No abstract

The effect of the supplementation of nitrous oxide-oxygen anaesthesia with either fentanyl 15 micrograms kg-1 or 0.5% halothane on the beta-endorphin, ACTH, glucoregulatory hormonal and metabolic response to pelvic surgery was investigated. Fentanyl inhibited the increases in circulating beta-endorphin, ACTH, growth hormone, cortisol and glucose concentrations found in the patients receiving halothane. Changes in circulating beta-endorphin concentrations during surgery probably reflect alterations in pituitary secretion and appear to have no major metabolic effects. The suppression of pituitary secretion persisted for at least 4 h after the start of surgery.

The direct effects of ketoconazole on ACTH secretion have been investigated using a rat pituitary cell culture system. Ketoconazole had no significant effects on basal ACTH secretion, corticotrophin-releasing factor- or arginine vasopressin-stimulated ACTH secretion, nor did it affect dexamethasone inhibition of ACTH secretion. In-vivo studies demonstrated an increased ACTH level (168 vs 76 ng/l) accompanied by a fall in plasma corticosterone (193 vs 307 micrograms/l) in normal rats given ketoconazole (24 mg/kg, five oral doses given 8 hourly). No effects were seen in adrenalectomized rats or at lower doses (6 mg/kg) in normal or adrenalectomized rats. A high dose of ketoconazole (24 mg/kg, twice daily oral doses) also caused increased ACTH levels in normal rats (129 vs 86 ng/l) when given for 7 days. No effects were seen in adrenalectomized rats or on plasma corticosterone levels in normal rats. Our data suggest that ketoconazole at these doses has no direct effects on pituitary ACTH secretion but causes an increase in plasma ACTH due to its inhibition of adrenal steroid synthesis.

Two novel dopaminergic drugs, designated CV 205-502 and CQP 201-403 have recently been developed by Sandoz Pharmaceuticals Ltd (Basle,Switzerland). The effects of these drugs on PRL and GH secretion by normal rat and tumorous human pituitary cells in vitro have been investigated. Low doses of both CV 205-502 and CQP 201-403 immediately and profoundly suppressed PRL secretion, which failed to recover up to 7 h after removal of the drugs. Similarly, CQP 201-403 significantly suppressed basal GH secretion by human pituitary somatotropic tumours in culture, and both drugs significantly reduced the stimulatory effect of GHRH. These effects are more potent and longer acting than the previously described in vitro effects of bromocriptine. It is concluded that CV 205-502 and CQP 201-403 hold potential for the treatment of patients with hyperprolactinaemia and, possibly, also in patients with acromegaly.

The responses to brief maximal exercise of 10 male subjects have been studied. During 30 s of exercise on a non-motorized treadmill, the mean power output (mean +/- SD) was 424.8 +/- 41.9 W, peak power 653.3 +/- 103.0 W and the distance covered was 167.3 +/- 9.7 m. In response to the exercise blood lactate concentrations increased from 0.60 +/- 0.26 to 13.46 +/- 1.71 mmol.l-1 (p less than 0.001) and blood glucose concentrations from 4.25 +/- 0.45 to 5.59 +/- 0.67 mmol.l-1 (p less than 0.001). The severe nature of the exercise is indicated by the fall in blood pH from 7.38 +/- 0.02 to 7.16 +/- 0.07 (p less than 0.001) and the estimated decrease in plasma volume of 11.5 +/- 3.4% (p less than 0.001). The plasma catecholamine concentrations increased from 2.2 +/- 0.6 to 13.4 +/- 6.4 nmol.l-1 (p less than 0.001) and 0.2 +/- 0.2 to 1.4 +/- 0.6 nmol.l-1 (p less than 0.001) for noradrenaline (NA) and adrenaline (AD) respectively. The plasma concentration of the opioid beta-endorphin increased in response to the exercise from less than 5.0 to 10.2 +/- 3.9 p mol.l-1. The post-exercise AD concentrations correlated with those for lactate as well as with changes in pH and the decrease in plasma volume. Post-exercise beta-endorphin levels correlated with the peak speed attained during the sprint and the subjects peak power to weight ratio. These results suggest that the increases in plasma adrenaline are related to those factors that reflect the stress of the exercise and the contribution of anaerobic metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)