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Sample records for teratogens

  1. Piperidine alkaloids: human and food animal teratogens.

    Science.gov (United States)

    Green, Benedict T; Lee, Stephen T; Panter, Kip E; Brown, David R

    2012-06-01

    Piperidine alkaloids are acutely toxic to adult livestock species and produce musculoskeletal deformities in neonatal animals. These teratogenic effects include multiple congenital contracture (MCC) deformities and cleft palate in cattle, pigs, sheep, and goats. Poisonous plants containing teratogenic piperidine alkaloids include poison hemlock (Conium maculatum), lupine (Lupinus spp.), and tobacco (Nicotiana tabacum) [including wild tree tobacco (Nicotiana glauca)]. There is abundant epidemiological evidence in humans that link maternal tobacco use with a high incidence of oral clefting in newborns; this association may be partly attributable to the presence of piperidine alkaloids in tobacco products. In this review, we summarize the evidence for piperidine alkaloids that act as teratogens in livestock, piperidine alkaloid structure-activity relationships and their potential implications for human health. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. [Thalidomide teratogenicity and its direct target identification].

    Science.gov (United States)

    Ito, Takumi; Ando, Hideki; Handa, Hiroshi

    2015-01-01

    Half a century ago, thalidomide was developed as a sedative drug and was wildly used over 40 countries. However the drug has serious birth defects such as amelia and phocomelia. Now thalidomide is regarded as a clinically effective drug and used for the treatment of multiple myeloma under strict controls. The direct target of thalidomide had been a long-standing question. We identified cereblon as a primary direct target protein for thalidomide teratogenicity using new affinity bead technology in 2010. In this review, we introduce an overview of thalidomide teratogenicity, a story about how we identified cereblon, and recent advances in cereblon studies.

  3. Teratogenia da vitamina A Vitamin A teratogenicity

    Directory of Open Access Journals (Sweden)

    Maria Helena de Castro Chagas

    2003-09-01

    Full Text Available A vitamina A é essencial à preservação e ao funcionamento normal dos tecidos, assim como, ao crescimento e desenvolvimento. No humano há evidência indireta que a vitamina A em excesso, durante as primeiras semanas de gestação é teratogênica. Do contrário, não há dúvidas sobre os efeitos deletérios, de uma alimentação carente neste micronutriente e sobre a disponibilidade do conhecimento técnico para evitá-los. A preocupação com o fato de que a vitamina A conduziria a teratogenia em humanos, tem retardado a implementação de programas de combate a carência de vitamina A, atingindo principalmente os programas de enriquecimento de alimentos. A literatura é controvertida e dispõe de poucas informações sobre as doses para suplementação de gestantes. Como o retinol circulante materno é controlado homeostaticamente após o consumo de alimentos fonte de vitamina A, espera-se a mesma resposta metabólica após o consumo de alimentos fortificados, indicando que não há risco de teratogenia. Consequentemente, parece altamente improvável que o consumo de alimentos enriquecidos ou de suplementos de vitamina A pré-formada, nas doses unitárias habituais, tenha efeito teratogênico no homem.The vitamin A is essential to the preservation and the normal functioning of tissues, as well as, to the growth and development. In the human being it has indirect evidence that the vitamin A in excess, during the first weeks of gestation is teratogenic. Of the opposite, it does not have doubts on the deleterious effect, of a devoid feeding in this micronutrient and on the availability of the knowledge technician to prevent them. The concern with the fact of that the vitamin A would lead it the teratogenicity in human beings, has delayed the implementation of combat programs the vitamin A lack, mainly reaching the programs of food enrichment. Literature is controverted and makes use of few information on the doses for supplementation of

  4. Teratogenic effect of formaldehyde in rabbits

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    A. A. Al–Saraj

    2009-01-01

    Full Text Available Thirty three pregnant rabbits were exposed to vapour of 10% formaldehyde (12 ppm throughout the gestation period to know its effect on newborns. The results showed no abortion or foetal mortality but there were some anomalies (23.8% among the newborns rabbits which includes: meromelia (6.8%, encephalocele (6.1%, Oligodactyly (4.1%, Umbilical hernia (3.4% and Short tail (3.4%; besides that small for date and decrease in the body weight of the newborns were also noticed. These findings suggest that formaldehyde is a teratogenic agent.

