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

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Adenosine is a neuromodulator that operates via the most abundant inhibitory adenosine A1 receptors (A1Rs) and the less abundant, but widespread, facilitatory A2ARs. It is commonly assumed that A1Rs play a key role in neuroprotection since they decrease glutamate release and hyperpolarize neurons. In fact, A1R activation at the onset of neuronal injury attenuates brain damage, whereas its blockade exacerbates damage in adult animals. However, there is a down-regulation of central A1Rs in chronic noxious situations. In contrast, A2ARs are up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection in adult animals. The brain neuroprotective effect of A2AR antagonists is maintained in chronic noxious brain conditions without observable peripheral effects, thus justifying the interest of A2AR antagonists as novel protective agents in neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, ischemic brain damage and epilepsy. The greater interest of A2AR blockade compared to A1R activation does not mean that A1R activation is irrelevant for a neuroprotective strategy. In fact, it is proposed that coupling A2AR antagonists with strategies aimed at bursting the levels of extracellular adenosine (by inhibiting adenosine kinase) to activate A1Rs might constitute the more robust brain neuroprotective strategy based on the adenosine neuromodulatory system. This strategy should be useful in adult animals and especially in the elderly (where brain pathologies are prevalent) but is not valid for fetus or newborns where the impact of adenosine receptors on brain damage is different

National guidelines for the prevention and clinical management of dental trauma in individuals during their developmental age

Annali di Igiene are happy to publish - in issue 6, 2013 - the “National Guidelines for the Prevention and Clinical Management of Dental Trauma in Individuals during their Developmental Age”, which have been prepared by a multidisciplinary team of experts on behalf of the italian Ministry of Health and revised by the WHO Centre “Epidemiology and Community Dentistry” at the Medical School of the State University of Milan. The need for such Guidelines emerges from the fact that the application of correct procedures after a dental trauma is presently far from being satisfactory, only 4% of the cases being managed correctly according to the literature. Actually, compared to the increasing cases of dental trauma due to the growing dynamism of the daily life, especially for the youngsters, many emergency structures are not ready to gather the full set of experts who only are in the position, working together, to obtain a successful aesthetic and functional recovery of the patient. The Guidelines consider the problem gradually, starting from the necessary psychological approach to the traumatized young patient, continuing with the complex diagnostic procedures and the correct therapeutic interventions, ending with the planning of the necessary follow-up, designed to guarantee a correct evolution of the trauma toward the full recover

National guidelines for the prevention and clinical management of dental trauma in individuals during their developmental age.

Annali di Igiene are happy to publish - in issue 6, 2013 - the “National Guidelines for the Prevention and Clinical Management of Dental Trauma in Individuals during their Developmental Age”, which have been prepared by a multidisciplinary team of experts on behalf of the italian Ministry of Health and revised by the WHO Centre “Epidemiology and Community Dentistry” at the Medical School of the State University of Milan. The need for such Guidelines emerges from the fact that the application of correct procedures after a dental trauma is presently far from being satisfactory, only 4% of the cases being managed correctly according to the literature. Actually, compared to the increasing cases of dental trauma due to the growing dynamism of the daily life, especially for the youngsters, many emergency structures are not ready to gather the full set of experts who only are in the position, working together, to obtain a successful aesthetic and functional recovery of the patient. The Guidelines consider the problem gradually, starting from the necessary psychological approach to the traumatized young patient, continuing with the complex diagnostic procedures and the correct therapeutic interventions, ending with the planning of the necessary follow-up, designed to guarantee a correct evolution of the trauma toward the full recover