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

Secondary abdominal compartment syndrome after complicated traumatic lower extremity vascular injuries

Secondary abdominal compartment syndrome (ACS) can occur in trauma patients without abdominal injuries. Surgical management of patients presenting with secondary ACS after isolated traumatic lower extremity vascular injury (LEVI) continues to evolve, and associated outcomes remain unknown. From January 2006 to September 2011, 191 adult trauma patients presented to the Ryder Trauma Center, an urban level I trauma center in Miami, Florida with traumatic LEVIs. Among them 10 (5.2 %) patients were diagnosed with secondary ACS. Variables collected included age, gender, mechanism of injury, and clinical status at presentation. Surgical data included vessel injury, technical aspects of repair, associated complications, and outcomes. Mean age was 37.4 ± 18.0 years (range 16-66 years), and the majority of patients were males (8 patients, 80 %). There were 7 (70 %) penetrating injuries (5 gunshot wounds and 2 stab wounds), and 3 blunt injuries with mean Injury Severity Score (ISS) 21.9 ± 14.3 (range 9-50). Surgical management of LEVIs included ligation (4 patients, 40 %), primary repair (1 patient, 10 %), reverse saphenous vein graft (2 patients, 20 %), and PTFE interposition grafting (3 patients, 30 %). The overall mortality rate in this series was 60 %. The association between secondary ACS and lower extremity vascular injuries carries high morbidity and mortality rates. Further research efforts should focus at identifying parameters to accurately determine resuscitation goals, and therefore, prevent such a devastating condition