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BACKGROUND: Neosaxitoxin (NeoSTX) and related paralytics shellfish toxins has been successfully used as local anesthetic and muscle relaxants to treat a variety of ailments. The primary mechanism of action of these toxins occurs by blocking voltage-gated sodium channels with compounds such as TTX, lidocaine, or derivatives. However, most of these non-classical sodium channel blockers act with a reduced time effect as well as ensuing neurotoxicity. NEW METHOD: In this report, we show that the use of local NeoSTX injections inactivates the hippocampal neuronal activity reversibly with a by long-term dynamics, without neuronal damage. RESULTS: A single 10 ng/µl injection of NeoSTX in the dorsal CA1 region abolished for up to 48 h memory capacities and neuronal activity measured by the neuronal marker c-fos. After 72 h of toxin injection, the animals fully recover their memory capacities and hippocampal neuronal activity. The histological inspection of NeoSTX injected brain regions revealed no damage to the tissue or reactive gliosis, similar to vehicle injection. Acute electrophysiological recording in vivo shows, also, minimal spreading of the NeoSTX in the cerebral tissue. COMPARISON WITH EXISTING METHODS: Intracerebral NeoSTX injection showed longer effects than other voltage sodium channel blocker, with minimal spreading and no neuronal damage. CONCLUSION: NeoSTX is a new useful tool that reversibly inactivates different brains region for a long time, with minimal diffusion and without neuronal damage. Moreover, NeoSTX can be used as a valuable sodium channel blocker for many studies in vivo and with potential therapeutic uses.
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Región CA1 Hipocampal/efectos de los fármacos , Neuronas/efectos de los fármacos , Saxitoxina/análogos & derivados , Bloqueadores de los Canales de Sodio/administración & dosificación , Memoria Espacial/efectos de los fármacos , Amnesia/inducido químicamente , Animales , Región CA1 Hipocampal/fisiología , Masculino , Neuronas/fisiología , Ratas Sprague-Dawley , Reconocimiento en Psicología/efectos de los fármacos , Saxitoxina/administración & dosificaciónRESUMEN
The anti-reflective effect of dielectric coatings used in silicon solar cells has traditionally been the subject of intensive studies and practical applications. In recent years the interest has permanently grown in plasmonic layers based on metal nanoparticles, which are shown to increase light trapping in the underlying silicon. In the present work we have combined these two concepts by means of in situ synthesis of Au nanoparticles in a dielectric matrix (TiO2), which is commonly used as an anti-reflective coating in silicon solar cells, and added the third element: a 10-20% porosity in the matrix. The porosity is formed by means of a controllable wet etching by low concentration HF. As a consequence, the experimentally measured reflectance of silicon coated by such a plasmonic layer decreases to practically zero in a broad wavelength region around the localized surface plasmon resonance. Furthermore, we demonstrate that extinction and reflectance spectra of silicon coated by the plasmonic films can be successfully accounted for by means of Fresnel formulae, in which a double refractive index of the metal-dielectric material is used. This double refractive index cannot be explained by effective medium theory (Maxwell-Garnett, for example) and appears when the contribution of Au nanoparticles located at the TiO2/Si interface is high enough to result in formation of interface surface plasmon modes.
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Oxygen interruption leads to death when re-oxygenation is not promptly re-established. Re-oxygenation triggers a cascade of biochemical events for restoring function at the cost of improper homeostasis. The effects observed long after perinatal asphyxia (PA) have been explained by over-expression of sentinel proteins, such as poly(ADP-ribose) polymerase-1 (PARP-1), competing for NAD(+) during re-oxygenation, leading to the idea that sentinel protein inhibition constitutes a therapeutic strategy. We studied the effects of nicotinamide and theophylline on PARP-1 activity assayed in brain and peripheral (heart) rat tissue 1-24 h after birth, as well as on changes in behaviour and monoamine neurotransmission in adult rats. PA was induced by immersing rat foetuses into a water bath for 0 or 21 min. After resuscitation, the pups were treated with nicotinamide (0.8 mmol/kg, i.p.), theophylline (0.14 mmol/kg, i.p.) or saline (0.9% NaCl) and nurtured by surrogate dams, pending behavioural and microdialysis experiments, or euthanised after birth for assaying PARP-1 activity. To estimate the in vivo distribution of a single dose of nicotinamide or theophylline into brain and peripheral compartment, a series of animals were implanted with microdialysis probes, one into the brain and other subcutaneously, 1 h after birth, assaying the drugs with a HPLC-UV system. Nicotinamide, but not theophylline prevented the long-term effects induced by PA. Only nicotinamide produced a consistent decrease in PARP-1 activity in brain and heart, whether assayed in control or asphyxia-exposed pups. The present results support the idea that the long-term effects induced by PA imply PARP-1 over-activation.
