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Biomedical subjects

C E Day

Publications and source records attributed to C E Day.

53 records · Page 3Linked to original sources
PubMed1977

Response to the hypobetalipoproteinemic agent adamantyloxyphenyl piperidine in hyperlipemic rats.

The hypobetalipoproteinemic activity of U-41,792 (1-[p-(1-adamantyloxy)-phenyl]-piperidine) is a marked and selective reduction of heparin precipitating lipoproteins (low density plus very low density lipoproteins) in cholesterol-cholic acid induced hypercholesterolemic rats. This activity consists of both a reduction in heparin precipitating lipoproteins (HPL) and an increase in high density lipoproteins that are not precipitated by heparin. The increase in high density lipoproteins is routinely noted by decreases in HPL/cholesterol ratios. The pattern of response following single 100 mg/kg doses of U-418792 was determined. After an I.V. dose was administered in a cottonseed oil emulsion, serum cholesterol levels were reduced, beginning at 8 hr after administration and persisting for 96 hr. Similar results, though delayed somewhat, were obtained after a single oral dose. Activity was accompanied by increases in weight and cholesterol content of livers. After multiple, daily, oral doses, liver weights, total lipids, and cholesterol contents were reduced. Hypobetalipopreteinmeic activity was enhanced by prolonged treatments as demonstrated by analyses of serum obtained weekly throughout 7 wk.

Adamantane↗
PubMed1977

Utility of selected line (SEA) of the Japanese quail (Coturnix coturnix japonica) for the discovery of new anti-atherosclerosis drugs.

A special line of the Japanese quail (Coturnix coturnix japonica) was developed by selective breeding to screen for new drugs that are effective in either preventing or reversing atherosclerosis. By the fourth or fifth generation, approximately 95% of the males of the selected line developed aortic atherosclerosis in response to a 2% cholesterol atherogenic diet. The arterial cholesterol level was significantly elevated after 1 week on the diet and was 14 times the control level after 14 weeks. Significant macroscopic lesions developed as early as 4 weeks. Neither arterial cholesterol nor grossly visible fatty plaques regressed after return to a normal diet for 8 weeks. After 2 weeks on the atherogenic diet, both serum cholesterol and heparin precipitating lipoproteins were maximally elevated. Serum cholecterol returned to normal within 1 month after removal from the diet, and by 2 months, the heparin precipitating lipoproteins had almost returned to baseline values. The male of the selected line of Japanese quail was shown to be an economical and practical animal model for the screening of anti-atherosclerosis drugs; it is small, inexpensive, and readily develops atherosclerosis.

Animals↗
PubMed1976

High volume screening procedures for hypobetalipoproteinemic activity in rats.

We describe high volume screening tests for hypobetalipoproteinemic agents in which compounds are administered orally to cholesterol-cholic acid fed (hypercholesterolemic( or normally fed weanling rats for 4 days. In these tests total serum cholesterol levels and heparin precipitating lipoproteins (HPL) are determined by automated analyses interfaced with a computer which eliminates all manual data reduction and provides necessary reports. The hypercholesterolemic rat test detects compounds which specifically reduce HPL (beta and pre beta lipoproteins) causing a decrease in the HPL: cholesterol ratio. Such activity is called hypobetalipoproteinemia. This activity is exhibited by bicyclo (2.2.2)-octyloxyaniline (U-26328) but not by any of the familiar hypocholesterolemic agents including clofibrats, lifibrats, nicotinic acid, probucol, triparanol, lentysine, D-throxine or the estrogens estrone and diethylstilbestrol.

Analog-Digital Conversion↗
PubMed1976

Biological activity of a hypobetalipoproteinemic agent.

A new -ind of pharmacologic activity called hypobetalipoproteinemia is described. Iperationally the activity consists of a marked reduction of heparin precipitating lipoproteins (beta and/or pre-beta electrophoretic mobility) in hypercholesterolemic animals with a simultaneous decrease in the heparin precipitating lipoprotein: cholesterol ratio. As determined by ultracentrifugal fractionation of the lipoproteins from hypercholesterolemic rat serum, this activity consists of both a reduction in heparin precipitating lipoproteins and an increase high density lipoproteins that are not precipitated by heparin. Changes in composition were also induced in both lipoprotein fractions. The greatest changes were observed for free and esterified cholesterol, which were markedly reduced in the heparin precipitating lipoproteins and concomitantly increased in the high density lipoproteins. The hypobetalipoproteinemic agent exhibiting this activity is 1-[p-(1'-adamantyloxy) phenyl]-piperidine (U-41792). This agent is active in hypercholesterolemic rats, mice, quail, and pigeons.

