Inhibition by ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and channeling to adenosine A1 receptors

© 1998 Society for NeuroscienceATP analogs substituted in the γ-phosphorus (ATPγS, β, γ-imido-ATP, and β, γ-methylene-ATP) were used to probe the involvement of P2 receptors in the modulation of synaptic transmission in the hippocampus, because their extracellular catabolism was virtually not detected in CA1 slices. ATP and γ-substituted analogs were equipotent to inhibit synaptic transmission in CA1 pyramid synapses (IC50 of 17–22 μM). The inhibitory effect of ATP and γ-phosphorus-substituted ATP analogs (30 μM) was not modified by the P2 receptor antagonist suramin (100 μM), was inhibited by 42–49% by the ecto-5’- nucleotidase inhibitor and α, β-methylene ADP (100 μM), was inhibited by 74–85% by 2 U/ml adenosine deaminase (which converts adenosine into its inactive metabolite-inosine), and was nearly prevented by the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (10 nM). Stronger support for the involvement of extracellular adenosine formation as a main requirement for the inhibitory effect of ATP and γ-substituted ATP analogs was the observation that an inhibitor of adenosine uptake, dipyridamole (20 μM), potentiated by 92–124% the inhibitory effect of ATP and γ-substituted ATP analogs (10 μM), a potentiation similar to that obtained for 10 μM adenosine (113%). Thus, the present results indicate that inhibition by extracellular ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ectonucleotidases and channeling of the generated adenosine to adenosine A1 receptors.This work was supported by Junta Nacional de Investigação Cientifica e Tecnológica, Praxis XXI, Gulbenkian Foundation, and European Union (BIOMED 2 programme

Oral magnesium supplementation improves endothelial function and attenuates subclinical atherosclerosis in thiazide-treated hypertensive women

Background: Epidemiological studies demonstrate an inverse association between serum magnesium and incidence of cardiovascular disease. Diuretics commonly cause hypomagneseamia. Method: We evaluated effects of magnesium supplementation on blood pressure (BP) and vascular function in thiazide-treated hypertensive women in a randomized, double-blind, clinical trial. Hypertensive women (40–65 years) on hydrochlorothiazide and mean 24-h BP at least 130/80 mmHg were divided into placebo and supplementation (magnesium chelate 600 mg/day) groups. Patients were evaluated for nutritional and biochemical parameters, office and ambulatory blood pressure monitoring, brachial flow-mediated dilatation (FMD), peripheral arterial tonometry, assessment of carotid intima–media thickness, central hemodynamic parameters and pulse wave velocity at inclusion and after 6-month follow-up. Results: The magnesium group had a significant reduction in SBP (144 ± 17 vs. 134 ± 14 mmHg, P = 0.036) and DBP (88 ± 9 vs. 81 ± 8 mmHg, P = 0.005) at 6 months, without effect on plasma glucose, lipids, or arterial stiffness parameters. The placebo group showed a significant increase in carotid intima-media thickness (0.78 ± 0.13 vs. 0.89 ± 0.14 mm, P = 0.033) without change in the magnesium group (0.79 ± 0.16 vs. 0.79 ± 0.19 mm, P = 0.716) after 6 months. The magnesium group demonstrated a significant increase in variation of FMD vs. the placebo group (+3.7 ± 2.1 vs. 2.4 ± 1.2%, P = 0.015). There was a significant correlation between the intracellular magnesium variation and FMD (r = 0.44, P = 0.011). Conclusion: Magnesium supplementation was associated with better BP control, improved endothelial function and amelioration of subclinical atherosclerosis in these thiazide-treated hypertensive women

Studies on the reaction of morita-baylis-hillman with indole and carbazole derivatives

Fundação para a Ciência e a Tecnologia (FCT)and FEDE

Fish and cephalopods associated with the squid Loligo vulgaris Lamarck, 1798 in Portuguese waters

