Bmf upregulation through the AMP-activated protein kinase pathway may protect the brain from seizure-induced cell death.

Prolonged seizures (status epilepticus, SE) can cause neuronal death within brain regions such as the hippocampus. This may contribute to impairments in cognitive functioning and trigger or exacerbate epilepsy. Seizure-induced neuronal death is mediated, at least in part, by apoptosis-associated signaling pathways. Indeed, mice lacking certain members of the potently proapoptotic BH3-only subfamily of Bcl-2 proteins are protected against hippocampal damage caused by status epilepticus. The recently identified BH3-only protein Bcl-2-modifying factor (Bmf) normally interacts with the cytoskeleton, but upon certain cellular stresses, such as loss of extracellular matrix adhesion or energy crisis, Bmf relocalizes to mitochondria, where it can promote Bax activation and mitochondrial dysfunction. Although Bmf has been widely reported in the hematopoietic system to exert a proapoptotic effect, no studies have been undertaken in models of neurological disorders. To examine whether Bmf is important for seizure-induced neuronal death, we studied Bmf induction after prolonged seizures induced by intra-amygdala kainic acid (KA) in mice, and examined the effect of Bmf-deficiency on seizures and damage caused by SE. Seizures triggered an early (1-8 h) transcriptional activation and accumulation of Bax in the cell death-susceptible hippocampal CA3 subfield. Bmf mRNA was biphasically upregulated beginning at 1 h after SE and returning to normal by 8 h, while again being found elevated in the hippocampus of epileptic mice. Bmf upregulation was prevented by Compound C, an inhibitor of adenosine monophosphate-activated protein kinase, indicating Bmf expression may be induced in response to bioenergetic stress. Bmf-deficient mice showed normal sensitivity to the convulsant effects of KA, but, surprisingly, displayed significantly more neuronal death in the hippocampal CA1 and CA3 subfields after SE. These are the first studies investigating Bmf in a model of neurologic injury, and suggest that Bmf may protect neurons against seizure-induced neuronal death in vivo.

Epilepsy and microRNA.

MicroRNA (miRNA) is a class of small non-coding RNA which regulates post-transcriptional gene expression by repressing and thereby fine-tuning protein production, mainly via sequence-specific binding within the 3'untranslated region of mRNA transcripts. Although in humans there are only ∼1600 miRNAs, bioinformatics, systems studies and advanced quantitative proteomics reveal miRNA regulation of over half of all protein-coding genes and that each miRNA can regulate multiple proteins. Epilepsy is a common, serious neurologic disorder characterized by recurring unprovoked seizures that result from abnormal firing of populations of neurons in the brain. The brain expresses several unique miRNAs which control dendritic morphology as well as ion channel levels, neuronal migration and glial function. There is an emerging view that the patho-mechanisms underlying the process of epileptogenesis, as well as maintenance and progression of the epileptic state, involve miRNAs that control multiple genes and proteins on a systems level. Expression profiling studies reveal select changes to brain miRNA levels following prolonged seizures (status epilepticus) in animal models. Inflammation, stress signaling and neuronal excitation are among the pathways most impacted. Analysis of miRNA expression in human epilepsy has also been performed, where again neuroinflammatory processes were prominent. These studies suggest that miRNAs may regulate certain key processes but are not necessarily broadly altering all patho-mechanisms in epilepsy. Functional studies employing antagomirs have identified contributions from miR-34a and miR-132 to seizure-induced neuronal death whereas silencing miR-134 potently reduced status epilepticus, seizure-damage and the later occurrence of spontaneous seizures. Efforts to identify the in vivo target(s) of epilepsy-regulated miRNAs, is now a priority. Last, miRNAs are stable, information-carrying (paracrine) signals. Profiling miRNA in biofluids may represent a novel source of disease biomarkers in epilepsy. In summary, miRNA is emerging as a critical new layer of gene expression control with implications for the cause and treatment of epilepsy.

MicroRNA-34a upregulation during seizure-induced neuronal death.

