Influence of Chemical Enhancers and Iontophoresis on the In Vitro Transdermal Permeation of Propranolol: Evaluation by Dermatopharmacokinetics

[EN] The aims of this study were to assess, in vitro, the possibility of administering propranolol transdermally and to evaluate the usefulness of the dermatopharmacokinetic (DPK) method in assessing the transport of drugs through stratum corneum, using propranolol as a model compound. Four chemical enhancers (decenoic and oleic acid, laurocapram, and R-(+)-limonene) and iontophoresis at two current densities, 0.25 and 0.5 mA/cm(2) were tested. R-(+)-limonene, and iontophoresis at 0.5 mA/cm(2) were proven to be the most efficient in increasing propranolol transdermal flux, both doubled the original propranolol transdermal flux. Iontophoresis was demonstrated to be superior than the chemical enhancer because it allowed faster delivery of the drug. The DPK method was sufficiently sensitive to detect subtle vehicle-induced effects on the skin permeation of propranolol. The shorter duration of these experiments and their ability to provide mechanistic information about partition between vehicle and skin and diffusivity through skin place them as practical and potentially insightful approach to quantify and, ultimately, optimize topical bioavailability.This research was funded by Ministerio de Ciencia e Innovación (AP2007-03456) and the Universidad CEU Cardenal Herrera.Calatayud-Pascual, M.; Sebastian-Morelló, M.; Balaguer-Fernandez, C.; Delgado-Charro, M.; Lopez-Castellano, A.; Merino Sanjuán, V. (2018). Influence of Chemical Enhancers and Iontophoresis on the In Vitro Transdermal Permeation of Propranolol: Evaluation by Dermatopharmacokinetics. Pharmaceutics. 10(4):1-15. https://doi.org/10.3390/pharmaceutics10040265S11510

Iniciación a la investigación en un laboratorio integrado de química

El reto planteado por la Convergencia al Espacio Europeo en la Educación Superior (EEES) supone una oportunidad para la reflexión y la puesta en marcha de iniciativas de mejora de la calidad en el ámbito de la docencia universitaria. Aprovechando este impulso, se propone un Proyecto de Innovación Docente en la asignatura troncal de “Experimentación en Química Inorgánica” del tercer curso de la Licenciatura en Química de la Universidad de Jaén.El trabajo presentado recoge la actuación en un laboratorio integrado de Química en el que se desarrollará el proceso de aplicación de los conocimientos adquiridos por los alumnos en las diversas asignaturas cursadas sobre sólidos inorgánicos, caracterización de sólidos adsorbentes, estudio de superficies, procesos de adsorción, técnicas quimiométricas y valorización de subproductos y concienciación medioambiental

Simple model for scanning tunneling spectroscopy of noble metal surfaces with adsorbed Kondo impurities

A simple model is introduced to describe conductance measurements between a scanning tunneling microscope (STM) tip and a noble metal surface with adsorbed transition metal atoms which display the Kondo effect. The model assumes a realistic parameterization of the potential created by the surface and a d3z2-r2 orbital for the description of the adsorbate. Fano lineshapes associated with the Kondo resonance are found to be sensitive to details of the adsorbate-substrate interaction. For instance, bringing the adsorbate closer to the surface leads to more asymmetric lineshapes while their dependence on the tip distance is weak. We find that it is important to use a realistic surface potential, to properly include the tunnelling matrix elements to the tip and to use substrate states which are orthogonal to the adsorbate and tip states. An application of our model to Co adsorbed on Cu explains the difference in the lineshapes observed between Cu(100) and Cu(111) surfaces.Comment: 11 pages, 8 eps figure

Synthesis, biological and in silico evaluation of pure nucleobase-containing spiro (Indane-Isoxazolidine) derivatives as potential inhibitors of MDM2-p53 interaction

Nucleobase-containing isoxazolidines spiro-bonded to an indane core have been synthesized in very good yields by regio- and diastereoselective 1, 3-dipolar cycloaddition starting from indanyl nitrones and N-vinylnucleobases by using environmentally benign microwave technology. The contemporary presence of various structural groups that are individually active scaffolds of different typology of drugs, has directed us to speculate that these compounds may act as inhibitors of MDM2-p53 interaction. Therefore, both computational calculations and antiproliferative screening against A549 human lung adenocarcinoma cells and human SH-SY5Y neuroblastoma cells were carried out to support this hypothesis