Fish and cephalopod taxa occurring in association with Loligo vulgaris, in Portuguese waters between Lisbon and Vila Real de Santo António, were investigated by sampling with bottom trawling equipment between 1990-1991 and 1993-1995. The family Triglidae, the genera Pagellus and Trachurus and the four species Alloteuthis subulata, Boops boops, Callionymus lyra, and Merluccius merluccius were found, on average, in at least 75% of the trawls with L. vulgaris. Conversely, that cephalopod was found in at least 75% of the trawls with the family Trachinidae, the genera Dentex, Diplodus, Liza and Torpedo and the six species, Hyperoplus lanceolatus, Pagrus pagrus, Pomatoschistus m. minutus, Psetta m. maxima, Scophthalmus rhombus and Spicara flexuosa. An index of "affinity" (ranging from -∞ to 1) between L. vulgaris and the other taxa was used in order to highlight co-occurrences of an unlikely coincidental nature. Lists of taxa with high affinity index scores (0.5 to 1) are given for 5 different situations: all samples together; samples grouped by bottom depth; samples grouped by research cruise; research cruises grouped by season and by year. Pair wise comparisons between all taxa lists for each of the 5 situations were made, indicating a greater influence of depth than any other factor in the composition of the lists. The significance of the degree of similarity between lists of taxa, "preferred" under different circumstances and the reasons for those "preferences" are discussed

Differential phenolic production of Vitis vinifera cv. Alvarinho leaves affected with Esca disease

Esca is a destructive disease that affects Vitis vinifera around the world leading to important losses in wine production. Information on the response of Vitis vinifera plants to this disease is still scarce. To study the defence mechanisms of Vitis plants to Esca, we analysed leaves from both infected and non-affected boughs of Vitis vinifera cv. Alvarinho, of the Vinho Verde region (North of Portugal). Phenolics were analysed by HPLC-DAD-MS and by multivariate statistical analysis.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/17944/200

Synthesis of several precursors of glycoconjugates containing a 1,2,3-triazole unit

Preparation of some alkynyl amino acids (Gly, Phe, Tyr, Ala, Ser), alkynyl derivatives of hydroxycoumarins and acetylenic carbohydrate derivativesFundação para a Ciência e Tecnologia and FEDER, for National NMR Network (Bruker Avance III 400

Advanced treatment for arthritic diseases based on the capture and inactivation of interleukin-6 by biofunctionalized polymeric nanoparticles

Arthritic diseases, such as osteoarthritis and rheumatoid arthritis, are associated with synovium inflammation (synovitis). Several pro-inflammatory cytokines, especially tumor necrosis factor-α (TNFα) and interleukins (IL), are important mediators of inflammation and articular cartilage destruction, supporting a potential possibility of anticytokine therapy in these diseases. IL-6 is one of the key regulators of the inflammatory response. Thus, human monoclonal antibodies against IL-6 may prevent its action, and consequently reduce inflammation after intra-articular (IA) injection. Indeed, several clinical trials have already demonstrated positive outcomes over disease progression. Although these treatments are very attractive, they are associated with limited efficacy because of the rapid clearance of antibodies by the synovium. A solution to overcome this problem is using nanoparticles (NPs) as a substrate to protect and extend the action of the antibodies. Natural-derived polymers, like chitosan (Ch) and hyaluronic acid (HA), are biocompatible and biodegradable polysaccharides, being HA a natural component of the extracellular matrix of articular cartilage. Therefore, biodegradable polymeric NPs represent a good candidate for IA administration. In the present work we propose natural biodegradable polymeric NPs biofunctionalized with immobilized antibodies that selectively capture and inactivate the pro-inflammatory cytokine IL-6, reducing synovium inflammation. Ch-HA NPs were successfully prepared by polyelectrolyte complexation and further stabilized through carbodiimide chemistry (ethyl(dimethylaminopropyl) carbodiimide (EDC)/Nhydroxysuccinimide (NHS)). The particle size and zeta potential of the NPs were optimized. Stable NPs with 121.8 ± 2.4 of particle diameter, 0.11 ± 0.01 of polydispersity index and +25.12 ± 1.86 mV of zeta potential were produced with 0.25 mg/mL of initial polymers concentrations, at pH 5 and with 50/200 mM of EDC/NHS concentration. The anti-IL-6 antibody was immobilized at the surface of Ch-HA NPs. After determining the maximum antibody immobilization ability (7 µg/mL), the capacity to capture the recombinant IL-6 was evaluated. The efficacy was around 94-97%. Biological assays demonstrated not only the cytocompatibility of the produced NPs with human articular chondrocytes (hACs) (Fig 1) and human macrophages, but also the benefits of the capture and inactivation of IL-6 after stimulation with monocyte-derived macrophage conditioned medium. In conclusion, it is foreseeable that these NPs will overcome the limitations of the abovementioned treatments, since such NPs will increase the therapeutic efficacy due to their subcellular size, non-toxicity and high stability, being a promising approach for the local and sustained treatment of arthritic diseases.info:eu-repo/semantics/publishedVersio

