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The effect of erdosteine, a mucoactive drug, on hypochlorous acid (HOCl)-induced lung injury, and the lipopolysaccharide (LPS)-induced increase in tumour necrosis factor-α (TNF-α) production and neutrophil recruitment into the airway, was investigated. Male BALB/c mice were orally administered erdosteine (3–100 mg kg−1), ambroxol hydrochloride (ambroxol) (3–30 mg kg−1), S-carboxymethyl-L-cysteine (S-CMC) (100–600 mg kg−1) or prednisolone (10 mg kg−1), 1h before intratracheal injection of HOC1 or LPS. In the HOCl-injected mice, erdosteine markedly suppressed increases in the ratios of lung wet weight to bodyweight and lung dry weight to bodyweight, whereas the other mucoactive drugs ambroxol and S-CMC had little effect. Erdosteine also inhibited the LPS-induced neutrophil influx, although it did not affect the increased level of TNF-α in the bronchoalveolar lavage fluid. The results suggest that attenuation of reactive oxygen species and neutrophil recruitment is involved in the clinical efficacy of erdosteine in the treatment of chronic bronchitis.

The fundamental problem of the decelerating laminar boundary layer defined in the title has been analyzed theoretically. The original, phenomenological viscous diffusion theory and the numerical analysis using a rational nondimensionalizing scaling technique based on the said phenomenological theory, which were both developed in our previous research for the simpler, linearly retarded flows on a semi-infinite flat plate and near a front stagnation point, are expanded and applied successively to the present problem. As the result the interesting flow behaviors of the decelerating stagnation boundary layer over the whole time region from the far past to the deceleration terminal at which the wall has just stopped, and further up to the distant future where the wall is permanently at rest, have been clarified not only numerically but also phenomenologically

The fundamental problem of the decelerating laminar boundary layer defined in the title has been analyzed theoretically. The original, phenomenological viscous diffusion theory and the numerical analysis using a rational nondimensionalizing scaling technique based on the said phenomenological theory, which were both developed in our previous research for the similar unsteady problem of a linearly retarded semi-infinite flat plate, are applied successively to the present problem. As the result the interesting flow behaviors of the decelerating stagnation boundary layer over the entire time region from the distant past to the deceleration terminal at which the wall has just stopped, and further up to the distant future where the wall is continuously at rest, have been clarified not only numerically but also phenomenologically.

New antiinflammatory agents 4-hydroxy-2(1H)-oxo-1-phenyl-1,8-naphthyridine-3- carboxamides 7 were designed and synthesized via a valuable intermediate, 1-phenyl-2H-pyrido[2,3-d][1,3]oxazine-2,4(1H)-dione (9). The nature of substituents on the amide nitrogen had a pronounced effect on antiinflamatory activity. Studies of structure-activity relationships led to compounds 33 and 34 bearing a pyridine ring on the amide nitrogen. Compounds 33 and 34 were active against carrageenin-, zymosan-, and arachidonic acid-induced rat paw edemas and also potently inhibited the reversed passive Arthus reaction in rats. Thus, they possess a broader spectrum of antiinflammatory activity than the classical nonsteroidal antiinflammatory drugs (NSAIDs) such as indomethacin and piroxicam.

Erdosteine (CAS 84611-23-4) and its active metabolite (M1) decrease the luminol-dependent chemiluminescence (LDCL). In this study, the scavenging effects of erdosteine and M1 on each reactive oxygen species, hypochlorous acid (HOCl), hydrogen peroxide (H2O2) and superoxide anion (O2-), were investigated. M1 interacted with HOCl at high activity, whereas erdosteine exhibited low activity. Although erdosteine interacted with H2O2 only at 1 mmol/l, M1 could significantly decrease H2O2 (> 0.1 mmol/l). Erdosteine and M1 did not interact with O2-. These results suggest that M1 possesses scavenging activities against H2O2 and HOCl in vitro.

To investigate the influence of erdosteine, a new homocysteine-derived expectorant, on airway clearance we studied the effects of the drug on the viscosity of mucin, on the mucociliary transport rate in quails, on airway secretion in rats and on the cough reflex in guinea-pigs. The active metabolite of erdosteine, M1 (10 μM to 1 mM), significantly reduced the viscosity of porcine stomach mucin. Erdosteine by itself did not reduce viscosity. Erdosteine significantly promoted mucociliary transport in quails and increased airway secretion in rats. The effect was still apparent 24 h after administration. Erdosteine significantly suppressed citric acid-induced cough reflexes in guinea-pigs but did not suppress mechanical stimuli-induced cough reflexes. Erdosteine suppressed the reduction of the recovery volume of bronchoalveolar lavage fluid and albumin leakage into the fluid in citric acid-exposed guinea-pigs. These results indicate that erdosteine removes sputum by reducing its viscosity, and by promoting mucociliary transport and sustained enhancement of airway secretion. It also suppressed the chemical stimulation-induced cough reflex and plasma leakage into the airway. These results suggest that erdosteine is an excellent expectorant with several modes of action.

Erdosteine is a new homocysteine-derived expectorant and has been reported to have many mucolytic effects. In this report, we studied the activities of erdosteine on mucociliary clearance in normal and airway-inflammation-induced rats. In normal rats, erdosteine at doses of 100–600 mg/kg significantly promoted mucociliary clearance. However, erdosteine did not change the concentrations of mucopolysaccharides in bronchoalveolar lavage fluid (BALF). In the LPS-instillated rats, the mucociliary clearance was inhibited and the number of inflammatory cells, albumin concentration, and mucopolysaccharides concentration in BALF were increased. Erdosteine at doses of 100–600 mg/kg significantly attenuated the inhibition of mucociliary clearance and the increase of inflammatory cells, however, it did not prevent the increase of albumin and mucopolysaccharides. Other mucolytic drugs which are ambroxol and S-carboxymethylcysteine, had no effect. These results indicate that erdosteine promotes the mucociliary clearance in normal and airway-inflammation-induced rats.