High temperature synthesis of nanocrystals in non-polar solvents typically produces materials with narrow size distribution and high yields. However, the mechanism leading to the preservation of monodispersity on depletion of monomers is not understood, for example, in the case of iron oxide nanoparticles. In our study, it was found that oleic acid, a surfactant added to the mixture of iron precursor and solvent, gradually decomposed to release carbon monoxide at 320°C. This strong reducing gaseous product had a substantial impact on the size distribution of nanocrystals produced. The reduced forms of iron oxide catalyzed the disproportionation of carbon monoxide resulting in a graphitic carbon deposit on the surface of nanoparticles. The graphite coating inhibited further growth of particles and prevented Ostwald ripening. Graphite presence was demonstrated by Raman spectroscopy and Fourier transform infrared spectroscopy. It was found that the amount of graphite deposited on the surface of nanocrystals increased with time at 320°C. Quantitative data regarding the carbon content was obtained by thermo gravimetric analysis and energy dispersive spectrometry. The surface activity of the nanocrystals was shown to be affected by the carbon coating in applications such as arsenic removal.

The aim of this study is to demonstrate the possibility of production of nanocables as an alternative to the other one dimensional metal/polymer composite structures like nanowires and nanorods. There is no certain definition of nanocables / however they could be considered as assemblies of nanowires. Nanocable structure can be defined as a core-shell structure formed by a polymeric shell and a metal core that runs continuously within this shell. To produce nanocables, two main steps were carried out. Firstly, monodispersed silver metal nanoparticles to be aligned within the cable core were produced. Investigations on reduction reactions in the presence of strong and weak reducing agents and different capping agents revealed the importance of the kinetics of reduction in the production of monodispersed nanoparticles. Use of capping agents to give a positive reduction potential, resulted in the slow reduction rates that was critical for fine tuning of the final particle sizes between 1-10 nm. Hydrazine hydrate and oleylamine/ oleic acid systems were used as strong and weak reducing agents, respectively. By using weak reducing agent, monodisperse spherical silver nanoparticles with the diameter of 2.7 nm were produced. It was shown that particles with controlled diameter and size distribution can be obtained by tuning the system parameters. Secondly, particles produced as such were electrospun within the core of the polymer nanofibers and long continuous nanocables were produced. Polyvinyl pyrrolidone and polycaprolactone were used in shell part of nanocables. Transmission electron microscopy (TEM), scanning electron microscopy (SEM), photon correlation spectroscopy (PCS), X-ray diffraction (XRD) and surface plasmon resonance spectroscopy (SPR) analyses were carried out in order to understand the mechanism by which the nanoparticles were reduced and for further characterization of the product.

Oxidative stress and inflammation are important factors involved in the progression of heart failure. An important cytokine produced during myocardial infarction (MI) is tumor necrosis factor alpha (TNF-α). TNF-α may induce oxidative stress, cell damage, apoptosis and cardiac dysfunction. Considering the anti-inflammatory and anti-oxidant properties of extra-virgin olive oil and its major component (80%) oleic acid (OA), and their benefits to the cardiovascular system, we hypothesized that the negative effects of TNF-α in the pathogenesis of heart failure will be mitigated by olive oil consumption. This hypothesis was tested by examining the effects of a special diet supplemented with 10% olive oil, in coronary artery ligated animal model of MI. Corn oil (10%) supplementation was used as a control for matching caloric intake. Animals in the sham and ligated groups fed regular chow, olive oil, and corn oil were studied at 4 and 16 weeks post myocardial infarction (PMI). Mortality, diet consumption, weight gain and conduction system abnormalities were comparable among all ligated groups. Echocardiography showed that MI deteriorated cardiac function, and olive oil restored the function. At 16 weeks PMI, only corn oil fed groups showed significant increase in both total cholesterol and HDL. Corn oil was not able to offer protection to the heart, suggesting that the beneficial effects of olive oil are not due to increased caloric intake or increased HDL. MI increased myocardial TNF-α, oxidative stress, lipid peroxidation, pro-apoptotic protein expression (Bax, cleaved Caspase 3, cleaved PARP, TGFβ, Bnip3), cytochrome C release, MAP kinase activation (p38, JNK) and decreased anti-apoptotic protein Bcl-xL expression at both 4 and 16 weeks PMI, and these changes were modulated by olive oil. In order to further test the central role of TNF-α PMI, we examined the possible miti-gation of TNF-α induced changes by OA in isolated adult rat cardiomyocytes. TNF-α in-creased oxidative stress, cell damage, cell death, and apoptosis, while OA treatment miti-gated these TNF-α induced effects. We concluded that TNF-α is implicated in the progression of heart failure subsequent to MI and that OA in olive oil may prevent this progression, through its anti-oxidant, anti-inflammatory, anti-hypertensive, and inotropic effects.

