Characterization of Pinus spp. needles by gas chromatography and mass spectrometry: Application to plant-insect interactions

Dissertação apresentada para obtenção do Grau de Doutor em Ciências do Ambiente pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecn

Implementação de alertas de interações medicamentosas na construção de uma farmácia online

Os sistemas de apoio à decisão clinica têm-se revelado essenciais no dia-a-dia da população, nomeadamente dos profissionais e dos pacientes. Estes sistemas podem ser aplicados com diferentes objetivos: como sistemas de alerta; de prevenção de doenças; sistemas para dosagem de medicação e prescrição; entre outras. Atualmente é notório o aumento de interesse por parte da população em entender e em possuir um papel ativo nas decisões médicas. Para conseguirem fazê-lo necessitam de procurar informação. O meio mais utilizado para obter essa informação é a internet, onde a informação se encontra em grande quantidade e muito dispersa. Para além da quantidade é imprescindível encontrar informação credível, para que não haja indução da pessoa em erro. Para ajudar a solucionar estes problemas surgiram os sistemas de recomendação na saúde. Estes sistemas foram idealizados para fornecer informações às quais os utilizadores podem recorrer para tomar decisões conscientes e seguras sobre a sua saúde. Também os sistemas de alerta se têm revelado importantes na área da saúde. Estes sistemas podem ser usados em diferentes contextos e sobre diferentes assuntos, como por exemplo, a alteração do estado clínico de um paciente monitorizado, em tempo real, ou em interações medicamentosas. As interações medicamentosas podem advir da automedicação do utente ou da larga quantidade de medicação que, a partir de determinada idade, os utentes ingerem. Pode ter como causa medicação que administrem regularmente, ou até mesmo diariamente, ou doenças/estados que o utente possua que, em simultâneo com determinada medicação pode causar reações adversas. Neste trabalho foi desenvolvido um protótipo de uma farmácia online (FoAM) que fornece, ao utilizador, alertas quando há possibilidade de interações. As causas de interações consideradas foram os medicamentos que o utilizador consuma e/ou doenças/estados que possua. O objetivo é alertar para o caso das causas que o utilizador possui interagirem com o(s) medicamento(s) que este deseja adquirir. Para alcançar esse objetivo foi necessário selecionar os medicamentos a disponibilizar assim como as suas interações. Essa seleção foi baseada no prontuário terapêutico 2013 disponibilizado pelo INFARMED. Depois de recolhida e analisada a informação, foi possível compreender que informações clínicas o sistema necessita para que consiga identificar os medicamentos que não são aconselháveis adquirir. Para isso, é necessário que o utilizador forneça essas informações clínicas pessoais, necessidade que vai de encontro à posição defendida por diversos autores que apontam o uso de registos eletrónicos de saúde muito benéfico para conseguir alertas mais personalizados suprindo assim as necessidades do utilizador. É também preponderante que o utilizador perceba o porquê de determinado medicamento não ser aconselhável, por isso, ao ser emitido o alerta é também apresentada a justificação do mesmo, ou seja, é disponibilizado ao utilizador qual a causa que indicou no formulário responsável pela interação.

Gold nanoparticle to antibody conjugates for diagnosis applications: molecular interactions and immunoassay development

Thesis for the Master degree in Structural and Functional Biochemistry

Development of paper-based color test-strip for drug detection in aquatic environment: Application to oxytetracycline

The wide use of antibiotics in aquaculture has led to the emergence of resistant microbial species. It should be avoided/minimized by controlling the amount of drug employed in fish farming. For this purpose, the present work proposes test-strip papers aiming at the detection/semi-quantitative determination of organic drugs by visual comparison of color changes, in a similar analytical procedure to that of pH monitoring by universal pH paper. This is done by establishing suitable chemical changes upon cellulose, attributing the paper the ability to react with the organic drug and to produce a color change. Quantitative data is also enabled by taking a picture and applying a suitable mathematical treatment to the color coordinates given by the HSL system used by windows. As proof of concept, this approach was applied to oxytetracycline (OXY), one of the antibiotics frequently used in aquaculture. A bottom-up modification of paper was established, starting by the reaction of the glucose moieties on the paper with 3-triethoxysilylpropylamine (APTES). The so-formed amine layer allowed binding to a metal ion by coordination chemistry, while the metal ion reacted after with the drug to produce a colored compound. The most suitable metals to carry out such modification were selected by bulk studies, and the several stages of the paper modification were optimized to produce an intense color change against the concentration of the drug. The paper strips were applied to the analysis of spiked environmental water, allowing a quantitative determination for OXY concentrations as low as 30 ng/mL. In general, this work provided a simple, method to screen and discriminate tetracycline drugs, in aquaculture, being a promising tool for local, quick and cheap monitoring of drugs.

