Studies on some lipids of clinical interest

Chapter I reports studies on a number of common drugs and metabolites, some of which were found to affect lipids. Quantitative studies of drug‚ÄövÑvÆinduced release of cholesterol esters from lipoproteins in vitro are described. Tetracycline was found to act an both lipoproteins and proteins, causing marked denaturation of the latter and a strong delipidation of the former. Similar effects were noted in the cases of Atromid S and Phenformin. These drugs were also reacted with serum in combination with magnesium lactate alone, and in combination with pyridoxine, and in the latter case some enhancement of delipidating effects were seen. Similar tests on a number of amino acids were negative. Spectrophotometric, electrophoretic and immunoelectrophoretic investigations of the type and degree of binding of tetracycline and nitrofurantoin to serum proteins are reported in Chapter II. Competitive binding of tetracycline with displacement of lipids from their binding sites support the findings of Baer, Palmer Schmitt and Chargaff. Evidence is presented on competition between serum protein fractions for the denaturing drug. The main aim of the work described in Chapter III was to ascertain whether chemical features of serum sphingolipids are of diagnostic value. Quantitation of free ceramides showed that, while total serum ceramides (which correlate well with serum triglycerides) seldom vary beyond normal limits, fractions rich in hydroxy-acids indicate atherosclerotic risk. Such diagnostic data appear more reliable than indications from cholesterol assays. The free serum ceramides noted were assigned origins from sphingomyelin and glycosphingolipids respectively. A routine method for the assay of free serum ceramides has been developed; it is based on a thin‚ÄövÑvÆlayer chromatographic technique followed by densitometric scanning. The patterns of fatty acid moiety in diagnostically interesting free serum ceramides have been established by gas‚ÄövÑvÆliquid chromatography. The concomitant variation of base moieties appears of less practical interest.