Effect of steroids and diethylstilbestrol on cocaine toxicity, plasma concentrations and urinary excretion.

Comparative experiments were performed on female rats given pregnenolone-16 alpha-carbonitrile (PCN), spironolactone, triamcinolone, estradiol or diethylstilbestrol to study correlations between the toxic effect of cocaine, its blood clearance and its urinary excretion. PCN and estradiol significantly reduced the toxicity of the drug as well as its plasma levels and urinary excretion. Diethylstilbestrol and spironolactone, unlike triamcinolone, also diminished cocaine toxicity and plasma concentrations.

Effect of pregnenolone-16alpha-carbonitrile on the rat liver.

In female rats, pregnenolone-16alpha-carbonitrile [PCN (a known microsomal enzyme inducer)] augmented liver weight and significantly increased hepatic protein, total lipid, phospholipid and ATP concentrations. These changes were correlated with hepatic drug-metabolizing enzyme induction. PCN did not alter body weight, or water, ash, triglyceride and cholesterol levels in the liver, but caused a mild reduction of hepatic glycogen.

3Beta-hydroxy-20-oxo-pregn-5-ene-16 alpha-carbonitrile, a potent catatoxic steroid devoid of an abortifacient effect.

PCN (3beta-Hydroxy-20-oxo-pregn-5-ene-16alpha-carbonitrile), a potent catatoxic steroid devoid of all other classic hormonal properties, given in doses amply sufficient to induce hepatic drug-metabolizing enzymes and inhibit the anesthesia caused by massive amounts of progesterone in pregnant rats, did not modify: 1. the pregnant:mated ratio, 2. the length of gestation, 3. the number of implantation sites, and 4. the size of the litter. The viability and postpartum development of the offspring were normal, as judged by gross macroscopic examination. PCN had no adverse effects on pregnancy after hypophysectomy (day 12), or ovariectomy (day 8) in rats treated with maintenance doses of progesterone and estrone. It would therefore appear that the pregnancy-maintaining capacity of endogenous or exogenous steroids (administered as substitution therapy following the glandular extirpations) was not altered by PCN and that hypothalamo-hypophyseal regulatory mechanisms were not responsible for the failure of the steroid to provoke abortion. As judged by our in vivo experiment, this pure hepatic microsomal exzyme inducer does not modify the steady state of steroid-dependent physiologic functions.

Confusion and controversy in the stress field.

An attempt is made to further clarify present areas of controversy in the stress field, in response to a two-part article by Dr. John W. Mason which concludes in this issue of the Journal of Human Stress. The author tries to elucidate each source of confusion enumerated by Dr. Mason. The continued use of the word "stress" for the nonspecific response to any demand is deemed most desirable. The once vague term can now be applied in a well-defined sense and is accepted in all foreign languages as well, including those in which no such word existed previously in any sense. Subdivision of the stress concept has become necessary as more recent work has led to such notions as "eustress," "distress," "systemic stress" and "local stress." Confusion between stress as both an agent and a result can be avoided only by the distinction between "stress" and "stressor". It is explained that the stress syndrome is--by definition--nonspecific in its causation. However, depending upon conditioning factors, which can selectively influence the reactivity of certain organs, the same stressor can elicit different manifestations in different individuals.