The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
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Reactive oxygen species play an important role in the pathogenesis of acute lung injury and pulmonary fibrosis. The present authors hypothesise that edaravone, a free-radical scavenger, is able to attenuate bleomycin (BLM)-induced lung injury in mice by decreasing oxidative stress. Lung injury was induced in female ICR mice by intratracheal instillation of 5 mg x kg(-1) of BLM. ⋯ The fibrotic change in the lung on day 28 was ameliorated by edaravone, as evaluated by histological examination and measurement of hydroxyproline contents. In addition, edaravone significantly increased the prostaglandin E(2) concentration in BALF on day 2. In summary, edaravone was shown to inhibit lung injury and fibrosis via the repression of lipid hydroperoxide production and the elevation of prostaglandin E(2) production in the present experimental murine system.
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Desmosine (DES) and isodesmosine (IDES) are two unusual, tetrafunctional, pyridinium ring-containing amino acids involved in elastin cross-linking. Being amino acids unique to mature, cross-linked elastin, they are useful for discriminating peptides derived from elastin breakdown from precursor elastin peptides. According to these features, DES and IDES have been extensively discussed as potentially attractive indicators of elevated lung elastic fibre turnover and markers of the effectiveness of agents with the potential to reduce elastin breakdown. ⋯ The results of the application of DES and IDES as surrogate end-points in early clinical trials in COPD are also reported. Finally, recent advances in detection techniques, including liquid chromatography tandem mass spectrometry and high-performance capillary electrophoresis with laser-induced fluorescence, are discussed. These techniques allow detection of DES and IDES at very low concentration in body fluids other than urine, such as plasma or sputum, and will help the understanding of whether DES and IDES are potentially useful in monitoring therapeutic intervention in COPD.
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Peak oxygen uptake (V'(O(2))) remains the gold standard measurement of exercise capacity and has been associated with survival. A modified BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index replacing the 6-min walk distance (6MWD) with V'(O(2)) as % predicted (mBODE%) has been developed and found to have excellent correlation with the conventional BODE index. The objectives of the present study were to compare the ability of the conventional BODE and the mBODE% to predict mortality in 444 patients with chronic obstructive pulmonary disease (COPD) followed for a mean+/-SD period of 71+/-34 months. ⋯ Logistic regression analysis with COPD survival as the dependent variable identified the BODE index, Charlson's and exercise capacity (in W) as variables associated with this outcome. In conclusion, the conventional BODE index, which uses the 6-min walk distance, predicts mortality in chronic obstructive pulmonary disease as well as the modified index using peak oxygen uptake. The results support the use of the simpler index, which includes the 6-min walk distance in the comprehensive evaluation of patients with chronic obstructive pulmonary disease.
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Sandblasting denim using silica has emerged as a new cause of silicosis in Turkey. Following the discovery of several cases of silicosis in (young) workers who used this process, the frequency and main occupational risk factors of silicosis among former denim sandblasters in the region of Erzurum (Turkey) were evaluated. Demographic characteristics and information on working conditions were obtained by questionnaire and interview. ⋯ These subjects had lower forced expiratory volume in one second and forced vital capacity. The risk of silicosis correlated with seniority (i.e. working as a foreman), exposure duration and number of places of work. Considering the high prevalence rate of silicosis in such workplaces, further problems are inevitable in the future unless effective measures are taken.
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Alterations of the nitric oxide receptor, soluble guanylate cyclase (sGC) may contribute to the pathophysiology of pulmonary arterial hypertension (PAH). In the present study, the expression of sGC in explanted lung tissue of PAH patients was studied and the effects of the sGC stimulator BAY 63-2521 on enzyme activity, and haemodynamics and vascular remodelling were investigated in two independent animal models of PAH. Strong upregulation of sGC in pulmonary arterial vessels in the idiopathic PAH lungs compared with healthy donor lungs was demonstrated by immunohistochemistry. ⋯ Upregulation of soluble guanylate cyclase in pulmonary arterial smooth muscle cells was noted in human idiopathic pulmonary arterial hypertension lungs and lungs from animal models of pulmonary arterial hypertension. Stimulation of soluble guanylate cyclase reversed right heart hypertrophy and structural lung vascular remodelling. Soluble guanylate cyclase may thus offer a new target for therapeutic intervention in pulmonary arterial hypertension.