A new and efficient synthesis of N3-cycloalkylamino-6,8-diaminopurines

[Excerpt] The purine core is a privileged scaffold in medicinal chemistry and the biological relevance of purine derivatives makes them attractive targets in the preparation of combinatorial libraries.1,2 In particular, there is a great interest in the synthesis of 8-substituted purines due to their important potential as antiviral and anticancer agents.3 Reports on 8-aminopurines are limited and general methods to obtain these purine derivatives are still needed.4 Cyclic amines and hydrazines are key structural motifs in various bioactive agents.5 Here we report a novel, efficient and inexpensive method for the synthesis of 6,8-diaminopurines 4 incorporating cycloalkylamino substituents at N3position of the purine ring. (...)

Aromatic amines sources, environmental impact and remediation

Aromatic amines are widely used industrial chemicals as their major sources in the environment include several chemical industry sectors such as oil refining, synthetic polymers, dyes, adhesives, rubbers, perfume, pharmaceuticals, pesticides and explosives. They result also from diesel exhaust, combustion of wood chips and rubber and tobacco smoke. Some types of aromatic amines are generated during cooking, special grilled meat and fish, as well. The intensive use and production of these compounds explains its occurrence in the environment such as in air, water and soil, thereby creating a potential for human exposure. Since aromatic amines are potential carcinogenic and toxic agents, they constitute an important class of environmental pollutants of enormous concern, which efficient removal is a crucial task for researchers, so several methods have been investigated and applied. In this chapter the types and general properties of aromatic amine compounds are reviewed. As aromatic amines are continuously entering the environment from various sources and have been designated as high priority pollutants, their presence in the environment must be monitored at concentration levels lower than 30 mg L1, compatible with the limits allowed by the regulations. Consequently, most relevant analytical methods to detect the aromatic amines composition in environmental matrices, and for monitoring their degradation, are essential and will be presented. Those include Spectroscopy, namely UV/visible and Fourier Transform Infrared Spectroscopy (FTIR); Chromatography, in particular Thin Layer (TLC), High Performance Liquid (HPLC) and Gas chromatography (GC); Capillary electrophoresis (CE); Mass spectrometry (MS) and combination of different methods including GC-MS, HPLC-MS and CE-MS. Choosing the best methods depend on their availability, costs, detection limit and sample concentration, which sometimes need to be concentrate or pretreated. However, combined methods may give more complete results based on the complementary information. The environmental impact, toxicity and carcinogenicity of many aromatic amines have been reported and are emphasized in this chapter too. Lately, the conventional aromatic amines degradation and the alternative biodegradation processes are highlighted. Parameters affecting biodegradation, role of different electron acceptors in aerobic and anaerobic biodegradation and kinetics are discussed. Conventional processes including extraction, adsorption onto activated carbon, chemical oxidation, advanced oxidation, electrochemical techniques and irradiation suffer from drawbacks including high costs, formation of hazardous by-products and low efficiency. Biological processes, taking advantage of the naturally processes occurring in environment, have been developed and tested, proved as an economic, energy efficient and environmentally feasible alternative. Aerobic biodegradation is one of the most promising techniques for aromatic amines remediation, but has the drawback of aromatic amines autooxidation once they are exposed to oxygen, instead of their degradation. Higher costs, especially due to power consumption for aeration, can also limit its application. Anaerobic degradation technology is the novel path for treatment of a wide variety of aromatic amines, including industrial wastewater, and will be discussed. However, some are difficult to degrade under anaerobic conditions and, thus, other electron acceptors such as nitrate, iron, sulphate, manganese and carbonate have, alternatively, been tested.

Production and extraction of polysaccharides and oligosaccharides and their use as new food additives

Polysaccharides and oligosaccharides can improve quality and enhance nutritional value of final food products due to their technological and nutritional features ranging from their capacity to improve texture to their effect as dietary fibers. For this reason, they are among the most studied ingredients in the food industry. The use of natural polysaccharides and oligosaccharides as food additives has been a reality since the food industry understood their potential technological and nutritional applications. Currently, the replacement of traditional ingredients and/or the synergy between traditional ingredients and polysaccharides and oligosaccharides are perceived as promising approaches by the food industry. Traditionally, polysaccharides have been used as thickening, emulsifying, and stabilizing agents, however, at this moment polysaccharides and oligosaccharides claim health and nutritional advantages, thus opening a new market of nutritional and functional foods. Indeed, their use as nutritional food ingredients enabled the food industry to develop a countless number of applications, e.g., fat replacers, prebiotics, dietary fiber, and antiulcer agents. Based on this, among the scientific community and food industry, in the last years many research studies and commercial products showed the possibility of using either new or already used sources (though with changed properties) of polysaccharides for the production of food additives with new and enhanced properties. The increasing interest in such products is clearly illustrated by the market figures and consumption trends. As an example, the sole market of hydrocolloids is estimated to reach $7 billion in 2018. Moreover, oligosaccharides can be found in more than 500 food products resulting in a significant daily consumption. A recent study from the Transparency Market Research on Prebiotic Ingredients Market reported that prebiotics' demand was worth $2.3 billion in 2012 and it is estimated to reach $4.5 billion in 2018, growing at a compound annual growth rate of 11.4% between 2012 and 2018. The entrance of this new generation of food additives in the market, often claiming health and nutritional benefits, imposes an impartial analysis by the legal authorities regarding the accomplishment of requirements that have been established for introducing novel ingredients/food, including new poly- and oligosaccharides. This chapter deals with the potential use of polysaccharides and oligosaccharides as food additives, as well as alternative sources of these compounds and their possible applications in food products. Moreover, the regulation process to introduce novel polysaccharides and oligosaccharides in the market as food additives and to assign them health claims is discussed.

