After 7 weeks of bupropion SR treatment, more than twice as many smokers with CVD had quit smoking at 1 year compared with placebo. The safety profile of bupropion SR was similar to that previously observed in general smoking populations.
and the 2Clinical Pharmacology Unit, Royal Bath Hospital, Harrogate SUMMARY An enzyme linked immunoassay (ELISA) for the collagen cross link, pyridinoline, has been developed using affinity purified antibodies, with a sensitivity down to about 0.1 ng of cross link. Measurements of urinary pyridinoline were made in patients with rheumatoid arthritis (RA), osteoarthritis (OA), and a control group showing no signs of joint disease. Expressed relative to creatinine values, pyridinoline was significantly increased in both RA and OA groups compared with controls: these differences were much larger than could be attributed to any age related effects or to changes in urinary creatinine concentrations. These findings were confirmed by analysis of a series of 24 h urine collections which showed that the total pyridinoline excretions were significantly higher in both RA and OA groups than in the controls. As pyridinoline is much more prevalent in cartilage than in bone collagen, measurement of this compound in urine may provide an index for monitoring the increased joint destruction that occurs in arthritic disease. for collagen degradation based on the release of cross linking components has potential advantages over previous methods both in specificity and sensitivity. In particular, measurement of cross links would indicate degradation of mature collagen fibrils rather than release from all intermediates formed during the extensive postribosomal processing of collagen.Pyridinoline is a 3-hydroxypyridinium compound9 that is formed by interactions involving an intermediate bifunctional cross linkl 01 to give a stable amino acid derivative linking three collagen chains.'2 The compound is most prevalent in cartil-
BackgroundLong-acting β2-adrenergic agonists (LABAs) are recommended in combination with inhaled corticosteroids (ICSs) for asthma management. Abediterol is a novel, selective, potent, once-daily LABA in development for treatment of asthma and chronic obstructive pulmonary disease. This study aimed to determine abediterol doses with similar peak bronchodilatory effect to salbutamol 400 μg, and duration of action compatible with once-daily dosing in patients with persistent, stable asthma.MethodsThis was a Phase II, randomized, double-blind, double-dummy, crossover, placebo-controlled, dose-ranging study (ClinicalTrials.gov NCT01425801) in 62 patients with mild-to-moderate asthma who were also receiving an ICS. Patients received single doses of abediterol 0.313, 0.625, 1.25, or 2.5 μg, salbutamol 400 μg, or placebo in the morning. Spirometry was performed up to 36 h post-dose; safety and tolerability were assessed throughout the study. The primary endpoint was change from baseline in peak forced expiratory volume in 1 s (FEV1). Additional endpoints included trough FEV1, normalized area under the FEV1 curve (FEV1 AUC) up to 24 h post-dose, and peak and trough forced vital capacity (FVC).ResultsAbediterol produced dose-dependent improvements in peak FEV1 from baseline compared with placebo, from 0.274 (95% CI 0.221, 0.327) to 0.405 L (95% CI 0.353, 0.458) for abediterol 0.313 to 2.5 μg, respectively (p < 0.0001 all doses). Abediterol 0.625, 1.25, and 2.5 μg had similar magnitude of peak FEV1 effect to salbutamol. Dose-dependent changes from baseline in trough FEV1 versus placebo were 0.219 (95% CI 0.136, 0.302) to 0.400 L (95% CI 0.317, 0.483) for abediterol 0.313 to 2.5 μg, respectively (p < 0.0001). All abediterol doses achieved significant improvements versus placebo in FEV1 AUC 0–6, 0–12, and 0–24 h, and peak and trough FVC (p < 0.05). Less than 10% of patients experienced treatment-related adverse events for each dose of abediterol; most were mild to moderate in intensity and the most common were headache and nasopharyngitis. There were no clinically relevant changes in heart rate.ConclusionsAbediterol 0.625–2.5 μg provided dose-dependent, clinically and statistically significant bronchodilation versus placebo in patients with asthma, with a peak effect similar to salbutamol and duration of action compatible with once-daily dosing. All doses of abediterol were well tolerated.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2466-14-176) contains supplementary material, which is available to authorized users.
Thirty patients (22 women) with active rheumatoid arthritis participated in an open study of 6 months' treatment with either enteric-coated sulphasalazine (SASP) or SASP plus D-penicillamine (DPA). Patients were assessed at regular intervals using a number of clinical and biochemical tests designed to detect specific antirheumatic activity. There were significant improvements in clinical and laboratory variables with both regimens consistent with second-line activity. Improvements were greater and more numerous with combination therapy. At the end of the trial period, there were nine 'responders' in the SASP/DPA group but only six in the SASP group. Neither efficacy nor toxicity could be related to patient acetylator status. Nausea and dyspepsia were frequent problems with both treatment regimens but dysgeusia and thrombocytopenia were confined to the SASP/DPA group. Study withdrawals were twice as common with combination therapy. These results suggest that a combination of SASP and DPA is more potent than SASP alone but at the expense of poorer patient tolerance.
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