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Single doses of p38 MAP kinase inhibitors or prednisolone affect CRP and IL-6 in patients with active Rheumatoid Arthritis (RA)

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Open Journal of Immunology 2012年第3期2卷 85-97页

作者： Pauline T. Lukey Hayley C. Perry Shuying Yang simon parry Marion C. Dickson Virginia H. Norris Paul G. Russell Marie Watissée Inmaculada Rioja Keith P. Ray Scott Crowe Michael Binks GlaxoSmithKline R&D Medicines Research Centre Stevenage UK

Purpose: To investigate the effects of single doses of losmapimod, dilmapimod (inhibitors of p38 MAPK) and prednisolone on biomarkers of systemic inflammation (serum C-reactive protein (CRP) and interleukin (IL)-6) in subjects with active rheumatoid arthritis (RA). Methods: Two randomized, double blind, placebo controlled, parallel group, single dose studies investigated the CRP and IL-6 dose-response relationships for losmapimod (study A) and dilmapimod and prednisolone (study B) in patients with active RA on stable weekly doses of methotrexate. CRP, IL-6 and other exploratory biomarkers were measured in blood at baseline and up to 72 hours post-dosing. Results: In study A, 51 subjects were randomized to receive losmapimod (7.5, 20 and 60 mg) or placebo and in study B, 77 subjects were randomized to receive dilmapimod (7.5, 15 and 25 mg) or prednisolone (10, 20 and 50 mg) or placebo. Single doses of prednisolone caused a decrease in circulating IL-6 detectable at 3 and 24 hours post-dose as well as a CRP single-dose relationship at 48 hours post-dose in patients with active RA. All doses of losmapimod produced a statistically significant reduction in serum IL-6, 3 hours post-dose but had no effect on CRP. Dilmapimod had no effect on IL-6 or CRP at any dose or time. Conclusion: This single-dose response clinical study design could be useful in the early clinical development of anti-inflammatory agents for the treatment of rheumatoid arthritis. Inhibition of both circulating IL-6 and CRP would increase confidence that a new chemical entity may have the potential to deliver clinical benefit in RA. Trial registration: [***: NCT00256919 and NCT00134693].

关键词： p38 MAPK Prednisolone RA Biomarkers Proof of Mechanism Randomised Controlled Trial

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Single doses of p38 MAP kinase inhibitors or prednisolone affect CRP and IL-6 in patients with active Rheumatoid Arthritis (RA)

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Open Journal of Immunology（免疫学期刊） 2012年第3期

作者： Pauline T. Lukey Hayley C. Perry Shuying Yang simon parry Marion C. Dickson Virginia H. Norris Paul G. Russell Marie Watissée Inmaculada Rioja Keith P. Ray Scott Crowe Michael Binks

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Building the new international science of the agriculture-food-water-environment Nexus in China and the world

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Ecosystem Health and Sustainability 2016年第11期2卷 2-8页

作者： Xinguang Zhu Martin parry Yonglong Lu Matthew Heard Guangguo Ying simon Vaughan Jianbo Shen Alan Jenkins Yunpeng Wang Silvia Lacorte Tingping Ouyang Francisco Pedrero Salcedo Jun Niu John Quinton Chunling Luo Fusuo Zhang Gan Zhang William Davies Kevin Jones David Tyfield CAS Key laboratory for Computational Biology CAS-MPG Partner Institute for Computational BiologyChinese Academy of SciencesShanghaiChina Lancaster Environment Centre Lancaster UniversityLancasterUK Research Centre for Eco-Environmental Sciences Chinese Academy of SciencesBeijingChina Centre for Ecology and Hydrology WallingfordUK Guangzhou Institute of Geochemistry Chinese Academy of SciencesGuangzhouChina Rothamsted Research HarpendenUK China Agricultural University BeijingChina Centre for Ecology and Hydrology LancasterUK Consuejo Superior de Investigaciones Cientificas BarcelonaSpain International Research and Innovation Centre for the Environment(I-RICE) GuangzhouChina

The multiple,complex and systemic problems of the agriculture-food-water-environment nexus(“Nexus”)are among the most significant challenges of the 21st *** is a key site for Nexus research amidst profound socio-environmental *** policy implications of these problems have been authoritatively summarized *** study presents discussions at an international workshop in Guangzhou that asked instead“What science is needed to deliver the growing policy commitments regarding these challenges?And,What changes are needed to the science itself?”Understanding and effective intervention regarding the Nexus calls for a paradigm shift:to a new kind of science of(capacity for)international,interdisciplinary,and impactful research working with and within complex socio-natural *** here argue that science must become proactive in approach,striving only for“minimal harm”not“silver bullet”solutions,and adopting an explicitly long-term strategic ***,these arguments lead to calls for reorienting science and science policy in three ways:from short-term remediation to longer-term optimization;from a focus on environmental threats to one on the opportunities for international collaborative learning;and toward supporting new forms of scientific *** bring these points together by recommending a new form of scientific institution:a global network of collaborative Nexus Centres,under the umbrella of a global Food Nexus Organization akin to those of the human genome and proteome.

关键词： agriculture-food-water-environment Nexus China complex systems food security international col-laboration new science.

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