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

Enhanced magnetic coercivity of α-FeO obtained from carbonated 2-line ferrihydrite

We report the physical properties of α-FeO (hematite), synthesized by dry-heating (350-1,000°C) of a new, poorly ordered iron oxyhydroxide precursor compound that we name carbonated 2-line ferrihydrite. This precursor was characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, electron microscopy, and thermogravimetric analysis, whereas the α-FeO was studied with X-ray diffraction, scanning and transmission electron microscopy, and magnetic techniques. α-FeO synthesized at 350°C consisted of single-nanocrystal particles (length × width 20 ± 6 nm (L) × 15 ± 4 nm (W)), which at room temperature exhibited very narrow hysteresis loops of low coercivities (<300 Oe). However, α-FeO synthesized at higher temperatures (1,000°C) was composed of larger nanocrystalline particle aggregates (352 ± 109 nm (L) × 277 ± 103 nm (W)) that also showed wide-open hysteresis loops of high magnetic coercivities (∼5 kOe). We suggest that these synthesis-temperature-dependent coercivity values are a consequence of the subparticle structure induced by the different particle and crystallite size growth rates at increasing annealing temperature

How apoptotic cells aid in the removal of their own cold dead bodies

Apoptotic cell clearance facilitates the removal of aged, damaged, infected or dangerous cells although minimizing perturbation of surrounding tissues, and is a vital process in the development and homeostasis of multicellular organisms. Importantly, failure to correctly execute programmed cell death and subsequent corpse clearance is broadly associated with chronic inflammatory and/or autoimmune diseases such as systemic lupus erythematosus. Apoptotic cells develop dramatic morphological changes including contraction, membrane blebbing and apoptotic body formation, which were among the first and most readily identifiable features of cellular suicide. However, understanding the purpose of apoptotic cell morphological changes has proven to be elusive, and recent studies have made somewhat surprising, and occasionally opposing, conclusions about the contribution of blebbing to phagocytic clearance and prevention of inflammatory/autoimmune disease. We review the evidence indicating how apoptotic blebs actively promote corpse recognition, uptake, and generation of auto-reactive antibodies