O impacto da inclusão do dador na avaliação ergonómica dos locais de colheita de sangue

Dissertação de mestrado em Engenharia Humana

Libertação fotocontrolada de moléculas bioativas a partir de conjugados de cumarinas

Dissertação de mestrado em Química Medicinal

“It’s a complicated situation”. Harm in everyday experiences with technology. A qualitative study with school-aged children

Tese de Doutoramento em Ciências da Educação (Especialidade de Tecnologia Educativa)

Abordagem histórica e institucional da mudança em contabilidade de gestão: o caso da normalização nos hospitais públicos portugueses

A teoria institucional constituiu o enquadramento no qual foi suportada a pergunta geral desta investigação: como e porquê a Normalização da Contabilidade de Gestão (NCG) nos hospitais públicos portugueses surgiu e evoluiu? O objetivo geral foi compreender de forma profunda o surgimento e a mudança nas regras de NCG dos hospitais públicos portugueses no período histórico 1954-2011. Face ao enquadramento institucional que justificou uma investigação interpretativa, foi usado como método de investigação um estudo de caso explanatório. A evidência sobre o caso da NCG nos hospitais públicos portugueses foi recolhida em documentos e através de 58 entrevistas realizadas em 47 unidades de análise (nos serviços centrais de contabilidade do Ministério da Saúde e em 46 hospitais públicos, num total de 53 existentes). Quanto aos principais resultados obtidos, no período 1954-1974, as regras criadas pelo poder político para controlo dos gastos públicos e a contabilidade orçamental de base de caixa estiveram na génese dos primeiros conceitos de Contabilidade de Gestão (CG) para os serviços públicos de saúde portugueses. A transição de um regime ditatorial para um regime democrático (25 de Abril de 1974), a criação do Plano Oficial de Contabilidade (POC/77) e a implementação de um estado social com Serviço Nacional de Saúde (SNS) criaram a conjuntura crítica necessária para o surgimento de um Plano Oficial de Contabilidade para os Serviços de Saúde (POCSS/80) que incluiu regras de CG. A primeira edição do Plano de Contabilidade Analítica dos Hospitais (PCAH), aprovada em 1996, não foi uma construção de raiz, mas antes uma adaptação para os hospitais das regras de CG incluídas no POCSS/91 que havia revisto o POCSS/80. Após o início da implementação do PCAH, em 1998, ocorreram sequências de autorreforço institucionalizadoras destas normas, no período 1998-2011, por influência de pressões isomórficas coercivas que delinearam um processo de evolução incremental cujo resultado foi uma reprodução por adaptação, num contexto de dependência de recursos. Vários agentes internos e externos pressionaram, no período 2003-2011, através de sequências reativas para a desinstitucionalização do PCAH em resposta ao persistente fenómeno de loose coupling. Mas o PCAH só foi descontinuado nos hospitais com privatização da governação e rejeição dos anteriores sistemas de informação. Ao nível da extensão da teoria, este estudo de caso adotou o institucionalismo histórico na investigação em CG, quanto se sabe pela primeira vez, que se mostra útil na interpretação dos processos e dos resultados da criação e evolução de instituições de CG num determinado contexto histórico. Na condição de dependência de recursos, as sequências de autorreforço, via isomorfismo coercivo, tendem para uma institucionalização com fenómeno de loose coupling. Como resposta a este fenómeno, ocorrem sequências reativas no sentido da desinstitucionalização. Perante as pressões (políticas, funcionais, sociais e tecnológicas) desinstitucionalizadoras, o fator governação privada acelera o processo de desinstitucionalização, enquanto o fator governação pública impede ou abranda esse processo.

Plano de revitalização do centro histórico de Braga

Dissertação de mestrado em Políticas Comunitárias e Cooperação Territorial

Critical events in mechanically ventilated patients

Mechanical Ventilation is an artificial way to help a Patient to breathe. This procedure is used to support patients with respiratory diseases however in many cases it can provoke lung damages, Acute Respiratory Diseases or organ failure. With the goal to early detect possible patient breath problems a set of limit values was defined to some variables monitored by the ventilator (Average Ventilation Pressure, Compliance Dynamic, Flow, Peak, Plateau and Support Pressure, Positive end-expiratory pressure, Respiratory Rate) in order to create critical events. A critical event is verified when a patient has a value higher or lower than the normal range defined for a certain period of time. The values were defined after elaborate a literature review and meeting with physicians specialized in the area. This work uses data streaming and intelligent agents to process the values collected in real-time and classify them as critical or not. Real data provided by an Intensive Care Unit were used to design and test the solution. In this study it was possible to understand the importance of introduce critical events for Mechanically Ventilated Patients. In some cases a value is considered critical (can trigger an alarm) however it is a single event (instantaneous) and it has not a clinical significance for the patient. The introduction of critical events which crosses a range of values and a pre-defined duration contributes to improve the decision-making process by decreasing the number of false positives and having a better comprehension of the patient condition.

