Betão betuminoso com betume anti-querosene Formulação, aplicação e comportamento

Mestrado em Engenharia Geotécnica e Geoambiente

Force and pressure analysis during occasional loaded gait

O documento em anexo encontra-se na versão pre-print (versão inicial enviada para o editor).

Analysis of ground reaction force and electromyographic activity of the gastrocnemius muscle during double support

O documento em anexo encontra-se na versão post-print (versão corrigida pelo editor).

Administração de anti-infecciosos orais por sonda de nutrição entérica

Com o crescente recurso à nutrição entérica surgem novos desafios, designadamente pela utilização crescente do mesmo dispositivo de acesso na administração da terapêutica farmacológica (Magnuson, Clifford, Hoskins & Bernard, 2005). Desta situação resulta uma necessidade por parte dos profissionais de saúde de conhecer o potencial de complicações e limitações associadas e este método (Williams, 2008), agravada por estudos que têm vindo a revelar técnicas inapropriadas na administração de formulações orais por sonda de nutrição (Belknap, Seiferd & Petermann, 1997) (Hanssens, Woods, Alsulaiti, Adheir, Al-Meer & Obaidan, 2006) (Seifert & Jonhston, 2005). Entre essas complicações encontramos as interacções fármaco-nutriente, que podem conduzir ao compromisso do estado nutricional do doente ou dos objectivos terapêuticos (August, et al., 2002), podendo resultar em obstrução da sonda, alteração da libertação ou biodisponibilidade do fármaco ou nutriente ou alteração da função gastrointestinal (Robin, Boulatta, Brantley, Corkins, Guenter, & et al, 2009). Considerando os riscos associados ao inadequado cumprimento da terapêutica com anti-infecciosos, o presente trabalho pretende conhecer a viabilidade de administração por sonda dos anti-infecciosos disponíveis para prescrição no Centro Hospitalar de São João, EPE (CHSJ,EPE).

Anti-pneumoscystis carinni activitiy of primaquine imidazolidin-4-ones

Pneumocystis pneumonia (PCP) is one of the most frequent causes of mortality among HIV-infected patients. Primaquine (PQ) is an antimalarial 8-aminoquinoline effective against PCP when given in combination with clindamycin. This has drawn the attention of Medicinal Chemists towards the anti-PCP activity of 8-aminoquinolines, not only confined to those exhibiting antimalarial activity [1]. It is thought that anti-PCP 8-aminoquinolines exert their anti-PCP activity by acting on the electronic transport and redox system of the P. carinii pathogen [1]. Recently, our research group has been developing imidazolidin-4-one derivatives of PQ (Scheme 1), targeting novel compounds with improved therapeutic action, namely, higher resistance to metabolic inactivation, lower toxicity and equal or higher antimalarial activity than that of the parent drug [2,3]. These imidazolidin-4-ones were seen to block the transmission of rodent malaria, caused by Plasmodium berghei on BalbC mice, to the mosquito vector Anopheles stephensi [3]. The anti-PCP activity of our PQ derivatives is now under study and preliminary in vitro assays [4] show that some of the compounds exhibit slight to moderate activity after a 72 h incubation period against P. carinii. In one case, the IC50 was comparable to that of parent PQ. Both these studies and forthcoming results from ongoing biological assays will be presented and discussed.

Development and biological evaluation of API-ILs based on anti-bacterial and anti-fungal drugs