The consumption of high-fat hamburger enriched with saturated fatty acids (SFA) and trans-fatty acids (TFA) may increase risk factors for cardiovascular disease, whereas hamburger enriched with monounsaturated fatty acids (MUFA) may have the opposite effect. Ten mildly hypercholesterolemic men consumed five, 114-g hamburger patties per week for two consecutive phases. Participants consumed low-MUFA (high SFA) hamburger (MUFA:SFA = 0.95; produced from pasture-fed cattle) for 5 wk, consumed their habitual diets for 3 wk, and then consumed high-MUFA hamburger (MUFA:SFA = 1.31; produced from grain-fed cattle) for 5 wk. These MUFA:SFA were typical of ranges observed for retail ground beef. Relative to habitual levels and levels during the high-MUFA phase, the low-MUFA hamburger: increased plasma palmitic acid, palmitoleic acid, and triacylglycerols (P < 0.01); decreased HDL cholesterol (HDL-C) and LDL particle diameter percentile distributions (P < 0.05); and had no effect on LDL-C or plasma glucose (P > 0.10). Plasma palmitoleic acid was positively correlated with triacylglycerols (r = 0.90), VLDL-C (r = 0.73), and the LDL:HDL (r = 0.45), and was negatively correlated with plasma HDL-C (r = -0.58), whereas plasma palmitic, stearic, and oleic acid were negatively correlated with LDL particle diameter (all P <= 0.05). Because plasma palmitoleic acid was derived from [delta]9 desaturation of palmitic acid in the liver, we conclude that alterations in hepatic stearoyl-CoA desaturase activity may have been responsible for the variation in HDL-C and triacylglycerols caused by the low-MUFA and high-MUFA hamburgers. Cattle with a genetic predisposition to deposit MUFA in their lean and fat tissues, such as Wagyu cattle can be used to produce beef products that are especially enriched with oleic acid and lower in SFA and TFA, and feeding practices can further enhance the composition of beef fat. This indicates that ground beef or hamburger products can be produced that are naturally enriched with oleic acid, and conversely that certain production practices can impair the nutritional quality of beef fat. Finally, we cannot discern from this study design whether the high-MUFA hamburger reversed the effects of the low-MUFA hamburger, or whether the subjects gradually adapted to the elevated intake of total fat. It is clear, however, that the high-MUFA hamburger did not exacerbate any of the effects of the low-MUFA hamburger and can be viewed as at least neutral in its effects on HDL-C and triacylglycerols.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Methylmalonic acidemias are inherited metabolic disorders characterized by methylmalonate (MMA) accumulation and neurological dysfunction, including seizures. Dietary fatty acids are known as an important energy source and reduce seizure activity in selected acute animal models. This study investigates whether the chronic treatment with fish oil or with oleic acid attenuates MMA-induced seizures. Adult male Wistar rats were treated with fish oil (85 mg/kg), oleic acid (85 mg/kg) or vehicle (0.42 % aqueous Cremophor EL , 4 mL/kg/body weight/day), p.o., for 75 days. In the 73th day were implanted a cannula in the right lateral ventricle with electrodes over the parietal cortex for EEG recording. In the 76th day half the animals from each group were injected with NaCl (2.5 μmol/2.5 μL, i.c.v.), and the other half with MMA (2.5 μmol/2.5 μL, i.c.v.), and seizure activity was