Herman D. Ratish

Urinary Excretion of Vitamin C in Pneumonia

In previous work 1 on the tissues of laboratory animals we have found the vitamin C content to be reduced in many infections and intoxications. This suggested that cevitamic acid acted not only as an oxidative factor, in normal respiratory processes—but also had a neutralizing rôle in various pathological conditions other than scurvy. Yavorsky, Almaden and King 2 examined human tissues from autopsy for their vitamin C content, and noted that generalized infections were more common among those having a low vitamin C content in their tissues. Worringer and Sala 3 reported scurvy in infants following diphtheria and pertussis. Ten cases of pneumonia were examined on the Pneumonia Service of Doctor Bullowa at Harlem Hospital. The method of Hess and Benjamin, 4 and Birch, Harris and Ray 5 was followed using the dye 2,6,dichlorophenolindophenol. These authors noted that in normal individuals after the ingestion of large doses of vitamin C it was rapidly eliminated in great quantities in the urine. Recently Harris and Ray 6 found that when vitamin C was low in the diet individuals tend to excrete less vitamin C in urine than well-nourished ones. However, more reliable results as to the state of vitamin C saturation or unsaturation of the tissues can be obtained by examining the urinary excretion after administering large test doses of the vitamin. A normal excretion for adults per day the authors estimate as 15–30 mg. The technique of Harris and Ray was followed as closely as possible. Occasionally, however, it has been impossible to get every specimen of urine in the 24 hours, and this has been noted in our calculations. Of the 10 cases 5 were given no saturation test.∗ Two of these were fatal cases. In the first, (a pneumococcus type I† pneumonia with empyema) in 3 specimens of urine voided 12 hours before death 8.6 mg. of cevitamic acid was excreted suggesting a normal output.

Cevitamic Acid Excretion in Pneumonias and Some Other Pathological Conditions

Previous studies by Harde, 1 and Harde and Philippe, 2 Harde and Benjamin, 3 Harde and Greenwald, 4 have shown a lowering of vitamin C content of the tissues of laboratory animals in many infections and intoxications. King 5 and his associates noted a similar fact in studies of human autopsies, and later in work on guinea pigs. 6 These observations suggested to us that vitamin C in infectious diseases unrelated to scurvy, such as pneumonia, may be lowered. The examinations of urines for vitamin C from pneumonia and other pathological conditions permitted verification of this hypothesis. A reducing substance in the urine of normal individuals, probably in large part cevitamic acid, has been studied by Hess and Benjamin 7 and by Birch, Harris and Ray. 8 The latter authors found a relation between vitamin C content of the diet and the urinary excretion of the reducing substance.

Pharmacology of Sodium Sulfanilylsulfanilate.

Sodium sulfanilylsulfanilate, a derivative of sulfanilamide, was first used therapeutically by Dochez and Slanetz 1 against a fatal infection in ferrets supposed to be due to and resembling dog distemper. Maclntyre and Montgomerie 2 in England employed this drug unsuccessfully in infections due to the distemper virus described by Carre-Laidlaw-Durkin. Oakley 3 used it without benefit in experimental influenza. Coggeshall 4 tested sodium sulfanilylsulfanilate in avian malaria. Hebb, Sullivan, and Felton 5 recommended sodium sulfanilylsulfanilate and sodium sulfanilate for the treatment of lymphopathia venereum. This report deals with the pharmacology and toxicity of sodum sulfanilylsulfanilate. Sodium sulfanilylsuilate was determined by the Marshall 6 method using alpha dimethylnaphthylamine in alcoholic solution as the coupling component. Determinations were made on whole blood, urine, and fecal discharges. The fate of single and repeated doses were studied in some normal subjects and in patients, following oral and intravenous administration. Six subjects were given single 5 g doses of sodium sulfanilylsulfanilate. In all 6 cases only traces were observed in the blood. The drug, however, may be recovered in the urine and feces. As shown in Table I, only 4.5% of the total ingested was excreted in the urine while the fecal excretion was 39.5%. In 10 patients repeated oral doses of 5 g statim and 1 g every 4 hours yielded only traces in the systemic circulation. In 2 subjects 10 g 3 times daily resulted in systemic blood levels of 1.0 mg % per 100 ml or less. When 50 ml of a 10% solution of sodium sulfanilylsulfanilate was administered intravenously immediate high blood concentrations were observed. However, as is usual with intravenous sulfonamide therapy, though the rise in concentration is rapid, the fall is equally fast. It will be noted in Chart II that 15 minutes following a 5 g intravenous administration the concentration in the blood was 12 mg per 100 ml.