Biomedical subjects
A Ashford
Publications and source records attributed to A Ashford.
Lameness in kittens after vaccination.
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Studies of the effects of insulin, bradykinin, and captopril on blood glucose levels of alloxan-diabetic rats.
Infusion of bradykinin (1 microgram/min) or saline vehicle for 30 minutes into alloxan-diabetic rats produced no change in the very high levels of blood glucose. Furthermore, intravenous injection of captopril (3 mg/Kg body weight) into the diabetic rats did not result in a significant change of glucose concentrations over a period of 60 minutes. However, infusion of bradykinin 15 minutes after intravenous injection of captopril resulted in a marked decrease of glucose levels (p less than 0.01, compared to pretreatment) by 20 minutes after the start of the infusion. Thus, the captopril potentiated the effect of the kinin, possibly by inhibition of kininase II. Using a spectrophotometric assay with Bz-Gly-Gly-Gly as substrate insulin was shown to be an inhibitor of kininase II purified from hog lungs with an I50 of 1.6 X 10(-5)M compared to captopril with I50 of 2.2 X 10(-9)M. Furthermore, it was found that in vivo infusion of as little as 50 mU insulin over a period of 30 minutes, a dose that by itself was ineffective, potentiated the glucose-lowering activity of a bradykinin infusion in alloxanized rats. Interestingly, the infusion of insulin 15 minutes after injection of captopril, at doses of each compound which alone were inactive, did produce a significant fall (p less than 0.005) in glucose concentrations. Overall, the results show that captopril, insulin and bradykinin can interact to promote a reduction in blood glucose of alloxan-diabetic rats.
Absence of "cheese effect" during deprenyl therapy: some recent studies.
Although the selective monoamine oxidase (MAO) B inhibitor, (-)deprenyl, has been shown to be free from the "cheese effect" in man after tyramine challenge, the reason for this is far from clear: it may well be independent of the selective inhibitory action of the drug, for during chronic administration there is some evidence to suggest that both A and B forms of the enzyme are equally inhibited. By-passing the putative MAO A gut barrier in the pig (chosen because it possesses MAO B alone in all other tissues) by intravenous tyramine administration into the deprenyl-pretreated animal failed to provoke a pressor response, despite substantial MAO inhibition. Conversely, clorgyline (MAO A inhibitor) pretreatment, which resulted in minimal MAO inhibition, produced a profound hypertensive response, resembling that observed with the non-MAO-inhibiting drug, isoniazid. The most parsimonious explanation for these findings may be that two separate but closely associated pharmacological effects are normally found with "orthodox" MAO inhibitors, enzyme inhibition proper and facilitation of noradrenaline release from its binding sites during tyramine challenge.
Comparative effects of acebutolol and practolol on the lipolytic response to isoprenaline.
1 The effects of beta-adrenoceptor blockade on the metabolic responses to isoprenaline have been studied in an in vitro system of isolated fat cells and in six normal subjects. 2 The inhibitory effects of varying concentrations of acebutolol, practolol and propranolol on free fatty acid (FFA) release produced by isoprenaline (10(-7) M) were compared in isolated fat cells prepared from rat epididymal adipose tissue. Acebutolol and practolol, at equimolar concentrations, showed a similar inhibitory effect whilst propranolol was approximately 100 times more potent then either drug. At 10(-5)M concentration of propranolol, lipolysis was virtually abolished whilst at the same molar concentration, acebutolol and practolol halved the response. 3 Six healthy volunteers received three successive 15 min intravenous isoprenaline challenges (0.03 mug kg-1 min-1) per individual experiment. The first acted as a control whilst the following two were given either after single oral doses of placebo, acebutolol or practolol. The mean (+/- s.e. mean) basal FFA level was 0.77 +/- 0.06 mE1/1 and subsequent resting values after the administration of placebo or beta-adrenoceptor blocker were not significantly different. 4 Acebutolol inhibited the respective mean rises in FFA, produced by both post-control isoprenaline challenges, by (mean +/- s.e. mean) 70 +/- 4% and 84% +/- 5%. The comparable figures for practolol were 33 +/- 15% and 24 +/- 20%. The higher serum concentration of acebutolol produced greater inhibition but correlation of log serum concentration of the drug with percentage inhibition of FFA rise did not achieve significance. 5 Administration of isoprenaline, acebutolol or practolol did not significantly alter serum glucose, triglyceride or cholesterol levels. 6 Acebutolol and practolol effectively blocked the isoprenaline-induced tachycardia. The degree of blockade produced by practolol was greater than its inhibitory effect on FFA release. The diatolic fall in blood pressure in response to isoprenaline was abolished by acebutolol suggesting that its beta-adrenoceptor blocking action encompasses peripheral vascular sites. The comparable effect with practolol was a partial inhibition of the diastolic fall.
[Effects of adrenergic blockade on adipose tissue lipolysis provoked in cats and humans by intravenous perfusion of isoprenaline].
An intravenous infusion of isoprenaline (1 mug/kg/mn during 4 h) elicited a rise in serum free fatty acids (FFA) and glucose in anaesthetised cats. The effect reached a peak in 1 h and was then maintained at a plateau level for the remainder of the infusion. Acebutolol and practolol (0,1-10 mg/kg, p.o.) were more potent in reducing the concentration of free fatty acids (FFA) than in lowering glucose. Propranolol was roughly equipotent on FFA and glucose. In 6 fasted human volunteers, an intravenous infusion of isoprenaline (0,03 mug/kg/mn during 15 min) stimulated a rise in serum FFA. Peak values were attained rapidly and FFA levels began to fall soon after the end of the infusion. Blood glucose concentration was not changed. A placebo, given after the first infusion of isoprenaline, did not significantly affect the response to 2 further infusions at 2 and 4 h later. An oral dose of acebutolol (300 mg) largely suppressed the lipolytic effect of the 2nd and 3rd isoprenaline infusions, the degrees of inhibition being 70 p.cent and 85 p.cent respectively. The same dose of practolol was considerably less effective in inhibiting lipolysis (37 p.cent and 25 p.cent inhibition).