6,963 publications from this institution
Current drug therapy for asthma is highly effective and has evolved from naturally occurring substances through logical pharmaceutical developments. Pharmacology has played a critical role in asthma drug development and several key experimental observations have been published in this journal. Understanding the pharmacology of effective drug therapies has also taught us much about the underlying mechanisms of asthma. β 2 ‐Adrenoceptor agonists are the most effective bronchodilators and evolved from catecholamines from the adrenal medulla, whereas corticosteroids, from the adrenal cortex, are by far the most effective controllers of the underlying inflammatory process in the airways. The current ‘gold standard’ of asthma therapy is a combination inhaler containing a long‐acting β 2 ‐agonist with a corticosteroid – an improved form of adrenal gland extract. Cromoglycate, derived from a plant product and theophylline, a dietary methyl xanthine, have also been extensively used in the therapy of asthma, but we still do not understand their molecular mechanisms. Pharmacology has played an important role in improving natural products to make effective long lasting and safe asthma therapies, but has so far been challenged to produce new classes of antiasthma therapy. The only novel class of antiasthma therapy introduced in the last 30 years are leukotriene antagonists, which are less effective than existing treatments. New, more specific, therapies targeted at specific cytokines are less effective than corticosteroids, whereas more effective therapies carry a risk of side effects that may not be acceptable. It seems likely that pharmacology, rather than molecular genetics, will remain the main approach to the further improvement of treatment for asthma. British Journal of Pharmacology (2006) 147 , S297–S303. doi: 10.1038/sj.bjp.0706437
The structural performance and design of concrete-filled double skin tubular (CFDST) cross-sections with square stainless steel outer tubes are studied herein. A total of 17 four-point bending tests on CFDST cross-sections with varying concrete grades, together with accompanying material tests, were first conducted. The details of the test rig and procedures, as well as the key experimental results are reported. Following the physical testing, a numerical modelling campaign was carried out. A finite element (FE) model was initially validated against the tests, and then adopted to conduct a parametric study to acquire further FE data, covering a broader spectrum of material strengths and cross-section slendernesses. The obtained test and FE results were used to evaluate the applicability of the general design provisions for concrete-filled carbon steel members in the current European and American design codes. Overall, the examined design codes are shown to provide unduly conservative (less so for the higher concrete grades) and rather scattered moment resistance predictions, though some moment resistances predicted using the European code were on the unsafe side. Modifications to the European design treatment in relation to the assumed stress distribution, to take due account of the partial spread of plasticity in the outer tube, and the effective compressive strength of the concrete infill, to reflect the reduced relative effectiveness of using higher concrete grades, are proposed and shown to improve the consistency of the resistance predictions.
Nedocromil sodium is a pyranoquinoline derivative that has been developed for the treatment of asthma. We report the results of a double blind randomised study of the effect of two doses of nedocromil sodium (2 and 4 mg) and matched placebo, delivered by metered dose pressurised aerosol, on bronchoconstriction induced by sulphur dioxide in six asthmatic subjects. Nedocromil sodium had no effect on baseline lung function. The magnitude of sulphur dioxide induced bronchoconstriction monitored by partial forced expiratory flow at 30% of reference vital capacity was significantly inhibited by nedocromil sodium 4 mg (p less than 0.05) but not by 2 mg. The maximum changes after placebo and after nedocromil 2 mg and 4 mg were -44.7, -32.7, and -11.8 l min-1. The area under the curve monitoring the effect over 6 minutes was significantly inhibited by both doses to the same extent, the mean changes after placebo and after nedocromil 2 mg and 4 mg being -349.3, -31.2, and 44.6 l. Dyspnoea was monitored by visual analogue scale and showed a significant reduction over 6 minutes with both doses of nedocromil. After placebo and after nedocromil 2 mg and 4 mg the mean maximum changes were 31.5, 13.7, and 15.7 mm, and the mean changes in area under the visual analogue scale-time curve were 289, 194, and 151 mm.min respectively.
