Avaliação dos Resultados do Cross-Linking de Colagénio Corneano em Doentes com Queratocone: a Nossa Experiência

Objectivo: Avaliar os resultados visuais e queratométricos do tratamento com cross-linking de colagénio corneano (CXL) no queratocone progressivo realizado no Centro Hospitalar de Entre Douro e Vouga durante o período de 1 ano. Material e Métodos: Estudo retrospetivo no qual foram incluídos 15 olhos (15 doentes) com queratocone progressivo. Todos os pacientes foram submetidos ao tratamento com CXL com riboflavina e luz ultravioleta-A segundo o protocolo de Dresden. 8 olhos completaram 12 meses de seguimento e, 7 olhos completaram 6 meses. Avaliámos a acuidade visual com e sem correcção, cilindro refractivo e equivalente esférico, topografia corneana e paquimetria com Pentacam®, assim como os parâmetros obtidos com o Ocular Response Analyzer®. Resultados: Verificou-se uma melhoria da melhor acuidade visual corrigida média de 0.56 +/- 0.18 para 0.60 +/- 0.18 aos 3 meses, atingindo aos 6 meses 0.69, diferença estatisticamente significativa (p=0.007) e aos 12 meses 0.72 (p=0.003). Os valores do cilindro refractivo e equivalente esférico diminuíram após o procedimento mas sem significado estatístico. Em todos os olhos tratados verificou-se estabilização da progressão. A média da queratometria máxima diminui significativamente de 51.11D pré-operatório para 49.63D (p=0.002) aos 6 meses e para 50.0 D aos 12 meses (p=0.01). Conclusões: O CXL de colagénio é um tratamento promissor para o queratocone evolutivo pois permite atrasar a progressão da doença e, em alguns casos, melhorar os parâmetros visuais, refractivos e topográficos. Os nossos resultados mostram uma melhoria funcional e morfológica, com a estabilização da progressão da doença, sendo necessário, no entanto, resultados a longo prazo.info:eu-repo/semantics/publishedVersio

Chemical and biological analysis of 4-acyloxy-3-nitrocoumarins as trypanocidal agents

Chagas disease is the most widespread contagious tropical disease in Latin America, being an important public health problem. Treatments against this disease are still very ineffective, presenting several side effects. Therefore, the search for alternative therapeutic solutions is urgent. In the present work, we evaluate the trypanocidal activity and the mechanism of action of a select series of synthetic 4-acyloxy-3-nitrocoumarins. All the coumarin derivatives showed moderate trypanocidal activity in trypomastigotes, along with low cytotoxicity. In addition, compound 1 decreased the number of infected Vero cells in an intracellular T. cruzi model. Electron spin resonance and electrochemical studies showed the formation of nitro radical anions. The Fukui index provided additional information to elucidate the proposed reduction mechanism. Furthermore, in vitro radical formation studies demonstrated the potential of these compounds to achieve higher concentrations of intracellular free radicals, proposing oxidative stress as a possible trypanocidal mechanism. Furthermore, no correlation was observed between the diffusion of these compounds, which shows that lipophilicity is not a predominant factor for activity. Elsevier Ltd. All rights reservedThis project was partially supported by the University of Porto and University of Santiago de Compostela. MJM would like to thank Xunta de Galicia (Galician Plan of Research, Innovation and Growth 2011–2015, Plan I2C, ED481B 2014/086–0 and ED481B 2018/007) and Fundação para a Ciência e Tecnologia (CEECIND/02423/2018 and UIDB/00081/2020). FS would like to thank FONDECYT 1190340 and REDES170126, COA would like to thank FONDECYT 1190340, JDM would like to thank FONDECYT 1170126 and ANID/PCI REDES 170126, and MMB would like to thank FONDECYT Postdoctoral 3190449S

Combinatorial activity of flavonoids with antibiotics against drug resistant Staphylococcus aureus

