Herbert C. Stoerk

Prevention of Loss of Body Fat by Cortisone

Summary and conclusions Adrenalectomized rats, partially starved for 5 days, lost approximately 4 times as much adipose tissue as similar animals injected with 2 mg of compound E daily and twice as much as sham operated controls. The daily injection of 2 mg of DCA did not prevent the excessive loss of fat in adrenalectomized animals. The weight changes of the adipose tissue were paralleled by changes in the content of neutral-fat in the carcasses and livers of the same animals. No appreciable lag in recovery of adipose tissue was observed when starved rats were adrenalectomized and then fed ad libitum.

Studies on the toxicologic and pharmacologic properties of thiabendazole

Abstract Thiabendazole is a potent, orally effective, broad-spectrum anthelmintic. It is also highly active against fungi in vitro . Acute, subacute, and chronic oral toxicity studies proved thiabendazole to be well tolerated by a variety of laboratory animals. Thiabendazole appears to be inert in so far as acute pharmacologic effects are concerned.

The Blood Calcium Lowering Effect of Hvdrocortisone in Parathyroidectomized Rats

Summary and Conclusions PTX rats, 6 hours after injection of hydrocortisone, exhibited more pronounced hypocalcemia than PTX controls. In non-PTX rats the serum Ca was not lowered after injection of the steroid. Comparing the effect of graded doses of bovine PTE (5–90 U.S.P. units) upon the serum Ca of PTX, hydrocortisone-injected rats and of PTX controls 3.5 times more PTE had to be administered to the hydrocortisone-injected group to sustain normal serum Ca concentrations in the 2 groups of PTX animals. Thus it appears that the parathyroids of hydrocortisone-injected rats secrete about 3 times more hormone than those of non-injected controls. The serum Ca-lowering effect of hydrocortisone was not a transient one and was demonstrable after 3 weeks of daily treatment. The effect of hydrocortisone upon the blood Ca of PTX rats was not mediated by circulating citrate.

Complete Regression of Lymphosarcoma Implants Following Temporary Induction of Riboflavin Deficiency in Mice.

Summary Marked regression of established lymphosarcoma (6 C3H-ED) implants occurred in all of 48 C3H mice rendered temporarily deficient in riboflavin either by the feeding of a diet low in this vitamin or by the administration of an antagonist. In most cases survival was significantly prolonged and 15 mice survived without recurrence of the tumors for more than 200 days. When animals which had survived 60 days or more were reinoculated with lymphosarcoma tissue, the second implant failed to take. Established lymphosarcoma implants in 81 control mice on a diet supplemented with adequate amounts of riboflavin, grew continuously and killed all animals within about 4 weeks.

Growth Retardation of Lymphosarcoma Implants in Pyridoxine-Deficient Rats by Testosterone and Cortisone

Summary Marked retardation of growth of lymphosarcoma implants was observed in pyridoxine-deficient rats injected with 2 mg daily of cortisone or of methyl testosterone. Survival of pyridoxine-dencient, tumor-bearing rats was prolonged by testosterone and shortened by cortisone. Thanks are due to Mr. T. C. Bielinski and Miss T. Visotsky for valuable assistance.

Loss of protection by vaccination following cortisone treatment in mice with experimentally induced tuberculosis.

Summary 1. Treatment with cortisone overcame the beneficial effect of vaccination in mice infected with a highly virulent strain of M. tuberculosis, human type, but did not significantly enhance the lethality in non-vaccinated mice. 2. Treatment with cortisone increased the susceptibility of mice to infection with M. tuberculosis of reduced virulence.

CORTISONE AND IMMUNITY TO HOMOIOGENEOUS TISSUE—LOSS OF “INDIVIDUALITY DIFFERENTIALS” FROM TISSUES OF CORTISONE-TREATED RATS

The group of diseases that is alleviated by the administration of cortisone is generally considered to be of allergic etiology. Thus far, the immunological basis of these allergic conditions remains undisclosed, and it is therefore impossible to decide whether or not cortisone depresses immunity to such unknown antigens. None of the “collagen diseases” have found their exact counterpart in sensitized experimental animals, but it appears from such experiments that certain manifestations of the “delayed” rather than those of the “immediate” type of hyperreactivity resemble more closely lesions in these human diseases. In previous studies,’, it was observed that the delayed (tuberculin) type of hyperreactivity was strikingly suppressed when cortisone was administered several days before the reactions were elicited. Under the same treatment (at the dose level of cortisone employed), manifestations of the immediate type of hypersensitivity (phenomenon of Arthus, anaphylaxis) could be provoked with undiminished intensity, indicating that no general loss of reactivity of tissues or blood vessels had occurred. The failure of a short treatment with cortisone to suppress established (immediate) reactivity due to circulating antibody of the classic type appeared quite expected. Although the administration of cortisone was shown to inhibit the formation of this type of immune body,3* it had no action upon its degradation16 so that, following a short course of treatment, the loss of antibody is far from complete and sufficient antibody remains to react with the specific antigen. In the delayed (tuberculin) type of hyperreactivity, a different situation obtains. This form of hyperreactivity was shown by Landsteiner and Chase6 to be transferable only by viable lymphoid cells and not by injured cells or serum. Since the immune principle involved, a t least as far as it is available for circulation, is directly dependent upon the integrity of lymphoid cells, one may expect a priori that the well-knbwn destructive action of cortisone upon these cells should be associated with a diminished reactivity. An immune principle sessile in viable lymphoid cells, strikingly resembling that of 1,andsteiner and Chase, was observed by Kidd and Toolan’ to be associated with acquired resistance to grafting with tumor cells. The finding that this type of immunity also is diminished when lymphoid tissue is suppressed by the administration of cortisone,s points to another similarity between these two forms of immunity associated with “sensitized” cells. From circumstantial evidence it has been suggested in the past that the success of homoiotransplants of neoplastic tissue is largely dependent upon the same factors that determine the compatibility of homoiografts of normal tissue. Quite in keeping with this idea was the finding by Medawar et al. that homologous skin grafts persisted several times longer in cortisone-treated rabbits than in untreated controls.9

Enhancement of Metastatic Calcification Produced with Parathyroid Extract by Parathyroidectomy and Adrenalectomy

Summary Groups of rats were injected with 150 units of bovine PTE over 28 hours. At the end of experiment they were injected intravenously with a standard dose of Ca45Cl2. The extent of the calcific changes was judged from von Kossa stained sections and from concentrations of Ca45/mg tissue. Striking enhancement of metastatic calcifications was observed in parathyroidectomized and in adrenalectomized rats. DOCA and hydrocortisone prevented the appearance of the calcific changes in adrenalectomized rats.

Effect of Adrenalin on Resistance of Adrenalectomized Rats to Certain Toxic Agents

Summary 1. Administration of adrenalin prolongs survival time of adrenalectomized rats injected with KG, formaldehyde, and sodium arsenite. 2. Under conditions of our experiments, adrenalin was more effective than cortisone in providing protection against these agents. 3. This protective effect is abolished by simultaneous administration of sympatholytic drugs. 4. The mechanism of protection appears to be through the prevention of vascular collapse. 5. It is suggested that the medullary secretion is an important factor in resisting traumatic shock.