In recent years Ionic Liquids (ILs) are being applied in life sciences. ILs are being produce with active pharmaceutical drugs (API) as they can reduce polymorphism and drug solubility problems [1] Also ILs are being applied as a drug delivery device in innovative therapies What is appealing in ILs is the ILs building up platform, the counter-ion can be carefully chosen in order to avoid undesirable side effects or to give innovative therapies in which two active ions are paired. This work shows ILs based on ampicillin (an anti-bacterial agent) and ILs based on Amphotericin B. Also we show studies that indicate that ILs based on Ampicillin could reverse resistance in some bacteria. The ILs produced in this work were synthetized by the neutralization method described in Ferraz et. al. [2] Ampicillin anion was combined with the following organic cations 1-ethyl-3-methylimidazolium, [EMIM]; 1-hydroxy-ethyl-3-methylimidazolium, [C2OHMIM]; choline, [cholin]; tetraethylammonium, [TEA]; cetylpyridinium, [C16pyr] and trihexyltetradecylphosphonium, [P6,6,6,14]. Amphotericin B was combined with [C16pyr], [cholin] and 1-metohyethyl-3-methylimidazolium, [C3OMIM]. The ILs-APIs based on ampicillin[2] were tested against sensitive Gram-negative bacteria Escherichia coli ATCC 25922 and Klebsiella pneumonia (clinical isolated), as well as on Gram positive Staphylococcus Aureus ATCC 25923, Staphylococcus epidermidis and Enterococcus faecalis. The arising resistance developed by bacteria to antibiotics is a serious public health threat and needs new and urgent measures. We study the bacterial activity of these compounds against a panel of resistant bacteria (clinical isolated strains): E. coli CTX M9, E. coli TEM CTX M9, E. coli TEM1, E. coli CTX M2, E. coli AmpC Mox2. In this work we demonstrate that is possible to produce ILs from anti-bacterial and anti-fungal compounds. We show here that the new ILs can reverse the bacteria resistance. With the careful choice of the organic cation, it is possible to create important biological and physic-chemical properties. This work also shows that the ion-pair is fundamental in ampicillin mechanism of action.

Voltammetric immunosensor for the diagnosis of celiac disease based on the quantification of anti-gliadin antibodies

Antibodies against gliadin are used to detect celiac disease (CD) in patients. An electrochemical immunosensor for the voltammetric detection of human anti-gliadin antibodies (AGA) IgA and AGA IgG in real serum samples is proposed. The transducer surface consists of screen-printed carbon electrodes modified with a carbon nanotube/gold nanoparticle hybrid system, which provides a very useful surface for the amplification of the immunological interactions. The immunosensing strategy is based on the immobilization of gliadin, the antigen for the autoantibodies of interest, onto the nanostructured surface. The antigen–antibody interaction is recorded using alkaline phosphatase labeled anti-human antibodies and a mixture of 3-indoxyl phosphate with silver ions (3-IP/Ag+) was used as the substrate. The analytical signal is based on the anodic redissolution of the enzymatically generated silver by cyclic voltammetry. The electrochemical behavior of this immunosensor was carefully evaluated assessing aspects as sensitivity, non-specific binding and matrix effects, and repeatability and reproducibility. The results were supported with a commercial ELISA test.

Task-force para revitalização dos sistemas de informação

Este trabalho descreve as actividades desenvolvidas no âmbito de uma task-force para revitalizar a função Sistemas de Informação de uma grande empresa nacional. Apresenta, em particular, o sistema de indicadores de gestão definido nesse contexto

Influência da crioterapia no tendão quadricipital na força máxima, na sensação de força produzida e na funcionalidade do membro inferior

Enquadramento: A aplicação de crioterapia utiliza-se como coadjuvante na reeducação neuromuscular e tem como objetivo atingir o mais rápido possível a capacidade funcional, devido aos seus efeitos analgésicos e anti- inflamatórios, contudo, o seu efeito negativo ao nível da propriocepção tem vindo a ser questionado. Objetivo: Verificar se a aplicação de crioterapia no tendão quadricipital tem influência na força máxima, na sensação de força produzida e na funcionalidade do membro inferior. Metodologia: Tratou-se de um estudo experimental, do tipo laboratorial e com um desenho cruzado. Quarenta sujeitos foram distribuídos inicialmente e de forma aleatória em um grupo experimental e um grupo controlo, sendo que, após uma semana os elementos que pertenceram ao grupo experimental passaram para grupo controlo e vice-versa. O grupo experimental foi submetido a um programa com gelo dinâmico durante 10 minutos, avaliando-se a força máxima, sensação de força produzida e funcionalidade do membro, enquanto grupo controlo esteve em repouso o mesmo período de tempo. Resultados: Verificaram-se que não houve diferenças estatisticamente significativas relativas a todas variáveis estudadas (p>0,05). Conclusão: O uso da crioterapia na região mio-tendinosa do quadrícipete não provoca défices significativos ao nível das respostas sensório-motoras do joelho, e que à luz destes resultados, esta pode ser utilizada antes da realização de outras técnicas terapêuticas, sem qualquer risco adicional a nível motor.

