986 resultados para Mechanisms action
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Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Engenharia Electrotécnica e de Computadores
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The very high antiproliferative activity of [Co(Cl)(H2O)(phendione)(2)][BF4] (phendione is 1,10-phenanthroline-5,6-dione) against three human tumor cell lines (half-maximal inhibitory concentration below 1 mu M) and its slight selectivity for the colorectal tumor cell line compared with healthy human fibroblasts led us to explore the mechanisms of action underlying this promising antitumor potential. As previously shown by our group, this complex induces cell cycle arrest in S phase and subsequent cell death by apoptosis and it also reduces the expression of proteins typically upregulated in tumors. In the present work, we demonstrate that [Co(Cl)(phendione)(2)(H2O)][BF4] (1) does not reduce the viability of nontumorigenic breast epithelial cells by more than 85 % at 1 mu M, (2) promotes the upregulation of proapoptotic Bax and cell-cycle-related p21, and (3) induces release of lactate dehydrogenase, which is partially reversed by ursodeoxycholic acid. DNA interaction studies were performed to uncover the genotoxicity of the complex and demonstrate that even though it displays K (b) (+/- A standard error of the mean) of (3.48 +/- A 0.03) x 10(5) M-1 and is able to produce double-strand breaks in a concentration-dependent manner, it does not exert any clastogenic effect ex vivo, ruling out DNA as a major cellular target for the complex. Steady-state and time-resolved fluorescence spectroscopy studies are indicative of a strong and specific interaction of the complex with human serum albumin, involving one binding site, at a distance of approximately 1.5 nm for the Trp214 indole side chain with log K (b) similar to 4.7, thus suggesting that this complex can be efficiently transported by albumin in the blood plasma.
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A melhoria progressiva na prestação de cuidados de saúde que se verifica nos dias de hoje, deve-se maioritariamente ao desenvolvimento de novas tecnologias médicas, que se traduzem na criação de inovadores dispositivos médicos, cujo fim é auxiliar no diagnóstico, prevenção e tratamento de doenças, melhorando assim as condições de trabalho e os cuidados oferecidos aos pacientes. No entanto estas melhorias apenas são vantajosas quando as novas tecnologias são utilizadas de forma segura, o que leva a uma preocupação crescente com a segurança dos profissionais de saúde e dos pacientes em ambiente hospitalar. Como forma de reduzir e controlar os riscos existentes, as unidades de saúde introduziram mecanismos de gestão que permitem o conhecimento das fontes de risco e respetivos mecanismos de ação. A presente dissertação de mestrado apresenta uma proposta de modelo de Manual de Procedimentos para Gestão de Risco de Dispositivos Médicos, aplicável a todos os dispositivos médicos existentes nas Unidades de Saúde. Para a criação deste manual, foram utilizados por meio de adaptação, as etapas da gestão de risco definidas na Norma ISO 14971:2007 em conjunto com o método de gestão de risco utilizado pela Unidade Local de Saúde de Matosinhos O desenvolvimento deste manual de procedimentos permitirá a esta unidade de saúde, a aquisição e fornecimento de informações úteis na tomada de decisão sobre os procedimentos de controlo de risco de dispositivos médicos, com o objetivo de manter o risco destes dispositivos dentro dos níveis previamente estabelecidos e auxiliar a tomada de decisão de programas de manutenção preventiva e de aquisição de dispositivos médicos.
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A random, double-blind, parallel group clinical trial program was carried out to compare praziquantel, a recently developed anti-helmintic drug, and oxamniquine, an already established agent for treating mansoni schistosomiasis. Both drugs were administered orally as a single dose, on the average, praziquantel 55 mg/kg and oxamniquine 16 mg/kg BWT. The diagnosis and the parasitological follow-up lasting for a minimum of six months, were based on stool examinations according to Kato/Katz technique. A patient was considered cured if all results were negative and if he had performed at least three post-treatment controls, each one comprising three stool examinations. The finding of a single S. mansoni egg in any stool examination indicated, a therapeutical failure. A total of 267, cases were treated with praziquantel and 272 with oxamniquine. The two groups were homogeneous in regard to patients, age, clinical form of the disease, risk of reinfection and worm burden, relevant factors in the therapeutical response. The incidence and severity of untoward, effects were similar in both groups but abdominal distress and diarrhoea were more frequently reported under praziquantel and dizzines under oxamniquine (p < 0.05). In the former group a marked urticariform reaction was observed whereas in the latter one patient presented convulsion. The laboratory work-up. failed to disclose any significant alteration although the AST, ALT and y-GT mean values revealed a tendence to increase on the 7th day after oxamniquine intake. The overall parasitological cure rates were 75.5% (139/ 184) with praziquantel and 69.8% (134/192) with oxamniquine (p > 0.05). Amongst the noncured aptients a reduction of 88.6% and 74.6% in the mean number of eggs/g of feces Was seen following the treatment with praziquantel and oxamniquine, respectively (p < 0.05). In conclusion, in spite of their different chemical, pharmacological and toxicological profiles as well as mechanisms-of-action, inclusively praziquantel already had proved to be 100% active against S. mansoni strains resistant to oxamniquine, both drugs showed comparable tolerance and therapeutical efficacy.
