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1. Removal of one adrenal in the albino rat is followed by hypertrophy of the remaining gland. In the case of female rats 90 days of age this compensatory hypertrophy amounted to 61 per cent. 2. The increase in size of the whole gland is due entirely to hypertrophy of the cortex. This increase in cortical tissue amounted to approximately 91 per cent and was due in large part if not entirely to an increase in the size of the cells. 3. No increase in the size of the medulla or its cells was found.

The addition of an excess of inorganic phosphate in the form of orthophosphoric acid, acid, basic or neutral sodium or potassium phosphate to the diet of albino rats results in the development of an interesting and permanent renal lesion. The phosphate renal lesion is characterized by a necrosis of the cells of the convoluted tubules commencing at the terminal end, followed by a regeneration of atypical epithelium and calcification of the necrotic debris that fills the tubules. The entire outer stripe of the outer zone of the medulla is transformed into a zone of distorted structures and there is an increase in the interstitial connective tissue. The adjoining cortex is also involved with cystic dilatation of tubules and collapse. Such areas may reach the free surface of the organ and produce a retracted scar. In the gross the kidneys are enlarged and firm on section with a pebbled surface produced by numerous scars. The maximum changes in the kidney structure are reached after some 15 days although necrosis of the convoluted tubule cells is evident after a single day of phosphate feeding. The renal structure is not restored to its normal form when the excess of phosphate is removed from the diet.

The production of an experimental uremia in the albino rat by removal of both kidneys is followed by hypertrophy of the adrenal glands. In the case of male rats 90 days of age this adrenal enlargement amounted to 65 per cent and in the case of female rats 180 days of age 47 per cent. The increase in the size of the whole gland is due entirely to hypertrophy of the cortex. This increase in the volume of cortical tissue amounted to approximately 40 per cent for males and 61 per cent for females and was due in large part to an increase in the size of the cells. The content of water and material soluble in fat solvents was higher in the uremic than the control glands. However after subtraction of such storage materials a true hypertrophy of the cortex still remained. It amounted to 21 per cent. Histologically the stainable fat had a more irregular distribution and was present in lesser amount in the adrenals from the uremic animals. The capillaries of the medulla and reticular cortex were distended. The nuclei of both the cortical and medullary cells were swollen and stained faintly.

BY KETOSIS we understand the occurrence or accumulation in the blood in significant amounts of the so-called ketone bodies, namely beta-hydroxybutyric acid, acetoacetic (or diacetic) acid and, secondarily, acetone. In normal subjects on a general diet ketone bodies are present in the blood in inconsiderable amounts (Barnes and Wick, 1939). They appear in largest quantities in cases of severe diabetes and with normal subjects only when fasting or when the food carbohydrate is greatly restricted. Hirschfeld in 1895 (42) first showed that the factor common to these conditions and responsible for the ketosis is the absence of carbohydrate from the food or, as in the diabetic, from his metabolism. Today there is no question that ketosis is due to carbohydrate lack. Antiketogenesis versus Ketolysis Our ideas of how carbohydrate lack produces a ketosis have undergone many alterations. The old idea, first advanced by Geelmuyden in 1909 (39), that the ketone bodies represented incomplete oxidation products of the ...

Compensatory hypertrophy of the kidney in albino rats is increased by an increase in the protein intake. The effect is greater in old rats than young rats. Successive increases in the protein intake are followed by a reduction in the increase in the degree of compensatory renal hypertrophy.

ConclusionsAn active adrenal cortex extract has been found to increase the ketosis of fasting female rats when administered in large doses. The ketosis of fasting male rats is only slightly increased. Adrenal cortex extract abolishes the partial oxidation of B-hydroxybutyric acid when fed to fasting rats.

When one adrenal is removed the cortex of the remaining gland undergoes hypertrophy.1 This does not occur if the hypophysis is removed simultaneously, and in time if hypophysectomy is done, the cortex of the remaining gland, or if the animal has both glands, all of the cortical tissue, atrophies.2 Cortical repair follows anterior pituitary transplants.3 An anterior pituitary extract is now available which prevents the adrenal cortex atrophy in the hypophysectomized organism and stimulates the cortical tissue in normal animals.4 It is fairly obvious that the integrity of the adrenal cortex is, therefore, dependent upon the hypophysis. As far as compensatory hypertrophy of the adrenal cortex is concerned, a reasonable hypothesis is as follows. The maintenance of a normal amount of adrenal cortex tissue is dependent upon the concentration of adrenal cortex hormone circulating in the organism. When one adrenal is removed, the adrenal cortex secretion is reduced and the stimulation received by the other gland ...

A linear relationship exists in the albino rat between the heart weight and the basal metabolic rate when varied by the administration of active thyroid material. It is suggested that this increase in heart weight which follows the increase in metabolism after thyroid is in the nature of a simple work hypertrophy of the myocardium.