Effect of acid or alkaline catalyst and of different capping agents on the optical properties of CdS nanoparticles incorporated within a diureasil hybrid matrix

CdS nanoparticles (NPs) were synthesized using colloidal methods and incorporated within a diureasil hybrid matrix. The surface capping of the CdS NPs by 3-mercaptopropyltrimethoxysilane (MPTMS) and 3-aminopropyltrimethoxysilane (APTMS) organic ligands during the incorporation of the NPs within the hybrid matrix has been investigated. The matrix is based on poly(ethylene oxide)/poly(propylene oxide) chains grafted to a siliceous skeleton through urea bonds and was produced by sol–gel process. Both alkaline and acidic catalysis of the sol–gel reaction were used to evaluate the effect of each organic ligand on the optical properties of the CdS NPs. The hybrid materials were characterized by absorption, steady-state and time-resolved photoluminescence spectroscopy and High Resolution Transmission Electron Microscopy (HR-TEM). The preservation of the optical properties of the CdS NPs within the diureasil hybrids was dependent on the experimental conditions used. Both organic ligands (APTMS and MPTMS) demonstrated to be crucial in avoiding the increase of size distribution and clustering of the NPs within the hybrid matrix. The use of organic ligands was also shown to influence the level of interaction between the hybrid host and the CdS NPs. The CdS NPs showed large Stokes shifts and long average lifetimes, both in colloidal solution and in the xerogels, due to the origin of the PL emission in surface states. The CdS NPs capped with MPTMS have lower PL lifetimes compared to the other xerogel samples but still larger than the CdS NPs in the original colloidal solution. An increase in PL lifetimes of the NPs after their incorporation within the hybrid matrix is related to interaction between the NPs and the hybrid host matrix.

Impact of Delftia tsuruhatensis and Achromobacter xylosoxidans on Escherichia coli dual-species biofilms treated with antibiotic agents

Recently it was demonstrated that for urinary tract infections species with a lower or unproven pathogenic potential, such as Delftia tsuruhatensis and Achromobacter xylosoxidans, might interact with conventional pathogenic agents such as Escherichia coli. Here, single- and dual-species biofilms of these microorganisms were characterized in terms of microbial composition over time, the average fitness of E. coli, the spatial organization and the biofilm antimicrobial profile. The results revealed a positive impact of these species on the fitness of E. coli and a greater tolerance to the antibiotic agents. In dual-species biofilms exposed to antibiotics, E. coli was able to dominate the microbial consortia in spite of being the most sensitive strain. This is the first study demonstrating the protective effect of less common species over E. coli under adverse conditions imposed by the use of antibiotic agents.

Removal of ochratoxin A from contaminated white and red wines using oenological fining agents

Mycotoxins are toxic secondary metabolites produced by certain moulds, being ochratoxin A (OTA) one of the most relevant. Its chemical structure is a dihydro-isocoumarin connected at the 7-carboxy group to a molecule of L--phenylalanine via an amide bond. OTA contamination of wines might be a risk to consumer health, thus requiring treatments to achieve acceptable standards for human consumption [1]. According to the Regulation No. 1881/2006 of the European Commission, the maximum limit for OTA in wine is 2 µg/kg [2]. Therefore, the aim of this work was to know the effect of different fining agents on OTA removal, as well as their impact on white and red wine physicochemical characteristics. To evaluate their efficiency, 11 commercial fining agents (mineral, synthetic, animal and vegetable proteins) were used to get new approaches on OTA removal from white and red wines. Trials were performed in wines artificially supplemented (at a final concentration of 10 µg/L) with OTA. The most effective fining agent in removing OTA (80%) from white wine was a commercial formulation that contains gelatine, bentonite and activated carbon. Removals between 10-30% were obtained with potassium caseinate, yeast cell walls and pea protein. With bentonites, carboxymethylcellulose, polyvinylpolypyrrolidone and chitosan no considerable OTA removal was verified. In red wine, removals between 6-19% were obtained with egg albumin, yeast cell walls, pea protein, isinglass, gelatine, polyvinylpolypyrrolidone and chitosan. The most effective fining agents in removing OTA from red wine were an activated carbon (66%) followed again by the commercial formulation (55%), being activated carbon a well-known adsorbent of mycotoxins. These results may provide useful information for winemakers, namely for the selection of the most appropriate oenological product for OTA removal, reducing wine toxicity and simultaneously enhancing food safety and wine quality.