• Journal of Radiation Protection and Research
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• v.24 no.1
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• pp.23-30
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• 1999

Pregnant ICR mice were treated with 137Cs gamma-ray / ultrasound on day 8 of gestation. In combined treatments, pregnant mice were treated with both 1.5 Gy of radiation and $1.0W/cm^2$ ultrasound at time intervals of -1, 0, 1, 3 and 6 hours. The mortalities and external malformations were investigated on day 18 of gestation. The threshold dose of mortality induced by radiation on day 8 of gestation was between 0.5 and 1.0 Gy, and that which was induced by ultrasound was between 1.0 and $1.5W/cm^2$. The mortalities in the late-stage of gestation induced by combined treatment with radiation and ultrasound increased synergistically. The threshold dose of exencephaly and anophthalmia induced by radiation were between 0.5 and 1.0 Gy and between 1.0 and 1.5 Gy, respectively. Those of exencephaly and anophthalmia induced by ultrasound were between 1.0 and $1.5W/cm^2$ and more than $1.5W/cm^2$, respectively. In combined treatments, the incidence of exencephaly and anophthalmia were found to increase synergistically. In the mice treated with both agents at a time interval of one hour, the incidence of exencephaly and anophthalmia reached maximum levels.

• Journal of radiological science and technology
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• v.14 no.2
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• pp.37-44
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• 1991

The combined effect of radiation and ultrasound has been studied in mouse embryos. Radiation and/or ultrasound were adminstered to ICR mice on day 8 of gestation. Intrauterine death, gross malformation, and fetal body weight were selected as indicators of effects. Does of whole-body ${\gamma}-irradiation$ were 0.5 to 2.5 Gy and those of ultrasound were $0.5\;W/cm^2$ to $3\;W/cm^2$. Intrautrine mortality increased with increasing radiation dose ; this trend was more remarkable in combination with ultrasound. Gross malformations such as exencephaly and anophthalmia/microphthalmia appeared frequently in the fetuses treated with both radiation and ultrasound. Decreased fetal weight was observed even in mice treated with 1.5 Gy of radiation or $1\;W/cm^2$ of ultrasound. There was a linear relationship between dose and reduction of fetal weight. The fetal weight was sensitive, precise and easy-to-handle indicator for the effects of growth retardation. Intrauterine mortality and frequencies of exencephaly and anophthalmia/microphthalmia were higher than the sum of those induced by radiation and by ultrasound. The results indicatied that the combined action of radiation and ultrasound on intrauterine death and malformations was synergistic.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.10
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• pp.1282-1290
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• 2010

The study was carried out to assess the developmental abnormalities induced by Cytotec in mice during intrauterine life. Pregnant mice were exposed to a single dose of 0, 0.02, 0.04, 0.06, 0.08 and $0.1{\mu}g$/g BW on day 8 of gestation. Fetuses were recovered on day 18 of gestation. These fetuses were subjected to morphological and morphometric studies. Morphological studies showed abnormalities like anophthalmia, microophthalmia, micromelia and syndactyly. In addition to these, resorptions were also encountered in the higher dose groups. Morphometric analysis showed an overall reduction in body weight, crown rump length, brain and eye circumference, pinna and snout size, length of fore and hind limb and tail size with a significant difference (p<0.001) compared to controls. The outcomes of histological studies revealed some brain defects like hydrocephaly, enlarged third ventricle and undifferentiated ectoneural cells and abnormalities of the heart included right auricle thrombosis and degeneration of trabecular zone.

• Clinical and Experimental Pediatrics
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• v.46 no.1
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• pp.83-85
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• 2003

Deletion of the short arm of chromosome 6 is relatively rare, with the characteristic features of craniofacial malformations, hypotonia, and defects of the heart and kidney, with hydrocephalus and eye abnormalities. Here author reports a premature girl with bilateral anophthalmia, bilateral hydrocephalus and marked hypotonia, whose chromosome analysis revealed a 46, XX, del(6)(p23) chromosome constitution.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.8
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• pp.1053-1059
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• 2011

