Blinded patient preference for morphine compared to placebo in the setting of chronic refractory breathlessness – an exploratory study

Context Patients’ preference for morphine therapy has received little attention in the setting of chronic refractory breathlessness. However, this is one important factor in considering longer term therapy. Objectives The aim of this secondary analysis is to explore blinded patient preference of morphine compared to placebo for this indication and to define any predictors of preference. Methods Data were pooled from three randomized, double-blind, crossover, placebo-controlled studies of morphine (four days each) in chronic refractory breathlessness. Blinded patient preferences were chosen at the end of each study. A multivariable regression model was used to establish patient predictors of preference. Results Sixty-five participants provided sufficient data (60 males; median age 74 years; heart failure 55%, chronic obstructive pulmonary disease 45%; median Eastern Cooperative Oncology Group performance status 2). Forty-three percent of participants preferred morphine (32% placebo and 25% no preference). Morphine preference and younger age were strongly associated: odds ratio = 0.85, 95% confidence interval 0.78, 0.93;

Clitocybe alexandri extract induces apoptosis in a lung cancer cell line: identification of phenolic acids with cytotoxic potential

Natural products which grow in adverse conditions, such as fungi, are a possible rich source of biologically active compounds with potential for drug discovery [1,2]. We have recently reported the growth inhibitory activity of extracts from Clitocybe alexandri, a wild mushroom collected from the northwest of Portugal, in human tumour cell lines (NCI-H460, MCF-7, HCT-15 and AGS) [3]. The ethanolic extract was the most potent one, particularly in NCI-H460 cells (GI50 24.8 ± 2.3 μg/ml) [3]. The aim of this work was to further study the potential of this extract as a possible source of cytotoxic compounds. In order to understand the mechanism of action of this extract in the NCI-H460 cells, the effects on cell cycle (following PI labelling) and apoptosis (following AnnexinV/PI labelling) were evaluated by flow cytometry. Furthermore, the involvement of proteins related to cellular apoptosis was investigated by Western blot. The ethanolic extract was characterized regarding its phenolic composition by HPLC-DAD/ESI. The isolated compounds were also studied regarding their growth inhibitory activity, by SBR assay. The effect of isolated or combined compounds on viable cell number was also evaluated using the Trypan blue exclusion assay. It was observed that the Clitocybe alexandri extract induced an S-phase cell cycle arrest and increased the percentage of apoptotic cells. In addition, treatment with the GI50 concentration for 48h caused an increase in the levels of wt p53, cleaved caspase-3 and cleaved PARP. The main components identified in this extract were protocatechuic acid (16.4 ± 2.2 mg/kg dw), p-hydroxybenzoic acid (8.3 ± 0.4 mg/kg) and cinnamic acid (6.4 ± 0.3 mg/kg). Cinnamic acid was found to be the most potent compound regarding cell growth inhibition. Finally, it was verified that their concomitant use provided the strongest decrease in viable cell number

A study of the antitumour potential of three Portuguese wild mushrooms

Natural matrixes such as mushrooms represent a rich source of biologically active compounds with recognized potential in drug discovery and development [1,2]. Indeed, many pre-clinical studies have been conducted in human tumour cell lines and in some cases, a number of compounds extracted from mushrooms have entered clinical trials [3]. Our previous results showed that extracts from Agaricus arvensis, Suillus collinitus and Clytocibe alexandri are promising sources of low molecular weight bioactive compounds [4]. The aim of the present work was to study the antitumour potential of the extracts and isolated compounds from three Portuguese wild mushrooms by verifying their effect on various human tumour cell lines in what concerns effect on cell growth, cell cycle profile and programmed cell death. Wild mushrooms were collected from the Northeast of Portugal and classified as Agaricus arvensis, Suillus collinitus and Clitocybe alexandri. Phenolic (methanolic and ethanolic) and polissacharidic extracts were prepared. The effect of the extracts on tumour cell growth inhibition was verified with the SRB assay and the GI50 of each extract was determined for each of the cell lines studied (NCI-H460, MCF-7, AGS and HCT-15). Our preliminary results revealed that all the extracts from Clitocybe alexandri are capable of causing cell growth inhibition and provided GI50 concentrations bellow 60µg/ml in all the cell lines tested [4]. Regarding the effect of the Agaricus arvensis extracts, they all caused an inhibition of cell growth in all cell lines, particularly the methanolic extract which revealed to be a very potent inhibitor of cell growth, especially in the MCF-7 cell line. The evaluation of the effect of the Suillus collinitus extracts will be carried out as well as cell cycle and apoptosis analyses, by flow cytometry. Finally, the isolation and characterization of compounds from these extracts will also be carried out, using HPLC-DAD or HPLC-RI. The structures of the compounds will be established by NMR spectral analysis (1H, 13C, DEPT, COSY, HSQC and HMBC).FCT and COMPETE/QREN/UE- project PTDC/AGR-ALI/110062/200

