Este trabalho descreve a síntese, caracterização e aplicação de sistemas poliméricos baseados em polímeros condutores em sistemas de liberação controlada de drogas. Esta tese pode ser dividida em duas partes: na primeira se apresentam os resultados da aplicação de filmes de polianilina e polipirrol na liberação de drogasmodelo como a dopamina protonada e o ácido salicílico. Na liberação de salicilato utilizou-se um filme polianilina eletrosintetizado e dopado com íons cloreto. Já para a liberação de dopamina protonada (um cátion) a liberação foi conduzida a partir de um sistema bicamadas, com um filme de polianilina recoberta com uma camada de Náfion. É mostrada a liberação controlada nos dois casos, porém também se discutem limitaçãoes deste tipo de sistema que levaram ao estudo de uma forma alternativa de controle eletroquímico utilizando polímeros condutores. A segunda parte do trabalho mostra então esta nova metodologia que se baseia em compósitos de poianilina eletropolimerizada no interior de hidrogéis de poliacrilamida. É mostrado que este novo material é eletroativo e mantém as características de intumescimento dos hidrogéis, tanto necessárias ao desenvolvimento destes sistemas de liberação controlada. Mecanismos para o crescimento e distribuição da polianilina na matriz isolante e para a atuação do compósito no controle eletroquímico da liberação são propostos com base nos dados de microscopia de força atômica, Raman e eletrônica de varredura, além de testes de liberação controlada com moléculas de diferentes cargas. / This work describes the synthesis, characterization and application of polimeric systems based on contucting polymers for electrochemical release devices. The thesis is divided into two parts: frrst, results conceming the application of polyaniline and polypyrrole films in the controlled release of dopamine and salicilyc acid, are showed. An electrosyntetized polyaniline film doped with chloride ions was used in the salicilate release. On the other hand, for the controlled release of protonated dopamine, a bilayer system consisting of a polyaniline film recovered with Nafion was employed. The release control was reached in both cases, but this kind of actuator show serious limitations that lead to the conclusion that a new type of electrochemical control based in conducting polymers must be developped. The second part shows the new methodology based on composites of polyaniline grown inside polyacrylamide hydrogels. It\'s showed that this new material is electroactive and still maintains the hydrogel\'s swelling properties, which makes it an interesting and suitable material for drug delivery devices. Raman Microscopy, Scaning Electron Microscopy and Atomic Force Microscopy, and controlled release tests of different charged molecules were tools for the elucidation of polyaniline\'s growth and distribuition inside the hydrogels and for the mecanism of actuation in the controlled release.

O presente estudo foi desenvolvido à partir de dois experimentos. No primeiro objetivou-se foi avaliar a utilização de uréia encapsulada de liberação lenta em dietas de novilhos Nelore canulados no rúmen e seus efeitos sobre o consumo e digestibilidade dos nutrientes, fermentação e produção microbiana ruminal, balanço de nitrogênio, e as concentrações de parâmetros sangüíneos. Foram utilizados 8 novilhos canulados da raça Nelore, mantidos em regime de confinamento, alocados em baias individuais cobertas, tipo tie stall. Os animais foram distribuídos aleatoriamente em 2 quadrados latinos 4 x 4 balanceados e contemporâneos, para receber as seguintes rações experimentais: 1) Controle (C), composta por ração sem a inclusão de uréia; 2) Uréia pecuária (Reforce N) (U), com a utilização de 2,0% de uréia pecuária na ração, baseada na matéria seca; 3) Uréia encapsulada 1 (UE-1), a utilização de 2,0% de uréia encapsulada com o polímero 1 na ração, baseada na matéria seca; e 4) Uréia encapsulada 2 (UE-2), com a utilização de 2,0% de uréia encapsulada com o polímero 2 na ração, baseada na matéria seca. O volumoso foi a silagem de milho, sendo a proporção volumoso: concentrado da dieta de 50:50. Foi observado maior consumo de MS, MO, PB, EE, CNF, FDN, FDN e consumo de MS em relação a %PV nos animais controle em relação aos alimentados com uréia. Foi observado menor digestibilidade da PB nos animais controle em relação aos alimentados com uréia. Maiores concentrações de N-NH3 ruminal foram observadas nos animais alimentados com uréia comum em relação aos alimentados com uréia encapsulada e maiores concentrações de propionato foram encontradas nos animais alimentados com uréia encapsulada em relação aos com uréia comum. Foi observado maior consumo de energia bruta, energia digestível, energia líquida, produção de energia líquida de ganho e eficiência energia líquida de produção nos animais submetidos a dieta controle em relação aos alimentados com uréia. Também foi observado maior consumo de nitrogênio (N) (g/dia) nos animais controle em relação aos com uréia, ainda maior quantidade de N e %N total nas fezes nos animais controle em relação aos alimentados com uréia e maior quantidade de N e %N urinário nos animais alimentados com uréia comum em relação aos com uréia encapsulada. Observou-se maiores concentrações de colesterol sérico nos animais controle em relação aos com uréia e maiores concentrações de uréia e N-ureico séricos nos animais alimentados com uréia em relação aos com uréia encapsulada. A utilização de uréia encapsulada alterou positivamente a fermentação ruminal, porém níveis de inclusão de 2% diminui o consumo dos animais. No segundo experimento, objetivou-se avaliar a utilização de uréia encapsulada de liberação lenta em dietas de novilhos Nelore em confinamento e seus efeitos sobre o desempenho animal, qualidade de carcaça e parâmetros sanguíneos. Foram utilizados 84 animais novilhos inteiros, da raça Nelore, com idade aproximada de 18 meses e peso vivo inicial médio de 350 kg. Os animais foram confinados por um período de 84 dias, precedido de um período de adaptação, de 7 dias para receber as seguintes rações experimentais: 1) Controle (C), composta por ração sem a inclusão de uréia; 2) Uréia pecuária (Reforce N) (U-1), com a utilização