Ischemic necrosis: prevention by stress.

Complete interruption of the circulation, by means of a special clip, in a skin flap during 9 hours results in necrosis of the ischemic area. Prior treatment with various severe stressors (spinal-cord transection, prolonged restraint, quadriplegia due to transection of motor nerves, forced exercise, or cold baths), as well as systemic injection of epinephrine, norepinephrine, or chlorpromazine, offers virtually complete protection against this form of topical tissue injury.

Mercury poisoning: prevention by spironolactone.

The renal tubular necrosis and calcification as well as the mortality induced by mercuric chloride in the rat are readily prevented by prior treatment with well-tolerated amounts of spironolactone.

Mast cells and necrosis.

Subcutaneous injections of normally well tolerated amounts of hypertonic NaCl or urea solutions produce extensive topical necroses in rats systemically treated with various mast-cell dischargers and mast-cell products. This response is considered to be closely related to mitast-cell function, for it cannot be duplicated by systemic treatment with a variety of other agents.

Calcergy inhibited by calciphylactic challengers.

The subcutaneous calcification effected in the rat at sites directly treated with calcergens, such as lead acetate, CeCl(3), CaCl(2), and KMnO(4), is inhibited by simultaneous local application of various calciphylactic challengers, but not by many other compounds.

Digitoxin poisoning: prevention by spironolactone.

Spironolactone (Aldactone(R)) protects the rat against the production of myocardial necroses and other manifestations of digitoxin poisoning.

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.

Effect of spironolactone and norbolethone on the toxicity of digitalis compounds in the rat.

1. In the rat, both spironolactone (an antimineralocorticoid) and norbolethone (an anabolic steroid) inhibit the characteristic neuromuscular disturbances and the mortality produced by digitoxin, gitalin, proscillaridin, digoxin and digitalin. The corresponding effects of strophanthin K, ouabain and digitoxigenin could not be prevented.2. It may be concluded that, in our experimental conditions, both spironolactone and norbolethone counteract the toxicity of some, but not all, digitalis compounds tested and that both the protective steroids affect the toxicity of the same digitalis derivatives.3. This antidigitalis effect is not merely a secondary consequence of either antimineralocorticoid or anabolic potency because spironolactone lacks anabolic and norbolethone lacks antimineralocorticoid properties. Indeed, it appears that the ability to antagonize the toxicity of digitalis compounds represents a pharmacological property independent of all known steroid hormone actions, since spironolactone is virtually devoid of these.

Predisposition to thrombosis not reflected by the blood coagulogram.

Experiments on rats indicate that thrombosis of large veins can develop while blood coagulability is decreased. Hence, coagulation tests have only a limited value in predicting a thrombotic tendency, although they do show characteristic changes during the formation of thrombi.

Influence of steroids and stress on toxicity and disposition of tetraethylammonium bromide.

In female rats, pretreatment with dexamethasone acetate or triamcinolone reduced the toxicity and plasma concentrations of tetraethylammonium bromide while increasing its level in urine. Pretreatment with corticosterone acetate or pregnenolone-16alpha-carbonitrile shared none of these effects. Although starvation or restraint neither diminished the tetraethylammonium bromide concentrations in plasma nor accelerated its urinary excretion, its toxicity was diminished by the stress induced with spinal cord lesions, heat, cold, hydrocortisone, or reserpine as well as starvation or restraint. The protection offered against the toxicant by stress and by the potent glucocorticoids seemed to be mediated, at least partly, via different mechanisms. Stress-induced resistance to tetraethylammonium bromide could not be attributed to elevated plasma corticosterone levels, whereas glucocorticoid-induced resistance could be partially ascribed to increased urinary excretion of the toxicant.

Stress and distress.

I must ask the reader's indulgence for this article's concern with applications of the stress concept, which are distinct from, although related to clinical medicine. It has not been my object to deal with the way physicians have been aided by stress research in the practice of medicine--that information is already widely available. Rather, I have attempted to sketch briefly the history of the stress theory and to demonstrate how this information can help anyone, physician or layman, lead a more complete and satisfying life. The applications of the stress theory have been dealt with at length elsewhere. I believe that we can find within scientifically verified observations the basis of a code of behavior suited to our century. The great laws of nature that regulate the defenses of living beings against stress of any kind are essentially the same at all levels of life, from individual cells to entire complex human organisms and societies. It helps a great deal to understand the fundamental advantages and disadvantages of catatoxic and syntoxic attitudes by studying the biologic basis of self-preservation as reflected in syntoxic and catatoxic chemical mechanisms. When applied to everyday problems, this understanding should lead to choices most likely to provide us the pleasant eustress (from the Greek eu meaning good, as in euphoria) involved in achieving fulfillment and victory, thereby avoiding the self-destructive distress of frustration and failure. So the translation of the laws governing resistance of cells and organs to a code of behavior comes down to three basic precepts: 1. Find your own natural stress level. People differ with regard to the amount and kind of work they consider worth doing to meet the exigencies of daily life and to assure their future security and happiness. In this respect, all of us are influenced by hereditary predispositions and the expectations of our society. Only through planned self-analysis can we establish what we really want; too many people suffer all their lives because they are too conservative to risk a radical change by breaking with hiabits or traditions. 2. Altruistic egoism. The selfish (i.e., self-interested) hoarding of the goodwill, respect, esteem, support, and love of our neighbors is the most efficient way to give vent to our pent-up energy and to create a more enjoyable, beautiful, or useful environment.3. Earn thy neighbor's love. This motto--which is merely a rewording of the command to "love thy neighbor as thyself"--is compatible with man's natural structure, and although it is based on altruistic egoism, it could hardly be attacked as unethical. Who would blame the man who wants to assure his own homeostasis and happiness only by accumulating the treasure of other poeple's benevolence and love? Yet this makes him virtually unassailable, for nobody wants to attack and destroy those upon whom he depends.