Detrimental Effect of Cannabidiol on the Early Onset of Diabetic Nephropathy in Male Mice

Anti-inflammatory and antidiabetogenic properties have been ascribed to cannabidiol (CBD). CBD-based medicinal drugs have been approved for over a lustrum, and a boom in the commercialization of CBD products started in parallel. Herein, we explored the efficacy of CBD in streptozotocin (STZ)-induced diabetic mice to prevent diabetic nephropathy at onset. Eight-to-ten-week-old C57BL6J male mice were treated daily intraperitoneally with 10 mg/kg of CBD or vehicle for 14 days. After 8 days of treatment, mice were challenged with STZ or vehicle (healthy-control). At the end of the study, non-fasting blood glucose (FBG) level was 276 ± 42 mg/dL in vehicle-STZ-treated compared to 147 ± 9 mg/dL (p ≤ 0.01) in healthy-control mice. FBG was 114 ± 8 mg/dL in vehicle-STZ-treated compared to 89 ± 4 mg/dL in healthy-control mice (p ≤ 0.05). CBD treatment did not prevent STZ-induced hyperglycemia, and non-FBG and FBG levels were 341 ± 40 and 133 ± 26 mg/dL, respectively. Additionally, treatment with CBD did not avert STZ-induced glucose intolerance or pancreatic beta cell mass loss compared to vehicle-STZ-treated mice. Anatomopathological examination showed that kidneys from vehicle-STZ-treated mice had a 35% increase of glomerular size compared to healthy-control mice (p ≤ 0.001) and presented lesions with a 43% increase in fibrosis and T cell infiltration (p ≤ 0.001). Although treatment with CBD prevented glomerular hypertrophy and reduced T cell infiltration, it significantly worsened overall renal damage (p ≤ 0.05 compared to vehicle-STZ mice), leading to a more severe renal dysfunction than STZ alone. In conclusion, we showed that CBD could be detrimental for patients with type 1 diabetes, particularly those undergoing complications such as diabetic nephropathy

Peroxiredoxin 6 Down-Regulation Induces Metabolic Remodeling and Cell Cycle Arrest in HepG2 Cells

Peroxiredoxin 6 (Prdx6) is the only member of 1-Cys subfamily of peroxiredoxins in human cells. It is the only Prdx acting on phospholipid hydroperoxides possessing two additional sites with phospholipase A2 (PLA2) and lysophosphatidylcholine-acyl transferase (LPCAT) activities. There are contrasting reports on the roles and mechanisms of multifunctional Prdx6 in several pathologies and on its sensitivity to, and influence on, the redox environment. We have down-regulated Prdx6 with specific siRNA in hepatoblastoma HepG2 cells to study its role in cell proliferation, redox homeostasis, and metabolic programming. Cell proliferation and cell number decreased while cell volume increased; import of glucose and nucleotide biosynthesis also diminished while polyamines, phospholipids, and most glycolipids increased. A proteomic quantitative analysis suggested changes in membrane arrangement and vesicle trafficking as well as redox changes in enzymes of carbon and glutathione metabolism, pentose-phosphate pathway, citrate cycle, fatty acid metabolism, biosynthesis of aminoacids, and Glycolysis/Gluconeogenesis. Specific redox changes in Hexokinase-2 (HK2), Prdx6, intracellular chloride ion channel-1 (CLIC1), PEP-carboxykinase-2 (PCK2), and 3-phosphoglycerate dehydrogenase (PHGDH) are compatible with the metabolic remodeling toward a predominant gluconeogenic flow from aminoacids with diversion at 3-phospohglycerate toward serine and other biosynthetic pathways thereon and with cell cycle arrest at G1/S transition

