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R W Stevenson

Publications and source records attributed to R W Stevenson.

82 records · Page 5Linked to original sources

Evidence that protease inhibitors reduce the degradation of parathyroid hormone and calcitonin injected subcutaneously.

1 Agents known to delay absorption from a subcutaneous site were tested in chicks for their ability to prolong the hypercalcaemic response to parathyroid hormone (PTH). 2 Polyvinylpyrrolidone was found to enhance the response but gelatine greatly reduced the 2 h hypercalcaemia. 3 The reduction by gelatine was reversed when the protease inhibitor aprotinin was added to the injection vehicle, and hypercalcaemia then persisted for more than 8 h. 4 Of other protease inhibitors studied, epsilon-aminocaproic acid was also found to enhance the hypercalcaemic response to subcutaneous PTH and its fragments but, unlike aprotinin, it was ineffective in the presence of gelatine. 5 By radioimmunoassay and bioassay respectively, it was confirmed that aprotinin raised circulating levels of PTH and also of another peptide hormone, calcitonin, injected subcutaneously. 6 Addition of calcium to the solutions injected subcutaneously abolished the hypercalcaemic response to PTH while injection of calcium and PTH simultaneously but at separate sites left the response unaltered. 7 The two protease inhibitors, epsilon-aminocaproic acid and aprotinin, each restored the response to subcutaneous PTH despite the presence of calcium at the injection site. 8 It was concluded that protease inhibitors injected subcutaneously with PTH and calcitonin in the chick reduced the rate of degradation of these hormones and that the proteases responsible for hormone degradation at the subcutaneous injection site may be released or activated by calcium ions.

Animals↗

Insulin infusion into the portal and peripheral circulations of unanaesthetized dogs.

Changes in glucose, phosphate, potassium, non-esterified fatty acids (NEFA) and insulin in peripheral venous blood were compared in five unrestrained fasted dogs during different rates of insulin infusion by the portal and peripheral circulation. The 'low' rate of insulin infusion was that required to produce a fall in plasma glucose of 0.56-0.83 mmol/l (0.024 u/kg/h female, 0.012 u/kg/h male). Two-fold and four-fold higher rates are referred to as 'medium' and 'high' rates, respectively. In all dogs, dose-related reductions in the glucose concentration of peripheral blood resulted from increasing the rate of insulin by either route. At 'low' and 'high' rates of infusion the net response was independent of the route of administration, but the 'medium' rate of insulin infusion led to a greater degree of hypoglycaemia when given peripherally than intraportally. As expected, insulin infused peripherally resulted in graded increases in peripheral insulin levels as the rate of infusion was increased from low to high while, paradoxically, intraportal administration at low and medium infusion rates resulted in a mean decrease of peripheral insulin levels from control, the low-dose producing the most consistent fall. The fact that hypoglycaemia accompanied this fall during portal infusion suggests that these low doses of insulin had a direct effect on plasma phosphate resulting from the change in route of administration of insulin (i.e. increase during portal and decrease during peripheral infusion) also suggests a direct hepatic effect of insulin given intraportally.

Animals↗