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Increasingly, it is being recognised that a balanced modulation of several targets can provide a superior therapeutic effect and side effect profile compared to the action of a selective ligand. Rational approaches in which structural features from selective ligands are combined have produced designed multiple ligands that span a wide variety of targets and(More)
Contrast sensitivity was measured in 12 subjects for different spatial frequencies of sinusoidal grating patterns, generated by oscilloscope, for pupil diameters 2-8 mm and for defocus of +1-4 D, following homatropine eyedrops. Changes in pupil diameter, without correction for the change in retinal illumination, had no significant effect on contrast(More)
Identification of peptide substrates for proteases can be a major undertaking. To overcome issues such as feasibility and deconvolution, associated with large peptide libraries, a 'small but smart' generic fluorescence resonance energy transfer rapid endopeptidase profiling library (REPLi) was synthesised as a tool for rapidly identifying protease(More)
Instillation of 0.25% physostigmine sulphate eyedrops in twelve subjects caused a sustained miosis, a transient reduction in near-point and a transient increase in the amplitude of accommodation. The latter had a peak at 30 min and had recovered by 90 min, though its amplitude varied widely between subjects. Contrast sensitivity to stationary grating(More)
An intramuscular injection of 2 mg atropine sulphate was given at either 8 or 120 min prior to instillation of 0.25% physostigmine sulphate eyedrops. In this way, the maximum accommodative change and the concomitant reduction in contrast sensitivity caused by physostigmine coincided with, respectively, the peak plasma atropine concentration or the fully(More)
A method is described whereby stable isotopic signatures were partially incorporated into both termini of a peptide sequence giving rise to a characteristic cluster of four peaks in the mass spectral analysis. Cleavage of this peptide by a protease between the labeled positions generates two fragments both displaying their own individual signature peaks.(More)
The effects of a single intramuscular injection of 2 mg atropine sulphate on visual function were studied in volunteer subjects. The well-known effects of increased heart rate, dryness of the mouth, increased pupil diameter and reduced accommodative range were confirmed. Visual acuity, stereoacuity, red-green colour balance and reaction time to a visual(More)
Although resin-based chemistry offers many practical advantages over conventional solution phase for the synthesis of combinatorial libraries, effective monitoring of reactions conducted on the support remains a challenge. A number of techniques have been developed to enable the analysis of solid phase organic synthesis either by monitoring the resin-bound(More)
A method for the detection of specific IgE in human serum is described, using a modified radioimmune assay termed the Inhibition Assay Technique (IAT) The technique is based on the ability of specific IgE to bind with allergen. The difference in total IgE before incubation with the allergen and after incubation with the allergen gives a relative(More)
The effects on vision of ingestion of the anticholinesterase pyridostigmine bromide (60 mg), assessed from pharmacokinetic data to provide at least 20% inhibition of blood cholinesterase over the 1 1/2-4 1/2 h experimental period, was compared with 60 mg lactose in a double-blind crossover protocol. Contrast sensitivity to stationary oscilloscope-generated(More)
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