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Background: Children are the most vulnerable population exposed to the use of antibiotics often incorrectly prescribed for the treatment of infections really due to viruses rather than to bacteria. We designed the MAREA study which consisted of two different studies: i) a surveillance study to monitor the safety/efficacy of the antibiotics for the treatment of pneumonia (CAP), pharyngotonsillitis and acute otitis media in children younger than 14 yrs old, living in Liguria, North-West Italy and ii) a pre-/post-interventional study to evaluate the appropriateness of antibiotic prescription for the treatment these infections. In this paper, we show only results of the appropriateness study about the antibiotic prescription for the treatment of pneumonia. Methods: Patients included in this study met the following inclusion criteria: i) admission to the Emergency/ Inpatient Dpt/outpatient clinic of primary care pediatricians for pneumonia requiring antibiotics, ii) informed written consent. The practice of prescribing antibiotics was evaluated before-and-after a 1 day-educational intervention on International/National recommendations. Results: Global adherence to guidelines was fulfilled in 45%: main reason for discordance was duration (shorter than recommended). Macrolide monotherapy and cephalosporins were highly prescribed; ampicillin/amoxicillin use was limited. 61% of patients received >1 antibiotic; parenteral route was used in 33%. After intervention, i) in all CAP, cephalosporin prescription decreased (-23%) and the inappropriate macrolide prescriptions was halved and, ii) in not hospitalized CAP (notH-CAP), macrolides were prescribed less frequently (-25%) and global adherence to guidelines improved (+39%); and iii) in H-CAP antibiotic choice appropriateness increase. Conclusion: Prescribing practices were sufficiently appropriate but widespread preference for multidrug empirical regimens or macrolide in monotherapy deserve closer investigation. [ABSTRACT FROM AUTHOR]

Extracellular [K+] can increase during some pathological conditions, resulting into excessive glutamate release through multiple mechanisms. We here investigate the overflow of [3H]d-aspartate ([3H]d-ASP) and of endogenous glutamate elicited by increasing [K+] from purified rat cerebrocortical synaptosomes. Depolarization with [K+] ≤ 15 mmol/L provoked [3H]d-ASP and glutamate overflows almost totally dependent on external Ca2+. Consistent with release by exocytosis, the overflow of [3H]d-ASP evoked by 12 mmol/L K+ was sensitive to clostridial toxins. The overflows evoked by 35/50 mmol/L K+ remained external Ca2+-dependent by more than 50%. The Ca2+-independent components of the [3H]d-ASP overflows evoked by [K+] > 15 mmol/L were prevented by the glutamate transporter inhibitorsdl- threo-beta-benzyloxyaspartate (dl-TBOA) and dihydrokainate. Differently, the overflows of endogenous glutamate provoked by [K+] > 15 mmol/L were insensitive to both inhibitors; the external Ca2+-independent glutamate overflow caused by 50 mmol/L KCl was prevented by bafilomycin, by chelating intraterminal Ca2+, by blocking the mitochondrial Na+/Ca2+ exchanger and, for a small portion, by blocking anion channels. In contrast to purified synaptosomes, the 50 mmol/L K+-evoked release of endogenous glutamate or [3H]D-ASP was inhibited bydl-TBOA in crude synaptosomes; moreover, it was external Ca2+-insensitive and blocked bydl-TBOA in purified gliosomes, suggesting that carrier-mediated release of endogenous glutamate provoked by excessive [K+] in CNS tissues largely originates from glia. [ABSTRACT FROM AUTHOR]

Glutamate release induced by mild depolarization was studied in astroglial preparations from the adult rat cerebral cortex, that is acutely isolated glial sub-cellular particles (gliosomes), cultured adult or neonatal astrocytes, and neuron-conditioned astrocytes. K+ (15, 35 mmol/L), 4-aminopyridine (0.1, 1 mmol/L) or veratrine (1, 10 μmol/L) increased endogenous glutamate or [3H]d-aspartate release from gliosomes. Neurotransmitter release was partly dependent on external Ca2+, suggesting the involvement of exocytotic-like processes, and partly because of the reversal of glutamate transporters. K+ increased gliosomal membrane potential, cytosolic Ca2+ concentration [Ca2+]i, and vesicle fusion rate. Ca2+ entry into gliosomes and glutamate release were independent from voltage-sensitive Ca2+ channel opening; they were instead abolished by 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiurea (KB-R7943), suggesting a role for the Na+/Ca2+ exchanger working in reverse mode. K+ (15, 35 mmol/L) elicited increase of [Ca2+]i and Ca2+-dependent endogenous glutamate release in adult, not in neonatal, astrocytes in culture. Glutamate release was even more marked in in vitro neuron-conditioned adult astrocytes. As seen for gliosomes, K+-induced Ca2+ influx and glutamate release were abolished by KB-R7943 also in cultured adult astrocytes. To conclude, depolarization triggers in vitro glutamate exocytosis from in situ matured adult astrocytes; an aptitude grounding on Ca2+ influx driven by the Na+/Ca2+ exchanger working in the reverse mode. [ABSTRACT FROM AUTHOR]

Abstract: The Ca2+-dependent exocytotic release of [3H]d-aspartate and [3H]GABA evoked by 15mM KCl depolarization was studied in wobbler mice, an animal model of selective motor neuron degeneration in the cervical tract of the spinal cord. Neurotransmitters release was studied in superfusion using synaptosomes purified from the cervical or lumbar tract of the spinal cord. The early symptomatic stage (4 weeks) and the late symptomatic stage (12 weeks) of the disease were considered. Results showed that the KCl-induced release of [3H]d-aspartate was significantly increased in synaptosomes of the cervical region in wobbler mice with respect to healthy control mice, while the basal outflow was unchanged; this alteration was present both at 4 and 12 weeks. On the contrary, the KCl-induced release of [3H]d-aspartate from the lumbar spinal cord did not differ in wobbler and control mice. The KCl-induced release of [3H]GABA from cervical and lumbar spinal cord synaptosomes was unmodified at 4 weeks of age while it was moderately but significantly reduced in wobbler mice at 12 weeks, selectively in the cervical spinal cord. No changes in K m and V max for [3H]l-glutamate uptake were found in spinal cord synaptosomes from wobbler mice, compared to controls, both at 4 and 12 weeks of age. Taken together our data indicate the presence of an increased glutamate release in the affected region of spinal cord in wobbler mice, suggesting a possible involvement of altered glutamate homeostasis already in early stages of the wobbler disease, in the absence of appreciable changes in the uptake process. [Copyright &y& Elsevier]