœur-dendron de type ester, par une réaction de Mitsunobu avec le cœur, l'acide 1,3,5-benzènetricarboxylique. D'autre part, les dendrons de première et seconde génération substitués par une fonction phénol ont été synthétisés. Ils nous ont permis d'obtenir les dendrimères de liaison cœur-dendron de type ester (à partir du 1,3,5-trichlorure de benzoyle) ou de type éther (à partir du 1,3,5-trisbromométhylbenzène) (dendrimères "linéaires"). De plus, des dendrimères dont le nombre de branches croît en fonction de la génération ont été synthétisés, ces dendrimères dits "dédoublés" de première génération se caractérisent par une masse moléculaire équivalente aux dendrimères dits "linéaires" de seconde génération. Dans le but d'améliorer la solubilité dans l'eau de ces dendrimères, des fonctions esters d'alkyles fonctionnalisés par des groupements aminés (susceptibles de former des sels d'ammonium) ont été introduites par une réaction de trans-estérification. Les tests biologiques de ces dendrimères restent à réaliser enfin de déterminer leur cytotoxicité
Ecologie de Legionella pneumophila dans les réseaux de distribution d'eau potable by Vincent Thomas( Book )

2 editions published in 2004 in French and held by 3 WorldCat member libraries worldwide

Since it has been isolated in 1977, pneumonia epidemics involving Legionella pneumophila (Lp) are in constant progress. Contamination essentially occurs by inhalation of water droplets generated from water distribution networks. The ecology of Lp is complex, this bacteria growths inside protozoa and can persist in biofilms in the viable but not cultivable state. The objective of this work was to understand better this ecology. Incubators allowing the sampling of biofilm were installed in situ in an internal network; the colonization in cold and in warm water was followed during 1 year. A pilot unit reproducing an internal network allowed to compare the efficiency of various disinfection treatments. Finally, the search for auto-inducers molecules that could explain the exacerbation of the virulence during the intracellular growth was led in various conditions. Incubators allowed the detection of L. pneumophila by culture in cold water and resulted in a stabilization of the population in warm water. The use of specific probes did not allow to improve the detection in biofilms. During the disinfection assays with the pilot unit, the populations of biofilms were analyzed with molecular tools (FISH, viability staining) and by cultivation. Classification of treatments in order of efficiency is as follow: chlorine dioxide > chlorine > ozone > monochloramine > copper-silver. Only the chlorine dioxide has a residual activity in the dead leg flushed daily with treated water. Amoebas resist to treatments, and Lp returns to its initial level of population a few days only after their interruption. Finally, we could not detect any auto-inducer molecule, and the incubation of Lp with these molecules does not seem to modify the invasion of amoebas
Etude chimique et biologique de lignanes isolés de Justicia Patentiflora (Hemsl.) : synthèse d'analogues glycosylés by Sophie Susplugas( Book )

2 editions published in 2004 in French and held by 3 WorldCat member libraries worldwide

Dans le cadre de la recherche de nouvelles molécules antitumorales, nous avons entrepris l'étude chimique d'une espèce vietnamienne hautement cytotoxique
Réactivité d'aldimines dans les alcools fluorés : cycloadditions et réaction de Mannich vinylogue by Maria Vittoria Spanedda( Book )

2 editions published in 2004 in French and held by 3 WorldCat member libraries worldwide

Hexafluoroisopropanol and trifluoroethanol are relatively acid, poor nucleophiles, and they show a high ionising power as well as a strong attitude to hydrogen bonding. This work is focused on the study of the reactivity of aldimines (Schiff bases and trifluoromethyl imines) in these solvents towards cycloadditions and vinylogous Mannich reactions. These reactions are efficient from Schiff bases without Lewis acids, while from fluorinated aldimines a catalyst is always required. However, in hexafluoroisopropanol with Lewis acids it is possible to perform a one pot reaction from p-methoxyaniline and fluoral ethyl hemiacetal, which was unsuccessful in classical organic solvents. We also investigated the reactivity of fluorinated aldimines in methylene chloride with Lewis acids
Implication du facteur de transcription de la famille ETS, ESE-1 dans les processus inflammatoires by Franck Grall( Book )

2 editions published in 2004 in French and held by 3 WorldCat member libraries worldwide

The ETS transcription factor ESE-1 was so far know as a factor specific of the epithelial. We now report that it can be induced in non-epithelials cells in response to pro-inflammatory stimuli such as IL-1, TNF-a and the lipopolysaccharides. This induction is noted in several cell types such as chondrocytes, monocytes ans smooth muscle cells.. We were able to show an expression of ESE-1 dring the rhumatoid arthritis and endotoxxemia. This induction of ESE-1 is mediated by NF-kB as it is shown by transctivation, EMSA and chromtin immunoprecipitation. ESE-1 is then capable of activating the expression of several genes important in inflammation such as COX-2 et iNOS. This activation happens in collaboration with other transcriptions factors such as NF-kB and NFAT. We pressent evidences that a neutralisation of ESE-1 via dominant negative constructs of ESE-1 could inhibit the expression levels of COX-2
 
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Alternative Names
ED 425

ED425

Université Paris-Sud 11. Ecole doctorale Innovation thérapeutique

Université Paris-Sud 11. Faculté de pharmacie (Châtenay-Malabry, Haut-de-Seine). Ecole doctorale Innovation thérapeutique

Université Paris-Sud 11. UFR de pharmacie (Châtenay-Malabry, Haut-de-Seine). Ecole doctorale Innovation thérapeutique

Languages
French (40)