Anti-tumoral effect of the non-nucleoside DNMT inhibitor RG108 in human prostate cancer cells

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.

Pre-meal tomato (Lycopersicon esculentum) intake can have anti-obesity effects in young women?

The effect of pre-meal tomato intake in the anthropometric indices and blood levels of triglycerides, cholesterol, glucose, and uric acid of a young women population (n=35, 19.6 ± 1.3 years) was evaluated. During 4 weeks, daily, participants ingested a raw ripe tomato (~90 g) before lunch. Their anthropometric and biochemical parameters were measured repeatedly during the follow-up time. At the end of the 4 weeks, significant reductions were observed on body weight (-1.09 ± 0.12 kg on average), % fat (-1.54 ± 0.52%), fasting blood glucose (-5.29 ± 0.80 mg/dl), triglycerides (-8.31 ± 1.34 mg/dl), cholesterol (-10.17 ± 1.21 mg/ dl), and uric acid (-0.16 ± 0.04 mg/dl) of the participants. The tomato pre-meal ingestion seemed to interfere positively in body weight, fat percentage, and blood levels of glucose, triglycerides, cholesterol, and uric acid of the young adult women that participated in this study.

Anti-neoplastic properties of hydralazine in prostate cancer

Prostate cancer (PCa) is a major cause of cancer-related morbidity and mortality worldwide. Although early disease is often efficiently managed therapeutically, available options for advanced disease are mostly ineffective. Aberrant DNA methylation associated with gene-silencing of cancer-related genes is a common feature of PCa. Therefore, DNA methylation inhibitors might constitute an attractive alternative therapy. Herein, we evaluated the anti-cancer properties of hydralazine, a non-nucleoside DNA methyltransferases (DNMT) inhibitor, in PCa cell lines. In vitro assays showed that hydralazine exposure led to a significant dose and time dependent growth inhibition, increased apoptotic rate and decreased invasiveness. Furthermore, it also induced cell cycle arrest and DNA damage. These phenotypic effects were particularly prominent in DU145 cells. Following hydralazine exposure, decreased levels of DNMT1, DNMT3a and DNMT3b mRNA and DNMT1 protein were depicted. Moreover, a significant decrease in GSTP1, BCL2 and CCND2 promoter methylation levels, with concomitant transcript re-expression, was also observed. Interestingly, hydralazine restored androgen receptor expression, with upregulation of its target p21 in DU145 cell line. Protein array analysis suggested that blockage of EGF receptor signaling pathway is likely to be the main mechanism of hydralazine action in DU145 cells. Our data demonstrate that hydralazine attenuated the malignant phenotype of PCa cells, and might constitute a useful therapeutic tool.

