No abstract

We examined the differentiation activity of retinoyl p-D-glucuronide, a biologically active physiological metabolite of vitamin A, using the human promyelocytic leukemic cell line HL-60, which can be induced to differentiate with retinoic acid. Retinoyl /3-D-glucuronide (1 ,AM) inhibited HL-60 cell proliferation by 55-75%, inhibited tritiated thymidine incorporation into DNA by 63-80%, and induced 38-50% of the cells to differentiate into mature granulocytes. The potency of growth inhibition and induction of differentiation by retinoyl .8-D-glucuronide was similar to that of all-trans-retinoic acid. The continuous presence of either retinoyl .l-Dglucuronide or all-trans-retinoic acid was not required to obtain maximum growth arrest and differentiation: a 1-hr exposure of HL-60 cells to the retinoids gave the same response (measured after a total incubation time of 48 hr) as a 24-hr or 48-hr continuous treatment. Retinoyl j3-D-glucuronide (0.1-0.2 mM) was 50% less cytotoxic to HL-60 cells than all-trans-retinoic acid at an equimolar concentration. Retinoyl P-D-glucuronide was not significantly metabolized to other retinoids; retinoic acid was not formed during incubation. We conclude that retinoyl ,8-D-glucuronide can arrest HL-60 cell proliferation and induce their differentiation into mature granulocytes; it may act by itself or by being hydrolyzed to retinoic acid, which could be immediately utilized and metabolized. The therapeutic use of this retinoid as an antineoplastic agent is suggested.

No abstract

Salivary cortisol is an acceptable surrogate for free serum cortisol when satisfactory salivary volumes are procured. Due to inadequate sample volumes, and contamination, it should not be generally adopted in the ICU. We identified discordance between free and total cortisol in interpreting AI, suggesting reinterpretation of seminal trials investigating physiologic corticosteroid replacement on the basis of total cortisol levels. The analysis of both free serum cortisol via ultrafiltration and salivary cortisol involved two steps: sample centrifugation followed by ELISA, suggesting consideration of widespread adoption of free serum cortisol in future investigations.