Lung surfactant is a complex mixture of phospholipids and specific proteins but its role in the pathogenesis of interstitial lung diseases is not established. Herein, we analyzed the effects of three representative phospholipid components, that is, dipalmitoilphosphatidylcoline (DPPC), phosphatidylglycerol (PG) and phosphatidylethanolamine (PE), on collagen expression, apoptosis and Ca2+ signaling in normal human lung fibroblasts (NHLF) and probed their effect in an experimental model of lung fibrosis. Collagen expression was measured with RT-PCR, apoptosis was measured by using either the APOPercentage assay kit (Biocolor Ltd., Northern Ireland, UK) or the Caspase-Glo 3/7 assay (Promega, Madison, WI, USA) and Ca2+ signaling by conventional epifluorescence imaging. The effect in vivo was tested in bleomycin-induced lung fibrosis in mice. DPPC and PG did not affect collagen expression, which was downregulated by PE. Furthermore, PE promoted apoptosis and induced a dose-dependent Ca2+ signal. PE-induced Ca2+ signal and apoptosis were both blocked by phospholipase C, endoplasmic reticulum pump and store-operated Ca2+ entry inhibition. PE-induced decrease in collagen expression was attenuated by blocking phospholipase C. Finally, surfactant enriched with PE and PE itself attenuated bleomycin-induced lung fibrosis and decreased the soluble collagen concentration in mice lungs. This study demonstrates that PE strongly contributes to the surfactant-induced inhibition of collagen expression in NHLF through a Ca2+ signal and that early administration of Beractant enriched with PE diminishes lung fibrosis in vivo.
Background: Mandibular segment loss due to tumoral resection or infectious sequelae causes functional alterations with disorders in mastication, swallowing, speech, and aesthetic alterations with facial asymmetry due to deformity secondary to soft tissue collapse. Reconstructive treatment should recover function and aesthetics. This paper presents a low-cost method of mandibular reconstruction in a series of 6 patients with different years of follow-up (average follow-up time of 11.6 years) using the fibula and scapula free flaps. Methods: Five female patients and 1 male patient received mandibular reconstruction using osseous free flaps, 5 with the fibula and 1 with the scapula osseous free flap. The patient’s ages at the time of surgery ranged from 8 to 62 years (mean 33.1 years). Stainless steel wire was used as the osteosynthesis material, with intermaxillary fixation for 40 days postoperatively and masticatory rehabilitation using mucodental-supported prostheses. Results: To evaluate the aesthetic result and the facial symmetry, a questionnaire and the photographs of all the cases were sent to 8 plastic surgeons. The functional result was evaluated in 5 of the 6 patients using the Spanish version of the Oral Health Impact Profile. All flaps survived, dental occlusion was achieved in all patients, no tumors recurred, masticatory function was normal without swallowing or speech alterations, and the transplanted bone hypertrophied and spontaneously remodeled, providing facial symmetry with good aesthetic results. Conclusion: We present a low-cost and universally applicable mandibular reconstruction method, with long-term follow-up and good aesthetic and functional results.
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