30 resultados para THERAPEUTIC STRATEGIES

em Instituto Politécnico do Porto, Portugal


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With the increase of bacterial resistance a large number of therapeutic strategies have been used to fight different kind of infections. In recent years ionic liquids (ILs) have been increasing the popularity and the number of applications. First ionic liquids were used mainly as solvent in organic synthesis, but now they are used in analytical chemistry, separation chemistry and material science among others. Additional to significant developments in their chemical properties and applications, ionic liquids are now bringing unexpected opportunities at the interface of chemistry with the life sciences Ionic liquids (ILs) are currently defined as salts that are composed solely of cations and anions which melt below 100ºC. Our goal in this work is to explore the dual activity of the ionic liquids, due to the presence of two different ions, an ion with bacterial activity as a beta-lactam antibiotic and different kinds of cations. In this work the anions of ILs and salts were derived from three different antibiotics: ampicillin, penicillin and amoxicillin. The cations were derived from substituted ammonium, phosphonium pyridinium and methylimidazolium salts, such as: tetraethyl ammonium, trihexiltetradecilphosphonium, cetylpyridinium, choline (an essential nutrient), 1-ethyl-3-methylimidazolium, and 1-ethanol-3-methyl imidazolium structures. Commercial ammonium and phosponium halogen salts were first transformed into hydroxides. on ionic exchange column (Amberlite IRA-400) in methanol. The prepared hydroxides were then neutralized with beta-lactam antibiotics. After crystallization we obtained pure ILs and salts containing beta-lactam antibiotics. This work presents a novel method for preparation of new salts of antibiotics with low melting point and their characterization.

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Background: Current therapeutic strategies for advanced prostate cancer (PCa) are largely ineffective. Because aberrant DNA methylation associated with inappropriate gene-silencing is a common feature of PCa, DNA methylation inhibitors might constitute an alternative therapy. In this study we aimed to evaluate the anti-cancer properties of RG108, a novel non-nucleoside inhibitor of DNA methyltransferases (DNMT), in PCa cell lines. Methods: The anti-tumoral impact of RG108 in LNCaP, 22Rv1, DU145 and PC-3 cell lines was assessed through standard cell viability, apoptosis and cell cycle assays. Likewise, DNMT activity, DNMT1 expression and global levels of DNA methylation were evaluated in the same cell lines. The effectiveness of DNA demethylation was further assessed through the determination of promoter methylation and transcript levels of GSTP1, APC and RAR-β2, by quantitative methylation-specific PCR and RT-PCR, respectively. Results: RG108 led to a significant dose and time dependent growth inhibition and apoptosis induction in LNCaP, 22Rv1 and DU145. LNCaP and 22Rv1 also displayed decreased DNMT activity, DNMT1 expression and global DNA methylation. Interestingly, chronic treatment with RG108 significantly decreased GSTP1, APC and RAR-β2 promoter hypermethylation levels, although mRNA re-expression was only attained GSTP1 and APC. Conclusions: RG108 is an effective tumor growth suppressor in most PCa cell lines tested. This effect is likely mediated by reversion of aberrant DNA methylation affecting cancer related-genes epigenetically silenced in PCa. However, additional mechanism might underlie the anti-tumor effects of RG108. In vivo studies are now mandatory to confirm these promising results and evaluate the potential of this compound for PCa therapy.

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Background Iron is vital for almost all living organisms by participating in a wide range of metabolic processes. However, iron concentration in body tissues must be tightly regulated since excessive iron may lead to microbial infections or cause tissue damage. Disorders of iron metabolism are among the most common human diseases and cover several conditions with varied clinical manifestations. Methods An extensive literature review on the basic aspects of iron metabolism was performed, and the most recent findings on this field were highlighted as well. Results New insights on iron metabolism have shed light into its real complexity, and its role in both healthy and pathological states has been recognized. Important discoveries about the iron regulatory machine and imbalances in its regulation have been made, which may lead in a near future to the development of new therapeutic strategies against iron disorders. Besides, the toxicity of free iron and its association with several pathologies has been addressed, although it requires further investigations. Conclusion This review will provide students in the fields of biochemistry and health sciences a brief and clear overview of iron physiology and toxicity, as well as imbalances in the iron homeostasis and associated pathological conditions.

