Biological evaluation of carbohydrate-based aprepitant analogs for neuroblastoma treatment.

Different studies using Aprepitant, a NK1R antagonist currently used as a clinical drug for treating chemotherapy-related nausea and vomiting, have demonstrated that pharmacological inhibition of NK1R effectively reduces the growth of several tumor types such as neuroblastoma (NB). In a previous work, we demonstrated that a series of carbohydrate-based Aprepitant analogs, derived from either d-galactose or l-arabinose, have shown high affinity and NK1R antagonistic activity with a broad-spectrum anticancer activity and an important selectivity. In this new study, we explore the selective cytotoxic effects of these derivatives for the treatment of NB. Furthermore, we describe the design and stereoselective synthesis of a new generation of d-glucose derivatives as Aprepitant analogs, supported by docking studies. This approach showed that most of our carbohydrate-based analogs are significantly more selective than Aprepitant. The galactosyl derivative 2α, has demonstrated a marked in vitro selective cytotoxic activity against NB, with IC50 values in the same range as those of Aprepitant and its prodrug Fosaprepitant. Interestingly, the derivative 2α has shown similar apoptotic effect to that of Aprepitant. Moreover, we can select the glucosyl amino derivative 10α as an interesting hit exhibiting higher in vitro cytotoxic activity against NB than Aprepitant, being 1.2 times more selective.

Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer Activity.

NK1R antagonists, investigated for the treatment of several pathologies, have shown encouraging results in the treatment of several cancers. In the present study, we report on the synthesis of carbohydrate-based NK1R antagonists and their evaluation as anticancer agents against a wide range of cancer cells. All of the prepared compounds, derived from either d-galactose or l-arabinose, have shown high affinity and NK1R antagonistic activity with a broad-spectrum anticancer activity and an important selectivity, comparable to Cisplatin. This strategy has allowed us to identify the galactosyl derivative 14α, as an interesting hit exhibiting significant NK1R antagonist effect (kinact 0.209 ± 0.103 µM) and high binding affinity for NK1R (IC50 = 50.4 nM, Ki = 22.4 nM by measuring the displacement of [125I] SP from NK1R). Interestingly, this galactosyl derivative has shown marked selective cytotoxic activity against 12 different types of cancer cell lines.

Estrategias de aprendizaje de los residentes en Medicina General Integral del Centro Oftalmológico José Martí / Learning strategies of resident of Integral General Medicine from the "José Martí" Opthalmology Center

Se realizó un estudio descriptivo de corte transversal con el objetivo de describir las estrategias de aprendizaje de los residentes en Medicina General Integral del Centro Oftalmológico José Martí en el periodo comprendido entre los meses de julio y septiembre del año 2008. El universo estuvo constituido por los seis residentes en Medicina General Integral del Centro Oftalmológico José Martí. El instrumento aplicado fue una versión elaborada por los autores del Inventario de estrategias de estudio y aprendizaje (LASSI) el cual respeta las escalas originales y solo se hacen modificaciones en sus ítems, adaptándolos al contexto que se evalúa. Las escalas a evaluar son: actitud, motivación, administración del tiempo, ansiedad, concentración, selección de ideas principales, ayudas de estudio y preparación y presentación de exámenes. Una vez aplicado el instrumento se encontró que los residentes tienen una excelente actitud y una buena motivación para estudiar dicha especialidad, es suficiente la administración que hacen del tiempo de estudio, la concentración que logran al estudiar, el procesamiento de la información cuando estudian y la preparación que realizan antes de los exámenes. Se evaluaron como deficientes el nivel de ansiedad y la utilización de técnicas de estudio.

A cross-sectional and descriptive study was conducted to describe the learning strategies of residents in Integral General Medicine from the "José Martí" Ophthalmology Center during July and September, 2008. Sample included 6 residents of this center. Tool applied by authors was a designed version of studies and learning study strategies Inventory (LASSI) which considers the original scales and only they made modifications in their items adjusting to assessed context. (Anex I). Scales assessed are: Attitude, motivation, time use, anxiety level, concentration, selection of main ideas, Study assistance and examinations preparation and presentation. When tool is applied we found that residents have an excellent attitude and a good motivation to study such specialty, time use is enough, a significant concentration in study, the information processing when they are studying and a satisfactory preparation before examinations. We assessed as deficient the anxiety level and the use of study techniques.