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

Doença de Crohn e farmacobezoar intestinal: relato de caso Crohn's disease and bowel pharmacobezoar: case report

Bezoares são concreções de materiais diversos, parcialmente ou não digeridos, que podem ser encontrados em qualquer porção do tubo digestivo. Raramente são compostos por fármacos, nestes casos denominados farmacobezoares. Este artigo visa relatar o caso de um paciente com Doença de Crohn complicada por fístula entero-cutânea e áreas de estenoses no íleo terminal apresentando bezoar de mesalazina. Foi enfatizado o caráter multifatorial da gênese dos farmacobezoares, assim como a variada gama de apresentações clínicas e exames diagnósticos úteis no esclarecimento dos casos. Devemos ainda salientar a necessidade de individualização do tratamento para melhor eficácia do mesmo.<br>Bezoars are masses composed of foreign material, partially digested or not, found in any portion of the gastrointestinal tract. Rarely bezoars are composed by medication tablets, becoming known as Pharmacobezoars. This article reports a patient with the Crohn's disease complicated by enteric fistulae and stenotic areas in the ileum presenting Mesalazine pharmacobezoars. The author emphasizes the multi-factorial origin of pharmacobezoars, the wide range of clinical presentations and the diagnostic tools useful in these cases. The individualized treatment necessary to obtain the satisfactory clinical results is also highlighted

A simple paradigm for nooconomics, the economy of knowledge

International audienceThe human noosphere and its inner dynamic are forming a fascinating yet poorly understood multiscale complex system, in which one may represent the interaction of individual knowledge holders and their collective dynamic. Here I propose a simple, improvable paradigm for noodynamics (the study of knowledge flows) and nooconomics at large (the economy of knowledge) based on two intrinsic properties of knowledge-its prolificity and collegiality-and on three simple transfer laws capturing some fundamental differences between material and immaterial economics, namely 1) that knowledge exchanges , unlike property exchanges, are flows, and thus time-dependent, 2) that knowledge exchanges are positive sum, unlike material exchanges and 3) that combinations of knowledge are non linear. I then make a suggestion for a basic knowledge flow equation, namely that transferred knowledge is proportional to the product of spent attention and time, and discuss some of its social and political implications. keywords: knowledge economy, noosphere, multiscale dynamic, knowledge flow, noodynam-ics The purpose of this article is to outline a simple and improvable paradigm for noody-namics, the study of knowledge flows. If we endow this paradigm with an economic perspective, and consider its agents buyers and sellers, it can then also be considered an early working paradigm, or more precisely, an early building block towards a working paradigm, for nooconomics, the economy of knowledge. I thus attempt to demonstrate that noodynamics can be codified extremely simply, although not entirely , and will leave the many exceptions to the present paradigm to discussion

Efficient developmental mis-targeting by the sporamin NTPP vacuolar signal to plastids in young leaves of sugarcane and Arabidopsis

Plant vacuoles are multi-functional, developmentally varied and can occupy up to 90% of plant cells. The N-terminal propeptide (NTPP) of sweet potato sporamin and the C-terminal propeptide (CTPP) of tobacco chitinase have been developed as models to target some heterologous proteins to vacuoles but so far tested on only a few plant species, vacuole types and payload proteins. Most studies have focused on lytic and protein-storage vacuoles, which may differ substantially from the sugar-storage vacuoles in crops like sugarcane. Our results extend the evidence that NTPP of sporamin can direct heterologous proteins to vacuoles in diverse plant species and indicate that sugarcane sucrose-storage vacuoles (like the lytic vacuoles in other plant species) are hostile to heterologous proteins. A low level of cytosolic NTPP-GFP (green fluorescent protein) was detectable in most cell types in sugarcane and Arabidopsis, but only Arabidopsis mature leaf mesophyll cells accumulated NTPP-GFP to detectable levels in vacuoles. Unexpectedly, efficient developmental mis-trafficking of NTPP-GFP to chloroplasts was found in young leaf mesophyll cells of both species. Vacuolar targeting by tobacco chitinase CTPP was inefficient in sugarcane, leaving substantial cytoplasmic activity of rat lysosomal beta-glucuronidase (GUS) [ER (endoplasmic reticulum)-RGUS-CTPP]. Sporamin NTPP is a promising targeting signal for studies of vacuolar function and for metabolic engineering. Such applications must take account of the efficient developmental mis-targeting by the signal and the instability of most introduced proteins, even in storage vacuoles