Mary E. Zanetti

Synthesis of cholesterol from glucose-U14C in the liver and extrahepatic tissues of the mouse

Abstract The incorporation of glucose-U- 14 C into cholesterol and other sterols of liver and extrahepatic tissues has been studied in two experiments in mice fed a purified diet containing 20% corn oil or this diet supplemented with 1% cholesterol or 1% cholestyramine. In each experiment the mice were given 250 mg glucose-U- 14 C (20 μCi) orally and killed in 1 hr. Sterols were isolated from various tissues by digitonin precipitation and separated first on silica gel G and then on alumina impregnated with AgNO 3 . Cholestanol and Δ 7 -cholestenol, which had similar mobilities in these systems, were separated by epoxidation on silica gel G plates. In mice fed the basal diet 2–6 times more cholesterol synthesized from glucose-U- 14 C was found in extrahepatic tissues than in the liver. Approximately two-thirds of the extrahepatic labeled cholesterol was found in the gastrointestinal tract. More Δ 7 -cholestenol was synthesized from glucose in extrahepatic tissues than the total amount of cholesterol synthesized in liver and carcass combined with approximately two-thirds of the newly synthesized Δ 7 -cholestenol found in the skin. Cholesterol feeding reduced the level of radioactivity in liver and carcass cholesterol 90–98% and 35–38% respectively. The overall reduction in cholesterol synthesis in cholesterol-fed mice was 45–55%. Cholestyramine feeding increased the incorporation of label into liver cholesterol 4- to 10-fold and into carcass cholesterol 60–70%. Based on the data obtained in these experiments it has been calculated that in mice fed the control diet, 35–43 μg cholesterol was synthesized out of 250 mg glucose-U- 14 C given. Of this newly synthesized cholesterol 5–13 μg were isolated from liver and 30 μg from extra-hepatic tissues.

Plasma Cholesterol Concentrations in Cockerels and Dogs Treated with Bile Acid Binding Polymer and Cholesterol Synthesis Inhibitors

Summary In normocholesterolemic cockerels the bile acid binding polymer, cholestyramine resin (MK-135), lowered plasma cholesterol concentrations when fed in the diet; the hepatic cholesterol synthesis inhibitor, benzmalecene, lowered cholesterol levels when given by injection, but not when fed in the diet. In combination, their effect was additive. In dogs, feeding of cholestyramine resin plus benzmalecene or triparanol (MER-29) had additive cholesterol-lowering effect.

Hormonal hypercholesterolemia in the dog: influence of niacin, niacinamide, benzmalecene, and cholestyramine resin.

Summary Pseudopregnant female dogs exhibited a characteristic hypercholesterolemia that was similar to that seen in true pregnancy in this laboratory. Daily subcutaneous injection of progesterone or prolactin raised blood cholesterol concentrations in male, anestrous female, and ovariectomized female dogs. The two hormones differed in their action. Niacin feeding counteracted the hypercholesterolemia of pseudopregnancy, and lowered plasma cholesterol levels in progesterone-injected or prolactin-injected ovariectomized female dogs. It had no effect on cholesterol concentrations of normal male or progesterone-injected male dogs. Niacinamide generally increased plasma cholesterol levels. Sodium benzmalecene lowered the blood cholesterol of a prolactin and a progesterone-injected female, and of a progesterone-injected male dog. Cholestyramine resin decreased the elevated cholesterol level of a progesterone-injected male dog.

Extent of Agreement between Two Methods for Estimating Acute Directional Changes of Cardiac Stroke Index

Cardiovascular physiologists frequently infer directional changes in cardiac stroke volume and cardiac output from changes in aortic pulse pressure and atrial pressure. Errors are probably not infrequent. The Hamilton and Remington pressure pulse contour method can also indicate directional fluctuations in cardiac stroke volume. Comparison of the results of the two methods of analysis in situations where cardiac stroke index was changed acutely revealed good correspondence of indicated changes under conditions of simple alterations in venous return, but poor correspondence under more complex conditions such as after injections of pressor amines.

EFFECT OF PROTEIN RESERVES ON LIVER REGENERATION AFTER PARTIAL HEPATECTOMY.

Summary The regeneration of rat liver after partial hepatectomy in rats fed a protein-free diet has been used in an attempt to assess the importance of protein reserves. Groups of protein-depleted adult male rats were fed diets of varying protein quality for one week, and then subjected to removal of two-thirds of the liver. Recovery periods of 3 and 7 days were studied during which time a protein-free diet was fed. No effect of the previous dietary history on the weight of new liver tissue formed was observed. Plasma protein levels were significantly lower after 3 and 7 days protein-depletion in animals previously fed gluten as compared with those fed egg. Levels also were significantly depressed as a result of the partial hepatectomy, and the effects of poor quality dietary protein and liver resection were additive. It is suggested that under the conditions investigated, the existence of fuller protein stores was of physiological advantage to the organism and possibly of survival value.

The effect of cholanic acid on sterol and fatty acid synthesis

Abstract The effects of cholanic acid on incorporation of glucose-U-14C into digitonin-precipitable sterol (DPS) and fatty acid in liver and extrahepatic tissues of mice and rats have been investigated. Cholanic acid lowers plasma triglycerides in both species, but lowers cholesterol only in mice. Incorporation of glucose-U-14C into liver fatty acid was lowered by cholanic acid in both mice and rats, as was the percentage by weight of this fraction. Incorporation into liver DPS in both species was reduced after 1-day treatment with cholanic acid, but was considerably elevated when the cholanic acid was fed for a 7-day period. Cholanic acid caused the percentage by weight of DPS in the liver to decrease in mice but to increase in rats. Incorporation of glucose-U-14C into extrahepatic fatty acid or DPS was not influenced in rats or mice by feeding cholanic acid in the diet for up to 7 days. When fed in the diet to mice for 6 weeks cholanic acid caused the percentage of body fat as well as the weight of the epididymal fat pads to be reduced approximately 35%. Under these conditions incorporation of glucose-U-14C into fatty acid in epididymal fat was stimulated 3-fold.

An Attempt to Demonstrate Arterial Pressure-Volume Relationships in the Intact Dog by an Ultra-Rapid Bleeding Technic

The response of arterial pressure to very rapid central venous bleeding has been utilized in an attempt to establish an arterial pressure-volume relation in the intact dog. When dogs were bled for a brief period at rates between 200 and 500 cc. per minute the arterial pressure declined as a rectilinear function of the bleeding volume. The compensatory mechanisms of cardiac acceleration and vasoconstriction do not influence this relationship. Abolition of the vasomotor pathways does, however, increase the slope of the blood pressure decline curve. This is explained on the basis of a decrease in the initial volume of the arterial reservoir.