Imunidade celular: caracterização das proteínas celulares que inibem a infecção viral

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Concreto celular polimérico: influência na adição de resíduo de poliéster insaturado termofixo

This work addresses the production of lightweight concrete building elements, such as plates, prefabricated slabs for pre-molded and panels of fencing, presenting a singular concrete: the Lightweight Concrete, with special properties such low density and good strength, by means of the joint use of industrial waste of thermosetting unsaturated polyesters and biodegradable foaming agent, named Polymeric Lightweight Concrete. This study covered various features of the materials used in the composition of the Polymeric Lightweight Concrete, using a planning of factorial design 23, aiming at studying of the strength, production, dosage processes, characterization of mechanical properties and microstructural analysis of the transition zone between the light artificial aggregate and the matrix of cement. The results of the mechanical strength tests were analyzed using a computational statistics tool (Statistica software) to understand the behavior and obtain the ideal quantity of each material used in the formula of the Polymeric Lightweight Concrete. The definition of the ideal formula has the purpose of obtaining a material with the lowest possible dry density and resistance to compression in accordance with NBR 12.646/92 (≥ 2.5 MPa after 28 days). In the microstructural characterization by scanning electron microscopy it was observed an influence of the materials in the process of cement hydration, showing good interaction between the wrinkled face of the residue of unsaturated polyesters thermosetting and putty and, consequently, the final strength. The attaining of an ideal formula, given the Brazilian standards, the experimental results obtained in the characterization and comparison of these results with conventional materials, confirmed that the developed Polymeric Lightweight Concrete is suitable for the production of building elements that are advantageous for construction

Síntese verde de nanopartículas de prata a partir de extrato aquoso do tubérculo de Curcuma longa associadas à quitosana e avaliação da atividade antitumoral in vitro em câncer de pele não melanoma (linhagem A431)

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Biológicas, Programa de Pós-Graduação Nanociência e Nanobiotecnologia, 2016.

Síntese, estudos fotofísicos e imageamento celular de peptóides-cumarínicos fluorescentes baseados em Reações de Ugi

Dissertação (mestrado)—Universidade de Brasília, Instituto de Química, Programa de Pós-Graduação em Química, 2016.

Poli-líquidos iônicos e complexos solúveis de Eu3+ e Tb3+ : bioimageamento celular seletivo

Dissertação (mestrado)—Universidade de Brasília, Instituto de Química, Programa de Pós-Graduação em Química, 2015.

Reguladores da expressão do gene da proteía Gla da matriz (MGP) numa linha celular derivada de peixe

Dissertação de mest. em Biotecnologia, Faculdade de Engenharia de Recursos Naturais, Univ. do Algarve, 2004

Citotoxicidade de curcumina presente em nanoparticulas de quitosana/sultato de condroitina contendo lecitina

Dissertação (mestrado)–Universidade de Brasília, Universidade UnB de Planaltina, Programa de Pós-Graduação em Ciência de Materiais, 2015.

siRNAs sintéticos direcionados à no sintase neuronal : efeitos sobre a expressão gênica e viabilidade celular do glioma

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Agronomia e Medicina Veterinária, Programa de Pós-Graduação em Saúde Animal, 2011.

Enhancement of non-viral transfection efficiency with nuclear localization signal peptides

Dissertação de Mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2016

Definição dos mecanismos de polaridade celular durante a citocinese

Dissertação de Mestrado, Oncobiologia – Mecanismos Moleculares do Cancro, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2016

Eficacia de las terapias celular y génica como agentes inmunomoduladores en el tratamiento de la esclerosis múltiple

