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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Hur Effektivt är Behandling med Entecavir jämfört med Lamivudin mot Kronisk Hepatit B Infektion?

Westerblad, Sofie January 2013 (has links)
Hepatit B är en virusinfektion som orsaks av Hepatit B virus (HBV). Hos de flesta människor orsakar detta virus inte några större problem men hos cirka 5-10% av de drabbade utvecklas en kronisk form som kan vara allvarlig. Detta beror på att vid den kroniska formen finns det en risk att levercirrhos och hepatocellulärt carcinom utvecklas. Idag finns det effektiv men ej botande behandling mot kronisk hepatit B. Målen vid behandlingen av kronisk hepatit B är att minimera risken för utveckling av cirrhos, leversvikt och hepatocellulärt carcinom, vilket görs genom inhibering av HBV virusreplikation. Syftet med detta arbete var att undersöka effektiviteten av entecavir jämfört med lamivudin vid behandling av kronisk hepatit B. Undersökningen genomfördes genom utvärdering av fem randomiserade och kontrollerade studier, vilka hämtades från databasen PubMed. Studierna visade att entecavir var mer potent än lamivudin i att minimera virusreplikation vilket resulterade i omätbara nivåer av HBV DNA i proverna. Dessutom normaliserade entecavir koncentrationerna av leverenzymet alaninaminotransferas, ALAT, och resulterade i serokonversion mot HBV och förlust av cirkulerande HBeAg i större utsträckning än lamivudin. Ingen resistens mot entecavir upptäcktes i någon av studierna. Slutsatsen är att entecavir är mera effektivt än lamivudin i att inhibera HBV virusreplikationen och att reducera inflammationen i kronisk hepatit B. Däremot behövs det flera och längre studier som undersöker huruvida effekten av kombinationsbehandling av kronisk hepatit där entecavir är ett av de antivirala medlen som används.
2

Synthèse et étude cinétique de l'homolyse de biomolécules utilisables comme agents théranostiques / Synthesis and kinetic study of the homolyse of biomolecules usable like theranostic agents

Obame Nkoghe, Germain 17 July 2013 (has links)
Ce travail est présenté en 2 parties. La première partie aborde la synthèse stéréocontrôlée de 2 séries de carbonucléosides de structures méthylènecyclopropane. Les molécules cibles sont des analogues de l’entécavir, une prodrogue utilisée en trithérapie pour lutter contre le VHB. Les synthèses des carbonucléosides cibles de la série I utilisent un chiron commun, un alcool obtenu par désymétrisation enzymatique d’un diol méso. La transformation chimique de cet intermédiaire clé permet d’obtenir le carbonucléoside (+)-17 en 8 étapes mettant en œuvre comme étapes cruciales un réarrangement de Curtius et la construction de la base uracile avec un rendement global de 23%. Le carbonucléoside appartenant à la série II, a été synthétisé en 10 étapes mettant en jeu une réaction de Mitsunobu, une acylation chimique et contrairement à l’approche précédente, la désymétrisation enzymatique d’un diol méso n’a pas permis d’obtenir le carbonucléoside cible énantiopure. La seconde partie est consacrée à l’activation et l’homolyse des alcoxyamines pour une application en théranostique. La synthèse de l’alcoxyamine modèle présente un groupement vinyl pyridine et un nitroxyde SG1. L’activation est réalisée par protonation, oxydation, méthylation et benzylation de la partie pyridyle et met en évidence l’importance de la polarité. Elle a permis d’obtenir des espèces hautement labiles qui libèrent un radical alkyle et le nitroxyde SG1, avec notamment des valeurs de la constante de dissociation kd plus élevées et donc des énergies d’activation Ea plus faibles par rapport à l’alcoxyamine non activée. / This work is presented in 2 parts. The first part is dedicated to the stereocontrolled synthesis of 2 series of carbonucleosides of methylenecyclopropane structure. The target molecules are analogs of entecavir, a prodrug used in triple therapy to fight against HBV. The syntheses of the carbonucleosides targets of the series I use a common chiron, an alcohol obtained by enzymatic desymmetrization of meso-diol. For example, the chemical transformation of this key intermediate allows to obtain carbonucleoside (+)-16 in 8 steps as crucial steps involving a Curtius rearrangement and the construction of the uracil base with 23% overall yield. The carbonucleoside belonging to the series II was first synthesized in 10 steps involving a reaction of Mitsunobu, a chemical acylation. Howerer the enzymatic desymmetrization of a meso-diol did not get the target carbonucleoside in an enantiopur form. The second part is dedicated to the activation and the homolysis of the alcoxyamines for a theranostic application. The synthesis of the model alcoxyamine is made from vinyl pyridine and nitroxide SG1. Activation is carried out by protonation, oxidation, methylation and benzylation of the pyridyl part and highlights the importance of polarity. It allowed getting highly labile species that release an alkyl radical and nitroxide SG1, with notably higher kd dissociation constant values and therefore activation energies Ea lower compared to the alcoxyamine not enabled.
3

Role lékových transportérů v placentárním přestupu entekaviru / Role of drug transporters in placental transfer of entecavir

Křečková, Veronika January 2019 (has links)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Veronika Křečková Supervisor: PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: Role of drug transporters in placental transfer of entecavir Entecavir (ETV), an analogue of guanosine, is a highly efficient anti-hepatitis B antiviral drug. It is the first-line therapy for both adults and children. Its use in pregnancy is limited due to a number of factors, including lack of data on placental pharmacokinetics. The placental transition of drugs is frequently controlled by drug transporters. ATP-binding (ABC) transporters, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) or multidrug resistance-associated protein 2 (MRP2) localized in the apical membrane of syncytiotrophoblast and pumping their substrates in the feto-maternal direction belong to most significant determinants of placental pharmacokinetics. Moreover placental transport of nucleoside-derived drugs can be affected by the activity of nucleoside transporters (NTs); equilibrative nucleoside transporters (ENTs) mediate facilitated diffussion, while the concentrative nucleoside transporters (CNTs) control active influx of their substrates. The aim of the diploma thesis was to describe the role of P-gp, BCRP, MRP2 and NTs (ENTs and...

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