摘要:

AbstractMalformations have been produced in fish embryos ofOryzias latipesfollowing exposure to the sulfonylurea sodium tolbutamide during day 1 of development (Smithberg '62).Our present objectives were to determine (1) whether glucose 1‐14C would be differentially incorporated by embryos after drug treatment; and (2) whether the incorporated radioglucose would be converted to glycogen and lipid following drug treatment Total glycogen and total lipid were also measured in a normal and teratogenic environment.We confirmed the results of others that total glycogen decreased during the first three days of normal development and then slowly regained its initial level. During treatment with tolbutamide significantly more glycogen was utilized during the first three days. Total lipid tended to be lower in embryos after 48 hours of treatment compared to corresponding control embryos.Incorporation of radioglucose was inhibited by the drug, and the degree of inhibition varied with its concentration, although the conversion of glucose (or its products) into glycogen and lipid was not different in control and experimental embryos. It is suggested that tolbutamide may affect the permeability of the fish embryo membran

ISSN:0040-3709    

DOI:10.1002/tera.1420010402

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1968

数据来源: WILEY

摘要:

AbstractA teratogenic dose of trypan blue (1% dissolved in saline) was injected into the yolk sac of 48‐hour chick embryos. Twelve hours later the embryo preparations (embryo plus area opaca) were isolated and placed in Warburg vessels in a protein‐free culture medium containing glucose and a buffered saline. Oxygen consumption was measured in these dye‐treated preparations and in two classes of controls, unopened and saline‐injected.Qo2(μl O2consumed/mg dry wt/hr) in trypan blue‐treated preparations was significantly higher than in either class of controls. This is apparently a result of two combined effects of the dye on the tissues studied: (1) a true increase in oxygen consumption; and (2) a decrease in dry weight.These results show that the teratogenic effects of trypan blue can be detected at the biochemical level within 12 hours of treatment. It is suggested that trypan blue acts as an uncoupling agent on the tissues of the early ch

ISSN:0040-3709    

DOI:10.1002/tera.1420010403

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1968

数据来源: WILEY

摘要:

AbstractAbnormally developing embryos from maternal rats treated with the teratogenic folic acid antagonist 9‐methyl pteroylglutamic acid were evaluated for their capacity to consume oxygen in a Warburg constant volume respirometer. Experimental and control embryonic preparations, with extraembryonic membranes intact, were maintained individually in culture media during the full time course of a manometric determination.During the period of the vitamin deficiency the experimental embryonic preparations were found to consume oxygen at a significantly greater rate than did control embryos of the same age. The Qo2for the abnormally developing embryos returned to the control value 24 hours after maternal treatment was terminated. During the period of vitamin deficiency the dry and wet weights of the experimental embryos were less than those of the controls. Subsequent to the deficiency period these attributes gradually returned to control levels.Changes in the oxygen consumption of experimental embryonic preparations were related to the embryo itself and not to the surrounding extraembryonic membrane

ISSN:0040-3709    

DOI:10.1002/tera.1420010404

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1968

数据来源: WILEY

摘要:

AbstractPrenatal treatment with tolbutamide (sodium) has been shown to cause skeletal malformations in mice. The possibility that this agent interferes with sulfur metabolism in the developing mesenchyme‐cartilage‐bone system was tested.Pregnant female mice of the C57BL/6J and 129/Sv‐Sl strains were injected with single doses of sodium‐35S‐sulfate (2 μC/g) on day 9, 10, 11, or 12, and C57BL/6J females were given single doses of35S‐methionine (1 μC/g) at the same times in pregnancy. Experimental animals of both groups then received a teratogenic dose (10 mg) of sodium tolbutamide (Orinase, Upjohn). Twenty‐four hours later (day 10, 11, 12, or 13), the embryos were retrieved and homogenized and aliquots of homogenate were processed for the determination of total embryonic protein and of the level of uptake of isotope. The remaining homogenate was treated with trichloroacetic acid (TCA). The TCA‐precipitable protein content was determined and the level of associated radioactivity ascertained.Results revealed no statistically significant alteration of total embryonic protein weight or TCA‐protein after exposure to tolbutamide, in either strain. There was a statistically significant reduction in the level of uptake of radiosulfate in the experimental groups of both strains. The level of uptake of35S‐methionine was similar for both control and experimental groups. These results suggest that tolbutamide does not interfere with the incorporation or utilization of the amino acid. The possibility is proposed that this agent interferes with sulfate metabolism during the formation of the sulfated mucopolysaccharides vital to the formati

ISSN:0040-3709    

DOI:10.1002/tera.1420010405

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1968

数据来源: WILEY

摘要:

AbstractMaternal nontoxic dosages of cyclophosphamide are teratogenic in Swiss‐Webster mice. Phenobarbital induces and SKF 525‐A inhibits liver drug‐metabolizing enzymes in mice. The purpose of this study was to evaluate the effect of SKF 525‐A and phenobarbital on the teratogenicity and development of alkylating activity after cyclophosphamide. Mice were pretreated intraperitoneally with SKF 525‐A (32 mg/kg) or phenobarbital (50 or 100 mg/kg) on days 8, 9, and 10 of gestation. Cyclophosphamide (20 mg/kg, ip) was administered to all groups on day 10. Phenobarbital and SKF 525‐A were not teratogenic. Cyclophosphamide significantly (P<0.05) reduced the weight of fetuses examined on day 18 of gestation (control, 1.52 vs 0.89 g). SKF 525‐A pretreatment on days 8, 9, and 10 significantly reduced fetal weight from cyclophosphamide (0.79 vs 0.89 g). Phenobarbital pretreatment significantly reversed cyclophosphamide weight effect (1.23 vs. 0.89 g). SKF 525‐A significantly increased the incidence of resorptions, open eyes, polydactyly, aphakia, hydronephrosis, absence or nonossification of ribs, bone fusion. and bone curvature. Phenobarbital abolished cyclophosphamide‐induced limb defects, hydrocephalus, exencephaly, cleft palate, aphakia, and hydronephrosis. Phenobarbital did not affect cyclophosphamide‐induced polydactyly or open eyes. Phenobarbital pretreatment increased and SKF 525‐A pretreatment decreased the concentration of nitrobenzyl pyridine alkylating product of cyclophosphamide (100 mg/kg) in plasma. The teratogenicity of cyclophosphamide may be separate from it

ISSN:0040-3709    

DOI:10.1002/tera.1420010406

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1968

数据来源: WILEY

摘要:

AbstractA high incidence of abortion was produced in Duroc pigs (Sus scrofa) by maternal treatment during organogenesis with 5.5 mg/kg chlorcyclizine. The same dose of chlorcyclizine or hydroxyzine administered to pregnant rhesus monkeys (Macaca mulatta) also resulted in a high frequency of abortion. Species differences in the rate of chlorcyclizine metabolism were shown to exist. Chlorcyclizine was administered to nonpregnant rats, monkeys, and pigs on consecutive days, at teratogenic or abortive doses, and blood levels of norchlorcyclizine, the demethylated derivative of chlorcyclizine, were used as an indication of the rate of metabolism. A comparison of the three species in the rate of conversion to norchlorcyclizine showed that measurable amounts of norchlorcyclizine were present in rat blood 24 hours after the initial dose whereas this metabolite was undetectable in either pig or monkey blood at a similar time period. A comparision of chlorcyclizine metabolism showed that there was more rapid demethylation in monkeys than in pigs as indicated by the fact that chlorcyclizine became undetectable in the blood of monkeys ten days before it did in that of a pig.

ISSN:0040-3709    

DOI:10.1002/tera.1420010407

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1968

数据来源: WILEY

摘要:

AbstractSheep were given subcutaneous injections of aminopterin at different times and for different intervals during gestation. Congenital malformations occurred after treatment at all periods. The principal malformations observed were rotational and flexing deformities of the appendicular skeleton, kyphosis, scoliosis, torticollis, aplasia of the mandible, overflexion of the carpal joint, hypermobility and dorsiflexion of the hock and stifle joints, and relaxation of the fetlock joints. Aplastic ears were also noted.

ISSN:0040-3709    

DOI:10.1002/tera.1420010408

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1968

数据来源: WILEY

摘要:

AbstractThe spontaneous occurrence and teratogenic production of atrial septal defect in A/J mice and ventricular septal defect in C57BL/6J mice lead to the proposal that these strains may represent animal homologies of these congenital heart diseases in human beings. Such models permit investigation into the mechanisms by which nongenetic factors cause genetically predisposed individuals to reach a particular threshold of developmental abnormality and develop a specific type of cardiac malformation.

ISSN:0040-3709    

DOI:10.1002/tera.1420010409

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1968

数据来源: WILEY

摘要:

Abstract“Lid gap,” a congenital defect in the C3H/Ml mouse strain determined by a single autosomal recessive, gene (lgMl) with incomplete penetrance, can be prevented by a single prenatal injection of cortisone (Watney and Miller, '64). In the present study the eyes of normal, lid gap, and cortisone‐treated lid gap embryos were studied histologically at the time of normal eyelid closure (days 14 to 18 of gestation). The earliest consistent difference observed between the normal and lid gap eyes was an adhesion between the corneal epithelium and the epidermis of the lid tip in lid gap embryos on day 15 of gestation. The normally linear orientation of nuclei in the lid tip epidermis was subsequently disrupted. It is suggested that such an adhesion could be the cause of the lid gap d

ISSN:0040-3709    

DOI:10.1002/tera.1420010410

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1968

数据来源: WILEY

摘要:

AbstractA study was made of normal palate embryology in rhesus monkeys. Rotation and initial fusion of the palatal shelves occurred during day 46 of gestation. By day 50 degeneration of both the nasal and midpalatal epithelia along the line of fusion was occurring. The stages of palate development in the rhesus monkey agree very well with those reported for human embryos of approximately the same age.

ISSN:0040-3709    

DOI:10.1002/tera.1420010411

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1968

数据来源: WILEY