Síntese e aplicações de inibidores peptídicos de topoisomerases associados a sistemas de liberação controlada de fármacos

O uso de novas tecnologias para o desenvolvimento de medicamentos constitui uma estratégia promissora no campo da biotecnologia. Nesse sentido, peptídeos com efeito antimicrobiano, produzidos por plantas, animais e microrganismos estão sendo utilizados como modelos para o desenvolvimento de novos medicamentos com aplicações em saúde. Resultados promissores têm sido obtidos em relação à inibição da atividade das enzimas bacterianas DNA girase e topoisomerase IV por derivados peptídicos de toxinas bacterianas, comprovados em ensaios in vitro. Porém, ensaios in vivo não demonstraram reprodutibilidade, basicamente devido à baixa permeabilidade da célula bacteriana a estes compostos. Desta forma, o objetivo deste projeto consiste em aplicar sistemas eficientes para promover o acesso de moléculas peptídicas sintéticas derivadas de toxinas bacterianas, ao meio intracelular e, consequentemente, aos seus alvos intracelulares: as enzimas DNA girase e/ou topoisomerase IV. Com isso, pretendemos solucionar a barreira técnica em que se encontram as aplicações dessa classe de biomoléculas como precursores de novos agentes antibacterianos, o que certamente causaria um importante avanço nas pesquisas desenvolvidas pelo grupo

Otimização da extração alcalina com peróxido de hidrogênio em seqüência de branqueamento com aplicação de baixo fator kappa

The new market, focused on sustainability and other environmental concerns, refers to innovations that seek alternative forms of production. In pulp and paper bleaching alternative reagents are studied, for example, hydrogen peroxide, in partial substitution of chlorine dioxide in order to reduce the formation of organochlorines. In this context, this study examined the burden of hydrogen peroxide (H2O2) on alkaline extraction stage (stage Ep) required for the bleaching of pulp with eucalyptus kraft pulp, pre-oxygen delignified to obtain equivalent brightness at 90 ± 0.5% ISO, as well as its effect on quality of pulp produced. The pulp was bleached by the sequence D(Ep)DP, with the application of factor kappa of 0.14 and varying the concentration of hydrogen peroxide in Ep stage three, five, seven and nine kilograms of reagent per ton of pulp absolutely drought. The final P stage was optimized with the use of six, nine and twelve pounds of hydrogen peroxide per ton of absolutely dry pulp to achieve the required brightness. The quality of the pulp produced was analyzed based on the kappa number, the brightness and the viscosity. The methods were performed according to standards set by the standard TAPPI (Technical Association of the Pulp and Paper Industry). The best result was obtained using the following D0Ep(7)D1P(6), which showed a viscosity of 19.9 cP, 89.6% ISO brightness, consumption of 94.9 kg / t of reagents and reagent costs of US$ 28.15, because it showed better pulp quality for a lower cost compared to the others. It was found that the greater the amount of hydrogen peroxide in alkaline extraction, the lower the kappa number and increased the amount of residual hydrogen peroxide. The higher the charge of hydrogen peroxide in Ep stage, the lower the need for hydrogen peroxide in the final P stage, reducing the cost of bleaching

Apocinina versus diapocinina como inibidor da produção de peróxido de hidrogênio e ácido hipocloroso por neutrófilos ativados

Apocynin has been used as an efficient inhibitor of the multi-enzymatic complex NADPH oxidase in many experimental models involving phagocytic and nonphagocytic cells. The mechanism of inhibition has been linked with the previous activation of apocynin through the action of cellular peroxidases leading to the formation of a dimeric oxidation product, diapocynin. In this study we compared apocynin with pure diapocynin regarding their effects as scavenger of hydrogen peroxide and hypochlorous generated by glucose/glucose oxidase and myeloperoxidase respectively, and as inhibitors of the production of hydrogen peroxide and hypochlorous acid by activated neutrophils. The production of hydrogen peroxide was measured by the oxidation of the fluorescent substance Amplex Red and the production of hypochlorous acid by was measured as taurine-chloramine derivative using the chromogenic substrate 3,3’,5,5’- tetramethylbenzidine (TMB). Neutrophils (1 x106 cells/mL) were pre-incubated in PBS buffer supplemented with 1 mM calcium chloride, 0.5 mM magnesium chloride, 1 mg/mL glucose and 5 mM taurine in the presence or absence of inhibitors. The reactions were triggered by adding the soluble stimulus Forbol Miristate Acetate PMA or zymosan and incubated by additional 30 minutes. We found that pure diapocynin was not better than apocynin regarding its scavenger and inhibitory properties. These results suggest that the formation of diapocynin is not essential for the action of apocynin as inhibitor of NADPH oxidase activation