The objective of this study was to assess the teratogenic and embryotoxic effects of clomiphene citrate in mice. The pregnant mice were administered a single dose of clomiphene citrate at different concentrations i.e 1.0, 2.0, 4.0 and 6.0 ${\mu}g/g$ BW on day 8 of gestation. Fetuses recovered on day 18 of gestation were analyzed on morphological, morphometric and histological basis. Morphological observations showed defects like open eyelids, anophthalmia, fore and hindlimb micromelia, meromelia, amelia, sacral hygroma, hydrocephaly, hemorrhagic spots, kyphosis and clubbed feet. Morphometric analysis indicated a significant (p<0.001) reduction in fetal body weight, crown rump length, head circumference, eye circumference, forelimb and hindlimb lengths and tail size against controls. The histological observations showed brain defects like hydrocephaly, enlarged ventricles and undifferentiated neuroglial cells in cerebellum. Cleft palate, underdeveloped pharynx and atrophy of jaw muscles were the common anatomical defects of pharyngeal region. It is concluded that the concentrations of clomiphene citrate used during the present study proved teratogenic in mice fetuses.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.40
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• pp.9.1-9.4
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• 2018

Background: Bilateral Tessier number 3 clefts are extremely rare, and their surgical treatments have not been well established. Case presentation: The authors describe the case of a patient with a right Tessier number 3, 11 facial cleft with microphthalmia, a left Tessier number 3 facial cleft with anophthalmia, and cleft palate. We repaired simultaneously the bilateral soft tissue clefts by premaxillary repositioning, cleft lip repair, facial cleft repair by nasal lengthening, midfacial advancement, and an upper eyelid transposition flap with repositioning both the medial canthi. Postoperatively, the patient showed an esthetically acceptable face without unnatural scars. Conclusions: We achieved good results functionally and esthetically by midfacial advancement with facial muscle reposition instead of traditional interdigitating Z-plasties. The surgical modality of our anatomical repair and 3 months follow-up results are presented.

• Toxicological Research
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• v.26 no.3
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• pp.209-216
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• 2010

Limb bud (LB) and central nerve system (CNS) cells were prepared from 12.5 day old pregnant female Crj:CD (SD) rats and treated with olaquindox and vitamin A. Cytotoxicity and inhibition on differentiation were measured in each cell. Three doses of olaquindox (4, 21 and 100 mgkg), and 0.2 and 75 mg/kg of vitamin A were administered to pregnant rat for 11 days from $6^{th}$ to $16^{th}$ of pregnancy. $IC_{50}$ values of olaquindox for proliferation and differentiation in CNS cell were 22.74 and $28.32\;{\mu}g/ml$ and 79.34 and $23.29\;{\mu}g/ml$ in LB cell and those values of vitamin A were 8.13 and $5.94\;{\mu}g/ml$ in CNS cell and 0.81 and $0.05\;{\mu}g/ml$ in LB cell, respectively. Mean body weights of pregnant rats were decreased at high dose of olaquindox (110 mg/kg) but relative ovary weight, number of corpus lutea, and number of implantation were not changed. Resorption and dead fetus were increased at high dose of olaquindox, and relative ovary weight, the number of corpus lutea and implantation, and sex ratio of male to female were not significantly changed in all dose of olaquindox. Mean fetal and placenta weights were significantly (p < 0.01) decreased in rats of high group. Seven fetuses out of 103 showed external anomaly like bent tail, and 10 out of 114 fetuses showed visceral anomalies at high group. The ossification of sternebrae and metacarpals were significantly (p < 0.01) increased by low and middle dose of olaquindox but it was significantly (p < 0.01) prohibited by high dose of olaquindox. In rats treated with vitamin A, the resorption and dead fetus were increased by high dose. Mean fetal weights were significantly (p < 0.01) increased by low dose but significantly (p < 0.01) decreased by high dose. Thirty four fetuses out of 52 showed external anomaly; bent tail (1), cranioarchschisis (14), exencephaly (14), dome shaped head (22), anophthalmia (15), brcahynathia (10) and others (19). Forty five fetuses out of 52 showed soft tissue anomaly; cleft palate (42/52) and anophthalmia (22/52) by high dose of vitamin A. Sixty one fetuses out of 61 (85.2%) showed skull anomaly; defect of frontal, partial and occipital bone (21/61), defect of palatine bone (52/61) and others (50/61). In summary, we support that vitamin A is strong teratogen based on our micromass and in vivo data, and olaquindox has a weak teratogenic potential in LB cell but not in CNS cell. We provide the in vivo evidence that a high dose of olaquindox could have weak embryotoxic potential in rats.

