39 resultados para impermeability


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

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Pós-graduação em Engenharia Civil - FEIS

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Functional expression of the multidrug resistance protein P-glycoprotein (P-gp) in Escherichia coli is providing an appropriate system for structure/function studies and might provide an invaluable tool to screen potential P-gp substrates and inhibitors. The major problem encountered in such studies, however, is the impermeability of the outer membrane of Gram-negative bacteria, which protects microorganisms against the cytotoxic effects of many lipophilic cancer drugs and blocks accessibility of P-gp reversal agents. In the present study we have constructed, by mutagenesis, a "leaky" (containing a permeable outer membrane) strain of E. coli, which is significantly more susceptible to the toxic effect of known P-gp substrates and cytotoxic agents. Expression of mouse Mdr1 in the mutant confers cross-resistance to daunomycin, quinidine, chloroquine, rhodamine 6G, and puromycin. Most importantly, reserpine and doxorubicin completely abolish Mdr1-mediated rhodamine resistance. The results provide strong support for previous observations, suggesting that Mdr1 can be expressed functionally in E. coli and indicate that the leaky mutant will be useful for further structure/function studies of the heterologously expressed eukaryotic drug efflux protein.

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O crescimento desordenado e a ausência de políticas públicas mais eficientes levaram a uma diversificação quanto ao uso dos recursos naturais, principalmente no que se refere à água para o saneamento básico. O marco regulatório estabelecido na década de 1980 registrou as políticas públicas para o meio ambiente, que trouxeram avanços sobre o tema, desencadeando uma série de ações voltadas tanto para a estrutura burocrática e da prevenção, quanto solução para os problemas de degradação e esgotamento dos recursos naturais. Com o advento das leis específicas de proteção aos mananciais e mediante a lei 13.579/09 do Estado de São Paulo que trata sobre a área da Billings, percebeu-se um avanço na questão do gerenciamento para proteção e desenvolvimento de acordo com as características da região. Instrumentos de políticas públicas para conter as ações referentes aos danos causados ao meio ambiente, como a lei contra crimes ambientais foram às ações práticas do Estado para conter tais ações. O Objetivo desta pesquisa é analisar as possíveis discrepâncias entre as penalidades financeiras aplicadas na ocorrência das infrações ambientais e os modelos de valoração dos ativos ambientais, utilizando a simulação de implantação de um hotel em áreas de proteção e recuperação de manancial no Município de São Bernardo do Campo no Estado de São Paulo. O desenvolvimento da pesquisa se baseou no método de custo de reposição (MCR) para dimensionar os possíveis impactos gerados por um empreendimento hoteleiro e seu respectivo valor econômico. Posteriormente, os impactos ambientais foram relacionados com a legislação do município para determinar os valores das possíveis penalidades aplicáveis ao dano causado. Dentre os resultados levantados, verificou-se uma significativa discrepância entre a valoração econômica e as multas aplicáveis, sendo que nos impactos referentes a impermeabilidade do solo e contaminação do lençol freático, com diferenças superiores em relação às penalidades de R$ 804.922,78 e R$ 453.333,33 respectivamente. A partir da metodologia aplicada na pesquisa, observou-se que as penalidades incidentes em casos de danos ao meio ambiente, muitas vezes não atinge o objetivo, que é inibir a ação do infrator, pois o real custo econômico não é medido na aplicação do valor da multa.

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Brain is one of the safe sanctuaries for HIV and, in turn, continuously supplies active viruses to the periphery. Additionally, HIV infection in brain results in several mild-to-severe neuro-immunological complications termed neuroAIDS. One-tenth of HIV-infected population is addicted to recreational drugs such as opiates, alcohol, nicotine, marijuana, etc. which share common target-areas in the brain with HIV. Interestingly, intensity of neuropathogenesis is remarkably enhanced due to exposure of recreational drugs during HIV infection. Current treatments to alleviate either the individual or synergistic effects of abusive drugs and HIV on neuronal modulations are less effective at CNS level, basically due to impermeability of therapeutic molecules across blood-brain barrier (BBB). Despite exciting advancement of nanotechnology in drug delivery, existing nanovehicles such as dendrimers, polymers, micelles, etc. suffer from the lack of adequate BBB penetrability before the drugs are engulfed by the reticuloendothelial system cells as well as the uncertainty that if and when the nanocarrier reaches the brain. Therefore, in order to develop a fast, target-specific, safe, and effective approach for brain delivery of anti-addiction, anti-viral and neuroprotective drugs, we exploited the potential of magnetic nanoparticles (MNPs) which, in recent years, has attracted significant importance in biomedical applications. We hypothesize that under the influence of external (non-invasive) magnetic force, MNPs can deliver these drugs across BBB in most effective manner. Accordingly, in this dissertation, I delineated the pharmacokinetics and dynamics of MNPs bound anti-opioid, anti-HIV and neuroprotective drugs for delivery in brain. I have developed a liposome-based novel magnetized nanovehicle which, under the influence of external magnetic forces, can transmigrate and effectively deliver drugs across BBB without compromising its integrity. It is expected that the developed nanoformulations may be of high therapeutic significance for neuroAIDS and for drug addiction as well.

