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

Comparison of a biopsychosocial therapy (BT) with a conventional biomedical therapy (MT) of subacute low back pain in the first episode of sick leave: a randomized controlled trial

This randomized controlled clinical trial compares the effectiveness of a biopsychosocial treatment with a solely conventional biomedical therapy in patients with subacute low back pain using parameters for pain intensity, functional status, depressive dysfunction and work performance. Sixty-four patients with a first-time sick leave between 3 and 12 weeks due to low back pain were randomly assigned to either a conventional biomedical therapy (MT; n=33) group, or a biopsychosocial therapy (BT; n=31) group including a psychotherapeutic module; both in accordance with a standardized 3 weeks inpatient treatment. Pain intensity, functional back capacity, clinical parameters and depressive dysfunction revealed significant improvement in both treatment groups at end of 3 weeks therapy (T1). However, at 6 months (T2), analysis revealed significant better results for nearly all parameters in the BT group that showed further improvement from T1 to T2, whereas the values in the MT group deteriorated from T1 back to the baseline values. During the 2-year period after therapy, 10% in MT and 59% in BT required no further sick leave due to low back pain. The results of the study indicate that a psychotherapeutic element in the treatment of low back pain appears to positively influence pain, functional status and work performance when conducted at an early stage of chronification and helps in the achievement of a better outcome