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“There are few alternatives to glucocorticosteroids for treatment of asthma. We assessed the activity of a novel protein drug designated ISU201, the extracellular domain
of the human cell surface protein BST2, stabilised by fusion with the Fc region of IgG, in mouse models of mild chronic asthma and an acute exacerbation of asthma. The ability of ISU201 to suppress airway inflammation and remodelling was compared with that of dexamethasone. Female BALB/c mice were systemically sensitised with ovalbumin, then received controlled low-level challenge with aerosolised ovalbumin for 6 weeks, which induced lesions of mild chronic asthma, and were treated with drugs during the final 2 weeks. Alternatively, sensitised mice received 4 weeks of chronic low-level challenge and were treated 24 and 2 hours before a final single moderate-level challenge, which triggered acute airway inflammation RG-7112 cost simulating an asthmatic exacerbation. Inflammation and remodelling were quantified, as was the Entinostat order expression of pro-inflammatory cytokines in bronchoalveolar lavage fluid and tissues. To identify cellular targets of ISU201, we assessed the effects of the drug on activated lymphocytes, macrophages and airway epithelial cells. In the model of mild chronic asthma, ISU201 was as effective as dexamethasone in suppressing airway inflammation and most
changes of remodelling. In the model of an allergen-induced acute exacerbation of chronic asthma, ISU201 was also an effective anti-inflammatory agent, although it was less active than dexamethasone. The drug acted on multiple cellular targets, suppressing production of pro-inflammatory cytokines by lymphocytes and macrophages. ISU201 significantly reduced acetylation selleckchem of histone H4 in airway epithelial cells, suggesting at least one potential mechanism of action. We conclude that in these models of asthma, ISU201 is a broad-spectrum inhibitor of both airway inflammation and remodelling. Thus, unlike drugs which target specific mediators, it could potentially be an alternative or an adjunct to glucocorticoids for the treatment of asthma.”
“We have performed surface acoustic wave (SAW) measurements
to examine vacancies in a surface layer of a borondoped silicon wafer currently used in semiconductor industry. A SAW with a frequency of f(s) = 517MHz was optimally generated by an interdigital transducer with a comb gap of w = 2: 5 mu m on a piezoelectric ZnO film deposited on the (001) silicon surface. The SAW propagating along the [100] axis with a velocity of v(s) = 4: 967 km/s is in agreement with the Rayleigh wave, which shows an ellipsoidal trajectory motion in the displacement components u(x) and u(z) within a penetration depth of lambda(p) = 3.5 mu m. The elastic constant C-s of the SAW revealed the softening of Delta C-s/C-s = 1.9 x 10(-4) below 2K down to 23 mK. Applied magnetic fields of up to 2 T completely suppress the softening.