Ronald F. Gautieri

Morphine-induced fetal malformations I. Exencephaly and axial skeletal fusions

High subcutaneous doses of morphine sulfate, 100–500 mg./kg., administered to CF-1 mice on Day 8 or Day 9 of gestation are teratogenic and result in a large number of fetuses with exencephaly and axial skeletal fusions. Retardation in food consumption is not primarily responsible for these effects even though fasting alone affects embryonic development. Based upon the narrow range between the maternal LD50 and the teratogenic doses in this species, the teratogenic potential of morphine sulfate is low.

Research ArticlesMorphine-Induced Fetal Malformations I: Exencephaly and Axial Skeletal Fusions

High subcutaneous doses of morphine sulfate, 100–500 mg./kg., administered to CF-1 mice on Day 8 or Day 9 of gestation are teratogenic and result in a large number of fetuses with exencephaly and axial skeletal fusions. Retardation in food consumption is not primarily responsible for these effects even though fasting alone affects embryonic development. Based upon the narrow range between the maternal LD50 and the teratogenic doses in this species, the teratogenic potential of morphine sulfate is low.

Teratogenic and Behavioral Anomalies Induced by Acute Exposure of Mice to Ethanol and Their Possible Relation to Fetal Brain DNA Synthesis

Physical and behavioral anomalies of fetal alcohol syndrome were studied after the i.p. administration of a single 3- or 6-g/kg dose of ethanol (25%, v/v) to gravid mice on either day 15 or day 18 of gestation. The physical effects of ethanol administered on either day 8, day 10, or day 12 of gestation (N = 6/group) were also examined and compared to the saline-administered controls. The identification of these anomalies and the effect of ethanol on the rate of fetal brain DNA synthesis were investigated. The physical anomalies were identified by standard procedures. Behavioral anomalies were measured as the inhibition of the development of various neonatal reflexes (N = 6–13/group) as compared to the saline-administered controls. The possible mechanism for these ethanol-induced abnormalities was identified by using [3H]thymidine to measure the rate of DNA synthesis (N = 6/ group) in fetal mouse brains. Blood alcohol concentrations (N = 6/group) ranged from 410.2 mg/dl at 30 min to 25.8 mg/dl at 4.5 hr following the dosage of 3 g/kg of ethanol. Concentrations following the dosage of 6 g/kg of ethanol ranged from 753.7 mg/dl at 15 min to 127.1 mg/dl at 10.5 hr postinjection. Fetal and maternal weight gains were significantly inhibited compared to those of the controls. Various cranial facial, urogenital, skeletal, and cardiovascular anomalies were observed (P ≤ 0.05). Delays in the onset of the air and surface righting, visual placing, and negative geotaxis reflexes were observed for the ethanol-treated neonates, as compared to control values. The rate of DNA synthesis in the ethanol-group fetal mouse brains was significantly less than the control values.

Effect of certain drugs on perfused human placenta VIII. Angiotensin‐II antagonists

The majority of the drugs tested as angiotensin antagonists in this investigation were from two pharmacologic classes: negative musculotropic agents (papaverine, sodium cobaltinitrite, isosorbide dinitrate, nitroglycerin, sodium nitrite, and dipyridamole) and agents which selectively block α-adrenergic receptors (dibenamine, phentolamine, tolazoline, and hydralazine). Of the direct smooth muscle depressants, sodium nitrite and dipyridamole were the most effective; dibenamine and phentolamine were the most potent adrenergic blocking agents employed. Atropine, cocaine, and cyproheptadine were also tested as antagonists of the pressor effect of angiotensin and exhibited only moderate effectiveness. Lidoflazine, a specific angiotensin antagonist, was the most potent compound tested in this study; the degree of antagonism exhibited by it, however, was only slightly greater than either dibenamine or phentolamine. The results indicate that the pressor effect of angiotensin in the perfused human placenta is primarily the result of a direct stimulation of vascular smooth muscle and secondarily to a stimulation of α-adrenergic receptors.

Reduced inflammatory root canal medication

Abstract Some of the presently available root canal medicaments were studied with the hope of combining and altering them so as to retain their antimicrobial activity while reducing their inflammatory potential. In the laboratory phases of the study, antimicrobial activity was measured by means of the filter-paper disk technique. The rabbit eye was used in tests for inflammatory potential. The following compounds and combinations were tested in both the laboratory and the clinic: (1) dichlorophene, (2) hexachlorophene, (3) camphorated monochlorophenol, (4) hexachlorophene plus camphorated monochlorophenol, (5) thymol 5 per cent plus camphorated monochlorophenol, in equal parts of Xylocaine ointment, plus hexachlorophene 1 per cent. The last combination seemed to have the most desirable properties of all the compounds tested. It had excellent antimicrobial activity; it was almost completely free of inflammatory potential when tested in the clinic and in the rabbits eye in the laboratory; it had excellent residual activity in the root canal; and it was easy to use.

A technique for chronic submucosal administration in the dog

Abstract A method which allows the ad libitum local administration of agents to any layer of the gastrointestinal wall, in the unanesthetized dog, is described. Particular emphasis is placed on the administration of agents to the submucosa of the colon.