El interferón beta (IFNb) ha sido uno de los fármacos más utilizados en el tratamiento de la esclerosis múltiple (EM), gracias a su efecto inmunomodulador, antiproliferativo y antiviral. Sin embargo, existe un porcentaje de pacientes que responden de forma subóptima al tratamiento, sugiriendo la necesidad de buscar alternativas terapéuticas innovadoras. En este contexto se ha observado que las células madre mesenquimales derivadas del tejido adiposo (AdMSCs) presentan capacidad inmunomoduladora, neuroprotectora y regeneradora del tejido dañado en ensayos preclínicos con el modelo animal más frecuentemente usado en el estudio de la EM, la Encefalomielitis Autoinmune Experimental (EAE), lo que las hace buenas candidatas como terapia alternativa para la EM. Además, su capacidad de migración hacia el tejido dañado les confiere potencial para ser utilizadas como transportadoras de factores terapéuticos hacia las zonas lesionadas del SNC. Por ello, nos planteamos evaluar la eficacia terapéutica de las terapias celular con AdMSCs y génica con AdMSCs modificadas genéticamente para producir IFNb, en modelos de EAE. Para llevarlo a cabo se realizó la caracterización de la población de AdMSCs de la cepa de ratón SJL/jCrL (SJL-AdMSCs), usando como control las AdMSCs de la cepa C57BL/6, ampliamente caracterizadas en la literatura, la generación de líneas de AdMSCs secretoras de IFNb (AdMSCs-IFNb) mediante lentivirus y su posterior caracterización y comparación con las mismas células sin transducir, la evaluación de los efectos de las terapias celulares autóloga, alogénica y génica en los modelos de EAE crónico progresivo (EAE-CP) y remitente recurrente (EAE-RR) y el estudio de la migración de las AdMSCs administradas como terapia autóloga y de las AdMSCs-IFNb. Los resultados obtenidos en cada uno de los objetivos planteados nos condujeron a una serie de conclusiones: las SJL-AdMSCs aisladas, cultivadas y expandidas bajo nuestras condiciones experimentales, cumplen los criterios mínimos determinados para ser consideradas células madre mesenquimales. Además, estas células presentan eficacia clínica y efectos neuroinmunomoduladores al ser utilizadas como transplantes autólogos y alogénicos en animales con EAE-RR y EAE-CP respectivamente. Por otro lado, las SJL-AdMSCs constituyen una población apta para dar soporte al desarrollo de la terapia génica, ya que la alteración de su material genético por la inserción del IFNb no supone la modificación de sus propiedades biológicas ni funcionales en estudios preclínicos en modelos de EM. Estas AdMSCs-IFNb, constituyen una línea de células mesenquimales de crecimiento estable que produce elevados niveles de IFNb de forma constitutiva. Además, los transplantes con AdMSCs-IFNb son eficaces como tratamiento terapéutico en animales con EAE-RR y EAE-CP al modular tanto la sintomatología como los procesos inflamatorios y neurodegenerativos propios de la enfermedad. Sin embargo, los resultados no permiten discriminar si los efectos observados son debidos a las propiedades del inmunomodulador secretado, a las propias células mesenquimales o a la acción conjunta de ambos. En último lugar, la migración celular de las AdMSCs autólogas se potencia por los estados de inflamación activa en ambos modelos de EAE, mostrando una amplia biodistribución celular. La localización prioritaria fue inicialmente en pulmones y, posteriormente en zona de órganos linfáticos, como hígado y bazo, y del SNC a nivel de la médula espinal. La señal bioluminiscente de las AdMSCs-IFNb en el modelo EAE-CP es mayor que la emitida por las células de la terapia autóloga. Sin embargo, la migración de las células transfectadas no aparece fuertemente influenciada por los procesos proinflamatorios. En el modelo EAE-RR estas diferencias entre terapias son incluso más moderadas. Las áreas donde se registra señal son similares a las de las células autólogas, apareciendo principalmente en zonas correspondientes a pulmones, hígado, bazo y médula espinal a lo largo del tiempo experimental.

