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

Analysis of cutaneous and internal gill gas exchange morphology in early larval amphibians, Pseudophryne bibronii and Crinia georgiana

This study uses stereological techniques to examine body, internal gill and cardiovascular morphology of two larval amphibians, Pseudophryne bibronii and Crinia georgiana, to evaluate the roles of diffusive and convective gas exchange. Gosner stage 27 specimens were prepared for light microscopy and six parallel sections of equal distance taken through the body as well as a further six through the heart and internal gills. Body, internal gill and heart volume as well as body and internal gill surface areas were determined. The harmonic mean distance across the internal gills was also measured and used to estimate oxygen diffusive conductance, DO2. The species were of similar body size and surface area, but the heart and internal gills were larger in P. bibronii, which may represent precursors for greater growth of the species beyond stage 27. The much larger surface area of the skin compared to the internal gills in both species suggests it is the main site for gas exchange, with the gills supplementing oxygen uptake. The sparse cutaneous capillary network suggests diffusion is the main oxygen transport mechanism across the skin and directly into deeper tissues. A numerical model that simplifies larval shape, and has an internal (axial vessels) and external oxygen source, confirms that diffusion is able to maintain tissue oxygen with limited convective input.Casey A. Mueller, Roger S. Seymou