(3R,5R)-Clavulanic acid, a clinically used inhibitor of serine beta-lactamases, is produced by fermentation of Streptomyces clavuligerus. The early steps in clavulanic acid biosynthesis leading to the bicyclic beta-lactam intermediate (3S,5S)-clavaminic acid have been defined. However, the mechanism by which (3S,5S)-clavaminic acid is converted to the penultimate intermediate (3R,5R)-clavaldehyde is unclear.
View Article and Find Full Text PDFTwo new classes of inhibitors of LpPLA2 have been identified in fermentations of Pseudomonas fluorescens. The two structurally isomeric series differ in the geometry of closure of the bicyclic carbamate and comprise a range of compounds varying only in length of their lipophilic sidechain. The most abundant species were extracted from the cells and purified by silica and C18 chromatography.
View Article and Find Full Text PDFSixty-three patients with mild to moderate hypertension completed a double-blind, randomised crossover trial of atenolol 100 mg daily, enalapril 20 mg daily and the fixed combination atenolol 50 mg and nifedipine retard 20 mg (Tenif) once daily. In the three areas of efficacy that the study compared-24-hour post dose blood pressure, control of blood pressure over the dosing period with particular reference to the waking day and attenuation of systolic blood pressure on exercise-atenolol and the fixed combination demonstrated greater efficacy than enalapril.
View Article and Find Full Text PDFThis randomised, double-blind, crossover study investigated the haemodynamic effects of a beta-blocker (atenolol 50mg) and a calcium antagonist (sustained release nifedipine 20mg) given either separately or in combination in 3 groups of patients with mild to moderate essential hypertension. Each treatment was administered twice daily. The fixed combination given twice daily for 4 weeks produced reductions in blood pressure which lasted for at least 12 hours after administration of the final dose.
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