The pharmacological activity of glycerol has raised the question of the relationship between this substance and glucose since some of the manifestations induced by glycerol could be obtained with glucose. The same effect is seen on local pH in the second day wound crust. Glucose administered for a few days prior to, and immediately following, wound induction shifts local pH toward more acid values. A similar effect is obtained on the pH of tumors. (173) Glucose decreases intensity of pain of the alkaline pattern and increases pain of acid pattern. We were able to induce convulsions in rats by injecting 20 to 25 cc. of an isotonic solution of glucose subcutaneously twice daily. After 4 to 6 days, convulsions appeared and often led to death. In some terminal cancer patients with brain metastases, who had had previous convulsions, intravenous administration of glucose as a therapeutic procedure produced convulsions. We have even seen lethal convulsions in a patient after a few days of intravenous administration of glucose in saline solution in conjunction with intramuscular doses of 1 mg. twice daily of deoxycorticosterone.

Although rarer than for glycerol, hemorrhages occurred after each glucose administration in some patients with previously bleeding ulcerated lesions. Bleeding stopped when glucose administration was discontinued. Renewed administration was followed each time by renewed bleeding. We want to emphasize this relationship of glucose to hemorrhage because of its clinical importance.

It seems possible that glyceric aldehyde and glyceric acid, which appear during glucose metabolism, play a role in the manifestations mentioned above.

Pharmacodynamic Activity Of Glycerophosphoric Acid

The ability to relate the pharmacological activity of glycerol to its bond with fatty acids, has led us to consider another substance able to bind fatty acids, glycerophosphoric acid. The bond of this acid with quaternary bases such as choline or ethanolamine, and the fatty acids results in phospholipids which take part in the formation of boundaries and separating membranes. Although various fatty acids, both saturated and especially unsaturated, enter into these phospholipids, resulting in a variety of compounds, their general biological behavior appears to be the same. Certain fatty acids, the di- and tri ethenic, however, are preferentially bound as phospholipids when they pass from the intestine into the circulation.

In investigating its influence as an anti fatty acid agent, we administered glycerophosphoric acid, 50 cc. of a n/10 solution diluted in 1000 cc. of isotonic saline, glucose or other solutions, intravenously or subcutaneously. It had salutary effects upon pain of an alkaline pattern and upon corresponding lesions. A manifest influence was exerted upon the systemic acid base balance, especially in cases with high urinary pH and with all other analyses showing an offbalance of type D. No influence was observed upon evolution of tumors in animals or humans.

The increased basal metabolism and a marked increase in work capacity, which are observed in subjects taking sodium glycerophosphate for long periods, has made us suspect a possible effect upon thyroid secretion. The appearance of thyrotoxicosis in a subject who had inadvertently taken a large dose of sodium glycerophosphate seemed to confirm this view.