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

Assisted reproductive technology in Europe, 2000 : results generated from European registers by ESHRE

European results of assisted reproductive techniques from treatments initiated during 2000 are presented in this fourth annual report. Data were collected mainly from pre-existing national registers. From 22 countries, 569 clinics reported 279 267 cycles: IVF 126 961, ICSI 99 976, frozen embryo replacement (FER) 45 800 and oocyte donations (OD) 6530. In nine countries where all clinics reported to the register, a total of 142 174 cycles were performed in a population of 166 million, corresponding to 856 cycles per million inhabitants. After IVF and ICSI, the distribution of transfer of one, two, three and greater than or equal to4 embryos was 12.1, 46.7, 33.3 and 6.8%, respectively. Huge differences existed between countries. For IVF, the clinical pregnancy rate per aspiration and per transfer was 24.7 and 28.4%, respectively. For ICSI, the corresponding rates were 26,6% and 28,7%. These figures represent increases of 0.7 and 0.8% compared with 1999. The distribution of singleton, twin, triplet and quadruplet deliveries for IVF and ICSI combined was 73.6, 24.4, 2.0 and 0.04%. This gives a total multiple delivery rate of 26.4%. The range of triplet deliveries after IVF and ICSI ranged from 0.3 to 7.0% between countries. Compared with 1999, the number of reported cycles was increased by 8% and the clinical pregnancy rate per transfer was increased by 0.7% after IVF and by 0.8% after ICSI. The total multiple delivery rates after IVF and ICSI remain unchanged during the last 4 years

Tau Reduction Diminishes Spatial Learning and Memory Deficits after Mild Repetitive Traumatic Brain Injury in Mice

<div><p>Objective</p><p>Because reduction of the microtubule-associated protein Tau has beneficial effects in mouse models of Alzheimer's disease and epilepsy, we wanted to determine whether this strategy can also improve the outcome of mild traumatic brain injury (TBI).</p><p>Methods</p><p>We adapted a mild frontal impact model of TBI for wildtype C57Bl/6J mice and characterized the behavioral deficits it causes in these animals. The Barnes maze, Y maze, contextual and cued fear conditioning, elevated plus maze, open field, balance beam, and forced swim test were used to assess different behavioral functions. Magnetic resonance imaging (MRI, 7 Tesla) and histological analysis of brain sections were used to look for neuropathological alterations. We also compared the functional effects of this TBI model and of controlled cortical impact in mice with two, one or no <i>Tau</i> alleles.</p><p>Results</p><p>Repeated (2-hit), but not single (1-hit), mild frontal impact impaired spatial learning and memory in wildtype mice as determined by testing of mice in the Barnes maze one month after the injury. Locomotor activity, anxiety, depression and fear related behaviors did not differ between injured and sham-injured mice. MRI imaging did not reveal focal injury or mass lesions shortly after the injury. Complete ablation or partial reduction of tau prevented deficits in spatial learning and memory after repeated mild frontal impact. Complete tau ablation also showed a trend towards protection after a single controlled cortical impact. Complete or partial reduction of tau also reduced the level of axonopathy in the corpus callosum after repeated mild frontal impact.</p><p>Interpretation</p><p>Tau promotes or enables the development of learning and memory deficits and of axonopathy after mild TBI, and tau reduction counteracts these adverse effects.</p></div