MicroRNAs (miRNAs) are short, noncoding RNAs that function as posttranscriptional regulators of gene expression by controlling translation of mRNAs. A subset of miRNAs may be critical for the control of cell death, including the p53-regulated miRNA, miR-34a. Because seizures activate p53, and p53-deficient mice are reportedly resistant to damage caused by prolonged seizures, we investigated the role of miR-34a in seizure-induced neuronal death in vivo. Status epilepticus was induced by intra-amygdala microinjection of kainic acid in mice. This led to an early (2 h) multifold upregulation of miR-34a in the CA3 and CA1 hippocampal subfields and lower protein levels of mitogen-activated kinase kinase kinase 9, a validated miR-34a target. Immunoprecipitation of the RNA-induced silencing complex component, Argonaute-2, eluted significantly higher levels of miR-34a after seizures. Injection of mice with pifithrin-α, a putative p53 inhibitor, prevented miR-34a upregulation after seizures. Intracerebroventricular injection of antagomirs targeting miR-34a reduced hippocampal miR-34a levels and had a small modulatory effect on apoptosis-associated signaling, but did not prevent hippocampal neuronal death in models of either severe or moderate severity status epilepticus. Thus, prolonged seizures cause subfield-specific, temporally restricted upregulation of miR-34a, which may be p53 dependent, but miR-34a is probably not important for seizure-induced neuronal death in this model.

Epileptic tolerance is associated with enduring neuroprotection and uncoupling of the relationship between CA3 damage, neuropeptide Y rearrangement and spontaneous seizures following intra-amygdala kainic acid-induced status epilepticus in mice.

Brief, non-harmful seizures can activate endogenous protective programmes which render the brain resistant to damage caused by prolonged seizure episodes. Whether protection in epileptic tolerance is long-lasting or influences the subsequent development of epilepsy is uncertain. Presently, we investigated the relationship between hippocampal pathology, neuropeptide Y rearrangement and spontaneous seizures in sham- and seizure-preconditioned mice after status epilepticus induced by intra-amygdala kainate. Seizure-induced neuronal death at 24 h was significantly reduced in the ipsilateral hippocampal CA3 and hilus of tolerance mice compared to sham-preconditioned animals subject to status epilepticus. Damage to the CA3-hilus remained reduced in tolerance mice 21 days post-status. In sham-preconditioned mice subject to status epilepticus correlative statistics showed there was a strong inverse relationship between CA3, but not hilar, neuron counts and the number of spontaneous seizures. A strong positive association was also found between neuropeptide Y score and spontaneous seizure count in these mice. In contrast, there was no significant association between spontaneous seizure count and CA3 neuron loss or neuropeptide Y rearrangement in the tolerance mice. These data show that tolerance-conferred neuroprotection is long-lasting and that tolerance disrupts the normal association between CA3 damage, synaptic rearrangement and occurrence of spontaneous seizures in this model.

Contrasting patterns of Bim induction and neuroprotection in Bim-deficient mice between hippocampus and neocortex after status epilepticus.

Prolonged seizures (status epilepticus) are associated with brain region-specific regulation of apoptosis-associated signaling pathways. Bcl-2 homology domain 3-only (BH3) members of the Bcl-2 gene family are of interest as possible initiators of mitochondrial dysfunction and release of apoptogenic molecules after seizures. Previously, we showed that expression of the BH3-only protein, Bcl-2 interacting mediator of cell death (Bim), increased in the rat hippocampus but not in the neocortex after focal-onset status epilepticus. In this study, we examined Bim expression in mice and compared seizure damage between wild-type and Bim-deficient animals. Status epilepticus induced by intra-amygdala kainic acid (KA) caused extensive neuronal death within the ipsilateral hippocampal CA3 region. Hippocampal activation of factors associated with transcriptional and posttranslational activation of Bim, such as CHOP and c-Jun NH(2)-terminal kinases, was significant within 1 h. Upregulation of bim mRNA was evident after 2 h and Bim protein increased between 4 and 24 h. Hippocampal CA3 neurodegeneration was reduced in Bim-deficient mice compared with wild-type animals after seizures in vivo, and short interfering RNA molecules targeting bim reduced cell death after KA treatment of hippocampal organotypic cultures. In contrast, neocortical Bim expression declined after status epilepticus, and neocortex damage in Bim-deficient mice was comparable with that in wild-type animals. These results show region-specific differential contributions of Bim to seizure-induced neuronal death.

