Harry J. Robinson

Chemotherapeutic Properties of Streptomycin.

Summary Streptomycin seems to possess some advantages over streptothricin particularly from the point of view of toxicity and its greater action against certain gram-negative and gram-positive bacteria in vivo. Although certain batches of streptomycin appear to have the same order of toxicity as streptothricin, the findings suggest that under proper conditions a relatively non-toxic preparation can be obtained. Streptothricin seems to be much more effective in vitro against pathogenic fungi than streptomycin.

Studies on the toxicologic and pharmacologic properties of thiabendazole

Abstract Thiabendazole is a potent, orally effective, broad-spectrum anthelmintic. It is also highly active against fungi in vitro . Acute, subacute, and chronic oral toxicity studies proved thiabendazole to be well tolerated by a variety of laboratory animals. Thiabendazole appears to be inert in so far as acute pharmacologic effects are concerned.

Oral and Parenteral Toxicity of Vitamin K1, Phthiocol and 2 Methyl 1, 4, Naphthoquinone

Summary The acute and chronic toxicity of Phthiocol, 2-methyl-1,4-naphthoquinone and vitamin K1 was studied in mice, rats, and chicks. The oral L.D. 50 in mice was found to be approximately 0.2 g per kg for Phthiocol and 0.5 g per kg for 2-methyl-1,4-naphtho-quinone; no lethal effect could be produced by doses up to 25 g per kg of vitamin K1. In the chronic experiments in rats, daily feeding over a period of 30 consecutive days of 0.35 g per kg of Phthiocol, and 0.5 g per kg of 2-methyl-1,4-naphthoquinone was toxic; doses of 0.1 g per kg of Phthiocol and 0.35 g per kg of 2-methyl-1,4-naphthoquinone produced a marked fall of the erythrocyte count and hemoglobin. No such effects were observed following vitamin K1 administration. In the abdominal cavity of animals sacrificed 10 days after an intraperitoneal injection of vitamin K1 considerable amounts of an oily suspension could be observed, indicating an extremely slow rate of absorption of vitamin K1.

Beneficial Effects of Cortisone on Survival of Rats Infected with D. pneumoniae.

Summary The data demonstrate that cortisone in the dosage range of 2.5-5.0 mg/day can enhance the survival of intact and adrenal-ectomized rats subjected to the stress of experimental pneumococcal infection. The results of bacteremia studies suggest that optimal doses of cortisone operate by enhancing host resistance to the infectious agent. On the other hand, doses larger than 5 mg per rat per day lower the resistance of rats to this infection. Hence, in cortisone therapy, as in the case with certain other hormones, optimum dosage is important and this may vary with different conditions.

The toxicological and antifungal properties of thiabendazole

Abstract Thiabendazole is a colorless, odorless, steble compound which possesses high, broad-spectrum activity against many genera of fungi causing plant disease. The compound is readily absorbed by the roots and distributed to all parts of the plant. Extensive field testing under practical use conditions worldwide indicates that thiabendazole is useful for the control of pathogenic fungi affecting a wide variety of plants. The high degree of safety on plants, combined with a low order of toxicity to humans and animals, serves as a sound basis for the wide acceptance of thiabendazole as a useful fungicide.

Effect of Cholestyramine, a Bile Acid Binding Polymer, on Vitamin K1 Absorption in Dogs:

Summary Studies were undertaken to determine whether or not cholestyramine, a bile acid binding resin, would interfere with the intestinal absorption of fat-soluble vitamins. The studies were designed to give the resin an optimal opportunity to interfere with Vit. K1 absorption. Administration of cholestyramine in a dose range recommended for human use had no effect on Vit. K1 absorption. Large doses of the resin, administered before and shortly after feeding the vitamin, did delay and decrease the absorption of this vitamin. However, very large doses of cholestyramine given 17 hours before feeding Vit. K1 had no affect on the availability of the vitamin. These studies suggest that cholestyramine would not be expected to interfere with the absorption of Vit. K when the resin is used under practical clinical conditions in man. However, the resin may be a useful experimental tool to investigate the role of bile acids in fat absorption.

Studies on the Absorption and Excretion of Streptomycin in Animals.

Summary and Conclusions The findings reported in this communication show that streptomycin is rapidly absorbed and excreted following parenteral administration. The rapid disappearance of streptomycin from the blood is largely accounted for by its early appearance in the urine. Approximately 60-80% of the drug is excreted in the urine of dogs within a 24-hour period after parenteral administration. Somewhat smaller amounts were excreted in the urine of monkeys. When the drug is given perorally relatively small amounts are detected in the blood. This is largely due to the lack of absorption of streptomycin from the gastro-intestinal tract as shown by the large amount of the drug recovered in the feces. Therapeutic blood concentrations can be maintained by repeated intramuscular injection. Following intravenous administration of streptomycin, only 5-10% of the dose can be demonstrated in the bile.

GENERAL PHARMACOLOGY OF ANTIBIOTICS

An attempt will be made to give a brief r6sumC of some of the more important pharmacological properties of antibiotics. The data presented under four headings are: (1) the source, physical and chemical properties; (2) the antimicrobial spectrum; (3) the toxicity or tolerance of antibiotics; and (4) the absorption, distribution, and excretion. Group 1 is composed of penicillin, streptomycin, dihydrostreptomcyin, chloramphenicol, aureomycin, and terramycin. These antibiotics enjoy wide clinical usage and, in general, are well tolerated by patients. Group 2, represented by bacitracin, neomycin, tyrothricin, and polymyxin B, consists of antibiotics that have restricted clinical usage in comparison with the antibiotics of group 1. Group 3 contains antibiotics that still require a great deal of additional chemical and pharmacological study and hence their ultimate value to medicine remains to be established. The latter group includes viomycin, mycomycin, subtilin, and actidione. It is possible that, upon further purification or chemical modification, the antibiotics of groups 2 and 3 may be improved and ultimately added to group 1. A number of other antibiotics, some 50-60, have also appeared in the literature, but little is known about these agents and many of them have not been named. None of these antibiotics will be considered in this article.

Effect of adrenocorticotropic hormone on pneumococcal infections in rabbits.

Summary ACTH, given at frequent intervals and in large doses, lowers the resistance of rabbits to a Type I pneumococcal infection. ACTH appears to suppress inflammation at the bacterial injection site sufficiently to permit early and rapid invasion of the blood stream and surrounding tissues.

Some Chemotherapeutic Properties of Sulfaquinoxaline.

Summary Sulfaquinoxaline was found to be active against certain bacteria both in vitro and in vivo. Single daily doses of this drug were more effective than single daily doses of sulfadiazine or sulfathiazole. These findings may be explained by the fact that sulfaquinoxaline remains in the blood for long periods of time.