Microtubule plus-end tracking proteins:novel modulators of cardiac sodium channels and arrhythmogenesis

The cardiac sodium channel NaV1.5 is an essential modulator of cardiac excitability, with decreased NaV1.5 levels at the plasma membrane and consequent reduction in sodium current (INa) leading to potentially lethal cardiac arrhythmias. NaV1.5 is distributed in a specific pattern at the plasma membrane of cardiomyocytes, with localization at the crests, grooves, and T-tubules of the lateral membrane and particularly high levels at the intercalated disc region. NaV1.5 forms a large macromolecular complex with and is regulated by interacting proteins, some of which are specifically localized at either the lateral membrane or intercalated disc. One of the NaV1.5 trafficking routes is via microtubules (MTs), which are regulated by MT plus-end tracking proteins (+TIPs). In our search for mechanisms involved in targeted delivery of NaV1.5, we here provide an overview of previously demonstrated interactions between NaV1.5 interacting proteins and +TIPs, which potentially (in)directly impact on NaV1.5 trafficking. Strikingly, +TIPs interact extensively with several intercalated disc- and lateral membrane-specific NaV1.5 interacting proteins. Recent work indicates that this interplay of +TIPs and NaV1.5 interacting proteins mediates the targeted delivery of NaV1.5 at specific cardiomyocyte subcellular domains, while also being potentially relevant for the trafficking of other ion channels. These observations are especially relevant for diseases associated with loss of NaV1.5 specifically at the lateral membrane (such as Duchenne muscular dystrophy), or at the intercalated disc (for example, arrhythmogenic cardiomyopathy), and open up potential avenues for development of new anti-arrhythmic therapies.</p

Modified Douglas splitting methods for reaction–diffusion equations

We present modifications of the second-order Douglas stabilizing corrections method, which is a splitting method based on the implicit trapezoidal rule. Inclusion of an explicit term in a forward Euler way is straightforward, but this will lower the order of convergence. In the modifications considered here, explicit terms are included in a second-order fashion. For these modified methods, results on linear stability and convergence are derived. Stability holds for important classes of reaction–diffusion equations, and for such problems the modified Douglas methods are seen to be often more efficient than related methods from the literature

Modified Douglas Splitting Methods for Reaction-Diffusion Equations

We present modifications of the second-order Douglas stabilizing corrections method, which is a splitting method based on the implicit trapezoidal rule. Inclusion of an explicit term in a forward Euler way is straightforward, but this will lower the order of convergence. In the modifications considered here, explicit terms are included in a second-order fashion. For these modified methods, results on linear stability and convergence are derived. Stability holds for important classes of reaction-diffusion equations, and for such problems the modified Douglas methods are seen to be often more efficient than related methods from the literature

Estudio tecnológico sobre la prevención y mecanismos de extinción de incendios

El objetivo de dicho proyecto ha sido hacer un balance general y dar a conocer los aspectos más significativos sobre un tema que cada día está más presente en la vida cotidiana de las personas como es la prevención de incendios. El proyecto también ha tratado de englobar aspectos relacionados con el desarrollo y extinción de los incendios en diferentes ámbitos y condicione

Epifisiolisis de cabeza de radio asociadas a luxación de codo y reducción espontánea

Realizamos un estudio retrospectivo de 10 casos de la epifisiolisis de cabeza de radio ocurridas durante el periodo 1992 a 1997, con un desplazamiento mayor de 60º que según los criterios de O'Brien corresponderían a un grado III. De todas las revisadas seleccionamos 6 casos en los que había una angulación mayor de 90º, creemos ocurren después de luxación o reducción espontánea de luxación de codo; por ser las más frecuentes, las que más problemas presentan en el tratamiento y las que producen más secuelas. Nuestro objetivo es valorar los resultados obtenidos con nuestros tratamientos y realizar una revisión bibliográfica.We have done a retrospective study of ten cases of radial head epiphysiolysis occurred between 1992 and 1997, displaced more than 60º. (O'Brien's grade III). Amongst them we have selected those which were displaced more than 90º (six cases) probably occurred after an elbow luxation or after the spontaneous reduction of an elbow luxation; because the are more infrequent, more troublesome and they give more secuelae. Our aim is to evaluate the results obtained with the treatment and to review the literature

Tratamiento quirúrgico de fracturas toracolumbares por vía posterior con instrumentación y fusión bisegmentaria

Analizamos de forma retrospectiva, los resultados clínico-radiológicos y funcionales de pacientes con fracturas vertebrales con y sin afección neurológica, intervenidos quirúrgicamente mediante instrumentación vertebral pedicular de los dos segmentos adyacentes a la vértebra fracturada. Se estudian 30 pacientes que presentan fractura vertebral inestable del segmento toracolumbar, intervenidos desde enero de 1993 hasta diciembre de 2000. En todos los casos se realizó abordaje posterior, con inclusión en 8 casos de la vértebra fracturada y artrodesis posterolateral en todos los casos con injerto antólogo córtico-esponjoso. En dos casos con déficit neurológico se asoció laminectomía con descompresión posterolateral. El resultado clínico-funcional lo valoramos según la escala de Smiley-Webster con resultados excelentes en 22 pacientes. El índice sagital preoperatorio fue de 14,4 grados y postoperatorio de 4,2 grados. La altura media del cuerpo vertebral preoperatorio fue de 46% y postoperatoria de 78%. Los resultados obtenidos con esta fijación son similares a los obtenidos con otras técnicas, que requieren instrumentaciones y fusiones más largas o segundas intervenciones para retirar la fijación.We evaluate retrospectively the clinical, radiologic and functional outcomes of patients admitted to our hospital with unstable vertebral fractures with or without neurologic lesion treated with posterior fusion and transpedicular instrumentation of the upper and lower segment to the fractured vertebra. Thirty patients with unstable vertebral fracture of the thoracolumbar segment surgically managed between January 1993 and December 2000 are studied. The surgical approach was posterior in all cases, with posterolateral fusion with autologous corticocancellous graft. In 8 patients the fractured vertebra was also included. In two cases with neurologic impairment, a posterolateral decompression and laminectomy were associated. The Smiley-Webster score was used for the clinical and functional outcome with excellent results in 22 patients. The preoperative sagittal index was 14,4 degrees and improved to 4,2 degrees after surgery. The mean of vertebral body height was 46% preoperatively, and 78% postoperatively. The results obtained with this fixation are similar to other devices which require longer fusion and instrumentation or a second procedure to remove the hardware