Propolis efficacy: the quest for eco-friendly solvents

Propolis, a natural product made by bees with resins and balsams, is known for its complex chemical composition and remarkable bioactivities. In this study, propolis extraction was studied seeking extracts with strong bioactivities using less orthodox solvents, with some derived from apiary products. For that, a propolis sample collected from Gerês apiary in 2018 (G18) was extracted by maceration with six different solvents: absolute ethanol, ethanol/water (7:3), honey brandy, mead, propylene glycol and water. The solvent influence on the chemical composition and antioxidant and antimicrobial activities of the extracts was investigated. Antioxidant potential was assessed by the DPPH free-radical-scavenging assay and the antimicrobial activity by the agar dilution method. Chemical composition of the extracts was determined in vitro by three colorimetric assays: total ortho-diphenols, phenolics and flavonoids contents and the LC-MS technique. To our knowledge, this is the first time that solvents such as honey brandy and mead have been studied. Honey brandy showed considerable potential to extract propolis active compounds able to inhibit the growth of bacteria such as the methicillin-sensitive Staphylococcus aureus and Propionibacterium acnes (MIC values of 100 and 200 µg/mL, respectively) and the fungi Candida albicans and Saccharomyces cerevisiae (MIC=500 µg/mL, for both). Mead extracts displayed high antioxidant capacity (EC50=1.63 ± 0.27 µg/mL) and great activity against resistant bacteria such as the methicillin-resistant Staphylococcus aureus and Escherichia coli (MIC=750 µg/mL, for both). The production of such solvents made from beehive products further promotes a diversification of apiary products and the exploration of new applications using eco-friendly solutions.Ana Freitas acknowledges the financial support provided by national funds through FCT—Portuguese Foundation for Science and Technology (PD/BD/128276/2017), under the Doctoral Programme “Agricultural Production Chains—from fork to farm” (PD/00122/2012), and from the European Social Funds and the Regional Operational Programme Norte 2020. This study was also supported by CITAB research unit (UIDB/04033/2020), CBMA research unit (Contrato-Programa UIDB/04050/2020), Centre of Chemistry (UID/QUI/0686/2016), BioTecNorte (operation NORTE-01-0145-FEDER-000004), supported by the Northern Portugal Regional Operational Programme (NORTE 2020), LAQV (projects UIDB/50006/2020, UIDP/50006/2020, and UID/BIA/04004/2020) funded by national funds through the FCT I.P.info:eu-repo/semantics/publishedVersio

Caracóis endémicos dos Açores : estivação como mecanismo de resposta aos fatores ambientais

A secção Biologia é coordenada pelo Professor Universitário Armindo Rodrigues.[…] Estudos realizados sobre caracóis terrestres endémicos dos Açores têm revelado que estes, ao contrário do observado noutras espécies de moluscos da América do Sul e do Norte, tem a capacidade de se reproduzir durante todo o ano, o que tem sido atribuído a características climáticas propicias verificadas no arquipélago, em termos de temperatura, precipitação ou humidade do solo. A montanha do Pico (Ilha do Pico) é o melhor “laboratório” dos Açores para avaliar como fatores abióticos, que variam ao longo de um gradiente altitudinal, podem desencadear respostas fisiológicas e comportamentais numa espécie, com significado na sua reprodução e sobrevivência. […]info:eu-repo/semantics/publishedVersio