Marjorie M. Nelson

Congenital Cardiovascular Anomalies Induced by Pteroylglutamic Acid Deficiency during Gestation in the Rat

Congenital cardiovascular anomalies were observed in the offspring when rats were placed on a dietary regimen deficient in pteroylglutamic (“folic”) acid during gestation. These cardiovascular malformations occurred only when the mothers were given this diet for specific periods, as short as two or three days, in early pregnancy, at a time when the heart and aortic arches were in the initial stages of development.

Multiple congenital abnormalities in the rat resulting from acute maternal niacin deficiency during pregnancy.

Summary Pregnant rats were given a purified niacin-deficient diet containing the niacinamide antimetabolite, 6-aminonicotinamide (100 mg/kg of diet), on days 7–9, 8–10, 9–11 or 10–13 of pregnancy. Days 8–10 appeared to be the period of greatest sensitivity as 80% embryonic mortality or abnormality was observed at autopsy on day 21 of pregnancy. A high incidence of embryonic mortality with resorption and a low incidence of abnormal young were observed, regardless of when the diet was first instituted. Malformations in 21-day fetuses from mothers consuming 1–2 mg of 6-AN included defects of the skeleton, central nervous system and eye, urinary system, trunk, thyroid and thymus glands.

Persistent Right Umbilical Vein as a Result of Vitamin Deficiency During Gestation

Of the two umbilical veins formed in young rat embryos, the right regresses early while the left persists until birth. In a number of rat fetuses from mothers subjected to a transitory deficiency of pteroylglutamic (“folic”) acid during pregnancy, this pattern was reversed and the right, instead of the left, umbilical vein persisted until birth. In such cases, the ductus venosus was always absent. No record of persistent right umbilical vein has been found in the literature.

Effect of 36-hour period of pteroylglutamic acid deficiency on fetal development in the rat.

Summary Fetal development in the rat was severely affected by a 36-hour period of pteroylglutamic acid deficiency when instituted early in the second week of pregnancy. The incidence of fetal death or abnormality was higher when the vitamin-deficient diet was started on the 8th day of pregnancy than on the 7 th day but decreased rapidly thereafter with increasing fetal age.

THE EFFECT OF CHRONIC VITAMIN E DEFICIENCY ON THE NERVOUS SYSTEM IN THE RAT.

The problem of whether the neuromuscular disturbances seen in E-deficient rats are characterized by lesions in the nervous system, by changes in the skeletal muscles, or by a combination of both, still remains controversial. On the one hand I,ipshutz,l Einarson and Ringsted,2 M ~ n n i e r , ~ and tle Gutierrez-Mahoney and his associates4 described definite changes in various parts of the central and peripheral nervous system. On the other hand, very definite and early myopathic changes were reported by Olcott.” Wolf and Pappenheimere also studied the nervous system and found no lesions there. They were inclined to attribute the conflicting observations chiefly to variations in technique resulting in different interpretations of the findings. For these reasons, we have considered it worth-while to reinvestigate the pathology underlying E deficiency and have considered that there would be a greater likelihood of detecting changes in the nervous system by the use, first, of animals which resembled those employed by Einarson and Ringsted in that they had long been held on an E-deficient diet.

Reproduction in the Rat on Purified Diets Containing Succinylsulfathiazole.

Summary Adult rats maintained on a purified diet containing succinylsulfathiazole and supplemented with all the known vitamins except pteroylglutamic acid from one to 3 months before breeding showed impaired reproduction.

Changes in endochondral ossification of the tibia accompanying acute pantothenic acid deficiency in young rats.

Summary The changes in endochondral ossification of the tibia accompanying acute pantothenic acid: deficiency in young rats have been investigated. Twenty deficient animals, 13 male and 7 female rats, were autopsied together with their controls at ages ranging from 3 to 16 weeks. The histologic changes observed were decreased growth of the tibia with marked impairment in chondrogenesis, osteogenesis and hematopoiesis. Four stages of morphologic changes were observed. Stage I, in which the ages of the rats ranged from 21 to 33 days, was characterized by unusual trabecular resorption, decreased osteoblast proliferation and edema of the bone marrow. In Stage II the ages ranged from 33 to 63 days and marked retardation of osteogenesis with some calcification in the epiphysis and blunt diaphyseal trabeculae was observed. The dominant feature of Stage III, from 45 to 72 days, was the beginning of epiphyseal cartilage calcification and the cessation of osteogenesis. Stage IV, from 78 to 109 days, was characterized by complete absence of trabeculae and the formation of a heavy layer of sealing-off bone below the epiphyseal cartilage. The role of pantothenic .atid and off additional factors such as pteroylglutamic acid, unknown vitamins and caloric restriction in these histologic changes is discussed.

Sparing action of protein on the pantothenic acid requirement of the rat.

Summary Rats maintained either from birth or from weaning on a pantothenic aciddeficient diet containing 64% casein grow more and survive longer than littermates maintained on a 24% casein-deficient diet under the same conditions. Several possible explanations for this sparing action are given.

Sulfur Amino Acid Requirement for Lactation in the Rat.

Summary A short-term lactation test has been used to study the effects of cystine supplementation for purified diets containing casein as sole protein source. Supplementation of 12, 18, and 24% casein diets with 0.5% L-cystine markedly improved lactation performance as judged by weaning weights of young and mother. Cystine supplementation of 30% casein diet improved weaning weights of young significantly with less beneficial effects on maternal weight. The data indicate that total sulfur amino acid requirement for optimal lactation in the Long-Evans rat may be placed at slightly more than 1% of the diet and that cystine may furnish at least half of this requirement.

Reduced growth hormone content in anterior pituitaries of rats on protein-free diets.

Summary Anterior pituitaries of protein-depleted and of control female rats were bio-assayed for growth-stimulating activity. Absence of dietary protein for 5 weeks reduced growth hormone content of hypophysis to 1/4 that found in normal glands or 1/2 normal amount/mg tissue. There was a parallel decrease in number and size of pituitary acidophils. Growth-promoting potency could be detected in plasma of protein-depleted animals but appeared to be reduced below normal levels.