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Effect of desoxycorticosterone glucoside (DCG) upon cerebral metabolism in man
Western Society for Clinical Research stituents,
albumin,
and mucoprotein;
globulin, excretion
gamma-globulin of 17-ketosteroids;
hcmatologic changes and excretion and serum levels of sodium, potassium chloride, inorganic phosphate and creatinine. Thrre was a marked increase in appetite which became apparent on the first day of treatment in all four patients. In two patients the liver biopsy section showed a lessening of the fat and inflammatory reaction. In two patients there was a significant rise in hemoglobin and hematocrit despite the large amounts of blood (about 1,000 ml.) drawn for studies. The protein changes
were not striking
although
tended to show a rise in albumin gamma-globulin
and mucoprotein
the patients and a drop in values.
The
renal clearances were unaffected by the ACTH therapy in the moderate doses used. The results of the other studies were in accord with the usual effects of ACTH. ACTH seems of some value in the treatment of cirrhosis of the liver and merits further trial. The main salutory effects were an increased appetite and hematopoiesis. There was no change in renal function and no deleterious effect on the liver could be demonstrated by ,4CTH therapy. ORAL CORTISONE. Ephraim P. Engleman,* Marcus A. Krupp, * Peter Kunkel, Joseph E. Welsh and Mr. H. Wrenn, Veterans Administration Hospital, San Francisco, Calif. During the past six months forty-six patients have been treated with oral cortisone, using both tablets and cortisone suspension in syrup. Each patient had a disease known to respond favorably to intramuscular cortisone and severe enough to warrant the use of this hormone. The effects of oral and intramuscular cortisone have been compared as follows: (1) The oral dose of cortisone is similar to the intramuscular dose in its physiologic as well as therapeutic effects. This is substantiated by observations on twelve patients in whom both routes of administration were compared. (2) The therapeutic effect of oral cortisone is more prompt, a particular advantage in the treatment of acute disease. (3) The duration of action of a dose of oral cortisone is shorter, permitting prompt termination of the effects of cortisone should dangerous reactions occur. The clinical impressions concerning the speed of absorption and excretion of orally administered cortisone have been substantiated by
77’
urinary method It is method EFFECT
recover)- experiments according to the of Porter and Silber. concluded that the oral route is the of choice for therapy with cortisone. OF DESOXYCORTICOSTERONE GLUCOSIDE UPON CEREBRAL METABOLISM IN (DCG) MAN. Richard C. Bentinck, Giliwrt S. Gordon, * John I?. Adams, Tillie B. Leake and Thomas J. Huff, Divisions of Medicine and Neurological Surgery and the Metabolic Research La boratory of the University of California School of Medicine, and the Langley Porter Clinic, State Department of Mental Hygiene, San Francisco, Calif. The striking mental manifestations which often accompany steroid administration in man have stimulated the authors to quantitate certain aspects of these compounds on cerebral meatbolism. In the course of this study we have previously reported that the intravenous administration of desoxycorticosterone glucoside (DCG) to human subjects results in the liberation of a reducing substance from the brain into the cerebral venous blood. Further in uiuo studies to determine the nature of this reducing substance and its possible precursors have indicated that the material is non-fermentable and presumably galactose. Serial biopsy specimens of human brain obtained during therapeutic prefrontal lobotomy in psychotic patients, taken immediately before and after the administration of DCG, show a significant decrease in the gray matter glycogen content and an increase in the white matter glycogen. In addition, the reducing substance content of the methanol-chloroform-soluble fraction of the ethanol-insoluble moiety derived from a white matter alkaline hydrolysate is diminished, suggesting that the bulk of the reducing substance is derived from ccrcbrosides. Further characterization of the compounds involved is in progress. These studies and other data, to be presented, indicate that the steroids exert specific effects upon human cerebral metabolism. PAPERS READ BY TITLE URINARY EXCRETION OF EXO~;ENOUS URONIC ACIDS. H. C. Bergman* and H. S. Whittingham, Research Laboratory, Primorganics, Inc., Los Angeles, Calif. There are numerous reports on endogenous glucuronide excretion after administration of phenolic and other chemicals. However, no
albumin,
and mucoprotein;
globulin, excretion
gamma-globulin of 17-ketosteroids;
hcmatologic changes and excretion and serum levels of sodium, potassium chloride, inorganic phosphate and creatinine. Thrre was a marked increase in appetite which became apparent on the first day of treatment in all four patients. In two patients the liver biopsy section showed a lessening of the fat and inflammatory reaction. In two patients there was a significant rise in hemoglobin and hematocrit despite the large amounts of blood (about 1,000 ml.) drawn for studies. The protein changes
were not striking
although
tended to show a rise in albumin gamma-globulin
and mucoprotein
the patients and a drop in values.
