Mortalidad perinatal en los partos únicos asistidos a término en España entre 1995 y 2009 según ocurrieran en domicilio particular o en centro sanitario

Objetivo principal: Evidenciar posibles diferencias en la mortalidad perinatal de los partos únicos asistidos a término en España entre 1995 y 2009, según ocurrieran en domicilio particular o en centro sanitario. Metodología: Estudio de cohorte retrospectivo a partir del registro de partos del Instituto Nacional de Estadística de España (INE). Resultados principales: Entre 1995 y 2009 ocurrieron 23 muertes del feto o del recién nacido (hasta las primeras 24 horas de vida) sobre un total de 14.614 partos únicos asistidos a término en domicilio particular (1,57 muertes cada mil partos). El número de muertes en partos de las mismas características ocurridos en centros sanitarios fue de 7.548 sobre un total de 4.716.956 partos (1,60 muertes cada mil partos). OR=0,98 IC(95%)=0,65-1,48. Conclusión principal: Entre 1995 y 2009 no se han dado diferencias estadísticamente significativas en relación con la mortalidad del feto o el recién nacido registrada en el Boletín Estadístico del Parto, entre los partos únicos asistidos a término en domicilio particular y los partos de las mismas características atendidos en centro sanitario.

Muscle-Type Nicotinic Receptor Blockade by Diethylamine, the Hydrophilic Moiety of Lidocaine

Lidocaine bears in its structure both an aromatic ring and a terminal amine, which can be protonated at physiological pH, linked by an amide group. Since lidocaine causes multiple inhibitory actions on nicotinic acetylcholine receptors (nAChRs), this work was aimed to determine the inhibitory effects of diethylamine (DEA), a small molecule resembling the hydrophilic moiety of lidocaine, on Torpedo marmorata nAChRs microtransplanted to Xenopus oocytes. Similarly to lidocaine, DEA reversibly blocked acetylcholine-elicited currents (IACh) in a dose-dependent manner (IC50 close to 70 μM), but unlike lidocaine, DEA did not affect IACh desensitization. IACh inhibition by DEA was more pronounced at negative potentials, suggesting an open-channel blockade of nAChRs, although roughly 30% inhibition persisted at positive potentials, indicating additional binding sites outside the pore. DEA block of nAChRs in the resting state (closed channel) was confirmed by the enhanced IACh inhibition when pre-applying DEA before its co-application with ACh, as compared with solely DEA and ACh co-application. Virtual docking assays provide a plausible explanation to the experimental observations in terms of the involvement of different sets of drug binding sites. So, at the nAChR transmembrane (TM) domain, DEA and lidocaine shared binding sites within the channel pore, giving support to their open-channel blockade; besides, lidocaine, but not DEA, interacted with residues at cavities among the M1, M2, M3, and M4 segments of each subunit and also at intersubunit crevices. At the extracellular (EC) domain, DEA and lidocaine binding sites were broadly distributed, which aids to explain the closed channel blockade observed. Interestingly, some DEA clusters were located at the α-γ interphase of the EC domain, in a cavity near the orthosteric binding site pocket; by contrast, lidocaine contacted with all α-subunit loops conforming the ACh binding site, both in α-γ and α-δ and interphases, likely because of its larger size. Together, these results indicate that DEA mimics some, but not all, inhibitory actions of lidocaine on nAChRs and that even this small polar molecule acts by different mechanisms on this receptor. The presented results contribute to a better understanding of the structural determinants of nAChR modulation.