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

Epidemiology of Syncope in Hospitalized Patients

OBJECTIVE: To describe the etiologies of syncope in hospitalized patients and determine the factors that influence survival after discharge. DESIGN: Observational retrospective cohort. SETTING: Department of Veterans Affairs hospital, group-model HMO, and Medicare population in Oregon. PATIENTS: Hospitalized individuals (n = 1,516; mean age ± SD, 73.0 ± 13.4 years) with an admission or discharge diagnosis of syncope (ICD-9-CM 780.2) during 1992, 1993, or 1994. MEASUREMENTS AND MAIN RESULTS: During a median hospital stay of 3 days, most individuals received an electrocardiogram (97%) and prolonged electrocardiographic monitoring (90%), but few underwent electrophysiology testing (2%) or tilt-table testing (0.7%). The treating clinicians identified cardiovascular causes of syncope in 19% of individuals and noncardiovascular causes in 40%. The remaining 42% of individuals were discharged with unexplained syncope. Complete heart block (2.4%) and ventricular tachycardia (2.3%) were rarely identified as the cause of syncope. Pacemakers were implanted in 28% of the patients with cardiovascular syncope and 0.4% of the others. No patient received an implantable defibrillator. All-cause mortality ± SE was 1.1%± 0.3% during the admission, 13%± 1% at 1 year, and 41%± 2% at 4 years. The adjusted relative risk (RR) of dying for individuals with cardiovascular syncope (RR 1.18; 95% confidence interval [CI] 0.92, 1.50) did not differ from that for unexplained syncope (RR 1.0) and noncardiovascular syncope (RR 0.94; 95% CI 0.77, 1.16). CONCLUSIONS: Among these elderly patients hospitalized with syncope, noncardiovascular causes were twice as common as cardiovascular causes. Because survival was not related to the cause of syncope, clinicians cannot be reassured that hospitalized elderly patients with noncardiovascular and unexplained syncope will have excellent outcomes

The effect of acute pomegranate extract supplementation on oxygen uptake in highly-trained cyclists during high-intensity exercise in a high altitude environment

Abstract Background Recent research has indicated that pomegranate extract (POMx) may improve performance during aerobic exercise by enhancing the matching of vascular oxygen (O2) provision to muscular requirements. POMx is rich in ellagitannin polyphenols and nitrates (NO3 −), which are both associated with improvements in blood flow and O2 delivery. Primarily, this study aimed to determine whether POMx improves performance in a cycling time trial to exhaustion at 100%VO2max (TTE100%) in highly-trained cyclists. In addition, we investigated if the O2 cost (VO2) of submaximal exercise was lower with POMx, and whether any changes were greater at high altitude where O2 delivery is impaired. Methods Eight cyclists exercised at three submaximal intensities before completing a TTE100% at sea-level (SEA) and at 1657 m of altitude (ALT), with pre-exercise consumption of 1000 mg of POMx or a placebo (PLAC) in a randomized, double-blind, crossover design. Data were analysed using a three way (treatment x altitude x intensity) or two-way (treatment x altitude) repeated measures ANOVA with a Fisher’s LSD post-hoc analysis. Significance was set at p ≤ 0.05. The effect size of significant interactions was calculated using Cohen’s d. Results TTE100% performance was reduced in ALT but was not influenced by POMx (p > 0.05). Plasma NO3 − were 10.3 μmol greater with POMx vs. PLAC (95% CI, 0.8, 19.7,F 1,7 = 7.83, p  0.05). Submaximal VO2 values were not affected by POMx (p ≥ 0.05). Conclusions The restoration of SEA VO2 values at ALT is likely driven by the high polyphenol content of POMx, which is proposed to improve nitric oxide bioavailability. Despite an increase in VO2, no change in exercise performance occurred and therefore this study does not support the use of POMx as an ergogenic supplement