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a b s t r a c tNanocrystalline CeO 2 with a regular size of 9.5 nm was prepared by a freeze-drying method, and subsequent impregnated with a Cu(II) acetate solution, varying the loading of Cu (3, 6, 12 wt.%). The resulting CuO/CeO 2 materials were characterized by N 2 physisorption at −196 • C, HRTEM, H 2 -TPR, X-ray diffraction, Raman spectroscopy and XPS and tested as catalysts in the preferential CO oxidation in a H 2 -rich stream (CO-PROX) in the temperature range • C. In spite of their low specific surface areas the catalysts exhibited a good catalytic performance, resulting active and selective in the CO-PROX reaction at low temperatures. The inhibiting effect of the simultaneous presence of CO 2 (15 vol.%) and H 2 O (10 vol.%) in the reaction mixture on the performance of CuO-CeO 2 catalysts was also investigated. The addition of CO 2 and water in the gas stream depressed CO oxidation up to 160• C, its effect being negligible at higher temperatures. Nevertheless, despite these expected deactivation phenomena, a CO conversion value higher than 90% and a CO 2 selectivity of about 90% was achieved for all the samples at 160• C. The excellent performance, especially shown by the catalyst with 6 wt%. of copper, has been related to the wide dispersion of the copper active sites associated with the high amount of Ce 4+ species before reaction.

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CHF6001 [(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoyloxy)ethyl)pyridine 1-oxide] is a novel phosphodiesterase 4 (PDE4) inhibitor designed for use in pulmonary diseases by inhaled administration. Intratracheal administration of CHF6001 to ovalbumin-sensitized Brown-Norway rats suppressed the antigen-induced decline of lung functions (ED 50 5 0.1 mmol/kg) and antigen-induced eosinophilia (ED 50 5 0.03 mmol/kg) when administered (0.09 mmol/kg) up to 24 hours before antigen challenge, in agreement with CHF6001-sustained lung concentrations up to 72 hours after intratracheal treatment (mean residence time 26 hours). Intranasal, once daily administration of CHF6001 inhibited neutrophil infiltration observed after 11 days of tobacco smoke exposure in mice, both upon prophylactic (0.15-0.45 mmol/kg per day) or interventional (0.045-0.45 mmol/kg per day) treatment. CHF6001 was ineffective in reversing ketamine/xylazine-induced anesthesia (a surrogate of emesis in rat) up to 5 mmol/kg administered intratracheally, a dose 50-to 150-fold higher than anti-inflammatory ED 50 observed in rats. When given topically to ferrets, no emesis and nausea were evident up to 10 to 20 mmol/kg, respectively, whereas the PDE4 inhibitor GSK-256066 (6-[3-(dimethylcarbamoyl)phenyl]sulfonyl-4-(3-methoxyanilino)-8-methylquinoline-3-carboxamide) induced nausea at 1 mmol/kg intratracheally. A 14-day inhalation toxicology study in rats showed a no-observed-adverse-effect level dose of 4.4 mmol/kg per day for CHF6001, lower than the 0.015 mmol/kg per day for GSK-256066. CHF6001 was found effective and extremely well tolerated upon topical administration in relevant animal models, and may represent a step forward in PDE4 inhibition for the treatment of asthma and chronic obstructive respiratory disease.