1,480 research outputs found

    New cinnamic – N-benzylpiperidine and cinnamic – N,N-dibenzyl(N-methyl)amine hybrids as Alzheimer-directed multitarget drugs with antioxidant, cholinergic, neuroprotective and neurogenic properties

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    Here we describe new families of multi-target directed ligands obtained by linking antioxidant cinnamic-related structures with N-benzylpiperidine (NBP) or N,N-dibenzyl(N-methyl)amine (DBMA) fragments. Resulting hybrids, in addition to their antioxidant and neuroprotective properties against mitochondrial oxidative stress, are active at relevant molecular targets in Alzheimer’s disease, such as cholinesterases (hAChE and hBuChE) and monoamine oxidases (hMAO-A and hMAO-B). Hybrids derived from umbellic – NBP (8), caffeic – NBP (9), and ferulic – DBMA (12) displayed balanced biological profiles, with IC50s in the low-micromolar and submicromolar range for hChEs and hMAOs, and an antioxidant potency comparable to vitamin E. Moreover, the caffeic – NBP hybrid 9 is able to improve the differentiation of adult SGZ-derived neural stem cells into a neuronal phenotype in vitro.Financial support from the Spanish Ministry of Economy and Competitiveness (MINECO, grants SAF2012-31035 and SAF2015-64948-C2-1-R to MIRF; grant SAF2014-52940-R to APC) partially financed by FEDER funds, and Consejo Superior de Investigaciones Científicas (CSIC, grant PIE-201580E109) is gratefully acknowledged. ME thanks COLCIENCIAS (Colombia) for a Ph.D. fellowship.Peer reviewe

    Neurogenic inducers based on the chromone scaffold, a new family of multitarget directed ligands for Alzheimer's disease

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    Resumen del trabajo presentado a la XXXVIII Reunión Anual del Grupo Español de Neurotransmisión y Neuroprotección (GENN), celebrada en Almagro (Ciudad Real) del 13 al 15 de diciembre de 2017.The highly complex pathophysiology of Alzheimer's disease (AD) and other neurodegenerative illnesses have led to replace the traditional one-drug - one-target by the multi-target-directed ligands (MTDLs) paradigm, in which a single molecule is designed to be active against several pharmacological targets. Continuing with our interest in neuroprotective and neurogenic compounds, in this work we describe a new family of donepezil flavonoid hybrids exhibiting nanomolar affinities for the sigma-1 receptor and a combined inhibition of key enzymes in AD, such as 5-lipoxygenase, acetylcholinesterase, and monoaminoxidases. In general, they scavenge free radical species and are predicted to be brain-permeable. In phenotypic assays, new hybrids protect neuronal cells against mitochondrial oxidative stress and promote maturation of neural stem cells into a neuronal phenotype. Therefore, new donepezil - flavonoid hybrids could contribute to the protection and even, the reparation of neuronal tissues, of great therapeutic interest in AD and neurodegenerative diseases.Spanish Ministry of Economy and Competitiveness MINECO (grant SAF2015-64948-C2-1-R) and Spanish National Research Council CSIC (grant PIE-201580E109).Peer Reviewe

    Design of a low-cost system for the monitoring and control of public lighting

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    The public lighting poles are part of the public lighting system, so its operation is important and is offered as a welfare mechanism for citizens, it has the disadvantage of the high cost of operation because it is in operation all night for 365 days of the year, in this work a low-cost system is designed to be able to supply power to the public lighting poles, based on a solar panel system and with sensors to be able to measure luminosity, voltages and current, this system sends the information to a base station using the XBEE protocol and viewed using LABVIEW software.Campus At

    Structure and tree diversity of secondary dry tropical forests in the Sierra de Huautla Biosphere Reserve, Morelos

