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- 1,2-dihydroxyxanthone: effect on A375-C5 melanoma cell growth associated with interference with THP-1 human macrophage activityPublication . Silva, Viviana; Cerqueira, Fátima; Nazareth, Nair; Medeiros, R.; Sarmento, Amélia; Sousa, Emília; Pinto, MadalenaXanthones have been suggested as prospective candidates for cancer treatment. 1,2- dihydroxyxanthone (1,2-DHX) is known to interfere with the growth of several cancer cell lines. We investigated the effects of 1,2-DHX on the growth of the A375-C5 melanoma cell line and THP-1 human macrophage activity. 1,2-DHX showed a moderate growth inhibition of A375-C5 melanoma cells (concentration that causes a 50% inhibition of cell growth (GI50) = 55.0 ±2.3 µM), but strongly interfered with THP-1 human macrophage activity. Supernatants from lipopolysaccharide (LPS)-stimulated THP-1 macrophage cultures exposed to 1,2-DHX significantly increased growth inhibition of A375-C5 cells, when compared to supernatants from untreated LPS-stimulated macrophages or to direct treatment with 1,2-DHX only. 1,2-DHX decreased THP-1 secretion of interleukin-1β (IL-1β) and interleukin-10 (IL-10), but stimulated tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) production. This xanthone also inhibited nitric oxide (NO) production by RAW 264.7 murine macrophages, possibly through inhibition of inducible NO synthase production. In conclusion, these findings suggest a potential impact of 1,2-DHX in melanoma treatment, not only due to a direct effect on cancer cells but also by modulation of macrophage activity.
- 160 Fatty Acid Composition of Human Milk in a Portuguese Urban Population:Prospective Study from 7 Days to 16 Weeks of LactationPublication . Ribeiro, M; Balcão, Victor; Guimaraes, H; Rocha, G; Moutinho, Carla; Casal, S; Oliveira, B; Guerra, A
- 1964-2000, Duas casas de Alcino Soutinho - Casa Rio Maior, 1964; Casa Rua Júlio Dantas, 2000Publication . Ferreira, João C CastroAnálise comparada da Casa em Rio Maior e da Casa na Rua Júlio Dantas, no Porto, projectadas por Alcino Soutinho em 1964 e 2000, respectivamente. Desenvolveremos esta análise a partir de tópicos/temas de análise: linguagem, contexto, luz e matéria, público/privado, geometria/ortogonalidade, céu e terra, organização funcional. Permanecem as preocupações (temas de projecto), variam as soluções. Dos temas que permanecem, destacamos: a linguagem, contexto, luz e matéria, público/privado, céu, terra, regular/irregular, função/disposição, procurando-se detectar elementos de continuidade e diferença entre dois momentos tão diversos da longa carreira profissional de Soutinho. A diversidade e variedade de respostas que cada um dos projectos encerra correspondem à procura das respostas mais adequadas a cada programa, lugar e tempo, em e na liberdade por que o autor lutou.
- "2º Ciclo de seminários em biopatologia"- o sucesso da iniciativaPublication . Castro, Ana Rita; Soares, SandraO II Ciclo de Seminários em Biopatologia, realizado na Universidade Fernando Pessoa, entre os dias 9 de Janeiro e 12 de Março de 2008, teve por objectivo continuar a dar a conhecer as múltiplas vertentes da Investigação Científica desenvolvida em Portugal, nomeadamente em áreas como células estaminais, cancro, doenças infecciosas, entre outras. The 2nd series of Seminars in Biopathology occurred in Universidade Fernando Pessoa, between January 9th and 12th of March, and the objective was to present the multiple approaches of the scientific research in Portugal in areas like stem cells, cancer, infectious disease and others.
- Os 3 farros. Descida aos infermos. Currespondências de Alberto Pimenta e de António Aragão: textualidades criativas sobre um país e um mundo à derivaPublication . Coelho, Leonor MartinsPretendemos traçar as linhas gerais que atravessam os 3 farros. descida aos infermos. currespondências. Trata-se de um artefacto com acento posto numa textualidade que sublinha a inquietação criativa, a agitação estética e a consciência crítica de Alberto pimenta (a) e de António Aragão (A). nas missivas trocadas entre os dois autores, o efeito do enigma e de estranhamento, a irrisão paródica e uma observação desencantada dos padrões culturais, políticos e morais da época observada, acentuará o carácter irreverente e a maliciosa ironia das quarenta cartas que compõem o livro.
