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Le développement des inhibiteurs de protéase à sérine NS3/4 dans l'hépatite C chronique
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Year: 2016 Publisher: Bruxelles: UCL. Faculté de pharmacie et des sciences biomédicales,

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Hepatitis C is an epidemic that affects about 200 million people worldwide. It is a liver inflammation caused by a virus of the flavivirus family. Depending on the country, hepatitis C does not have the same distribution within the population of the same country and between countries. HCV is transmitted through blood and all derived products, poorly sterilized material and re-use of needles. In the majority of cases a chronic phase installs that can progress to liver cirrhosis or cancer of the liver. HCV is a single-stranded positive-strand RNA virus. It is characterized by an important genetic polymorphism resulting in a varied genotype and a tropism immune and liver high. The degree of liver damage and type of genotype determines the decision to treat and support global infection. Pegylated dual is the classical treatment used mainly in countries with lower income. With the arrival of NS3/4A protease inhibitors, triple therapy replaces the dual therapy especially in genotype 1. One of the critical target for the replication process is the NS3/4A protease of HCV. Also a better understanding of the viral cycle development in testing effectives in vitro methods and characterization of NS3/4A viral protease, as potential target, has opened the door to the discovery of new molecules protease inhibitors. The first wave of its new drugs (boceprevir and telaprevir) which have been put on the market as early as 2011 are linear reversible covalent inhibitors. A second wave consists of non-covalent reversible inhibitors structure macrocyclic P1-P3 and P2-P4 either structure linear. Finally, other inhibitions strategies non peptidomimetrics are under investigations. L’hépatite C est une épidémie qui affecte environ 200 millions de personnes dans le monde. C’est une inflammation hépatique causée par un virus de la famille des flavivirus. L’hépatite C n’a pas la même distribution au sein de la population d’un même pays et entre les pays. Le VHC est transmis par le sang et tous les produits dérivés, les matériels ma stérilisés et les réutilisations des aiguilles. Dans la majorité des cas, une phase chronique s’installe pouvant évoluer vers une cirrhose hépatique, voire vers un cancer du foie. Le VHC est un virus à ARN monocaténaire à brin positif. Il est caractérisé par un polymorphisme génétique important se traduisant par un génotype varié et un tropisme hépatique et immunitaire élevé. Le degré de l’atteinte hépatique et le type de génotype conditionne la décision de traiter la prise en charge global de l’infection. La bithérapie pégylée est le traitement classique utilisé surtout dans les pays à moindre revenu. Ave l’arrivé des inhibiteurs de protéase NS3/4A, la trithérapie remplace la bithérapie particulièrement dans le génotype 1. L’une des cibles critiques est la protéase à sérine NS3/4A du VHC, impliquée dans la réplication. Aussi une meilleure compréhension du cycle viral par la mise au point de méthodes d’expérimentation in vitro efficaces et la caractérisation de la protéase NS3/4S, comme cible potentielle, a ouvert la porte à la découverte de nouvelles molécules antiprotéases. La première vague de ses nouveaux médicaments (bocéprévir et télaprévir) qui sont des inhibiteurs covalents linéaires réversibles. Une seconde vague est constitué par des inhibiteurs non covalents réversibles soit de structures macrocycliques P1-P3 ou P2-P4 soit de structure linéaires enfin d’autres stratégies d’inhibitions non peptidomimetiques sont en cours d’investigations.


Dissertation
Etude de l'efficacité de diverses molécules en tant que bio-insecticides potentiels : effet sur le modèle puceron
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Year: 2010 Publisher: [S.l. : chez l'auteur],

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Dissertation
Defence strategies in pulmonary inflammation
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Year: 1994 Publisher: Leiden s.n.

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Dissertation
Antileukoprotease and experimental emphysema
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Year: 1992 Publisher: 's-Gravenhage Pasmans

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Dissertation
Etude fonctionnelle d'un oncogène humain impliqué dans le Sarcome d'Ewing, oncTre210, homologue à deux gènes levuriens, MSB3 et MSB4
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Year: 2009 Publisher: [S.l.] : [chez l'auteur],

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Book
New edge of antibiotic development : antimicrobial peptides and corresponding resistance
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ISBN: 9782889193011 Year: 2014 Publisher: Frontiers Media SA

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Increased pathogen resistance to conventional drugs is partially due to increased numbers of immune-compromised patients, therefore the development of alternative antibiotic therapies able to circumvent this problem is one of the intriguing challenges of modern medicine. The discovery of antimicrobial peptides has been considered, in recent years, to be essential for the solution to infections caused by bacterial and fungal diseases, owing to their commonly observed and naturally occurring resistance against pathogens. In addition to the obvious antimicrobial activity commonly associated with membrane disruption, such peptides also have shown auxiliary activities such as immunomodulatory, anti-tumor and biofilm-disruption. Moreover, antibiotic peptides have been considered critical as therapeutic agents for the control of infectious bacterial diseases; the resistance to antibiotics has become a globally recognized public health problem. In most bacterial species, after exposing microorganisms to antibiotic peptides, several systems are affected such as energy and nitrogen metabolism regulation, glucan biosynthesis, amino acid, protein, and nucleotide synthesis, and, moreover, various proteins show a stress response. Despite some articles having been published about bacterial resistance toward antimicrobial peptides, multiple gaps need to be filled in order to better understand this mechanism. In this view, this edition proposes the analyses of these unusual and interesting peptides and will provide a clearer understanding of such bacterial resistance towards AMPs. In summary, this proposal focuses on AMPs and their multiple activities as well as on AMP bacterial resistance, attracting several researchers from different areas.

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