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

Analysis of patient outcomes following proton radiation therapy for retinoblastoma

Purpose: Proton radiation therapy (PRT) is used to treat patients with retinoblastoma (RB) and has the potential to minimize exposure of normal tissue to radiation and thus decrease the risk of toxicity and second malignancies. However, comprehensive analyses of long-term patient outcomes are not available. Methods and materials: Patients with RB who were treated with PRT at our institution between 1986 and 2012 were invited to participate in a study that was designed to assess long-term outcomes. Patients who were enrolled in the study underwent a comprehensive analysis that included oncologic, ophthalmic, endocrine, cephalometric, and quality of life (QOL) assessments. Results: A total of 12 patients were enrolled in this study. The average length of follow-up was 12.9 years (range, 4.8-22.2 years). All study patients had bilateral disease, and the disease and visual outcomes were similar to the outcomes for all patients with RB who were treated with PRT over the same time period at our institution. An analysis of endocrine-related test results revealed no growth abnormalities or hormonal deficiencies across the cohort. Magnetic resonance imaging scans and external cephalometry showed that PRT was associated with less facial hypoplasia than enucleation. Patient and parent-proxy QOL assessments revealed that treatment for RB did not appear to severely affect long-term QOL. Conclusions: In addition to providing an opportunity for long-term disease control and functional eye preservation, PRT does not appear to be associated with unexpected late visual, endocrine, or QOL effects in this cohort of patients with RB

Feedbacks from Filter Feeders: Review on the Role of Mussels in Cycling and Storage of Nutrients in Oligo- Meso- and Eutrophic Cultivation Areas

Cultured and wild bivalve stocks provide ecosystem services through regulation of nutrient dynamics; both by regeneration of nutrients that become available again for phytoplankton production (positive feedback), and by extractionof nutrients through filtration and storage in tissue (negative feedback). Consequently, bivalves may fulfil a role in water quality management. The magnitude of regulating services by filter feeding bivalves varies between coastal ecosystems. This review uses the blue mussel as a model species and evaluates how cultured mussel stocks regulate nutrient dynamics in oligo- meso- and eutrophic ecosystems. We thereby examine (i) the eco-physiological response of mussels, and (ii) the positive and negative feedback mechanisms between mussel stocks and the surrounding ecosystem. Mussel culture in nutrient-poor areas (deep Norwegian fjords) are compared with cultures in other coastal systems with medium- to rich nutrient conditions. It was found that despite differences in eco-physiological rates under nutrient-poor conditions (higher clearance, lower egestion, similar excretion and tissue storage rates), the proportion of nutrients regenerated was similar between (deep) nutrient-poorand (shallow) nutrient-rich areas. Of the filtered nutrients, 40–50% is regeneratedand thus made available again for phytoplankton growth, and 10–50% of thefiltered nutrients is stored in tissue and could be removed from the system by harvest. A priori, we inferred that as a consequence of low background nutrient levels, mussels would potentially have a larger effect on ecosystem functioning in nutrient-poor systems and/or seasons. However, this review showed that due to the physical characteristics (volume, water residence time) and low mussel densities in nutrient-poor Norwegian fjord systems, the effects were lower for these sites, while estimates were more profound in shallow nutrient-rich areas with more intensive aquaculture activities, especially in terms of the negative feedback mechanisms (filtration intensity)