Sidney Q. Cohlan

The Effect of the Administration of Tetracycline on the Development of Teeth

Several investigators1-0 have shown that the tetracyclines complex with several metallic ions. It has also been shown that tetracycline or a fluorophore of this drug is incorporated into growing bones.4-5 In our own studies6-7 it was shown that not only is the drug incorporated in developing skeletons, but that at appropriate levels a marked inhibition of skeletal development also occurs. The present study was designed to amplify our previous findings, to ascertain the effect of the administration of tetracycline on developing teeth. We selected young rats 2 weeks old for this purpose, since at this age both incisors and molars undergo rapid growth and mineralization-a situation somewhat comparable to that which obtains in the human when the deciduous and mixed dentition are being formed.

Comparative absorption, excretion, and storage of oily and aqueous preparations of vitamin A

Summary The administration of an aqueous preparation of vitamin A brought aboutmuch higher blood levels of vitamin A in infants, children, and adults than did an oily preparation. The fecal excretion of vitamin A was determined in seven infants receiving vitamin A dispersed in an oily and in an aqueous vehicle. The amount of vitamin A excreted in the stools was considerably higher when the oily preparation was given. Thus, 38 per cent of the vitamin A intake was recovered in the stools when the oily preparation was administered, as compared with an excretion of 7 per cent following the ingestion of the aqueous product. These results, therefore, indicate that the oily preparation was poorly absorbed and, conversely, the aqueous preparation well absorbed, and explain the wide divergence of blood levels following both preparations. Experiments in guinea pigs and in rats revealed the same findings, namely, higher blood levels and lower fecal excretion of vitamin A following the administration of the aqueous preparation. Furthermore, the vitamin A storage in the liver was considerably higher when the aqueous preparation was given. In conditions affecting the absorption of fat, as, for example, cystic fibrosisof the pancreas and obstructive jaundice, the administration of vitamin A dispersed in an aqueous vehicle brought about excellent rises in the vitamin A concentration in the blood, in contrast to the flat absorption curve obtained with the use of an oily preparation. The oily product contained vitamin A esters dispersed in fish liver oil, whereas the aqueous preparation consisted of vitamin A alcohol dispersed in an aqueous solution of propylene glycol containing vitamin B components, ascorbic acid, and a solubilizer, mannitan monolaurate. Experiments carried out in rats, in guinea pigs, and in children indicated that the superiority of the aqueous preparation was not due to the presence of vitamin A alcohol, vitamin B components, or ascorbic acid, but rather to the dispersion of vitamin A (by means of the solubilizer) in an aqueous-propylene glycol vehicle.

Fetal Homeostasis in Maternal Malnutrition. II. Magnesium Deprivation

Extract: In rats, supplied with an adequate dietary intake of magnesium, the mean fetal magnesium concentration in plasma was 2.4 mEq/liter compared with a maternal concentration of 1.6 mEq/liter. Equilibrium dialysis experiments resulted in a disappearance of the fetal to maternal gradient, with maternal levels becoming slightly higher than fetal levels. Determination of ultrafiltrable magnesium concentrations also demonstrated a slightly lower binding capacity for magnesium in fetal plasma so that the fetal to maternal gradient reflected the unbound magnesium.When a diet containing magnesium in a concentration of 0.88 mEq/kg (compared with a control diet containing 120 mEq/kg) was introduced on day 2 of gestation, only one of eight pregnant rats bore a litter to term. If the diet was introduced on day 10 of gestation, pregnancy continued until term but there was an increased resorp-tion rate and the surviving fetuses were small, weak, and anemic. Analyses of maternal muscle for magnesium, calcium, sodium, and potassium revealed normal concentrations, even though magnesium concentrations in plasma rapidly fell to 20% of the normal level. There appeared to be a reduction in bone magnesium. The significant changes in the fetus were a reduction in magnesium levels in plasma with a disappearance of the fetal to maternal gradient and an elevation in sodium levels. Analysis of the total fetus demonstrated a reduction in magnesium and potassium and an increase in calcium concentrations. The last was also evident in the placenta.Speculation: “Fetal parasitism” as a general concept appears to be. an over-simplification which can be denned with accuracy only by the study of deprivations of specific nutrients, and eventually by the interaction of such nutrients.

The teratogenic effect of vincaleukoblastine in the pregnant rat

Vincaleukoblastine (VLB), a mitosis-inhibiting chemotherapeutic agent is teratogenic in the pregnant rat, producing a 9 per cent incidence of gross developmental malformations. Transplacentally acquired VLB inhibits cell mitosis in fetal tissues as evidenced by a sixfold increase in mitotic figures after a single injection of VLB. Glutamic acid which inhibits the effect of VLB in tissue culture does not protect the rat fetus from its teratogenic effect.

Teratogenic agents and congenital malformations

T H E recent thalidomide tragedy has focused worldwide medical concern on the problem of human teratology and renewed the interest in environmentally induced malformations which was generated over twenty years ago by the recognition of the rubella malformation syndrome. Until 30 years ago, with the exception of fetal irradiation, human malformations were considered to be almost entirely genetically determined. Though laboratory experience had demonstrated that a variety of agents could affect development in lower animals, it was confidently believed that, in the mammal, the placenta served as an effective defensive barrier protecting the fetus from teratogenic insult. The era of active investigation of mammalian teratology began with the observation in swine by Hale, 1 and later in

Handbook of Congenital Malformations.

This handbook compiled by Dr. Rubin with the help of 21 collaborators, consists of a synopsis description of some 700 malformations with brief collateral information on incidence, heredity, prognosis, and treatment. Unfortunately, there is a paucity of clinical photographs to augment the descriptions. In a book of over 700 syndromes, there are only 35 photographs, 17 of which are concentrated in the ophthalmology section. The interpretation of the background literature of some of the malformations is oversimplified and at times uncritical. An obvious example is the citing of an old reference on amelia in which the absence of an arm is attributed to maternal stress in the third and fourth week of gestation and carpal absence to stress in the fifth and sixth week. The practitioner or student looking for identification of an unfamiliar anomaly will probably find it in this book, but the brief descriptions, lack of illustrative