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.

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

Mestrado em Engenharia Geotécnica e Geoambiente

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.

Adaptive learning in agents behaviour: a framework for electricity markets simulation

Electricity markets are complex environments with very particular characteristics. A critical issue regarding these specific characteristics concerns the constant changes they are subject to. This is a result of the electricity markets’ restructuring, which was performed so that the competitiveness could be increased, but it also had exponential implications in the increase of the complexity and unpredictability in those markets scope. The constant growth in markets unpredictability resulted in an amplified need for market intervenient entities in foreseeing market behaviour. The need for understanding the market mechanisms and how the involved players’ interaction affects the outcomes of the markets, contributed to the growth of usage of simulation tools. Multi-agent based software is particularly well fitted to analyze dynamic and adaptive systems with complex interactions among its constituents, such as electricity markets. This dissertation presents ALBidS – Adaptive Learning strategic Bidding System, a multiagent system created to provide decision support to market negotiating players. This system is integrated with the MASCEM electricity market simulator, so that its advantage in supporting a market player can be tested using cases based on real markets’ data. ALBidS considers several different methodologies based on very distinct approaches, to provide alternative suggestions of which are the best actions for the supported player to perform. The approach chosen as the players’ actual action is selected by the employment of reinforcement learning algorithms, which for each different situation, simulation circumstances and context, decides which proposed action is the one with higher possibility of achieving the most success. Some of the considered approaches are supported by a mechanism that creates profiles of competitor players. These profiles are built accordingly to their observed past actions and reactions when faced with specific situations, such as success and failure. The system’s context awareness and simulation circumstances analysis, both in terms of results performance and execution time adaptation, are complementary mechanisms, which endow ALBidS with further adaptation and learning capabilities.

Oxidative behaviour of apomorphine and its metabolites

The metabolism of apomorphine is quite complex due to interactions with proteins and other tissue components that affect its pharmacokinetic profile. The electrochemical oxidation mechanism of apomorphine and of some synthesised apomorphine derivatives was studied. It was found to be related to the reaction of o-diphenol and tertiary amine groups and strongly dependent on pH.

Sorption behaviour of bifenthrin on cork

Biphentrin, a known pyrethroid, was studied, aiming its removal from aqueous solutions by granulated cork sorption. Batch experiments, either for equilibrium or for kinetics, with two granulated cork sizes were performed and results were compared with those obtained with of activated carbon sorption. Langmuir and Freundlich adsorption isotherms were obtained both showing high linear correlations. Bifenthrin desorption was evaluated for cork and results varied with the granule size of sorbent. The results obtained in this work indicate that cork wastes may be used as a cheap natural sorbent for bifenthrin or similar compounds removal from wastewaters.

Study of the voltammetric behaviour of metam and its application to an amperometric flow system

The electrochemical behaviour of the pesticide metam (MT) at a glassy carbon working electrode (GCE) and at a hanging mercury drop electrode (HMDE) was investigated. Different voltammetric techniques, including cyclic voltammetry (CV) and square wave voltammetry (SWV), were used. An anodic peak (independent of pH) at +1.46 V vs AgCl/Ag was observed in MTaqueous solution using the GCE. SWV calibration curves were plotted under optimized conditions (pH 2.5 and frequency 50 Hz), which showed a linear response for 17–29 mg L−1. Electrochemical reduction was also explored, using the HMDE. A well defined cathodic peak was recorded at −0.72 V vs AgCl/ Ag, dependent on pH. After optimizing the operating conditions (pH 10.1, frequency 150 Hz, potential deposition −0.20 V for 10 s), calibration curves was measured in the concentration range 2.5×10−1 to 1.0 mg L−1 using SWV. The electrochemical behaviour of this compound facilitated the development of a flow injection analysis (FIA) system with amperometric detection for the quantification of MT in commercial formulations and spiked water samples. An assessment of the optimal FIA conditions indicated that the best analytical results were obtained at a potential of +1.30 V, an injection volume of 207 μL and an overall flow rate of 2.4 ml min−1. Real samples were analysed via calibration curves over the concentration range 1.3×10−2 to 1.3 mg L−1. Recoveries from the real samples (spiked waters and commercial formulations) were between 97.4 and 105.5%. The precision of the proposed method was evaluated by assessing the relative standard deviation (RSD %) of ten consecutive determinations of one sample (1.0 mg L−1), and the value obtained was 1.5%.