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1st ASPIC International Congress

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Supported by U. Porto/Santander Totta (IJUP) (PP-IJUP2011-320)

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Int’l J. of Information and Communication Technology Education, 3(2), 1-14, April-June 2007

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Objectivo: Pretendeu-se avaliar as modificações no comportamento neuro-motor a nível da funcionalidade do membro superior predominantemente afectado e a sua influência no ciclo da marcha de dois indivíduos com Acidente Vascular Cerebral, face a um programa de intervenção em fisioterapia, segundo uma abordagem baseada no Conceito de Bobath. Foi também objectivo averiguar o impacto qualitativo nos componentes e estados de saúde. Metodologia: A avaliação foi realizada em dois indivíduos com sequelas de Acidente Vascular Cerebral, antes e após o plano de intervenção segundo o Conceito de Bobath, através do registo observacional, da Classificação Internacional de Funcionalidade, Incapacidade e Saúde, da Performance-Oriented Mobility Assessment POMA I, da Time Up and Go Test, da Motor Assessement Scale e da Motor Evaluation Scale for Upper Extremity in Patients. Resultados: Obteve-se um incremento da funcionalidade do membro superior predominantemente afectado, com uma atribuição na Classificação Internacional de Funcionalidade, Incapacidade e Saúde de qualificadores correspondentes a dificuldade ligeira a moderada ao nível da mobilidade e dos auto cuidado após o plano de intervenção, repercutindo-se assim numa diminuição da restrição na participação e limitação da actividade. Houve um aumento de score total em todos os instrumentos e escalas de medidas de avaliação utilizadas, tendo os indivíduos alcançado uma maior funcionalidade do membro superior e um padrão de marcha mais eficiente, com uma menor necessidade de recorrer a estratégias compensatórias de movimento. Conclusão: O plano de intervenção, baseado numa abordagem segundo o Conceito de Bobath, essencialmente dirigido para a obtenção de ganhos funcionais ao nível do membro superior predominantemente afectado nos indivíduos em estudo, parece ter contribuído para induzir mudanças no comportamento neuro-motor, verificando-se uma influência no ciclo de marcha ao nível da qualidade e eficiência do movimento.

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This paper presents a Multi-Agent Market simulator designed for developing new agent market strategies based on a complete understanding of buyer and seller behaviors, preference models and pricing algorithms, considering user risk preferences and game theory for scenario analysis. This tool studies negotiations based on different market mechanisms and, time and behavior dependent strategies. The results of the negotiations between agents are analyzed by data mining algorithms in order to extract rules that give agents feedback to improve their strategies. The system also includes agents that are capable of improving their performance with their own experience, by adapting to the market conditions, and capable of considering other agent reactions.

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This paper presents MASCEM - a multi-agent based electricity market simulator. MASCEM uses game theory, machine learning techniques, scenario analysis and optimisation techniques to model market agents and to provide them with decision-support. This paper mainly focus on the MASCEM ability to provide the means to model and simulate Virtual Power Producers (VPP). VPPs are represented as a coalition of agents, with specific characteristics and goals. The paper detail some of the most important aspects considered in VPP formation and in the aggregation of new producers and includes a case study.

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Distributed energy resources will provide a significant amount of the electricity generation and will be a normal profitable business. In the new decentralized grid, customers will be among the many decentralized players and may even help to co-produce the required energy services such as demand-side management and load shedding. So, they will gain the opportunity to be more active market players. The aggregation of DG plants gives place to a new concept: the Virtual Power Producer (VPP). VPPs can reinforce the importance of these generation technologies making them valuable in electricity markets. In this paper we propose the improvement of MASCEM, a multi-agent simulation tool to study negotiations in electricity spot markets based on different market mechanisms and behavior strategies, in order to take account of decentralized players such as VPP.

