La causalidad del bien en Santo Tomás

This paper examines the influence of the Neoplatonic tradition on the thought of St. Thomas with respect to the causality of God’s goodness. The maxim “bonum est diffusivum sui,” generally attributed to Pseudo-Dionysius, will be discussed and interpreted in terms of final causality

Protective effects of ursolic acid and luteolin against oxidative DNA damage include enhancement of DNA repair in Caco-2 cells

Consumption of fruits and vegetables is associated with a reduced risk of developing a wide range of cancers including colon cancer. In this study, we evaluated the effects of two compounds present in fruits and vegetables, ursolic acid, a triterpenoid, and luteolin, a flavonoid, on DNA protection and DNA repair in Caco-2 cells using the comet assay. Ursolic acid and luteolin showed a protective effect against H2O2-induced DNA damage. Repair rate (rejoining of strand breaks) after treatment with H2O2 was increased by pre-treatment of Caco-2 cells for 24 h with ursolic acid or luteolin. To evaluate effects on induction of base oxidation, we exposed cells to the photosensitizer Ro 19-8022 plus visible light to induce 8-oxoguanine. Luteolin protected against this damage in Caco-2 cells after a short period of incubation. We also measured the incision activity of a cell extract from Caco-2 cells treated for 24 h with test compounds, on a DNA substrate containing specific damage (8-oxoGua), to evaluate effects on base excision repair activity. Preincubation for 24 h with ursolic acid enhanced incision activity in Caco-2 cells. In conclusion, we demonstrated for the first time that ursolic acid and luteolin not only protect DNA from oxidative damage but also increase repair activity in Caco-2 cells. These effects of ursolic acid and luteolin may contribute to their anti-carcinogenic effects.Fundação para a Ciência e a Tecnologia (FCT

Antigenotoxic effects of quercetin, rutin and ursolic acid on HepG2 cells : evaluation by the comet assay

In the present study, the chemoprotective effects of quercetin, rutin and ursolic acid on tert-butyl hydroperoxide (t-BHP)-induced DNA damage in a human hepatoma cell line (HepG2) were investigated by the comet assay. To determine whether protection was due to direct chemical interactions alone or to cellular-mediated responses three different types of treatments were used: simultaneous incubation of cells with individual test compounds and the toxicant; pre-treatment with test compound before addition of the toxicant followed or not by a recovery period. The expression of Hsp70 was quantified by Western blotting to test the involvement of heat shock proteins in the cellular responses to the test compounds. In addition, effects on proliferation were evaluated by the MTT assay. The results show that quercetin and ursolic acid prevented DNA damage and had antiproliferative properties in HepG2 cells suggesting an anticarcinogenic potential for these compounds. The protective effects of quercetin against t-BHP-induced DNA damage seem to be due to both direct effects on t-BHP toxicity and to cellularly mediated indirect effects which reflect the potentiation of the cellular antioxidant defenses. Ursolic acid seems to exert effects only through cellularly mediated mechanisms since it was not protective in simultaneous incubation. Quercetin and ursolic acid also showed to increase the rate of DNA repair. Rutin did not have effects at any level. These results, obtained with liver cells, emphasize and confirm the chemopreventive potential of quercetin and ursolic acid, which may help explain the lower cancer incidence in human population with high dietary intakes of fruits and vegetables. These results also demonstrate that Hsp70 is not involved in the observed effects in HepG2.Fundação para a Ciência e a Tecnologia (FCT) - UMINHO/POCI-62040/BI/1/06, SFRH/BPD/26316/2006, POCI/AGR/62040/2004

Development of a new application of the comet assay to assess levels of O6-methylguanine in genomic DNA (CoMeth)

O6-methylguanine (O6meG) is one of the most premutagenic, precarcinogenic, and precytotoxic DNA lesions formed by alkylating agents. Repair of this DNA damage is achieved by the protein MGMT, which transfers the alkyl groups from the O6 position of guanine to a cysteine residue in its active center. Because O6meG repair by MGMT is a stoichiometric reaction that irreversibly inactivates MGMT, which is subsequently degraded, the repair capacity of O6meG lesions is dependent on existing active MGMT molecules. In the absence of active MGMT, O6meG is not repaired, and during replication, O6meG:T mispairs are formed. The MMR system recognizes these mispairs and introduces a gap into the strand. If O6meG remains in one of the template strands the futile MMR repair process will be repeated, generating more strand breaks (SBs). The toxicity of O6meG is, therefore, dependent on MMR and DNA SB induction of cell death. MGMT, on the other hand, protects against O6meG toxicity by removing the methyl residue from the guanine. Although removal of O6meG makes MGMT an important anticarcinogenic mechanism of DNA repair, its activity significantly decreases the efficacy of cancer chemotherapeutic drugs that aim at achieving cell death through the action of the MMR system on unrepaired O6meG lesions. Here, we report on a modification of the comet assay (CoMeth) that allows the qualitative assessment of O6meG lesions after their conversion to strand breaks in proliferating MMR-proficient cells after MGMT inhibition. This functional assay allows the testing of compounds with effects on O6meG levels, as well as on MGMT or MMR activity, in a proliferating cell system. The expression of MGMT and MMR genes is often altered by promoter methylation, and new epigenetically active compounds are being designed to increase chemotherapeutic efficacy. The CoMeth assay allows the testing of compounds with effects on O6meG, MGMT, or MMR activity. This proliferating cell system complements other methodologies that look at effects on these parameters individually through analytical chemistry or in vitro assays with recombinant proteins.We thank the COST Action TD0905 “Epigenetics: From Bench to Bedside” for financial support. A.A. Ramos and D. Pedro are supported by the Foundation for Science and Technology, Portugal, Grant SFRH/BD/35672/2007 and SFRH/BD/64817/2009, respectively. The work was supported by FCT research grant PEst-C/BIA/UI4050/2011, which is co-funded by the program COMPETE from QREN with co-participation from the European Community fund FEDER

