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

Quantitative microbiological monitoring of hemodialysis fluids: evaluation of methods and demonstration of lack of test relevance in single-pass hemodialysis machines with automatic dialysate proportioning with reverse osmosis-treated tap water

Two methods for estimating the quantity of microorganisms present in hemodialysis fluid, a blood agar surface-spread plate method and a total-count water tester device impregnated with modified standard plate count agar (Millipore Corp., Bedford, Mass.), were evaluated. Both methods exhibited comparable precision; however, colony counts obtained with the total-count water tester were consistently and unacceptably low. The need for routine quantitative microbiological monitoring of hemodialysis fluids such as that recommended by the American Public Health Association was not supported by the results of this study. Such testing was not of value in predicting untoward reactions for patients undergoing hemodialysis, nor did quantitative testing of hemodialysis fluids identify the buildup of potentially hazardous levels of contamination within hemodialysis systems. Finally, the kinds of organisms found in hemodialysis systems, i.e., gram-negative water-borne bacilli, were elucidated.</jats:p

Myeloid and lymphoid dendritic cells in normal pregnancy and pre-eclampsia

The aim of our study was to estimate the populations of peripheral blood myeloid and lymphoid dendritic cells (CD1c(+), BDCA-2(+)) and the CD1c(+) : BDCA-2(+) ratio in normal pregnant women and in patients with pre-eclampsia. Fifteen women in the first, second and third trimesters of normal pregnancy, and 25 patients with pre-eclampsia were included in the study. The dendritic cells were isolated from peripheral blood, stained with monoclonal antibodies against blood dendritic cell antigens (anti-CD1c, anti-BDCA-2) and estimated using the flow cytometric method. CD1c(+) and BDCA-2(+) dendritic cells were present in women during all trimesters of physiological pregnancy and in pre-eclamptic patients. It was observed that the numbers of dendritic cells were significantly lower in the second trimester when compared with the first and third trimesters of normal pregnancy. Furthermore, in the second trimester, CD1c(+) : BDCA-2(+) ratio was higher than in the other trimesters of physiological pregnancy. All populations of dendritic cells and CD1c(+) : BDCA-2(+) ratio did not differ in the first and third trimesters of normal pregnancy. The percentage of BDCA-2(+) dendritic cells was significantly lower in pre-eclampsia in comparison with healthy women in the third trimester of physiological pregnancy, while CD1c(+) : BDCA-2(+) ratio was significantly higher in pre-eclamptic patients when compared with control groups. We concluded that dendritic cells may be involved in the immune regulation during physiological pregnancy. CD1c(+) and BDCA-2(+) cells can influence the Th2 phenomenon which is observed during physiological pregnancy. Furthermore, it seems possible that lower BDCA-2(+) cells percentage and higher CD1c(+) : BDCA-2(+) ratio can be associated with increased Th1-type immunity in patients with pre-eclampsia