The use of resistance-modifying agents is a potential strategy that is used to prolong the effective life of antibiotics in the face of increasing antibiotic resistance. Since certain flavonoids are potent bacterial efflux pump inhibitors, we assessed morin, rutin, quercetin, hesperidin, and (+)-catechin for their combined activity with the antibiotics ciprofloxacin, tetracycline, erythromycin, oxacillin, and ampicillin against drug-resistant strains of Staphylococcus aureus, including methicillin-resistant S. aureus. Four established methods were used to determine the combined efficacy of each combination: microdilution checkerboard assays, time-kill determinations, the Etest, and dual disc-diffusion methods. The cytotoxicity of the flavonoids was additionally evaluated in a mouse fibroblast cell line. Quercetin and its isomer morin decreased by 3- to 16-fold the minimal inhibitory concentration of ciprofloxacin, tetracycline, and erythromycin against some S. aureus strains. Rutin, hesperidin, and (+)-catechin did not promote any potentiation of antibiotics. Despite the potential cytotoxicity of these phytochemicals at a high concentration (fibroblast IC50 of 41.8 and 67.5mg/L, respectively), quercetin is commonly used as a supplement for several therapeutic purposes. All the methods, with exception of the time-kill assay, presented a high degree of congruence without any apparent strain specificity.This work was supported by Operational Program for Competitiveness Factors—COMPETE, FCT/MEC (PIDDAC), and FEDER through Projects Bioresist—PTDC/EBB-EBI/ 105085/2008; Phytodisinfectants—PTDC/DTP-SAP/1078/ 2012 (COMPETE: FCOMP-01-0124-FEDER-028765) and the PhD grants awarded to Ana Abreu (SFRH/BD/84393/ 2012) and Anabela Borges (SFRH/BD/63398/2009). The authors are very grateful to Professor Simon Gibbons (De- partment of Pharmaceutical and Biological Chemistry, The School of Pharmacy, UCL School of Pharmacy, London) for providing the bacterial strains.info:eu-repo/semantics/publishedVersio

Working Group Report: Heavy-Ion Physics and Quark-Gluon Plasma

This is the report of Heavy Ion Physics and Quark-Gluon Plasma at WHEPP-09 which was part of Working Group-4. Discussion and work on some aspects of Quark-Gluon Plasma believed to have created in heavy-ion collisions and in early universe are reported.Comment: 20 pages, 6 eps figures, Heavy-ion physics and QGP activity report in "IX Workshop on High Energy Physics Phenomenology (WHEPP-09)" held in Institute of Physics, Bhubaneswar, India, during January 3-14, 2006. To be published in PRAMANA - Journal of Physics (Indian Academy of Science

Clinical oxidative stress during leprosy multidrug therapy:impact of dapsone oxidation

This study aims to assess the oxidative stress in leprosy patients under multidrug therapy (MDT; dapsone, clofazimine and rifampicin), evaluating the nitric oxide (NO) concentration, catalase (CAT) and superoxide dismutase (SOD) activities, glutathione (GSH) levels, total antioxidant capacity, lipid peroxidation, and methemoglobin formation. For this, we analyzed 23 leprosy patients and 20 healthy individuals from the Amazon region, Brazil, aged between 20 and 45 years. Blood sampling enabled the evaluation of leprosy patients prior to starting multidrug therapy (called MDT 0) and until the third month of multidrug therapy (MDT 3). With regard to dapsone (DDS) plasma levels, we showed that there was no statistical difference in drug plasma levels between multibacillary (0.518±0.029 μg/mL) and paucibacillary (0.662±0.123 μg/mL) patients. The methemoglobin levels and numbers of Heinz bodies were significantly enhanced after the third MDTsupervised dose, but this treatment did not significantly change the lipid peroxidation and NO levels in these leprosy patients. In addition, CAT activity was significantly reduced in MDT-treated leprosy patients, while GSH content was increased in these patients. However, SOD and Trolox equivalent antioxidant capacity levels were similar in patients with and without treatment. These data suggest that MDT can reduce the activity of some antioxidant enzyme and influence ROS accumulation, which may induce hematological changes, such as methemoglobinemia in patients with leprosy. We also explored some redox mechanisms associated with DDS and its main oxidative metabolite DDS-NHOH and we explored the possible binding of DDS to the active site of CYP2C19 with the aid of molecular modeling software

