Cocoa Polyphenol Extract Inhibits Cellular Senescence via Modulation of SIRT1 and SIRT3 in Auditory Cells.

Cocoa, rich in polyphenols, has been reported to provide many health benefits due to its antioxidant properties. In this study, we investigated the effect of Cocoa polyphenols extract (CPE) against oxidative stress-induced cellular senescence using a hydrogen peroxide (H2O2)-induced cellular senescence model in three auditory cells lines derived from the auditory organ of a transgenic mouse: House Ear Institute-Organ of Corti 1 (HEI-OC1), Organ of Corti-3 (OC-k3), and Stria Vascularis (SV-k1) cells. Our results showed that CPE attenuated senescent phenotypes, including senescence-associated ß-galactosidase expression, cell proliferation, alterations of morphology, oxidative DNA damage, mitochondrial dysfunction by inhibiting mitochondrial reactive oxygen species (mtROS) generation, and related molecules expressions such as forkhead box O3 (FOXO3) and p53. In addition, we determined that CPE induces expression of sirtuin 1 (SIRT1) and sirtuin 3 (SIRT3), and it has a protective role against cellular senescence by upregulation of SIRT1 and SIRT3. These data indicate that CPE protects against senescence through SIRT1, SIRT3, FOXO3, and p53 in auditory cells. In conclusion, these results suggest that Cocoa has therapeutic potential against age-related hearing loss (ARHL).

Role of Oxidative Stress in the Senescence Pattern of Auditory Cells in Age-Related Hearing Loss.

Age-related hearing loss (ARHL) is an increasing and gradual sensorineural hearing dysfunction. Oxidative stress is an essential factor in developing ARHL; additionally, premature senescence of auditory cells induced by oxidative stress can produce hearing loss. Hydrogen peroxide (H2O2) represents a method commonly used to generate cellular senescence in vitro. The objective of the present paper is to study H2O2-induced senescence patterns in three auditory cell lines (House Ear Institute-Organ of Corti 1, HEI-OC1; organ of Corti, OC-k3, and stria vascularis, SV-k1 cells) to elucidate the intrinsic mechanisms responsible for ARHL. The auditory cells were exposed to H2O2 at different concentrations and times. The results obtained show different responses of the hearing cells concerning cell growth, ß-galactosidase activity, morphological changes, mitochondrial activation, levels of oxidative stress, and other markers of cell damage (Forkhead box O3a, FoxO3a, and 8-oxoguanine, 8-oxoG). Comparison between the responses of these auditory cells to H2O2 is a helpful method to evaluate the molecular mechanisms responsible for these auditory cells' senescence. Furthermore, this in vitro model could help develop anti-senescent therapeutic strategies for the treatment of AHRL.

Valoración del uso del índice ictérico como parámetro para la gestión de la determinación de la bilirrubina total / Use of icteric index as a parameter for the management of the determination of total bilirubin

Introducción: El exceso de pruebas enviadas al laboratorio, en numerosas ocasiones, no aporta un valor añadido, lo que nos lleva a plantearnos su uso eficiente. La bilirrubina es una magnitud bioquímica clásica para el estudio de la alteración hepática, y el índice ictérico es una medida indirecta para la determinación semicuantitativa de la bilirrubina. Objetivos: Evaluar la utilidad del índice ictérico para detectar a pacientes con concentraciones de bilirrubina en suero superiores o inferiores a 1,20mg/dL, de manera que interese valorar la determinación de bilirrubina, y calcular el ahorro que supondría la aplicación de este algoritmo. Material y métodos: Se realizó un estudio retrospectivo para determinar la correlación entre el índice ictérico y la bilirrubina, y un análisis de regresión. La eficacia diagnóstica del índice ictérico se estudió mediante una curva Receiver Operating Characteristic, determinando el valor de corte del índice ictérico que permite discriminar valores de bilirrubina superiores e inferiores a 1,20mg/dL. Se calculó la sensibilidad, especificidad, valor predictivo positivo y valor predictivo negativo. Resultados y discusión: El análisis estadístico indicó una buena correlación entre ambas variables. El estudio de eficacia diagnóstica mostró que el punto de corte índice ictérico=2 tiene un alto valor predictivo negativo y una alta sensibilidad y especificidad. Conclusiones: Los valores de índice ictérico correlacionan bien con la bilirrubina, permitiendo el cribado de la hiperbilirrubinemia. Así se evitaría realizar el 89,72% de las bilirrubinas, informándose como<1,20mg/dL aquellas muestras con índice ictérico≤1, suponiendo un ahorro importante al laboratorio

Introduction: As too many laboratory tests may not represent significant improvements, their efficient use should be considered. Bilirubin is a classical biochemical marker of hepatic alterations, and the icteric index is an indirect measure for the semi-quantitative determination of jaundice. Objectives: To evaluate the use of the icteric index in the identification of patients with serum bilirubin concentrations with values higher or lower than 1.20mg/dL, as well as to assess the determination of bilirubin, and to evaluate the savings that the application of this algorithm would represent. Material and methods: A retrospective study was performed to determine the relationship between icteric index and total bilirubin. A regression analysis was also performed. The diagnostic efficiency of the index was studied using a Receiver Operating Characteristic curve to determine the cut-off value that would allow to distinguish bilirubin values higher and lower than 1.20mg/dL. The sensitivity and specificity, positive predictive value and negative predictive value were also calculated. Results and discussion: The statistical analysis showed a high correlation between both variables. The study of diagnostic efficacy showed that to use an icteric index equal to 2 as a cut-off point yields a high negative predictive value, sensitivity and specificity. Conclusions: Icteric index values are well correlated with bilirubin, which allows filtering for hyperbilirubinaemia. Therefore, 89.72% of bilirubin requests would not be needed. With those samples with icteric index ≤ 1 subsequently being reported as<1.20mg/dL, thus representing a savings to the laboratory

Prácticas tuteladas en farmacia comunitaria: descripción de una experiencia / No disponible

Se describen las rotaciones de una alumna de prácticas, en el Servicio de Farmacia de Atención Primaria y en el Centro de Salud de nuestra Zona Básica. Se detallan las actividades realizadas para conocer el programa de uso racional de medicamentos y los indicadores de calidad del Área de Salud y la participación con los médicos en consulta para conocer las razones que motivaban su conducta terapéutica. Se discuten las razones estimuladoras de una actitud activa ante el paciente y un interés por la formación continuada generadas. Se concluye la conveniencia de realizar más experiencias de este tipo y valorarlas (AU)

A new programme, of in-practice teaching for pre-registration pharmacists, developed in a community pharmacy is described. It included a practice period with primary care physicians in a Health Centre and another period with primary care pharmacists working for Area Health Authorities. Activities to know the existing programmes for rational use of medicines, by physicians, quality indicators used and participation with physicians attending patient’s consultations, to know the reasons motivating their prescriptions, are described. The reasons why this programme motivates a proactive attitude in the students and an interest for continuing education are discussed. The need for more experiences of the kind to be done and evaluated is concluded (AU)