Loss of p53 results in protracted electrographic seizures and development of an aggravated epileptic phenotype following status epilepticus.

The p53 tumor suppressor is a multifunctional protein, which regulates cell cycle, differentiation, DNA repair and apoptosis. Experimental seizures up-regulate p53 in the brain, and acute seizure-induced neuronal death can be reduced by genetic deletion or pharmacologic inhibition of p53. However, few long-term functional consequences of p53 deficiency have been explored. Here, we investigated the development of epilepsy triggered by status epilepticus in wild-type and p53-deficient mice. Analysis of electroencephalogram (EEG) recordings during status epilepticus induced by intra-amygdala kainic acid (KA) showed that seizures lasted significantly longer in p53-deficient mice compared with wild-type animals. Nevertheless, neuronal death in the hippocampal CA3 subfield and the neocortex was significantly reduced at 72 h in p53-deficient mice. Long-term continuous EEG telemetry recordings after status epilepticus determined that the sum duration of spontaneous seizures was significantly longer in p53-deficient compared with wild-type mice. Hippocampal damage and neuropeptide Y distribution at the end of chronic recordings was found to be similar between p53-deficient and wild-type mice. The present study identifies protracted KA-induced electrographic status as a novel outcome of p53 deficiency and shows that the absence of p53 leads to an exacerbated epileptic phenotype. Accordingly, targeting p53 to protect against status epilepticus or related neurologic insults may be offset by deleterious consequences of reduced p53 function during epileptogenesis or in chronic epilepsy.

Efectos electrofisiológicos del sevoflurano versus propofol en niños con síndrome de Wolff-Parkinson-White / Electrophysiological effects of sevoflurane in comparison with propofol in children with Wolff-Parkinson-White syndrome

OBJETIVOS: Evaluar los efectos electrofisiológicos delsevoflurano en niños con síndrome de Wolff-Parkinson-White (WPW) sometidos a ablación por radiofrecuencia(RF).MÉTODOs: Se estudiaron de forma prospectiva 15pacientes con síndrome de WPW, programados paraestudio electrofiosológico (EEF) y ablación por RF.La inducción anestésica se realizó con fentanilo (2 μkg–1), propofol (3 mg kg–1) y vecuronio (0,1 mg kg–1) y el mantenimiento con propofol (100 μ kg–1 min–1), bolus de fentanilo y vecuronio según necesidades. El EEF(EEFpropofol) se practicó mediante la introducción de cuatro electrocatéteres intracardiacos. Se determinaron la función del nodo sinusal, la conducción sinoatrial, períodos refractarios (auricular, nodo AV, anterógrado y retrógrado de la vía accesoria, ventricular)y características de la taquicardia ortodrómicainducida. Posteriormente, se intercambió propofol por sevoflurano (1 MAC según edad) repitiendo las mediciones(EEFsevoflurano). Los parámetros EEFpropofol y EEFsevoflurano se compararon mediante el test de Wilcoxon. RESULTADOS: La edad media fue de 9,3 ± 6 años. Trasla administración de sevoflurano se produjo un alargamiento del período refractario efectivo anterógrado de la vía accesoria (EEFpropofol 283 ± 22 ms; EEFsevoflurano 298 ± 25 ms; p = 0,004), y del ciclo mínimo de estimulación con conducción ventrículo-atrial 1:1 (EEFpropofol 244 ± 41 ms; EEFsevoflurano 273 ± 28 ms; p = 0,028). No hubo cambios significativosen el resto de los parámetros. En todos lospacientes se consiguió la ablación de la vía accesoria.CONCLUSIONES: El sevoflurano modificó parcialmentelas propiedades de la vía accesoria, aunque esto no impidióla ablación de la misma