de 1,0% de uréia pecuária na ração, baseada na matéria seca; 3) Uréia pecuária (Reforce N) (U-2), com a utilização de 2,0% de uréia pecuária na ração, baseada na matéria seca; 4) Uréia encapsulada 1 (UE1-1), a utilização de 1,0% de uréia encapsulada com o polímero 1 na ração, baseada na matéria seca; 5) Uréia encapsulada 1 (UE1-2), a utilização de 2,0% de uréia encapsulada com o polímero 1 na ração, baseada na matéria seca; e 6) Uréia encapsulada 2 (UE2-1), com a utilização de 1,0% de uréia encapsulada com o polímero 2 na ração, baseada na matéria seca; e 7) Uréia encapsulada 2 (UE2-2), com a utilização de 2,0% de uréia encapsulada com o polímero 2 na ração, baseada na matéria seca. O volumoso utilizado foi a silagem de milho, sendo a proporção volumoso: concentrado da dieta de 50:50. As amostras de sangue foram coletadas no 28º, 56º e 84º dias, junto com a pesagem dos animais. Após 84 dias de experimento os animais foram abatidos, foi avaliado, área de olho de lombo (AOL cm2) e espessura de gordura subcutânea (EGS mm) do músculo Longissimus. Foi observado maior ganho de peso (kg/dia) e peso final (kg) nos animais alimentados com a dieta controle em relação aos alimentados com uréia e também maior ganho de peso nos animais alimentados com a dieta controle em relação aos alimentados com dietas contendo 2% de uréia. Também foi observado maior ganho de peso nos animais alimentados com dietas contendo 1% de uréia em relação aos alimentados com dietas contendo 2% de uréia. Observou-se menores concentrações de glicose sérica (mg/dl) e AST (UI/L) nos animais alimentados com uréia pecuária em relação aos alimentados com uréia encapsulada. Maiores concentrações (mg/dl) de uréia e nitrogênio ureico sérico foram observados nos animais alimentados com dietas contendo 2% de uréia em relação aos com 1% de uréia. A utilização de uréia encapsulada, independente dos níveis de inclusão na dieta, não influenciou na qualidade da carcaça dos animais. Quando utilizada com inclusão de 2% na dieta, influenciou negativamente o desempenho dos animais. / The present study was developed from two experiments. At first the aim was to evaluate the use of polymer-coatedslow release urea in rations of Nelore bulls with ruminal cannulas and its effect on consumption and nutrient digestibility, rumen fermentation and microbial production, nitrogen balance, and blood parameters concentrations. Eight Nelore bulls with ruminal cannulas, kept in individual tie stalls, were assigned to two 4 x 4 contemporary Latin squares balanced to receive the following experimental diets: 1) Control (C), consisting of diet without the addition of urea, 2) Feed-grade Urea (FGU) with 2,0% urea in ration, based on dry matter (DM), 3) Polymer-coated urea1 (PCU-1), with 2.0% PCU1 in the ration, based on DM, and 4) Polymer-coated urea 2 (PCU-2) with 2.0% PCU2 in the ration based on DM. The forage source was corn silage, and the proportion forage:concentrate diet was 50:50. There was higher dry matter intake (DMI), original matter intake (OMI), crude protein (PB), ether extract (EE), non-fiber carbohydrates (NFC) and neutral detergent fiber (NDF) in relation to percentage of body weight (BW%) in control animals compared with those fed urea. Lower digestibility of CP was observed in control animals compared with those fed urea. Higher concentrations of ruminal NH3-N were found in animals fed urea compared to those fed PCU and higher concentrations of propionate were found in animals fed PCU compared to those fed FGU. There was a higher consumption of gross energy, digestible energy, net energy, net energy production and efficiency gains net energy production in animals receiving control diet than those fed urea. There was a greater consumption of nitrogen (N) (g/day) in animals receiving control diet compared to urea fed groups, even greater amount of N and total % N in feces in control animals than urea fed groups and higher N and % urinary Nin ureafed animals compared to those fed PCU. Higher concentrations were observed in serum cholesterol in the control group compared urea fed groups and higher concentrations of urea and serum urea-N in FGU group compared to PCU group. The use of PCU positively affected ruminal fermentation, however inclusion levels of 2% decreases the intake of animals. In the second experiment, to evaluate the use of PCU in diets of bull calves in confinement and its effect on intake, animal performance, carcass quality and blood parameters. Animals were used 84 whole steers, Nellore, aged approximately 18 months and initial weight of 350 kg. The animals were confined for a period of 84 days, preceded by an adaptation period of 7 days to receive the following experimental diets: 1) Control (C), consisting of diet without the addition of urea, 2) 1FGU-1, with 1.0% urea in ration based on DM, 3) 2FGU-1, with 2.0% urea in ration, based on DM, 4) 1PCU-1, with 1.0% PCU1in ration, based on DM, 5) 2PCU-1 with 2.0% PCU1in ration, based on DM and 6) 1PCU-2, with 1.0% PCU2 in ration, based on DM, and 7) 2PCU-2, with2.0% PCU2 in ration, based on DM. The forage source was corn silage, and the proportion forage: concentrate diet was 50:50. Blood samples were collected at the 28th, 56th and 84th days with the weighing of the animals. After the 84thof the experiment the animals were slaughtered, was evaluated rib eye area (REA square centimeters) and subcutaneous fat thickness (SFT mm) of the Longissimus muscle. There was more weight gain (kg/day) and final weight (kg) in animals fed the control diet than those fed urea and these parameters were also higher in animals fed the control diet than those fed diets containing 2 % urea and was even higher higher in animals fed diets containing 1% urea than those fed diets containing 2% urea. It was observed lower concentrations of serum glucose (mg/dl) and AST (IU L) in animals fed FGU than those fed PCU. Also, higher concentrations (mg/dl) of urea and serum urea nitrogen levels were observed in animals fed diets containing 2% urea compared to those with 1% urea in rations. The use of PCU, regardless the levels in diet did not influenced the carcass quality When used with inclusion of 2% in the ration, had a negative effect on animal performance.

