Esta é uma avaliação ecocardiográfica de indivíduos pré-hipertensos e hipertensos estágio I, aninhada no ensaio clínico randomizado PREVER. Ecocardiogramas foram realizados no início e após 18 meses de tratamento (clortalidona/amilorida ou placebo em pré-hipertensos, clortalidona/amilorida ou losartana em hipertensos estágio I). Comparando-se os ecocardiogramas basais de pré-hipertensos e hipertensos, observou-se que pré-hipertensão está associada a alterações ecocardiográficas de dano hipertensivo em órgão alvo semelhantes à hipertensão estágio I, com exceção da massa ventricular esquerda, que foi maior em mulheres hipertensas do que nas pré-hipertensas. Em hipertensos estágio I, após 18 meses de tratamento houve redução significativa no volume do AE, na massa do VE e na espessura relativa. Não houve redução significativa na massa do VE quando a redução da pressão arterial sistólica foi menor que 6,2 mmHg. Observou-se redução na proporção de remodelamento concêntrico do VE (60% para 41,8%) e aumento na proporção de geometria ventricular esquerda normal (30,9% para 49%). Comparando-se as medicações anti-hipertensivas em hipertensão estágio I, a regressão na massa ventricular esquerda, a redução no volume atrial esquerdo e as mudanças nos parâmetros de função diastólica após 18 meses de tratamento foram semelhantes para clortalidona/amilorida e losartana. Conclui-se que os parâmetros ecocardiográficos basais de dano hipertensivo em órgão alvo são semelhantes em pré-hipertensos e hipertensos estágio I. Em indivíduos com hipertensão estágio I, tratamento anti-hipertensivo por 18 meses promove efeitos benéficos na massa ventricular esquerda, volume atrial esquerdo e remodelamento concêntrico do VE, sem diferença entre os grupos de tratamento. Esses achados podem ter impacto nas consequências da cardiomiopatia hipertensiva, especialmente na insuficiência cardíaca com fração de ejeção preservada.

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No. of bitstreams: 6 Dissertação - Camila Regina do Vale - 2012.pdf: 3235850 bytes, checksum: 687e2cdf37b9bac962f29a62c285b353 (MD5) Dissertação - Camila Regina do Vale - pt 1.pdf: 149467 bytes, checksum: 7f1815d7489ba931bb9892b778028608 (MD5) Dissertação - Camila Regina do Vale - pt 2.pdf: 213195 bytes, checksum: d971df42608e298f9a5b9ef182198144 (MD5) Dissertação - Camila Regina do Vale - pt 3.pdf: 135423 bytes, checksum: 05f3ace3a177dce48ae73b89c7dcafa5 (MD5) Dissertação - Camila Regina do Vale - pt 4.pdf: 209379 bytes, checksum: 0d8927034cc8da946756c3ffc2fd1539 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2012-10-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Hymenaea courbaril L. (Family Fabaceae), popularly known in Brazil as jatobá, is a tropical species that occurs in semi-deciduous forest of the South America. The species has been used in Brazil for culinary purposes and in folk medicine to treat arthritis, gastric dysfunction, inflammation and respiratory diseases. Due to the spreading use of this plant as a therapeutic resource and food, the present study aimed to evaluate the toxic, genotoxic, recombinogenic and antigenotoxic effects of Hymenaea courbaril sap (Hycs) using the mouse bone marrow micronucleus test and somatic mutation and recombination test (SMART) in Drosophila melanogaster. To evaluate the clastogenic and aneugenic activities by micronucleos test the animals were treated with 3 concentrations of Hycs (5, 10 and 15 mL/kg body weight). To evaluate the anti-clastogenic and anti-aneugenic activities, the animals were simultaneously treated with Hycs and mitomycin C (4mg/kg body weight). To evaluate the mutagenic and recombinogenic activities by SMART, three-day-old larvae derived from standard (ST) and high bioactivation (HB) crosses were treated with 3 doses of Hycs (0.3, 1.5 or 3 mL) for approximately 48 hours. To evaluate the antimutagenic and antirecombinogenic activities, larvae derived from both crosses were cotreated with 3 doses of Hycs (0.3, 1.5 or 3 mL) and doxorubicin (0.125 mg/mL). Our results in the mouse bone marrow micronucleus test showed that SHyc exhibited no cytotoxic, clastogenic and/or aneugenic effects, but showed anticytotoxic, anti-clastogenic and /or anti-aneugenic activities in mouse bone marrow. The results for the SMART test showed no mutagenic and recombinagenic effects, but antimutagenic and anti-recombinogenic activities were found in both crosses in somatic cells of Drosophila melanogaster. / Hymenaea courbaril L. (família Fabaceae), popularmente conhecida no Brasil como jatobá, é uma espécie tropical que ocorre na floresta semi-decídua da América do Sul. A espécie tem sido utilizada no Brasil para fins culinários e na medicina popular para tratar artrite, disfunção gástrica, inflamação e doenças respiratórias. Devido ao uso generalizado dessa planta como um recurso terapêutico e alimentar, o presente estudo teve como objetivo avaliar os efeitos tóxicos, genotóxicos, recombinogênicos e antigenotóxicos da seiva de Hymenaea courbaril (SHyc), usando o teste do micronúcleo em medula óssea de camundongo e o teste de recombinação e mutação somática (SMART) em Drosophila melanogaster. Para avaliar a ação clastogênica e aneugênica pelo ensaio do micronúcleo, os animais foram tratados com 3 concentrações de SHyc (5, 10 e 15 mL/kg de peso corporal). Para avaliar a atividade anticlastogênica e antianeugênica , os animais foram tratados simultaneamente com SHyc e mitomicina C (4mg/kg de peso corporal). Para avaliar as atividades mutagênica e recombinagênica pelo teste SMART, larvas de terceiro estágio provenientes dos cruzamentos padrão (ST) e alta bioativação (HB) foram tratadas com 3 doses de SHyc (0,3; 1,5 ou 3 mL), por aproximadamente 48 horas. Para avaliar a atividade antimutagênica e anti-recombinogênica, larvas provenientes de ambos os cruzamentos foram co-tratadas com 3 doses de SHyc (0,3, 1,5 ou 3 mL) e doxorubicina (0,125 mg/mL). Nossos resultados para o teste do micronúcleo em medula óssea de camundongos mostraram que SHyc não apresentou efeitos citotóxicos, clastogênicos e/ou aneugênicos , mas apresentou atividade ancitotóxica, anticlastogênica e/ou antianeugênica em medula óssea de camundongos. Os resultados para o teste SMART/asa não demonstraram efeitos mutagênicos e recombinagênicos, mas a acão antimutagênica e anti-recombinogênica foi evidenciado em células somáticas de Drosophila melanogaster.

Tese de mestrado. Estruturas de Engenharia Civil. 2004. Faculdade de Engenharia. Universidade do Porto

Tese de mestrado. Estruturas de Engenharia Civil. 2005. Faculdade de Engenharia. Universidade do Porto

Treze folhas são desdobráveis / Tese de mestrado integrado. Engenharia Civil (Especialização em Estruturas). Faculdade de Engenharia. Universidade do Porto. 2009

Tese de doutoramento. Engenharia Civil. Universidade do Porto. Faculdade de Engenharia. 2011

Doctor of Philosophy(PhD) / Iron (Fe) is essential for cell growth and replication as many Fe-containing proteins catalyse key reactions involved in energy metabolism (cytochromes, mitochondrial aconitase and Fe-S proteins of the electron transport chain), respiration (hemoglobin and myoglobin) and DNA synthesis (ribonucleotide reductase). If not appropriately shielded, Fe could participate in one-electron transfer reactions that lead to the production of extremely toxic free radicals. The Fe storage protein, ferritin, is essential to protect cells against Fe-mediated oxidative stress by accommodating excess Fe into its protein shell (Xu et al., 2005). However, despite intensive research over the last few decades, many questions relating to intracellular Fe metabolism, e.g. Fe release from ferritin remain unanswered. Therefore, it is important to elucidate the molecular mechanisms of Fe trafficking in cells. At the beginning of my candidature, little was understood regarding the effect of anti-cancer agents, anthracyclines on the Fe-regulated genes, including transferrin receptor-1 (TfR1), N-myc downstream-regulated gene-1 (Ndrg1) and ferritin. Furthermore, the mechanisms of ferritin-Fe release and anthracycline-mediated ferritin-Fe accumulation are unclear. The work presented in Chapters 3 and 4 has addressed these issues. Apart from the studies examining the molecular interactions of anthracyclines with Fe, a mouse model with perturbed Fe metabolism was used and the marked alterations of protein expression in the heart of this knockout mouse model was discussed in Chapter 5. Chapter 3 Anthracyclines are effective anti-cancer agents. However, their use is limited by cardiotoxicity, an effect linked to their ability to chelate iron (Fe) and perturb Fe metabolism (Xu et al., 2005). These effects on Fe-trafficking remain poorly understood, but are important to decipher as treatment for anthracycline cardiotoxicity utilises the chelator, dexrazoxane. Incubation of cells with doxorubicin (DOX) up-regulated mRNA levels of the Fe-regulated genes, transferrin receptor-1 (TfR1) and N-myc downstream-regulated gene-1 (Ndrg1). This effect was mediated by Fe-depletion, as it was reversed by adding Fe and was prevented by saturating the anthracycline metal-binding site with Fe. However, DOX did not act like a typical chelator, as it did not induce cellular Fe mobilisation. In the presence of DOX and 59Fe-transferrin, Fe-trafficking studies demonstrated ferritin-59Fe accumulation and decreased cytosolic-59Fe incorporation. This could induce cytosolic Fe-deficiency and increase TfR1 and Ndrg1 mRNA. Up-regulation of TfR1 and Ndrg1 by DOX was independent of anthracycline-mediated radical generation and occurred via HIF-1α-independent mechanisms. Despite increased TfR1 and Ndrg1 mRNA after DOX treatment, this agent decreased TfR1 and Ndrg1 protein expression. Hence, the effects of DOX on Fe metabolism were complex due to its multiple effector mechanisms. Chapter 4 The Fe storage protein, ferritin, can accommodate up to 4500 atoms of Fe in its protein shell (Harrison and Arosio, 1996). However, the underlying mechanism of ferritin-Fe release remains unknown. Previous studies demonstrated that anti-cancer agents, anthracyclines, led to ferritin-59Fe accumulation (Kwok and Richardson, 2003). The increase in ferritin-59Fe was shown to be due to a decrease in the release of Fe from this protein. It could be speculated that DOX may impair the Fe release pathway by preventing the synthesis of essential ferritin partner proteins that induce Fe release. In this study, a native protein purification technique has been utilised to isolate ferritin-associated partners by combining ultra-centrifugation, anion-exchange chromatography, size exclusion chromatography and native gel electrophoresis. In addition to cells in culture (namely, SK-Mel-28 melanoma cells), liver taken from the mouse was used as a physiological in vivo model, as this organ is a major source of ferritin. Four potential partner proteins were identified along with