measured by EEG recording with concomitant behavior monitoring. The effect of prostaglandin E2 (PGE2) on Na+,K+-ATPase activity of slices of cerebral cortex from NaCl-injected (control) animals was determined. Fish oil administration increased the latency for MMA-induced tonic-clonic seizures and reduced the mean amplitude of ictal EEG recordings. Oleic acid decreased mean amplitude of ictal EEG recordings. Treatment with fish oil prevented PGE2-induced decrease of Na+,K+-ATPase activity in cortical slices in vitro. The results support a major anticonvulsant role for fish oil against MMA-induced seizures. The decreased sensitivity of Na+,K+-ATPase from fish oil-treated animals to the inhibitory effect of PGE2 may be related to its currently reported anticonvulsant activity. / A acidemia metilmalônica é um erro inato do metabolismo caracterizado pelo acúmulo tecidual de ácido metilmalônico (MMA) e disfunção neurológica, incluindo convulsões. Os ácidos graxos dietéticos são conhecidos como fonte de energia e reduzem a atividade convulsivante em determinados modelos experimentais agudos de convulsão. Este estudo investiga se o tratamento crônico com óleo de peixe ou com ácido oléico atenua as convulsões induzidas por MMA. Ratos Wistar machos adultos foram tratados com óleo de peixe (85 mg / kg), ácido oléico (85 mg / kg) ou veículo (solução aquosa de Cremophor EL® 0,42%, 4 mL / kg de peso corporal / dia), via oral, por 75 dias. No 73º dia foi implantada uma cânula no ventrículo lateral direito e dois eletrodos sobre o córtex parietal para o registro eletroencefalográfico. No 76º dia metade dos animais de cada grupo foi injetada com NaCl (2,5 Smol / 2,5 SL, i.c.v.), e outra metade com MMA (2,5 Smol / 2,5 SL, i.c.v.), e a atividade convulsiva foi medida por EEG e monitoramento comportamental concomitantemente. O efeito da prostaglandina E2 (PGE2) na atividade Na+, K+-ATPase foi determinada em fatias de córtex cerebral dos animais injetados com NaCl (controle). A administração de óleo de peixe aumentou a latência para as convulsões tônico-clônicas induzidas por MMA e reduziu a amplitude média dos registros ictais de EEG. O ácido oléico diminuiu a amplitude média dos registros ictais de EEG. O tratamento com óleo de peixe preveniu a diminuição da atividade da Na+, K+-ATPase induzida por PGE2 em fatias corticais in vitro. Os resultados suportam um papel importante anticonvulsivante do óleo de peixe sobre as convulsões induzidas por MMA. A prevenção da redução da Na+, K+-ATPase induzida por PGE2 nos animais tratados com óleo de peixe pode estar relacionada à sua atividade anticonvulsivante atualmente relatada.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / This works investigated the curing reaction of epoxidized oleic acid starshaped with different anhydrides, forming product as oligoésteres and polyesters. Oleic acid modified was obtained by esterification of oleic acid with an aminoalcohol to the resulting aminoester, followed by epoxidation of the double bond. The polymerization reactions were carried out from the opening of epoxy rings in the presence of different cyclic acid anhydrides: phthalic anhydride (PA), maleic anhydride (MA) and succinic anhydride (SA). The structures of the products in these reactions were elucidated by nuclear magnetic resonance (NMR) 1H and 13C and infrared spectroscopy (FT-IR). The technique of Differential Scanning Calorimetry (DSC) allowed the study of the crosslinking process of