OBJECTIVE: To evaluate the electrophysiologicaleffects of sevoflurane in children with Wolff-Parkinson-White (WPW) syndrome undergoing radiofrequencyablation.METHODS: We performed a prospective study of 15patients with WPW syndrome who were scheduled foran electrophysiological study (EPS) and radiofrequencyablation.Anesthesia was induced with fentanyl (2 μg/kg),propofol (3 mg/kg), and vecuronium (0.1 mg/kg), andinitially maintained using propofol (100 μg/kg), withbolus administration of fentanyl and vecuronium asrequired. Four intracardiac catheters were introducedfor the EPSpropofol, which included measurements ofsinus-node function, sinoatrial-node conduction,refractory periods (atrial, AV-node, accessory pathwayanterograde and retrograde, and ventricular), and thecharacteristics of induced orthodromic tachycardia.The propofol was then replaced with sevoflurane (1MAC adjusted for age) and the measurements wererepeated (EPSsevoflurane). The EPSpropofol and EPSsevoflurane data were compared using the Wilcoxon signed-rank test.RESULTS: The mean (SD) age was 9.3 (6 ) years. Afteradministration of sevoflurane, the duration of the antegrade effective refractory period of the accessory pathway increased (EPSpropofol, 283 (22) ms; EPSsevoflurane, 298 (25) ms; P = .004), as did the duration of the minimum pacing cycle with 1:1 atrioventricular conduction (EPSpropofol, 244 (41) ms; EPSsevoflurane, 273 (28) ms; P = .028). No significant changes were observed in the other parameters. Ablation of the accessory pathway was achieved in all patients.CONCLUSIONS: Sevoflurane partially modified the properties of the accessory pathway but did not prevent ablation

Microarray profile of seizure damage-refractory hippocampal CA3 in a mouse model of epileptic preconditioning.

A neuroprotected state can be acquired by preconditioning brain with a stimulus that is subthreshold for damage (tolerance). Acquisition of tolerance involves coordinate, bi-directional changes to gene expression levels and the re-programmed phenotype is determined by the preconditioning stimulus. While best studied in ischemic brain there is evidence brief seizures can confer tolerance against prolonged seizures (status epilepticus). Presently, we developed a model of epileptic preconditioning in mice and used microarrays to gain insight into the transcriptional phenotype within the target hippocampus at the time tolerance had been acquired. Epileptic tolerance was induced by an episode of non-damaging seizures in adult C57Bl/6 mice using a systemic injection of kainic acid. Neuron and DNA damage-positive cell counts 24 h after status epilepticus induced by intraamygdala microinjection of kainic acid revealed preconditioning given 24 h prior reduced CA3 neuronal death by approximately 45% compared with non-tolerant seizure mice. Microarray analysis of over 39,000 transcripts (Affymetrix 430 2.0 chip) from microdissected CA3 subfields was undertaken at the point at which tolerance was acquired. Results revealed a unique profile of small numbers of equivalently up- and down-regulated genes with biological functions that included transport and localization, ubiquitin metabolism, apoptosis and cell cycle control. Select microarray findings were validated post hoc by real-time polymerase chain reaction and Western blotting. The present study defines a paradigm for inducing epileptic preconditioning in mice and first insight into the global transcriptome of the seizure-damage refractory brain.

Exposición laboral a los anestésicos inhalatorios: medidas de control / Labour exposure to the inhalatory anaesthetic gases: control measurements

La exposición laboral a los residuos ambientales anestésicos durante la anestesia inhalatoria supone un riesgo importante para la salud, cuando los niveles de exposición superan los límites recomendados. La medición ambiental periódica junto con una metodología adecuada en el manejo de la anestesia inhalatoria y en el mantenimiento de las instalaciones son estrategias fundamentales para control de contaminación ambiental y exposición laboral. De estas medidas destacan por su eficacia la ventilación adecuada de los quirófanos y el empleo de sistemas de evacuación de gases anestésicos, ya que reducen el nivel de exposición un 50 y 90% respectivamente

The labour exposure to the environmental anaesthetic residues during the inhalatory anaesthesia means a risk for health if exposure levels overcome the recommended limits. A periodical analysis of environmental conditions, an adequate methodology during the inhalatory anaesthesia, and an appropriate maintenance of the facilities are necessary strategies to control the environmental pollution and therefore the labour exposure. Some of the most efficient actions to take are a suitable ventilation of the operating room and the use of an anaesthetic gases evacuation system since they may reduce the exposure levels 50 and 90 % respectively

Exposición laboral al óxido nitroso y sevoflurano durante la anestesia en pediatría: evaluación de un dispositivo de extracción de gases anestésicos / Occupational exposure to nitrous oxide and sevoflurane during pediatric anesthesia: evaluation of an anesthetic gas extractor

