P. H. Joubert

Miglitol may have a blood glucose lowering effect unrelated to inhibition of alpha-glucosidase

SummaryMiglitol is an alpha-glucosidase inhibitor which lowers blood glucose and insulin concentrations in healthy volunteers after a starch meal. It also lowers blood glucose concentrations after a starch meal in patients with non-insulin-dependent diabetes mellitus, but under these circumstances insulin is unaffected.We have studied the effect of miglitol after a glucose load in six healthy male volunteers. Although one would expect an alpha-glucosidase inhibitor to have no effect on blood glucose concentrations after a glucose load, miglitol produced a significant decrease in blood glucose concentrations after the absorption peak. This could be due to enhancement of insulin effects or to depression of anti-insulin factors.

Effect of an alpha-glucosidase inhibitor (BAY m 1099) on post-prandial blood glucose and insulin in type II diabetics

SummaryThe effect of a new alpha-glucosidase inhibitor (BAY m 1099), a 1-deoxynojirimycin derivative, was studied in 10 black patients with Type II diabetes mellitus. It produced significant lowering of blood glucose concentration after standardized maize porridge meals. No significant untoward effects were noted. BAY m 1099 appears to offer potential benefit in the management of Type II diabetics, and more extensive clinical investigation is warranted.

The effect of a 1-deoxynojirimycin derivative on post-prandial blood glucose and insulin levels in healthy black and white volunteers

SummaryBAY m1099 (a 1-deoxynojirimycin derivative) is a glucose analogue which is an α-glucosidase inhibitor. Its effects on post-prandial blood glucose and insulin levels was compared with a placebo in 12 healthy male volunteers (6 Blacks and 6 Whites). It produced a similar, significant depression of post-prandial blood glucose and insulin leveles when the groups were assessed separately and when the data were pooled. Although blood insulin levels in Whites were higher than in Blacks, as previously reported, the difference was not statistically significant and did not appear to influence the response to the drug. BAY 1099 produced no objective or subjective untoward effects and appears to warrant further investigation as an adjuvant to dietary control of diabetes mellitus.

Effects of essential fatty acids on mild to moderate essential hypertension

A double-blind placebo-controlled study with a crossover design was conducted on 25 non-obese black patients with mild-moderate uncomplicated essential hypertension. They were randomly assigned into two groups. After having received placebo capsules for 4 weeks, they received dietary supplementation with either Efamol-marine (containing desaturated n-6 and n3 essential fatty acids), or sunflower seed and linseed oil capsules for 12 weeks. Thereafter a second 4 weeks placebo phase and a subsequent second 12-week active phase were entered into during which a crossover of the dietary supplementation of the groups was brought about. The mean systolic blood pressure of patients receiving Efamol-marine was significantly lowered after 8 and 12 weeks, while those receiving sunflower/linseed oil supplementation had no significant reduction of blood pressure. This observation may indicate that defective desaturation of the essential fatty acids by the enzyme delta-6-desaturase, could play an important role in the etiology of essential hypertension.

Ethnic Differences in Response to Beta-Blockade: Fact or Artefact? A Study with Bisoprolol and Propranolol

SummaryA randomized, double-blind, placebo-controlled study was performed in 8 white and 8 black volunteers matched for sex, age and mass. The effect of 3 intravenous doses of a new, cardiose-lective beta-adrenergic blocker, bisoprolol, on the heart rate increase after standardized exercise was compared to that of 3 doses of propranolol.As described previously for propranolol, black volunteers showed less response than whites to beta-blockade assessed in terms of the reduction in exercise-induced tachycardia. The effects of the two beta-blockers were similar and the apparent ethnic difference was seen with both drugs.It has previously been shown that black volunteers have a higher intrinsic heart rate (i.e. heart rate after parasympathetic and beta-adrenergic blockade of the heart) than whites, but their resting heart rates are similar because of greater parasympathetic tone in blacks. When exercise-load was calculated as increase in heart rate above that after atropinization, no ethnic differences were seen.It is suggested that in populations that are heterogenous in terms of the heart rate increase after atropine, work load should be standardized in terms of the increase in heart rate over the atropine heart rate rather than on absolute heart rate.The apparent ethnic difference represents a flaw in methodology as applied to a heterogenous volunteer population.