Development and evaluation of an emulsion containing lycopene for combating acceleration of skin aging

Licopeno é um carotenóide com potente atividade antioxidante encontrado em grande quantidade no tomate e usado no combate a diversas doenças como doenças cardiovasculares e diferentes tipos de cânceres, incluindo o câncer de próstata. O objetivo desse trabalho foi desenvolver uma emulsão contendo extrato de licopeno obtido do tomate salada e avaliar a citotoxicidade do extrato, a estabilidade, o comportamento reológico, atividade antioxidante e permeação do fitocosmético. O cosmético foi desenvolvido utilizando fase oleosa contendo derivados de Karité e submetido à avaliação da estabilidade físico-química, espalhabilidade, análise térmica, comportamento reológico, qualidade microbiológica, citotoxicidade, atividade antioxidante e testes de permeação e retenção cutânea. Os resultados demonstraram que o fitocosmético é estável, apresenta comportamento reológico desejável para uma formulação tópica e é um produto promissor para ser utilizado no combate à aceleração do envelhecimento cutâneo.Lycopene, a carotenoid and potent antioxidant is found in large quantities in tomatoes. Lycopene combats diseases, such as cardiovascular disease and different types of cancer, including prostate cancer. However, its topical use in emulsion form for the combat of skin aging is under-explored. The aim of the present study was to develop an emulsion containing lycopene extracted from salad tomatoes and evaluate its cytotoxicity, stability, rheological behavior, antioxidant activity and phytocosmetic permeation. The developed cosmetic comprised an oil phase made up of shea derivatives and was evaluated in terms of its physiochemical stability, spreadability, thermal analysis, rheological behavior, microbiological quality, cytotoxicity, antioxidant activity, cutaneous permeation and retention. The results demonstrate that this phytocosmetic is stable, exhibits satisfactory rheological behavior for a topical formula and is a promising product for combating skin aging

Evaluation of the best method to assess antibiotic potentiation by phytochemicals against staphylococcus aureus

The increasing occurrence of bacterial resistance to antibiotics has now reached a critical level. Finding antibiotic coadjuvants capable to inhibit the bacterial resistance mechanisms would be a valuable mid-term solution, until new classes of antibiotics are discovered. Selected plant alkaloids were combined with 5 antibiotics against 10 Staphylococcus aureus strains, including strains expressing distinct efflux pumps and methicillin-resistant S. aureus strains. The efficacy of each combination was assessed using the microdilution checkerboard, time-kill, Etest, and disc diffusion methods. The cytotoxicity of the alkaloids was evaluated in a mouse fibroblast cell line. Potentiation was obtained in 6% of all 190 combinations, especially with the combination of: ciprofloxacin with reserpine (RES), pyrrolidine (PYR), and quinine (QUIN); tetracycline with RES; and erythromycin with PYR. The highest cytotoxicity values were found for QUIN (half maximal inhibitory concentration [IC50] = 25 ± 2.2 mg/L) and theophylline (IC50 = 100 ± 4.7 mg/L).The authors are very grateful to Professor Simon Gibbons (Department of Pharmaceutical and Biological Chemistry, The School of Pharmacy, UCL School of Pharmacy, London) for providing some of the bacterial strains. This work was supported by Operational Programme for Competitiveness Factors - COMPETE and by FCT Portuguese Foundation for Science and Technology through Projects Bioresist - PTDC/EBB-EBI/105085/2008; Phytodisinfectants - PTDC/DTP-SAP/1078/2012 and the PhD grants awarded to Ana Abreu (SFRH/BD/84393/2012) and Anabela Borges (SFRH/BD/63398/2009)