2-arachidonyl glycerol activates platelets via conversion to arachidonic acid and not by direct activation of cannabinoid receptors.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: There are conflicting views in the literature as to whether cannabinoids have an impact on platelet activity and to what extent cannabinoid receptors are involved. This is an important issue to resolve because platelet effects of putative therapeutic cannabinoid inhibitors and stimulators will have an impact on their potential benefits and safety. WHAT THIS PAPER ADDS: The data presented in this manuscript clearly show that the endocannabinoid 2-arrachidonyl glycerol can activate platelet activity, but that the effects are mediated through an aspirin-sensitive pathway that is not affected by cannabinoid receptor antagonists or FAAH inhibition, but is abolished by MAGL inhibition. The findings question the role of cannabinoid receptors in platelet function and suggest that platelet function is unlikely to be directly affected by cannabinoid receptor antagonists, at least in the acute phase. AIMS: Cannabinoid receptor-1 (CB(1)) antagonists suppress appetite and induce weight loss. Direct antagonism of CB(1) receptors on platelets might be an additional benefit for CB(1) antagonists, but the role of CB(1) receptors in platelets is controversial. We tested the hypothesis that the endocannabinoid, 2-arachidonyl glycerol (2-AG), induces platelet aggregation by a COX-mediated mechanism rather than through CB(1) receptor activation, in blood obtained from healthy volunteers and patients with coronary artery disease receiving low dose aspirin. METHODS: Aggregatory responses to the cannabinoids 2-AG and Delta(9)-THC were examined in blood sampled from healthy volunteers (n= 8) and patients (n= 12) with coronary artery disease receiving aspirin using whole blood aggregometry. The effects of CB(1) (AM251) and CB(2) (AM630) antagonists, as well as fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) inhibitors and aspirin on 2-AG-induced aggregation were also assessed. RESULTS: AM251 (100 nm-30 microm) had no effect on platelet aggregation induced by either ADP (P= 0.90) or thrombin (P= 0.86). 2-AG, but not Delta(9)-THC, induced aggregation. 2-AG-induced aggregation was unaffected by AM251 and AM630 but was abolished by aspirin (P < 0.001) and by the MAGL inhibitor, URB602 (P < 0.001). Moreover, the aggregatory response to 2-AG was depressed (by >75%, P < 0.001) in blood from patients with coronary artery disease receiving aspirin compared with that from healthy volunteers. CONCLUSIONS: 2-AG-mediated activation of platelets is via metabolism to arachidonic acid by MAGL, and not through direct action on CB(1) or CB(2) receptors, at least in the acute phase.

The Science And Art Of Delivery: Accelerating The Diffusion Of Health Care Innovation.

There is a widely acknowledged time lag in health care between an invention or innovation and its widespread use across a health system. Much is known about the factors that can aid the uptake of innovations within discrete organizations. Less is known about what needs to be done to enable innovations to transform large systems of health care. This article describes the results of in-depth case studies aimed at assessing the role of key agents and agencies that facilitate the rapid adoption of innovations. The case studies-from Argentina, England, Nepal, Singapore, Sweden, the United States, and Zambia-represent widely varying health systems and economies. The implications of the findings for policy makers are discussed in terms of key factors within a phased approach for creating a climate for change, engaging and enabling the whole organization, and implementing and sustaining change. Purposeful and directed change management is needed to drive system transformation.

Antimicrobial resistance: addressing the global threat through greater awareness and transformative action.

Antimicrobial therapies have played an unquestionably important role in advancing modern medical and surgical care, treating animals, reducing the global burden of communicable disease, and prolonging human life expectancy. These transformational benefits are threatened because of the rapidly advancing phenomenon of antimicrobial resistance. As a result of complex factors across many sectors and international actors, the global impact of antimicrobial resistance is an escalating economic and health crisis. This article draws on the collective expertise and summit report of the Antimicrobial Resistance Working Group from the 2013 World Innovation Summit for Health, in Doha, Qatar. It defines a framework of principles and tasks for key policy makers to raise international awareness of antimicrobial resistance and lead transformative action through policy-driven improvements in sanitation, antimicrobial conservation, agricultural practices, and research and development.

Lessons from eight countries on diffusing innovation in health care.

Health care systems are under increasing pressure to cope with shifting demographics, the threat of chronic and noncommunicable disease, and rising health care costs. The uptake of innovations to meet these challenges and to advance medicine and health care delivery is not as rapid as the pace of change. Greater emphasis on the diffusion of innovation and greater understanding of the structural and organizational levers that can be used to facilitate systemwide improvement are essential. This article describes the results of a qualitative and quantitative study to assess the factors and behaviors that foster the adoption of health care innovation in eight countries: Australia, Brazil, England, India, Qatar, South Africa, Spain, and the United States. It describes the front-line cultural dynamics that must be fostered to achieve cost-effective and high-impact transformation of health care, and it argues that there is a necessity for greater focus on vital, yet currently underused, organizational action to support the adoption of innovation.