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    "Se estudió la recuperación en riqueza, composición, estructura y diversidad arbórea en 3 condiciones de bosque tropical caducifolio secundario con diferente tiempo de abandono (C35, C45 y C65 años) en el sureste del estado de Morelos. En cada condición se establecieron 3 unidades de muestreo de 50 × 50 m (2,500 m2) y se midieron a todos los individuos ≥ 2.5 cm de diámetro normal (DN). En total se registraron 2,791 individuos, pertenecientes a 79 especies, 53 géneros y 30 familias. Fabaceae fue la familia con el mayor número de especies e individuos. C45 presentó la mayor riqueza de especies (57), seguida de C35 (48) y C65 (43). Las condiciones fueron diferentes (p < 0.0001) en área basal, altura total, DN y cobertura de copa. Las especies con mayores índices relativos de valor de importancia (IVIR) y de valor forestal (IVFR) fueron Pachycereus grandis (IVIR = 22.6, IVFR = 28.7), Amphipterygium adstringens (IVIR = 20.9, IVFR = 17.0), Lysiloma divaricatum (IVIR = 11.2, IVFR = 18.9) y Quercus glaucoides (IVIR = 10.5, IVFR = 13.1). Se encontraron diferencias altamente significativas (p < 0.001) entre condiciones de abandono para la heterogeneidad (Shannon-Wiener: H´), y valores significativamente (p < 0.05) mayores en C65 para el recíproco de Simpson (1/D), así como en C35 y C45 para los índices de Margalef (DMG) y α de Fisher (S). La semejanza florística (Sorensen: Is) fue máxima entre condiciones con menor tiempo de abandono (72%) y mínima con la condición de mayor tiempo (54%). El procedimiento de permutación de respuesta múltiple indicó diferencias significativas (p < 0.05) en la composición de especies entre condiciones tempranas (C35 y C45) y tardías (C65). Estos resultados explican el proceso de la sucesión secundaria en los bosques tropicales caducifolios del área de estudio y dan elementos para efectuar una mejor planificación de las actividades conducentes a su conservación.""The recovery in richness, composition, structure and tree diversity was studied in three conditions of secondary tropical deciduous forest with different time of abandonment (C35, C45 and C65 years) in the southeast of the state of Morelos. In each condition, three plots of 50 × 50 m (2,500 m2) were established and all individuals ≥ 2.5 cm of normal diameter (ND) were measured. In total, 2,791 individuals belonging to 79 species, 53 genera and 30 families were registered. Fabaceae was the family with the largest number of species and individuals. C45 had the highest species richness (57), followed by C35 (48) and C65 (43). The conditions were different (p < 0.0001) in basal area, total height, ND and crown coverage. The species with the highest relative value of importance (IVIR) and forest value (IVFR) were Pachycereus grandis (IVIR = 22.6, IVFR = 28.7), Amphipterygium adstringens (IVIR = 20.9, IVFR = 17.0), Lysiloma divaricatum (IVIR =11.2, IVFR = 18.9) and Quercus glaucoides (IVIR = 10.5, IVFR = 13.1). High significant differences (p < 0.001) between abandonment conditions were found for heterogeneity (Shannon-Wiener: H’), and highest significant values (p < 0.05) for Simpson reciprocal index (1/D) in C65, as well as to Margalef (DMG) and Fisher’s α (S) indexes in C35 and C45. The floristic similarity (Sorensen: Is) was highest among conditions with less time of abandonment (72%) and minimum with the condition of greater time (54%). The multiple response permutation procedure indicated significant differences (p < 0.05) in the species composition between early (C35 and C45) and late (C65) conditions. These results explain the process of secondary succession in the tropical deciduous forests of the study area and provide elements for improve planning of the activities leading to its conservation.

    Reporte de Mercados Financieros - tercer trimestre de 2016

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    El Banco de la República (BR) genera información para la toma de decisiones, la rendición de cuentas y la difusión al público. En particular, el Reporte de Mercados Financieros está enmarcado dentro del principio de difusión al público y contribuye a cumplir con el servicio que presta el Banco de ofrecer información e investigación económica de calidad

    Reporte de Mercados Financieros - primer trimestre de 2018

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    El Banco de la República (BR) genera información para la toma de decisiones, la rendición de cuentas y la difusión al público. En particular, el Reporte de Mercados Financieros está enmarcado dentro del principio de difusión al público y contribuye a cumplir con el servicio que presta el Banco de ofrecer información e investigación económica de calidad

    Reporte de Mercados Financieros - primer trimestre de 2017

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    El Banco de la República (BR) genera información para la toma de decisiones, la rendición de cuentas y la difusión al público. En particular, el Reporte de Mercados Financieros está enmarcado dentro del principio de difusión al público y contribuye a cumplir con el servicio que presta el Banco de ofrecer información e investigación económica de calidad

    Reporte de Mercados Financieros - tercer trimestre de 2018

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    El Banco de la República (BR) genera información para la toma de decisiones, la rendición de cuentas y la difusión al público. En particular, el Reporte de Mercados Financieros está enmarcado dentro del principio de difusión al público y contribuye a cumplir con el servicio que presta el Banco de ofrecer información e investigación económica de calidad

    Reporte de Mercados Financieros - segundo trimestre de 2017

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    El Banco de la República (BR) genera información para la toma de decisiones, la rendición de cuentas y la difusión al público. En particular, el Reporte de Mercados Financieros está enmarcado dentro del principio de difusión al público y contribuye a cumplir con el servicio que presta el Banco de ofrecer información e investigación económica de calidad

    Compromising between European and US allergen immunotherapy schools: Discussions from GUIMIT, the Mexican immunotherapy guidelines

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    Background: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. Methods: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, see Supplementary data) concluded the following: Results: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50–200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. Conclusions: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed
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