Penbutolol in the Treatment of Mild to Moderate Essential Hypertension in Black South Africans

The antihypertensive effects of penbutolol, a nonselective beta‐adrenoceptor antagonist with intrinsic sympathomimetic activity, was assessed in nonobese black South Africans aged 25 to 65 years with uncomplicated mild to moderate essential hypertension. After a 4‐week placebo run‐in period 50 patients entered a randomized placebo‐controlled study with a crossover design. For 8 weeks they received a once daily dose of 40 mg penbutolol (or placebo) which was increased to 80 mg per day for the next 4 weeks in poor responders. This was followed by a 4‐week placebo washout period after which a crossover of treatment was achieved and a second 12‐week period of treatment initiated. Thirty‐five patients completed the whole study and in 15 patients diastolic blood pressure was reduced below 95 mm Hg. The mean systolic pressures of these patients decreased by 21 mm Hg and their mean diastolic pressure decreased by 11 mm Hg during treatment with penbutolol. These results suggest that penbutolol monotherapy is an alternative therapeutic approach to hypertension in black South Africans.

A comparison of the effects of digoxin and digitoxin on systolic time intervals and colour vision

SummaryAnimal studies suggest that for the same inotropism hydrophilic cardiac glycosides produce greater depression of atrioventricular (AV) conduction than lipophilic ones. This has been explained on the basis of a greater vagomimetic effect with hydrophilic agents and a greater sympathomimetic effect with lipophilic agents.In this randomized, cross-over study we investigated the effects of placebo, digoxin (relatively hydrophilic), and digitoxin (relatively lipophilic) in twelve healthy volunteers. For both drugs steady-state serum concentrations in the mid-therapeutic range were achieved.Both drugs produced the same positive inotropic effect as measured by systolic time intervals (QS2c). There was a trend for digoxin to have a greater effect on AV conduction than digitoxin.After atropine or propranolol there was no difference between the effect of the two cardiac glycosides on AV conduction. No significant effects on colour vision were seen. We conclude that, there do not seem to be pharmacodynamic differences between digoxin and digitoxin at mid-therapeutic serum concentrations.

Effects of digoxin and acetyl-digitoxin on basal and CO2-stimulated ventilation

SummaryEight healthy volunteers were studied to ascertain the effect of digoxin and the relatively more lipophylic cardiac glycoside, acetyl-digitoxin on ventilation. Baseline ventilation as well as the response to the inspiration of 2.2% and 4.8% carbon dioxide were assessed. Digoxin produced a depression of minute volume and oxygen consumption whereas acetyl-digitoxin produced the opposite effect. This could be the result of a relatively greater vagomimetic effect with digoxin and a greater symphatomimetic effect with acetyl-digitoxin. These findings might have clinical implications in cardiac patients who have pulmonary disease.

The IgA immune system in epileptics on anticonvulsant therapy

SummaryDisturbances in IgA have often been reported in white epileptics on anticonvulsant therapy. The clinical significance of these disorders is of interest as this aspect does not appear to have been sufficiently explored. In a previous study neither African nor Caucasian epileptics on treatment showed a deficiency of serum IgA. Since secretory IgA is the main defence factor in protecting mucosal surfaces, the object of the present study was simultaneously to determine serum and salivary IgA in suitable subjects and to monitor related clinical events. A similar elevation of salivary IgA level was found in Black and White epileptics on treatment. Clinical events were rare and were not related either to serum or secretory IgA concentrations. It is concluded that at present epileptics do not seem to require special immunological or clinical monitoring.