Effect of dietary cholesterol on erythrocyte peroxidant stress in vitro and in vivo.

The effect of dietary variation of plasma cholesterol concentrations on the susceptibility of erythrocytes to in vitro and in vivo peroxidant stress was studied in rats. Malonyldialdehyde, produced in vivo (endogenous malonyldialdehyde) or following in vitro exposure of cells to 10 mM H2O2 (H2O2 malonyldialdehyde), was used as a measure of peroxidant stress. After 5 weeks, the plasma cholesterol concentrations in rats receiving 1.2% cholesterol + 0.6% cholic acid in their diet rose to 6-times that of control rats receiving a diet without added cholesterol; at the same time, erythrocyte H2O2 malonyldialdehyde in the cholesterol-fed rats decreased significantly relative to the control rats. During subsequent exposure of both groups to in vivo peroxidant stress with phenylhydrazine in two separate dose trials, erythrocyte peroxidant stress remained significantly lower in the cholesterol-fed rats: at a dose of 100 mumol/100 g body weight, H2O2 malonyldialdehyde was lower; at a dose of 25 mumol/100 g body weight, both endogenous and H2O2 malonyldialdehyde were lower. Erythrocyte membrane cholesterol concentrations were 12% higher in the cholesterol-fed rats than in controls. The effects of in vivo peroxidant stress on plasma cholesterol were also studied. In vivo peroxidant stress at the higher dose of phenylhydrazine produced a decrease in plasma cholesterol concentrations of control rats. The lower dose had no effect on this group and the plasma cholesterol concentrations were unchanged in the cholesterol-fed rats during both treatments. The data suggest that elevated plasma cholesterol concentrations are protective against erythrocyte peroxidant stress. The mechanism of cholesterol's protective effect is probably mediated through elevated membrane cholesterol concentrations.

Association of calmodulin inhibition, erythrocyte membrane stabilization and pharmacological effects of drugs.

The present study was designed to determine whether there is an association of drug-induced inhibition of calmodulin functions, drug-induced membrane stabilization (protection against osmotic lysis), and pharmacological effects of drugs. First, data on drugs which have been studied for both calmodulin inhibition and membrane antihemolysis were collected from the literature and an association of the two properties was established. Second, ten additional drugs were selected for study of all three properties. Four drugs, with known antihemolytic effects, were studied for calmodulin inhibition. One drug, which was a known calmodulin inhibitor, was studied for antihemolysis. Our results show that membrane-stabilizing drugs are usually calmodulin inhibitors, and vice versa; that drugs in certain therapeutic classes inhibit calmodulin-activated functions and protect against osmotic lysis; and finally, that there is a significant correlation (P less than 0.01) in terms of potency between these two actions of drugs. Data from the literature which bear on these mechanisms of drug actions suggest that the interactions between drugs and calmodulin, and drugs and the membrane, appear to be hydrophobic in nature. At this point, we do not know whether there is some causal relationship between calmodulin inhibition and the antihemolytic effect of drugs, or whether the two are simply a result of hydrophobic properties of drugs. Similarly, the roles of calmodulin inhibition and/or membrane antihemolysis in producing therapeutic efficacy are unknown.

Carpal length in children--a useful measurement in the diagnosis of rheumatoid arthritis and some concenital malformation syndromes.

The distance between the midpoint of the distal radial epiphyseal growth plate and the proximal end of the third metacarpal offers a useful measure for determining wrist size. Standards of this distance as compared to intermetacarpal width and second metacarpal length are presented. These measures (or ratios) should be useful in evaluating patients with juvenile rheumatoid arthritis and a number of congenital malformation syndromes, particularly when the carpals are still not fully ossified. Shortening of the carpus occurs in multiple epiphyseal dysplasia, the otopalatodigital syndromes, Turner syndrome, arthrogryposis, and in juvenile rheumatoid arthritis. A relatively large carpus is present in achondroplasia.