O objetivo deste estudo foi avaliar o cimento de ionômero de vidro modificado por resina de nanopartículas Ketac&trade;N100, por meio de três metodologias diferentes: resposta tecidual em subcutâneo de camundongos isogênicos, liberação de flúor e tensão de contração de polimerização, in vitro. Foram utilizados 90 camundongos isogênicos da linhagem BALB/c, divididos em 9 grupos (n=10), nos quais foram implantados tubos de polietileno contendo o Ketac&trade; 100, ChemFilR (ionômero de vidro convencional) ou tubo vazio. Nos períodos experimentais de 7, 21 e 63 dias o tubo e o tecido adjacente foram removidos para análise microscópica. Para o ensaio de avaliação da tensão de contração de polimerização, foram utilizados dois bastões de vidro fixados a uma máquina de ensaio universal. Nos bastões foi acoplado um extensômetro para medição da força de contração de polimerização de cinco materiais (Resina Filtek&trade;Z350, CompoglassR F, VitremerMR, Ketac&trade;N100 e ChemFilR), com 10 corpos de prova para cada material. Para o ensaio de liberação de flúor, foram confeccionados 8 corpos de prova de 3 diferentes materiais (Ketac&trade; 100, Vidrion R e Resina Filtek&trade; Z250), colocados individualmente em 1 ml de saliva artificial. O corpo de prova foi trocado a cada dia por 15 dias e a solução obtida utilizada para a leitura do íon fluoreto.Os resultados microscópicos evidenciaram que a inflamação presente na abertura dos tubos, aos 7 dias, sofreu uma diminuição em área e espessura até os 63 dias, nos 2 materiais e no grupo controle. Comparando a área da reação inflamatória o Ketac&trade;N100 foi diferente estatisticamente do ChemFilR, nos períodos de 7 e 21 dias (p>0,05), com uma área menor para o Ketac&trade;N100. A espessura da reação inflamatória nos períodos de 7 e 21 dias apresentou valores semelhantes entre o Ketac&trade;N100 e ChemFilR (p>0,05). Aos 63 dias, os valores foram estatisticamente diferentes, com um pequeno aumento de espessura para o Ketac&trade;N100. Os valores de tensão de contração de polimerização obtidos seguiram a seguinte ordem crescente: ChemFilR < VitremerMR < Ketac&trade;N100 < CompoglassR F ~ Filtek&trade;Z350 (p>0,05). Quando comparados dois a dois, o ionômero modificado por resina de nanopartículas Ketac&trade;N100 se aproximou mais dos valores da resina Filtek&trade; Z350 (p>0,05) do que do ionômero de vidro convencional ChemFilR (p<0,05). A sua liberação de flúor ocorreu mais significativamente nos dois primeiros dias, com valores médios 33% menores em comparação ao Vidrion R. Concluímos que o ionômero resinoso nanoparticulado Ketac&trade;N100 é um material que induz uma resposta inflamatória tecidual satisfatória em subcutâneo de camundongos isogênicos. Sua contração de polimerização foi menor do que de a resina Filtek&trade; Z350 e a liberação de flúor foi um terço menor do que a dos ionômeros convencionais. / The aim of this study was to evaluate the resin modified nano ionomer Ketac&trade;N100, by three different methodologies: tissue response in of isogenic mice subcutaneous, fluoride release and shrinkage stress of polymerization in vitro. We used 90 isogenic mice (BALB / c), divided into 9 groups (n = 10), which were implanted with polyethylene tubes containing Ketac&trade; 100, ChemFilR (Ionomer conventional) or empty tube. In the experimental periods of 7, 21 and 63 days the tube and the surrounding tissue were removed for microscopic analysis. To evaluating the stress of contraction of polymerization, we used two glass rods attached to a universal testing machine. In the rods was attached to an extensometer to obtain the measure of the polymerization shrinkage strength of five materials (resin Filtek&trade;Z350, CompoglassR F, VitremerMR F, Ketac&trade; 100 and ChemFilR), with 10 specimens for each material. In the fluoride release test, 8 specimens of 3 different materials (Ketac&trade; 100, Vidrion R and Resin Filtek&trade; Z250) placed individually in 1 ml of artificial saliva. The specimens were changed each day for 15 days and we use this solution used for reading the fluoride ion. The microscopic results showed that the inflammation in the opening of the tubes at 7 days decreased in area and thickness up to 63 days in 2 materials and the control group. Comparing the inflammatory reaction area, Ketac&trade;N100 was statistically different from ChemFilR, in periods of 7 and 21 days (p> 0.05), with a smaller area for Ketac&trade;N100. The inflammatory reaction in the periods of 7 and 21 days showed similar values between the Ketac&trade;N100 and ChemFilR (p> 0.05). At 63 days, the values were statistically different, with a small increase in thickness to Ketac&trade;N100. The values of polymerization shrinkage strength obtained after polymerization followed this ascending order: ChemFilR < VitremerMR F < Ketac&trade; 100 < CompoglassR F ~ Filtek&trade;Z350 (p> 0.05). When compared two by two, the resin modified nano ionomer Ketac&trade;N100 approached most of the values of resin Filtek&trade; Z350(p> 0.05) than the conventional glass Ionomer ChemFilR (p <0.05). The fluoride release occurred more significantly in the first two days, with average 33% lower compared with Vidrion R. We conclude that the resin modified nano ionomer Ketac&trade;N100 is a material that induces an satisfactory inflammatory response in subcutaneous tissue of isogenic mice. Its polymerization shrinkage strength was lower than the resin Filtek&trade; Z350 and fluoride release was a third lower than the conventional glass ionomer.