the different systems studied, allowing the determination of kinetic and thermodynamic parameters. The kinetic parameters of curing reaction systems of ME/AM and ME/AS were determined by methods Osawa, Kissinger and Barret. The thermal behavior of the products obtained was analyzed using thermogravimetric analysis (TGA). It was evident that the nature of anhydrides affects the thermodynamic and kinetics parameters of the crosslinking reaction. Values of DH for the reactions of epoxy ring opening are related to factors such as the steric size of the molecule and the position of the oxirane ring in the structure of the ME. The addition of BADGE in the mixture ME/anhydride increased molar mass and improves thermal and mechanical properties of polyester. By varying the composition of the system characteristics of the samples obtained were thermoplastic or crosslinked materials. The GPC results showed that the materials in the absence of BADGE are essentially oligomers. The rheology results indicated that all samples exhibit Newtonian fluid behavior. The viscosity values of the samples without BADGE indicated that these materials exhibited characteristics of highly viscous fluids and the samples in the presence of BADGE exhibited characteristics typical of solid. / Este trabalho investigou a reação de cura do ácido oleico epoxidado (ME) com forma estrela com diferentes anidridos, originando oligoésteres e poliésteres. O ácido oleico modificado foi obtido pela esterificação do ácido oleico com um aminoálcool dando origem ao aminoéster, seguido da epoxidação da dupla ligação. As reações de polimerização foram realizadas a partir da abertura dos anéis epóxi na presença de diferentes anidridos de ácido cíclico: anidrido ftálico (AF), anidrido maleico (AM) e anidrido succínico (AS). As estruturas dos produtos das reações foram elucidadas por Ressonância Magnética Nuclear (RMN) de 1H e 13C e Espectroscopia de Infravermelho (FT-IR). A técnica de Calorimetria Exploratória Diferencial (DSC) permitiu o estudo do processo de reticulação dos diferentes sistemas estudados, possibilitando a determinação de parâmetros cinéticos e termodinâmicos. Os parâmetros cinéticos da reação de cura dos sistemas ME/AM e ME/AS foram determinados pelos métodos Osawa, Kissinger e Barret. O comportamento térmico dos produtos obtidos foi estudado utilizando a técnica de DSC e Análise Termogravimétrica (TGA). Evidenciou-se que a natureza dos anidridos influencia nos parâmetros termodinâmicos e cinéticos da reação de reticulação. Os valores de DH para as reações de abertura do anel epóxi estão relacionados a fatores estéricos como o tamanho da molécula e a posição do anel oxirano na estrutura do ME. A adição de BADGE na mistura ME/anidrido aumentou a massa molar e melhorou as propriedades térmicas e mecânicas dos poliésteres. Variando a composição do sistema as características dos materiais obtidos passaram de termoplásticos a termorrígidos. Os resultados de GPC mostraram que os materiais sem BADGE consistem essencialmente de oligômeros e as resinas com BADGE se apresentaram insolúveis e com aspecto de resinas poliméricas sólidas. Os resultados de reologia indicaram que, todas as amostras apresentaram comportamento de fluido newtoniano. Os valores de viscosidade das amostras sem BADGE indicaram que estes materiais apresentaram características de fluidos altamente viscosos e as amostras na presença de BADGE apresentaram características típicas de sólido.

