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

Electron microscopy of crack/particle interactions in Al2O3/SiC nanocomposites

Crack/particle interactions in alumina/silicon carbide nanocomposites have been investigated by scanning electron microscopy and transmission electron microscopy, with cracks induced by Vickers microindentation. Intergranular cracks are frequently deflected into grains by SiC particles on grain boundaries inclined to the average direction of crack propagation, This mechanism is proposed to explain the change in the fracture mode from intergranular fracture for monolithic alumina to predominantly transgranular fracture for the nanocomposites. Neither stress-induced microcracking around SiC particles nor significant crack deflection by intragranular particles was found to occur in the nanocomposites. It is argued that an addition of nanoparticles may not be a promising approach for increasing the toughness of alumina