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Introduction: The present paper deals with the issue of the increasing usage of corporation mergers and acquisitions strategies within pharmaceutical industry environment. The aim is to identify the triggers of such business phenomenon and the immediate impact on the financial outcome of two powerful biopharmaceutical corporations: Pfizer and GlaxoSmithKline, which have been sampled due to their successful approach of the tactics in question. Materials and Methods: In order to create an overview of the development steps through mergers and acquisitions, the historical data of the two corporations has been consulted, from their official websites. The most relevant events were then associated with adequate information from the financial reports and statements of the two corporations indulged by web-based financial data providers. Results and Discussions: In the past few decades Pfizer and GlaxoSmithKline have purchased or merged with various companies in order to monopolize new markets, diversify products and services portfolios, survive and surpass competitors. The consequences proved to be positive although this approach implies certain capital availability. Conclusions: Results reveal the fact that, as far as the two sampled companies are concerned, acquisitions and mergers are reactions at the pressure of the highly competitive environment. Moreover, the continuous diversification of the market’s needs is also a consistent motive. However, the prevalence and the eminence of mergers and acquisition strategies are conditioned by the tender offer, the announcer’s caliber, research and development status and further other factors determined by the internal and external actors of the market.

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In the present paper we will consider strategies of innovation, risk and proactivity as entre/ intrapreneurship strategies. This study was done in a Portuguese and in a Polish region. In Portugal the region was Vale do Sousa, located in the northern Portugal. The Polish region was Lublin Voivodeship and it is situated in the south-eastern part of the country. The study focused on Industrial and Construction sectors. In order to get a valid sample, a group of 251 firms were analysed in Portugal, and 215 in Poland. However, the minimum sample size in Poland should be 323. Since this is a work in progress, we are aiming for this number of questionnaires. Each strategy was analysed individually for both regions and the results pointed to a lack of culture of entrepreneurship in firms’ management. Only Proactivity presented a positive result in firms’ management. Polish firms tend to be more innovative and more risk takers, while in proactivity Portuguese ones present a slightly higher result. Combining the strategy results, it was possible to identify that 61.2% of Portuguese firms present a low level of entrepreneurship, while 60% of Polish firms present a moderate level. Considering intrapreneurship good levels, while Portugal account for 5.2% this figure is 19.1% in Poland.

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The goal of the present paper is to analyse the classic entrepreneurship strategies (Innovation, Risk and Proactivity) in small and medium-sized businesses. However as presented in the title, the study will go further by comparing the results of those strategies in familiar and nonfamiliar businesses. This study was carried on in construction and industry sectors, in the region of Vale do Sousa, in the north of Portugal. In order to classify businesses as familiar or non-familiar types two criterion were adopted: (1) Management Control, (2) Family Employability. On the opposite to some studies that present a larger percentage of familiar businesses in national and European entrepreneurial fabric, the criterion used leaded to a larger number of non-familiar businesses (53%). The results showed that in general SMEs in this region are not following entrepreneurship strategies. Analysing the entire sample without a separation of businesses by nature (familiar/non-familiar) only proactivity showed to be more present in the managerial decisions. There is a lack of innovation and risk culture. Comparing the groups only on proactivity tests was possible to verify some differences. It was concluded that non-familiar businesses are more proactive than familiar ones. Between those groups there are no statistical differences on the means of the variables innovation and risk. At the same time some tests were conducted to test the differences on the variable entrepreneurship. The results were similar to innovation and risk strategies: There are no significant differences on entrepreneurship between these groups of businesses.

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Mestrado em Engenharia Informática

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We study a fractional model for malaria transmission under control strategies.Weconsider the integer order model proposed by Chiyaka et al. (2008) in [15] and modify it to become a fractional order model. We study numerically the model for variation of the values of the fractional derivative and of the parameter that models personal protection, b. From observation of the figures we conclude that as b is increased from 0 to 1 there is a corresponding decrease in the number of infectious humans and infectious mosquitoes, for all values of α. This means that this result is invariant for variation of fractional derivative, in the values tested. These results are in agreement with those obtained in Chiyaka et al.(2008) [15] for α = 1.0 and suggest that our fractional model is epidemiologically wellposed.