Harry W. Margraf

Adrenocortical function in alcoholics

Abstract The diminished adrenocortical responsiveness of chronic alcoholics to surgical trauma has been investigated. It is concluded that alterations in steroid metabolism and not adrenal cortical function are important accompaniments of chronic alcoholism.

Isolation and identification of adrenocortical steroids in human peripheral blood: II. Isolation of the Naturally Occurring Acetates of Cortisol and Corticosterone and the Quantitative Distribution of Cortisol Acetate, Cortisol and Corticosterone in Normal Human Blood

Abstract Cortisol acetate and corticosterone acetate were isolated from large quantities of normal human peripheral blood and identified by infrared spectroscopy. It has been demonstrated that 50% or more of the “Porter-Silber chromogens” present in circulating whole blood are cortisol acetate. Heparinized whole blood, when collected in glass containers and allowed to stand for 30 minutes at room temperature, contains only 15–30% of the cortisol acetate present in whole blood shed directly into a protein precipitating solvent mixture. Results are presented which indicate that free cortisol is present only in plasma, while cortisol acetate and 17-deoxycorticosteroids are distributed between red cells and plasma.

A method for the enzymic determination of corticosteroids in extracts from whole blood, plasma and urine

An enzymic procedure based on the reduction of the 20-oxo group of corticosteroids by 20β-hydroxysteroid dehydrogenase (20β-SD) and the simultaneous oxidation of stoichiometric amounts of DPNH to DPN has been modified and applied to the quantitative measurement of corticosteroids in extracts from biological fluids. Experimental data are presented concerning the specificity, sensitivity and accuracy of this procedure. Selective solvent partition techniques allow to differentiate between 17-hydroxycorticosteroids and 17-deoxycorticosteroids, possessing the C-20-oxo group. Esterification at carbon 21 prevents the enzymic reaction. Certain applications and advantages over other methods of corticosteroid analysis are discussed.

Human Metabolism of Orally Ingested Glycyrrhetinic Acid and Monoammonium Glycyrrhizinate.

Summary Orally administered glycyrrhetinic acid and monoammonium glycyrrhizinate were poorly absorbed from the gastrointestinal tract as indicated by blood, bile and urine levels of radioactivity. The bulk of fed materials are excreted directly in the feces, and, in the case of G.A., at least in part as unchanged compound. Small quantities of glycyrrhetinic acid have been isolated from urines of subjects fed each of above compounds. Many problems relating to stereoisomerism of G.A. remain to be clarified.

Studies on bile salt deconjugation following small bowel bypass procedures.

Using the glycine-1–14C-chjolis acid (14C-GCA) test, bile salt deconjugation ad excreation wer studied in 26 subjects wit moerbid exogejous obesity before land at selected intervals after jujuno-illeal bypass. In the preoperaetive group there was no malabsorption or intestinal bacterial deconjgation of the bile salts. In the immediate postoperative period (with relative sterilization of the bowel) ther was only a trace of 14C in the brath, but the fecal 14C was highly elevated, indicating severe malabsorption without bacterial activity. In the 8 to 10 day postoperative period both the breath and fecal 14 content were highlyelevated, indicating malabsorption and normal bacterial activity. Five to 8 months postoperatively both the breath and fecal 14 content showed only moderate elevation, indicating adaptation. It is suggested that the 14C-CCA test is usefl in evaluating the adequacy of small bowel bypass procudres and also in folowing the adaptive response after the bypass. A significant increase in the breath and fecal 14C soon after surgery folowed by rapid decrease suggests an adequte bypas and unusaully fast adaptation. If the increase in the breath and fecal 14C soon after the bypass is onlyy moderate, then that suggests an inadequate bypass.

The use of silver-zinc-allantoin powder for the prehospital treatment of burns

We describe our experimental studies of a powder formulated to treat serious burn wounds on-the-scene. The wound powder comprises two parts silver-citro-allantoinate, two parts zinc allantoinate and 96 parts pure allantoin. The back skin of 62 rats was shaved and exposed to actively boiling water for ten seconds, resulting in third degree burns of 20% of the total body surface. Immediately, 1 ml of a culture containing 2 X 10(8) Pseudomonas aeruginosa was applied to the burn. The animals were isolated. Of the 30 control rats, six were powdered with allantoin only. Thirty-two rats were dusted with the silver-zinc-allantoin powder within 15 minutes of burning. Cultures were taken at 48 hour intervals. Eighty-seven percent of the control animals died an average of six days postburn. In the treated animals, the mortality was 15%. A mean of 27% of the applied silver (0.35 gm) became incorporated in the eschar. In all control rats, sepsis was detected under the eschar. In treated animals, bacterial concentration fell from an initial average of 5 X 10(4) at 4 hours postburn to 6 X 10(2) at 96 hours.

Cortisol 2i-acetate: apparently abnormal plasma levels in patients with rheumatoid arthritis

Abstract Cortisol acetate has been isolated from pooled plasma from patients with rheumatoid arthritis and its identity confirmed by I-R spectroscopy. On the assumption that the difference between the total Porter-Silber chromogens and the enzymatically determined corticosteroid level represents cortisol 21-acetate, an average of 63% of the total consisted of the acetylated compound in the rheumatoid arthritis patients, but only 8% in the control group. Evidence in support of this assumption is presented and the results suggest a metabolic abnormality of clinical significance since acetylation may affect the availability at tissue sites and delay or inhibit biological activity.

Effect of citrus bioflavonoids on metabolism of hydrocortisone in man.

Summary Administration to normal humans of certain phenolic compounds, such as citrus bioflavonoids and N-acetyl-p-aminophenol (NAPA) significantly decreased the rate of disappearance from the plasma of parenterally administered hydrocortisone. The authors acknowledge the cooperation of Drs. H. H. Weathers, J. E. White and L. M. Harlow, Jr. and thank Joanne Roberts, Christine Olah, Leon Ashford and Lawrence La Valle for valuable technical assistance.