• Proceedings of the Korean Society of Veterinary Clinics Conference
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• 2007.05a
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• pp.174-174
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• 2007

• Clinical and Experimental Pediatrics
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• v.59 no.sup1
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• pp.139-144
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• 2016

Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous syndrome that affects ectomesodermal tissues (skin, eyes, adipose tissue, and brain). The neurologic manifestations associated with ECCL are various including seizures. However, ECCL patients very rarely develop brain tumors that originate from the neuroepithelium. This is the first described case of ECCL in combination with dysembryoplastic neuroepithelial tumor (DNET) that presented with intractable seizures. A 7-year-old girl was admitted to our center because of ECCL and associated uncontrolled seizures. She was born with right anophthalmia and lipomatosis in the right temporal area and endured right temporal lipoma excision at 3 years of age. Seizures began when she was 3 years old, but did not respond to multiple antiepileptic drugs. Brain magnetic resonance (MR) imaging performed at 8 and 10 years of age revealed an interval increase of multifocal hyperintense lesions in the basal ganglia, thalamus, cerebellum, periventricular white matter, and, especially, the right temporal area. A nodular mass near the right hippocampus demonstrated the absence of N-acetylaspartate decrease on brain MR spectroscopy and mildly increased methionine uptake on brain positron emission tomography, suggesting low-grade tumor. Twenty-four-hour video electroencephalographic monitoring also indicated seizures originating from the right temporal area. Right temporal lobectomy was performed without complications, and the nodular lesion was pathologically identified as DNET. The patient has been seizure-free for 14 months since surgery. Although ECCL-associated brain tumors are very rare, careful follow-up imaging and surgical resection is recommended for patients with intractable seizures.

• Journal of Radiation Protection and Research
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• v.21 no.4
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• pp.273-284
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• 1996

Embryos and fetuses are more sensitive to various environmental agents than are adults or children. The biological effects such as intrauterine death and malformation are closely connected with prenatal exposure very various agents. The sensitivity of these embryonic/fetal effects depends on the stage of pregnancy. From the viewpoint of fetal development, embryonic and fetal stages can be divided into three stages : Preimplantation, organogenetic and fetal. Each stage corresponds to 0 to 4.5days, 4.5 to 13.5days, and 13.5days of gestation in mice, respectively. Many studies on the biologcal effects of mice irradiated by ${\gamma}-rays$ at various stages during organogenesis and fetal period have been performed. Based on these results, the dose-effect and dose-response relationships in malformations, intrauterine death, or retardation of the physical growth have been practically modeled by the ICRP(International Commission on Radiological Protection) and other international bodies for radiation protection. Many experimental studies on mice have made it clear that mice embryos in the preimplantation period have a higher sensitivity to radiation for lethal effects than the embryos/fetuses on other prenatal periods. However, no eratogenic effects of radiation at preimplantation stages of mice have been described in many textbooks. It has been believed that 'all or none action results' for radiation of mice during the preimplantation period were applied. The teratogenic and lethal effects during the preimplantation stage are one of the most important problems from the viewpoint of radiological protection, since the preimplantation stage is the period when the pregnancy itself is not noticed by a pregnant woman. There are many physical or chemical agents which affect embryos/fetuses in the environment. It is assumed that each agents indirectly effects a human. Then, a safety criterion on each agent is determined independently. The pregnant ICR mice on 2, 48, 72 or 96 hours post-conception (hpc), at which are preimplantation stage of embryos, were irradiated whole body Cesium-gamma radiation at doses of 0.1, 0.25, 0.5, 1.5, and 2.5 Gy with dose rate of 0.2 Gy/min. In the embryos from the fetuses from the mice irradiated at various period in preimplantation, embryonic/fetal mortalities, incidence of external gross malformation, fetal body weight and sex ratio were observed at day 18 of gestation. The sensitivity of embryonic mortalities in the mice irradiated at the stage of preimplantation were higher than those in the mice irradiated at the stage of organogenesis. And the more sensitive periods of preimplantation stage for embryonic death were 2 and 48 hpc, at which embryos were one cell and 4 to 7 cell stage, respectively. Many types of the external gross malformations such as exencephaly, cleft palate and anophthalmia were observed in the fetuses from the mice irradiated at 2, 72 and 96 hpc. However, no malformations were observed in the mice irradiated at 48 hpc, at which stage the embryos were about 6 cell stage precompacted embryos. So far, it is believed that the embryos on preimplantation stage are not susceptible to teratogens such as radiation and chemical agents. In this study, the sensitivity for external malformations in the fetuses from the mice irradiated at preimplantation were higher than those in the fetuses on stage of organogenesis.