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The present research concerns about outdoor s thermal comfort conditions in hot-humid climate cities, understanding that life quality is a result of the urban object s type built for the human being in an environment with specific climate and morphological characteristics. It is presented as object of study the correlation between the neighborhood Renascença II s microclimate in São Luis /MA-Brazil, hot-humid climate city, and its urban morphological changes. As well as the thermal comfort s satisfaction level of its outdoor users. The research has as general goal to diagnosis the way these transformations caused by the urbanization influence the Renascença II s microclimate, identifying critical spots of the studied area, in order to contribute with land use recommendations based on bioclimatic architecture concepts and supply bases to urban design decisions adequate to the São Luis climate. It is presented as theoretical bases the urban climate, its concepts and elements. After that, the thermal comfort conditioners and its prediction models of thermal comfort sensation in outdoor are presented. The predictive models are presented along with bioclimatic assessment methods. Finally the use of bioclimatic assessment as an effective tool to identify places that need changes or preservation in order to seek environment quality. The applied methodology was based on the studies of Katzschner (1997), complemented by Oliveira s (1988) and Bustos Romero s (2001) studies that suggest an analysis and evaluation of maps of topography, buildings floors, land use, green areas and land covering, in order to overlap their characteristics and identify climate variable s measurements points; then a quantitative analysis of the climate variables (air temperature and humidity, wind speed and direction) of the chosen points takes place. It was perceived that Renaissance II has no permanence areas as squares or parks, its outdoor has little vegetation and presets high land impermeability and built density levels. The majority of the people interviewed said that was comfortable in a range of air temperature between 27,28ºC and 30,71ºC. The elaboration of a neighborhood master plan is important, which defines strategies for improvement of the life quality of its inhabitants

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The present research concerns about outdoor s thermal comfort conditions in hot-humid climate cities, understanding that life quality is a result of the urban object s type built for the human being in an environment with specific climate and morphological characteristics. It is presented as object of study the correlation between the neighborhood Renascença II s microclimate in São Luis /MA-Brazil, hot-humid climate city, and its urban morphological changes. As well as the thermal comfort s satisfaction level of its outdoor users. The research has as general goal to diagnosis the way these transformations caused by the urbanization influence the Renascença II s microclimate, identifying critical spots of the studied area, in order to contribute with land use recommendations based on bioclimatic architecture concepts and supply bases to urban design decisions adequate to the São Luis climate. It is presented as theoretical bases the urban climate, its concepts and elements. After that, the thermal comfort conditioners and its prediction models of thermal comfort sensation in outdoor are presented. The predictive models are presented along with bioclimatic assessment methods. Finally the use of bioclimatic assessment as an effective tool to identify places that need changes or preservation in order to seek environment quality. The applied methodology was based on the studies of Katzschner (1997), complemented by Oliveira s (1988) and Bustos Romero s (2001) studies that suggest an analysis and evaluation of maps of topography, buildings floors, land use, green areas and land covering, in order to overlap their characteristics and identify climate variable s measurements points; then a quantitative analysis of the climate variables (air temperature and humidity, wind speed and direction) of the chosen points takes place. It was perceived that Renaissance II has no permanence areas as squares or parks, its outdoor has little vegetation and presets high land impermeability and built density levels. The majority of the people interviewed said that was comfortable in a range of air temperature between 27,28ºC and 30,71ºC. The elaboration of a neighborhood master plan is important, which defines strategies for improvement of the life quality of its inhabitants

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Brain is one of the safe sanctuaries for HIV and, in turn, continuously supplies active viruses to the periphery. Additionally, HIV infection in brain results in several mild-to-severe neuro-immunological complications termed neuroAIDS. One-tenth of HIV-infected population is addicted to recreational drugs such as opiates, alcohol, nicotine, marijuana, etc. which share common target-areas in the brain with HIV. Interestingly, intensity of neuropathogenesis is remarkably enhanced due to exposure of recreational drugs during HIV infection. Current treatments to alleviate either the individual or synergistic effects of abusive drugs and HIV on neuronal modulations are less effective at CNS level, basically due to impermeability of therapeutic molecules across blood-brain barrier (BBB). Despite exciting advancement of nanotechnology in drug delivery, existing nanovehicles such as dendrimers, polymers, micelles, etc. suffer from the lack of adequate BBB penetrability before the drugs are engulfed by the reticuloendothelial system cells as well as the uncertainty that if and when the nanocarrier reaches the brain. Therefore, in order to develop a fast, target-specific, safe, and effective approach for brain delivery of anti-addiction, anti-viral and neuroprotective drugs, we exploited the potential of magnetic nanoparticles (MNPs) which, in recent years, has attracted significant importance in biomedical applications. We hypothesize that under the influence of external (non-invasive) magnetic force, MNPs can deliver these drugs across BBB in most effective manner. Accordingly, in this dissertation, I delineated the pharmacokinetics and dynamics of MNPs bound anti-opioid, anti-HIV and neuroprotective drugs for delivery in brain. I have developed a liposome-based novel magnetized nanovehicle which, under the influence of external magnetic forces, can transmigrate and effectively deliver drugs across BBB without compromising its integrity. It is expected that the developed nanoformulations may be of high therapeutic significance for neuroAIDS and for drug addiction as well.