A rabdomiólise está associada à febre dengue em um paciente lúpico

ResumoEsse relato descreve o caso de uma mulher com lúpus eritematoso sistêmico (LES) que sofreu rabdomiólise em seguida à sua infecção pelo vírus da dengue. Foram relatados apenas alguns casos de LES com manifestação de rabdomiólise, nenhum deles associados à febre dengue.A princípio, a paciente apresentava‐se com febre alta, mialgia, astenia muscular, leve cefaleia, poliartralgia e trombocitopenia, lembrando uma exacerbação lúpica, mas considerando que o número de pessoas infectadas pela dengue na época era alto e tendo em vista que os sintomas das duas condições são parecidos, foi solicitada sorologia para dengue. Trans‐corridos alguns dias, a paciente apresentou rabdomiólise, tendo então sido tratada com medicamentos imunossupressivos, alcalinização urinária e hidratação vigorosa, medidas que melhoraram seus danos musculares e a condição inflamatória. A sorologia positiva para dengue nos foi disponibilizada apenas depois da instauração do tratamento descrito acima. A paciente recebeu alta em estado assintomático.Esse caso demonstra a grande semelhança entre a febre dengue e uma exacerbação lúpica; isso deve alertar o clínico para que, especialmente durante uma epidemia, faça uma cuidadosa diferenciação entre essas doenças, de forma a estabelecer uma terapia correta e eficiente.AbstractThis report describes the case of a woman with systemic lupus erythematous (SLE) that developed rhabdomyolysis after being infected by dengue virus. There are only a few cases of SLE accompanied by rhabdomyolysis, none of them associated with dengue fever.Initially, the woman presented high fever, myalgia, muscular weakness, mild headache, polyarthralgia and thrombocytopenia reminding a lupus flare, but since the number of people infected by dengue at that time was high and the symptoms from both conditions are similar, a dengue serology was requested. After a few days, the patient developed rhabdomyolysis. She was then submitted to immunosuppressive drugs, urinary alkalization and vigorous hydration, which improved her muscle damage and inflammatory condition. The positive dengue serology was only available after the therapy above had been established. She was discharged in an asymptomatic state.This case demonstrates how alike dengue fever and a lupus flare are, warning clinicians that, especially during an epidemic, both diseases should be carefully differentiated in order to establish a correct and efficient therapy

Integrated pest management strategies for cabbage stem flea beetle (Psylliodes chrysocephala) in oilseed rape

Oilseed rape (OSR) is the second largest source of vegetable oil globally and the most important biofuel feedstock in the European Union (EU) but production of this important crop is threatened by a small insect; Psylliodes chrysocepaha – the cabbage stem flea beetle (CSFB). The EU ban on use of neonicotinoid seed treatments and resistance of CSFB to pyrethroid insecticides have left farmers with limited control options resulting in drastic reductions in production. Integrated pest management (IPM) may offer a solution. We review the lifecycle of CSFB and the current options available, or in the research pipeline, for the eight IPM principles of the EU Sustainable Use of Pesticides Directive (Directive-2009/128/EC). A full IPM strategy for CSFB barely exists. Although there are a range of preventative measures these require scientific validation; critically, resistant/tolerant OSR cultivars are not yet available. Existing monitoring methods are time consuming and there are no commercial models to enable decision support based on predictions migration timing or population size. Available thresholds are not based on physiological tolerances of the plant making it hard to adapt them to changing market prices for the crop and costs of control. Non-synthetic alternatives tested and registered for use against CSFB are lacking, making resistance management impossible. CSFB control is therefore dependent upon conservation biocontrol. Natural enemies of CSFB are present, but quantification of their effects is needed and habitat management strategies to exploit their potential. Although some EU countries have local initiatives to reduce insecticide use and encourage use of ‘greener’ alternatives, there is no formal process for ranking these and little information available to help farmers make choices. We summarise the main knowledge gaps and future research needed to improve measures for CSFB control and to facilitate development of a full IPM strategy for this pest -and sustainable oilseeds production