OBJETIVOS: Determinar el grado de exposición laboral alos gases anestésicos en ausencia de extracción de gases y evaluarla efectividad de un sistema extractor, original y diseñadoal efecto, durante la anestesia inhalatoria en pediatría.MÉTODOS: Veinticuatro niños sometidos a adenoamigdalectomía.En grupo ASP se aplicó extracción de gasesanestésicos (n=12) y grupo No ASP no se aplicó (n=12).Se hizo inducción inhalatoria mediante circuito MaplesonC con sevoflurano 8%, N2O 60%, oxígeno 40% y flujode gas 8 l.min-1. El mantenimiento se hizo con sevoflurano2% con el mismo flujo y mezcla anestésica, enventilación espontánea con tubo endotraqueal y circuitoMapleson D. Los circuitos disponen de válvula APL (airwaypressure-limiting) que permite la conexión al extractorde gases anestésicos. Se midieron niveles ambientalesde sevoflurano y N2O en la zona respiratoria del anestesiólogo.Se realizó encuesta a cirujano y enfermera sobresíntomas relacionados con la exposición laboral.RESULTADOS: Durante el periodo anestésico el promediode exposición al N2O y sevoflurano fue en No ASP:423±290 y 12±10,9 ppm respectivamente; disminuyendoun 94% y 91% en ASP: 24,7±26 y 1,1±1 ppm; p<0,001.Se detectó más incidencia de “olor a gas” en NoASP:87% frente ASP:11% (p=0,003), malestar general:62% versus 11% (p=0,05), náuseas: 62% versus 0%(p=0,009) y cefalea: 62% versus 0% (p=0,009).CONCLUSIONES: La extracción de gases disminuyó hastaun 94% el nivel de exposición, consiguiendo nivelesinferiores a los límites recomendados y reduciendo intensamentelos riesgos para la salud de los trabajadores

OBJETIVES: To determine the level of occupationalexposure to anesthetic gases in the absence of anextractor during pediatric anesthesia and to assess theefficacy of a purpose-built extraction system.METHODS: The patients were 24 children undergoingtonsillectomy and adenoidectomy. Gases were extractedfrom the room for 1 group and were not extracted forthe other group (n=12 in each group). Induction waswith 8% sevoflurane, 60% nitrous oxide (N2O), 40%oxygen at a flow rate of 8 L·min–1 through a Mapleson Ccircuit. Maintenance was with 2% sevoflurane at thesame flow rate and gas mixture under spontaneousventilation with an endotracheal tube and a Mapleson Dcircuit. The circuits were equipped with an airwaypressure-limiting valve to allow connection to ananesthetic gas extractor. Ambient levels of sevofluraneand N2O were measured in the breathing area aroundthe anesthesiologist. The surgeon and the nurse wereasked about symptoms related to occupational exposure.RESULTS: The mean (SD) exposure to N2O andsevoflurane in the group without an extractor was 423(290) and 12 (10.9) parts per million (ppm), respectively.In the group working with the extractor, exposure was94% and 91% lower: 24.7 (26) and 1.1 (1) ppm (P<.001).A higher incidence of noticing a "smell of gas" wasregistered for the group without an extractor (87% vs11% in the extractor group, P=.003). Higher rates werealso found for general discomfort (62% vs 11%, P=.05),nausea (62% vs 0%, P=.009), and headache (62% vs0%, P=.009) in the absence of the extractor.CONCLUSIONS: Gas extraction decreased the level ofexposure by up to 94%, achieving levels that were belowthe recommended limits and greatly reducing occupationalrisk

Exposición laboral a los anestésicos inhalatorios: riesgos para la salud, monitorización ambiental y legislación / Labour exposure to the anesthetic gases: risks for the health, environmental monitoring, and legislation

