RESUMO
Pulmonary fibrosis (PF) is a life-threatening non-tumorous disease characterized by progressive fibrosis and worsening lung function. Various drugs, such as bleomycin, can contribute to lung injury and PF, with lung injury potentially occurring in 10% of bleomycin users. Bleomycin is the most commonly used drug in the establishment of an animal model of PF in rats. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) serve an important role in controlling tissue organization and fibrosis following injury. The present study examined the effect of bosentan on fibrotic lung tissue in rats administrated with bleomycin. In total, 48 Wistar rats were administrated with bleomycin, with or without bosentan, while the control rats received saline. The lung tissues were microscopically examined by staining with hematoxylin and eosin and Masson's trichome. ELISA was also used to detect the MMP-9 and TIMP-1 concentrations in the plasma. The results indicated that the bosentan-treated groups on the next day and the 15th day showed significant reversal of pathological findings. In addition, the concentrations of MMP-9 and TIMP-1 appeared to be altered following bosentan treatment, improving the bleomycin-induced PF. Masson's trichome staining showed high collagen deposition in the lung tissue sections, which may be a direct result of the activity of MMP-9 and TIMP-1. Furthermore, the deposition of collagen was significantly inhibited in bosentan-treated groups. In conclusion, these results demonstrated that bosentan inhibited lung fibrosis induced by bleomycin and it may be used as an inhibitor of PF.
RESUMO
OBJECTIVES: The relationship between REM sleep behavior disorder (RBD) and obstructive sleep apnea (OSA) remains unclear. We aimed to (1) explore the association of REM-related EMG activity (REMREEA) with OSA in RBD patients; (2) compare the severity of OSA between RBD patients with OSA (RBD-OSA) and their age-, sex-, AHI-, and BMI- matched OSA controls. DESIGN: a. Correlation study in consecutive RBD subjects and b. case-control study SETTING: Sleep laboratory PARTICIPANTS: 71 RBD patients in the correlation study and 55 subjects (28 RBD-OSA cases and 27 OSA controls) in the case-control study. INTERVENTION: N/A METHODS: Polysomnographic assessment to document the sleep architecture, sleep apnea related parameters, and REMREEA. RESULTS: (1) In the correlation study, increased REMREEA was associated with lower severity of OSA in RBD patients, including total AHI (r = -0.263), NREM AHI (r = -0.242), obstructive AHI (r = -0.265), and mean apnea duration (r = -0.353) (P < 0.05). (2) In the case-control study, RBD-OSA patients had lesser severity of sleep apnea parameters than OSA controls in terms of higher nadir SpO(2) (85.7% ± 4.9% vs 80.8% ± 5.9%, P < 0.01), shorter maximum hypopnea duration (53.8 ± 16.7 vs 69.4 ± 22.4 seconds, P < 0.05), and maximum (45.8 ± 20.5 vs 60.8 ± 19.6 sec, P < 0.01) and mean apnea duration (22.3 ± 8.1 vs 26.3 ± 5.8 sec, P < 0.05). Significant interaction effects indicated that the usual REM sleep exacerbation of sleep apneas was seen only in OSA controls but not in RBD subjects. CONCLUSIONS: This study demonstrated that excessive EMG activity in RBD might protect patients against severe OSA and suggests this may be a naturalistic model for understanding neuromuscular control of OSA.
