Treatment with antisense oligonucleotides in Duchenne’s disease

Se revisa el estado actual de los tratamientos de modificación del ARN de distrofina, que persiguen convertir la forma grave de la distrofia muscular de Duchenne a una forma leve (Becker), especialmente con la omisión del exón 51 mediante oligonucleótidos en antisentido y la terapia de restauración de la lectura de la distrofina, suprimiendo un codón de terminación prematura mediante PTC124. Constituyen un avance notable en el tratamiento. Consiguen una producción significativa de distrofina en el músculo esquelético, aunque, por el momento, los resultados clínicos son menos notables. Es de esperar que modificaciones químicas en la liberación y distribución corporal, así como en la captación celular de estos oligonucleótidos, aumenten su eficacia y seguridad, permitiendo el tratamiento crónico de la distrofia muscular de DuchenneIn this paper I review the results of the treatments directed to modify the mRNA of dystrophin with the goal of converting the severe Duchenne type to the milder Becker muscular dystrophy. Antisense oligomers potential to modify Duchenne muscular dystrophy (DMD) gene expression and therapeutic strategies to induce ribosomal read-through of nonsense mutations (PTC124) are described. They are an important advance in the treatment of DMD, so far unspecific. Significant expression of new dystrophin is observed in biopsies of peripheral muscle, although the functional improvement is not so encouraging. New modification of chemistries are expected to improve the liberation, broad distribution in muscles, as well as their efficacy and safety enough to allow a positive chronic treatment of DM

Corpus callosum tumor as the presenting symptom of neurofibromatosis type 1 in a patient and literature review

Introducción. La neurofibromatosis tipo 1 (NF1) es uno de los síndromes neurocutáneos más frecuentes y puede asociarse a tumores intracraneales en cualquier localización, pero excepcionalmente en el cuerpo calloso. Objetivos. Presentar un caso de NF1 que se manifiesta como un tumor de cuerpo calloso y llevar a cabo una revisión de la incidencia de tumores del cuerpo calloso en nuestra casuística y en la bibliografía. Caso clínico. Niño visto desde los 3 años con criterios diagnósticos de NF1 (sin comprobación genética), que fue estudiado por resonancia magnética (RM) y RM espectroscópica. La RM mostró objetos brillantes en la neurofibromatosis en diversas zonas cerebrales y cerebelosas, posible tumor en el tronco cerebral (parte bulbar) y tumor en la zona derecha del esplenio del cuerpo calloso. La RM espectroscópica del posible tumor del tronco mostró hallazgos compatibles con tumoración glial de bajo grado. Se siguió su evolución hasta los 19 años sin que hubieran existido cambios clínicos ni en el tamaño de los tumores en las dos localizaciones. Sólo existen seis casos publicados de tumor del cuerpo calloso en pacientes con NF1. Conclusión. Presentamos un nuevo caso de un paciente con tumor del cuerpo calloso en un paciente con NF1. Las características de la imagen y la evolución clínica van a favor del carácter benigno de este tipo de tumorIntroduction. Neurofibromatosis type 1 (NF1) is one of the most frequent neurocutaneous syndromes. NF1 can be associated with intracranial tumors in any location, but only rarely in the corpus callosum. Aims. To describe a case of NF1 presenting as a tumor of the corpus callosum and to carry out a review of the incidence of the tumors of corpus callosum in our series and in the literature. Case report. We present a child who was studied since 3 years of age because of complete NF1 clinical diagnostic criteria (without genetic study). He was studied by MR and magnetic resonance spectroscopy (MRS). MR study showed neurofibromatosis bright objects distributed over several regions of the cerebral hemispheres and cerebellum, a possible brain stem tumor (bulbar zone) and the splenium of the corpus callosum. The MRS of the brain stem tumor showed changes consistent with a low grade glial tumor. The patient was followed until 19-years of age without demonstrating any changes in the clinical features or the tumor size in both locations Only six cases of corpus callosum tumor in patients with NF1 have been published to date. Conclusions. We present a new case with tumor of the corpus callosum and NF1. The imaging characteristics and the clinical course were in favour of the benign nature of this type of tumo