Simulador em Realidade Virtual para Aprendizagem da Física

A forma como aprendemos depende do contexto tecnológico e sociocultural que nos rodeia, actualmente a inclusão de tecnologia recente na sala de aula não é mais considerada opcional, mas sim uma necessidade pois a forma como o aluno aprende está em constante evolução. Tendo em atenção esta necessidade, foi desenvolvido no decorrer desta tese um simulador em realidade virtual que utiliza comandos/interfaces hápticos. O objectivo deste simulador é ensinar conceitos de física de forma interactiva. Os dispositivos hápticos permitem adicionar o sentido táctil ou de toque à interacção entre homem e máquina, permitindo assim aceder a novas sensações relativas ao seu uso nomeadamente com objectivos de aprendizagem. O simulador desenvolvido designado por “Forces of Physics” aborda três tipos de forças da física: forças de atrito, forças gravitacionais e forças aerodinâmicas. Cada tipo de força corresponde a um módulo do simulador contendo uma simulação individual em que são explicados conceitos específicos dessa força num ambiente visual estimulante e com uma interacção mais realista devido à inclusão do dispositivo háptico Novint Falcon. O simulador foi apresentado a vários utilizadores bem como á comunidade científica através de apresentações em conferências. A avaliação foi realizada com recurso a um questionário com dez perguntas, cinco de sobre aprendizagem e cinco sobre a utilização, tendo sido preenchido por 14 utilizadores. O simulador obteve uma boa recepção por parte dos utilizadores, tendo vários utilizadores expressado as suas opiniões sobre estado actual do simulador, do futuro do mesmo e da respectiva validade para uso na sala de aula.

Disposable immunosensor using a simple method for oriented antibody immobilization for label-free real-time detection of an oxidative stress biomarker implicated in cancer diseases

This work proposes a novel approach for a suitable orientation of antibodies (Ab) on an immunosensing platform, applied here to the determination of 8-hydroxy-2′-deoxyguanosine (8OHdG), a biomarker of oxidative stress that has been associated to chronic diseases, such as cancer. The anti-8OHdG was bound to an amine modified gold support through its Fc region after activation of its carboxylic functions. Non-oriented approaches of Ab binding to the platform were tested in parallel, in order to show that the presented methodology favored Ab/Ag affinity and immunodetection of the antigen. The immunosensor design was evaluated by quartz-crystal microbalance with dissipation, atomic force microscopy, electrochemical impedance spectroscopy (EIS) and square-wave voltammetry. EIS was also a suitable technique to follow the analytical behavior of the device against 8OHdG. The affinity binding between 8OHdG and the antibody immobilized in the gold modified platform increased the charge transfer resistance across the electrochemical set-up. The observed behavior was linear from 0.02 to 7.0 ng/mL of 8OHdG concentrations. The interference from glucose, urea and creatinine was found negligible. An attempt of application to synthetic samples was also successfully conducted. Overall, the presented approach enabled the production of suitably oriented Abs over a gold platform by means of a much simpler process than other oriented-Ab binding approaches described in the literature, as far as we know, and was successful in terms of analytical features and sample application.

Disposable immunosensor with simple antibody orientation for label-free real-time detection of a cancer biomarker

This work proposes a novel approach for a suitable orientation of antibodies (Ab) on an immunosensing platform, applied here to the determination of 8-hydroxy-2’-deoxyguanosine (8OHdG), a biomarker of oxidative stress that has been associated to chronic diseases, such as cancer. The Anti-8OHdG was bound to an amine modified gold support through its Fc region after activation of its carboxylic functions. Non-oriented approaches of Ab binding to the platform were tested in parallel, in order to show that the presented proposal favored Ab/Ag affinity. The immunosensor design was evaluated by Quartz-Crystal microbalance with Dissipation, Atomic Force Microscopy, Electrochemical Impedance Spectroscopy (EIS) and Square-Wave Voltammetry. EIS was also a suitable technique to follow the analytical behavior of the device against 8OHdG. The affinity binding between 8OHdG and the antibody immobilized in the gold modified platform increased the charged transfer resistance across the electrochemical sep-up. The observed behavior was linear from 0.02 to 7.0 ng/mL of 8OHdG concentrations. The interference from Glucose, Urea and Creatinine was found negligible. An attempt of application to synthetic samples was also successfully conducted. Overall, the presented approach enabled the production of suitably oriented Abs over a gold platform by means of a much simpler process than other oriented-Ab binding approaches described in the literature, as far as we know, and was successful in terms of analytical features and sample application.