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

Improvement in outcomes after implantation of a novel polyurethane meniscal scaffold for the treatment of medial meniscus deficiency

© 2014, Springer-Verlag Berlin Heidelberg. Purpose: Meniscal injury resulting in segmental loss of meniscal tissue is a major risk factor for the development of osteoarthritis. Tissue engineering strategies have provided scaffolds for meniscal regeneration in order to establish a treatment option for patients with limited opportunities for meniscal reconstruction. The purpose of this study was to assess the clinical and magnetic resonance imaging (MRI) results 2 years after implantation of a polyurethane scaffold for chronic segmental medial meniscus deficiency following partial medial meniscectomy. Methods: Eighteen patients were treated with arthroscopic implantation of an ActiFit® (Orteq Sports Medicine) polyurethane meniscal scaffold for meniscus deficiency of the medial meniscus. Patients were followed up at 6, 12, and 24 months. Clinical outcome was assessed using patient-reported outcome scores (KOOS, KSS, UCLA activity scale, VAS for pain). Radiological outcome was assessed using MRI at 6, 12, and 24 months by evaluating scaffold morphology, scaffold integration, and additional joint injury, as well as joint inflammation. Results: Eighteen patients with a median age of 32.5 years (range 17–49) were enrolled. Statistically significant improvements were present in all patients, but one at 2 years compared to baseline in all categories. Complete resorption of the scaffold occurred in one patient representing a failure to treatment. MRI showed abnormal signal intensity of the scaffold when compared to residual meniscal tissue but without synovitis or joint inflammation. Extrusion of the scaffold was present in four patients. No correlation between scaffold extrusion and clinical outcome was observed. Conclusion: Arthroscopic implantation of a polyurethane meniscal scaffold in patients with chronic segmental medial meniscus deficiency is not only a safe procedure but leads to good clinical results at a 2-year follow-up. Scaffold extrusion did not appear to affect clinical outcome. Level of evidence: IV