Elaine B. Feldman

Hypertriglyceridemia in Gout

Serum triglyceride levels were significantly higher in 34 patients with gout (42 mg. per 100 ml.) in comparison to the levels in 28 healthy men over 35 years of age (100 mg. per 100 ml.). There was no significant predictive relation between levels of serum uric acid and triglycerides in either group. No significant difference in serum cholesterol levels nor lipoprotein profile was apparent between the two groups. The patients with gout had been selected to exclude any manifestations of atherosclerosis or other disease known to be associated with abnormalities in circulating lipids. The results provide support for possible linkage of genetic factors influencing uric acid and triglyceride metabolism. The presence of hypertriglyceridemia in gout may be correlated with the increased incidence of arteriosclerosis.

Adipokinetic Effect of Intravenous Cortisol in Human Subjects.

Summary 1. Intravenous injection of cortisol caused a significant rise in serum free fatty acids of 103% and a fall of 38% in serum triglycerides in healthy fasting human subjects. 2. Injection of either saline or cortisol vehicle induced a significantly lesser rise in serum free fatty acid levels and no significant change in serum triglyceride levels.

Effects of Halofenate on Glucose Tolerance in Patients with Hyperlipoproteinemia

Halofenate, a triglyceride- and uric acid-lowering drug, potentiated the effect of oral hypoglycemics. Its effect on serial glucose tolerance was evaluated in ten patients with hypertriglyceridemia without overt diabetes. Six-hour oral glucose tolerance tests were done during a control period and every 24 weeks over two years of halofenate treatment. Abnormal glucose tolerance (chemical diabetes) was observed during the control period in six of ten patients. The number of abnormal tests gradually decreased to none by 48 weeks. Plasma glucose, insulin, and free fatty acid values during the glucose tolerance tests were reduced significantly. Halofenate induced significant serum uric acid reduction. No significant regressions were observed among levels of lipids, hormones, glucose, and uric acid. The mechanisms by which lipid-lowering drugs improve glucose tolerance are as yet unexplained.

Metabolic effects of mestranol in high dosage

Abstract Metabolic effects of mestranol, given in continuous high dosage for 3 or more months, were investigated in 4 postmenopausal women with metastatic breast cancer. Three women improved subjectively; in 1 patient objective remission of disease occurred. Adverse effects included: peripheral edema, weight gain of variable duration, hypertension, pruritus, increased skin pigmentation. In 1 patient, at 1 and 2 months of treatment, bromsulphthalein retention occurred; serum bilirubin, glutamic-oxalacetic transaminase and alkaline phosphatase levels were increased transiently. These values returned to normal by 4 months, and remained normal for almost 3 years of treatment. With treatment, average values of plasma cholesterol were increased slightly, phospholipid levels were 20% greater, and triglycerides increased 40%. Circulating free fatty acid levels were decreased. Plasma alpha-lipoprotein increased by 40%. Blood sugar values were less. Plasma cortisol increased greatly; plasma growth hormone increased 3-fold: urinary gonadotrophin excretion diminished. There was a modest increase in serum protein-bound iodine values; thyroxine-binding globulin capacity doubled.

Surfactants and bioelectric properties of rat jejunum

The effects of surfactants on bioelectric properties of rat jejunum were determined. Tween 80 (nonionic) and sodium dodecylsulfate (anionic) increased transmural potential differences 20–34% over values in Krebs-Ringer bicarbonate buffer. Short-circuit currents increased 66–112% and net tissue resistance decreased 19–30%. The cationic surfactant cetrimide decreased transmural potential 23%; short-circuit current decreased 32%, and resistance increased 22%. When sulfate replaced chloride in buffer, surfactant effects were minimized or reversed suggesting a role of C1− flux in the bioelectric effects. Cationic surfactant effects on current and resistance were in the same direction as, but of greater and lesser magnitude, respectively, than alterations observed with bile salts. The nonionic and anionic surfactant increase of transmural potential differences was half that of bile salts. Current and resistance changed in directions opposite to bile salt and cationic surfactant. The current increase was of greater magnitude and resistance decrease less marked. Surfactant molecules may interact specifically with membranes in a more complex manner than simple “detergency.”

Physiochemical processes in sterol absorption

Abstract Enhancement of intestinal absorption of cholesterol by micellar solubilization was demonstrated in experiments with intestinal rings. The rate of uptake during the first 8 minutes of incubation at 37° was one-third faster when cholesterol was offered as a mixed micelle with monoolein and Na-taurodeoxycholate compared to a micelle which contained in addition fatty acid, di- and triglyceride. Smaller particle size and greater sterol micellar dispersion were considered factors responsible for the faster uptake. The kinetics and temperature coefficient of uptake from micellar solutions suggest that cholesterol initially diffuses into or is adsorbed onto the plasma membrane. Binding to membrane components with appreciable sterol content or with very high affinity are possible alternative mechanisms.

ABNORMALITIES OF CIRCULATING LIPIDS. AN APPRAISAL OF CURRENT METHODS OF STUDY.

Abstract In studies of 537 sets of determinations of serum lipids and lipoproteins in 247 subjects, a high degree of correlation was found among methods which measure beta-lipoprotein by preparative ultracentrifugation, paper electrophoresis or immunoprecipitation. A lower correlation was found between beta-lipoprotein levels and either triglycerides or cholesterol. The lowest correlation was found between the two classes of lipids, triglycerides and cholesterol. In lipoprotein analyses, methods which permit quantitation of alpha- as well as beta-lipoprotein offered more significant information. It appeared important to have information about lipoprotein distribution in addition to obtaining levels of the lipid classes. These data were useful in describing changes occurring with age, weight gain, cessation of ovarian function and in various disease states including hyperlipidemias, thyroid dysfunction and gout. In a study comparing 60 patients with coronary heart disease separated into 34 patients selected for normal cholesterol levels and 26 patients with hypercholesteremia, a similar degree of hyperbeta-lipoproteinemia and hypertriglyceridemia was observed. These data support the importance of these substances in contrast to hypercholesteremia in association with manifest clinical coronary heart disease.

Bile Salts and Bioelectric Properties of Rat Jejunum

Addition of conjugated bile salts increased transmural- and transserosal-potential, differences of sheets of rat jejunum. Removal of Cl− from buffer solutions minimized the bilesalt induced bioelectric changes. Bile-salt induced doubling of tissue resistance was not explained by an observed increase in net Cl− serosa → mucosa flux. Electrical effects were unrelated to concentration and were observed only when bile-salt solutions perfused the jejunal mucosa. The molecular events associated with bile-salt interactions with the plasma membrane affecting ion fluxes may relate to their unique effects on sterol absorption.

In vivo metabolism of D-homotestosterone

Abstract D-Homotestosterone and D-homo-5β-androstane-3α,17aβ-diol were isolated from the urine of a patient after oral administration of D-homotestosterone. That they were isolated only after β-glucuronidase or acid hydrolysis indicates conjugation of a high order. Approximately 5% of the administered steroid was recovered as the unchanged material and another 5% as the identified metabolite for a total recovery of 10%. The previously unknown 5β-dihydro-D-homotestosterone and D-homo-5β-androstane-3α,17aβ-diol were prepared by alkaline catalytic reduction to the 5β-dihydro and subsequent reduction of the ketone by sodium borohydride.