Oscar Hechter

Comparison Between Gravimetric and Reduction Methods for Determination of Pregnandiol Glucuronidate.

Summary The results presented indicate the necessity for determination of the purity of the P.G. isolated from non-pregnant urine. It has been clearly shown that the modifications reported by Venning 1 do not necessarily remove all impurities from the final product. The implications of these findings, for much of the data in the literature, are clear. In the light of our results, the finding (first reported by Hamblen, et al., 2 that P.G. may be present in the absence of a secretory endometrium, particularly warrants critical reëxamination.

Ineffectiveness of adrenocortical hormones, thiamine, ascorbic acid, nupercaine, and posttraumatic serum in shock due to scalding burns

Abstract Our results demonstrate that, under the conditions of these experiments, neither desoxycorticosterone acetate, adrenal cortical extract, thiamine, ascorbic acid, nupercaine, nor posttraumatic convalescent serum from burned rats possessed significant antiburn shock activity. Of the agents tested, all seemed definitely ineffective, with the possible exception of thiamine, which, although it did not decrease mortality, did somewhat increase the average survival. It will be seen that this beneficial effect was not consistent. Therefore, we conclude that, although thiamine may be slightly effective in burn shock, its activity is small as compared to the results obtained with a highly effective agent such as large volumes of saline solution or pretreatment with liver extract. 1 Examination of the results with all of the agents under investigation reveals that, in any single test, using twenty animals per group, apparently positive results are obtainable; but, when the tests are repeated, and the results are evaluated in composite form, it is evident that the so-called positive effects are due to variability of the method. Although we cannot state definitely that similar variations are encountered in evaluating antishock activity with other methods, it does appear possible that some of the conflicting results regarding various agents in shock may be explicable in terms of variability factors which were not taken into account. It is not intended to imply that our observations necessarily apply to other forms of shock, produced by other procedures, for there is now evidence that the cause and treatment of various types of shock may be fundamentally dissimilar. 28, 29

Possible Physiologic Significance of the Zinc Content of Insulin

It is known that the effectiveness of insulin in lowering the blood sugar level is dependent upon the integrity of the S-S groups which form part of its protein structure. 1 This suggested the possibility that insulin might exert its physiologic action through the influence of its S-S groups upon such tissue enzymes as are dependent upon S-H groups for their activity. 2-5 We therefore studied the in vitro effect of insulin upon succino-oxidase activity. A significant effect was found. But, it soon became apparent that this in vitro action of insulin did not depend upon its S-S groups, but rather upon its zinc content. Methods and Results. An active succino-oxidase preparation was obtained from minced, fresh beef heart. Its activity was determined by measuring the oxygen consumption in the presence of excess succinate in the Warburg apparatus (38°C; gas phase—air; pH 7.4). Table I presents a typical experiment of a large number which consistently showed a significant inhibition of the succino-oxidase system by crystalline insulin.†

Reduced Glutathione of Tissues and Insulin Sensitivity

The sensitivity of an animal to insulin is usually judged by the extent and duration of the depression of the blood sugar level after the administration of insulin. The factors which are usually considered to exert an important influence upon the insulin depression curve are: the available carbohydrate stores in the liver and the ease with which these stores may be mobilized. 1 The state of the endocrine glands is important in both these respects, and it is well known that adrenalectomy, 2 hypophysectomy, 3 and thyroidectomy 4 increase the sensitivity to insulin. Another important factor in insulin sensitivity, to which less attention has been paid, is the rate of destruction or inactivation of insulin by the tissues of the body. That this factor is significant is shown by the well-established fact that the same amount of insulin becomes more effective when administered in divided doses or by prolonged constant injection than when given in a single dose. 5 The exact mode of insulin inactivation in the body is unknown, but ever since it was shown that insulin is a protein, the supposition has been that it is destroyed by proteolytic enzyme systems. 6 However, it is also known that the physiological action of insulin depends upon the integrity of its S-S groups, 7 , 8 and that the in vitro reduction of these groups by sulphydryl compounds renders the insulin inert upon subsequent injection. 9-13 That a similar mode of inactivation applies to insulin in the living organism is indicated by the work of Jacobs, who has recently demonstrated that the administration of cysteine decreases the reaction to subsequently injected insulin. 14

Further studies on the liver principle which is effective against burn shock

These experiments demonstrate that liver extract, which has significant antiburn shock activity, either when administered parenterally, as in previous work,1 or orally, as in the present study, is without comparable activity in the shock states which follow hind-leg ischemia or bacterial infection. It has been demonstrated that the mechanism of tourniquet shock in rats is complicated by several factors which are difficult to control. Before a final conclusion regarding the ineffectiveness of liver extract in this type of shock could be drawn, it would appear necessary that complicating factors be controlled. The negative results obtained with liver extract after acute exsanguination permit no conclusions to be drawn regarding liver activity in hemorrhagic shock. n nThe fact that liver is effective in burn shock, but not in tourniquet or bacterial shock, is further evidence for the concept that there are different mechanisms responsible for various types of shock, although all may give rise to a similar terminal picture. It further indicates that therapeutic measures must be evaluated individually for each type of shock, and that results obtained with one type of shock cannot be justifiably transferred to other types of shock.