Tensile behaviour of a structural adhesive at high temperatures by the extended finite element method

Component joining is typically performed by welding, fastening, or adhesive-bonding. For bonded aerospace applications, adhesives must withstand high-temperatures (200°C or above, depending on the application), which implies their mechanical characterization under identical conditions. The extended finite element method (XFEM) is an enhancement of the finite element method (FEM) that can be used for the strength prediction of bonded structures. This work proposes and validates damage laws for a thin layer of an epoxy adhesive at room temperature (RT), 100, 150, and 200°C using the XFEM. The fracture toughness (G Ic ) and maximum load ( ); in pure tensile loading were defined by testing double-cantilever beam (DCB) and bulk tensile specimens, respectively, which permitted building the damage laws for each temperature. The bulk test results revealed that decreased gradually with the temperature. On the other hand, the value of G Ic of the adhesive, extracted from the DCB data, was shown to be relatively insensitive to temperature up to the glass transition temperature (T g ), while above T g (at 200°C) a great reduction took place. The output of the DCB numerical simulations for the various temperatures showed a good agreement with the experimental results, which validated the obtained data for strength prediction of bonded joints in tension. By the obtained results, the XFEM proved to be an alternative for the accurate strength prediction of bonded structures.

Characterizing the timing behaviour of power-line communication by means of simulation

Although power-line communication (PLC) is not a new technology, its use to support communication with timing requirements is still the focus of ongoing research. Recently, a new infrastructure was presented, intended for communication using power lines from a central location to geographically dispersed nodes using inexpensive devices. This new infrastructure uses a two-level hierarchical power-line system, together with an IP-based network. Within this infrastructure, in order to provide end-toend communication through the two levels of the powerline system, it is necessary to fully understand the behaviour of the underlying network layers. The masterslave behaviour of the PLC MAC, together with the inherent dynamic topology of power-line networks are important issues that must be fully characterised. Therefore, in this paper we present a simulation model which is being used to study and characterise the behaviour of power-line communication.

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.

Dynamical behaviour of multi-particle large-scale systems

Collective behaviours can be observed in both natural and man-made systems composed of a large number of elemental subsystems. Typically, each elemental subsystem has its own dynamics but, whenever interaction between individuals occurs, the individual behaviours tend to be relaxed, and collective behaviours emerge. In this paper, the collective behaviour of a large-scale system composed of several coupled elemental particles is analysed. The dynamics of the particles are governed by the same type of equations but having different parameter values and initial conditions. Coupling between particles is based on statistical feedback, which means that each particle is affected by the average behaviour of its neighbours. It is shown that the global system may unveil several types of collective behaviours, corresponding to partial synchronisation, characterised by the existence of several clusters of synchronised subsystems, and global synchronisation between particles, where all the elemental particles synchronise completely.

Real-time communications over cluster-tree sensor networks with mobile sink behaviour

Modelling the fundamental performance limits of wireless sensor networks (WSNs) is of paramount importance to understand the behaviour of WSN under worst case conditions and to make the appropriate design choices. In that direction, this paper contributes with a methodology for modelling cluster tree WSNs with a mobile sink. We propose closed form recurrent expressions for computing the worst case end to end delays, buffering and bandwidth requirements across any source-destination path in the cluster tree assuming error free channel. We show how to apply our theoretical results to the specific case of IEEE 802.15.4/ZigBee WSNs. Finally, we demonstrate the validity and analyze the accuracy of our methodology through a comprehensive experimental study, therefore validating the theoretical results through experimentation.

Using a cohesive damage model to predict the tensile behaviour of CFRP single-strap repairs

This work addresses both experimental and numerical analyses regarding the tensile behaviour of CFRP single-strap repairs. Two fundamental geometrical parameters were studied: overlap length and patch thickness. The numerical model used ABAQUS® software and a developed cohesive mixed-mode damage model adequate for ductile adhesives, and implemented within interface finite elements. Stress analyses and strength predictions were carried out. Experimental and numerical comparisons were performed on failure modes, failure load and equivalent stiffness of the repair. Good correlation was found between experimental and numerical results, showing that the proposed model can be successfully applied to bonded joints or repairs.