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

Transverse Atlantal Ligament Disruption Associated With Odontoid Fractures

Objectives. The authors evaluated transverse atlantal ligament integrity in patients with fractures of the odontoid process of the axis. Summary of Background Data. Injuries of the transverse atlantal ligament can result in atlantoaxial instability after fractures of the atlas or axis, even if osseous healing occurs. Methods. The clinical histories and follow-up examinations and radiographic data of 30 patients with odontoid fractures were reviewed, using a combination of magnetic resonance (MR) imaging, thin-cut computed tomography (CT), and plain radiographs to evaluate osseous and ligamentous injuries. Results and Conclusions. Osteoperiosteal ligamentous avulsion injuries were identified on MR imaging in three patients and were associated with acute and delayed instability and nonunion. The combination of MR imaging, CT, and plain radiographs is useful in evaluating unstable odontoid fractures to facilitate rational treatment planning. Odontoid fractures with transverse ligament injuries should be considered for early surgical stabilization because this combination of injuries is unlikely to heal nonoperatively. Anterior odontoid screw fixation should be avoided when the ligament is injured. © 1994, J.B. Lippincott Company