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A double-blind clinical trial involving 120 patients with chronic schistosomiasis was carried out to compare the tolerability and efficacy of praziquantel and oxamniquine. The patients were randomly allocated into two groups. One was treated with praziquantel, 55 mg/kg of body weight CBWT), and the other one with oxamniquine, 15mg/kg bwt, administered in a single oral dose. The diagnosis and the parasitological follow-up was based on stool examinations by quantitative Kato-Katz method and on rectal biopsies. Side-effects mainly dizziness, sleepness, abdominal distress, headache, nausea and diarrhea were observed in 87% of the cases. Their incidence, intensity and duration were similar for both drugs but abdominal pain was significantly more frequent after praziquantel intake and severe dizziness was more commonly reported after oxamniquine. A significant increase of alanine-aminotransferase and y-glutamyltransferase was found with the latter drug and of total bilirubin with the former one. A total of 48 patients treated with praziquantel and 46 with oxamniquine completed with negative findings the required three post-treatment parasitological controls three slides of each stool sample on the first, third and sixth month. The achieved cure rates were 79.2% and 84.8%, respectively, a difference without statistical significance. The non-cured cases showed a mean reduction in the number of eggs per gram of feces of 93.5% after praziquantel and of 84.1% after oxamniquine. This diference also was not significant. Five patients retreated with praziquantel were cured but only one out of three treated a second time with oxamniquine. These findings show that both drugs despite their different chemical structures, pharmacological properties and mechanisms-of-action induce similar side-effects as well as a comparable therapeutical efficacy, in agreement with the results reported from analogous investigations.
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Coral snakes, the New World Elapidae, are included in the genera Micniroides and Micrurus. The genus Mlcrurus comprises nearly all coral snake species and those which are responsible for human snake-bite accidents. The following generalizations concerning the effects induced by their venoms, and their venom-properties can be made. Coral snake venoms are neurotoxic, producing loss of muscle strenght and death by respiratory paralysis. Local edema and necrosis are not induced nor blood coagulation or hemorrhages. Proteolysis activity is absent or of very low grade. They display phospholipase A2 activity. Nephrotoxic effects are not evoked. The main toxins from elapid venoms are postsynaptic and presynaptic neurotoxins and cardiotoxins. Phospholipases A2 endowed with myonecrotic or cardiotoxin-like properties are important toxic components from some elapid venoms. The mode of action of Micrurus frontalis, M. lemniscatus, M. corallinus and M. fulvius venoms has been investigated in isolated muscle preparations and is here discussed. It is shown that while M. frontalis and M. lemniscatus venoms must contain only neurotoxins that act at the cholinergic end-plate receptor (postsynaptic neurotoxins), M. corallinus venom also inhibits evoked acetylcholine release by the motor nerve endings (presynaptic neurotoxin-like effect) and M. fulvius induces muscle fiber membrane depolarization (cardiotoxin-like effect). The effects produced by M. corallinus and M. fulvius venoms in vivo in dogs and M. frontalis venom in dogs and monkeys are also reported.
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Engineering education practices have evolved not only due to the natural changes in the contents of the curricula and skills but also, and more recently, due to the requirements imposed by the Bologna revision process. In addition, industry is becoming more demanding, as society is becoming more and more aware of the global needs and consequences of industrial practices. Under this scope, higher education needs not only to follow but also to lead these trends. Therefore, the School of Engineering of the Polytechnic Institute of Porto (ISEP), a Global Reporting Initiative (GRI) training partner in Portugal, prepared and presented its Sustainability Action Plan (PASUS), with the main objective of creating a new kind of engineers, with Sustainable Development at the core of their graduation and MsC degrees. In this paper, the main strategies and activities of the referred plan along with the strategic approach, which guided its development and implementation, will be presented in detail. Additionally, a reflection about the above mentioned bridge between concept and application will be established and justified, in the framework of the action plan. Although in most of the situations, there was no prior discussion or specific request, many of the graduation and post-graduation programmes offered by ISEP already include courses that attend to PASUS philosophy. As a consequence, the number of Master thesis, Graduation projects and R&D projects that address sustainability problems has grown substantially, a proof that for ISEP community, sustainability really matters!
