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

Cardiac retransplantation is an efficacious therapy for primary cardiac allograft failure

<p>Abstract</p> <p>Background</p> <p>Although orthotopic heart transplantation has been an effective treatment for end-stage heart failure, the incidence of allograft failure has increased, necessitating treatment options. Cardiac retransplantation remains the only viable long-term solution for end-stage cardiac allograft failure. Given the limited number of available donor hearts, the long term results of this treatment option need to be evaluated.</p> <p>Methods</p> <p>709 heart transplants were performed over a 20 year period at our institution. Repeat cardiac transplantation was performed in 15 patients (2.1%). A retrospective analysis was performed to determine the efficacy of cardiac retransplantation. Variables investigated included: 1 yr and 5 yr survival, length of hospitalization, post-operative complications, allograft failure, recipient and donor demographics, renal function, allograft ischemic time, UNOS listing status, blood group, allograft rejection, and hemodynamic function.</p> <p>Results</p> <p>Etiology of primary graft failure included transplant arteriopathy (n = 10), acute rejection (n = 3), hyperacute rejection (n = 1), and a post-transplant diagnosis of metastatic melanoma in the donor (n = 1). Mean age at retransplantation was 45.5 ± 9.7 years. 1 and 5 year survival for retransplantation were 86.6% and 71.4% respectively, as compared to 90.9% and 79.1% for primary transplantation. Mean ejection fraction was 67.3 ± 12.2% at a mean follow-up of 32.6 ± 18.5 mos post-retransplant; follow-up biopsy demonstrated either ISHLT grade 1A or 0 rejection (77.5 ± 95.7 mos post-transplant).</p> <p>Conclusion</p> <p>Cardiac retransplantation is an efficacious treatment strategy for cardiac allograft failure.</p

Wrist Injuries in Tennis Players: A Narrative Review

The wrist/hand complex forms the crucial final link in the kinetic chain between the body and the racquet and therefore has a number of important roles in the production of all tennis strokes. However, the internal and external loads that are created at the wrist during these strokes have the potential to contribute to pain and injury. Therefore, the purposes of this narrative review are to (1) determine the extent of the problem of wrist pain/injury in tennis players, (2) identify bony and soft tissue structures of the wrist that are susceptible to damage as a result of tennis play and (3) explore factors that may influence the development of wrist pain/injury in tennis players. The epidemiological data revealed two important points. First, some evidence suggests wrist pain/injury accounts for a higher percentage of total injuries in more recent studies (2014–2015) than in early studies (1986–1995). Second, the relative frequency of wrist pain/injury compared with other well-recognized problem areas for tennis players such as the shoulder complex, elbow and lumbar spine is noticeably higher in more recent studies (2014–2015) than in early studies (1986–1995), particularly among females. Collectively, this would seem to indicate that the problem of wrist pain/injury has increased in the modern game. In fact, some wrist injuries appear to be related to the use of certain forehand grip types and the predominant use of the two-handed backhand. While the loads experienced at the wrist during tennis stroke production seem to be below threshold levels for a single event, the cumulative effects of these loads through repetition would appear to be an important consideration, especially when inadequate time is allowed to complete normal processes of repair and adaptation. This is supported by the evidence that most wrist injuries in tennis are associated with overuse and a chronic time course. The complex interaction between load, repetition, and training practices in tennis, particularly among young developing players who choose a path of early specialization, needs to be further explored