La mentoría en la Escuela Universitaria Politécnica de la Universidad de Sevilla

XVIII Congreso Universitario de Innovación Educativa en las Enseñanzas Técnicas. Escuela Técnica Superior de Ingenieros Industriales y de Telecomunicación. Universidad de Cantabria : Santander, 6 a 9 de julio de 2010Con el fin de integrar a los alumnos de nuevo ingreso, la Escuela Universitaria Politécnica de la Universidad de Sevilla ha puesto en marcha en el curso 2008-09 un Plan de Acción Tutorial (EUPAT) basado en una red en la que participan el profesorado tutor, alumnado mentor y alumnado tutorizado. En el presente trabajo se resumirá el proceso de formación del alumnado mentor y el trabajo desarrollado por el mismo dentro del Plan de Acción Tutorial. Así mismo, se analizarán las dificultades encontradas durante el transcurso de su formación y realización de la labor de mentoría y el nivel de satisfacción alcanzado. Finalmente, se hará una reflexión sobre las debilidades y los puntos de mejora que se pueden deducir del desarrollo hasta el momento de esta acción tutorialIn order to integrate new students, the Polytechnic School of the University of Seville has launched in the year 2008-09 an Tutorial Action Plan (EUPAT) based on a network involving teachers, mentor students and tutored students. In this paper we resume the formation of mentor students and work developed by the same within the Tutorial Action Plan. Also, analyzing the difficulties encountered during the course of their training and carrying out the work of mentoring and the satisfaction level achieved. Finally, we will reflect on the weaknesses and areas for improvement that can be deducted from the development until the time of this action tutorial

Protagonismo del mentor en una actividad tutorial de carácter multidisciplinar en Ingeniería

XIX Congreso Universitario de Innovación Educativa en las Enseñanzas Técnicas : Barcelona, 6 a 8 de julio de 2011En la Escuela Politécnica Superior (EPS) de la Universidad de Sevilla se ha trabajado, por tercer curso consecutivo, en un Plan de Acción Tutorial desarrollado por 16 profesores tutores y 20 alumnos mentores de 5 titulaciones de Ingeniería Técnica. El objetivo perseguido en este curso ha sido potenciar actividades que han surgido del propio albedrío de los alumnos mentores, lo que ha dado como resultado la realización de una serie de actividades de mentoría motivadas y dirigidas desde el principio por los alumnos mentores. La actividad conjunta de todos ellos ha llevado a organizar unos subgrupos de mentorías en función de determinadas características del alumnado de primer curso (deportistas, trabajadores, becarios de otras universidades…), a realizar reuniones presenciales de mentores para puesta a punto de estas actividades así como de puesta al día de los resultados que se iban consiguiendo, además de organizar una segunda captación de mentorizados tras las notas del primer cuatrimestre, y la protagonización de una Jornada de Mentoría al final del curso.A third edition with 16 tutorial lecturers and 20 tutorial students from five different degrees (Technical Engineering of the Polytechnical School, EPS, at University of Seville) in a Tutorial Plan development, has been prepared. During the present year, the main characteristic has been a serial of mentoring actions motivated and directed by these mentors. This activity has been organized considering several subgroups of mentoring depending on special characteristics in first year students (sportsplayers, workers, grant holders from other universities…), moreover the organization of a second recruiting of new students after the first term marks, updating meetings for mentors only, and to be main figures in a Congress on Mentoring at the end of the academic year

Actualidad y prospectiva de la investigación científica en el Centro Universitario Amecameca de la Universidad Autónoma del Estado de México

Con responsabilidad, se organizó un programa cuya finalidad fuera publicitar con transparencia dichos avances, a través de un esfuerzo de rendición de cuentas a la comunidad inmediata, la universitaria, y a la comunidad abierta, la sociedad que la principal referencia para tal efecto. El programa se concretiza a través del presente libro, conformado con una inspiración de investigación multidisciplinaria; sin embargo, para llegar a tal fin, el reto es realizar el proceso de búsqueda y generación de conocimiento transitando hacia la colaboración de los cuerpos académicos, que puedan construir nuevos conocimientos fortalecidos por la convergencia de diferentes campos del saber. En consecuencia, la primera etapa de esta estrategia es la publicidad de los trabajos investigativos ejercidos, para hacer un balance al día, pero también proyectar el futuro de cada campo y área del conocimiento. La organización explicativa está organizada por tres bloques representativos del quehacer en la generación de conocimiento del Centro Universitario, un primer bloque centra el interés en las humanidades, educación y sustentabilidad; el segundo bloque lo integra la reflexión científica sobre la construcción democrática, derechos humanos y equidad de género; en el tercer segmento se destina a la seguridad alimentaria, salud pública y sistemas agropecuarios. La actualidad de la investigación eleva la producción lograda y lo que en el momento se encuentra en construcción y los alcances que produce para la docencia, la investigación misma, y para la sociedad en general. La prospectiva es un área que todos los capítulos desarrollan con el propósito de delinear los alcances innovadores por andar en teoría, metodología e incluso en los saberes mismo