Orientadores: Antonio Jose de Almeida Meirelles, Roberta Ceriani / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-12T23:42:39Z (GMT). No. of bitstreams: 1 Silva_SimoneMonteiroe_M.pdf: 2957959 bytes, checksum: f87550c181a2c8385702e38ac3b23215 (MD5) Previous issue date: 2009 / Resumo: O óleo de buriti (Mauritia flexuosa), obtido do fruto de uma palmeira nativa do Brasil, é uma fonte rica em b-caroteno e tocoferóis. Sua alta acidez (geralmente superior a 2,0%, expressos em ácido oléico), em conjunto com seus baixos teores de fósforo (10 mg/kg), torna interessante o seu refino por via física. Dessa forma, o objetivo deste trabalho é estudar a desacidificação por via física do óleo de buriti, visando manter os compostos nutracêuticos. Na primeira fase deste trabalho foi avaliada variabilidade do óleo de buriti de diversas procedências, pois o valor nutricional do óleo bruto pode variar com a sazonalidade e também com o processo de extração. Foi verificado que os óleos obtidos artesanalmente possuem maior valor nutracêutico. Entretanto, eles não são produzidos em larga escala, e em quantidades suficientes para a utilização comercial. Por isso foi utilizado um blend formado por um óleo de buriti artesanal obtido em uma feira popular e um industrial adquirido da empresa BERACA-SABARÁ. A utilização desse blend foi a melhor combinação entre qualidade e quantidade. O blend de óleo de buriti foi completamente caracterizado em termos da composição em ácidos graxos, classes de acilgliceróis e características físico-químicas. Estas análises, além de permitir conhecer de fato o sistema em estudo, tornam possível a modelagem e simulação dos experimentos. Os experimentos de desacidificação foram realizados no desodorizador em batelada desenvolvido pelo grupo de pesquisa juntamente com a empresa MARCONI, seguindo planejamento fatorial completo com duas variáveis independentes, sendo elas temperatura e vazão de vapor. Foram retiradas amostras após 30 e 60 minutos de stripping, obtendo dois planejamentos. Em cada uma das amostras de óleo foram realizadas análises de acidez. Também foram determinados teor de carotenóides e tocoferóis totais por HPLC, seguindo metodologia desenvolvida durante este trabalho. Foram recolhidas as fases aquosas e oleosas do destilado, e determinadas acidez e teor de água. Estas análises possibilitaram a determinação por diferença da perda de óleo neutro no destilado e a realização de balanços de massa para averiguar a qualidade dos experimentos. Os dados experimentais foram comparados com os obtidos por um programa de simulação computacional desenvolvido no grupo de pesquisa, utilizando o software MatLabè, que descreve a desodorização em batelada. A desacidificação por via física se mostrou um processo interessante para reduzir a acidez do óleo de buriti. Para isso, deve-se priorizar a utilização de altas vazões de vapor para o óleo de buriti, pois minimiza a degradação de carotenos e a perda de tocoferóis. A simulação computacional desenvolvida foi eficiente na predição da acidez e tocoferóis no óleo final, e apresenta uma boa perspectiva auxiliar na melhora da qualidade do óleo final, através da definição dos parâmetros do processo de acordo com a matéria-prima e a especificação do produto final / Abstract: Buriti oil (Mauritia flexuosa), obtained from the fruit of a palm tree native to Brazil, is a rich source of b-carotene and tocopherols. Its high acidity (usually above 2.0%), in conjunction with their low levels of phospholipids (below 10 ppm), enables buriti oil to physical refining. This work aimed to investigate the physical refining of buriti oil maintaining nutraceuticals compounds. At the first step, the variability of oil from different proveniences was evaluated, because the nutritional value of crude oil may vary with the seasonality and also with the extraction process. It was found that the artisanal oils have greater nutraceutical value. However, they are not produced in large scale, and in sufficient quantities for commercial use. So we used a blend formed by an artesanal buriti oil obtained at a popular market and an industrial, acquired from BERACA SABARA company. The use of this blend was the best combination of quality and quantity. The blend of buriti oil has been completely characterized in terms of fatty acids composition, classes of acilglycerides, and physical and chemical characteristics. These analyses allows the study of a well know system and to make the modeling and simulation of the experiments. The experiments were conducted in batch deodorizer developed by the research group in cooperation with MARCONI Company, following a full factorial experimental design with two independent