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-05-17T11:32:08Z No. of bitstreams: 1 pedropaulosoldati.pdf: 1732705 bytes, checksum: 3dc5affce1644925cc37df52a9986961 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-06-28T13:31:38Z (GMT) No. of bitstreams: 1 pedropaulosoldati.pdf: 1732705 bytes, checksum: 3dc5affce1644925cc37df52a9986961 (MD5) / Made available in DSpace on 2016-06-28T13:31:38Z (GMT). No. of bitstreams: 1 pedropaulosoldati.pdf: 1732705 bytes, checksum: 3dc5affce1644925cc37df52a9986961 (MD5) Previous issue date: 2015-11-27 / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / Nanopartículas lipídicas sólidas (NLS) foram preparadas utilizando como fração lipídica a manteiga natural extraída das sementes de Theobroma grandiflorum (cupuaçu) para a liberação controlada de resveratrol visando a aplicação tópica. A manteiga natural foi avaliada por cromatografia gasosa para a identificação e quantificação dos principais componentes lipídicos, mostrando equilibrada composição entre ácidos graxos saturados e insaturados. As NLS foram preparadas pela técnica de homogeneização por alto cisalhamento e apresentaram tamanho de partícula na escala manométrica, com uma distribuição homogênea da dispersão, confirmada pelas técnicas de espalhamento dinâmico de luz e microscopia eletrônica de transmissão. Suas características físico-químicas, como carga superficial negativa, tamanho e índice de polidispersão, mantiveram-se inalteradas durante 30 dias, indicando boa estabilidade coloidal. O estudo de liberação in vitro utilizando células de difusão de Franz demonstraram uma liberação controlada do ativo, apresentando uma cinética de liberação controlada pela difusão do núcleoo lipídico, de acordo com o modelo de Higuchi. A NLS contendo o resveratrol (R-NLS) apresentou um aumento de 20% na atividade antioxidante em comparação com a solução etanólica de resveratrol (SER). O estudo de penetração cutânea, utilizando pele humana proveniente de abdominoplastia, indicou que a R-NLS aumentou a penetração e retenção do ativo nas camadas mais externas da pele, com um acréscimo de 2 vezes no estrato córneo quando comparado com a SER. Além disso, a NLS desenvolvida mostrou-se segura, visto que não apresentou citotixidade em linhagem de queratinócitos humanos. Por isso, o sistema de NLS preparado utilizando manteiga natural é capaz de promover uma liberação segura e controlada do ativo na pele, sendo promissor para sua utilização em formulações tópicas. / Solid lipid nanoparticles (SLN) based on natural seed butter extracted from Amazon tree Theobroma grandiflorum (cupuaçu) were prepared for the topical controlled release of resveratrol, a well-known lipophilic antioxidant. The natural butter was assessed by gas chromatography for the identification and quantification of the lipids, showing saturated and unsaturated fatty acids as the major constituents. Nanoparticles were then prepared by high shear homogenization and presented small particle size, with narrow size distribution, which was confirmed by dynamic light scattering measurements and transmission electronic microscopy images. The negative surface charge, size and polydispersity index remained unaltered for 30 days, indicating good colloidal stability. Moreover, the controlled release kinetics revealed a burst release followed by a sustained drug release from SLNs containing resveratrol (R-SLN), which fitted the Higuchi mathematical model, indicating that the releasing profile from the lipid core is diffusion-controlled. R-SLN showed an increased antioxidant activity in 20% compared to resveratrol ethanolic solution (RES). When applied to human skin, R-SLN increased the permeation and retention of resveratrol in the human skin, raising the amount of resveratrol over than 2-fold in stratum corneum compared to RES. In addition, there was no cytotoxicity of the SLN to human keratinocytes at tested conditions. This new SLN prepared with natural seed butter was able to permeate and deliver hydrophobic actives to the skin in a controlled manner, having the potential to ultimately be used in formulations that request topical delivery.