Produção de hidrogênio por reforma a vapor de biogás

A new approach to generating clean energy has been studied by several researchers, among which one can highlight the steam reforming of biogas. The Biogas is result of decomposition of organic matter and it hasn’t been availed in the global level, instead, the biogas has been burned in flare or discarded into the atmosphere providing damage to the environment. The generation of vector biogas energy can be realized through its steam reforming and this work examines briefly the types of digesters used for biogas generation, studying the process of steam reforming to generate hydrogen as energy vector, analyzing each step in detail, seeking to adapt its main features an ethanol reformer for a biogas reformer. Besides this it is estimated the yield of the reform process and the boiler efficiency for efficiency of the process

Comprimidos de HPMC contendo nimesulida: preparação, caracterização e estudo dos mecanismos que regem a liberação do fármaco

The pharmaceutical innovations, such as the use of polymers to control drug release, create possibilities for a better action of the drug in the body, which causes a a more effective therapeutic effect and a safer treatment for the patient. In this work, were prepared and characterized matrix tablets of hydroxypropylmethylcellulose (HPMC) containing nimesulide as model drug to evaluate the performance as a controlled release system. HPMC, a cellulose ester, is a hydrophilic polymer that undergoes swelling, i.e., absorbs water and forms a gel layer controlling drug release. The characterization of powders was performed by analysis of particle size and morphology, density, compressibility index determination, flow properties and determination of swelling profile. The tablets were evaluated according to their physical parameters of quality and to the in vitro release of nimesulide, as well as the analysis of the mechanisms of drug release by appropriate mathematical models. The set of results showed that the HPMC/Nimesulide mixture exhibited satisfactory physical characteristics (size, shape, density and flow). The release profile demonstrated an effective control upon drug release in enteric environment and presented more correlation with Korsmeyer-Peppas’ and Weibull’s mathematical models, indicating that the release of nimesulide occurs through the relaxation of the polymer chains

Formadores de filmes híbridos ureasil-poliéter para proteção da pele e liberação controlada de fármacos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeito da ativação física e química do gel clareador na velocidade de penetração do peróxido de hidrogênio: estudo in vitro

This study evaluated the effect of physical and chemical activation on the speed of penetration of hydrogen peroxide bleaching agents present in different concentrations through the enamel and dentin. One hundred and twenty bovine incisors were used, which were obtained enamel/dentin discs of the buccal surface, with 6 mm in diameter. The samples were divided into six groups: G1 - Hydrogen Peroxide Gel 20%, G2 - Hydrogen Peroxide Gel 20% with light activation, G3 - Hydrogen Peroxide Gel 20% with Manganese Gluconate; G4 - Hydrogen Peroxide Gel 35%; G5 - Hydrogen Peroxide Gel 35% with the light activation and G6 - Hydrogen Peroxide Gel 35% with Manganese Gluconate. The specimens were placed in a transparent support on which there was a substance sensitive to hydrogen peroxide immediately below and in contact with the specimen. After the procedures for applying the gel for each group, one video camera was positioned and operated to monitor the time of penetration of peroxide in each specimen. The recording ended after changing the color of the fluid revealed in all specimens and times were noted for comparison. ANOVA analysis showed that concentration and type of activation of bleaching gel significantly influenced the diffusion time of hydrogen peroxide (P 0.05). 35% hydrogen peroxide showed the lowest diffusion times compared to the groups with 20% hydrogen peroxide gel. The light activation of hydrogen peroxide decrease significantly the diffusion time compared to chemical activation. The highest diffusion time was obtained with 20% hydrogen peroxide chemically activated. The diffusion time of hydrogen peroxide was dependent on activation and concentration of hydrogen peroxide. The higher concentration of hydrogen peroxide diffused through dental tissues more quickly

Aspectos técnicos e ambientais da incorporação de novas tecnologias no setor sucroalcooleiro: produção de hidrogênio e gaseificação do bagaço

The purpose of this work is to study the incorporation of hydrogen production (Case A) and the process of gasification of sugarcane bagasse associated with combined cycle gas turbine and steam turbine (Case B) for Distillery Pioneers process. These technologies can be used to improve the energy supply in the sugarcane mill. Initially the processes for obtaining sugar and ethanol from sugarcane is discussed, with a theoretical introduction to hydrogen, the process of steam reforming and gasification of biomass (bagasse) by inserting a turbine associated with the recovery boiler gas. Subsequently makes up the energy and exergy analysis of the incorporation of the above technologies. In end stage makes it an ecological analysis considering or not the carbon cycle (photosynthesis), to determine the levels of emissions of pollutants, carbon dioxide equivalent, indicators of pollution and ecological efficiencies associated with technological developments proposed. It is concluded that hydrogen production by steam reforming of ethanol and gasification of bagasse are viable alternatives from the point of view of technical and environmental applications in the biofuels industry, contributing to the development of the sector in the country

Síntese, incorporação e liberação prolongada do tetradecapeptídeo OGP em celulose bacteriana

