K. Sune Larsson

Studies on closure of the ductus arteriosus. XII. In utero effect of indomethacin and sodium salicylate in rats and rabbits.

Administration of prostaglandin synthetase inhibitors to pregnant does and dams in late gestation was followed by in utero contraction of the fetal ductus arteriosus when studied by the whole-body freezing method. In the rat this contraction was well established within 6 h and persisted up to 36 h following 15 mg/kg indomethacin p.o. No effect was observed in the 18 d rat fetus but fetuses at 20 d and 22 d of gestation responded significantly to indomethacin. Doses of indomethacin approaching clinical usage (2.5 mg/kg also caused a positive response in utero. The rat was found to be sensitive also to sodium salicylate and in the rabbit both indomethacin and sodium salicylate were effective. Exposure in utero to prostaglandin synthetase inhibitors with resulting contraction of the ductus may seriously disturb cardiac function in the fetus.

Studies on closure of the ductus arteriosus. XI. Ductal closure in utero by a prostaglandin synthetase inhibitor

Abstract Intrauterine contraction of the ductus arteriosus in fetuses followed a single oral dose of 15 mg/kg indomethacin to pregnant rats 12 or 18 h prior to delivery. This ductal contraction studied by the whole-body freezing technique was markedly pronounced up to 30 min after delivery. Blood gas measurements showed a low pH at 30 min which returned to normal at 120 min. Cyanosis was persistant in the indomethacin groups. Intrauterine ductal closure may be a danger to the fetus and subsequent postnatal adjustment. The present results need confirmation in other species to predict a similar risk in the human fetus.

Studies on closure of the ductus arteriosus. X. In vivo effect of prostaglandin.

The effect of prostaglandins F2alpha, E1 and of 7-oxa-13-prostynoic acid on the newborn rabbit ductus can be studied using the whole-body freezing technique. PGF2alpha and PGE1 were able to re-open the closing ductus arteriosus in adequately oxygenated animals. PGF2alpha administration was accompanied by a strong physical reaction in the rat but less in the rabbit. PGE1 had sedative effects in both animals. A prostaglandin antagonist, 7-oxa-13-prostynoic acid had no effect on normal ductal closure nor did it counteract the effects of PGF2alpha and PGE1. The role of prostaglandins in homeostasis during the fetal and newborn period may be to modify ductal tone.

A teratologic study with the dyes amaranth and Ponceau 4R in mice.

A teratology study on amaranth and Ponceau 4R was carried out in NMRI mice. The substances were given by gavage either from day 0 through day 7 or from day 6 through day 18 in doses of 7.5, 30 or 100 mg/kg. Distilled water was given by gavage to the control dams from day 0 through day 18. The foetuses were removed on day 18 for detailed examinations. No effect of treatment with the dyes could be observed with regard to number of implantations, frequency of foetal death and resorptions, gross malformations, skeletal or internal malformations or retarded growth as judged by foetal weight. The results are discussed with particular reference to the evaluation of teratologic studies on food colouring in general and the various regulation proposals from the National Food Administration.

Alterations in the Metabolism of Glycosaminoglycans and Collagen

Glycosaminoglycans (GAG, previously acid mucopolysaccharides) and collagen are components of extracellular materials which surround the cells of all multicellular organisms. Extracellular matrix is an integral part of tissues and organs and provides the supportive framework on which the structural and functional organization of the body is based. The study of extracellular macromolecules, and the cells that synthesize them, is important to the developmental biologist who finds intriguing problems in cell differentiation, regulation of biosynthesis and secretion, interaction and functional organization of the secreted products, self-assembly, and pattern formation. Abnormality in any of these events or others, such as degradation, through the interference of intrinsic or extrinsic factors, would be expected to lead to faulty development of an organ.

Teratogenic interaction of two substances: Effect of sodium salicylate and defibrase upon pregnant mice

Abstract The effect of the combined treatment with Defibrase, a thrombin-like enzyme preparation purified from the venom of the snake Bothrops atrox, and sodium salicylate was studied in NMRI mice during early (7, 8, 9 day) and late (15, 16, 17 day) gestation period. Increased embryolethality and potentiation of the teratogenic and the foetal damaging effects of sodium salicylate by Defibrase were observed. Blood coagulation tests performed on mothers revealed no significant change in either the number of platelets or the prothrombin time, except for animals on combined treatment in late gestation period. Persisting defibrinogenation of the plasma was observed following Defibrase treatment. The possible risk of teratogenic synergism in clinical therapy of thrombosis with thrombin like enzymes in fertile women is indicated.

Anomalies of the teeth in a child with upper phocomelia: Report of a case☆

Abstract A case of anomalies of the teeth in a child with upper phocomelia has been reported. Aplasia of -02 was found. In the region of 03- and 02-, a single crown was seen which apparently was a fusion of 03- and 02-. There was also aplasia of 2- and -2. A yellow discoloration was observed on many teeth. According to the childs mother, she took a thalidomide tablet during pregnancy each day for 7 days from the twenty-eighth day of gestation. The child was treated with tetracycline during the first 2 years of life.