Voluminous plexiform neurofibromas of the neck region in neurofibromatosis 1

Objetivo. Presentar las características clínicas, de imagen y evolutivas de una serie de pacientes con neurofibromatosis tipo 1 que desarrollaron durante la infancia neurofibromas plexiformes voluminosos en el cuello (NFPVC). Pacientes y métodos. Nueve pacientes (cinco mujeres y cuatro varones) con edades entre 3 y 15 años en el momento del diagnóstico de los tumores, que podían extenderse también a la fosa posterior y a la zona torácica superior. El diagnóstico estuvo basado fundamentalmente en la clínica, la imagen y la histología. Resultados. Un tumor era intralaríngeo y causaba problemas respiratorios. Los otros ocho casos tenían su origen en varias raíces espinales de uno o de ambos lados y podían crecer también hacia el interior de la fosa posterior y de la región torácica en algunos pacientes, y desplazaban a las estructuras anatómicas vecinas, especialmente en tres casos, todos niñas, en las que el tumor creció hasta alcanzar gran volumen, especialmente por un lado, parándose el crecimiento entre los 11 y 12 años y no volviendo a crecer más tarde. Conclusiones. Los NFPVC son tumores histológicamente benignos. La extirpación es necesaria cuando están localizados en la laringe por los problemas respiratorios que causan, pero no en los de las otras regiones, pese a que el voluminoso tamaño que alcanzan en algunos casos puede causar exagerados desplazamientos de las estructuras vecinas. El estudio de nuestra serie parece indicar que al menos los tumores extralaríngeos sólo crecen hasta los 11-12 años. Puede ser recomendable retrasar la cirugía tanto como sea posible si no existe sintomatología aguda que la haga necesariaAim. To present the clinic, imaging and evolutive characteristics of a series of patients with neurofibromatosis 1 with voluminous plexiform neurofibromas in the neck (VPNFN) during childhood. Patients and methods. Nine patients (five females and four males) who were diagnosed as VPNFN at ages between 3 and 15 years. The VPNFN widespread to the posterior fossa or the upper thoracic region in some cases. The diagnosis was based on the clinical, imaging and histological findings. Results. One of the tumors was intralaryngeal and caused respiratory difficulties. The other eight patients had the origin of the tumor in several spinal roots of one or both sides and could growth to the posterior fossa and to the upper thoracic region in some cases with displacement of the surrounding organs, especially in three patients, all girls, in whom the tumor reached a voluminous size on one side, that was observed only until 10 to 11 years when the growth ceased. Conclusions. The VPNFN are histologically benign tumors. Those located in the larynx must be removed because of the respiratory problems, but it is not necessary in cases with other locations despite the voluminous size that can reach in some patients with great displacement of the surrounding organs. The analysis of the results of our series may demonstrate that al least the extralaryngeal tumors only grow to 11-12 years of age. This possibility may make recommendable to retard the surgical treatment as much as possible in cases that it is not necessar

Optimal generalized quantum measurements for arbitrary spin systems

Positive operator valued measurements on a finite number of N identically prepared systems of arbitrary spin J are discussed. Pure states are characterized in terms of Bloch-like vectors restricted by a SU(2 J+1) covariant constraint. This representation allows for a simple description of the equations to be fulfilled by optimal measurements. We explicitly find the minimal POVM for the N=2 case, a rigorous bound for N=3 and set up the analysis for arbitrary N.Comment: LateX, 12 page

Long-range repulsive interaction between TTF molecules on a metal surface induced by charge transfer

The low-coverage adsorption of a molecular electron donor, tetrathiafulvalene, on Au(111) is characterized by the spontaneous formation of superlattice of monomers, whose spacing exceeds the equilibrium distance of non-covalent interactions and depends on coverage. The origin of this peculiar growth mode is due to a long-range repulsive interaction between molecules. The analysis of molecular-pair distributions obtained by scanning tunneling microscopy measurements permits us to determine that the nature of TTF intermolecular interactions on Au (111) is electrostatic. A repulsion between molecules is caused by the accumulation of charge due to electron donation into the metal surface, as pictured through density functional theory calculations

Unconventional spin texture of a topologically nontrivial semimetal Sb(110)

The surfaces of antimony are characterized by the presence of spin-split states within the projected bulk band gap and the Fermi contour is thus expected to exhibit a spin texture. Using spin-resolved density functional theory calculations, we determine the spin polarization of the surface bands of Sb(110). The existence of the unconventional spin texture is corroborated by the investigations of the electron scattering on this surface. The charge interference patterns formed around single scattering impurities, imaged by scanning tunneling microscopy, reveal the absence of direct backscattering signal. We identify the allowed scattering vectors and analyze their bias evolution in relation to the surface-state dispersion.Comment: 10 pages, 5 figure

Minimal optimal generalized quantum measurements

Optimal and finite positive operator valued measurements on a finite number $N$ of identically prepared systems have been presented recently. With physical realization in mind we propose here optimal and minimal generalized quantum measurements for two-level systems. We explicitly construct them up to N=7 and verify that they are minimal up to N=5. We finally propose an expression which gives the size of the minimal optimal measurements for arbitrary $N$.Comment: 9 pages, Late