RESUMEN
BACKGROUND: This paper describes the development of a complex intervention to promote mental wellbeing using the revised framework for developing and evaluating complex interventions produced by the UK Medical Research Council (UKMRC). METHODS: Application of the first two phases of the framework is described--development and feasibility and piloting. The theoretical case and evidence base were examined analytically to explicate the theoretical and empirical foundations of the intervention. These findings informed the design of a 12-week mental wellbeing promotion programme providing early intervention for people showing signs of mental health difficulties. The programme is based on the theoretical constructs of self-efficacy, self-esteem, purpose in life, resilience and social support and comprises 10 steps. A mixed methods approach was used to conduct a feasibility study with community and voluntary sector service users and in primary care. RESULTS: A significant increase in mental wellbeing was observed following participation in the intervention. Qualitative data corroborated this finding and suggested that the intervention was feasible to deliver and acceptable to participants, facilitators and health professionals. CONCLUSIONS: The revised UKMRC framework can be successfully applied to the development of public health interventions.
Asunto(s)
Promoción de la Salud/métodos , Salud Mental , Modelos Teóricos , Medicina Basada en la Evidencia , Femenino , Investigación sobre Servicios de Salud , Humanos , Masculino , Desarrollo de Programa , Evaluación de Programas y Proyectos de Salud , Escalas de Valoración Psiquiátrica , Reino UnidoRESUMEN
Tyrosine hydroxylase (TH)-mRNA, assayed by in situ hybridization combined with TH immunocytochemistry, showed a selective increase in the ventral tegmental area (A-10) but not in the substantia nigra (A-9) midbrain dopaminergic (DAergic) neurons 3 days after reserpine treatment. TH-mRNA in locus ceruleus noradrenergic (A-4) neurons was increased by reserpine, as confirmed by RNA blot hybridization. These findings show that TH-mRNA is differentially regulated in midbrain DAergic neurons in response to reserpine.
Asunto(s)
Dopamina/fisiología , Mesencéfalo/metabolismo , Neuronas/metabolismo , ARN Mensajero/metabolismo , Reserpina/farmacología , Tirosina 3-Monooxigenasa/genética , Animales , Disección/métodos , Inmunohistoquímica , Masculino , Mesencéfalo/citología , Hibridación de Ácido Nucleico , Concentración Osmolar , Ratas , Ratas Endogámicas F344 , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
RNA coding for a 50 kDa polypeptide decreased by 50% in 5 brain regions after corticosterone (CORT) treatment (40 mg/kg for 3 days). By hybrid selection and in vitro translation, the 50 kDa polypeptide is identified as glial fibrillary acidic protein (GFAP). Hippocampal GFAP mRNA (2.9 kb) decreases in a dose-dependent manner in response to CORT by RNA blot hybridization using a mouse GFAP cRNA probe; a similar decrease in response to the glucocorticoid agonist, RU 28362, is consistent with a type II glucocorticoid receptor-mediated effect. GFAP mRNA is decreased in both hippocampus and cortex following acute (1-3 days) and chronic (3 days to 3 months) CORT treatment. GFAP gene expression is disinhibited in the rat hippocampus by 7 days post adrenalectomy but not by 3 days. Finally, two clones (CR46 and CR59) that were isolated from a rat hippocampal cDNA library by differential hybridization, show decreased RNA abundance in CORT-treated rats compared to controls. A partial DNA sequence derived from the two clones exhibits 94% nucleotide identity and 96% derived amino acid identity with mouse GFAP mRNA. These results indicate that GFAP mRNA is under negative regulation by glucocorticoids and suggests that glucocorticoids may be used to inhibit GFAP gene expression in vivo in order to assess the role of GFAP in temporal aspects of central nervous system damage.
Asunto(s)
Encéfalo/metabolismo , Corticosterona/farmacología , Regulación de la Expresión Génica , Proteína Ácida Fibrilar de la Glía/metabolismo , ARN Mensajero/metabolismo , Animales , Secuencia de Bases , Encéfalo/efectos de los fármacos , ADN/metabolismo , Masculino , Ratas , Ratas Endogámicas F344 , Homología de Secuencia de Ácido NucleicoRESUMEN
Corticosteroids influence a wide range of neuronal activities by binding to either of two different glucocorticoid receptors found in rat brain. To investigate genomic responses in brain to stress levels of circulating corticosterone (CORT), we isolated hippocampal total RNA and poly(A)-containing RNA from rats treated with 10 mg/day CORT or vehicle. RNA translation products were resolved by 2-dimensional gel electrophoresis and fluorography. Select changes in four translation products after acute CORT treatment were inferred from up to 100-fold increases in three polypeptides and a 2-fold decrease in another. While adrenalectomy decreased levels of the inducible RNA sequences (adrenalectomized vs. intact controls), CORT increased the inducible sequences above their levels in intact controls. Rapid increases within 2 h of CORT treatment were seen for RNAs coding for 35, 33, and 20 kilodalton polypeptides. However, RNA coding for a 50 kilodalton polypeptide had a delayed decrease, first seen after 32 h CORT. The CORT increases displayed type II glucocorticoid receptor-specificity: RU 28362 greater than or equal to CORT greater than aldosterone greater than dihydrotestosterone = control. Since type II receptors are only substantially occupied by stress levels of CORT, these changes in gene expression are candidates for molecular stress responses in the brain.