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Asfixia/metabolismo , Conducta Animal/efectos de los fármacos , Niacinamida/farmacología , Inhibidores de Fosfodiesterasa/farmacología , Poli(ADP-Ribosa) Polimerasas/metabolismo , Teofilina/farmacología , Complejo Vitamínico B/farmacología , Animales , Animales Recién Nacidos/metabolismo , Asfixia Neonatal/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Corazón/efectos de los fármacos , Humanos , Recién Nacido , Microdiálisis , Modelos Animales , Miocardio/metabolismo , Poli(ADP-Ribosa) Polimerasa-1 , Poli(ADP-Ribosa) Polimerasas/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
Polymer nanocomposites containing noble metal nanoparticles are promising materials for plasmonic applications. In this paper, we report on a high-resolution negative-tone nanocomposite resist based on poly(vinyl alcohol) where silver nanoparticles and nanopatterns are simultaneously generated by electron-beam lithography. Our results indicate nanostructures with a relatively high concentration of nanoparticles and, consequently, an electromagnetic coupling among the nanoparticles. Therefore, the patternable nanocomposite described in this work may be a suitable material for future plasmonic circuitry.
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Scanning near-field optical microscopy is capable of measuring the topography and optical signals at the same time. This fact makes this technique a valuable tool in the study of materials at nanometric scale and, in particular, of ferroelectric materials, as it permits the study of their domains structure without the need of chemical etching and, therefore, not damaging the surface (as will be demonstrated later). We have measured the scanning near-field optical microscopy transmission, as well as the topography, of an RbTiOPO(4) single crystalline slab, which exhibits two different of macroscopic ferroelectric domains. A chemical selective etching has been performed to distinguish between them, obtaining areas with a noticeable roughness (C(-) domain) in comparison with the original flat aspect of the other ones (C(+) domain). The effects of the selective chemical etching have been quantified in topographic images obtained by means of our fibre tip probe, and have been compared to topographic images obtained by Atomic Force Microscopy, with a better resolution. The near-field optical transmission images recorded have been obtained under different excitation wavelengths. These images are modulated by the light scattering due to the grains at the rough surface, which depends on the excitation wavelength used. In addition, they show a significant optical contrast due to the variations of the dielectric constant on the proximity of the ferroelectric domain wall.
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The time of food availability induces important behavioral and metabolic adaptations. Animals subjected to feeding restricted to a few daytime hours show increased locomotor activity and body temperature in anticipation of mealtime. In addition, animals under ad libitum feeding show a marked postprandial raise in body temperature and in thermogenesis. The areas of the brain commanding these responses to food are partially known. We investigated in the rat the role of the infralimbic area, located in the medial prefrontal cortex, and considered a visceral-autonomic motor area, in the responses to ad libitum or restricted feeding schedule. We performed infralimbic cortex excitotoxic lesions using injections of ibotenic acid, and measured body temperature and locomotor activity by telemetry in rats under ad libitum and restricted feeding conditions. We found that bilateral infralimbic area lesions prevented both the anticipatory and the postprandial increases in core temperature, decreased mean temperature by nearly 0.3 degrees C during both light/dark phases, and increased daily temperature variability. In contrast, the lesion caused a rapid induction of the anticipatory locomotor activity. These results show that behavioral and metabolic responses to the time of food availability are commanded separately and that the infralimbic area is a key structure to adjust the body temperature to an upcoming meal.
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Temperatura Corporal/fisiología , Conducta Alimentaria/fisiología , Sistema Límbico/fisiología , Actividad Motora/fisiología , Animales , Ritmo Circadiano , Agonistas de Aminoácidos Excitadores/farmacología , Ácido Iboténico/farmacología , Sistema Límbico/lesiones , Masculino , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Arousal depends on the concerted activity of the ascending arousal system (AAS) but specific stimuli may primarily activate some nuclei of this system. Motivated behaviours are characterized by behavioural arousal, although it is not known which AAS nuclei are active during a motivated behaviour. To address this issue, rats were rendered motivated for food by fasting them for 1 day and then were enticed with food that they could not obtain for varying periods of time. We studied the level of arousal by polysomnography or radiotelemetry, and Fos-ir in the AAS, during food enticing. We found a strong arousal and an early increase in Fos-ir in the histaminergic neurons from the tuberomammillary nucleus, after 30 min of enticing, followed by increased Fos-ir in the whole AAS if food enticing was prolonged to 1 or 2 hours. In contrast, food presentation to non-motivated rats did not increase arousal or Fos-ir in the tuberomammillary nucleus. As opposed to the active arousal of the motivated rats, passive arousal induced by sensory stimulation was associated with increased Fos-ir in the locus coeruleus and the orexin neurons, but not with increased Fos-ir in the tuberomammillary nucleus or in the other nuclei of the AAS. We conclude that the arousal during feeding-related motivated behaviour is associated primarily with the activation of the tuberomammillary nucleus, while the other arousal-related nuclei become active later on.
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Nivel de Alerta/fisiología , Conducta Alimentaria/fisiología , Regulación de la Expresión Génica/fisiología , Histamina/metabolismo , Motivación , Neuronas/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Vías Aferentes/citología , Vías Aferentes/metabolismo , Animales , Conducta Animal , Temperatura Corporal/fisiología , Recuento de Células/métodos , Alimentos , Hipotálamo/citología , Hipotálamo/metabolismo , Inmunohistoquímica/métodos , Masculino , Actividad Motora/fisiología , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Se presenta en este trabajo un análisis de la reestructuración de un centro hospitalario, el Hospital Civil del Complejo Hospitalario Carlos Haya de Málaga, abarcando el período 1996-2000, en el que se ha utilizado el concepto y el método de la reingeniería de empresas aplicándola a un medio hospitalario. El método utilizado ha sido descriptivo aunque sin embargo para la realización del cambio se han utilizado modelos prospectivos en los que han participado los autores (AU)
No disponible
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Humanos , Innovación Organizacional , Organización y Administración , Reestructuración Hospitalaria , Mal Uso de los Servicios de Salud/estadística & datos numéricos , Estadísticas HospitalariasRESUMEN
OBJECTIVE: To evaluate, using receiver operation characteristic (ROC) curves, the performance of several statistical indicators in the objective detection of 80 Hz steady state auditory evoked responses. DESIGN: Steady state auditory evoked responses elicited by amplitude modulated tones of 500 and 1000 Hz, were obtained in 16 normal adults. Recordings were made at intensities ranging from 80 to 30 dB SPL and without stimulation. Four statistics: coherence synchrony measure, circular T2, a new variant of Hotelling T2 (labeled HT2) and a test for hidden periodicity (F test) were calculated. The statistics were compared using ROC curves and bootstrapping techniques. Two outcome measures were considered: behavioral threshold prediction and averaging efficiency. RESULTS: All indicators were highly accurate to detect a response (8 to 9 dB above mean behavioral threshold for the 1000 Hz and 14 to 16 dB for the 500 Hz carrier). Responses could be reliable detected after averaging about five individual epochs of long duration. No statistically significant differences were evidenced though in their capability to predict behavioral threshold or their averaging efficiency. CONCLUSIONS: Despite the more adequate statistical properties of some of these indicators no significant differences were found in their performance. Thus all of these indicators could be recommended for automatic detection of 80 Hz auditory steady state responses.
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Potenciales Evocados Auditivos , Modelos Estadísticos , Adolescente , Adulto , Estimulación Eléctrica , Femenino , Humanos , Masculino , PeriodicidadRESUMEN
The predictive properties of EEG segments were analyzed. The sample included alpha, delta as well as spike and wave EEG activity recordings. Most of these segments are better described with non-linear autoregressive models, and a non-linear forecasting algorithm is routinely required. In terms of their predictive properties, segments can be divided into unpredictable, predictable and very predictable, these three groups being similarly represented among the alpha activity EEG segments. In EEG segments with alpha activity, poor predictability is associated with poor organization of the rhythmic pattern. Concerning dynamic properties, it was found that cyclic skeletons were highly represented among the very predictable segments, which reflect a contribution of the deterministic component of the autoregressive model to the predictability of the segments. Notable contributions of the noise component may explain the properties of unpredictable segments. These results point to a great diversity of predictive patterns among EEG recordings. Other factors besides the existence of chaotic dynamics must be regarded.
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Electroencefalografía , Dinámicas no Lineales , Algoritmos , Ritmo alfa , Ritmo Delta , Humanos , Funciones de Verosimilitud , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Procesamiento de Señales Asistido por Computador , Programas InformáticosRESUMEN
Percutaneous transluminal angioplasty (PTA) was performed in 34 patients with aortic coarctation (Ao Co). One of them with coarctation after surgical correction, the rest were native Ao Co. We used one balloon in 28 patients and two balloons simultaneously in 6. They were separated in three groups according to the degree of aortic arc hypoplasia. Group I (mild to moderate hypoplasia N = 9) the gradient dropped 39% with angiographic improvement of 48% during the follow-up (m = 13.1 months). Three cases with restenosis, 2 were satisfactory dilated and one was sent to surgery. In Group II (severe hypoplasia N = 4) the gradient dropped 31% with angiographic improvement of 30% (follow-up 16.3 months). Two cases with recoarctation were sent to surgery. In Group III (without hypoplasia N = 21) we obtained dropped of gradient of 71% with angiographic improvement of 60% (follow-up 18.5 months). Two cases were redilated successfully. The complications were: cerebral hemorrhage with death due to hypertensive crisis, (1) cerebral embolism, (1) thrombosis in the puncture site 1 and small aneurysm in dilated zone. (1) We think PTA is a good choice to conventional surgery with low rate of morbidity-mortality. The results depend basically on the anatomic type of coarctation and degree of aortic arch hypoplasia.