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

Seismic damage scenarios in Lefkas old town (W. Greece)

Damage scenarios were developed for the Lefkada old town (LOT). LOT is the historical center of the capital of Lefkas Island, part of the Ionian Islands, one of the most seismically prone areas within the Mediterranean region that suffered numerous devastating earthquakes in the past. The most recent strong earthquake with Mw = 6.2 occurred on 14 August 2003 at a distance of about 13 km from LOT. A peak ground acceleration (PGA) equal to 0.42 g was recorded in LOT, one of the highest values ever recorded in Greece. Nevertheless, the 2003 event produced limited damage to the buildings of LOT, comprising traditional construction practices of architectural significance and a high seismic behaviour. Towards the development of damage scenarios the following tasks were performed: (a) buildings inventory and vulnerability indices determination using EMS-98 along with behaviour modification scores, (b) subsoil response functions and 1D viscoelastic models calculation using microtremors and (c) stochastic PGA simulation using site amplification deduced from the subsoil response functions. Two scenarios were developed considering the sources of the 2003 M6.2 earthquake and a future M7 event, located at the same fault. The discrete damage probability was resolved by formulating a beta distribution of an average damage grade related to the vulnerability index and the simulated PGA through empirical equations. The deduced models are comparable with the observed 2003 damage distribution, hence they are likely useful for preparing future emergency plans. In the aftermath, although further investigation is needed to explain outliers, the implementation of the followed methodology into an automated procedure for near real time shake and damage maps generation in case of a seismic crisis is highly recommended. The work herein, with proper adaptations, is potentially fairly applicable for other towns and regions in Europe