Molecular, genetic and epigenetic pathways of peroxynitrite-induced cellular toxicity

Oxidative stress plays a key role in the pathogenesis of cancer and many metabolic diseases; therefore, an effective antioxidant therapy would be of great importance in these circumstances. Nevertheless, convincing randomized clinical trials revealed that antioxidant supplementations were not associated with significant reduction in incidence of cancer, chronic diseases and all-cause mortality. As oxidation of essential molecules continues, it turns to nitro-oxidative stress because of the involvement of nitric oxide in pathogenesis processes. Peroxynitrite damages via several distinctive mechanisms; first, it has direct toxic effects on all biomolecules and causes lipid peroxidation, protein oxidation and DNA damage. The second mechanism involves the induction of several transcription factors leading to cytokine-induced chronic inflammation. Finally, it causes epigenetic perturbations that exaggerate nuclear factor kappa-B mediated inflammatory gene expression. Lessons-learned from the treatment of several chronic disorders including pulmonary diseases suggest that, chronic inflammation and glucocorticoid resistance are regulated by prolonged peroxynitrite production

Estudos em modalidades esportivas de combate: estado da arte

O objetivo do presente texto foi apresentar o estado da arte dos estudos sobre as modalidades esportivas de combate (MEC). Inicialmente, é destacada a relevância destas modalidades, tanto do ponto de vista histórico, quanto em relação à sua representatividade em competições internacionais, como os Jogos Olímpicos. Também são apresentadas as áreas mais comuns de atuação do profissional de Esporte nas MEC, bem como as iniciativas de organização de eventos, publicações, grupos de estudos e instituições científicas direcionadas às MEC. Posteriormente, estudos com possibilidade de aplicação em diferentes áreas de intervenção - preparação física, técnica e tática, gestão e organização - por parte do profissional do Esporte foram destacados. Finalmente, perspectivas de novos estudos e aspectos relacionados à preparação profissional são evidenciados.The objective of the present text was to present the state of art of studies related to combat sports (CS). Initially, it is presented the relevancy of these sports, from a historical perspective to its representativeness in international competitions, as the Olympic Games. The common areas of Sport's professional intervention, the initiatives of events, publications, research groups and scientific organizations related to the CS are also presented. Additionally, studies applied to different areas of Sport's professional intervention - physical training, technical and tactical preparation, management and organization - were also illustrated. Finally, perspectives of new studies and aspects related to professional preparation were reported

Nuclear Interaction between ADR-Induced p65 and p53 Mediates Cardiac Injury in iNOS (−/−) Mice

Adriamycin (ADR) treatment causes an imbalance in the levels of nitric oxide ((•)NO) and superoxide (O(2) (•−)) production leading to cardiac injury. Previously we demonstrated that mice lacking inducible nitric oxide synthase (iNOS) have increased oxidative stress and mitochondrial injury. The molecular events leading to increased mitochondrial injury in iNOS deficient mice is unknown. ADR in the absence of iNOS preferentially activates a proapoptotic pathway without a concurrent increase in prosurvival pathways. Treatment with ADR leads to an increase in DNA binding activity of nuclear factor kappa B (NFκB) and p53 in wildtype mice. Following ADR treatment, p53, but not NFκB DNA binding activity, as well as the level of Bax, a p53 target gene, was increased in iNOS (−/−) mice. This apoptotic signaling effect in iNOS (−/−) is alleviated by overexpression of manganese superoxide dismutase (MnSOD). Increases in NFκB and p53 in ADR-treated wildtype mice did not lead to increases in target genes such as MnSOD, bcl-xL, or Bax. Moreover, co-immunoprecipitation analysis revealed that p65, a prominent member of the NFκB family, interacts with p53 in the nucleus. These results suggest that NFκB and p53 may counter act one another's actions in ADR-treated wildtype (WT) mice. Further, these results identify a novel mechanism by which oxidative stress may regulate transcription of proapoptotic genes