Mechanical responses of chromium-deficient developing rat heart.

Mechanical responses were compared between controls, developing Sprague-Dawley rat papillary muscle and age-matched weanlings fed with Torula yeast, a food source deficient in chromium. At 8 weeks postnatal, deficient rats differed in significant ways from their normal counterparts. Deficient rats in contrast to controls weighed less, their interval-force (I-F) relationship was more negative and their inotropic response to high calcium concentrations was greater. At this time, however, deficient and control rats responded equally to alpha (phenylephrine) and beta (isoproterenol) agonists. At 10 weeks of age, the controls exhibited a less negative I-F and a negative inotropic response to high calcium concentrations while the response to alpha and beta agonists was unchanged. In contrast, at 10 weeks of age, the chromium-deficient rats exhibited a highly negative I-F response and significant inotropic response to high calcium concentrations. The response of the deficient hearts to beta-agonists diminished. At 13 weeks postnatal, control hearts showed only a 10-15% negative I-F response, a persistent response to catecholamines and negative inotropic responses to high calcium concentrations. In deficient hearts, the negative I-F response was reduced and the response to beta-agonists was further diminished but a positive inotropic response to phenylephrine and high calcium concentrations persisted. These observations in deficient animals are explained in terms of a retarded development of the calcium handling elements in the heart and a lack of an insulin-like growth factor.

Effect of high-chromium brewer's yeast on human serum lipids.

A group of 11 normolipidemic and a group of 16 hyperlipidemic adult subjects were given orally 20 gm daily of a high-chromium brewer's yeast (2.4 micrograms Cr+++/gm, ie, 48 micrograms Cr+++ daily) for 8 weeks. A significant decrease in total cholesterol in both groups of subjects was observed (24-26 mg/dl). High density lipoprotein cholesterol (HDL-C) was significantly increased (5-6 mg/dl) in normo- and hyperlipidemic subjects by brewer's yeast supplementation. However, following supplementation, the triglyceride blood levels were not changed in either the normo- or hyperlipidemic group. When the multiple complex risk factor (total cholesterol/HDL-C) was calculated, 84% of all subjects receiving brewer's yeast showed a decrease in this ratio, and the mean decrease in this ratio in all subjects was significant at P less than 0.01. A second group of 19 normolipidemic, predominantly male, adult subjects was given orally 10 gm of a high-chromium brewer's yeast (2.4 micrograms/gm, ie, 24 micrograms Cr+++ daily) for 8 weeks. The total circulating serum cholesterol was significantly decreased by a modest amount in this group after supplementation. The HDL-C levels were significantly increased (4 mg/dl). The total cholesterol/HDL ratio was decreased in 79% of the subjects, and the mean TC/HDL-C decrease of the entire group was significant at P less than 0.01.

Mevalonic acid analogs as inhibitors of cholesterol biosynthesis.

A series of 20 mevalonic acid analogs was synthesized and tested for their ability to inhibit cholesterol biosynthesis from [2-14C]-mevalonate in rat liver homogenates. Removal of the 5-hydroxyl group from mevalonic acid produced an active inhibitor, 3-hydroxy-3-methylpentanoic acid. Removal of the 3-hydroxyl group, addition of an aromatic group in the 3-position, or insertion of a double bond reduced inhibitory activity. Compounds with an aromatic group or halide on the 5-position were active inhibitors. The most active inhibitor was 5-phenylpentanoic acid, with 50% inhibition at 0.064 mM.

Quantitation of lipid profiles from isolated serum lipoproteins using small volumes of human serum.

Methodology is described that isolates the individual serum lipoproteins, VLDL, LDL and HDL and quantitates the free cholesterol, esterified cholesterol, triglycerides and phospholipid classes in each fraction using 2-3 mL of serum. The determination of the methyl esters of fatty acids from the various lipid classes is described. The lipoproteins are isolated by non-linear density ultracentrifugation using 1 mL of serum per swinging bucket. The lipids are obtained by solvent extraction. The cholesterol, cholesterol esters and triglycerides are separated by TLC using a petroleum ether:diethyl ether system and the phospholipids are separated using a chloroform:methanol system. All lipid classes are quantitatively determined and recovery data are presented. Analysis of the fatty acid profiles of the lipid classes using GLC is described. The methodology can be adapted to partial determination if in-depth studies are not required.

Lack of adaptation in lipogenesis by hepatoma 9121.

The "minimal deviation" hepatoma 9121, implanted in rats, was shown to biosynthesize fatty acids from acetate-1-(14)C at the same rate as normal rat liver but faster than host liver. Feeding the host animals a fat-deficient diet caused fatty acid biosynthesis to be increased 3- to 13-fold in liver, but the dietary regimen did not influence fatty acid biosynthesis in the tumor tissue. Oxygen consumption and the oxidation of acetate and mevalonate to CO(2) were all affected by the dietary manipulation in liver but not in hepatoma. The fat-deficient diet decreased incorporation of acetate and mevalonate into cholesterol by the liver of control animals, increased it in the liver of host animals, and had no effect on this process in hepatoma. Thus, the transplantable tumor has lost the adaptive power of its parent tissue to respond to the dietary stimulus. The changes in fatty acid composition in total lipids in response to the fasting and refeeding were also markedly different in hepatoma from those in liver of the host animals. These results support the concept that this tumor is characterized by a loss of some metabolic controls.