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Diabetes is associated with altered cholesterol metabolism that may contribute to cardiovascular complications. Treatment of rats with pioglitazone hydrochloride, a novel antidiabetic compound that improves the general response of target cells to insulin, significantly lowered cholesterol levels in rats fed a hypercholesterolemic diet and produced a significant reduction in cholesterol absorption. Drug treatment was ineffective in rats that were not given dietary cholesterol. To determine whether these effects of pioglitazone hydrochloride might be related to the known ability of this compound to improve the response to circulating insulin, similar studies were conducted in streptozocin-induced diabetic rats with and without insulin replacement. Diabetic rats absorbed a greater percentage of dietary cholesterol than control rats. Treatment of insulin-deficient diabetic rats with pioglitazone alone did not affect cholesterol absorption; however, the combination of insulin and pioglitazone was synergistic to lower absorption of cholesterol and circulating cholesterol and triglycerides. Treatment of either normal rats or diabetic rats receiving insulin with pioglitazone hydrochloride produced a twofold decrease in the ratio of total cholesterol to high-density lipoprotein cholesterol. These results suggest that treatments that improve insulin sensitivity may also have a positive impact on coronary artery disease associated with diabetes.

The efficacy of linezolid, alone or in combination with rifampin, against methicillin-susceptible Staphylococcus aureus in rabbits with experimental endocarditis was investigated. Linezolid (50 or 75 mg/kg of body weight), rifampin, and linezolid (25, 50, or 75 mg/kg) plus rifampin produced statistically significant reductions in bacterial counts compared with those in untreated controls. Plasma or valvular vegetation levels of linezolid in the groups treated with the linezolid-rifampin combination were similar to those in the respective linezolid-only treatment groups. At therapeutic levels of linezolid, rifampin resistance was not observed. The results from this experimental model of endocarditis suggest that while rifampin did not provide synergy to the linezolid dosing, it did not antagonize the efficacy of linezolid.

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