variables, which are temperature and steam flow rate. Samples were removed after 30 and 60 minutes of stripping, getting two plans. Acidity was determined in the samples of oil. Carotenoids and tocopherols content was determined by HPLC, following methodology developed during this work. The aqueous and oily phases of distillate were collected, and its acidity and moisture content was determined. These analyses allowed the determination of neutral oil loss in distillate by difference and to make mass balances to assure the quality of the experiments. Experimental data were compared with those obtained by a computer simulation program which describes a batch deodorizer, developed in the research group, using the software MatLab è. The physical refining was an interesting process to reduce the acidity of the buriti oil. For this, it should prioritize the use of high flow of steam to the buriti oil, because it minimizes carotenes degradation and tocopherols loss. The simulation was efficient in predicting the acidity and tocopherols in the final oil, and gives a good perspective to help the quality of the final oil improving, by defining the process parameters according to raw material and final product specification / Mestrado / Mestre em Engenharia de Alimentos

O fluido multifásico complexo (suco de açaí) tem uma forte interação com membranas poliméricas ou cerâmicas de microfiltração e a formação de incrustação depende da composição e das condições de dinâmica de fluidos. Neste estudo experimental foi investigada a influência dos dois principais ácidos graxos presentes no açaí, ácido oleico e ácido palmítico, em misturas com água e no processo de microfiltração tangencial com membranas cerâmicas de alumina com um tamanho de poro nominal de 0,2 \'mü\'m. Mediu-se o fluxo de permeado em função do tempo, nas pressões transmembranas de 300 kPa, 400 kPa e 500 kPa. Para o fluxo da corrente de alimentação foram encontrados valores de Reynolds numa faixa de 9500 a 31000. Cada amostra de misturas de água/ácido oleico, água/ácido palmítico e água/ácidos oleico e palmítico, foi estudada em três séries de ensaios realizados durante 180 minutos e 72 minutos para a mistura água/ácido palmítico, a temperatura em 25 ºC. Analisou-se as incrustações resultantes e as fortes interações fluido/membrana utilizando o modelo de resistência em série e imagens tomadas por microscopia eletrônica de varredura (MEV). Os melhores resultados de permeado encontrados para a mistura de água/ácido oleico foram para Re = 33000, no entanto, resultados satisfatórios foram encontrados para Re = 20000. Agora para a água/ácido palmítico foram encontrados para Re = 20000. Os melhores resultados de permeado para a mistura água/ácidos oleico e palmítico foram para Re = 31000. De acordo com os resultados das resistências, a mistura água/ácido causa um bloqueio dos poros da membrana, resultando em uma maior diminuição do fluxo transmembrana. A limpeza foi eficiente para reduzir a resistência associada com a polarização. / The complex fluid multiphase (açaí juice) has a strong interaction with polymeric or ceramic membranes for microfiltration fouling and its formation depends on the fluid composition and fluid dynamics conditions. In this experimental study was investigated the influence of two major fatty acids present in açaí, oleic acid and palmitic acid in mixtures with water and in the process of crossflow microfiltration with ceramic membranes. In the separation process is used alumina ceramic membrane with a nominal pore size of 0.2 micrometers. The permeate flux was measured in function of time using the 300 kPa, 400 kPa and 500 kPa for the transmembrane pressure. The flow of feed stream and its respective value of Reynolds were in range of: 8900-3300. For each sample of mixtures oleic acid/water and palmitic acid/water and palmitic acid, oleic acid/ water, three series of experiments were conducted for 180 minutes and 72 minutes for mixture palmitic acid/water at temperature in 25 Celcius. For analyze of fouling resulting from strong interactions fluid/membrane was used the model of resistance in series and images taken via scanning electron microscopy (SEM). The best results for mixing oleic acid/water were to Re = 33000, however, satisfactory results were found for Re = 20000. Now for the palmitic acid/water were found to Re = 20000. For mixture palmitic acid, oleic acid/ water were found to Re = 31000. According to the results of the resistances, the mixture oleic acid/water cause a blockage of the pores of the membrane resulting in a greater decrease of the transmembrane flow. The cleaning is efficient for reducing the resistance associated with the polarization.

