Effects of ranolazine on astrocytes and neurons in primary culture

Ranolazine (Rn) is an antianginal agent used for the treatment of chronic angina pectoris when angina is not adequately controlled by other drugs. Rn also acts in the central nervous system and it has been proposed for the treatment of pain and epileptic disorders. Under the hypothesis that ranolazine could act as a neuroprotective drug, we studied its effects on astrocytes and neurons in primary culture. We incubated rat astrocytes and neurons in primary cultures for 24 hours with Rn (10−7, 10−6 and 10−5 M). Cell viability and proliferation were measured using trypan blue exclusion assay, MTT conversion assay and LDH release assay. Apoptosis was determined by Caspase 3 activity assay. The effects of Rn on proinflammatory mediators IL-β and TNF-α was determined by ELISA technique, and protein expression levels of Smac/Diablo, PPAR-γ, Mn-SOD and Cu/Zn-SOD by western blot technique. In cultured astrocytes, Rn significantly increased cell viability and proliferation at any concentration tested, and decreased LDH leakage, Smac/Diablo expression and Caspase 3 activity indicating less cell death. Rn also increased anti-inflammatory PPAR-γ protein expression and reduced pro-inflammatory proteins IL-1 β and TNFα levels. Furthermore, antioxidant proteins Cu/Zn-SOD and Mn-SOD significantly increased after Rn addition in cultured astrocytes. Conversely, Rn did not exert any effect on cultured neurons. In conclusion, Rn could act as a neuroprotective drug in the central nervous system by promoting astrocyte viability, preventing necrosis and apoptosis, inhibiting inflammatory phenomena and inducing anti-inflammatory and antioxidant agents

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Conflicts for control of Mapuche-Pehuenche land and natural resources in the Biobío highlands

Análisis de las políticas aplicadas por el Estado chileno y sus efectos en el uso del territorio por parte de las comunidades indígenas de la zona del Alto Bíobio. Se observa que históricamente las comunidades han ido perdiendo el control de sus tierra

Urbanization patterns and their impacts on social restructuring of urban space in Chilean mid-cities: The case of Los Angeles, Central Chile

El artículo analiza las relaciones entre los cambios de uso en el territorio rural de la región del Biobío y sus efectos en el crecimiento urbano y demográfico de una ciudad de tamaño medio. En forma específica se estudia el desarrollo de la industria forestal y sus efectos sobre el proceso urbano de Los Angeles

Sistemas de evaluación objetiva a distancia en métodos cuantitativos: valoración de plataformas alternativas

En este trabajo se describe un proyecto piloto para desarrollar e implantar sistemas de evaluación y auto-evaluación a distancia. Para ello se han desarrollado prototipos basados en tres conceptos distintos: campus virtual (Moodle), sistemas de encuesta online (Lime Survey) y documentos inteligentes (AcroTex). Estos prototipos se probaron mediante actividades de evaluación (exámenes) y auto-evaluación (trabajo práctico en un aula de informática o en el domicilio) con alumnos reales. A partir de esta experiencia, hemos llegado a un conjunto de conclusiones y recomendaciones para su implantación

Application of practical innovations and educational resources in differential psychology (Phase 2 of project no. 151)

El presente proyecto es la FASE 2 de continuación del proyecto nº 151 titulado: Innovaciones prácticas y recursos educativos en Psicología Diferencial (FASE 1), que se desarrolló durante el curso académico 2021-22, que dirigió el profesor Juan Francisco Díaz Morales y del que formaban parte como PDI los/as profesores/as: Inmaculada López, Pandelis Perakakis y Mª Dolores Merino. Los objetivos de dicho proyecto fueron: Desarrollar a) innovaciones prácticas y/o aplicadas en la enseñanza de los cinco grandes temas de la asignatura de Psicología Diferencial y b) crear un banco de recursos docentes accesibles en abierto. Dichos objetivos se alcanzaron con éxito. Esta segunda parte del proyecto de innovación está dirigida a la ampliación y utilización de dichos materiales dentro de la dinámica de la clase y a la evaluación de la eficacia de los mismos. Los resultados indican que la implantación de este modelo de aprendizaje activo es eficaz.Depto. de Psicología Social, del Trabajo y DiferencialFac. de PsicologíaFALSEsubmitte

Smac/Diablo protein expression.

<p>Astrocytes (panel A) or neurons (panel B) were incubated without Rn (control, C) or with Rn (10⁻⁷, 10⁻⁶, 10⁻⁵ M) for 24 h and collected to determine Smac/Diablo protein expression by Western blot. A representative immunoblot is shown in the top panel. Data are mean ± SD of four independent experiments (four different rats). *<i>p</i> < 0.05 vs. control.</p

Cell viability was determined by MTT assay in cells treated for 24 h.

<p>Astrocytes were incubated without Rn (control, C), with Rn (10⁻⁷, 10⁻⁶, 10⁻⁵ M), with Amyloid β_1–42 (15 μM) or with Amyloid β_1–42 (15 μM) + Rn (10⁻⁶ M) (panel A). Neurons were incubated without (control, C) or with Rn (10⁻⁷, 10⁻⁶, 10⁻⁵ M) (panel B). Data are mean ± SD of four independent experiments (four different rats). *<i>p</i> < 0.05 <i>vs</i>. control.</p

Mn-SOD protein expression.

<p>Astrocytes (panel A) or neurons (panel B) were incubated without Rn (control, C) or with Rn (10⁻⁷, 10⁻⁶, 10⁻⁵ M) for 24 h and collected to determine Mn-SOD protein expression by Western blot. A representative immunoblot is shown in the top panel. Data are mean ± SD of four independent experiments (four different rats). *p < 0.05 vs. control.</p

Cytokine TNF-α determination.

<p>Astrocytes (panel A) or neurons (panel B) were incubated without Rn (control, C) or with Rn (10⁻⁷, 10⁻⁶, 10⁻⁵ M) and cell culture supernatants were harvested. TNF-α secretion were determined by ELISA. Values are means ± SD of replicate experiments from four independent cell experiments (four different rats). *<i>p</i> < 0.05 <i>vs</i> control.</p