Atividade antimalárica de plantas medicinais da biorregião do Araripe-CE em modelo murino - Plasmodium berghei

Malaria, also popularly known as maleita , intermittent fever, paludism, impaludism, third fever or fourth fever, is an acute infectious febrile disease, which, in human beings, is caused by four species: Plasmodium falciparum, P. vivax, P. malariae and P. ovale. Malaria, one of the main infectious diseases in the world, is the most important parasitoses, with 250 million annual cases and more than 1 million deaths per year, mainly in children younger than live years of age. The prophylactic and therapeutic arsenal against malaria is quite restricted, since all the antimalarials currently in use have some limitation. Many plant species belonging to several families have been tested in vivo, using the murine experimental model Plasmodium berghei or in vitro against P. falciparum, and this search has been directed toward plants with antithermal, antimalarial or antiinflammatory properties used in popular Brazilian bolk medicine. Studies assessing the biological activity of medicinal plant essential oils have revealed activities of interest, such as insecticidal, spasmolytic and antiplasmodic action. It has also been scientifically established that around 60% of essential oils have antifungal properties and that 35% exhibit antibacterial properties. In our investigation, essential oils were obtained from the species Vanillosmopsis arborea, Lippia sidoides and Croton zethneri which are found in the bioregion of Araripe-Ceará. The chemical composition of these essential oils was partially characterized and the presence of monoterpenes and sesquiterpenes. The acute toxicity of these oils was assessed in healthy mice at different doses applied on a single day and on four consecutive days, and in vitro cytotoxicity in HeLa and Raw cell lines was determined at different concentrations. The in vivo tests obtained lethal dose values of 7,1 mg/Kg (doses administered on a single day) and 1,8 mg/Kg (doses administered over four days) for 50% of the animals. In the in vitro tests, the inhibitory concentration for 50% of cell growth in Hela cell lines was 588 μg/mL (essential oil from C. zethneri after 48 h), from 340-555 μg/mL (essential oil from L. sidoides, after 24 and 48 h). The essential oil from V. arborea showed no cytotoxicity and none of the essential oils were cytotoxic in Raw cell lines. These data suggest a moderate toxicity in the essential XVIII oils under study, a finding that does not impede their testing in in vivo antimalarial assays. Was shown the antimalarial activity of the essential oils in mice infected with P. berghei was assessed. The three species showed antimalarial activity from 36%-57% for the essential oil from the stem of V. arborea; from 32%-82% for the essential oil from the leaves of L. sidoides and from 40%-70% of reduction for the essential oil from the leaves of C. zethneri. This is the first study showing evidence of antimalarial activity with these species from northeast Brazil. Further studies to isolate the active ingredients of these oils are needed to determine if a single active ingredient accounts for the antimalarial activity or if a complex integration of all the compounds present occurs, a situation reflected in their biological activity

Avaliação do efeito citotóxico da lectina da esponja marinha Cliona varians contra células de leucemia mielóide crônica

In this study, a BCR-ABL expressing human chronic myelogenous leukaemia cell line (K562) was used to investigate the antitumoral potential of a novel lectin (CvL) purified from the marine sponge Cliona varians. CvL inhibited the growth of K562 cells with an IC50 value of 70 g/ml, but was ineffective to normal human peripheral blood lymphocytes in the same range of concentrations tested (180 g/ml). Cell death occurred after 72 h of exposure to the lectin and with sign of apoptosis as analysed by DAPI staining. Investigation of the possible effectors of this process showed that cell death occurred in the presence of Bcl-2 and Bax expression, and involved a caspase-independent pathway. Confocal fluorescence microscopy indicated a major role for the lysosomal protease cathepsin B in mediating cell death. Accordingly, pre-incubation of K562 cells with the cathepsin inhibitor L-trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane (E-64) abolished the cytotoxic effect of CvL. Furthermore, we found upregulation of tumor necrosis factor receptor 1 (TNFR1) and down-modulation of p65 subunit of nuclear factor kappa B (NFB) expression in CvL-treated cells. These effects were accompanied by increased levels of p21 and downmodulation of pRb, suggesting that CvL is capable of cell cycle arrest. Collectively, these findings suggest that cathepsin B acts as death mediator in CvL-induced cytotoxicity possibly in a still uncharacterized connection with the membrane death receptor pathway