Drug trials for treatment of human angiostrongyliasis

Abdominal and cerebral angiostrongyliasis are two important infections produced by metastrongylid worms, the former occurring in Central and South America and the later in Asia and Pacific Islands. Drug treatment is a challenge since the worms and its evolving larvae live or migrate inside vessels and efficient killing of the parasites may produce more severe lesions. Larvicidal effect of certain drugs appears to be more easily accomplished but this outcome is not useful in abdominal angiostrongyliasis since clinical manifestations appear to result from sexual maturation of the worms. We review the drug trials in murine experimental models and conclude that most of them could not be considered good candidates for treatment of human infection, except for PF1022A, pyrantel and flubendazole.

Multifunctional Biosensor Based on Localized Surface Plasmon Resonance for Monitoring Small Molecule–Protein Interaction

We report an optical sensor based on localized surface plasmon resonance (LSPR) to study small-molecule protein interaction combining high sensitivity refractive index sensing for quantitative binding information and subsequent conformation-sensitive plasmon-activated circular dichroism spectroscopy. The interaction of α-amylase and a small-size molecule (PGG, pentagalloyl glucose) was log concentration-dependent from 0.5 to 154 μM. In situ tests were additionally successfully applied to the analysis of real wine samples. These studies demonstrate that LSPR sensors to monitor small molecule–protein interactions in real time and in situ, which is a great advance within technological platforms for drug discovery.

Nonlinear dynamics of the patient’s response to drug effect during general anesthesia

In today’s healthcare paradigm, optimal sedation during anesthesia plays an important role both in patient welfare and in the socio-economic context. For the closed-loop control of general anesthesia, two drugs have proven to have stable, rapid onset times: propofol and remifentanil. These drugs are related to their effect in the bispectral index, a measure of EEG signal. In this paper wavelet time–frequency analysis is used to extract useful information from the clinical signals, since they are time-varying and mark important changes in patient’s response to drug dose. Model based predictive control algorithms are employed to regulate the depth of sedation by manipulating these two drugs. The results of identification from real data and the simulation of the closed loop control performance suggest that the proposed approach can bring an improvement of 9% in overall robustness and may be suitable for clinical practice.

Recent advances into vanadyl, vanadate and decavanadate interactions with actin

Metallomics. 2012 Jan 3;4(1):16-22

Decavanadate interactions with actin: cysteine oxidation and vanadyl formation

Dalton Trans., 2009, 7985–7994

Physical therapy with drug treatment in bell palsy: a focused review

ABSTRACT: The physical therapy (PT) associated with standard drug treatment (SDT) in Bell palsy has never been investigated. Randomized controlled trials or quasirandomized controlled trials have compared facial PT (except treatments such as acupuncture and osteopathic) combined with SDT against a control group with SDT alone. Participants included those older than 15 yrs with a clinical diagnosis of Bell palsy, and the primary outcome measure was motor function recovery by the House-Brackmann scale. The methodologic quality of each study was also independently assessed by two reviewers using the PEDro scale. Four studies met the inclusion criteria. Three trials indicate that PT in association with SDT supports higher motor function recovery than SDT alone between 15 days and 1 yr of follow-up. On the other hand, one trial showed that electrical stimulation added to conventional PT with SDT did not influence treatment outcomes. The present review suggests that the current practice of Bell palsy treatment by PT associated with SDT seems to have a positive effect on grade and time recovery compared with SDT alone. However, there is very little quality evidence from randomized controlled trials, and such evidence is insufficient to decide whether combined treatment is beneficial in the management of Bell palsy.