La exposición laboral a los residuos ambientales anestésicos durante la anestesia inhalatoria puede suponer un riesgo para la salud de los trabajadores expuestos que requiere la planificación e implantación de medidas de prevención efectivas. Cuando los niveles de exposición superan los límites recomendados se produce mayor incidencia de cefalea, náuseas, descenso del tiempo de reacción y de la habilidad motora, y en la exposición crónica mayor incidencia de aborto espontáneo y alteraciones en la función reproductora. El óxido nitroso es el principal agente involucrado en dichas alteraciones, con un mecanismo de toxicidad conocido y de peor control en las estrategias antipolución. Las principales fuentes de contaminación son la ventilación con mascarilla, la no utilización del extractor de gases, la anestesia pediátrica y fugas por inadecuado mantenimiento de las instalaciones. Establecer un plan preventivo que incluya, la vigilancia y control de la salud de los trabajadores, la medición ambiental periódica para identificar y solucionar las posibles fugas, implantar medidas correctoras y comprobar la eficacia de las medidas antipolución instauradas, cuyo objetivo será no sobrepasar los valores límite recomendados, hasta la fecha, por el Instituto Nacional de Seguridad e Higiene en el Trabajo siguiendo la Ley de Prevención de Riesgos Laborales y normativa que la desarrolla. Además es necesaria la creación de una Comisión de Vigilancia de los Gases para asegurar que se siguen las normativas vigentes de prevención y se instauran los avances científicos en este campo

The labour exposure to the environmental anaesthetic residue during the inhalatory anaesthesia supposes an important risk for the health without solution at present time. Among these risks, we may emphasize: headache, nauseas, decrement of the reactiontime and motor ability. Additionally, greater incidence inspontaneous abortion and alterations in the reproductive function may arise when the exposure levels overcome the recommended limits. The nitrous oxide is the main agent involved in the above mentioned alterations. Although its toxicity mechanism is wellknown, antipollution strategies are difficult to implement. The main pollution sources are the ventilation with face mask, no useof the gas extractor, the paediatric anaesthesia and the gas escapes due to an inadequate maintenance of the facilities. A periodical analyse of environmental conditions is basic to identify and to solve the escapes, and should be also used to check the efficiency of the antipollution measures implemented which should not exceed the recommended limits following the Law of Prevention for Labour Risks. Besides, it is necessary to create a commission which would be in charge of assuring the norms in use and also the accomplishment of the latest scientific advances

[Occupational exposure to nitrous oxide and sevoflurane during pediatric anesthesia: evaluation of an anesthetic gas extractor]. / Exposición laboral al óxido nitroso y sevoflurano durante la anestesia en pediatráa: evaluación de un dispositivo de extracción de gases anestésicos.

OBJECTIVES: To determine the level of occupational exposure to anesthetic gases in the absence of an extractor during pediatric anesthesia and to assess the efficacy of a purpose-built extraction system. METHODS: The patients were 24 children undergoing tonsillectomy and adenoidectomy. Gases were extracted from the room for 1 group and were not extracted for the other group (n=12 in each group). Induction was with 8% sevoflurane, 60% nitrous oxide (N2O), 40% oxygen at a flow rate of 8 L x min(-1) through a Mapleson C circuit. Maintenance was with 2% sevoflurane at the same flow rate and gas mixture under spontaneous ventilation with an endotracheal tube and a Mapleson D circuit. The circuits were equipped with an airway pressure-limiting valve to allow connection to an anesthetic gas extractor. Ambient levels of sevoflurane and N2O were measured in the breathing area around the anesthesiologist. The surgeon and the nurse were asked about symptoms related to occupational exposure. RESULTS: The mean (SD) exposure to N2O and sevoflurane in the group without an extractor was 423 (290) and 12 (10.9) parts per million (ppm), respectively. In the group working with the extractor, exposure was 94% and 91% lower: 24.7 (26) and 1.1 (1) ppm (P<.001). A higher incidence of noticing a "smell of gas" was registered for the group without an extractor (87% vs 11% in the extractor group, P=.003). Higher rates were also found for general discomfort (62% vs 11%, P=.05), nausea (62% vs 0%, P=.009), and headache (62% vs 0%, P=.009) in the absence of the extractor. CONCLUSIONS: Gas extraction decreased the level of exposure by up to 94%, achieving levels that were below the recommended limits and greatly reducing occupational risk.

