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Comparative effects of cetaben (PHB) and dichlormethylene diphosphonate (Cl2MDP) on the development of atherosclerosis in the cynomolgus monkey

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      Abstract

      The comparative effects of cetaben [sodium p-hexadecylaminobenzoate, (PHB)] and dichloromethylene diphosphate (Cl2MDP) on the development of atherosclerosis was investigated in the cynomolgus monkey. The atherosclerosis was induced by feeding a 2.5% cholesterol and 10% butter diet for 6 months and was assessed by morphological and biochemical examination of the arteries at necropsy. The experimental disease was also evaluated clinically by the electrocardiographic responses to isoproterenol and by measurements of regional myocardial blood flow using microspheres. Both the clinical and necropsy findings indicated that PHB was an effective antiatherosclerotic agent which reduced the extent and severity of the disease and protected against obstructive atherosclerotic disease of the coronary and peripheral arteries. On the other hand, (CL2MDP) was found to have no antiatherosclerotic effect except for preventing calcium deposition in the induced lesions. The atherosclerotic narrowing of the major coronary arteries in the PHB-treated group averaged about 27% as compared to 55% in the untreated animals. PHB also reduced the luminal narrowing of the carotid, subclavian, iliac and tibial arteries by 50% or more. The drug had actions on both the circulating blood and arteries that could account for its antiatherosclerotic effects. These actions included a lowering of plasma cholesterol and an effect on the plasma lipoproteins resulting in a decrease in LDL and an increase in HDL. Other important actions of PHB included the inhibition of calcium, cholesterol and cholesteryl ester deposition in the induced lesions as well as reduction in the fibrous protein content of the lesions.

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