Direct exposure in vitro of the protein αrantitrypsin (α1-AT; human neutrophil elastase inhibitor, α1-proteinase inhibitor) to gas phase cigarette smoke causes a loss of elastase-inhibitory capacity (EIC). This effect appears to be related to the formation of reactive oxygen species in the smoke that inactivate α1-AT by oxidizing the methionine terminal amino acid. Reducing agents such as glutathione and ascorbic acid prevent this inactivation. In the present investigation erdosteine, a novel thiol derivative, which contains two blocked SH groups with potential reducing properties, was tested in vitro for its capacity to protect human α1-AT. For the purpose, the compound, previously hydrolyzed with bicarbonate-carbonate buffer or with microsomal enzymes, was put in contact with α1-AT and exposed to gas phase cigarette smoke. The EIC of α1-AT was then measured by incubating the samples with leukocyte elastase and, subsequently, by titrating the residual elastolytic activity against a synthetic substrate. Under these conditions erdosteine effectively protected α1-AT against the smoke injury and, after alkaline hydrolysis, it appeared to be as active as glutathione and ascorbic acid (EC50 being respectively 6.4, 7.2 and 6.2 mM). This evidence suggests that the erdosteine SH groups, which can become free, may have an important role in the mechanism of action, by blocking highly reactive oxygen-free radicals. Erdosteine may have a therapeutic application in preventing oxidative lung damage induced by cigarette smoke
Twenty four patients with acute infective exacerbations of chronic bronchitis received amoxycillin alone or in combination with erdosteine (a mucolytic agent) for a week in a double blind, placebo controlled study. Clinical assessment scores, body temperature, serum and sputum amoxycillin concentrations, and sputum culture results were recorded in each group. Erdosteine significantly increased antibiotic concentrations in sputum but not in serum. The combined treatment also caused a more rapid decrease in sputum viscosity and in body temperature and faster sterilisation of the sputum. These results show that erdosteine increases amoxycillin concentration in sputum in patients with acute exacerbations of chronic bronchitis. This effect may be due to a reduction in the viscosity of the bronchial secretions produced by erdosteine.
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A new series of eledoisin-like peptides was synthesized with the object of obtaining long-lasting hypotensive drugs. Acyl residues were introduced into the molecule of the peptide R
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