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-03-07T12:02:26Z No. of bitstreams: 1 danielepiresmagalhaesespiritosanto.pdf: 19885258 bytes, checksum: cc404305a80b23fea7d1a26415bf75bf (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-03-07T15:03:55Z (GMT) No. of bitstreams: 1 danielepiresmagalhaesespiritosanto.pdf: 19885258 bytes, checksum: cc404305a80b23fea7d1a26415bf75bf (MD5) / Made available in DSpace on 2017-03-07T15:03:55Z (GMT). No. of bitstreams: 1 danielepiresmagalhaesespiritosanto.pdf: 19885258 bytes, checksum: cc404305a80b23fea7d1a26415bf75bf (MD5) Previous issue date: 2014-08-29 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A arritmia ventricular maligna é uma das principais causas de morte no mundo. Muitas vezes o início de um episódio de arritmia está associado a uma excitação inoportuna no coração, também denominada extra-sístole, ou Potencial de Ação Espontâneo (PAE). O surgimento de PAEs pode estar relacionado a mudanças estruturais ou moleculares nos canais iônicos e a alterações no ciclo de cálcio intracelular. Anormalidades no ciclo de cálcio podem gerar transientes de cálcio espontâneos (TCEs) e estes podem desencadear Potenciais de Ação Espontâneos (PAEs). Estudos experimentais mostram que o surgimento de TCEs é mais frequente sob a estimulação β-Adrenérgica. Em experimentos recentes, notou-se que a presença de episódios de TCEs em cardiomiócitos saudáveis não desencadeia a geração de PAEs. Em contrapartida, em camundongos com a mutação de super expressão da bomba NCX (NaCa), PAEs foram observados em miócitos isolados e foram relacionados a episódios de TCEs. O principal objetivo deste trabalho foi a simulação da formação de PAEs utilizando modelos computacionais desenvolvidos para cardiomiócitos do ventrículo esquerdo de camundongos. Em particular os modelos computacionais foram capazes de reproduzir os cenários experimentais descritos acima, relacionando a geração de PAEs com a estimulação β-Adrenérgica e alterações de canais iônicos como a mutação NCX. Dessa forma, as simulações computacionais apresentadas neste trabalho permitem uma melhor compreensão dos complexos fenômenos associados a arritmias cardíacas. / Malignant ventricular arrhythmias are the major cause of death around the world. The beginning of an episode of arrhythmia is often associated with ectopic beats in the heart, also called extrasystole, or Spontaneous Action Potential (SAP). The development of SAP may be related to structural or molecular changes in ion channels and changes in intracellular calcium cycle. Abnormalities in calcium cycle can result in Spontaneous Calcium Transientes (SCT) and these can trigger SAP. Experimental studies show that the development of SCT is more common under β1-adrenergic stimulation. However, we found, in recent experiments, that the presence of episodes of SCT in healthy cardiomyocytes does not trigger the development of SAP. On the other hand, on mice presenting mutation of overexpression of NCX (NaCa) pump, SAP were observed in isolated cardiomyocytes and were related to episodes of SCT. Thus, we aimed, in this study, to simulate development of SAP using computational models developed for cardiomyocytes of left ventricle of mice. The computational models were able to reproduce the experimental scenarios described above, relating the development of SAP to the β-adrenergic stimulation and to the changes of ion channels as the NCX mutation. Therefore, the computational simulations showed in this work allow the best comprehension of the complex phenomena associated with cardiac arrhythmia.

Esse estudo visa testar a eficiência informacional dos mercados acionários brasileiro e mexicano, através do desenvolvimento de um estudo de eventos. Para viabilização do estudo, o mercado brasileiro será representado pela BOVESPA - Bolsa de Valores de São Paulo e o mercado mexicano pela BMV - Bolsa Mexicana de Valores. Especificamente, esses mercados serão representados pelas ações de empresas que participaram da composição das carteiras teóricas dos Índices IBOVESPA e IpyC (Índice de Precios y Cotizaciones) durante todo o período compreendido entre Janeiro de 2001 e Janeiro de 2006. Foram analisadas as reações dos retornos das ações nesses mercados nos dias próximos às datas das divulgações de resultados trimestrais pelas empresas em busca de evidências de ineficiências. Os resultados encontrados mostraram indícios de eficiência informacional quando as empresas foram consideradas individualmente e indícios de ineficiência informacional quando considerada carteira toda. / This study aims to test the informational efficiency of the Brazilian and Mexican stock markets, through the development of an event study. For this purpose, BOVESPA, the Sao Paulo Stock Exchange will represent the Brazilian stock market while the Mexican Stock Exchange (BMV) will represent the Mexican stock market. Specifically, these markets will be represented by the company stocks that participated of the composition of their stock market indexes, IBOVESPA (BOVESPA Index) and IPyC (Mexican Stock Exchange Index), during the period of January 2001 through January 2006. Stock prices were analyzed for the days around the quarterly results release dates, searching for inefficiency evidence in these markets. The results show signs of information-efficiency when considering each company and information inefficiency when considering the market portfolio.

Made available in DSpace on 2014-08-20T14:30:08Z (GMT). No. of bitstreams: 1 Dissertacao_giane_silva_linhares.pdf: 488926 bytes, checksum: 2a1b87dca9f0a74faf913e8c6e40713e (MD5) Previous issue date: 2012-12-05 / The incorporation of light-curable resins has been proposed for Mineral Trioxide Aggregate (MTA) to improve its properties and reduce its setting time. The aim of the present study was to assess the pH, calcium-ion release and antibacterial activity of an experimental dual-cure Bis-EMA/MTA-based root-end filling material (E-MTA) in comparison with white-MTA (W-MTA); and to evaluate the influence of the addition of CaCl2 on these properties. Polyethylene tubes filled with the materials were immersed in deionized water for the measurement of pH (digital pH meter) and calcium release (atomic absorption spectrophotometry). The evaluations were performed at 3 and 24 hours and 7, 15 and 30 days. The direct contact test was used for evaluation of antibacterial activity of the materials against E. faecalis 30 min and 24 h after manipulation. All materials presented a variation from an alkaline to nearly neutral pH, and were capable of releasing calcium ions along the 30 days of the study. E-MTA showed a significant lower calcium ion release capacity when compared to W-MTA (P<0.05). The calcium release of E-MTA + 5% CaCl2 was similar to W-MTA (P> 0.05). All materials were 100% effective against E. faecalis at 30 min after manipulation. Reduction in the antibacterial activity was observed for E-MTA with or without the addition of CaCl2 after 24h. The monomer Bis-EMA added to MTA formed a material with lower capacity of calcium release and lower antibacterial activity than W-MTA, in spite of maintaining a similar pH. However, the addition of CaCl2 improved the calcium release of this material / A incorporação de resinas fotopolimerizadas ao agregado de trióxido mineral (MTA) tem sido proposta com o intuito de melhorar as suas propriedades e reduzir o tempo de presa. O objetivo do presente estudo foi avaliar o pH, a liberação de íons cálcio e a atividade antibacteriana de um material retrobturador experimental de polimerização dual a base de Bis-EMA/MTA (MTA-E) em comparação com o MTA-branco (MTA-B); e avaliar a influência da adição de CaCl2 sobre estas propriedades. Tubos de polietileno com os materiais foram imersos em água deionizada. Para medir o pH da água foi utilizado um peagâmetro digital. O cálcio liberado foi determinado pela técnica de espectrometria de absorção atômica. O Teste do Contato Direto foi utilizado para avaliar a atividade antibacteriana dos materiais contra E. faecalis 30 min e 24 h após a manipulação. Todos os materiais apresentaram uma variação de pH de alcalino para quase neutro e foram capazes de liberar íons cálcio durante os 30 dias do estudo. MTA-E mostrou uma capacidade de liberação de íons cálcio significativamente menor que o MTA-B (P<0,05). A liberação de cálcio do MTA-E + CaCl2 5% foi semelhante ao MTA-B (P>0,05). Todos os materiais foram 100% efetivos contra E. faecalis nos 30 minutos após a manipulação. Após 24h uma redução na atividade antibacteriana foi observada para o MTA-E, com ou sem a adição de CaCl2. O monómero Bis-EMA adicionado ao MTA formou um material com baixa capacidade de liberação de cálcio e menor atividade antibacteriana do que MTA-B, apesar de manter um pH semelhante. No entanto, a adição de CaCl2 melhorou a liberação de cálcio deste material

The thesis focuses on research of IT process weakness. In theoretical part are described basic terms and also frameworks or best practise of process maturity rating. Selected practice ITIL and COBIT are then used for rating in practical part. For this purpose is choosen one of process which is outsourced by external contractor. Rating is made using free accessible tools, which are offered by selected practice and which offer rating process. Result is established according to consultation with people involved in project and their rating using mentioned tools.

Au cours des dernières années, les autorités sanitaires ont recommandé une réduction de la teneur en sel et en gras dans la consommation alimentaire quotidienne. Cependant, les aliments à teneur réduite en sel et en gras sont souvent peu appréciés par les consommateurs, ce qui a amené au développement des recherches sur les stratégies possibles pour maintenir l’acceptabilité des aliments tout en réduisant les teneurs en ces ingrédients. Dans cette thèse, l’intégration multi-sensorielle et les cinétiques de libération du sel et des arômes mesurées in vitro ont été étudiés pour évaluer leur potentialité à compenser une réduction en sel et matière grasse d’un fromage modèle de composition variable et d’un fromage réel (type trappiste).Dans une première étape, une approche sensorielle a permis d’étudier les interactions multi-sensorielles arômes-saveurs-texture pour les formages modèles et réels. La structure et la perception sensorielle de vingt-quatre modèles fromagers variant en composition (2 niveaux de gras, 2 de sel, 2 de pH à l’emprésurage) et aromatisés avec un arôme de sardine (associé au sel), d'un arôme de beurre (associé au gras) ou non aromatisés (témoin) ont été caractérisés par des mesures rhéologiques (compression uniaxiale) et des mesures sensorielles (profil descriptif). Les résultats ont montré une influence de la composition sur la structure et