The efficacy and safety of budesonide/formoterol in a single inhaler compared with placebo, budesonide and formoterol were evaluated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).In a 12-month, randomised, double-blind, placebo-controlled, parallel-group study in 812 adults (mean age 64 yrs, mean forced expiratory volume in one second (FEV1) 36% predicted normal), patients received two inhalations twice daily of either budesonide/ formoterol (Symbicort1) 160/4.5 mg (delivered dose), budesonide 200 mg (metered dose), formoterol 4.5 mg or placebo. Severe exacerbations and FEV1 (primary variables), peak expiratory flow (PEF), COPD symptoms, health-related quality of life (HRQL), mild exacerbations, use of reliever b 2 -agonist and safety variables were recorded.Budesonide/formoterol reduced the mean number of severe exacerbations per patient per year by 24% versus placebo and 23% versus formoterol. FEV1 increased by 15% versus placebo and 9% versus budesonide. Morning PEF improved significantly on day 1 versus placebo and budesonide; after 1 week, morning PEF was improved versus placebo, budesonide and formoterol. Improvements in morning and evening PEF versus comparators were maintained over 12 months. Budesonide/formoterol decreased all symptom scores and use of reliever b 2 -agonists significantly versus placebo and budesonide, and improved HRQL versus placebo. All treatments were well tolerated.These results suggest a role for budesonide/formoterol in the long-term management of moderate-to-severe chronic obstructive pulmonary disease. Chronic obstructive pulmonary disease (COPD) is currently the fourth leading cause of death in the world [1], with increasing prevalence and mortality predicted in the coming decades [2]. COPD is a serious and disabling disease, which imposes a large burden on patients, healthcare systems and society.In patients with COPD, lung function deteriorates progressively over several years with increasing symptoms (e.g. dyspnoea, chest tightness, cough and sputum production); acute exacerbations are common, particularly in later stages, and these have considerable impact on patients9 daily activities and well-being [3]. Cigarette smoking is the major aetiological factor in COPD and smoking cessation is the only factor which has been shown to influence the decline in forced expiratory volume in one second (FEV1) [4,5]. However, the COPD-related inflammatory process in the airways initiated by smoking persists after cessation of smoking [6], and effective treatment is needed in past smokers with COPD [7].The pharmacotherapy of COPD largely consists of mucolytics, bronchodilators, such as b 2 -agonists, anticholinergics, theophylline and anti-inflammatory drugs i.e. inhaled corticosteroids, often taken in combination [2]. Consequently, there is a need for better treatment options to relieve symptoms, reduce exacerbations and to provide better health-related quality of life (HRQL) for individual patients. The long-acting b 2 -agonists formoterol a...

No abstract

Translation fidelity and efficiency require multiple ribosomal (r)RNA modifications that are mostly mediated by small nucleolar (sno)RNPs during ribosome production. Overlapping basepairing of snoRNAs with pre-rRNAs often necessitates sequential and efficient association and dissociation of the snoRNPs, however, how such hierarchy is established has remained unknown so far. Here, we identify several late-acting snoRNAs that bind pre-40S particles in human cells and show that their association and function in pre-40S complexes is regulated by the RNA helicase DDX21. We map DDX21 crosslinking sites on pre-rRNAs and show their overlap with the basepairing sites of the affected snoRNAs. While DDX21 activity is required for recruitment of the late-acting snoRNAs SNORD56 and SNORD68, earlier snoRNAs are not affected by DDX21 depletion. Together, these observations provide an understanding of the timing and ordered hierarchy of snoRNP action in pre-40S maturation and reveal a novel mode of regulation of snoRNP function by an RNA helicase in human cells.

Abstract. Porcine enzootic pneumonia (PEN), caused by Mycoplasma hyopneumoniae (Mh), has been described in pigs in all geographic areas. The disease is characterized by high morbidity and low mortality rates in intensive swine production systems. A morphologic and immunohistochemical study was done to determine the cellular populations present in lung parenchyma of infected pigs, with special attention to the bronchusassociated lymphoid tissue (BALT). Polyclonal and monoclonal antibodies were used for the detection of antigens of Mh, T lymphocytes (CD3 ϩ , CD4 ϩ , and CD8 ϩ ), IgG ϩ or IgA ϩ lymphocytes, and cells containing lysozyme, S-100 protein, major histocompatibility complex class II antigen or myeloid-histiocyte antigen. Findings in lung tissues associated with Mh infection were catarrhal bronchointerstitial pneumonia, with infiltration of inflammatory cells in the lamina propria of bronchi and bronchioles and alveolar septa. Hyperplasia of mononuclear cells in the BALT areas was the most significant histologic change. The BALT showed a high morphologic and cellular organization. Macrophages and B lymphocytes were the main cellular components of germinal centers. T lymphocytes were primarily located in perifollicular areas of the BALT, lamina propria and within the airway epithelium, and plasma cells containing IgG or IgA at the periphery of the BALT, in the lamina propria of bronchi and bronchioles, in alveolar septa, and around bronchial submucosal glands. The hyperplastic BALT in PEN cases consisted of macrophages, dendritic cells, T and B lymphocytes, and IgG ϩ and IgA ϩ plasma cells. CD4 ϩ cells predominated over CD8 ϩ cells. Local humoral immunity appears to play an important role in the infection.