Fisiología de las células cromafines de la glándula adrenal de rata en situación control y en la cirrosis hepática. Contribución a la cirrosis hepática inducida por CI4C

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Farmacología y Terapéutica. Fecha de lectura: 15-09-2017Esta tesis tiene embargado el acceso al texto completo hasta el 15-09-202

Monkey Adrenal Chromaffin Cells Express α6β4* Nicotinic Acetylcholine Receptors

<div><p>Nicotinic acetylcholine receptors (nAChRs) that contain α6 and β4 subunits have been demonstrated functionally in human adrenal chromaffin cells, rat dorsal root ganglion neurons, and on noradrenergic terminals in the hippocampus of adolescent mice. In human adrenal chromaffin cells, α6β4* nAChRs (the asterisk denotes the possible presence of additional subunits) are the predominant subtype whereas in rodents, the predominant nAChR is the α3β4* subtype. Here we present molecular and pharmacological evidence that chromaffin cells from monkey (<i>Macaca mulatta</i>) also express α6β4* receptors. PCR was used to show the presence of transcripts for α6 and β4 subunits and pharmacological characterization was performed using patch-clamp electrophysiology in combination with α-conotoxins that target the α6β4* subtype. Acetylcholine-evoked currents were sensitive to inhibition by BuIA[T5A,P6O] and MII[H9A,L15A]; α-conotoxins that inhibit α6-containing nAChRs. Two additional agonists were used to probe for the expression of α7 and β2-containing nAChRs. Cells with currents evoked by acetylcholine were relatively unresponsive to the α7-selctive agonist choline but responded to the agonist 5-I-A-85380. These studies provide further insights into the properties of natively expressed α6β4* nAChRs.</p></div

α-Ctx MII[H9A,L15A] and BuIA[T5A,P6O] potently inhibit the ACh-evoked currents in monkey chromaffin cells.

<p>A, Representative trace recordings of ACh-evoked currents and the inhibition by 100 nM and 1 μM MII[H9A,L15A]. B, Quantitative analysis of the inhibition by 100 nM (n = 5) and 1 μM MII[H9A,L15A] (n = 4). Error bars show average values ± S.E.M (n = 5); asterisks denote statistical significance (***<i>p</i><0.001) as determined by a one sample t-test. C,D, Trace recordings of ACh-evoked currents and the inhibition by 100 nM and 1 μM BuIA[T5A,P6O]. E, Quantitative analysis of the inhibition by 100 nM (n = 2) and 1 μM BuIA[T5A,P6O] (n = 4); error bars show average values ± S.E.M.</p

Sequence alignment of monkey and human α6 nAChR subunits.

<p>A, Sequence alignment of monkey and human α6 subunits identified a single residue in the extracellular ligand-binding domain at position 100 that differed between the two species. The asterisks identify residues that have previously shown to be important for α-Ctx binding <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094142#pone.0094142-Hone3" target="_blank">[47]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094142#pone.0094142-Azam5" target="_blank">[48]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094142#pone.0094142-Kim1" target="_blank">[49]</a>. Note that these residues are strictly conserved between the two species. TM indicates the transmembrane domains.</p

BuIA[T5A,P6O] inhibits 5-I-A-85380-evoked currents in monkey chromaffin cells.

<p>A, Representative trace recordings of 5-I-A-85380-evoked currents and the inhibition by 1 μM BuIA[T5A,P6O]. B, Quantitative analysis of the inhibition by 1 μM BuIA[T5A,P6O] (n = 4); error bars show average values ± S.E.M.</p