Differential cellular FGF-2 upregulation in the rat facial nucleus following axotomy, functional electrical stimulation and corticosterone: a possible therapeutic target to Bell's palsy

<p>Abstract</p> <p>Background</p> <p>The etiology of Bell's palsy can vary but anterograde axonal degeneration may delay spontaneous functional recovery leading the necessity of therapeutic interventions. Corticotherapy and/or complementary rehabilitation interventions have been employed. Thus the natural history of the disease reports to a neurotrophic resistance of adult facial motoneurons leading a favorable evolution however the related molecular mechanisms that might be therapeutically addressed in the resistant cases are not known. Fibroblast growth factor-2 (FGF-2) pathway signaling is a potential candidate for therapeutic development because its role on wound repair and autocrine/paracrine trophic mechanisms in the lesioned nervous system.</p> <p>Methods</p> <p>Adult rats received unilateral facial nerve crush, transection with amputation of nerve branches, or sham operation. Other group of unlesioned rats received a daily functional electrical stimulation in the levator labii superioris muscle (1 mA, 30 Hz, square wave) or systemic corticosterone (10 mgkg^-1). Animals were sacrificed seven days later.</p> <p>Results</p> <p>Crush and transection lesions promoted no changes in the number of neurons but increased the neurofilament in the neuronal neuropil of axotomized facial nuclei. Axotomy also elevated the number of GFAP astrocytes (143% after crush; 277% after transection) and nuclear FGF-2 (57% after transection) in astrocytes (confirmed by two-color immunoperoxidase) in the ipsilateral facial nucleus. Image analysis reveled that a seven days functional electrical stimulation or corticosterone led to elevations of FGF-2 in the cytoplasm of neurons and in the nucleus of reactive astrocytes, respectively, without astrocytic reaction.</p> <p>Conclusion</p> <p>FGF-2 may exert paracrine/autocrine trophic actions in the facial nucleus and may be relevant as a therapeutic target to Bell's palsy.</p

Quality of life as a prognostic marker in pulmonary arterial hypertension

Background: Improvement in quality of life together with better survival are the ultimate goals in the treatment of pulmonary arterial hypertension (PAH) patients. the objective of this study was to evaluate the health-related quality of life (HRQL) of pulmonary arterial hypertension (PAH) patients with the SF-36 generic questionnaire and to identify the prognostic implication of this assessment.Methods: Fifty-four consecutive newly diagnosed PAH patients (WHO classification group I) in a single PAH reference center were included. Patients were evaluated at baseline for clinical and hemodynamic parameters, and they subsequently received first-line therapy with either an endothelin receptor antagonist or a phosphodiesterase-5 inhibitor. After 16 weeks of specific PAH therapy, all patients were re-evaluated using a 6MWT and a SF 36 questionnaire, and then they were followed up for at least 36 months.Results: After treatment, the patients demonstrated an improved 6MWT (414 +/- 124 m vs. 440 +/- 113 m, p = 0.001). Specific PAH therapy also improved the HRQL scores.Patients with a baseline Physical Component Score (PCS) higher than 32 had a better survival rate than those who had a score under 32 (p = 0.04). Similarly, patients with a PCS of at least a 38 after the 16 week therapy period had a better survival rate when compared with those who did not achieve this value (p = 0.016). Unlike the absolute PCS values, the post-treatment PCS variability was unable to predict better survival rates (p = 0.58).Conclusions: Our findings suggest that HRQL is associated with prognosis in PAH. Furthermore, achieving pre-determined PCS scores might represent a specific goal to be reached in treatment-to-target strategies.Univ São Paulo, Sch Med, Pulm Dept, Inst Heart, BR-05403000 São Paulo, BrazilUniversidade Federal de São Paulo, Rheumatol Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Rheumatol Dept, São Paulo, BrazilWeb of Scienc

Lower production of IL-17A and increased susceptibility to Mycobacterium bovis in mice coinfected with Strongyloides venezuelensis

The presence of intestinal helminths can down-regulate the immune response required to control mycobacterial infection. BALB/c mice infected with Mycobacterium bovis following an infection with the intestinal helminth Strongyloides venezuelensis showed reduced interleukin-17A production by lung cells and increased bacterial burden. Also, small granulomas and a high accumulation of cells expressing the inhibitory molecule CTLA-4 were observed in the lung. These data suggest that intestinal helminth infection could have a detrimental effect on the control of tuberculosis (TB) and render coinfected individuals more susceptible to the development of TB