The role of ATP and adenosine in the brain under normoxic and ischemic conditions

By taking advantage of some recently synthesized compounds that are able to block ecto-ATPase activity, we demonstrated that adenosine triphosphate (ATP) in the hippocampus exerts an inhibitory action independent of its degradation to adenosine. In addition, tonic activation of P2 receptors contributes to the normally recorded excitatory neurotransmission. The role of P2 receptors becomes critical during ischemia when extracellular ATP concentrations increase. Under such conditions, P2 antagonism is protective. Although ATP exerts a detrimental role under ischemia, it also exerts a trophic role in terms of cell division and differentiation. We recently reported that ATP is spontaneously released from human mesenchymal stem cells (hMSCs) in culture. Moreover, it decreases hMSC proliferation rate at early stages of culture. Increased hMSC differentiation could account for an ATP-induced decrease in cell proliferation. ATP as a homeostatic regulator might exert a different effect on cell trophism according to the rate of its efflux and receptor expression during the cell life cycle. During ischemia, adenosine formed by intracellular ATP escapes from cells through the equilibrative transporter. The protective role of adenosine A1 receptors during ischemia is well accepted. However, the use of selective A1 agonists is hampered by unwanted peripheral effects, thus attention has been focused on A2A and A3 receptors. The protective effects of A2A antagonists in brain ischemia may be largely due to reduced glutamate outflow from neurones and glial cells. Reduced activation of p38 mitogen-activated protein kinases that are involved in neuronal death through transcriptional mechanisms may also contribute to protection by A2A antagonism. Evidence that A3 receptor antagonism may be protective after ischemia is also reported

Improving the Management of an Emergency Call Service by Combining Process Mining and Discrete Event Simulation Approaches

Part 10: Performance and OptimizationInternational audienceEach Emergency Medical Assistance Centre in France (SAMU), includes an emergency call service. It provides an adequate and immediate response to medical problems. The processing of the incoming calls can be seen as a collaborative process involving several stakeholders. The control of such a process is crucial. Indeed, the effectiveness of the response to these incoming calls strongly impacts the quality of service of these centres, which is the main information which the government relies for their funding. The aim of this paper is to analyse such a collaborative process, regarding the performance targets requested by the French government. To this end, we suggest applying a new approach, based on the combination of two well-known engineering techniques, in consecutive manner. We will first use process mining techniques to obtain meaningful knowledge about the studied collaborative processes, relying on real data from a French Emergency Medical Assistance Centre. Secondly, we will use a Discrete Event Simulation approach as an effective tool to assess the efficiency of the current management of this emergency call centre and to ask (and answer) some ‘what if?’ questions to identify possible ways of improving their effectiveness