Controversias respecto a la extubación inmediata en cirugía cardíaca pediátrica / Controversies related to early extubation after pediatric heart surgery

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Anestesia con sevoflurano para exploraciones de resonancia magnética en pediatría / Sevoflurane anesthesia for pediatric magnetic resonance imaging procedures

OBJETIVOS: Evaluar la eficacia y seguridad de la anestesia con sevoflurano en niños sometidos a exploraciones de resonancia magnética. MATERIAL Y MÉTODOS: En una serie de 105 pacientes pediátricos, ASA I-II, con un peso de 13ñ10 kg y edad media de 2,9 años (1 día-10 años), de los cuales veinte pacientes (19 por ciento) tenían menos de 3 meses de edad. Utilizamos una técnica anestésica basada en una inducción progresiva con sevoflurano hasta 6 vol. por ciento en una mezcla de óxido nitroso y oxígeno, seguido por un mantenimiento con sevoflurano al 1-2 por ciento en la misma mezcla, a través de mascarilla facial o cánulas nasales, mientras el paciente respira espontáneamente. RESULTADOS: Todas las exploraciones se realizaron satisfactoriamente. Diez minutos después del cese de la anestesia el 88 por ciento de los pacientes estaban totalmente despiertos. Ningún paciente presentó sedación prolongada. Ninguna complicación grave ocurrió durante el estudio. Los efectos adversos más comunes fueron: quince pacientes (14 por ciento) tuvieron descensos transitorios de la saturación de oxígeno, sin llegar a niveles críticos (SpO2 < 90 por ciento). Seis de estos pacientes tenían menos de 3 meses de edad. Tras el cese de la sedación trece pacientes (12 por ciento) tuvieron episodios de agitación no aceptable, transitoria, siendo más frecuente cinco minutos después del cese de la anestesia. Cinco pacientes (4,8 por ciento) presentaron vómitos en la sala de recuperación. CONCLUSIÓN: Este estudio indica que el sevoflurano es eficaz y seguro como técnica de sedación en niños, incluso recién nacidos, que van ser sometidos a exploraciones de resonancia magnética (AU)

Participation of structural microtubule-associated proteins (MAPs) in the development of neuronal polarity.

Several lines of evidence have indicated that changes in the structure of neuronal cytoskeleton provide the support for the dramatic morphological changes that occur during neuronal differentiation. It has been proposed that microtubule-associated proteins can contribute to the development of this phenomenon by controlling the dynamic properties of microtubules. In this report we have characterized the effect of the combined suppression of MAP1B and tau, and MAP1B and MAP2 on neuronal polarization in cultured hippocampal cells grown on a laminin-containing substrate. We have taken advantage of the use of a mouse line deficient in MAP1B expression obtained by the gene trapping approach. In addition to this engineered mice line we used the antisense oligonucleotide approach to induce the suppression of tau or MAP2, in wild type and MAP1B-deficient neurons. Together these results show a synergistic role for MAP1B/MAP2 and MAP1B/TAU.

[Sevoflurane anesthesia for magnetic resonance procedures in pediatrics]. / Anestesia con sevoflurano para exploraciones de resonancia magnética en pediatría.

OBJECTIVE: To assess the efficacy and safety of sevoflurane anesthesia in children during magnetic resonance imaging procedures. MATERIAL AND METHODS: The patients were 105 ASA-I-II children, mean weight 13 +/- 10 Kg and mean age 2.9 years (range 1 day-10 years), twenty (20%) of whom were under 3 months old. Induction was gradual with 6% sevoflurane in a mixture of nitrous oxide and oxygen, followed by maintenance with 1-2% sevoflurane in the same mixture through a face mask or nasal tubes while the patient breathed spontaneously. All procedures were performed satisfactorily. Ten minutes after anesthesia, 88% of the patients were fully awake. None suffered prolonged sedation and no serious complications occurred during the study period. The most common side effects were transient decreases in oxygen saturation in 15 patients (14%), although none reached the critical level (SpO2 < 90%). Six of those patients were under 3 months old. After recovering from sedation, 13 patients (12%) suffered transient episodes of excessive agitation, usually 5 minutes after awakening. Five patients (4.8%) vomited in the recovery room. CONCLUSIONS: This study indicates that sevoflurane is safe and effective for sedating children, including newborn infants, who must undergo magnetic resonance imaging.