Differential effects of an anti-oxidant intervention on cardiomyocyte expression of adrenomedullin and intermedin and their receptor components in chronic nitric oxide deficiency

Background: Chronic inhibition of nitric oxide (NO) synthesis is associated with hypertension, myocardial oxidative stress and hypertrophic remodeling. Up-regulation of the cardiomyocyte adrenomedullin (AM) / intermedin (IMD) receptor signaling cascade is also apparent in NO-deficient cardiomyocytes: augmented expression of AM and receptor activity modifying proteins RAMP2 and RAMP3 is prevented by blood pressure normalization while that of RAMP1 and intermedin (IMD) is not, indicating that the latter is regulated by a pressure-independent mechanism. Aims: to verify the ability of an anti-oxidant intervention to normalize cardiomyocyte oxidant status and to investigate the influence of such an intervention on expression of AM, IMD and their receptor components in NO-deficient cardiomyocytes. Methods: NO synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 35mg/kg/day) was given to rats for 8 weeks, with/without con-current administration of antioxidants (Vitamin C (25mg/kg/day) and Tempol (25mg/kg/day)). Results: In left ventricular cardiomyocytes isolated from L-NAME treated rats, increased oxidative stress was indicated by augmented (3.6 fold) membrane protein oxidation, enhanced expression of catalytic and regulatory subunits of pro-oxidant NADPH oxidases (NOX1, NOX2) and compensatory increases in expression of anti-oxidant glutathione peroxidase and Cu/Zn superoxide dismutases (SOD1, SOD3). Vitamin C plus Tempol did not reduce systolic blood pressure but normalized augmented plasma levels of IMD, but not of AM, and in cardiomyocytes: (i) abolished increased membrane protein oxidation; (ii) normalized augmented expression of prepro-IMD and RAMP1, but not prepro-AM, RAMP2 and RAMP3; (iii) attenuated (by 42%) increased width and normalized expression of hypertrophic markers, skeletal-�-actin and prepro-endothelin-1 similarly to blood pressure normalization but in contrast to blood pressure normalization did not attenuate augmented brain natriuretic peptide (BNP) expression. Conclusion: normalization specifically of augmented IMD/RAMP1 expression in NO-deficient cardiomyocytes by antioxidant intervention in the absence of blood pressure reduction indicates that these genes are likely to be induced directly by myocardial oxidative stress. Although oxidative stress contributed to cardiomyocyte hypertrophy, induction of IMD and RAMP1 is unlikely to be secondary to cardiomyocyte hypertrophy.

¡Abre los ojos! Un proyecto de mejora educativa para la prevención de drogas en adolescentes

La Educación para la Salud (EpS) es un tema transversal del currículo que adolece de propuestas didácticas novedosas para la intervención pedagógica. El objetivo del trabajo que se presenta es poner en marcha un plan de mejora para la prevención de drogadicciones en adolescentes. Para ello, se ha trabajado con un total de 142 estudiantes de 3º de Educación Secundaria Obligatoria (ESO) con edades comprendidas entre los 14 y los 16 años que cursan estudios en el Instituto “Francisco Salzillo” de la localidad de Alcantarilla (Murcia). Concretamente, este artículo da luz al Proyecto ¡Abre los ojos!, que forma parte del Plan de Acción Tutorial (PAT) y del Plan de Mejora para la Prevención de Drogas (PMPD) propuesto desde el Departamento de Orientación. Se exponen ad hoc las actividades implementadas durante las 3 sesiones trabajadas con cada uno de los 6 grupos-clase escolarizados en este nivel. Haciendo uso de la reflexión-acción, el alumnado ha desarrollado una conciencia crítica acerca de los riesgos que entraña para la salud el consumo de drogas. Asimismo, mediante la técnica de grupos de discusión los discentes han realizado un interesante debate cuyas ideas han sido organizadas en torno a tres aspectos clave: causas por las que se empieza a consumir, cómo evitar caer en las drogas, y alternativas de ocio y tiempo libre para una vida saludable. Finalmente, se especifica la necesidad de abordar tareas de prevención en los centros educativos así como de facilitar información y de resolver las inquietudes de los jóvenes acerca de esta temática.

Monitoring treatment fidelity in a randomised controlled trial of a complex intervention.

Aim. This paper is a report of a study to describe how treatment fidelity is being enhanced and monitored, using a model from the National Institutes of Health Behavior Change Consortium. Background. The objective of treatment fidelity is to minimize errors in interpreting research trial outcomes, and to ascribe those outcomes directly to the intervention at hand. Treatment fidelity procedures are included in trials of complex interventions to account for inferences made from study outcomes. Monitoring treatment fidelity can help improve study design, maximize reliability of results, increase statistical power, determine whether theory-based interventions are responsible for observed changes, and inform the research dissemination process. Methods. Treatment fidelity recommendations from the Behavior Change Consortium were applied to the SPHERE study (Secondary Prevention of Heart DiseasE in GeneRal PracticE), a randomized controlled trial of a complex intervention. Procedures to enhance and monitor intervention implementation included standardizing training sessions, observing intervention consultations, structuring patient recall systems, and using written practice and patient care plans. The research nurse plays an important role in monitoring intervention implementation. Findings. Several methods of applying treatment fidelity procedures to monitoring interventions are possible. The procedure used may be determined by availability of appropriate personnel, fiscal constraints, or time limits. Complex interventions are not straightforward and necessitate a monitoring process at trial stage. Conclusion. The Behavior Change Consortium’s model of treatment fidelity is useful for structuring a system to monitor the implementation of a complex intervention, and helps to increase the reliability and validity of evaluation findings.