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- Prostate cancer: antitumor effect of chalcones on androgen dependent and androgen-independent prostate cancer cell linesPublication . Horta, Bruno; Cerqueira, Fátima; Pinto, Madalena; Cidade, Honorina; Silva, Jani; Pereira, António; Medeiros, R.
- Miconazole-loaded Nanostructured Lipid Carriers (NLC) for local delivery to the oral mucosa: improving antifungal activityPublication . Mendes, A.I.; Silva, Ana Catarina; Catita, José; Cerqueira, Fátima; Gabriel, C.; Lopes, Carla MartinsMiconazole is a widely used antifungal agent with poor aqueous solubility, which requires the development of drug delivery systems able to improve its therapeutic activity. For this purpose, a miconazole-loaded nanostructured lipid carriers (NLC) dispersion was prepared and characterized. Further, the dispersion was used to prepare a NLC-based hydrogel formulation proposed as an alternative system to improve the local delivery of miconazole to the oral mucosa. NLC dispersion showed particles in the nanometer range (≈200 nm) with low polidispersity index (<0.3), good physical stability and high encapsulation efficiency (>87%). A controlled miconazole release was observed from NLC and NLCbased hydrogel formulations, in contrast to a commercial oral gel formulation, which demonstrated a faster release. Additionally, it was observed that the encapsulation of miconazole in the NLC improved its antifungal activity against Candida albicans. Therefore, it was demonstrated that the encapsulation of miconazole in NLC allows for obtaining the same therapeutic effect of a commercial oral gel formulation, using a 17-fold lower dose of miconazole.
- Coffee industrial waste as a natural source of bioactive compounds with antibacterial and antifungal activitiesPublication . Silva, Carla Sousa e; Gabriel, Carla; Cerqueira, Fátima; Manso, M. Conceição; Vinha, A. F.Coffee is one of the most popular and consumed beverages in the world, which leads to a high contents of solid residue known as spent coffee grounds (SCG). As is known, coffee beans contain several classes of health related chemicals, including phenolic compounds, melanoidins, diterpenes, xanthines and carotenoids which are associated with therapeutic and pharmaceutical effects, due to antimicrobial, antioxidant, anti-infectious and antitumour activities. Considering that this coffee industrial waste has no commercial value and are currently disposed as a solid waste or employed as fertilizers, we intend to highlight the use of SCG as a raw material with potential interest to the food and pharmaceutical industries. Moreover, this work seems to be valuable to promote the use of SCG as natural and an inexpensive food supplements or pharmaceutical additive. The phytochemical compounds content among the crude aqueous extracts of SCG followed this order: phenolics > flavonoids > carotenoids (mg/ g dry waste), respectively. Caffeine content found in SCG was ~ 0.82 g/100 g dry waste, 70 % lower than coffee roasting beans. Coffee ground extracts showed inhibition to S. aureus and E. coli growth for concentrations of 1.0 mg/ mL and a stronger inhibition was also observed against C. albicans, C. krusei and C. parapsilosis growth using lower concentration (0.5 mg/ mL).
- Microbiologia : protocolos laboratoriaisPublication . Sousa, João Carlos de; Cerqueira, Fátima; Abreu, Cristina
- 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.
- Inhibitory effect of 5-aminoimidazole-4-carbohydrazonamides derivatives against Candida spp. biofilm on nanohydroxyapatite substratePublication . Gabriel, C.; Grenho, L.; Cerqueira, Fátima; Medeiros, R.; Dias, A. M.; Ribeiro, A. I.; Proença, M. F.; Fernandes, M. H.; Sousa, J. C.; Monteiro, F. J.; Ferraz, M. P.Candida can adhere and form biofilm on biomaterials commonly used in medical devices which is a key attribute that enhances its ability to cause infections in humans. Furthermore, biomaterial-related infections represent a major therapeutic challenge since Candida biofilms are implicated in antifungal therapies failure. The goals of the present work were to investigate the effect of three 5-aminoimidazole-4-carbohydrazonamides, namely (Z)-5-amino-1-methyl-N'-aryl-1H-imidazole-4-carbohydrazonamides [aryl = phenyl (1a), 4-fluorophenyl (1b), 3-fluorophenyl (1c)], on Candida albicans and Candida krusei biofilm on nanohydroxyapatite substrate, a well-known bioactive ceramic material. To address these goals, both quantitative methods (by cultivable cell numbers) and qualitative evaluation (by scanning electron microscopy) were used. Compounds cytocompatibility towards osteoblast-like cells was also evaluated after 24 h of exposure, through resazurin assay. The three tested compounds displayed a strong inhibitory effect on biofilm development of both Candida species as potent in vitro activity against C. albicans sessile cells. Regarding cytocompatibility, a concentration-dependent effect was observed. Together, these findings indicated that the potent activity of imidazole derivatives on Candida spp. biofilms on nanohydroxyapatite substrate, in particular compound 1c, is worth further investigating.
- Effect of heptaphylline and two related secondary metabolites on cervical (HeLa) and prostate (LNCaP and PC-3) cancer cell linesPublication . Horta, Bruno; Cerqueira, Fátima; Pinto, Madalena; Sousa, Emília; Puthongking, Ploenthip; Pereira, António; Medeiros, R.
- Modulation of human lymphocyte proliferation by antibacterial drugsPublication . Gomes, Ema; Esteves, Alexandra; Silva, Ricardo; Sousa, João Carlos; Cerqueira, FátimaThe aim of this work was to perform a systematic study of the interference of the different antibiotics with phytohaemaglutinin (PHA) stimulated human lymphocytes proliferation. Twelve antibiotics from different therapeutic classes were chosen: b-lactams (amoxicillin; ceftriaxone; imipenem), glycopeptides (vancomycin), aminoglycosides (gentamicin), macrolides (erythromycin), tetracyclines (tetracycline), rifampicin, quinolones (ciprofloxacin; nalidixic acid), sulfonamides (sulfamethoxazole) and nitrofuran (nitrofurantoin). Nitrofurantoin showed the strongest antiproliferative effect while tetracycline and rifampicin showed only moderate activities. All the other antibiotics were inactive even at the maximum concentration tested (100mg/ml). O objectivo do trabalho foi o estudo sistemático da interferência dos diferentes antibióticos com a proliferação de linfócitos humanos estimulados com fitohemaglutinina (PHA). Foram seleccionados doze antibióticos pertencentes a diferentes grupos terapêuticos: b-lactâmicos (amoxicilina; ceftriaxona; imipenemo), glicopéptidos (vancomicina), aminoglicosídeos (gentamicina), macrólidos (eritromicina), tetraciclinas (tetraciclina), rifampicina, quinolonas (ciprofloxacina; ácido nalidíxico), sulfonamidas (sulfametoxazole) e nitrofuranos (nitrofurantoína). A nitrofurantoína mostrou ser um potente inibidor da proliferação dos linfócitos enquanto a tetraciclina e a rifampicina apenas exibiram actividades moderadas. Nenhum dos outros antibióticos foi activo mesmo na concentração máxima testada (100 mg/ml).