Search

Fibrosing mediastinitis (FM), also called sclerosing mediastinitis or mediastinal fibrosis, is a rare disease characterized by excessive fibrotic reaction in the mediastinum and may compromise the airway, the great vessels and other mediastinal structures, with a morbidity directly related to the location and extent of fibrosis. The cause is not always known but is often the result of a granulomatous disease, most often the histoplasmosis. We report a 43-year-old woman with a history of tuberculosis infection 23 years ago. She attended the pulmonology clinic for cough and dyspnea. Physical examination revealed jugular venous distention at 90°. In computed tomography scan of the chest with contrast (c/c), we observed a mediastinal nodal cast provoking cava compression and obliteration of main and intermediary right lobar bronchus. The pathological examination was FM.

9 páginas., Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disease most usually caused by point mutations in tRNA genes encoded by mtDNA. Here, we report on how this mutation affects mitochondrial function in primary fibroblast cultures established from 2 patients with MELAS who harbored the A3243G mutation. Both mitochondrial respiratory chain enzyme activities and coenzyme Q(10) (CoQ) levels were significantly decreased in MELAS fibroblasts. A similar decrease in mitochondrial membrane potential was found in intact MELAS fibroblasts. Mitochondrial dysfunction was associated with increased oxidative stress and the activation of mitochondrial permeability transition (MPT), which triggered the degradation of impaired mitochondria. Furthermore, we found defective autophagosome elimination in MELAS fibroblasts. Electron and fluorescence microscopy studies confirmed a massive degradation of mitochondria and accumulation of autophagosomes, suggesting mitophagy activation and deficient autophagic flux. Transmitochondrial cybrids harboring the A3243G mutation also showed CoQ deficiency and increased autophagy activity. All these abnormalities were partially restored by CoQ supplementation. Autophagy in MELAS fibroblasts was also abolished by treatment with antioxidants or cyclosporine, suggesting that both reactive oxygen species and MPT participate in this process. Furthermore, prevention of autophagy in MELAS fibroblasts resulted in apoptotic cell death, suggesting a protective role of autophagy in MELAS fibroblasts., This work was supported by Ministerio de Sanidad, Spain, grants FIS PI080500 and FIS EC08/00076, and by Asociación de Enfermos de Patología Mitocondrial (AEPMI) and Fundación Española de Enfermedades Lisosomales (FEEL). M. de la Mata is the recipient of a fellowship from Colegio Oficial de Farmacéuticos de Sevilla. This group was founded by the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII).