Propylthiouracil Is Teratogenic in Murine Embryos

Background: Hyperthyroidism during pregnancy is treated with the antithyroid drugs (ATD) propylthiouracil (PTU) and methimazole (MMI). PTU currently is recommended as the drug of choice during early pregnancy. Yet, despite widespread ATD use in pregnancy, formal studies of ATD teratogenic effects have not been performed. Methods: We examined the teratogenic effects of PTU and MMI during embryogenesis in mice. To span different periods of embryogenesis, dams were treated with compounds or vehicle daily from embryonic day (E) 7.5 to 9.5 or from E3.5 to E7.5. Embryos were examined for gross malformations at E10.5 or E18.5 followed by histological and micro-CT analysis. Influences of PTU on gene expression levels were examined by RNA microarray analysis. Results: When dams were treated from E7.5 to E9.5 with PTU, neural tube and cardiac abnormalities were observed at E10.5. Cranial neural tube defects were significantly more common among the PTU-exposed embryos than those exposed to MMI or vehicle. Blood in the pericardial sac, which is a feature indicative of abnormal cardiac function and/or abnormal vasculature, was observed more frequently in PTU-treated than MMI-treated or vehicle-treated embryos. Following PTU treatment, a total of 134 differentially expressed genes were identified. Disrupted genetic pathways were those associated with cytoskeleton remodeling and keratin filaments. At E 18.5, no gross malformations were evident in either ATD group, but the number of viable PTU embryos per dam at E18.5 was significantly lower from those at E10.5, indicating loss o

TIME VARIATIONS OF THE CALCIUM ELEMENTAL ABUNDANCE IN FLARES FROM NOAA ACTIVE REGIONS 2562 AND 2779

Analysis of flare spectra obtained with the Bent Crystal Spectrometer aboard the Solar Maximum Mission (SMM) satellite enables the determination of the fluxes in the resonance (w) line of Ca XIX and the near-by continuum. The line-to-continuum intensity ratio is a sensitive measure of the calcium elemental abundance (ACa) relative to hydrogen in the emitting plasma. In previous investigations we found the calcium abundance varies from flare to flare. In the present investigation we analyse the variations of ACa for flares which occurred in two active regions well observed by SMM. We conclude that it is not possible to correlate the abundance variations with the time of the flare occurrence as suggested in an earlier paper for flares produced from a single active region. Further, we find no convincing correlation of abundance variation with any other flare characteristics. This negative result will stimulate future work on the physical interpretation of the calcium abundance variation

Diaphragmatic hernia in the south-west of England.

A retrospective anatomical, family, and epidemiological study was made of 143 patients (81 female and 62 male) with diaphragmatic hernia who were born in the south-west of England between 1943 and 1974. Thirty-nine cases were stillborn. Seventy-five per cent of patients had a left-sided diaphragmatic defect, 22% had a right-sided defect, and 3% had a bilateral defect. Fifty per cent of the patients had other congenital malformations, most frequently of the nervous system. No maternal age or birth order effect was noted. Cases of diaphragmatic hernia without other malformations had in general a normal fetal growth rate. Eight per cent of the cases were illegitimate. There were two pairs of twins discordant for diaphragmatic hernia, one pair being dizygotic and the other monozygotic. In no case of diaphragmatic hernia was there a relative affected with a diaphragmatic hernia. The most common type of diaphragmatic defect was a posterolateral hernia (92%), followed in frequency by an eventration of the diaphragm (5%), the least common defect being a retrocostosternal hernia (2%). Diaphragmatic hernia appears to be aetiologically as well as anatomically heterogeneous. In this series there were two cases of trisomy 18, one case of trisomy 21, one case trisomic for a small part of chromosome 20, and two cases with the Pierre Robin syndrome. It seems likely that diaphragmatic hernia is a non-specific consequence of several teratological processes