- 3,4-Methylenedioxymethamphetamine hepatotoxicity under the heat stress condition: novel insights from in vitro metabolomic studiesPublication . Araújo, Ana Margarida; Enea, Maria; Fernandes, Eduarda; Carvalho, Félix; de Lourdes Bastos, Maria; Carvalho, Márcia; Guedes de Pinho, PaulaHyperthermia has been extensively reported as a life-threatening consequence of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) abuse. In this work, we used a sensitive untargeted metabolomic approach based on gas chromatography-mass spectrometry to evaluate the impact of hyperthermia on the hepatic metabolic changes caused by MDMA. For this purpose, primary mouse hepatocytes were exposed to subtoxic (LC01 and LC10) and toxic (LC30) concentrations of MDMA for 24 h, at 37 or 40.5 °C (simulating body temperature increase after MDMA consumption), and alterations on both intracellular metabolome and extracellular volatilome were evaluated. Multivariate analysis showed that metabolic patterns clearly discriminate MDMA treated cells from control cells, both in normothermic and hyperthermic conditions. The metabolic signature was found to be largely common to MDMA subtoxic and toxic concentrations, although with evident differences in the magnitude of response, with metabolic changes significantly more pronounced at 40.5 °C. Discriminant metabolites associated with MDMA-induced hepatotoxicity are mostly involved in the amino acid metabolism, aminoacyl tRNA biosynthesis, glutathione metabolism, tricarboxylic acid cycle, and pyruvate metabolism. Moreover, our metabolomic findings were corroborated by classical toxicity parameters, demonstrating the high sensitivity of this omic approach to assess molecular-level effects. Overall, this study indicates that MDMA triggers significant metabolic alterations on hepatic cells, even at low concentrations, that are clearly exacerbated at high temperatures. These findings provide new metabolic pieces to solve the puzzle of MDMA's hepatotoxicity mechanism and emphasize the increased risks of MDMA abuse due to the thermogenic action of the drug.
- 3,4-Methylenedioxypyrovalerone (MDPV): in vitro mechanisms of hepatotoxicity under normothermic and hyperthermic conditionsPublication . Valente, Maria João; Araújo, Ana Margarida; Silva, Renata; Bastos, Maria de Lourdes; Carvalho, Félix; Guedes de Pinho, Paula; Carvalho, MárciaSynthetic cathinones have emerged in recreational drug markets as legal alternatives for classical amphetamines. Though currently banned in several countries, 3,4-methylenedioxypyrovalerone (MDPV) is one of the most commonly abused cathinone derivatives worldwide. We have recently reported the potential of MDPV to induce hepatocellular damage, but the underlying mechanisms responsible for such toxicity remain to be elucidated. Similar to amphetamines, a prominent toxic effect of acute intoxications by MDPV is hyperthermia. Therefore, the present in vitro study aimed to provide insights into cellular mechanisms involved in MDPV-induced hepatotoxicity and also evaluate the contribution of hyperthermia to the observed toxic effects. Primary cultures of rat hepatocytes were exposed to 0.2-1.6 mM MDPV for 48 h, at 37 or 40.5 °C, simulating the rise in body temperature that follows MDPV intake. Cell viability was measured through the MTT reduction and LDH leakage assays. Oxidative stress endpoints and cell death pathways were evaluated, namely the production of reactive oxygen and nitrogen species (ROS and RNS), intracellular levels of reduced (GSH) and oxidized (GSSG) glutathione, adenosine triphosphate (ATP) and free calcium (Ca(2+)), as well as the activities of caspases 3, 8 and 9, and nuclear morphological changes with Hoechst 33342/PI double staining. At 37 °C, MDPV induced a concentration-dependent loss of cell viability that was accompanied by GSH depletion, as one of the first signs of toxicity, observed already at low concentrations of MDPV, with negligible changes on GSSG levels, followed by accumulation of ROS and RNS, depletion of ATP contents and increases in intracellular Ca(2+) concentrations. Additionally, activation of caspases 3, 8, and 9 and apoptotic nuclear morphological changes were found in primary rat hepatocytes exposed to MDPV, indicating that this cathinone derivative activates both intrinsic and extrinsic apoptotic death pathways. The cytotoxic potential of MDPV and all the studied endpoints were markedly aggravated under hyperthermic conditions (40.5 °C). In conclusion, these data suggest that MDPV toxicity in primary rat hepatocytes is mediated by oxidative stress, subsequent to GSH depletion and increased ROS and RNS accumulation, mitochondrial dysfunction, and impairment of Ca(2+) homeostasis. Furthermore, the rise in body temperature subsequent to MDPV abuse greatly exacerbates its hepatotoxic potential.
- 4,4′-(1,8-Naphthalene-1,8-diyl)dibenzonitrilePublication . Lima, Carlos F.; Gomes, Ligia R.; Santos, Luís M. N. B. F.; Low, John NicolsonIn the title mol-ecule, C(24)H(14)N(2), the exterior C-C-C angle of the naphthalene ring system involving the two phenyl-substituted C atoms is 126.06 (11)° and the dihedral angles between the mean plane of the naphthalene ring system and those of the benzene rings are 66.63 (5) and 67.89 (5)°. In the crystal, mol-ecules are linked into a ladders by four weak C-H⋯π inter-actions.
- Os 40 anos do InsólitoPublication . Dias, Manuel Barrote
- À volta da metodologia estruturalista: uma análise e uma proposta para a investigação em história da artePublication . Silva, Ilídio; Rui Leandro Maia; Luís Pinto de Faria; dir. Álvaro Monteiro