la texture perçue des produits. Par ailleurs, l’arôme sardine a conduit à une perception plus salé ; l’arôme de beurre a permis de renforcer la perception du caractère gras. Toutefois cette influence des arômes sur les autres dimensions sensorielles est fonction de la texture des produits donc de leur composition et de leur structure. Ces résultats ont été étendus à des fromages réels avec toutefois des spécificités. Si l’arôme sardine renforce la perception du sel, seul l’arôme de beurre associé à l’arôme de sardine permet de renforcer le caractère gras.Dans une deuxième étape, une approche physico-chimique a été développée pour explorer les cinétiques de libération des stimuli odorants et sapides dans des conditions simulant la mastication in vitro à l’aide d’un simulateur de mastication. L’objectif était d’utiliser les données ainsi obtenues pour expliquer l’influence de la structure des produits et de leur déstructuration lors de la mastication sur les effets sensoriels observés dans la première étape. Les modèles fromagers et les fromages réels ont été ainsi étudiés. La libération des composés volatils a été évaluée en connectant le simulateur de mastication à un spectromètre de masse à pression atmosphérique (PTR-MS) ; la libération du sodium a été suivie grâce à une sonde de conductivité. Les résultats ont montré une influence des trois paramètres de composition (teneur en matière grasse, en sel et pH à l’emprésurage) sur les cinétiques de la libération des arômes. Cette variation dépend néanmoins de la nature de l’arôme suivi ; les arômes plus hydrophobes étant moins sensibles aux variations de la teneur en matière grasse et plus sensibles aux variations de pH et donc à la structure du produit. La cinétique de libération du sel lors de la mastication in vitro est aussi largement influencée par la composition et la structure des produits. Outre la teneur en sel qui conditionne les quantités libérées, la teneur en matière grasse et le pH à l’emprésurage module la cinétique de libération du sel. Au final, ces travaux montrent une importante contribution de la cinétique de libération et donc probablement de la temporalité des sensations dans perception globale du sel et de la matière grasse lors de la consommation d’un aliment complexe. / In recent years, health authorities worldwide advise for a reduction of salt and fat in daily food consumption. However, foods with reduced salt and fat content are often not appreciated by consumers, Therefore, the formulation of low-salt-fat foods that maintain acceptability is a major concern in food research. In this thesis, the multi-sensory integration and release kinetics of flavor compounds were explored as strategies to compensate for salt and fat reduction in cheese products (model cheeses and real cheeses). The objective was to better understand the mechanisms leading to aroma and salt release during mastication and to evaluate how the matrix composition and structure influence salt and aroma release profile.Multisensory integration approach to compensate for salt and fat reduction was studied in a first step. The structure and sensory perception of 24 cheese models varying in composition (2 levels of fat, 2 salt, 2 pH at renneting) and flavored with either a sardine aroma (associated to salt), a butter aroma (associated to fat) or not flavoured (control) were characterised by rheological measurements (uniaxial compression) and sensory evaluation (descriptive analysis). The results demonstrated an influence of the composition on the products structure and perceived texture. Furthermore, a significant saltiness enhancement was induced by sardine aroma while significant fat perception enhancement was induced by butter aroma. However, this influence of the aroma on other sensory dimensions depends on the texture of the products thus on their composition and structure. These results have been extended to real cheeses but with specificities. If the sardine flavor enhanced the perception of salt, only butter-sardine-flavor enhanced the perception of fat.In a second step, a physico-chemical approach was developed to explore the release kinetic of flavor compounds during in vitro breakdown using a chewing simulator. The aim was to use these data to explain the influence of the structure of model cheeses and real cheeses and their breakdown during chewing on sensory effects observed in the first step. Volatile compounds release was monitored by connecting the chewing simulator to a proton transfer reaction-mass spectrometry (PTR-MS), while salt release was monitored using a conductivity probe. Results showed that product composition and structure (fat, salt and pH at renneting) influenced aroma release, which however depends on the nature of the aroma: the more hydrophobic compounds are less sensitive to variations in fat content and more sensitive to variations in pH and therefore to the products structure. The salt release kinetic during in vitro chewing was also influenced by the composition and structure of the products. Indeed, beyond salt content which determined the amount of salt released, fat content and the pH at renneting modulated the release kinetic. In conclusion, this work showed a significant impact of the flavor compounds release kinetic and probably of temporality of sensations on the overall perception of salt and fat when consuming a complex food.

