London, United Kingdom 2013 Poster Session Red Cerebrovasc Dis 2013; 35 (suppl 3)1-854 555 503 Translational stroke research Establishing and evaluating consumer involvement in the design and development of stroke research: a new model for stroke research in Germany? C. Moshona1, M. Wagner2, P.U. Heuschmann3, I. Wellwood4 Centre for Stroke Research Berlin, Charité-Universitätsmedizin, Berlin, GERMANY1, Stiftung Deutsche Schlaganfall-Hilfe, Gütersloh, GERMANY2, Institut für Klinische Epidemiologie und Biometrie, Universität Würzburg, Würzburg, GERMANY3, Centre for Stroke Research Berlin, Cha-rité- Universitätsmedizin, Berlin, GERMANY4 Background Consumer or “user” involvement is an established component of the translational re-search process with perceived benefits in a number of countries. So far this concept and its related structures remain relatively undeveloped in German healthcare research. We set out to establish and evaluate the impact of consumer involvement in a stroke research centre in Berlin. Methods We adapted a consumer group model from a translational research centre in London. Re-cruitment strategies included: posters, leaflets, website and purposive sampling of stroke patients attending outpatient clinics. Patients attend an information meeting and provide informed consent. The group meets regularly (4 – 6 weeks) with various stroke researchers to ask and answer questions about ongoing research and proposals. Levels of consumer involvement in studies were reviewed using recognized categories (no involvement, ‘consultation with consumers’, ‘collaboration with consumers’, ‘consumer-led‘ activity) in 9 established activities e.g. setting up project; designing project materials; dissemination of the research findings. Ethical approval was obtained. Results Since January 2012, approximately 200 patients and carers (age 29-78) were invited to join the group. 46 patients and carers expressed interest. Currently a pool of 19 patients and carers (age 49-78) have attended at least one meeting and want to participate regularly. The group has to date attracted less severely disabled stroke patients, but includes carers of more disabled patients. Four projects have now established “consultation with consumers”. Conclusion We successfully established a consumer group allowing a formal dialogue between re-searchers, stroke patients and their carers and raising consumer involvement levels. The project is ongoing but how increased consultation is likely to impact on the quality, quantity or relevance of local clinical stroke research needs to be established before the model is adopted more widely. 504a Translational stroke research L-arginine:glycine amidinotransferase regulates homoarginine levels and affects stroke out-come in humans and mice C.U. Choe1, D. Atzler2, P.S. Wild3, A.M. Carter4, O. Simova5, M. Stockebrand6, S. Blankenberg7, R.H. Böger8, C. Gerloff9, P.J. Grant10, T. Magnus11, T. Zeller12, E. Schwedhelm13, D. Isbrandt14 Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, GER-MANY1, Department of Clinical Pharmacology and Toxicology, University Medical Center Ham-burg- Eppendorf, Hamburg, GERMANY2, Department of Cardiology and Angiology, Johannes Gutenberg University, Mainz, Mainz, GERMANY3, Division of Cardiovascular and Diabetes Re-search, University of Leeds, Leeds, UNITED KINGDOM4, Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, GERMANY5, Experimental Neuropediatrics, Uni-versity Medical Center Hamburg-Eppendorf, Hamburg, GERMANY6, Clinic for General and Inter-ventional Cardiology, University Heart Center Hamburg, University Medical Center Hamburg-Ep-pendorf, Hamburg, GERMANY7, Department of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, GERMANY8, Department of Neurology, Univer-sity Medical Center Hamburg-Eppendorf, Hamburg, GERMANY9,Division of Cardiovascular and Diabetes Research, University of Leeds, Leeds, UNITED KINGDOM10, Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, GERMANY11, Clinic for General and Interventional Cardiology, University Heart Center Hamburg, University Medical Center Ham-burg- Eppendorf, Hamburg, GERMANY12, Department of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, GERMANY13, Experimental Neuropedi-atrics, University Medical Center Hamburg-Eppendorf, Hamburg, GERMANY14 Background: Endogenous arginine homologues, including homoarginine, have been identified as novel biomarkers for cardiovascular disease and outcomes. In the present study we investigated the involvement of the arginine homologue homoarginine and its metabolism in stroke pathology and outcome. Methods: All-cause mortality in Leeds Stroke Study, genome-wide association study (GWAS) in Gutenberg Health Study, middle cerebral artery occlusion (MCAO) in transgenic mouse models Results: Here we show that the arginine-derivative homoarginine is independently associated with decreased long-term all-cause mortality after acute ischemic stroke (7.4 years follow-up, HR for 1 SD increase in homoarginine: 0.79 95% CI: 0.64, 0.96, P = 0.019, n = 389). GWAS revealed that plasma homoarginine is strongly associated with SNPs in the L-arginine:glycine amidinotransferase (AGAT) gene (P < 10-9, n = 2.996). To investigate the link between plasma homoarginine and out-come after experimental ischemic stroke, we employed two mouse models: one with genetic AGAT deletion (AGAT-/-), and a second with AGAT upregulation (guanidinoacetate N-methyltransferase knockout, GAMT-/-). Homoarginine was absent in AGAT-/- and elevated in GAMT-/- mice in com-parison to wildtype littermates. Cerebral damage and neurological deficits in experimental stroke were increased in AGAT-/- mice as compared to wildtype mice and were less severe on homoargi-nine supplementation. In line with these findings, infarct sizes in GAMT-/- mice were reduced. Conclusion: Our data establish that AGAT synthesizes homoarginine in humans and mice. Ho-moarginine plasma levels predict mortality after acute stroke in humans and attenuate experimental stroke severity in mice.
Karger_ESC London_2013
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