Samuel Gordon

Passive transfer of arthritis by purified anticollagen immunoglobulin: Localization of 125I-labeled antibody

Intravenous administration of purified 125I-labeled anti-type II collagen immunoglobulin results in a polyarthritis in the recipient rats. Whole-animal radioautography indicates that the antibody is present in the various tissues that contain Type II collagen. However, the polyarthritic lesion is limited to the front and hind paws. These observations indicate that effector mechanisms subsequent to antibody binding are involved in the pathogenesis of Type II collagen-induced arthritis.

Biochemical and morphologic effects of cholesterol and its methyl ether in the gerbil.

A 6-week feeding experiment was carried out in growing, male gerbils using various dose levels of cholesterol and its methyl ether. Observations during life were limited to total blood cholesterol determinations at various time intervals and to body weight gain. Serum and liver sterols were analyzed in detail after 42 days, when all animals were sacrificed. Morphologic studies of essential organ systems were carried out to examine structural changes after sterol feeding in the gerbil. The results can be summarized as follows: The dietary administration of 1% cholesterol caused a marked elevation of total blood cholesterol which was already manifest at the tenth day of treatment and fell to an elevated plateau. Extreme liver lipoidosis was found in all these animals, whereas the adrenal gland showed only slight morphologic signs of lipid storage. No atheromata or other vascular changes indicative of lipid infiltration were noticeable in the arteries at the end of the experiment. The simultaneous administration of 3% cholesteryl methyl ether and 1% cholesterol in the diet did not inhibit the elevation of blood cholesterol level at various intervals during the experimental period. Final liver lipid and cholesterol determinations and morphologic studies showed no effect of the methyl ether upon the excessive storage of fat in the liver. Dietary administration of 1% cholesteryl methyl ether caused liver granulomata and fibrosis of mesenteric lymph nodes. Very small amounts of this compound were found in the liver, indicating minimal absorption. Small, supernumerary spleens were found in the pancreas in 1739 cases (42%), a very high incidence in contrast to other laboratory animals.

The metabolic fate of triamcinolone acetonide in laboratory animals

The metabolic fate of 9-fluoro-11beta,16alpha,17,21-tetrahydroxy-1,4-pregnadiene-3,20-dione cyclic 16,17-acetal with 2(-14)C-acetone, triamcinolone acetonide (TA) was studied in rabbits, dogs, monkeys and rats and found to be qualitatively similar in all species. In the dog, rat and monkey the major excretory route was the feces irrespective of the mode of administration. In the rabbit the excreted radioactivity was equally distributed between urine and feces. The metabolites were isolated by preparative thin layer chromatography, located by autoradiography, eluted and analyzed by MS, IR, UV and NMR. The major metabolites of triamcinolone acetonide (TA) were identified as the C-21 carboxylic acids of TA and of the 6beta hydroxy-TA, (6BETA-OH-TA) and the previously identified (1,2) 6beta-OH-TA. In addition MS and UV data indicate the presence of 9-fluoro-11beta,16alpha, 17-trihydroxy-3,20-dioxo-1,4,6-pregnatrien-21-oic acid cyclic 16,17 acetal with 2(-14)C-acetone.

Steroids and lipid metabolism. The hypocholesterolemic effect of 3-(β-dialkylaminoethoxy)-substituted steroids

Fourteen 3-dialkylaminoethoxy-steroids have been compared to triparanol as hyposterolemic agents in the rat. Three of these, 3β(β-dimethylaminoethoxy)-androst-5-en-17-one oxime(III), 3β-(β-diethylaminoethoxy)-androst-5-en-17-one methoxime hydrochloride (IV) and 3β-(β-dimethylaminoethoxy)-pregn-5-en-20-one (VI) possess an activity at least twenty times that of triparanol.

Comparison of serum cholesterol esters in gerbil and rat.

Summary The presence of only trace quantities of arachidonic acid in the CEFA of gerbil serum is at variance with the hypothesis of a negative correlation between arachidonic acid levels in CEFA and susceptibility to atherosclerosis. Fasting for 18 hours resulted in a 66% increase of arachidonic acid at the expense of linoleic acid in CEFA of the rat, while in the gerbil, CEFA remained unchanged. In both species, palmitoleic and oleic acids were the major acids associated with cholesterol transport. The CEFA pattern in cholesterol-fed animals suggests an incipient essential fatty acid deficiency.

Absorption of cholesteryl methyl ether and its effect on cholesterol absorption.

Summary Oral administration of the methyl ether of cholesterol-4-C14 to lymph duct cannulated rats resulted in approximately 20% recovery of C14 activity in a 24 hour lymph collection as compared to 35% recovery in the case of cholesterol-4-C14. Simultaneous administration of cholesteryl methyl ether with cholesterol-4-C14 had no effect on cholesterol-4-C14 absorption in the cannulated rat. In the rabbit, dietary cholesteryl methyl ether had negligible effect on sterol levels when given alone or in conjunction with cholesterol.

Effect of Warfarin (Coumadin) Sodium Administration During Lactation on Blood Coagulation of Nursling Rats.

Summary When a therapeutic dosage of the anticoagulant warfarin (Coumadin) sodium was fed to lactating rats, there was no effect on whole blood clotting time of the nurslings, or on their subsequent growth and reproduction. When toxic or lethal levels of warfarin sodium were fed to the mothers, clotting time was prolonged in the nurslings. This demonstrated that the anticoagulant effect could be transmitted through the milk when mothers received toxic dosages. However, at all dosages the anticoagulant effect was much less in nurslings than in mothers.