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Dissertação de Mestrado em Engenharia Informática
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Porto Polytechnical Engineering School (ISEP), a Global Reporting Initiative training partner in Portugal, has just presented its Sustainable Development Action Plan (PASUS), which main objective is the formation of a new kind of engineers, with a Sustainable Development (SD) philosophy in the core of their academic curricula courses.
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Portuguese northern forests are often and severely affected by wildfires during the summer season. Some preventive actions, such as prescribed (or controlled) burnings and clear-cut logging, are often used as a measure to reduce the occurrences of wildfires. In the particular case of Serra da Cabreira forest, due to extremely difficulties in operational field work, the prescribed (or controlled) burning technique is the the most common preventive action used to reduce the existing fuel load amount. This paper focuses on a Fuzzy Boolean Nets analysis of the changes in some forest soil properties, namely pH, moisture and organic matter content, after a controlled fire, and on the difficulties found during the sampling process and how they were overcome. The monitoring process was conducted during a three-month period in Anjos, Vieira do Minho, Portugal, an area located in a contact zone between a two-mica coarse-grained porphyritic granite and a biotite with plagioclase granite. The sampling sites were located in a spot dominated by quartzphyllite with quartz veins whose bedrock is partially altered and covered by slightly thick humus, which maintains low undergrowth vegetation.
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Controlled fires in forest areas are frequently used in most Mediterranean countries as a preventive technique to avoid severe wildfires in summer season. In Portugal, this forest management method of fuel mass availability is also used and has shown to be beneficial as annual statistical reports confirm that the decrease of wildfires occurrence have a direct relationship with the controlled fire practice. However prescribed fire can have serious side effects in some forest soil properties. This work shows the changes that occurred in some forest soils properties after a prescribed fire action. The experiments were carried out in soil cover over a natural site of Andaluzitic schist, in Gramelas, Caminha, Portugal, that had not been burn for four years. The composed soil samples were collected from five plots at three different layers (0-3cm, 3-6cm and 6-18cm) during a three-year monitoring period after the prescribed burning. Principal Component Analysis was used to reach the presented conclusions.
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Some of the main challenges in Incorporating Sustainable Development practices into Engineering Education reside in establishing the bridge between concept and application. In particular the relation between value creation and the knowledge economy, innovation and entrepreneurship, as the main vehicles to a relevant application of the sustainable development concept, is not yet part of the majority of the engineering curricula in schools. Porto Polytechnical Engineering School (ISEP), a Global Reporting Initiative training partner in Portugal, as just presented its Sustainable Development Action Plan, with the main objective of creating a new kind of engineers, with Sustainable Development at the core of their degrees. The plan has several issues like publish an annual sustainability report, sustainable buildings, minimization of energy consumption and water policy, waste management, sustainable mobility, green procurement, EMAS certification, research and postgraduate activity and promotion of lectures and seminars in Sustainable Development.
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Trabalho de Projeto submetido à Escola Superior de Teatro e Cinema para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Teatro - especialização em Encenação
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The fungicidal action of sodium hypochlorite (0.3, 1, 2.5, 5 and 10%); formaldehyde (2, 5, and 10%); and ethyl alcohol (70%) on yeast forms of Paracoccidioides brasiliensis Pb 18 and a newly-isolated Goiana strain was described. Contact between the fungus and the disinfectants was maintained for 1, 2, 24, 48 and 72 hours at room temperature. Viability was evaluated by the fluorescein diacetate-ethidium bromide treatment, culture in solid and liquid media (36ºC and 26ºC); yeast to mycelial germination at room temperature; and radiometric study of metabolic activity. All concentrations of disinfectants were found to be effective in inactivating Pb 18 and Goiana strains, except for the 1-hour contact with 2% formaldehyde, in which fluorescein diacetate-ethidium bromide treatment was found to reveal 40 and 27% of viable cells, respectively. The yeast to mycelial germination method was considered to reveal faster and similar results as compared to culture in solid and liquid media.
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Hydraulic systems are dynamically susceptible in the presence of entrapped air pockets, leading to amplified transient reactions. In order to model the dynamic action of an entrapped air pocket in a confined system, a heuristic mathematical formulation based on a conceptual analogy to a mechanical spring-damper system is proposed. The formulation is based on the polytropic relationship of an ideal gas and includes an additional term, which encompasses the combined damping effects associated with the thermodynamic deviations from the theoretical transformation, as well as those arising from the transient vorticity developed in both fluid domains (air and water). These effects represent the key factors that account for flow energy dissipation and pressure damping. Model validation was completed via numerical simulation of experimental measurements.