Drug Provocation Tests to Betalactam Antibiotics: Experience in a Paediatric Setting

Background: Few studies have been performed in children withs uspected betalactam allergy.We aimed to assess the role of the drug provocation test(DPT)with betalactams in a paediatric setting and to study the association between allergy to betalactam antibiotics and other allergic diseases. Methods:We included all the patients under 15 years old who were consecutively referred to the Immunoallergy Department, Dona Estefânia Hospital,Portugal(January 2002 to April 2008)for a compatible history of allergic reaction to betalactam. All were submitted to a DPT.Children were proposed to performs kintests(ST)to betalactam antibiotics followed by DPT. If they decline ST,a DPT with the culprit drug was performed. Results: We studied 161 children,60%were boys,with a median age of 5years old at the time of the DPT.Thirty-three patients(20.5%)had an immediate reaction and 33(20.5%)a non-immediate reaction. These verity of there porte dreactions was low in most cases. Skin tests to betalactams were performed in 47 children and were positive in 8.DPT was positive inonlyone(3.4%)of the patients skin tested and in 11(13.4%)of those not skin tested. These verity of the DPT reaction was low.Asthma and food allergy were associated with a positive DPT in the later group. Conclusions: DPT seems a safe procedure even in the absence of ST in non-severe cases. This could be a practical optionin infants and pre-school children,where ST are painful and difficult to perform.Additional caution should be taken in children with asthma and food allergy.

Sirolimus-Induced Drug Fever in a Renal Transplant Patient: a Case Report

Herein we have described the case of a male renal transplant recipient who developed drug fever apparently related to sirolimus. He had been stable under an immunosuppressive regimen of tacrolimus and mycophenolate mofetil, but developed acute cellular rejection at 5 years after transplantation due to noncompliance. Renal biopsy showed marked interstitial fibrosis, and immunosuppression was switched from mycophenolate to sirolimus, maintaining low tacrolimus levels. One month later he was admitted to our hospital for investigation of intermittently high fever, fatigue, myalgias, and diarrhea. Physical examination was unremarkable and drug levels were not increased. Lactic dehydrogenase and C-reactive protein were increased. The blood cell count and chest radiographic findings were normal. After extensive cultures, he was started on broad-spectrum antibiotics. Inflammatory markers and fever worsened, but diarrhea resolved. All serologic and imaging tests excluded infection, immune-mediated diseases, and malignancy. After 12 days antibiotics were stopped as no clinical improvement was achieved. Drug fever was suspected; sirolimus was replaced by mycophenolate mofetil. Fever and other symptoms disappeared after 24 hours; inflammatory markers normalized in a few days. After 1 month the patient was in good health with stable renal function. Although infrequent, the recognition of drug fever as a potential side effect of sirolimus may avoid unnecessary invasive diagnostic procedures. Nevertheless, exclusion of other common causes of fever is essential.

Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate

Candida glabrata is considered a major opportunistic fungal pathogen of humans. The capacity of this yeast species to cause infections is dependent on the ability to grow within the human host environment and to assimilate the carbon sources available. Previous studies have suggested that C. albicans can encounter glucose-poor microenvironments during infection and that the ability to use alternative non-fermentable carbon sources, such as carboxylic acids, contributes to the virulence of this fungus. Transcriptional studies on C. glabrata cells identified a similar response, upon nutrient deprivation. In this work, we aimed at analyzing biofilm formation, antifungal drug resistance, and phagocytosis of C. glabrata cells grown in the presence of acetic acid as an alternative carbon source. C. glabrata planktonic cells grown in media containing acetic acid were more susceptible to fluconazole and were better phagocytosed and killed by macrophages than when compared to media lacking acetic acid. Growth in acetic acid also affected the ability of C. glabrata to form biofilms. The genes ADY2a, ADY2b, FPS1, FPS2, and ATO3, encoding putative carboxylate transporters, were upregulated in C. glabrata planktonic and biofilm cells in the presence of acetic acid. Phagocytosis assays with fps1 and ady2a mutant strains suggested a potential role of FPS1 and ADY2a in the phagocytosis process. These results highlight how acidic pH niches, associated with the presence of acetic acid, can impact in the treatment of C. glabrata infections, in particular in vaginal candidiasis.

Cation transporters/channels in plants: Tools for nutrient biofortification

Cation transporters/channels are key players in a wide range of physiological functions in plants, including cell signaling, osmoregulation, plant nutrition and metal tolerance. The recent identification of genes encoding some of these transport systems has allowed new studies toward further understanding of their integrated roles in plant. This review summarizes recent discoveries regarding the function and regulation of the multiple systems involved in cation transport in plant cells. The role of membrane transport in the uptake, distribution and accumulation of cations in plant tissues, cell types and subcellular compartments is described. We also discuss how the knowledge of inter- and intra-species variation in cation uptake, transport and accumulation as well as the molecular mechanisms responsible for these processes can be used to increase nutrient phytoavailability and nutrients accumulation in the edible tissues of plants. The main trends for future research in the field of biofortification are proposed.