Hypercholesterolemia and 27-Hydroxycholesterol Increase S100A8 and RAGE Expression in the Brain: a Link Between Cholesterol, Alarmins, and Neurodegeneration

Alterations in cholesterol metabolism in the brain have a major role in the physiology of Alzheimer’s disease (AD). Oxysterols are cholesterol metabolites with multiple implications in memory functions and in neurodegeneration. Previous studies have shown detrimental effects of cholesterol metabolites in neurons, but its effect in glial cells is unknown. We used a high-fat/high-cholesterol diet in mice to study the effects of hypercholesterolemia over the alarmin S100A8 cascade in the hippocampus. Using CYP27Tg, a transgenic mouse model, we show that the hypercholesterolemia influence on the brain is mediated by the excess of 27-hydroxycholesterol (27-OH), a cholesterol metabolite. We also employed an acute model of 27-OH intraventricular injection in the brain to study RAGE and S100A8 response. We used primary cultures of neurons and astrocytes to study the effect of high levels of 27-OH over the S100A8 alarmin cascade. We report that a high-fat/high-cholesterol diet leads to an increase in S100A8 production in the brain. In CYP27Tg, we report an increase of S100A8 and its receptor RAGE in the hippocampus under elevated 27-OH in the brain. Using siRNA, we found that 27-OH upregulation of RAGE in astrocytes and neurons is mediated by the nuclear receptor RXRγ. Silencing RXRγ in neurons prevented 27-OH-mediated upregulation of RAGE. These results show that S100A8 alarmin and RAGE respond to high levels of 27-OH in the brain in both neurons and astrocytes through RXRγ. Our study supports the notion that 27-OH mediates detrimental effects of hypercholesterolemia to the brain via alarmin signaling.Open access funding provided by Karolinska Institute. This research was supported by the following Swedish foundations: Swedish Brain Power, the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, Strategic Neuroscience Program, Margaretha af Ugglas Foundation, Gun och Bertil Stohnes Stiftelse, Karolinska Institutet fund for geriatric research, Stiftelsen Gamla Tjänarinnor, Demensfonden,Lindhés Advokatbyrå, Hjärnfonden, and Alzheimerfonden. R. L.-V. was fnancially supported by Mexico’s National Council for Science and Technology (CONACYT) CVU, 209252, and by Olle Enqvist Foundation grant no. 2014/778. Ramon Areces Foundation, Spain, supported E. P., EMBO Long-Term Fellowship (ALTF 696–2013), the SSMF postdoctoral fellowship, and Juan de la Cierva-Incorporación. (IJCI-2016–27,658) supported P. M.-S

Magnetothemopower study of quasi two-dimensional organic conductor α\alpha-(BEDT-TTF)2_2KHg(SCN)4_4

We have used a low-frequency magneto-thermopower (MTEP) method to probe the high magnetic field ground state behavior of $\alpha$-(BEDT-TTF)$_2$KHg(SCN)$_4$ along all three principal crystallographic axes at low temperatures. The thermopower tensor coefficients ($S_{xx}, S_{yx}$ and $S_{zz}$) have been measured to 30 T, beyond the anomalous low temperature, field-induced transition at 22.5 T. We find a significant anisotropy in the MTEP signal, and also observe large quantum oscillations associated with the de Haas - van Alphen effect. The anisotropy indicates that the ground state properties are clearly driven by mechanisms that occur along specific directions for the in-plane electronic structure. Both transverse and longitudinal magnetothermopower show asymptotic behavior in field, which can be explained in terms of magnetic breakdown of compensated closed orbits.Comment: 9 pages, 10 figure

Especies de interés pesquero en Galicia, Asturias y Cantabria

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Dynamical 1/N approach to time-dependent currents through quantum dots

A systematic truncation of the many-body Hilbert space is implemented to study how electrons in a quantum dot attached to conducting leads respond to time-dependent biases. The method, which we call the dynamical 1/N approach, is first tested in the most unfavorable case, the case of spinless fermions (N=1). We recover the expected behavior, including transient ringing of the current in response to an abrupt change of bias. We then apply the approach to the physical case of spinning electrons, N=2, in the Kondo regime for the case of infinite intradot Coulomb repulsion. In agreement with previous calculations based on the non-crossing approximation (NCA), we find current oscillations associated with transitions between Kondo resonances situated at the Fermi levels of each lead. We show that this behavior persists for a more realistic model of semiconducting quantum dots in which the Coulomb repulsion is finite.Comment: 18 pages, 7 eps figures, discussion extended for spinless electrons and typo