A administração tópica do ácido 5-aminolevulínico (5-ALA) tem se destacado na Terapia Fotodinâmica (TFD) do câncer de pele pela eficiência no tratamento de tumores e pelos reduzidos efeitos colaterais fototóxicos. Entretanto, esta eficácia é limitada devido à baixa penetração do 5-ALA na pele. Uma proposta para aumentar a penetração do 5-ALA na pele é a utilização de promotores de absorção cutânea, que visam alterar a barreira cutânea para várias moléculas bioativas. O objetivo deste trabalho foi o desenvolvimento farmacotécnico de formulações contendo ácido oléico (AO) como promotor de absorção cutânea, visando o aumento da penetração cutânea do 5-ALA para a TFD do câncer de pele. O fluxo in vitro de 5-ALA das formulações contendo AO (10%) foi significativamente aumentado após 12 horas de experimento, em relação às formulações sem AO, principalmente para os grupos contendo 5% e 10% de 5-ALA. A retenção no estrato córneo (EC) e na[epiderme + derme] sem EC também aumentou significativamente, mostrando um efeito promotor do AO. Foram também realizados experimentos in vivo em camundongos, com o intuito de analisar o efeito da formulação sobre a produção e o acúmulo in vivo de protoporfirina IX (PpIX) na pele. Observou-se que a presença do promotor de absorção aumentou significativamente a quantidade de PpIX extraída da pele comparado às formulações sem este aditivo. Para visualizar a presença de PpIX no tecido, realizou-se microscopia confocal das peles de animais tratados com as formulações. As imagens foram condizentes com os experimentos in vivo, observando-se um aumento da intensidade de fluorescência nas amostras de pele que foram tratadas com as formulações contendo AO. Os resultados in vitro e in vivo mostraram a potencialidade das formulações contendo AO como promotor de absorção cutânea na liberação do 5-ALA na TFD do câncer de pele. / The topical administration of 5-ALA has been distinguished on skin cancer photodynamic therapy (PDT) because of its efficiency in the treatment of tumors and the reduced phototoxic collateral effects. However, this effectiveness is limited by its low penetration in the skin. A proposal to optimize the 5-ALA penetration in the skin is the use of cutaneous penetration enhancers, which seek to alter the cutaneous barrier for many bioactive molecules. The aim of this work was the pharmaceutical development of formulations containing oleic acid (OA) as a cutaneous penetration enhancer, seeking the increase of the cutaneous penetration of 5-ALA for skin cancer PDT. The in vitro flux of 5-ALA from formulations containing OA (10% w/w) was significantly increased after 12 hours of experiment, in comparison with formulations without OA, mainly for the groups containing 5% and 10% of 5-ALA. The stratum corneum (SC) and [epidermis + dermis] without SC retention were also significantly increased, showing an enhancer effect of the fatty acid. In addition, in vivo experiments were accomplished in mice, with the purpose of analyzing the formulation effect on the PpIX production and accumulation in the skin. It was observed that the penetration enhancer\'s presence significantly increased the amount of PpIX extracted from the skin, in contrast with formulations without this addition. To visualize the PpIX presence in the tissue, confocal microscopy of the treated animal skins was made. The images were suitable with the in vivo experiments, with increased intensity of fluorescence in the tissue samples that were treated with formulations containing OA. Both in vitro and in vivo results showed the potentiality of the formulations containing OA as a cutaneous penetration enhancer for 5-ALA delivery on the skin cancer PDT.

INTRODUÇÃO. O termo Lesão Pulmonar Aguda (LPA) é usado para descrever a resposta pulmonar à lesão que ocorre diretamente ou indiretamente nos pulmões. A quebra da barreira alvéolo-capilar determina o influxo de líquido rico em proteínas para dentro dos espaços alveolares, sendo necessária a reabsorção desse líquido no processo de resolução da LPA. A infusão intravenosa de Ácido Oleico (AO) em ratos provoca agudamente edema alveolar difuso e focos hemorrágicos intra-alveolares, sendo um bom modelo de indução. Estudos relatam que o Azul de Metileno (AM) atenua tais lesões, com efeito protetor, no tecido pulmonar, e reduz o edema presente na LPA em animais com sepse através da inibição da guanilato ciclase solúvel (GCs), uma enzima ativadora da via NO-GMPc. OBJETIVO. Estudar