SummaryThe rate of absorption of glucose from the intestinal tract of the rabbit decreases with time after the glucose is administered. This is apparently related to the decreasing amount of glucose entering the intestine from the stomach each hour for there is a relation between the rate and amount of glucose available for absorption.

The general cause of obesity is obviously the ingestion and utilization by an individual of calories in excess of those expended by the organism (1). But obesity is after all only a symptom and there is every reason to suppose that it may result from numerous causes, for it would be most unreasonable to assume that all types of obesity are alike. However, our present attempts to classify obese patients are based not on truly objective findings but rather on the broad and more or less uncertain grounds of clinical observation. A possible approach to the classification of obesity appeared to be through a study of the extent of the ketosis developed during fasting in these patients. The route of the normal oxidation of fat in the body is not known with certainty, but is generally assumed to be through such a route that the so called ‘ketone bodies’—beta hydroxybutyric acid, acetoacetic acid and acetone—are produced enroute to oxidation to carbon dioxide and water. Under conditions in which either the absolut...

SummaryThe administration of protamine zinc insulin which leads to a marked hyperalimentation in normal rats is without effect upon the depressed appetite of rats suffering from vitamin B1 deficiency. These deficient rats succumb in hypoglycemia without an increase in their food intake when the insulin is administered. When thiamin chloride is given to B1-deficient rats their appetite responds not only to the vitamin therapy but to protamine zinc insulin as do normal animals.

ConclusionsThe addition of a significant amount of desiccated beef liver or kidney to the diet of the albino rat impairs slightly the rate of growth. The deleterious influence of desiccated beef thymus is more pronounced. These effects are probably due to the nuclear material in these tissues for their influence is related to their content of purine nitrogen.

The degree of ketonemia is a better measure of the degree of ketosis than is the ketonuria.

SOME theoretical considerations led us to wonder whether the renal function and the amount of functioning renal tissue might not owe their relationship to body surface to an association with the basal metabolic rate. That the functional activity of the kidneys should vary with the basal metabolic rate just as do many other physiological processes, is almost without question, for the nitrogen and water metabolism with which renal activity is intimately concerned are both dependent in large measure on the basal metabolism. However, it is the full possible functional capacity of the organ and not the fluctuations in the level of its functional activity with which we are concerned here. In the normal organism, there always seems to be maintained a wide margin of safety between this ordinary level of functional activity and the total function of which an organ or tissue system is capable. In many conditions in which the usual level of functional activity is increased while the basal metabolism remains normal, ...

SummaryAlthough they do not offer direct proof our experiments support the view that the reduction in liver fat caused by the pancreas extract which Dragstedt has described as lipocaic is due to the sum of the lipotropic effects of the choline and protein which it contains. The influence of the pancreas extract upon the fat content of the livers of rats on a low protein and low choline but high fat diet is greater than that of a similar amount of protein in other forms. The ketosis which results when rats with such fatty livers are fasting is reduced about equally by the pancreas extract and an equivalent amount of casein. Althought both the choline and the protein contained in the pancreas extract affect the fat content of the liver, choline is without antiketogenic activity under the conditions studied here.

BECAUSE adrenalectomy reduced the ketonuria we concluded (MacKay and Barnes 1936, 1937) along with others (Evans, 1936 and Fry 1937) that this procedure had an antiketogenic action, reducing acetone body formation in the organism. Subsequent studies (Mirsky 1938, Shipley and Long 1938, and MacKay and Wick 1939) have shown that the changes in the ketonuria were due to changes in the renal threshold for the acetone bodies. The same observations invalidate the suggestion we once made (MacKay and Barnes 1938) that adrenalectomy increases the ketolytic activity of the organism. This has already been pointed out (MacKay and Wick 1939) where we concluded that “The influence of adrenalectomy upon ketolytic activity will have to be studied by the use of arterio-venous differences….” The results of such a study are presented here.

SATISFACTORY results have been attained in measuring cortin-like substances in urine by chemical methods. It has been possible to develop one of these based on the reduction of phosphomolybdic acid (Heard and Sobel, 1946), so that we can measure the concentration of lipid-soluble reducing substances in blood samples of reasonable size. With this method it is possible to recover 11-desoxy-corticosterone, corticosterone, 17- hydroxy-11-dehydrocorticosterone (Compound E), and the reducing compounds in cortical extracts from bovine adrenal glands, when added to rabbit blood plasma. Measured with a chemical method the excretion of cortin-like substances in the urine of human subjects is markedly increased by the administration of anterior pituitary adrenocorticotropic hormone (ACTH) (Mason et al., 1948; Forsham et al., 1948; Romanoff et al., 1949; Sprague et al., 1950). With our method we have found similar increases in blood plasma values using the rabbit as the experimental animal.