A Web Semântica e a Educação

Esse artigo discute a construção e aplicação de ontologias parasistemas educacionais baseados na Web. A Web existente hoje com umnúmero exponencial de páginas e de acessos exige uma mudança significativanos modelos de busca e entendimento dos conteúdos disponibilizados baseadoem páginas “estruturadas”, que utilizam ferramentas interativas eautomáticas, onde máquinas participam efetivamente interagindo entre si.Diversos domínios do conhecimento poderão fazer uso deste novo recurso,como sistemas educacionais. Esta “nova” web é denominada Web Semânticae utiliza ontologias para obter uma especificação formal, explícita ecompartilhada de conceitos

A Web Semântica e a Educação

Esse artigo discute a construção e aplicação de ontologias parasistemas educacionais baseados na Web. A Web existente hoje com umnúmero exponencial de páginas e de acessos exige uma mudança significativanos modelos de busca e entendimento dos conteúdos disponibilizados baseadoem páginas “estruturadas”, que utilizam ferramentas interativas eautomáticas, onde máquinas participam efetivamente interagindo entre si.Diversos domínios do conhecimento poderão fazer uso deste novo recurso,como sistemas educacionais. Esta “nova” web é denominada Web Semânticae utiliza ontologias para obter uma especificação formal, explícita ecompartilhada de conceitos

A Web Semântica e a Educação

Esse artigo discute a construção e aplicação de ontologias parasistemas educacionais baseados na Web. A Web existente hoje com umnúmero exponencial de páginas e de acessos exige uma mudança significativanos modelos de busca e entendimento dos conteúdos disponibilizados baseadoem páginas “estruturadas”, que utilizam ferramentas interativas eautomáticas, onde máquinas participam efetivamente interagindo entre si.Diversos domínios do conhecimento poderão fazer uso deste novo recurso,como sistemas educacionais. Esta “nova” web é denominada Web Semânticae utiliza ontologias para obter uma especificação formal, explícita ecompartilhada de conceitos

Salicornia ramosissima: secondary metabolites and testicular protection induced by ethanol extract

XXIII Encontro Nacional da Sociedade Portuguesa de Química. Aveiro, 12-14 de Junho 2013.The structure and spectroscopic characterization of the isolated compounds from etanol and dichloromethane extracts (PUFA omega3 ethylated, sterol and a rare wax) will be presented and discussed. Concerning the effect of ethanolic extract on mice testicular tissue under carbon tetrachloride exposure, it was clearly demonstrated that ethanol extract had a protective effect.University of Aveiro, Fundação para a Ciência e a Tecnologia (FCT) and FEDER for funding the QOPNA, CICECO, CESAM and the Portuguese National NMR Network (RNRMN)

The impact of IL-10 dynamic modulation on host immune response against visceral leishmaniasis

Leishmaniasis is a vector-borne disease caused by protozoan parasites from the genus Leishmania. The most severe form of disease is visceral leishmaniasis (VL), which is fatal if left untreated. It has been demonstrated that interleukin (IL)-10, is associated with disease progression and susceptibility. In this work, we took advantage of a transgenic mouse model that expresses high levels of IL-10 upon zinc sulfate administration (pMT-10). We addressed the role of IL-10 during the initial stages of L. donovani infection by analyzing the parasite burden in the spleen and liver of the infected pMT-10 and WT mice as well as the histopathological alterations upon IL-10 induction. Furthermore, the profile of cytokines expressed by T cells was assessed. Our results demonstrate that an increase in IL-10 production has an impact early but not later after infection. This specific temporal role for IL-10-mediated susceptibility to VL is of interest.Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013) and the Fundação para a Ciência e Tecnologia (FCT) (contracts SFRH/BD/120127/2016 to IM, PD/BDE/127830/2016 to CF, SFRH/BD/120371/2016 to AMB, IF/01147/2013 to RDO, IF/01390/2014 to ET, IF/00735/2014 to AC, SFRH/BPD/96176/2013 to CC and IF/00021/2014 to RS), and Infect-Era (project INLEISH). JE also thanks the Canada Research Chair program for financial assistanceinfo:eu-repo/semantics/publishedVersio