E. K. Marshall

THE GLOMERULAR DEVELOPMENT OF THE VERTEBRATE KIDNEY IN RELATION TO HABITAT

Evidence is presented for the view that the glomerular development of the kidneys of vertebrates is related to water excretion. The protovertebrate kidney was at one, stage probably aglomerular and the glomerulus was evolved as an adaptation to a fresh-water habitat. In the lower vertebrates remaining in fresh water (dipnoans, ganoids and fresh-water teleosts) and in those still in intimate dependence on it (Amphibia), the glomerular development is good; but with the secondary assumption of a marine habitat (marine teleosts) or with the asumption of terrestrial life in which water conservation becomes a necessity (arid-living reptiles and birds) the glomerular development is extremely poor. In the mammals (and possibly to some extent in lower vertebrates) the primitive water-excreting function of the gbomerulus has been secondarily diverted to a filtration-reabsorption system designed to excrete waste products without the loss from the body of excessive quantities of water. The relative importance of tubu...

Kidney Secretion in Reptiles

In birds there is now rather conclusive evidence that tubular secretion plays a major role in the excretion of uric acid by the kidney. 1 , 2 Uric acid is the main nitrogenous urinary constituent of the arid-living reptiles (snakes and lizards) but no data are available as to its mode of excretion. The experiments reported here indicate that in the lizard, it is chiefly excreted by tubular secretion. The urine/plasma ratio of uric acid has been compared with that of glucose after administration of phlorizin. Glucose is not secreted by the tubule 3 and phlorizin paralyzes the reabsorptive power of the tubule for glucose. Hence, the urine/plasma ratio for glucose should be a measure of the amount of glomerular filtrate if no glucose is reabsorbed under phlorizin. This error, if present, is probably small and would not affect appreciably the conclusions drawn from the present experiments. The iguana (Iguana iguana Shaw) has been used as the experimental animal. Phlorizin was injected subcutaneously in dosage of 250 mg. per kilo 2 hours before the experiment or in 2 doses of 200 mg. per kilo the afternoon before and early on the morning of the experiment. The iguanas were anesthetized with urethane (5 cc. of a 25% solution per kilo), the cloaca opened with a small incision, cannulae tied into the ureteral papillae, and urine collected for a period of 10 to 30 minutes. The abdominal cavity was then quickly opened and blood drawn from the aorta. The urine which was milky in appearance was diluted with hot water to an appropriate volume to obtain solution of all the uric acid. The plasma was precipitated with tungstic acid. Uric acid was determined by the method of Benedict 4 and glucose by the Hagedorn-Jensen method. 5

Determination of Para-Aminosalicylic Acid in Blood.∗

Since para-aminosalicylic acid has been found to have a definite chemotherapeutic effect in experimental tuberculosis, a simple method for its determination in blood appears desirable. The sulfonamide method in general use 1 cannot be employed without modification. In view of several requests for a method for determination of this substance, and since the slight modification of the sulfonamide method found necessary may prove useful with other aryl amines, we are publishing this short note. No color is obtained when a solution of p-aminosalicylic acid is subjected to the ordinary procedure for determining sulfonamides. If the acidity of the solution is increased a color is obtained. Maximum color is developed at room temperature when the solution is made about 3 N with hydrochloric acid. The results are, however, not consistent. Diazotization for one minute gives a more intense color than for 3 or 10 minutes. Obviously, either the diazo compound is unstable or a secondary reaction is occurring with the nitrous acid. Diazotization done with the solution at 1°C and made 1 N with hydrochloric acid yielded a more intense color than any other procedure which we have tried. The results under these conditions appear to be quite consistent and reproducible. Reagents. 1. A solution of trichloroacetic acid containing 15 g dissolved in water and diluted to 100 cc. 2. A 0.1% solution of sodium nitrite. 3. An aqueous solution of N-(1-naphthyl)-ethylenediamine dihydrochloride containing 100 mg per 100 cc. This solution should be kept in a dark colored bottle. 4. 6 N hydrochloric acid. 5. A solution of ammonium sulfamate, containing 0.5 g per 100 cc. 6. A standard solution of p-aminosalicylic acid prepared by suspending 50 mg of the compound in water and dissolving in slightly more than the theoretical amount of sodium hydroxide, and diluting to one liter.

Excretion of inorganic phosphate by the aglomerular kidney.

