Frank P. Underhill

The Influence of Amytal Upon Blood Sugar Content.

The statement of Page 1 that during amytal narcosis no perceptible changes in blood sugar content occur was so suggestive for new possibilities in the study of carbohydrate metabolism as to warrant a repetition of the experiments of Page. In our work, the rabbit served as the experimental animal. In a series of 10 experiments 8 gave evidence of a distinct hyperglycemia which usually appears within an hour, or somewhat later, and may last for several hours. The hyperglycemia is induced by doses ranging from 50 to 100 mg. per kilo of amytal whether given by mouth, subcutaneously or intraperitoneally. Since the completion of our work Weiss 2 has shown that amytal produces hyperglycemia also in the cat and dog. Illustrative examples of the experiments are given in Table I.

Concentration of Arsenic in Blood Subsequent to Serial Administion of Neoarsphenamine.

A number of investigations∗ have shown that when arsphenamine and neoarsphenamine are intravenously introduced, the arsenicals rapidly disappear from the blood stream, part apparently going to immediate excretion, and part to storage in the tissues. Usually, however, these results have been obtained from 1, or in some instances from 2 or 3 injections of the arsenical. To determine whether the number of injections would play any rôle in the disposition of arsenic we have followed the quantity of arsenic present in the blood after serial administration of neoarsphenamine to dogs, maintained upon a constant fixed diet. The drug was introduced into either the jugular or femoral vein, and blood was drawn from an artery, usually of the leg. Each animal received 0.3 gram neoarsphenamine at intervals of 4 days. The arsenic was determined in 10 cc. samples of blood, by the combined methods of Chittenden and Smith, and Sanger and Black, the total quantity in the body being derived from a calculation of the blood volume from the body weight. The results are detailed in Table I. From the table may be seen, as others have found, a rapid disappearance of arsenic from the blood within the first one-half hour, after which the decrease is more gradual. It is to be noted that in the case of Dog 1 traces of arsenic can still be found at 24 hours following each of the first 2 injections, but that after the fourth injection there is still a trace present at 48 hours. Following the fifth injection traces can be found at 72 hours and at 65 hours after the sixth injection. With Dog 2 no traces of arsenic can be found after 24 hours after each of the first 4 injections, but after the fifth, sixth and seventh injections traces of arsenic can be shown at 48 hours.

The production of glycosuria as a result of the intravenous injection of Witte's peptone

Renewed investigation concerning the phenomena provoked by intravenous administration of Wittes peptone has demonstrated the production of a marked glycosuria, following such injections. The appearance of sugar in the urine is accompanied by hyperglycæmia. The experiments were carried out for the most part upon dogs. When Wittes peptone is injected into the rabbit glycosuria is not in evidence, an observation which is in entire accord with the failure of this substance to induce certain other phenomena in this animal which are brought about in the dog. The tentative hypothesis is advanced that the presence of sugar in the urine is induced as a result of the respiratory disturbances set up by the “peptone” injection. The phenomena connected with the injection of “peptone” mixtures are being subjected to further investigation.

THE EFFECTS OF SALINE CATHARTICS IN CONDITIONS OF DEHYDRATION

Numerous investigations within recent years have demonstrated the importance of changes in blood concentration in various experimental and clinical conditions. It has been shown, 1 for example, that the saline purgatives produce their characteristic effect, in large measure at least, by withdrawing fluid from the blood. In view of the extensive use of saline purgatives, it is desirable to have knowledge of their effects on blood concentration in conditions associated with water deprivation. The present communication outlines the results of such an investigation. INFLUENCE OF SALINE PURGATIVES IN A CONDITION OF WATER DEPRIVATION Methods. —Normal adult female dogs were maintained without food and water during the period of experimentation. After periods of from seven to nine days, these animals were given, by stomach tube, doses of either potassium and sodium tartrate (Rochelle salt), sodium sulphate (Glaubers salt) or magnesium sulphate (Epsom salt). Hemoglobin estimations were made by the method of

The influence of subcutaneous injections of morphine upon the hydrogen ion concentration of the urine in the dog and rabbit

The subcutaneous administration of morphine (morphine sulphate, 10 mg. per kilo body weight) to fasting dogs results in the excretion of a strongly alkaline urine, which may persist for a period of twenty-four hours or more. The alkalinity is undoubtedly due to the presence of carbonates since addition of acid to the urine causes effervescence of carbon dioxide. After the urine has resumed its usual acid character a subsequent injection of morphine may fail to elicit an alkaline urine although the hydrogen ion concentration may be diminished appreciably. On the day of morphine introduction there is usually a definite increase in the elimination of the total urinary nitrogen. Rabbits fasted until they excrete a strongly acid urine show no significant change in the hydrogen ion concentration of the urine nor is the total nitrogen altered even though very large doses (80 mg. per kilo) of morphine are subcutaneously introduced. These results are in accord with the well-known resistance of rabbits to morphine narcosis.

The influence of tartrates upon phlorhizin diabetes

A recent communication of Baer and Blum (Archiv für Experimentelle Pathologie und Pharmakologie, 1911, 65, p. 1) shows that the subcutaneous administration of a number of organic compounds, containing two carboxyl groups, exercises a remarkable inhibitory influence upon the elimination of urinary nitrogen and dextrose in dogs with phlorhizin diabetes. Among the substances possessing this property may be mentioned glutaric and tartaric acids. In an endeavor to explain the mechanism of the unique influence exerted by these compounds investigations have been carried out with tartrates upon both dogs and rabbits under conditions similar to those established by Baer and Blum. We have been able to corroborate the findings of Baer and Blum with respect to the action of tartrates although Ringer (PROC. SOC. EXP. BIOL. and MED., 1912, 9, p. 54) failed to obtain the reported results with glutaric acid. Our interpretation of the diminution of the urinary constituents is, however, entirely different from that offered by Baer and Blum. Tartrates subcutaneously injected cause a prompt disintegration of the cellular elements of the kidney tubules, leading to partial or complete loss of secretory activity, and in many cases to anuria. Hence, in phlorhizin diabetes urinary nitrogen and sugar are not eliminated to an appreciable extent.

The Influence of Subcutaneous Injections of Dextrose upon Nitrogenous Metabolism

It has been frequently assumed that the large quantity of sugar present in the body in the condition of diabetes is responsible in part for some of the characteristic symptoms noted. For example, it has been asserted that various acids or acid derivatives may be formed giving rise to the condition of acidosis, as indicated by the well-known increased output of ammonia by diabetics. What influence the large quantity of sugar may have upon the distribution of nitrogen in the urine has received but scanty attention, especially with accurate methods. Recently Scott (J. Physiol., 18, p. 107) has attempted to imitate the condition which obtains in diabetes by injecting into dogs large quantities (seven grams per kilo) of dextrose subcutaneously, and has made a study of the distribution of the urea, non-urea, and ammonia nitrogen as compared with the distribution in the normal animal. He has shown that when the above mentioned quantity of dextrose is injected there is an increased protein metabolism. Further there is probably excreted an increased output of ammonia combined with an acid or acids derived from the decomposition of the dextrose. There is also a diminution in the proportion of nitrogen eliminated as urea and an increase in the output of the non-urea nitrogen. It was the purpose of the present investigation to study the character of this non-urea nitrogen. Accordingly the total nitrogen, urea nitrogen, ammonia nitrogen, creatinin nitrogen, uric-acid nitrogen, and purin nitrogen have been determined under conditions similar to those of Scotts experiments. In harmony with Scotts results, the authors found an increase in the total output of nitrogen due to increased metabolism, together with an increased elimination of oxalic acid.