a repercussão da inibição da GCs pelo AM na permeabilidade capilar pulmonar ministrando-o antes e após a indução da lesão pulmonar por AO. MÉTODO. Ratos Wistar foram divididos em 5 grupos: Sham com infusão de salina em bolus; AM com infusão de AM por 2h; AO com infusão de AO em bolus, AM/AO com infusão de AM por 2h, sendo que, após 5 min do início, recebeu AO simultaneamente em bolus e AO/AM com infusão de AO em bolus e, após 2h, infusão de AM por mais 2h. Após 4h foi realizada a coleta de materiais (sangue, lavado bronco-alveolar e tecido pulmonar) para análise do NO plasmático e tecidual, gasometria arterial, cálculo do peso úmido/peso seco (PU/PS) e histologia do tecido pulmonar de todos os grupos. A estatística utilizada foi a análise de variância (one-way ANOVA) com p<0.05. RESULTADO. Não foi encontrado hipoxemia grave após 4h de lesão. O grupo AO apresenta um aumento no número de proteínas no lavado bronco-alveolar e na relação PU/PS comparado aos grupos controle: Sham e AM, confirmando a presença de lesão e alteração de permeabilidade pulmonar. Os grupos tratados com AM apresentaram melhora na permeabilidade pulmonar, porém, apenas o grupo pré-tratamento (AM/AO) apresentou diferença estatística na redução do extravasamento de proteínas no lavado. Não foram encontradas diferenças significativas no NO plasmático e tecidual. Na microscopia, a congestão capilar foi intensa, acompanhada de múltiplos focos de edema alveolar, exsudato intra-alveolar proteico, áreas de hemorragia e infiltrado inflamatório neutrofílico, tanto no interstício quanto nos septos alveolares.Os grupos tratados com AM apresentaram diminuição das áreas de edema, exsudação e hemorragia, porém, com maior evidência no grupo AM/AO. CONCLUSÃO. O AM diminui a permeabilidade pulmonar quando administrado de maneira precoce amenizando os danos causados pela LPA induzida por AO. / BACKGROUND. The term Acute Lung Injury (ALI) is used to describe the response to lung injury that occurs directly or indirectly in the lungs. The rupture of the alveolar - capillary barrier determines the influx of protein-rich fluid into the alveolar spaces, the reabsorption of this fluid in the process of resolving the ALI is required. Intravenous infusion of oleic acid (OA) in rats acutely causes diffuse alveolar edema and intra-alveolar hemorrhagic foci, being a good role model induction. Studies have reported that Methylene Blue (MB) attenuates such injuries, with a protective effect in lung tissue and reduce edema present in the ALI present in with sepsis by inhibition of soluble guanylate cyclase (sGC), an activator of the enzyme NO- cGMP pathway. OBJECTIVE. To study the effect of inhibition of sGC by MB in pulmonary capillary permeability ministering to the before and after induction of lung injury by OA. METHOD. Wistar rats were divided into 5 groups: Sham infused with saline bolus, MB infused with MB for 2hrs, OA infused with OA bolus, MB/OA infused with MB for 2hrs, and after 5 min from the beginning, simultaneously received OA bolus and OA/MB infused with OA bolus and after 2hrs, MB infusion for 2hrs. After 4hrs the collection of materials was performed (blood, bronchoalveolar lavage and lung tissue) for analysis of plasma and tissue NO, arterial blood gases, calculation of the wet weight/dry weight (WW/DW) and histology of lung tissue from all groups. The statistic used was analysis of variance (one-way ANOVA) with p<0.05. RESULTS. Not found severe hypoxemia after 4hrs of injury. The OA group shows an increase in the number of proteins in bronchoalveolar lavage and in WW/DW ratio compared to the control groups: Sham and MB, confirming the presence of injury and alterations of lung permeability. The groups treated with MB showed improvement in lung permeability, however, only the pretreatment group (MB/OA) showed statistical significance in reducing the leakage of protein in the lavage. No significant differences were found in plasma and tissue NO. In microscopy, capillary congestion was intense, accompanied by multiple foci of alveolar edema, intra-alveolar proteinaceous exudates, areas of hemorrhage and neutrophilic inflammatory infiltrate in both the interstitium and in the alveolar septa. The groups treated with MB showed reduction in areas of edema, exudation and hemorrhage, however, most obviously in MB/OA group. CONCLUSION. The MB decreases lung permeability when administered as early as possible, mitigating the damage caused by OA-induced ALI.