The urine of the winter toadfish, Opsanus tau (aglomerular kidney), contains only the faintest trace of inorganic phosphate when the fish are kept in an aquarium in the laboratory. The injection of large amounts of either monobasic or dibasic sodium phosphate intramuscularly or intravenously raises the plasma inorganic phosphate to high levels, but does not cause the excretion of any inorganic phosphate in the urine. The excretion of inorganic phosphate has not resulted from various procedures (feeding, injection of glucose, parathyroid extract, insulin). The injection of sodium glycerophosphate results in a marked rise in the inorganic phosphate of the plasma, but in no excretion of inorganic phosphate by the kidney. The above findings are interesting in view of the fact that the goosefish (another aglomerular marine teleost) secretes urine which may contain large amounts of inorganic phosphate. 1 Since we have been unable to obtain freshly caught or summer toadfish, further investigation of phosphate excretion has been carried out upon the goosefish (Lophius piscatorius). Specimens of urine obtained from the bladders of 10 freshly caught summer goosefish contained from 0.7 to 45.0 millimols of phosphate∗ per liter. The plasma phosphate in the same fish varied from 4.2 to 7.7 millimols per liter. The high concentrations of phosphate observed initially in the urine of some of these fish decreased markedly when the fish were kept in live cars at the laboratory. The injection of inorganic phosphate into a goosefish does not increase the phosphate excretion. The following protocol is typical of many experiments. Goosefish 5. 2.6 kilos. 9:54—11:56 Urine, 10 cc. containing 3.0 mM phosphate per liter (excretion 0.015 mM per hour). 11:58 Plasma phosphate, 7.7 mM per liter. 12:00 Inject intramuscularly 17 mM disodium phosphate (40 cc. of 6%). 1:52 Plasma phosphate, 19.2 mM per liter. Summary. Injected inorganic phosphate is not secreted by the aglomerular kidney but the urine of the aglomerular fish may contain large amounts of inorganic phosphate. This suggests that the inorganic phosphate in the urine of these fish is formed in the kidney from some precursor. From the above results it would appear that injected inorganic phosphate should be excreted only by glomerular filtration in the glomerular kidney. In support of this hypothesis it has been found that the clearances of inorganic phosphate and xylose agree fairly closely in frogs.

Rate of metabolism of ethyl alcohol in the mouse.

Summary The rate of oxidation of alcohol has been studied in the mouse by determination of the rate of decline of the concentration of alcohol in the blood as well as by determination of the alcohol content of the whole animal at various times after administration of the drug. When observations are begun one hour after administration of alcohol, the rate of oxidation is constant and independent of the amount present. However, the rate of oxidation may be twice as great in the first hour as in subsequent hours. The effect is dependent on dose and to some extent on mode of administration.

Distribution of 3,4-Dimethyl-5-sulfanilamidoisoxazole in the Body.

Summary The distribution of 3,4 dimethyl-5-sulfanilamidoisoxazole has been studied in the log and in man. Its apparent volume of distribution in per cent of the body weight indicates that it is contained only in extracellular water.

Comparison of Certain Pharmacological and Antibacterial Properties of p-Hydroxaminobenzenesulfonamide and Sulfanilamide.

Summary The preparation, properties, stability, and colorimetric analysis of p-hydroxaminobenzenesulfonamide are described. When injected into dogs, this substance appears to be completely converted to sulfanilamide within 5 minutes. In vitro, under the conditions of our experiments, it is no more than ten times as active as sulfanilamide.

Effect of 3-Hydroxy-2-phenylcinchoninic Acid on Renal Secretion of Phenyl Red and Penicillin.

Summary Similar to carinamide, 3-hydroxy-2-phenylcinchoninic acid causes higher concentrations of penicillin in the plasma when injected before the administration of the penicillin. Both substances also decrease the rate of excretion of phenol red. The activities of the two drugs are roughly of the same order of magnitude. This increase in concentration of penicillin in the plasma and decrease in rate of excretion of phenol red is attributed to a blocking of the renal tubular secretory mechanism. We wish to thank Sara Ann Verplanck and Irene T. Payne for technical assistance.

Curative Action of Drugs in Lophurae Malaria of the Duck.

Summary A number of drugs have been examined for their curative action in lophurae malaria in the duck. Pamaquine appears to cure a fair percentage of the birds, while quinine, quinacrine, chloroquine and a number of other drugs do not.

THE THERAPEUTIC VALUE OF ORGANIC PHOSPHORUS COMPOUNDS

The prescribing of preparations of organically bound phosphorus rests mainly on the theory that such compounds are absorbed and stored as such by the organism, and that the needs of the body for organic phosphorus cannot be supplied by inorganic phosphates. Neither of these ideas, however, has any real scientific foundation, but the evidence is rather conclusive in the opposite direction. Phosphorus as taken into the organism as a food material exists in inorganic form and organic, for instance lecithins, glycerophosphoric acid, phytin, nucleic acid and phosphoproteins. The problem as to the relative utilization and nutritive value of inorganic and organically bound phosphorus has been approached from three main aspects: The search for enzymes in the organism capable of liberating phosphoric acid from organic compounds containing phosphorus. Metabolism studies of the phosphorus balance, with the feeding of diets containing inorganic or organically bound phosphorus. Studies on the ability of the