The cardiovascular and central nervous system effects of the kappa opioid receptor agonist U-62066E were investigated in ten normal male subjects who received U-62066E or placebo with low or high dose naloxone in a randomized, double blind study. Blood pressure and heart rate in the supine and standing position, plasma adrenaline and noradrenaline, regional Doppler blood velocity indices and psychometric assessments were recorded for 1.25 h before and 6 h following injection. U-62066E caused sedation and dysphoria but no euphoria. Plasma noradrenaline was increased by U62066E when compared with basal levels. This action of U62066E was prevented by high but not low dose naloxone. U-62066E had no significant effect on blood pressure, heart rate or regional blood flow indices in the vessels studied and no effect on plasma adrenaline levels. Since U62066E at a dose known to have marked kappa effects was not found to influence cardiovascular indices our results do not support a major role for kappa opioids in the control of the circulation. However, U62066E may influence noradrenaline release or clearance and cause sedation and psychotomimetic effects.
This study investigates whether aspirin injury to the human gastric mucosa can be prevented by profound acid suppression with omeprazole, in a randomised, double blind, crossover design according to latin square. It was concluded that profound acid suppression can prevent aspirin induced gastric mucosal injury in normal subjects. This approach may prevent the development of peptic ulcers and their complications in patients taking aspirin and other non-steroidal anti-inflammatory drugs.Aspirin and non-steroidal anti-inflammatory drugs are strongly associated with peptic ulcer complications in the elderly in Britain. Assuming that the association may be causative, a number of approaches have tried to reduce the extent of damage caused by these agents.6 Although old people appear to be at greatest risk, it is difficult to evaluate possible therapeutic manoeuvres in this population. We have therefore investigated healthy adult volunteers whose acute responses appear to reflect those of older patients.7 Our previous studies show that acid inhibition by ranitidine8 and famotidine9 results in a reduction in gastric mucosal damage, as quantified by the rate of gastric mucosal bleeding and endoscopic appearance, but aspirin induced damage was not totally abolished.In the present study we have examined the hypothesis that gastric acid is necessary for the occurrence of aspirin induced gastric damage. To achieve virtual gastric anacidity we used omeprazole, an irreversible inhibitor of the proton pump in gastric parietal cells.'0 Methods bd for the last 48 h; (c) omeprazole 20 mg each morning for seven days plus aspirin 900 mg bd for the last 48 h; and (d) omeprazole 40 mg bd for seven days plus aspirin 900 mg bd for the last 48 h. The last doses of omeprazole and aspirin (or the corresponding placebo) were taken at 07 00 h and 07 30 h -that is, 120 and 90 minutes, respectively, before measurement of gastric blood loss. Each of the above regimens was separated by a seven day washout period. The order of treatments was randomised according to a latin square design and the study conducted in double blind manner.
Reproducibility of Doppler blood velocity waveform measurements in external and internal carotid, middle cerebral, and brachial arteries and ascending aorta was determined in 8 normal male volunteers twice daily on three occasions each separated by two or more weeks. Measurements were made in supine and standing positions at rest and after taking glyceryl trinitrate and in the supine position after performing a standardized exercise test. The Doppler blood flow waveform indices showed a between days coefficient of variation of less than 15% both for baseline measurements and during haemodynamic change induced by exercise or glyceryl trinitrate. We conclude that Doppler blood velocity waveform measurement in different vascular beds is reproducible at baseline and when the cardiovascular system is interrupted pharmacologically or physiologically.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.