BACKGROUND: We had a case in which three consecutive pregnancies resulted in birth of three children with an orofacial cleft. Their mother suffered from bronchial asthma and was treated using symbicort (corticosteroid budesonide plus bronchodilator formoterol) during her pregnancies. A hypothesis was assessed: these anti-asthmatics can induce an orofacial cleft in experimental model. MATERIALS AND METHODS: A single administration of one of five increasing doses (including therapeutically used ones) of Symbicort, budesonide or formoterol was injected into the amnion of a chick embryo on day 4 or 5 of incubation. The teratogenic/lethal effects of the anti-asthmatics were assessed on a total of 600 embryos. RESULTS: For budesonide, the teratogenic/lethal effect started at a dose 0.003 μg per embryo, for formoterol at 0.3 μg and for Symbicort 0.03 μg. Orofacial clefts and gastroschisis after exposure were found for all three anti-asthmatics. Heart septum defects occurred after exposure to formoterol. CONCLUSION: The present results support those clinical/epidemiological studies pointing out that anti-asthmatics have the potential to induce orofacial clefts, gastroschisis and heart malformations during prenatal development in human.

• Klíčová slova
• Teratology, development, drug safety, embryogenesis, reproduction,
• MeSH
• antiastmatika * MeSH
• aplikace inhalační MeSH
• budesonid škodlivé účinky   MeSH
• dítě MeSH
• dvojitá slepá metoda MeSH
• ethanolaminy škodlivé účinky   MeSH
• formoterol fumarát škodlivé účinky   MeSH
• gastroschiza * chemicky indukované   MeSH
• kombinace léků budesonid a formoterol MeSH
• kuřecí embryo MeSH
• lidé MeSH
• rozštěp patra * chemicky indukované   MeSH
• rozštěp rtu * chemicky indukované   MeSH
• srdeční septum MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• kuřecí embryo MeSH
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiastmatika * MeSH
• budesonid MeSH
• ethanolaminy MeSH
• formoterol fumarát MeSH
• kombinace léků budesonid a formoterol MeSH

The primitive erythroid line cells of chick embryos were studied during embryonic days 2-14 by means of a cytochemical method to investigate the appearance and frequency of the main nucleolar types. The populations of erythroblasts and erythrocytes were classified according to the presence of functionally dominant nucleoli in their nuclei. In the course of primitive erythroid cell differentiation and maturation, compact nucleoli and nucleoli with nucleolonemas (both supposed to be RNA biosynthetically active) were gradually replaced by ring-shaped nucleoli and finally by micronucleoli reflecting the reversible and irreversible inhibition of RNA synthesis, respectively. The occurrence of the main nucleolar types and their values in primitive erythroid cells of the developing chick depend not only on the maturation stage of the blood cells, but also on the developmental stage of the chick embryo. In comparison with the definitive erythroid line of the post-hatching chick and hen, the cells of the chick embryonic primitive erythroid line possess relatively high values of "active" nucleolar types. These are still present in advanced maturation stages, and occur also as definitive erythroid lines of lower vertebrates.

• MeSH
• buněčná diferenciace fyziologie   MeSH
• buněčné jadérko metabolismus   ultrastruktura   MeSH
• buněčné linie MeSH
• erytroidní prekurzorové buňky cytologie   metabolismus   ultrastruktura   MeSH
• erytropoéza fyziologie   MeSH
• kuřecí embryo MeSH
• RNA metabolismus   MeSH
• zvířata MeSH
• Check Tag
• kuřecí embryo MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• RNA MeSH