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The important role of ascorbic acid (AA) as an anti-oxidant is particularly relevant in diabetes mellitus where plasma concentrations of AA are reduced. This study was conducted to evaluate the effects of treatment with AA or an aldose reductase inhibitor, tolrestat, on AA metabolism and urinary albumin excretion in diabetes. Blood and urine samples were collected at 0, 3, 6, 9, and 12 months from 20 diabetic subjects who were randomized into two groups to receive either oral AA 500 mg twice daily or placebo. Systolic and diastolic blood pressures, HbA1c, plasma lipids, urinary albumin, and total glycosaminoglycan excretion were measured at all time points, and heparan sulphate (glycosaminoglycan) was measured at 0 and 12 months. The same parameters, as well as urinary AA excretion, were determined at 0 and 3 months for 16 diabetes subjects receiving 200 mg tolrestat/day. AA treatment increased plasma AA (ANOVA, F ratio = 12.1, p = 0.004) and reduced albumin excretion rate (AER) after 9 months (ANOVA, F ratio = 3.2, p = 0.03), but did not change the other parameters measured. Tolrestat lowered plasma AA (Wilcoxon's signed-rank test, p < 0.05), but did not change AER or the other parameters measured. The ability of AA treatment to decrease AER may be related to changes in extracellular matrix or improvement in oxidative defence mechanism. Unlike the rat model of diabetes, inhibition of aldose reductase did not normalize plasma AA or AER in humans. In fact, tolrestat reduced the plasma AA concentration, a phenomenon which may be due to increased utilization of AA. Dietary supplementation of AA in diabetic subjects may have long-term benefits in attenuating the progression of diabetic complications.

Thirty-three rabbits on a cholesterol-enriched diet were randomized into 6 groups and treated with daily injections of either water, 20 micrograms of potassium chromate or 1, 5, 10 or 20 micrograms of chromium chloride, respectively, for 135 days with a 2- to 10-fold increase in serum chromium. There was a marked reduction in the percentage of aortic intimal surface covered by plaque, in aortic weight and cholesterol content in the treated animals. Rabbits treated with 20 micrograms of chromium chloride showed a better response than those treated with either 10 or 20 micrograms of potassium chromate.

Urinary clearance techniques have been employed to compare the renal sites of action of three phenoxyacetic acid diuretics in man: ethacrynic (etacrynic) acid and the two enantiomers of indacrinone (MK-196). The effects of these compounds on fractional free-water clearance and reabsorption during maximal hydration and hydropenia, respectively, indicate that whilst ethacrynic acid and (-)-indacrinone have their natriuretic site of action in the medullary portion of the thick ascending limb of Henle's Loop, the (+)-enantiomer of indacrinone acts in the 'cortical diluting segment' or early distal tubule. The natriuretic potencies of all three agents are different as is their effect on the renal handling of uric acid. Ethacrynic acid produces minor urate retention whilst both enantiomers of indacrinone produce uricosuria and hypouricaemia. The apparent difference in the renal sites of action of the enantiomers of indacrinone is discussed in relation to our current knowledge of stereo-selectivity in other pharmacological systems.

Fifteen patients (median age 73 years) with severe congestive heart failure were treated with Enalapril for a total of 12 weeks with a significant improvement in their right atrial pressures and in their functional state. Renal function, serum potassium, magnesium and calcium levels were unchanged. Lymphocyte sodium, potassium and calcium levels were generally lower than control values throughout the study but these differences were only statistically significant early in the study. Lymphocyte magnesium levels were unchanged. These findings are in contrast to those previously reported in the literature for such patients treated with conventional diuretics.