Jesse W. Huff

Effect of Cholestyramine, A Bile Acid Binding Polymer on Plasma Cholesterol and Fecal Bile Acid Excretion in the Rat

Summary Administration of cholestyramine, a bile acid binding polymer to rats on a normal diet was without effect on plasma or liver cholesterol concentration, but produced a rise in fecal bile acid excretion. These effects were accompanied by an increase in hepatic de novo cholesterol synthesis. Cholestyramine prevented the rise in plasma cholesterol resulting from administration of cholesterol and cholic acid. The fecal bile acids were increased slightly with a marked elevation in the dihydroxycholanic to cholic acid ratio.

Quantitative measurements of lipide peroxide formation by normal liver mitochondria under various conditions.

Abstract 1. 1. Ascorbic acid increases the residual amount of peroxide formed by normal liver mitochondria 10–20-fold. However, this stimulation is possible only within certain limits of mitochondrial concentration. With higher concentrations of mitochondria there is a definite decrease of peroxide formation even with increased amounts of ascorbic acid. The much smaller peroxide formation in the absence of ascorbic acid follows a linear curve (Tables I and II) up to almost 3 mg. nitrogen. 2. 2. In the presence of ascorbic acid, ferrous iron and to a lesser extent ferric iron tend to overcome the inhibition of increased concentrations of mitochondria on the production of peroxide. 3. 3. MnCl 2 as well as Versene and epinephrine inhibit the production of peroxide. 4. 4. The production of peroxide by mitochondria is independent of pH within the range of 5.6–8.4 and stable to heating and aging. Aging does, however, increase the inhibition of peroxide formation with increased concentrations of mitochondria.

The effects of mevinolin on serum cholesterol levels of rabbits with endogenous hypercholesterolemia

Mevinolin, a fungal metabolite isolated from cultures of Aspergillus terreus, is a potent competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, the rate-controlling enzyme in cholesterol biosynthesis. In the current studies we demonstrate that mevinolin significantly lowers serum cholesterol in rabbits fed a cholesterol free, low-fat semi-synthetic diet. Rabbits maintained on this diet developed endogenous hypercholesterolemia with average cholesterol concentrations of 310 mg/dl over a 66-day period. Treatment with mevinolin for 39 days at a dose of 2 mg/kg per day lowered serum cholesterol levels by an average of 37% (P less than 0.05), while a dose of 6 mg/kg per day resulted in a 48% (P less than 0.05) decrease when compared with the control group. When the administration of mevinolin was discontinued, serum cholesterol levels of the 6 mg/kg per day group increased significantly to a maximum post-treatment value of 319 mg/dl (P less than 0.0001). The results of this study demonstrate that rabbits with endogenous hypercholesterolemia are a useful animal model for the study of cholesterol biosynthesis inhibitors like mevinolin.

Lipide peroxide production and inhibition by tumor mitochondria

Abstract Under the conditions tested, most of the tumors did not contain factors inhibiting the production of a thiobarbituric-reacting substance nor did they produce this substance. However, mitochondria from some Novikoff hepatomas and butter-yellow tumors contain the substrate required for oxidation, but in lower amounts than in normal liver mitochondria. Some tumor preparations contain factors inhibitory to the production of the thiobarbituric-reacting substance regardless of whether per se they produce such a substance. Tissue cultures do not appear capable of producing a thiobarbituric-reacting substance.

A Nutritional Requirement for Bromine

Summary Addition of an iodinated casein with thyroid activity to a purified diet adequate in all known essential nutrients produced a growth retardation in mice. Growth inhibition was reversed by fractions of whey and by whey ash. The active inorganic component was found to be bromine.

Effect of Bromine on Chick Growth

Summary A growth response to trace addition of bromine to a semi-synthetic diet has been observed in chicks. The conditions required in order to obtain this effect are discussed.

The bile acid binding and hypocholesterolemic action of two water-soluble polymers

The in vitro bile acid binding properties of 2 water-soluble, linear, cationic resins, poly-[(dimethylimino)trimethylene chloride] or 3,3-ione C1, and poly-diallyldimethylammonium chloride) or CAT-FLOC were determined. Both polymers were substantially more active than cholestyramine. All were compared for hypocholesterolemic effect in normo-cholesterolemic dogs. CAT-FLOC and 3,3-ionene C1, administered at 1.8 and 1.2 g/day, respectively, exhibited cholesterol-lowering action equivalent to cholesteryramine given at 12 g/day. The results of this study suggest that effective reduction of plasma cholesterol may be achieved with significantly lower doses of bile acid sequestrants.

Benzmalecene Inhibition of Cholesterol Biosynthesis and Hypocholesteremic Effect in Rats

Summary Benzmalecene inhibited in vitro incorporation of 2-C14-mevalonic acid into cholesterol by rat liver homogenates. The inhibition proved to be non-competitive. Oral administration of this compound to normal rats resulted in a significant reduction in plasma cholesterol.

The hypolipemic properties of 2-acetoamidoethyl (p-chlorophenyl) (m-trifluoromethylphenoxy)acetate in the rat.

Summary 2-Acetoamidoethyl (p-chlorophenyl) (m-trifluoromethylphenoxy) acetate (halofenate) has been established as a potent hypolipemic agent in the rat, significantly lowering, in a dose-response relationship, plasma cholesterol, triglycerides, phospholipids, and free-fatty acids.

Thiobarbituric reacting substance(s) produced in normal liver fractions

Abstract The thiobarbituric reacting substance(s) (TBRS) is of potential interest in the cancer field since various publications have shown that tumors and rapidly proliferating tissues do not produce this material(s). With either mitochondria or microsomes from normal rat liver, the reported data suggest that TBRS can arise from an enzymatic reaction as well as the previously described ascorbate-catalyzed chemical reaction. The enzymatic reaction is mediated through TPN, ADP, and hexokinase with phosphate acting as an inhibitor. None of the above-mentioned additions influences the ascorbate reaction. From the differential behavior of the ascorbate and pyridine nucleotide systems in producing TBRS, the possibility exists that the precursors or substrates for these two reactions are not the same.