ferritin, e.g. aldehyde dehydrogenase 1 family, member L1 (ALDH1L1). Future studies are required to clarify the relationship of these proteins with cellular Fe metabolism and ferritin-Fe release. Chapter 5 A frequent cause of death in Friedreich’s ataxia patients is cardiomyopathy, but the molecular alterations underlying this condition are unknown. We performed two dimensional electrophoresis to characterise the changes in protein expression of hearts using the muscle creatine kinase frataxin conditional knockout (KO) mouse. Pronounced changes in the protein expression profile were observed in 9-week-old KO mice with severe cardiomyopathy. In contrast, only a few proteins showed altered expression in asymptomatic 4-week-old KO mice. In hearts from frataxin KO mice, components of the iron-dependent complex-I and -II of the mitochondrial electron transport chain and enzymes involved in ATP homeostasis (creatine kinase, adenylate kinase) displayed decreased expression. Interestingly, the KO hearts exhibited increased expression of enzymes involved in the citric acid cycle, catabolism of branched-chain amino acids, ketone body utilisation and pyruvate decarboxylation. This constitutes evidence of metabolic compensation due to decreased expression of electron transport proteins. There was also pronounced up-regulation of proteins involved in stress protection, such as a variety of chaperones, as well as altered expression of proteins involved in cellular structure, motility and general metabolism. This is the first report of the molecular changes at the protein level which could be involved in the cardiomyopathy of the frataxin KO mouse.

Thesis (M. Sc.(Agric.))(Food Science)--University of Pretoria, 2005. / Includes summary. Includes bibliographical references). Available on the Internet via the World Wide Web.

The debate over the "globalization" process has been influenced by the emergence of social movements who deplore this process. This research focuses on the French social movement ATTAC (Action for a Tobin Tax for the Aid of Citizens), that criticizes the problematic effects of globalization and of the new European constitutional order. This study contends that anti-globalization movements, such as ATTAC, are not only resisting what is perceived as an unjust economic system (neo-liberal globalization), but also what they perceive as cultural uniformization, or a threat to cultural identity and cultural diversity. I substantiate this claim by studying the membership of ATTAC: through qualitative research, including interviews and observations, I show the multiplicity of discourses in which members address the anti-globalization issue. This study will contribute to the research on transnational social movements, as it demonstrates the prevalence of culture and identity concerns over globalization, something that has been overlooked by previous studies of anti-globalization movements.

This thesis explores security planning policy in Canada. It provides a historical overview of the securing of cities from the threat of mass violence and demonstrates how violence affects urban populations and the form and function of cities as a result. A purposefully stampeded case study approach is used to determine the state of security planning in Canada and compare selected cities to a benchmark case of Washington D.C. This thesis contributes to the understanding of security planning within Canada in the post September 11, 2001 world and offers insight into strategies used in defense of urban areas The review of literature and discussion sections also provide a critical assessment of security planning which has occurred in the time following WWII, the IRA crisis in Britain the FLQ crisis in Quebec and the terrorist attacks in London and New York in the past decade. Research questions are answered through a case study and literature analysis approach. Results demonstrate that American responses to the threat of terrorism have motivated various governmental agencies to create policy and physical responses to respond to the threat of terrorism. This thesis concludes that Canada, in comparison to the United States and other areas has done little to secure itself against terrorist attack and more specifically that urban planning and municipalities in Canada have done little to integrate anti-terrorism security planning into their planning policy. It is argued that a lack of federal mandates, a lack of motivation and education in planning spheres as well as funding issues are contributing factors.