The
renal clearances were unaffected by the ACTH therapy in the moderate doses used. The results of the other studies were in accord with the usual effects of ACTH. ACTH seems of some value in the treatment of cirrhosis of the liver and merits further trial. The main salutory effects were an increased appetite and hematopoiesis. There was no change in renal function and no deleterious effect on the liver could be demonstrated by ,4CTH therapy. ORAL CORTISONE. Ephraim P. Engleman,* Marcus A. Krupp, * Peter Kunkel, Joseph E. Welsh and Mr. H. Wrenn, Veterans Administration Hospital, San Francisco, Calif. During the past six months forty-six patients have been treated with oral cortisone, using both tablets and cortisone suspension in syrup. Each patient had a disease known to respond favorably to intramuscular cortisone and severe enough to warrant the use of this hormone. The effects of oral and intramuscular cortisone have been compared as follows: (1) The oral dose of cortisone is similar to the intramuscular dose in its physiologic as well as therapeutic effects. This is substantiated by observations on twelve patients in whom both routes of administration were compared. (2) The therapeutic effect of oral cortisone is more prompt, a particular advantage in the treatment of acute disease. (3) The duration of action of a dose of oral cortisone is shorter, permitting prompt termination of the effects of cortisone should dangerous reactions occur. The clinical impressions concerning the speed of absorption and excretion of orally administered cortisone have been substantiated by
77’
urinary method It is method EFFECT
recover)- experiments according to the of Porter and Silber. concluded that the oral route is the of choice for therapy with cortisone. OF DESOXYCORTICOSTERONE GLUCOSIDE UPON CEREBRAL METABOLISM IN (DCG) MAN. Richard C. Bentinck, Giliwrt S. Gordon, * John I?. Adams, Tillie B. Leake and Thomas J. Huff, Divisions of Medicine and Neurological Surgery and the Metabolic Research La boratory of the University of California School of Medicine, and the Langley Porter Clinic, State Department of Mental Hygiene, San Francisco, Calif. The striking mental manifestations which often accompany steroid administration in man have stimulated the authors to quantitate certain aspects of these compounds on cerebral meatbolism. In the course of this study we have previously reported that the intravenous administration of desoxycorticosterone glucoside (DCG) to human subjects results in the liberation of a reducing substance from the brain into the cerebral venous blood. Further in uiuo studies to determine the nature of this reducing substance and its possible precursors have indicated that the material is non-fermentable and presumably galactose. Serial biopsy specimens of human brain obtained during therapeutic prefrontal lobotomy in psychotic patients, taken immediately before and after the administration of DCG, show a significant decrease in the gray matter glycogen content and an increase in the white matter glycogen. In addition, the reducing substance content of the methanol-chloroform-soluble fraction of the ethanol-insoluble moiety derived from a white matter alkaline hydrolysate is diminished, suggesting that the bulk of the reducing substance is derived from ccrcbrosides. Further characterization of the compounds involved is in progress. These studies and other data, to be presented, indicate that the steroids exert specific effects upon human cerebral metabolism. PAPERS READ BY TITLE URINARY EXCRETION OF EXO~;ENOUS URONIC ACIDS. H. C. Bergman* and H. S. Whittingham, Research Laboratory, Primorganics, Inc., Los Angeles, Calif. There are numerous reports on endogenous glucuronide excretion after administration of phenolic and other chemicals. However, no