Derivados del tamoxifeno, procedimiento de obtención y sus aplicaciones

La invención se refiere a derivados del tamoxifeno, y sus usos como composición farmacéutica en el tratamiento de enfermedades que cursan con activación de la señalización por estrógenos o como herramienta para la identificación dianas moleculares del tamoxifeno o como emisor laser molecular. Además, la presente invención se refiere al procedimiento de obtención de estos compuestos y a composiciones que los comprenden.Peer reviewedUniversidad de la Laguna, Consejo Superior de Investigaciones Científicas (España)A1 Solicitud de patente con informe sobre el estado de la técnic

Gestión por proyecto: una solución metodológica para lograr la eficiencia en contexto del aprendizaje de la lengua inglesa para la carrera de Estudios Socioculturales de la UNAH.

En el contexto de la enseñanza-aprendizaje de inglés en la Carrera de Estudios Socioculturales de la UNAH, la gestión por proyecto se argumenta como una necesidad metodológica que permita al docente y al estudiante alcanzar la eficiencia en la producción del conocimiento, entendido esto como el logro de la competencia comunicativa. Para mediar en el proceso del logro de esta competencia, se propone una batería de variables cualitativas, conformada por la “coherencia”, es decir, que las normas para el desempeño concuerden con el desempeño; la “pertinencia”, o el mayor valor social posible del proyecto; la “producción científica”, o la socialización del conocimiento resultante; la “relevancia”, o su mayor reconocimiento social posible; y el “impacto”, o la transformación más eficiente del objeto de investigación, en ese orden lógico, consecutivo, de subordinación metodológica. En este sentido, este artículo da a conocer la argumentación que sustenta esta propuesta, la cual debe resultar, como señalamos en el logro de la competencia comunicativa, como criterio del logro de la eficiencia.Eje: Educación universitaria: Experiencias educativasRed de Universidades con Carreras en Informática (RedUNCI

Ancestral Origin of the ATTCT Repeat Expansion in Spinocerebellar Ataxia Type 10 (SCA10)

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disease characterized by cerebellar ataxia and seizures. The disease is caused by a large ATTCT repeat expansion in the ATXN10 gene. The first families reported with SCA10 were of Mexican origin, but the disease was soon after described in Brazilian families of mixed Portuguese and Amerindian ancestry. The origin of the SCA10 expansion and a possible founder effect that would account for its geographical distribution have been the source of speculation over the last years. To unravel the mutational origin and spread of the SCA10 expansion, we performed an extensive haplotype study, using closely linked STR markers and intragenic SNPs, in families from Brazil and Mexico. Our results showed (1) a shared disease haplotype for all Brazilian and one of the Mexican families, and (2) closely-related haplotypes for the additional SCA10 Mexican families; (3) little or null genetic distance in small normal alleles of different repeat sizes, from the same SNP lineage, indicating that they are being originated by a single step mechanism; and (4) a shared haplotype for pure and interrupted expanded alleles, pointing to a gene conversion model for its generation. In conclusion, we show evidence for an ancestral common origin for SCA10 in Latin America, which might have arisen in an ancestral Amerindian population and later have been spread into the mixed populations of Mexico and Brazil

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Colocalization of estrogen receptors with the fluorescent tamoxifen derivative, FLTX1, analyzed by confocal microscopy

Tamoxifen is a selective estrogen receptor modulator that competitively binds the ligand-binding domain of estrogen receptors. Binding of tamoxifen displaces its cognate ligand, 17β-estradiol, thereby hampering the activation of estrogen receptors. Cellular labeling of ER is typically carried out using specific antibodies which require permeabilization of cells, incubation with secondary antibodies, and are expensive and time consuming. In this article, we describe the usefulness of FLTX1, a novel fluorescent tamoxifen derivative, which allows the labeling of estrogen receptors in immunocytochemistry and immunohistochemistry studies, both under permeabilized and non-permeabilized conditions. Further, besides labeling canonical estrogen receptors, this novel fluorescent probe is also suitable for the identification of unconventional targets such membrane estrogen receptors as well as other noncanonical targets, some of which are likely responsible for the number of undesired side effects reported during long-term tamoxifen treatments.This work has been supported by grants SAF2010-22114-C02-01/02 (MD & RM), SAF2014-61644-EXP (MD)and SAF-2013-48399-R (AB) from Ministerio de Economía y Competitividad (Spain)Peer Reviewe

Photovoltaic performance improvement in planar P3HT/CdS solar cells induced by structural, optical and electrical property modification in thermal annealed P3HT thin films

Bilayer hybrid solar cells were prepared by solution deposition of CdS thin films on conductive glass substrates (ITO), followed by spin-coating or drop-casting poly (3-hexylthiophene) (P3HT) solution on a CdS surface. After a slow drying process, the P3HT films of different thicknesses (from 100 to 725 nm) were annealed at temperatures (T1) from 110 to 190 °C, called pre-metal contact annealing. Then carbon paint was collocated on top of P3HT and gold was evaporated. The whole structure was annealed for the second time, called post-metal contact annealing, at temperature (T2) between 110 and 190 °C. The continuous increase of the (1 0 0) crystalline plane and the optical absorption coefficient of P3HT films with annealing temperatures indicates the improvement of molecular order inside the polymer films induced by the thermal annealing process. The better ordered P3HT films lead to lower series resistance and higher fill factor in the corresponding solar cells, suggesting the enlargement of charge carrier mobility in annealed P3HT films. On the other hand, the photovoltaic performance is also affected by T2 temperature; a low T2 improves the ohmic contact between P3HT and the metal contact to benefit the charge carrier extraction, whereas a high T2 may deteriorate that union. The same observation was obtained in CdS/P3HT solar cells with P3HT films of different thicknesses. The best energy conversion efficiency of 0.44% was obtained in CdS/P3HT cells with 305 nm thick P3HT annealed at T1 = 190 °C and T2 = 110 °C for 10 min each

