W. H. Sebrell

Prevention by cystine or methionine of hemorrhage and necrosis of the liver in rats.

Necrosis, hemorrhage and cirrhosis of the liver in rats were described by György and Goldblatt. 1 They attributed these lesions to a deficiency of a part of the vitamin B2 complex. By modifying the diet they were later 2 able to increase the incidence of the liver injury. In the report on this work, they stated that the pathogenesis of the necrosis and cirrhosis was related to the lipotropic effect of casein. Blumberg and McCollum 3 reported the production of liver cirrhosis in rats with or without accompanying necrosis and the prevention of the cirrhosis with choline. Daft, Sebrell and Lillie 4 described the production of liver cirrhosis in rats and its prevention by choline, methionine or casein. Lowry, Daft, Sebrell, Ashburn and Lillie 5 reported that treatment by choline or casein of rats with experimentally produced liver cirrhosis resulted in hyperplastic regeneration of liver cells and clinical improvement of the animals. In a paper describing the histology and histogenesis of this liver cirrhosis, Lillie, Ashburn, Sebrell, Daft and Lowry 6 stated that among the noteworthy features is the absence of hemorrhage and, in the earlier stages, of evident necrotic liver cells. The composition of the diets used in these 3 laboratories is given in Table I. It will be noted that our cirrhosis-producing diet No. 545 contains a much lower percentage both of casein and of fat than the diets of György and Goldblatt 1 2 and those of Blumberg and McCollum 3 and that our diet contains cornstarch while the others contain sucrose. Diet No. 545 also contains free cystine while the others do not. In view of the classic observations of Osborne and Mendel, 7 it is apparent that the 10% casein diets are deficient in the sulfur-containing amino acids.

BIOTIN DEFICIENCY AND OTHER CHANGES IN RATS GIVEN SULFANILYLGUANIDINE OR SUCCINYL SULFATHIAZOLE IN PURIFIED DIETS.

The following pathological changes have been observed in rats given sulfaguanidine or sulfasuxidine in purified diets. 1. A granulocytopenia, leukopenia, hypocellularity of bone marrow and, occasionally, an anemia. 2. Hyalinization, necrosis and calcification of voluntary muscle. 3. Hyaline sclerosis and calcification of blood vessels. 4. A dermatitis which can be prevented or successfully treated with crystalline biotin. We have also observed necrosis of heart muscle, hemorrhage into various organs and subcutaneous tissues, and liver damage.

Sulfonamides and Vitamin Deficiencies

Publisher Summary This chapter discusses the different aspects of sulfonamides and vitamin deficiencies. The most widely and successfully used drugs in nutrition experiments are the sulfonamides. The historical basis for the use of the sulfonamides is to be found in experiments dealing with the synthesis of vitamins by intestinal bacteria. Concentrates of the L . casei factor have been reported to possess additional activities for rats given sulfonnmides. It is found that concentrates of this factor prevented the development of hypoprothrombinemia in rats receiving sulfaguanidine. It is reported that certain concentrations containing this vitamin possessed chromotrichial activity for rats, which had become gray while receiving diets containing sulfaguanidine. The order of effectiveness of the sulfonamides in producing a deficiency of vitamin K approximates the order of their bacteriostatic potency against intestinal coliform organisms. Rats showing an acute deficiency of vitamin K following sulfonamide administration show no lack of ability to absorb and utilize the vitamin.

Dietary Granulocytopenia in Rats Corrected by Crystalline L. casei Factor (“Folic Acid”)

Summary 1. Granulocytopenia was observed in a small percentage of rats fed purified diets without sulfonamides. 2. Crystalline L. casei factor (“folic acid”) administered to 5 rats with granulocytopenia corrected the blood dyscrasia in every case. One or more relapses occurred in 3 of the rats. Crystalline L. casei factor (“folic acid”) corrected the granulocytopenia in relapse.

Vitamin E Deficiency in Rats Given Succinyl Sulfathiazole in Purified Diets

Conclusions (1) Hyalinization, necrosis and calcification of voluntary muscle occur in rats given succinyl sulfathiazole in certain purified diets. (2) These lesions may be prevented by the oral administration of α-tocopherol.

Dietary cirrhosis without ceroid in rats.

Conclusions 1. Hepatic cirrhosis without ceroid has been produced in rats by feeding certain purified diets. 2. The type of fat given to rats in low-choline, low-protein diets appears to have an important influence on the deposition of ceroid. It seems probable that some substance or substances which are present in cod liver oil causes the appearance of this pigment. We have not observed ceroid in rats receiving palmitric, stearic, oleic, linoleic, or linolenic acids. 3. Cirrhosis may be produced on a completely fat-free diet.

Granulocytopenia in rats given thiourea and thyroxin; the therapeutic effect of L. casei factor.

Summary Rats given thiourea in a purified diet develop anemia and, in lesser incidence, leucopenia. They also develop hemorrhage and necrosis of the adrenals. Animals which receive, concomitantly, thyroxin injections or thyroid powder become granulocytopenic and leucopenic, while the incidence of anemia and of adrenal hemorrhage and necrosis is greatly reduced. The granulocytopenia and leucopenia of these rats may be corrected by treatment with L. casei factor.

Effect of Riboflavin and Other B Complex Vitamins on Work of Perfused Frog Muscles

Summary The work output of the gastrocnemius muscle of the perfused frog has been determined following the addition of riboflavin to the perfusion fluid in concentrations ranging from 0.0000001 to 0.1 mM per liter. The total work output was significantly increased by the addition of 0.00001 mM riboflavin per liter. Concentrations below this level were ineffective. A significant improvement in total work output was observed with riboflavin concentrations up to and including 0.01 mM per liter; with concentrations of 0.05 and 0.1 mM per liter, the improvement was not statistically significant. The extent of muscle contraction after 8-11 minutes of work was significantly increased by the addition of 0.00001 to 0.01 mM of riboflavin per liter of perfusion fluid. When a mixture of thiamine hydrochloride, calcium pantothenate, nicotinic acid amide, pyridoxine hydrochloride and riboflavin, each at optimal concentrations is added to the perfusion fluid; the improvement in total work output is no greater than that observed with the most effective vitamins singly (thiamine hydrochloride, calcium pantothenate, and pyridoxine hydrochloride). The addition of 20 units of insulin per liter of perfusion fluid along with the vitamin mixture did not result in any greater increase in work output than that observed with the vitamins alone.