Este trabalho apresenta o estudo de dois sistemas de liberação prolongada, microemulsão e lipossomas, contendo peptídeo regulatório de fatores de crescimento, “osteogenic growth peptide” OGP, para aplicação em regeneração óssea. A base de adsorção para estes sistemas de liberação foi a celulose bacteriana (CB) produzida pela bactéria Gluconacetobacter xylinus. Foi escolhida devido às suas propriedades físicas e químicas, tais como como alta resistência à corrosão química, bio absorção, biocompatibilidade, porosidade e ainda boa resistência mecânica, o que a torna um biopolímero com grande potencial a ser explorado pela ciência biomédica. Estudos in vitro foram realizados para avaliar o perfil de liberação do peptídeo dos diferentes sistemas de liberação prolongada. O peptídeo OGP foi sintetizado pelo método da fase sólida (estratégia SPFS Fmoc); foi purificado e caracterizado por HPLC, espectrometria de massas e análise de aminoácidos e, em seguida, marcados com 5,6 carboxifluoresceína (CF) para análise por espectroscopia de fluorescência. O peptídeo marcado foi incorporado aos sistemas de liberação no momento do respectivo preparo, foram adsorvidos na CB por um período de 72h, seguido de sua liberação prolongada em sistema fechado de fluxo constante contendo tampão PBS pH 7,4, por um período de 24h. Após a análise da liberação, observou se que o sistema que obteve melhor resultado foi a microemulsão, sendo sua liberação prolongada nas primeiras 6,5 h, liberando 21,5% do valor teórico de peptídeo incorporado, seguido de uma liberação constante a partir desse período. Dessa forma, tem se que a microemulsão pode ser um sistema promissor para liberação prolongada do OGP em processos de regeneração óssea

Síntese e caracterização de hidrogéis de amido retrogradado e goma gelana utilizados como matriz em sistemas de liberação cólon específica de fármacos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Amido retrogradado como excipiente de comprimidos para liberação controlada de fármacos: obtenção e caracterização

Pós-graduação em Ciências Farmacêuticas - FCFAR

Incorporação de novas tecnologias no setor sucroalcooleiro: produção de hidrogênio e aumento da oferta de eletricidade

This work studies the incorporation of new technologies in the sugarcane sector. Are considered the ethanol steam reforming and the gasification of sugarcane bagasse(by-product) processes associated with combined cycle systems (Gas Turbine + Steam Turbine), aggregating hydrogen production and increased electricity supply in the sector, respectively. To verify the technical feasibility of the incorporation processes was performed a thermodynamic analysis, considering data from a typical Brazilian Sugar Cane Industry. In another step the economic viability study of the hydrogen production process was made, with consideration on hydrated and anhydrous ethanol steam reform, comparing the cost of hydrogen production. Also considered studies of economic engineering of the gasification process and the generation of electricity associated. As conclusions, it follows that the ethanol steam reforming is a great alternative for hydrogen production, presenting production cost relatively low, especially when is considered the steam reforming of hydrated ethanol. For the gasification process associated with combined cycle, can be observed an increase of 8.56 times of the electricity production in the sugar cane industry, indicating a positive annual saving when the sales price of the supply electricity is greater than 0.070 US$/kWh. Finally it can be concluded that the incorporation of these new processes allow greater profitability and operational flexibility of Brazilian sugarcane mills

Estudo da produção de hidrogênio eletrolítico a partir de fontes eólica, solar e hidrelétrica

Introduces technical, economic and environmentally competitive solutions in the energy market is a great challenge for society. This work examines each of these aspects considering the production of electrolytic hydrogen with energy from wind power, solar and hydropower, in order to ensure an overview of this energy carrier. Initially, an assessment of the technical aspects is made addressing existing electrolysers technologies, its main characteristics and differences. The geographical distribution of wind, solar and hydroelectric potential in Brazil is also mapped, and a configuration scheme of a hydrogen production system is discussed. Subsequently, the economic analysis calculates the cost of investment in the alkaline electrolyser of 60 Nm³ / h, similar to the Brazilian bus powered by hydrogen project, coordinated by EMTU. Since the main input of electrolysis is electricity, is analyzed the latest energy auctions of each primary source and it is calculated the cost of production of the wind, solar and hydropower hydrogen. Postponed to this, are investigated the intrinsic environmental impacts of electricity generation process, proposing a readjustment of an indicator of ecological efficiency for the production of hydrogen. Finally, the work discusses the concept of externalities and demonstrates how the incorporation of external costs can leverage the hydrogen economy. In short, it is evident that the wind and hydroelectric hydrogens are more promising compared to solar hydrogen, whether in the economic aspect, because it achieved lower costs, whether in the environmental aspect, because it reached the highest ecological efficiency

Imobilização de fosfatos em microesferas poliméricas contendo biochar: preparação, caracterização e liberação lenta em sistemas aquosos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Liberação de componentes do extrato de Casearia sylvestris Swartz empregando membranas de látex natural como suporte

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)