Whispering gallery mode laser based on antitumor drug-dye complex gain medium

Optofluidic lasers have emerged as a new research field over the past few years. Most frequently they use conventional dye molecules as the gain medium. In this Letter, we demonstrate a laser emission produced by the coupling of the evanescent whispering gallery modes that resonate in a cylindrical microresonator to a newly developed gain medium. This medium is formed by attachment of a 7-nitrobenzo [c] [1,2,5]-oxadiazol-4-yl fluorescent tag to tamoxifen, the most widely used drug in the treatment of breast cancer. The antitumor character of the gain medium paves the way to novel biophotonic applications

High efficiency amplified spontaneous emission from a fluorescent anticancer drug-dye complex

[EN] External amplified spontaneous emission (ASE) efficiency around 30% is reported for an optically active molecule, which at the same time shows antitumor activity. The complex is formed by the covalent binding of an anticancer drug, tamoxifen, commonly applied in breast cancer therapy, and nitro-2-1,3-benzoxadiazol-4-yl (NBD) dye, which is frequently used as a biomarker in hydrophobic environments, such as lipid membranes. A laser-like pump threshold around 100 kW/cm(2) was found in solutions of the fluorescent drug diluted in acetone or in oil. Agreement with an ASE spatial propagation model, as well as the lack of optical feedback in the walls of the dilution cuvette confirms that ASE is the physical mechanism that explains the high efficiency observed. The waveguide character and the polarization dependence of ASE are also studied. Highly efficient optical gain in such systems suggests new biophotonic applications. (C) 2013 Elsevier B. V. All rights reserved.This study has been supported by research grants from Agencia Canaria de Investigacion, Innovacion y Sociedad de la Informacion, Gobierno de Canarias, through Project Sol-SubC200801000088 and Ministerio de Economia y Competividad Grant Numbers SAF2010-22114-C02-01 and CTQ2009-07109.Lahoz, F.; Oton Nieto, CJ.; López, D.; Marrero-Alonso, J.; Boto, A.; Diaz González, M. (2013). High efficiency amplified spontaneous emission from a fluorescent anticancer drug-dye complex. Organic Electronics. 14(5):1225-1230. https://doi.org/10.1016/j.orgel.2013.02.015S1225123014

Unique SERM-like properties of the novel fluorescent tamoxifen derivative FLTX1

Tamoxifen is a selective estrogen receptor modulator extensively used on estrogen receptor-positive breast cancer treatment. However, clinical evidences demonstrate the increased incidence of undesirable side effects during chronic therapies, the most life threatening being uterine cancers. Some of these effects are related to tissue-dependent estrogenic actions of tamoxifen, but the exact mechanisms remain poorly understood. We have designed and synthesized a novel fluorescent tamoxifen derivative, FLTX1, and characterized its biological and pharmacological activities. Using confocal microscopy, we demonstrate that FLTX1 colocalizes with estrogen receptor α (ERα). Competition studies showed that FLTX1 binding was totally displaced by unlabeled tamoxifen and partially by estradiol, indicating the existence of non-ER-related triphenylethylene-binding sites. Ligand binding assays showed that FLTX1 exhibits similar affinity for ER than tamoxifen. FLTX1 exhibited antiestrogenic activity comparable to tamoxifen in MCF7 and T47D cells transfected with 3xERE-luciferase reporter. Interestingly, FLTX1 lacked the strong agonistic effect of tamoxifen on ERα-dependent transcriptional activity. Additionally, in vivo assays in mice revealed that unlike tamoxifen, FLTX1 was devoid of estrogenic uterotrophic effects, lacked of hyperplasic and hypertrophic effects, and failed to alter basal proliferating cell nuclear antigen immunoreactivity. In the rat uterine model of estrogenicity/antiestrogenicity, FLTX1 displayed antagonistic activity comparable to tamoxifen at lower doses, and only estrogenic uterotrophy at the highest dose. We conclude that the fluorescent derivative FLTX1 is not only a suitable probe for studies on the molecular pharmacology of tamoxifen, but also a potential therapeutic substitute to tamoxifen, endowed with potent antiestrogenic properties but devoid of uterine estrogenicity.This study was supported by Grants SAF2007-66148-C02-02 (MD), SAF2010-22114-C02-01/02 (MD/RM), SAF2009-13296-C02-02 (LFP), and CTQ2009-07109 (AB) from Spanish Ministry of Science and Innovation and European Regional Development Fund Programme. We are grateful to Fundación del Instituto Canario de Investigacion del Cancer (FICIC, Spain) for financial support in the period 2007–2012. J.M.A. was hired from FICIC.Peer Reviewe