Dobutamine in Paediatric Population: A Systematic Review in Juvenile Animal Models

Objective: Although dobutamine is widely used in neonatal clinical practice, the evidence for its use in this specific population is not clear. We conducted a systematic review of the use of dobutamine in juvenile animals to determine whether the evidence from juvenile animal experiments with dobutamine supported the design of clinical trials in neonatal/ paediatric population. Methods: Studies were identified by searching MEDLINE (1946-2012) and EMBASE (1974-2012). Articles retrieved were independently reviewed by three authors and only those concerning efficacy and safety of the drug in juvenile animals were included. Only original articles published in English and Spanish were included. Results: Following our literature search, 265 articles were retrieved and 24 studies were included in the review: 17 focused on neonatal models and 7 on young animal models. Although the aims and design of these studies, as well as the doses and ages analysed, were quite heterogeneous, the majority of authors agree that dobutamine infusion improves cardiac output in a dose dependent manner. Moreover, the cardiovascular effects of dobutamine are influenced by postnatal age, as well as by the dose used and the duration of the therapy. There is inadequate information about the effects of dobutamine on cerebral perfusion to draw conclusions. Conclusion: There is enough preclinical evidence to ensure that dobutamine improves cardiac output, however to better understand its effects in peripheral organs, such as the brain, more specific and well designed studies are required to provide additional data to support the design of clinical trials in a paediatric population.

Differential Neuroprotective Effects of 5 '-Deoxy-5 '-Methylthioadenosine

Background: 5'-deoxy-5'-methylthioadenosine (MTA) is an endogenous compound produced through the metabolism of polyamines. The therapeutic potential of MTA has been assayed mainly in liver diseases and, more recently, in animal models of multiple sclerosis. The aim of this study was to determine the neuroprotective effect of this molecule in vitro and to assess whether MTA can cross the blood brain barrier (BBB) in order to also analyze its potential neuroprotective efficacy in vivo. Methods: Neuroprotection was assessed in vitro using models of excitotoxicity in primary neurons, mixed astrocyte-neuron and primary oligodendrocyte cultures. The capacity of MTA to cross the BBB was measured in an artificial membrane assay and using an in vitro cell model. Finally, in vivo tests were performed in models of hypoxic brain damage, Parkinson's disease and epilepsy. Results: MTA displays a wide array of neuroprotective activities against different insults in vitro. While the data from the two complementary approaches adopted indicate that MTA is likely to cross the BBB, the in vivo data showed that MTA may provide therapeutic benefits in specific circumstances. Whereas MTA reduced the neuronal cell death in pilocarpine-induced status epilepticus and the size of the lesion in global but not focal ischemic brain damage, it was ineffective in preserving dopaminergic neurons of the substantia nigra in the 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)-mice model. However, in this model of Parkinson's disease the combined administration of MTA and an A(2A) adenosine receptor antagonist did produce significant neuroprotection in this brain region. Conclusion: MTA may potentially offer therapeutic neuroprotection.

Nuevos materiales arqueológicos de la cueva de «El Arco B» (Ramales de la Victoria, Cantabria)

[ES] Se presentan un colgante lítico decorado y una placa caliza con pintura localizados en la cueva de El Arco B. Ambas piezas fueron recuperadas en superficie, sin un contexto estratigráfico preciso. La evaluación de la materia prima, de la morfología del soporte y de la decoración del colgante apuntan a considerar, como probable, su pertenencia al Paleolítico superior inicial. La placa decorada no encuentra paralelos claros en el frente cantábrico, por lo cual no es posible precisar más allá de una genérica adscripción al Paleolítico superior. Los materiales arqueológicos y las pinturas rojas ya conocidos, y las nuevas evidencias aquí presentadas, apuntan a considerar el yacimiento de El Arco B como un importante centro de hábitat y de creación artística.

Aplicación del método de series de Uranio al grafismo rupestre de estilo paleolítico: el caso de la cavidad de Covalanas (Ramales de la Victoria, Cantabria)

[EN] Se ensaya la aplicación del procedimiento analítico de series de Uranio para el conocimiento de la seriación artística de obras parietales de estilo paleolítico. El resultado obtenido muestra la validez del método y abre nuevas vías para la obtención de fechas absolutas "ante quem" y "post quem" que sirvan para enmarcar momentos de ejecución de obras rupestres.

En torno al llamado «arte esquemático-abstracto»: a propósito de unas fechas de Covalanas (Ramales de la Victoria, Cantabria)

[ES] La introducción de técnicas físico-químicas al estudio del grafismo rupestre paleolítico está abriendo nuevos campos de conocimiento sobre los procedimientos técnicos, la cronología y la conservación de los motivos. La utilización de la técnica radiométrica de C14 A.M.S. ha sido aplicada en Covalanas. Las dataciones de época histórica de dos pequeños fragmentos de carbón procedentes de marcas negras sirven para reflexionar en torno al llamado «arte esquemático-abstracto».

Evaluation of Fentanyl Disposition and Effects in Newborn Piglets as an Experimental Model for Human Neonates

Background: Fentanyl is widely used off-label in NICU. Our aim was to investigate its cerebral, cardiovascular and pulmonary effects as well as pharmacokinetics in an experimental model for neonates. Methods: Fentanyl (5 mu g/kg bolus immediately followed by a 90 minute infusion of 3 mu g/kg/h) was administered to six mechanically ventilated newborn piglets. Cardiovascular, ventilation, pulmonary and oxygenation indexes as well as brain activity were monitored from T = 0 up to the end of experiments (T = 225-300 min). Also plasma samples for quantification of fentanyl were drawn. Results: A "reliable degree of sedation" was observed up to T = 210-240 min, consistent with the selected dosing regimen and the observed fentanyl plasma levels. Unlike cardiovascular parameters, which were unmodified except for an increasing trend in heart rate, some of the ventilation and oxygenation indexes as well as brain activity were significantly altered. The pulmonary and brain effects of fentanyl were mostly recovered from T = 210 min to the end of experiment. Conclusion: The newborn piglet was shown to be a suitable experimental model for studying fentanyl disposition as well as respiratory and cardiovascular effects in human neonates. Therefore, it could be extremely useful for further investigating the drug behaviour under pathophysiological conditions.