Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Práticas baseadas em evidências publicadas no Brasil: identificação e análise de suas vertentes e abordagens metodológicas

Revisão integrativa de estudos brasileiros sobre práticas baseadas em evidências (PBE) em saúde, publicados em periódicos ISI/JCR, nos últimos 10 anos. O objetivo foi identificar as especialidades que mais realizaram estes estudos, seus enfoques e abordagens metodológicas. A partir de critérios de inclusão, foram selecionados 144 trabalhos. Os resultados indicam que a maior quantidade de estudos feitos em PBE foram sobre infância e adolescência, infectologia, psiquiatria/saúde mental e cirurgia. Os enfoques predominantes foram prevenção, tratamento/reabilitação, diagnóstico e avaliação. As metodologias mais empregadas foram revisão sistemática sem ou com metanálise, revisão de protocolos ou síntese de estudos de evidências já disponíveis, e revisão integrativa. Constata-se forte expansão multiprofissional da PBE no Brasil, contribuindo para a busca de práticas mais criteriosas pela reunião, reconhecimento e análise crítica dos conhecimentos produzidos. O estudo contribui também para a própria análise dos modos de fazer pesquisa e novas possibilidades de investigação