Tuberculosis (TB) remains the main cause of death in people living with HIV (PLHIV). Indeed, PLHIV have a 20-30% greater risk of developing TB compared to HIV-uninfected subjects and have lower TB treatment success rates. In 2014, among the 9.6 million incident cases of TB reported worldwide, 12% occurred in PLHIV and 0.4 million deaths from HIV-associated TB were recorded.Mycobacterium tuberculosis is the main etiological agent for TB. For a majority of individuals, the immune response upon infection by M. tuberculosis is sufficient to prevent the development of disease, but insufficient to clear the bacteria. This leads to the persistence of viable M. tuberculosis in diverse cells with no resulting clinical manifestations, an entity known as latent tuberculosis infection (LTBI). The resulting reservoir of M. tuberculosis is vast, and an estimated one third of the world population is concerned. For subjects with LTBI, the life-time risk of reactivation and progression to TB lies between 5 and 10%. However, if co-infected with HIV, the risk is much greater and reaches 10% per year. According to a Cochrane review in 2010, the screening and treatment of LTBI in PLHIV reduces this risk by 30-60%. This prevention strategy is therefore widely recommended. However, the implementation of LTBI screening and treatment into standard HIV-care has been limited. In this work, three different approaches have been used to understand and address this issue, focusing on a low TB-incidence and high-income setting.The first approach was to assess the implementation of LTBI screening in HIV-care across Belgium and identify its barriers as perceived by the caregivers on the field. Raising awareness to this issue was an indirect objective of the study. A multi-choice questionnaire was sent to 55 physicians working in a Belgian AIDS reference center or satellite clinic. A response rate of 62% was obtained. Only 20% of participants performed LTBI screening on all their patients and notable variations in the screening methods used were observed. A large majority of participants were in favor of targeting LTBI screening to HIV-infected patients at highest risk of TB rather than a systematic screening of all PLHIV. These results have been communicated to the Belgian LTBI working group, currently updating the national LTBI screening guidelines. Indeed, targeting screening to those at highest risk of TB is an attractive strategy in low-TB incidence countries and is already recommended in the United Kingdom. However, to date, no score assessing the risk of TB in PLHIV has been validated. Among the barriers to LTBI screening identified by the participants of this first study, the most frequently reported were lack of sensitivity of screening tools, risk associated to polypharmacy and toxicity of treatment. Improving the sensitivity of LTBI screening was the cornerstone of the second approach. The available screening tools for LTBI are the tuberculin skin test (TST) and two Interferon-gamma release assays (IGRAs): the QuantiFERON-TB Gold-IT (QFT-GIT) and the T-SPOT.TB®. All three lack sensitivity in PLHIV. Various strategies to discover superior LTBI screening tools are therefore being explored, including the development of IGRAs in response to alternative M. tuberculosis antigens to those used in the QFT-GIT or T-SPOT.TB®. A potential candidate is the native Heparin-Binding Haemagglutin (nHBHA), a methylated M. tuberculosis protein regarded as a latency-associated antigen. An in-house IGRA based on nHBHA (nHBHA-IGRA) has been shown to be a promising LTBI screening tool both in immunocompetent adults and in hemodialysed patients. The contribution of this nHBHA-IGRA to the detection of M. tuberculosis in PLHIV was therefore investigated. Treatment-naïve HIV-infected subjects were recruited from 4 Brussels-based hospitals. Subjects underwent screening for latent TB using the nHBHA-IGRA in parallel to the classical method consisting of medical history, chest X-ray, TST and QFT-GIT. Prospective clinical and biological follow-up ensued, with repeated testing with nHBHA-IGRA. Among 48 candidates enrolled for screening, 9 were diagnosed with LTBI by combining the TST and QFT-GIT results (3 TST+/QFT-GIT+, 1 TST+/QFT-GIT- and 5 TST-/QFT-GIT+). All 3 TST+/QFT-GIT+ patients, the TST+/QFT-GIT- patient as well an additional 3 subjects screened positive with the nHBHA-IGRA. These 3 additional patients had known M. tuberculosis exposure risks compatible with LTBI. During follow-up (median 14 months) no case of TB was reported and nHBHA-IGRA results remained globally constant. Multiplex analysis confirmed IFN- as the best read-out for the assay. From this study, we concluded that the nHBHA-IGRA appears complementary to the QFT-GIT for the screening of LTBI in PLHIV and the combination of the two tests may increase the sensitivity of screening. A large-scale study is however necessary to determine whether combining nHBHA-IGRA and QFT-GIT offers sufficient sensitivity to dismiss TST, as suggested by our results. In the same study, a group of HIV-infected adults with clinical suspicion of active TB were also recruited and tested with nHBHA-IGRA. Contrary to results in HIV-uninfected subjects, the nHBHA-IGRA could not discriminate between LTBI and active TB in PLHIV. This is an important caveat as HIV-infected subjects may present subclinical TB.A different angle was used for the third approach to the problem of LTBI in PLHIV. Systemic immune activation (SIA) is one of the principal driving forces in the natural course of HIV-infection. Despite long-term viral suppression by combination antiretroviral treatment (cART), a low-level SIA persists and is associated with an early-onset of age-associated disorders such as cardiovascular disease, dementia and osteoporosis. Causes of SIA in PLHIV are multiple and certain chronic infections appear to be implicated. A recent study in South Africa found that LTBI in PLHIV was associated with an increase in circulating activated CD8+ T-cells. If LTBI should contribute to the persistence of SIA, its screening and treatment could have an additional benefit on the clinical outcome of PLHIV. To investigate this theory, the expression of T-cell activation markers (CD38 and HLADR) as well as the level of plasmatic markers of immune activation (IL-6, sCD14, D-Dimers) were compared between subjects presenting active TB, subjects with LTBI and M. tuberculosis-free persons, with and without HIV-infection. In accordance with previous studies, active TB was associated with higher levels of SIA biomarkers in both HIV-infected and -uninfected groups. Among the HIV-uninfected subjects, no significant difference in biomarker level was found between those presenting LTBI and those with no evidence of M. tuberculosis. The effect of LTBI on activation biomarkers in the HIV-infected groups remained inconclusive because of the small number of individuals in the HIV+/LTBI group. Further investigation is therefore warranted. Interestingly, it was found that plasmatic markers may have a greater sensitivity for the detection of M. tuberculosis-associated SIA than the T-cell activation markers, an important result for future studies.Overall, LTBI in PLHIV is a challenging topic, in particular because of the lack of a gold-standard for the diagnosis of LTBI. Despite suboptimal tools, the evident clinical impact of LTBI screening and treatment in PLHIV on TB incidence justifies its implementation in standard HIV-care. In low TB-incidence countries, who, when and how to screen for LTBI in PLHIV remains unclear. This work offers an overview on the subject with particular focus on possible measures for improvement in the field. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished