Le parvovirus adéno-associé (AAV) possède un génome à ADN linéaire simple brin de 4,7kb encadré par deux séquences palindromiques inversées et identiques de 145 nucléotides appelées ITRs, requises en cis pour la réplication et l’encapsidation de l’ADN viral. Dans un AAV recombinant (rAAV), la totalité de la partie codante du génome viral est remplacée par une cassette d’expression et seuls les ITRs sont conservés.<p>\ / Doctorat en sciences biomédicales / info:eu-repo/semantics/nonPublished

Early administration of broad-spectrum antibiotics is the first goal in sepsis treatment. Besides from bacteriostatic/bactericidal effects, some antibiotics may also modify the host´s response to infection. The novel antibiotic tigecycline may exert such properties; however, this property has not been evaluated in large-animal trials. We compared tigecycline with doxycycline and placebo in relation to anti-inflammatory, circulatory and organ dysfunction effects in a sterile pig model of sepsis. Doxycycline, but not tigecycline, reduced the inflammatory response as manifested by tumor necrosis factor alpha levels in plasma. Tigecycline, however, had a stabilizing effect on the circulation not exerted by doxycycline or placebo. To achieve rapid restoration of the circulating blood volume - another major goal in sepsis treatment - fluid bolus administration of is some-times practiced. In addition to crystalloids, albumin-containing solutions are suggested. Yet, some animal-experimental data suggests that rapid bolus administration of albumin reduces albumin’s plasma-expanding effect. We compared a rapid intravenous bolus of radiolabeled albumin with a slow infusion in a sterile pig model of sepsis. Rapid bolus of administration did not reduce plasma levels of albumin following administration and did not increase the amount of albumin that left the circulation. Inadequate oxygen delivery (DO2) by the circulation to the tissues may cause increased plasma lactate, which is the most striking effect of sepsis on the metabolism. However, experimental data and clinical trials refute this link, instead, suggesting other mechanisms, including impaired oxygen extraction, mitochondrial dysfunction and accelerated aerobic glycolysis. We investigated the impact of DO2, oxygen consumption (VO2), hemodynamic parameters and inflammatory response on plasma lactate and organ dysfunction in two experimental sepsis models. In the most severe cases of shock, with DO2, there was an increase in plasma lactate, but without a decrease in VO2, invalidating the assumption that the increase in lactate is due to anaerobic metabolism. To identify critical steps in the sepsis-induced increase in lactate, we inhibited the major energy-producing step in the electron transport chain (ETC). The combination of sepsis and ETC inhibition led to a cellular energy crisis. This finding suggests that early sepsis induces a partial mitochondrial dysfunction.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Adsorbent materials have been used to efficiently remove several chemical harmful compounds from water bodies. Searching to develop low-cost adsorbent materials, this work describes the features of new adsorbent materials using fish scales chemically modified with glutaraldehyde (GA) and amines in three sequential step reactions, as well as to apply the materials to remove doxycycline (DOX) from aqueous media. All adsorbents were characterized before and after DOX sorption. Thermal analysis by TG/DTG have shown increasing of thermal stability of the adsorbents, due mainly to cross-linking reactions by GA. Elementary analysis has shown increasing of carbon and nitrogen amounts in relation to the starting material. FTIR spectra have shown increasing of N-H and O-H stretching bands after chemical modifications of the scales. MEV micrographies have suggested changes of the surfaces of the adsorbents in relation to the pristine material, due probably to structural changes of fibrillar collagen on the scales. The presence of DOX was also clearly evidenced by characterization. The best results for the DOX sorption were obtained at 25°C, using solutions of DOX of initial concentration of 2.5x10 -5 mol L -1 , obtaining maximum DOX sorbed amounts of about 3.2 mol/g. The best DOX desorption results were obtained using aqueous solutions at pH of 4.0. The kinetic data of DOX sorption were best fitted to an order- variable kinetic model. The analysis of the kinetic results has indicated DOX sorption as exothermic in nature, with DOX interactions using most external sorption sites of the adsorbents as the main DOX sorption mechanism. The results have shown that GA/amines-chemically modified fish scales are promising materials for efficient removal of DOX from aqueous media. / Materiais adsorventes têm sido utilizados para remover eficientemente vários tipos de contaminantes químicos presentes em corpos d´água. Buscando desenvolver materiais adsorventes de baixos custos, o presente trabalho descreve as características de novos materiais adsorventes à base de escamas de peixe pescada amarela (Cynoscion acoupa), com posterior modificação química com glutaraldeído (GA) e aminas em três etapas reacionais consecutivas, bem como suas aplicações para remoção de doxiciclina (DOX) em meios aquosos. Todos os adsorventes foram caracterizados antes e após a sorção de DOX. Análises térmicas por TG/DTG indicaram aumentos nas estabilidades térmicas dos materiais após as modificações, devido principalmente aos processos de reticulação com GA. Análises elementares mostraram aumentos nos percentuais de carbono e nitrogênio para os materiais adsorventes em relação ao material de partida. Os espectros de FTIR mostraram aumentos nas intensidades das bandas na região correspondente aos estiramentos dos grupos N-H e O-H nos materiais após a modificação, quando comparados à escama pura. Após as modificações químicas com GA e as aminas, micrografias obtidas por MEV mostraram superfícies mais compactas dos materiais em relação à escama pura, devido à aproximação das estruturas fibrilares do colágeno das escamas, provocada pelas reações realizadas. A presença da DOX sorvida foi claramente evidenciada pelas caracterizações dos materiais. As melhores condições para sorção da DOX nos materiais foram obtidas em pH 6,0, com 50 mg dos adsorventes e com 20 mL de solução de DOX. A sorção da doxiciclina pelos materiais apresentou resultados satisfatórios, com a maior remoção da DOX em 25°C na concentração inicial de 2,5x10 -5 mol L -1 , obtendo-se uma quantidade máxima de sorção de cerca de 3,2 mol/g. Os processos de dessorção de DOX ocorreram mais eficientemente utilizando-se soluções aquosas em pH 4,0. Os dados experimentais cinéticos de sorção da DOX ajustaram-se melhor ao modelo cinético de ordem variável. As análises cinéticas evidenciaram que as sorções de DOX ocorreram por processos exotérmicos, apresentando adsorção em sítios de interação externos como o principal mecanismo de sorção da DOX pelos adsorventes. Os resultados mostraram que as escamas de peixe modificadas com GA e as aminas são materiais promissores para remoção adequada de DOX em meios aquosos.