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

Biomarkers of oxidative stress in critically ill patients: what should be measured, when and how?

Purpose of review This review is dedicated to updating the knowledge on oxidative stress in critically ill patients with an intense inflammatory reaction, and to link it with recent findings supporting the possible involvement of oxidative injuries in systems and organs that frequently fail in the critically ill. Recent findings Some direct or indirect biomarkers of oxidative stress have been validated in critically ill patients, and further support the major role of oxidative stress in these conditions. Summary The assessment of oxidative stress, defined as the association between an increased production of oxygen-derived species and an exhaustion of the stores of antioxidants, requires a multimodal approach. Oxidative damage itself can be much better estimated by quantifying the oxidative byproducts of the lipids and proteins associated with an evaluation of the remaining stores of the corresponding functional antioxidants, or the activity of antioxidant enzymes, than by global tests of the total oxidative damage or the total antioxidant stores. Recent clinical data confirm an important role of increased oxidative stress in the acute dysfunctions of the respiratory, renal and cerebral systems

Clinical Case of the Month. Acute Methanol Intoxication

peer reviewedWe report a fatal methanol intoxication and discuss its physiopathology, diagnosis and treatment

Single LiBH 4 nanocrystal stochastic impacts at a micro waterjionic liquid interface

International audienceLiBH 4 is often employed as a reducing agent for metal nanoparticle (NP) preparation but is inherently a solid-state H 2 hydrogen storage agent. Herein it is shown, through a combination of electron/optical microscopies and single entity electrochemical study, that LiBH 4 is stored in the solid state within an ionic liquid (IL) as nanocrystals (NCs). The electrochemical monitoring of an immiscible waterjIL (wjIL) micro-liquidjliquid interface (LLI) shows interfacial charge exchange associated with the stochastic impacts of single NCs. Meanwhile, in situ optical monitoring of a wjmetal or wjIL interface shows that such impacts are associated with the development of a H 2-in-IL micro/nano-foam related to the poor solu-bility of H 2. Both the presence of solid NCs and the latter H 2-in-IL foam suggest that H 2 release from LiBH 4-in-IL is a slow, but likely controlled process. The rate of H 2 production at a macroscopic LLI is further confirmed by gas chromatographic measurements, in very good agreement with microscopic observations. The electrochemical LLI provides unique investigative access to LiBH 4 NCs and offers insight into H 2 storage in ILs, or for direct borohydride fuel cells, as well as NP synthesis

Process Window for Seeded Growth of Arrays of Quasi-Spherical Substrate-Supported Au Nanoparticles

The controlled growth of surface-supported metal nanoparticles (NPs) is essential to a broad range of applications. To this end, we explore the seeded growth of highly ordered arrays of substrate-supported Au NPs through a fully orthogonal design of experiment (DoE) scheme applied to a reaction system consisting of HAuCl4, citrate, and hydrogen peroxide. Scanning electron microscopy in combination with digital image analysis (DIA) is used to quantitatively characterize the resultant NP populations in terms of both particle and array features. The effective optical properties of the NP arrays are additionally analyzed using spectroscopic ellipsometry (SE), allowing characteristics of the localized surface plasmon resonances (LSPRs) of the arrays to be quantified. We study the dependence of the DIA- and SE-extracted features on the different reagent concentrations through modeling using multiple linear regression with backward elimination of independent variables. A process window is identified for which uniform arrays of quasi-spherical Au NPs are grown over large surface areas. Aside from reagent concentrations the system is highly sensitive to the hydrodynamic conditions during the deposition. This issue is likely caused by an Au precursor mass-transport limitation of the reduction reaction and it is found that agitation of the growth medium is best avoided to ensure a macroscopically even deposition. Parasitic homogeneous nucleation can also be a challenge and was separately studied in a full DoE scheme with equivalent growth media but without substrates, using optical tracking of the solutions over time. Conditions yielding quasi-spherical surface-supported NPs are found to also be affiliated with strong tendencies for parasitic homogeneous nucleation and thereby loss of Au precursor, but addition of polyvinyl alcohol can possibly help alleviate this issue