Changes in salivary cortisol and corticosteroid receptor-alpha mRNA expression following a 3-week multidisciplinary treatment program in patients with fibromyalgia.

The aim of the present study was to investigate the effects of a 3-week residential multidisciplinary non-pharmacological treatment program (including individually prescribed aerobic exercise and cognitive-behavioral therapy) on fibromyalgia symptoms and hypothalamic-pituitary-adrenal (HPA) axis function. Salivary and venous blood samples were collected from 12 female patients with fibromyalgia (age: 25-58) the day before and the day after the treatment period: saliva, eight times (every two hours from 0800 to 2200 h); venous blood, at 0800 h. Peripheral blood mononuclear cells (PBMC) were separated and analyzed for glucocorticoid receptor-alpha (GR-alpha) mRNA expression by semi-quantitative RT-PCR, while the salivary cortisol concentration was determined by RIA. At the same time, pain and aerobic capacity were evaluated. Aerobic capacity improved at the end of the treatment program. The slope of the regression of salivary cortisol values on sampling time was steeper in all patients after treatment, indicating that the cortisol decline was more rapid. Concomitantly, the area under the cortisol curve "with respect to increase" (AUC(i)) was higher and there was a significant increase in GR-alpha mRNA expression in PBMC. The number of positive tender points, present pain, pain area and CES-D score were significantly reduced after the treatment, while the pressure pain threshold increased at most of the tender points. Our findings suggest that one of the active mechanisms underlying the effects of our treatment is an improvement of HPA axis function, consisting in increased resiliency and sensitivity of the stress system probably related to stimulation of GR-alpha synthesis by the components of the treatment.

Prepro-endothelin-1 mRNA and its mature peptide in human appendix.

Because the precise immunopathological events occurring in appendicitis are not completely understood, possible local production of endothelin-1 (ET-1) in human appendix was investigated. We used immunohistochemistry and in situ hybridization to detect the presence, distribution, and phenotype of ET-1-positive cells and prepro-ET-1 (pp-ET-1) mRNA-expressing cells. ET-1-positive stromal cells and pp-ET-1 mRNA-expressing cells were detected with different distributions and relative frequencies in normal control appendix, histologically normal appendix, and inflamed appendix. Six of 20 histologically normal appendixes from patients with a clinical diagnosis of acute appendicitis had many ET-1-positive stromal cells and high pp-ET-1 mRNA expression, similar to inflamed appendix. Forty percent of the pp-ET-1 mRNA-expressing cells were neutrophils, and the other positive cells were mast cells and macrophages. We suggest that local production of ET-1 by neutrophils and other inflammatory cells could be a molecular sign of focal inflammation in histologically normal appendixes and that ET-1 could be implicated, with other cytokines, in the pathogenesis of appendicitis by inducing appendiceal ischemia through vasoconstriction.