Adamantane↗
PubMed1976

Produced by selective breeding of Japanese quail animal model for experimental atherosclerosis.

The Japanese quail (Coturnix coturnix japonica) was bred selectively to produce a strain highly susceptible to experimental atherosclerosis. A population was produced where aortic atherosclerosis is contracted by 99% of the fourth generation males and 83% of the femlaes. Forty-three percent of the males exhibited severe atherosclerosis making this line of Japanese quail a suitable model for discovering and testing anti-atherosclerosis compounds. This feature is augmented by other features such as size, disposition, and abundance which qualify them as suitable experimental subjects. A second line of Japanese quail was bred to be resistant to dietary-induced atherosclerosis. This strain may be a useful research tool for characterizing the etiology of atherosclerosis.

Alkaline Phosphatase↗
PubMed1975

New animal model for atherosclerosis research.

Japanese quail were investigated for their utility as a model for the discovery and evaluation of anti-atherosclerosis compounds. Although they possessed suitable characteristics for a screening animal, their development of atherosclerosis was too variable to make them a practical model. A search was conducted to find a means to make quail uniformly atherosclerotic. To this end a line of quail susceptible to experimental atherosclerosis (SEA) were selectively bred. Thus, the SEA Japanese quail is a new animal model for atherosclerosis research.

Animals↗
PubMed1975

Hypo-beta-lipoproteinemic agents. 1. Bicyclo[2.2.2]octyloxyaniline and its derivatives.

A new assay for agents which normalize beta-lipoproteins in cholesterol-cholic acid fed rats is described. Both lowering of serum cholesterol and of serum heparin precipitable lipoproteins (HPL) were measured at the end of the treatment period. Compounds which shifted the ratio of the decrease in favor of HPL are considered hypo-beta-lipoproteinemic. p-(1-Bicyclo[2.2.2]octyloxy)aniline and several of its derivatives proved active in this assay. The synthesis of these compounds is described.

Aniline Compounds↗
PubMed1968

Determination of the molecular weight of apoprotein subunits from low density lipoprotein by gel filtration.

Another method has been developed for obtaining a soluble apoprotein from the low density lipoprotein (LDL) of human plasma in the density class 1.019 < d < 1.063. The approximate molecular weight of the apoprotein subunit from this lipoprotein density class was determined by gel filtration on Sephadex G-200 to be about 80,000. Both on gel filtration and analytical ultracentrifugation the soluble apoprotein showed one peak, but on cellulose acetate electrophoresis it showed two bands, which suggests two differently charged components. Because of the nature of the determination, the value of 80,000 probably represents an upper limit to the molecular weight of the LDL subunits.

Chemical Phenomena↗
PubMedDate not supplied

Control of the interaction of cholesterol ester-rich lipoproteins with arterial receptors.

Incorporation of 125I-labeled cholesterol ester rich lipoproteins from cholesterol fed rabbits into normal rabbit aorta in vitro was inhibited by heparin, lecithin, and collagenase and by succinylation of the lipoprotein. Aortic uptake of lipoprotein was increased by neuraminidase, proteases, lipase, and beta-glucuronidase. These results suggest that it may be possible to control atherogenesis by controlling the interaction of atherogenic lipoproteins with their arterial receptor.

Animals↗
PubMedDate not supplied

Activity of ethyl 5-(p-chlorophenoxy)-3-hydroxy-3-methylpentanoate, a new hypocholesterolemic compound, in male rats and SEA Japanese quail.

Ethyl 5-(p-chlorophenoxy)-3-hydroxy-3-methylpentanoate (HMP), a new hypocholesterolemic compound, was evaluated in male rats at dosage levels ranging from 25-800 mg/kg/day and in SEA Japanese quail at approximately 200 mg/kg/day. In the rat, the atherogenic lipoprotein cholesterol, that is, the combination of very low density plus low density lipoprotein cholesterol (VLDL-C + LDL-C), was reduced 20-27% at dosage levels over 100 mg/kg/day, while high density lipoprotein cholesterol (HDL-C) and total serum cholesterol (TSC) were significantly decreased 25-46%, respectively, at all dose levels of HMP. Liver weights with HMP treatment were significantly elevated (11-26%) in the rat. HMP was not active in the SEA Japanese quail, since an initial reduction in artery cholesterol could not be confirmed in subsequent tests.

Animals↗