A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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'Statins in retinal disease'

Statins are known for their blood cholesterol-lowering effect and are widely used in patients with cardiovascular and metabolic diseases. Research over the past three decades shows that statins have diverse effects on different pathophysiological pathways involved in angiogenesis, inflammation, apoptosis, and anti-oxidation, leading to new therapeutic options. Recently, statins have attracted considerable attention for their immunomodulatory effect. Since immune reactivity has been implicated in a number of retinal diseases, such as uveitis, age-related macular degeneration (AMD) and diabetic retinopathy, there is now a growing body of evidence supporting the beneficial effects of statins in these retinopathies. This review evaluates the relationship between statins and the pathophysiological basis of these diseases, focusing on their potential role in treatment. A PubMed database search and literature review was conducted. Among AMD patients, there is inconsistent evidence regarding protection against development of early AMD or delaying disease progression; though they have been found to reduce the risk of developing choroidal neovascular membranes (CNV). In patients with retinal vein occlusion, there was no evidence to support a therapeutic benefit or a protective role with statins. In patients with diabetic retinopathy, statins demonstrate a reduction in disease progression and improved resolution of diabetic macular oedema (DMO). Among patients with uveitis, statins have a protective effect by reducing the likelihood of uveitis development

The sheddase activity of ADAM17/TACE is regulated by the tetraspanin CD9

ADAM17/TACE is a metalloproteinase responsible for the shedding of the proinflammatory cytokine TNF-a and many other cell surface proteins involved in development, cell adhesion, migration, differentiation, and proliferation. Despite the important biological function of ADAM17, the mechanisms of regulation of its metalloproteinase activity remain largely unknown. We report here that the tetraspanin CD9 and ADAM17 partially co-localize on the surface of endothelial and monocytic cells. In situ proximity ligation, co-immunoprecipitation, crosslinking, and pull-down experiments collectively demonstrate a direct association between these molecules. Functional studies reveal that treatment with CD9-specific antibodies or neoexpression of CD9 exert negative regulatory effects on ADAM17 sheddase activity. Conversely, CD9 silencing increased the activity of ADAM17 against its substrates TNF-a and ICAM-1. Taken together, our results show that CD9 associates with ADAM17 and, through this interaction, negatively regulates the sheddase activity of ADAM17s. This work was supported by grants BFU2007-66443/BMC and BFU2010-19144/BMC from Ministerio de Ciencia e Innovación, a grant from Fundación de Investigación Médica Mutua Madrileña and by RETICS Program RD08/0075-RIER (Red de Inflamacio´n y Enfermedades Reumáticas) from Instituto de Salud Carlos III (to C.C.), a grant from Fundación de Investigación Médica Mutua Madrileña (to M.D.G.L.), and grants PI080794 from Instituto de Salud Carlos III (to M.Y-M) and SAF2007-60578 from Ministerio de Ciencia e Innovación (to E.M.L.). M.D.G.L. was supported by a contract associated to grant SAF2004-01715 from Ministerio de Ciencia e Innovacio´n. S.O. was supported by an I3P predoctoral Fellowship from Consejo Superior de Investigaciones Científicas (CSIC) and by a contract associated to grant BFU2007-66443/BMC from Ministerio de Ciencia e Innovacio´n. A.G. has been supported by a predoctoral Fellowship from Instituto de Salud Carlos III and by grant BFU2007-66443/BMC from Ministerio de Ciencia e Innovación.Peer reviewe