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

Phases and evolution of microstructures in Ti–60 at.% Al

The formation and stability of Al-rich Ti-Al phases is reviewed and the kinetics of the phase transformations and evolution of lamellar TiAl + r-TiAl2 microstructures is discussed. For this a couple of Ti-60 at.% Al alloys were processed by different techniques to generate different initial microstructures. The kinetics were studied by annealing the differently processed alloys for 1, 10, 100 and 1000 h at temperatures between 800 and 1000 degrees C and then analysing the quenched microstructures by optical, scanning electron, and transmission electron microscopy. In addition, in situ heating and cooling experiments using differential thermal analysis and transmission electron microscopy were performed to verify the results obtained for the quenched samples. The results conclusively show why the metastable phases h-TiAl2 and Ti3Al5 form. The stability and transformation of the metastable phases have been determined in dependence on time and temperature and the kinetics of the two different mechanisms by which the stable phase r-TiAl2 forms have been established. The effects of differing initial microstructures on the evolution of the microstructure with time and temperature are discussed. (C) 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved