Generation of Molecular Diversity from Amino Acids. A Source for the Discovery of New TRP Channel Modulators

Trabajo presentado en el IV RECI: New Horizons in Ion Channel Research, celebrado en Cuenca (España) del 12 al 13 de febrero de 2013.Ion channels are central and challenging targets in medicinal chemistry but, because of the scarce structural knowledge, rational approaches to ion channel modulators are still rare. Moreover, the multimodal activation of some channels, like TRPs, complicates still more the scenario for rational discovery programs. Due to these facts, most strategies directed to identify ion channel modulators rely on the screening of peptide and small-molecule libraries. In this context, we have been involved in the development of synthetic pathways for the generation of diverse, chiral, highly functionalized linear and heterocyclic scaffolds from amino acids, and in the production of discrete libraries from them. The screening of these libraries on different TRP channels has allowed the discovery of some innovative hits that have progressed to hit-to-lead optimization programs. This communication will deal with the synthesis, structural characterization, and biological evaluation of a collection of β,γ–diaminoester derivatives that display significant activity at TRPV1, TRPM8 and TRPA1 channels. Compound RGM04-7, a selective.Supported by MICINN grants: Consolider-Ingenio 2010 (CSD2008-00005 and CSD2006-00015), SAF2009-09323 and BFU2009-08346, and the Generalitat Valenciana (PROMETEO/2010/046)

Prevalencia De Sobrepeso U Obesidad En Escolares De Una Población Urbana Del Estado De Jalisco, México

Introduction. Urban populations in Mexico have not escaped the influence of today's world with an increase in sedentary lifestyles and inadequate food consumption patterns. These conditions have exacerbated the emerging and alarming problem of overweight and obesity in the country. Objective. To diagnose the nutritional status and determine the overweight and obesity prevalence in children between ages of 5 to 14 years of an urban community in the state of Jalisco, Mexico. Material and methods. Through a cross-sectional study, 188 students were evaluated. Weight and height were measured and compared with reference standards of the World Health Organization, the values obtained from the measurement of waist circumference percentiles were compared with the percentile charts made by Fernandez et al, 2004. Results. The combined prevalence of overweight and obesity in the total population was 36.7% (n = 69); in males the prevalence was 20.7% (12.2% for overweight and 8.5% for obesity) and in females was 16% (9.6% and 6.4%, respectively). Children from the fifth and sixth grade had a higher prevalence of both overweight and obesity. Conclusions. Our study shows the current nutritional problems manifested in urban areas, which is accentuated on children with higher increase between the 5th and 6th grades

1,3-diphenylpropan-1-ones as allosteric modulators of α7 nACh receptors with analgesic and antioxidant properties

Nicotine acethylcholine receptors (nAChRs) play critical roles in cognitive processes, neuroprotection and inflammation. Results: According to their substituents, 1,3-diphenylpropan-1-one derivatives act as α7 nAChRs negative allosteric modulators (NAM, OMe) or Type I positive allosteric modulators (PAMs, OH). Compounds 7 and 31 were the most effective (989 and 666% enhancement of ACh-induced currents) and potent (EC: 12.9 and 6.85 μM) PAMs. They exhibited strong radical scavenging values. Compound 31, selective over other neuronal nAChR subtypes and with acceptable pharmacokinetic profile, showed antinociceptive effects in a model of inflammatory pain. Conclusion: Compound 31 is a novel, potent and selective α7 nAChR PAM, displaying antioxidant and analgesic activities. The 1,3-diphenylpropan-1-one scaffold could be the base toward more advanced type I PAMs for the treatment of nAChR-mediated diseases.This work was supported by the Spanish MINECO: CSD2008-00005, The Spanish Ion Channel Initiative-CONSOLIDER INGENIO 2010, SAF2011-22802 and BFU2012-39092-C02. The Instituto de Neurociencias is a “Centre of Excellence Severo Ochoa”. We thank Susana Cámara Garrido for her assistance in the synthesis of some starting compounds and Susana Gerber for technical assistance. BBP thanks the CSIC for a predoctoral fellowship (JAE-Predoc from Junta para la Ampliación de Estudios, co-financed by FSE). Alpha7 nAChRPeer Reviewe

Factors influencing participation in colorectal cancer screening programs in Spain

To analyze the sociodemographic and organizational factors influencing participation in population-based colorectal cancer screening programs (CRCSP) in Spain, a retrospective study was conducted in a cohort of people invited to participate in the first 3 screening rounds of 6 CRCSP from 2000 to 2012. Mixed logistic regression models were used to analyze the relationship between sociodemographic and organizational factors, such as the type of fecal occult blood test (FOBT) used and the FOBT delivery type. The analysis was performed separately in groups (Initial screening-first invitation, Subsequent invitation for previous never-responders, Subsequent invitation-regular, Subsequent invitation-irregular intervals). The results showed that, in the Initial screening-first invitation group, participation was higher in women than in men in all age groups (OR 1.05 in persons aged 50–59 years and OR 1.12 in those aged 60–69 years). Participation was also higher when no action was required to receive the FOBT kit, independently of the type of screening (Initial screening-first invitation [OR 2.24], Subsequent invitation for previous never-responders [OR 2.14], Subsequent invitation-regular [OR 2.03], Subsequent invitation-irregular intervals [OR 9.38]) and when quantitative rather than qualitative immunological FOBT (FIT) was offered (Initial screening-first invitation [OR 0.70], Subsequent invitation for previous never-responders [OR 0.12], Subsequent invitation-regular [OR 0.20]) or guaiac testing (Initial screening-first invitation [OR 0.81], Subsequent invitation for previous never-responders [OR 0.88], Subsequent invitation-regular [OR 0.73]). In conclusion, the results of this study show that screening participation could be enhanced by inclusion of the FOBT kit with the screening invitation and the use of the quantitative FIT.This Project was funded by the Fondo de Investigación Sanitario with cofunding from FEDER [PI12/00944

3D‐Architected Alkaline‐Earth Perovskites

3D ceramic architectures are captivating geometrical features with an immense demand in optics. In this work, an additive manufacturing (AM) approach for printing alkaline-earth perovskite 3D microarchitectures is developed. The approach enables custom-made photoresists suited for two-photon lithography, permitting the production of alkaline-earth perovskite (BaZrO 3, CaZrO 3, and SrZrO 3) 3D structures shaped in the form of octet-truss lattices, gyroids, or inspired architectures like sodalite zeolite, and C 60 buckyballs with micrometric and nanometric feature sizes. Alkaline-earth perovskite morphological, structural, and chemical characteristics are studied. The optical properties of such perovskite architectures are investigated using cathodoluminescence and wide-field photoluminescence emission to estimate the lifetime rate and defects in BaZrO 3, CaZrO 3, and SrZrO 3. From a broad perspective, this AM methodology facilitates the production of 3D-structured mixed oxides. These findings are the first steps toward dimensionally refined high-refractive-index ceramics for micro-optics and other terrains like (photo/electro)catalysis.</p

Utilización de Internet para la enseñanza de sistemas digitales

Las nuevas tecnologías de la información y la comunicación han creado grandes expectativas en educación, pues permiten superar las limitaciones de tiempo y lugar, abaratando incluso los costes. Además, no debe olvidarse que los medios informáticos ofrecen una serie de características que favorecen el aprendizaje significativo a través de actividades de tipo interactivo. Por eso, nos parece importante su aplicación a la enseñanza de la Informática, y en particular de los sistemas digitales. En esta ponencia se presenta un sistema multimedia, basado en Internet, que se está desarrollando con el fin de aplicarlo a la docencia de sistemas digitales en la asignatura Fundamentos de Informática. La ponencia presenta una descripción general de dicho sistema, así como de las herramientas y métodos utilizados para su construcción

Psychophysiological condition in the performance of sanitary-military tasks with surgical mask

Using a quasi-experimental design with 19 health workers (33.7 ± 5.1 years), the importance of physical and cognitive condition and performance when wearing protective equipment with a surgical mask during training situations in significant contexts of military intervention has been analysed. Heart rate and its variability, glucose levels, thermoregulation, explosive strength and perceived effort in specific motor performance tasks (tapping test, tourniquet, ammunition), and cognitive and decisional performance (triage) were measured. The results indicate significant differences (p < 05) depending on the physical condition (blood glucose and explosive strength), gender (explosive strength and tourniquet), smoking habit (perceived effort) and specialty (glucose level) in the study group. In conclusion, the importance of physical and psychological training is highlighted to improve the operational response in health-military situations that require the use of a surgical maskSe ha analizado, mediante un diseño cuasi-experimental con 19 sanitarios (33.7 ± 5.1 años), la importancia de la condición física, cognitiva y el rendimiento al portar un equipo de protección con mascarilla quirúrgica durante situaciones de entrenamiento en contextos significativos de intervención militar. Se midieron la frecuencia cardíaca y su variabilidad, los niveles de glucosa, la termorregulación, la fuerza explosiva y el esfuerzo percibido en tareas de rendimiento motor específicas (tapping test, torniquete, municionamiento), y de rendimiento cognitivo y decisional (triaje). Los resultados indican diferencias significativas (p < 05) en función de la condición física (glucemia y fuerza explosiva), del género (fuerza explosiva y torniquete), del hábito tabáquico (esfuerzo percibido) y del cuerpo de pertenencia (nivel de glucemia) en el grupo de estudio. Como conclusión, se destaca la importancia del entrenamiento físico y psicológico para la mejora de la respuesta operativa en situaciones sanitario-militares que requieren el uso de mascarilla quirúrgic