65 research outputs found
Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (â„140âmmâHg systolic blood pressure orâ â„90âmmâHg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention
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
Guidelines for management of ischaemic stroke and transient ischaemic attack 2008
This article represents the update of the European Stroke Initiative Recommendations for Stroke Management. These guidelines cover both ischaemic stroke and transient ischaemic attacks, which are now considered to be a single entity. The article covers referral and emergency management, Stroke Unit service, diagnostics, primary and secondary prevention, general stroke treatment, specific treatment including acute management, management of complications, and rehabilitation
The impact of extreme low flows on the water quality of the lower Murray River and lakes (South Australia)
The impact of extreme low flows on the water quality of the Lower Murray River and Lower Lakes (Alexandrina and Albert) in South Australia was assessed by comparing water quality from five sites during an extreme low flow period (March 2007âNovember 2009) and a preceding reference period (March 2003âNovember 2005). Significant increases in salinity, total nitrogen, total phosphorus, chlorophyll a and turbidity were observed in the Lower Lakes during the low flow period. Consequently, water quality guidelines for the protection of aquatic ecosystems were greatly exceeded. Principal Component Analysis, empirical and mass balance model calculations suggested these changes could be attributed primarily to the lack of flushing resulting in concentration of dissolved and suspended material in the lakes, and increased sediment resuspension as the lakes became shallower. The river sites also showed significant but more minor salinity increases during the extreme low flow period, but nutrient and turbidity concentrations decreased. The most plausible reasons for these changes were decreased catchment inputs and increased influence of saline groundwater inputs. The results highlight the vulnerability of arid and semi-arid lake systems to reduced flow conditions as a result of climatic changes and/or water management decisions.Luke M. Mosley, Benjamin Zammit, Emily Leyden, Theresa M. Heneker, Matthew R. Hipsey, Dominic Skinner and Kane T. Aldridg
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