Antilipidemic Drug Research Articles

Lipid‐lowering therapy and violent death: Is depression a culprit?

AbstractLarge‐scale, controlled treatment studies of antilipidemic therapy have yielded consistent evidence of reduction in cardiovascular morbidity and mortality, but no reduction in total mortality. This counterhypothetical result appears to be due to a compensatory increase in cancer and violent death with treatment. ‘Violent death’ includes suicides, homocides and accidents. The present study took advantage of a dataset on 174 males undergoing coronary angiography which included presence/absence of an antilipidemic medication regimen and multiple measures of emotional distress/dysfunction to see if the two were associated. Self‐reported depression on the Ketterer Stress Symptom Frequency Checklist (KSSFC) was higher in these angiographic male patients if they were on medical treatment for hypercholesterolemia than if they were not. Comparisons across antilipidemic groupings of a number of potential confounding/mediating variables revealed no systematic differences which can account for these results. While only correlational in nature, present results are consistent with the hypothesis that antilipidemic drug treatment induces emotional distress in males undergoing coronary angiography.

粥状動脈硬化巣におけるマクロファージの役割

Intracellular accumulation of lipids occurs in macrophages and smooth muscle cells in atherosclotic vascular lesions and xanthomas associated with hypercholesterolemia. Blood monocytes are originally provided with receptors for native LDL, while macrophages are provided with another kind of receptors for denatured LDL named scavenger receptors. By treating the cells of a monocytic leukemia cell line, THP-1, by a phorbol ester, we could observe a rapid induction of the scavenger receptor with a decrease in LDL-receptor in a very short period of time (80% in 24hr). When we incubated the cells with acetylated LDL, the accumulation of cholesterol and other lipids took place and the cells were changed into foam cell. The cells can also synthesize and secrete apolipoprotein E. When we incubated the cells in the medium containing HDL or artificial lipid paricles containing apolipoprotein E, free cholesterol was released from the cell surface into the medium. The series of experiments provided us a convenient model for the study of development and regression of atherosclerosis. Probucol, a kind of antilipidemic drug provided with an activity as an antioxidant, prevented the lipid storage in macrophages. It inhibited the uptake of acetylated LDL and stimulated the release of cholesterol into the medium. Such in vitro observation explains why probucol is very effective in causing the regression of xanthomas and also in the prevention of atherosclerotic coronary heart diseases.

Dissociation of increased lauric acid ω-hydroxylase activity from the antilipidemic action of clofibrate

Clofibrate, an antilipidemic drug that acts by a still obscure mechanism, is known to specifically increase up to 30-fold the activity of the hepatic cytochrome P-450 isozyme that ω-hydroxlates lauric acid. The thesis that accelerated catabolism of medium-length fatty acids initiated by ω-hydroxylation contributes significantly to the antilipidemic action of clofibrate has been examined by measuring the impact on serum triglyceride levels of coadministering clofibrate and a suicide substrate that inactivates the hydroxylase. The results suggest that the antilipidemic action of clofibrate does not depend critically on the enhanced ω-hydroxylation of fatty acids.

ChemInform Abstract: DESIGN, SYNTHESIS, AND TESTING OF POTENTIAL ANTISICKLING AGENTS. 5. DISUBSTITUTED BENZOIC ACIDS DESIGNED FOR THE DONOR SITE AND PROLINE SALICYLATES DESIGNED FOR THE ACCEPTOR SITE

AbstractDargestellt und gegen Sichel‐ZeIlemAnämie untersucht werden die Verbindungen (IV), (VI) und (VIII).

Clinical Phanmacology of a Newly Synthesized Anti-lipidemic Agent (CGA)

p-Chlorophenoxy isobutyryl glycine amide (CGA) is a newly synthesized antilipidemic drug, which has been proved to lower serum concentrations of triglyceride and cholesterol in amimal experiments.The pharmacokinetics of CGA have been studied in six healthy volunteers. Determination of the drug and its metabolites in the blood and urine was carried out using high pressure liquid chromatography and gas chromatography-mass spectrometry.After oral ingestion of 500mg of CGA, CGA and its active metabolite p-chlorophenoxyisobutyric acid (CPIBA) were detected in blood samples.The peak concentration of CPIBA was observed after that of CGA.These results suggest that CGA is a so-called prodrug or latent form of CPIBA.A multiple dosing study (12-hour intervals for 3 days) reveals that ingestion of CGA at 1000 mg once daily might be sufficient to maintain steady-state plasma concentration of CPIBA.p-Chloroisobutyryl grycine (CG) was identified as a main metabolite in urine from the mass spectrum.