\n\nObjectives: We sought to create an early-onset mouse model of cigarette smoke-induced COPD that develops the hallmark features of the human condition in a short time-frame. We also sought to use this model to better understand pathogenesis and the roles of macrophages and mast cells (MCs) in patients with COPD.\n\nMethods: Tightly controlled amounts of cigarette smoke were delivered to the airways of mice, and the development of the pathologic features of COPD was assessed. The roles of macrophages and MC tryptase in pathogenesis were evaluated by using depletion and in vitro Selleckchem NSC 23766 studies and MC protease 6-deficient mice.\n\nResults: After just 8 weeks of smoke exposure, wild-type mice had
chronic inflammation, mucus hypersecretion, airway remodeling, emphysema, and reduced lung function. These characteristic features Z-DEVD-FMK in vivo of COPD were glucocorticoid resistant and did not spontaneously resolve. Systemic effects on skeletal muscle and the heart and increased susceptibility to respiratory tract
infections also were observed. Macrophages and tryptase-expressing MCs were required for the development of COPD. Recombinant MC tryptase induced proinflammatory responses from cultured macrophages.\n\nConclusion: A short-term mouse model of cigarette smoke-induced COPD was developed in which the characteristic features of the disease were induced more rapidly than in existing models. The model can be used to better understand COPD pathogenesis, and we show a requirement for macrophages and tryptase-expressing MCs. (J Allergy Clin Immunol 2013;131:752-62.)”
“Objective To assess current and intended future use of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) and characterise those attending sexual health clinics, the anticipated PrEP delivery setting.\n\nDesign Cross-sectional study.\n\nMethods Self-administered survey
of 842 HIV negative MSM recruited from social venues in London in 2011.\n\nResults One selleck chemicals in 10 (10.2%, 83/814, 95% CI 8.2% to 12.5%) and one in 50 (2.1%, 17/809, 95% CI 1.2% to 3.3%) reported having ever used post-exposure prophylaxis (PEP) and PrEP respectively. Half reported they would be likely to use PrEP if it became available as a daily pill (50.3%, 386/786, 95% CI 46.7% to 53.9%). MSM were more likely to consider future PrEP use if they were <35 years (adjusted OR (AOR) 1.57, 95% CI 1.16 to 2.14), had unprotected anal intercourse with casual partners (AOR 1.70, 95% CI 1.13 to 2.56), and had previously used PEP (AOR 1.94, 95% CI 1.17 to 3.24). Over half of MSM (54.8% 457/834 95% CI 51.3 to 58.2) attended a sexual health clinic the previous year. Independent factors associated with attendance were age <35 (AOR 2.29, 95% CI 1.68 to 3.13), and >= 10 anal sex partners in the last year (AOR 2.49, 95% CI 1.77 to 3.52).