摘要:

AbstractSingle ip injections of 500 mg/kg hydroxyurea (HU) to 11‐day pregnant rats produced minimal fetal mortality and malformations of the limbs, palate, jaw, and tail in 98.8% of fetuses surviving to day 21 of gestation. Simultaneous administration of 500 mg/kg HU and 700 mg/kg deoxycytidylic acid (CdMP) provided complete protection against HU teratogenesis. Lower doses of CdMP (3.7–500 mg/kg) gave partial, dose‐related, protection, as indicated by increased frequency of normal survivors and decreased severity of specific malformations. Maximal protection was provided to the forepaw and jaw and minimal to the tail. In experiments in which 700 mg/kg CdMP were given 15–60 minutes after or up to 150 minutes before HU administration, its protective effect gradually diminished with lengthening of time between the administration of the two compounds. The incidence and manifestation of individual malformations in both sets of experiments were time related. When a mixture of 700 mg/kg of CdMP and 500 mg/kg of HU was left at room temperature for 15 minutes before injection, the protective effect of CdMP was diminished by 15.1%. When the effects of several pyrimidine compounds were equated on the basis of biochemically equivalent doses (mmol/kg), among the cytidine derivatives CdMP was more effective at all doses than cytidine or deoxycytidine. All cytidine compounds gave greater protection than the uridine compounds, whereas thymidine and thymidylic acid did not protect the fetal rat against HU‐induced malf

ISSN:0040-3709    

DOI:10.1002/tera.1420070112

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

年代:1973

数据来源: WILEY

摘要:

AbstractPostnatal survivors were obtained after intrauterine neurosurgical lesions were made in fetal rats on the 14th–19th days of gestation. The operations included destruction of a hemispheric wall, unilateral destruction of a rhombic lip or of the nuclei gracilis and cuneatus, spinal cord transection, septal destruction, and optic enucleation. Of 1047 animals subjected to various neurosurgical operations 24% were recovered alive at term. A significant cause of fetal mortality and morbidity was drainage of amniotic fluid. In operations done before the 16th day of gestation, loss of fluid causes cleft palate in approximately 50% of the fetuses born alive. Animals with cleft palate die within hours of birth because they cannot nurse. Postnatal survivability of fetuses subjected to operations can be improved in several ways. Rat mothers vary greatly in handling and nursing their offspring and in their tendency to cannibalization. The experimenter can identify tolerant mothers, and they can be used to produce several litters of operated fetuses. Operations can be planned so that several operated and unoperated females deliver on the same day, so that when some operated females fail to deliver spontaneously many fetuses can still be recovered alive at cesarean section and cross‐fostered to unoperated moth

ISSN:0040-3709    

DOI:10.1002/tera.1420070113

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

年代:1973

数据来源: WILEY

摘要:

AbstractA reduction in alkaline phosphatase activity was demonstrated histochemically and biochemically in the hind limbs of brachypod fetal mice. Seventeen‐day brachypod tibias had a 2–3‐fold lower alkaline phosphatase activity than controls of a similar age. In mutant femurs of this age the decrease in activity was as much as 3–4‐fold. Brachypod fibulas never demonstrated enzyme activity in the stages studied. The enzyme from mutant limb tissues showed the same kinetics, thermal stability, and electrophoretic mobility as that from non‐mutant tissues. Embryo extract from 13‐day brachypod mice, reported to inhibit the growth of normal rudiments in vitro, had no effect on the activity of the normal enzyme. It is proposed that the reduction in enzyme activity is a secondary effect related to the disruption and retardation of limb development

ISSN:0040-3709    

DOI:10.1002/tera.1420070114

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

年代:1973

数据来源: WILEY

摘要:

AbstractTo investigate the claim that the teratogenic effects of histones in chick embryos are limited to a certain period of early development we used total calf thymus histone. After finding that 30 μg were effective at the somite stages, single doses of 0.3, 3, and 30 μg were applied subgerminally on day 2 and intraamniotically on days 3 and 4 to White Leghorn embryos. The teratogenic activity was much greater on days 3 and 4 than on day 2; treatment at the former times produced a characteristic syndrome consisting of cranioschisis, hyperlordosis, eventration, and transposition of the aorta. In view of these findings the opinion that histones lack teratogenic action at later developmental stages is no longer tenable. Furthermore the present results also support the view that the teratogenic effects of histone are caused by mechanisms other than suppression of genomic activit

ISSN:0040-3709    

DOI:10.1002/tera.1420070115

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

年代:1973

数据来源: WILEY

ISSN:0040-3709    

DOI:10.1002/tera.1420070116

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

年代:1973

数据来源: WILEY

ISSN:0040-3709    

DOI:10.1002/tera.1420070101

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

年代:1973

数据来源: WILEY