Imbalance of p75(NTR)/TrkB protein expression in Huntington's disease: Implication for neuroprotective therapies

Neuroprotective therapies based on brain-derived neurotrophic factor (BDNF) administration have been proposed for Huntington's disease (HD) treatment. However, our group has recently reported reduced levels of TrkB in HD mouse models and HD human brain suggesting that besides a decrease on BDNF levels a reduction of TrkB expression could also contribute to diminished neurotrophic support in HD. BDNF can also bind to p75 neurotrophin receptor (p75(NTR)) modulating TrkB signaling. Therefore, in this study we have analyzed the levels of p75(NTR) in several HD models, as well as in HD human brain. Our data demonstrates a p75(NTR)/TrkB imbalance in the striatum of two different HD mouse models, Hdh(Q111/111) homozygous knockin mice and R6/1 mice that was also manifested in the putamen of HD patients. The imbalance between TrkB and p75(NTR) levels in a HD cellular model did not affect BDNF-mediated TrkB activation of prosurvival pathways but induced activation of apoptotic cascades as demonstrated by increased JNK phosphorylation. Moreover, BDNF failed to protect mutant huntingtin striatal cells transfected with p75(NTR) against NMDA-mediated excitotoxicity, which was associated with decreased Akt phosphorylation. Interestingly, lack of Akt activation following BDNF and NMDA treatment correlated with increased PP1 levels. Accordingly, pharmacological inhibition of PP1 by okadaic acid (OA) prevented mutant huntingtin striatal cell death induced by NMDA and BDNF. Altogether, our findings demonstrate that the p75(NTR)/TrkB imbalance induced by mutant huntingtin in striatal cells associated with the aberrant activity of PP1 disturbs BDNF neuroprotection likely contributing to increasing striatal vulnerability in HD. On the basis of this data we hypothesize that normalization of p75(NTR) and/or TrkB expression or their signaling will improve BDNF neuroprotective therapies in HD. Cell Death and Disease (2013) 4, e595; doi:10.1038/cddis.2013.116; published online 18 April 201

Fractura de piso orbitario en un jugador de béisbol

Presentamos un caso de un paciente, jugador de béisbol que sufrió una fractura de piso orbitario al recibir un golpe directo (blowout) con un bate que se le escapó a otro jugador, esta fractura fue reparada con un bloque de Hidroxiapatita Porosa HAP -200 .Una vez reconstruido el defecto óseo, el paciente volvió a su vida normal y comenzó de nuevo a jugar béisbol, debido a que desaparecieron la diplopía y el enoftalmo, por lo que tuvo una completa rehabilitación estética y funcional. En los exámenes radiográficos postoperatorios se observó una excelente reconstrucción del piso de la orbita y una osteointegegración del material implantológicoWe attend one patient, baseball player that suffer floor orbital fracture when he received hit in his eye (blowout) during practice baseball. He was operating and repaired this fracture with Porous Hidroxyapatite HAP-200.After operation he returned to play baseball because disappear the signs and symptoms (diplopia and enophthalmo).The radiography study showed excellent result after one yea

Índice de Liam: prueba física funcional

Made very important test (Liam) in the medical students in Medical Faculty in Artemisa city, because with this examination proof the functional and physical conditions before and after training. All students after training received best results than before. It is very important to because the students obtained some abilities in this subject when will be doctorsSe realizó un análisis de la prueba funcional de Liam en un grupo de estudiantes de 2do año de Medicina de Artemisa con el objetivo de valorar el grado de aptitud cardiovascular y el nivel de entrenamiento de este grupo, donde se obtuvo que la mayoría de los estudiantes el 77,8% estaba apto físicamente y solo dos para un 22,2% se encontraba en la categoría de pobre en la prueba que se realizó al inicio del curso .Esta prueba es de gran utilidad en nuestra formación como futuro Medico Generales Integrales y sobre todo que es muy fácil su proceder y lo podemos aplicar en área de salud con nuestros pacientes ,una vez graduados como médicos .En el mes de Abril después de seis meses de práctica sistemática de ejercicios físicos todos los estudiantes mejoraron de forma considerable su aptitud cardiovascular y el nivel de entrenamiento a las categorías de muy bien y bie