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

Wiederherstellung der Immunabwehr nach schwerem Weichteiltrauma durch Reaktivierung von Natürlichen Killer-Zellen

Orbital tuning and understanding climate response to astronomical forcing in the Miocene require detailed knowledge of the effect of tidal dissipation (Td) and dynamical ellipticity (dE) on astronomical solutions used to compute insolation and orbital target curves for paleoclimatic studies. These Earth parameters affect precession and obliquity; the determination of their effect is of fundamental importance, as phase relations between astronomical forcing and climate response can only be accurately calculated when the relative phasing between precession and obliquity is known. This determination can be achieved through comparison of solutions having different values for Td and/or dE with well-understood paleoclimate data. In this paper we use quantitative color records of precession-obliquity interference recorded in two successive 2.4 Myr eccentricity minima (9–9.6 and 11.5–12.1 Ma) in the Monte dei Corvi section in northern Italy to constrain the effect of Td, using the assumption of a direct response of sapropels to insolation. This quantitative approach results in a minimum uncertainty of astronomically tuned age models of ± 0.8 kyr and Td values 0.95 and 1.05 for the 9–9.6 Ma interval and of +4/−1 kyr (Td values between 0.95 and 1.15) for the 11.5–12.1 Ma interval. This (un)certainty not only limits the precision of determining phase relations but also improves our understanding of the limitations of tuned time scales and determining phase relations in the Miocene