Bernard A. Sachs

Effect of oxandrolone on plasma lipids and lipoproteins of patients with disorders of lipid metabolism

Abstract The effect of oxandrolone (17 β-hydroxy-17α-methyl-2-oxa-5α-androstan-3-one) on plasma lipids, lipoproteins, proteins and glycoproteins has been studied in subjects with primary disorders of lipid metabolism. The effect of this steroid on plasma lipids was highly selective in that it produced profound lowering of all plasma lipids only when the lipid disorder was associated with carbohydrate-induced hypertriglyceridemia (hyper-pre-β-lipoprotenemia). Subjects with familial hypercholesterolemia (hyper-β-lipoproteinemia) showed either no change or elevations of plasma lipids. A patient with fat-induced hypertriglyceridemia (hyperchylomicronemia) showed further elevations in plasma triglyceride levels with administration of the compound. The steroid produced significant increases in α 2 -globulins and α 2 -glycoproteins. A conceptual scheme is presented which correlates the plasma lipid and glycoprotein findings with the response to the drug.

THIN LAYER CHROMATOGRAPHY OF BLOOD LIPIDS.

Summary A simple method is described for the fractionation of blood lipids by thin layer chromatography. Lipid patterns for different disorders of lipid metabolism were demonstrated. A difference was noted in the triglyceride fraction between plasma and serum.

Colestipol Therapy of Hyperlipidemia in Man

Summary Colestipol, a bile acid-sequestrant anion exchange resin, was given in doses of 15 g/day to 18 patients with familial hyperlipopro-teinemia, and its effect compared to seven patients with this disorder treated with placebo. No alterations in diet were made. The colestipol significantly lowered plasma cholesterol and phospholipid levels and produced little alteration in triglyceride concentration. The resin had good patient acceptability and appeared to be an effective addition to methods available for the treatment of hyperlipoproteinemia, particularly type II. We are grateful to Lynn Schwarz for technical assistance and to Harriet Bresnick for assistance in preparation of the manuscript.

Fate of Radiosulfate in Multiple Myeloma.

Summary Radiosulfur (S35) as sodium sulfate was administered intravenously in doses ranging from 0.867 to 2.07 mc, to 9 patients with multiple myeloma and to 10 patients with other neoplasms. The fate of administered sulfate was apparently the same for both groups of patients. S35 was rapidly turned over and excreted; 30 to 90% appeared in urine within 48 hours. Blood levels of S35 closely paralleled those of plasma and decreased rapidly. It was possible to demonstrate that 3 exponential rates governed the disappearance of S35 from whole blood and plasma. The mean zero-time radiosulfate space of dilution was 9.29 ± 2.16 liters for patients with multiple myeloma and 11.4 ± 2.87 liters for those with other neoplasms. By technics employed, a preferential retention of sulfate could not be demonstrated in multiple myeloma as compared to other neoplasms.

In vitro effect of soybean phosphatides on serum lipoproteins of normal and hyperlipemic subjects.

The oral administration of soybean lecithin has previously been reported to lower the serum cholesterol of man 1 and cholesterolfed rabbits 2 . The present study was initiated when preliminary experiments revealed that incubation of human serum. after addition of a fat emulsion prepared for intravenous administration. caused a shift of lipid from beta-globulin to alpha-globulin. as determined by paper electrophoresis. Because lecithin was used as a stabilizer in the fat emulsion, this phenomenon was investigated further using soybean phosphatides. The effects of not only the whole phosphatide complex, but also the alcohol-soluble and the alcoholinsoluble fraction were investigated. Material and methods. 1. Exp. A-Whole Phosphatide Complex. A purified extract of natural soybean phosphatidest containing approximately equal quantities of lecithin, cephalin and lipositol was used as follows: Five mg of soybean phosphatides were dissolved in 1 or 2 ml of sera from 6 normal subjects in the pust-absorptive state. In a similar manner, 10 or 20 mg of the phosphatide complex were dissolved in the sera of 5 patients with hyperlipemia.: Serum aliquots without added phosphatide served as controls. The control sera and sera with added phosphatide were immediately streaked on filter paper strips far electrophoretic analysis, which was promptly performed with Flynn and deMayos modification of Durrums apparatus 3 . The serum aliquots of 0.01 or 0.02 ml were streaked for protein or lipid staining respectively. The remaining control and experilmental sera were incubaited at 38°C for 24 hours. before being subjected to paper electrophoresis. Protein was stained with naphthalene black 12B200 and lipid with oil red O by technics previously described 4 . Total lipids were determined gravimetrioally 4 , and lipid phosphorus by a modified Fiske-SubbaRow procedure 5 in ahquots of serum extracted with Bloors reagent (alcohol 3 parts/anhydrous ether, 1 part).

Antithyroxine Properties of N-(2,5 Dihydroxyphenyl) Pyridinium Acetate.

Conclusions(1) N-(2,5-dihydroxyphenyl) pyridinium acetate inhibited the metamorphosis of tadpoles induced by thyroxine. The degree of inhibition of metamorphosis appeared proportional to the relative concentration of the drug. (2) N-(2,5-dihydroxyphenyl) pyridinium acetate, 200 mg/kg body weight, did not lower the rate of oxygen consumption of normal rats nor prevent the acceleration of oxygen consumption induced by dl-thyroxine, 2 mg/kg body weight.Conclusions (1) N-(2,5-dihydroxyphenyl) pyridinium acetate inhibited the metamorphosis of tadpoles induced by thyroxine. The degree of inhibition of metamorphosis appeared proportional to the relative concentration of the drug. (2) N-(2,5-dihydroxyphenyl) pyridinium acetate, 200 mg/kg body weight, did not lower the rate of oxygen consumption of normal rats nor prevent the acceleration of oxygen consumption induced by dl-thyroxine, 2 mg/kg body weight.

Mechanism and Identification of the Triglyceride Alteration Caused by a Plasma Factor

Conclusion The previously described plasma factor capable of producing an increase in the Rf value of triolein in TLC was shown to be bicarbonate acting as a catalyst in the production of ethyl esters of oleic acid from triolein. We are grateful to Dr. Donald B. Zilversmit for the GLC procedure which definitively identified the altered fraction, and to Drs. Jules Hirsch, Thomas Gallagher, Robert Rosenfeld, and Mr. Morris Wolf-man for help and criticism during various phases of this investigation.

A Plasma Factor Capable of Altering Triglyceride.

Summary A hitherto unknown factor has been found in human blood plasma capable of producing an increase in the Rf value of triglyceride in thin-layer chromatography. It has been shown that the factor is not protein-bound, appears in ultrafiltrates of plasma, and shows quantitative dose-response relationships. The activity is considered non-enzymatic.