  5. Propylthiouracil is teratogenic in murine embryos.

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    Valeria C Benavides

    Full Text Available 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.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.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 of malformed embryos. These data show that PTU exposure during embryogenesis is associated with delayed neural tube closure and cardiac abnormalities. In contrast, we did not observe structural or cardiac defects associated with MMI exposure except at the higher dose. We find that PTU exposure during embryogenesis is associated with fetal loss. These observations suggest that PTU has teratogenic potential.

  6. What Every Chemist Should Know About Teratogens--Chemicals that Cause Birth Defects.

    Science.gov (United States)

    Beyler, Roger E.; Meyers, Vera Kolb

    1982-01-01

    Teratogens are agents which act during pregnancy producing physical/functional defects in the embryo, fetus, or offspring. Discusses teratogenic hazards in the workplace and academic environment, classes of teratogenic compounds, precautions for interpreting Teratogen List from Registry of Toxic Effects of Chemical Substances (RTECS), and how…

  7. Identification of a primary target of thalidomide teratogenicity.

    Science.gov (United States)

    Ito, Takumi; Ando, Hideki; Suzuki, Takayuki; Ogura, Toshihiko; Hotta, Kentaro; Imamura, Yoshimasa; Yamaguchi, Yuki; Handa, Hiroshi

    2010-03-12

    Half a century ago, thalidomide was widely prescribed to pregnant women as a sedative but was found to be teratogenic, causing multiple birth defects. Today, thalidomide is still used in the treatment of leprosy and multiple myeloma, although how it causes limb malformation and other developmental defects is unknown. Here, we identified cereblon (CRBN) as a thalidomide-binding protein. CRBN forms an E3 ubiquitin ligase complex with damaged DNA binding protein 1 (DDB1) and Cul4A that is important for limb outgrowth and expression of the fibroblast growth factor Fgf8 in zebrafish and chicks. Thalidomide initiates its teratogenic effects by binding to CRBN and inhibiting the associated ubiquitin ligase activity. This study reveals a basis for thalidomide teratogenicity and may contribute to the development of new thalidomide derivatives without teratogenic activity.

  8. Teratogenicity and brain aromatase-induction of monosodium ...

    African Journals Online (AJOL)

    Teratogenicity and brain aromatase-induction of monosodium glutamate in estrogen-responsive mosaic transgenic zebra fish Danio rerio. Tamer Said Abdelkader, Chang Seo-Na, Kim Tae-Hyun, Song Juha, Kim Dongso, Jae-Hak Park ...

  9. Contraceptive Provision to Adolescent Females Prescribed Teratogenic Medications.

    Science.gov (United States)

    Stancil, Stephani L; Miller, Melissa; Briggs, Holley; Lynch, Daryl; Goggin, Kathy; Kearns, Gregory

    2016-01-01

    Rates of adult women receiving contraceptive provision when simultaneously prescribed a known teratogen are alarmingly low. The prevalence of this behavior among pediatric providers and their adolescent patients is unknown. The objective of this study was to describe pediatric provider behaviors for prescribing teratogens concurrently with counseling, referral, and/or prescribing of contraception (collectively called contraceptive provision) in the adolescent population. A retrospective review was conducted examining visits in 2008-2012 by adolescents aged 14 to 25 years in which a known teratogen (US Food and Drug Administration pregnancy risk category D or X) was prescribed. The electronic medical records were queried for demographic information, evidence of contraceptive provision, and menstrual and sexual histories. The data were analyzed using standard statistical methods. Within 4172 clinic visits, 1694 females received 4506 prescriptions for teratogenic medications. The most commonly prescribed teratogens were topiramate, methotrexate, diazepam, isotretinoin, and enalapril. The subspecialties prescribing teratogens most frequently were neurology, hematology-oncology, and dermatology. Overall, contraceptive provision was documented in 28.6% of the visits. Whites versus nonwhites and older versus younger girls were more likely to receive contraceptive provision. The presence of a federal risk mitigation system for the teratogen also increased the likelihood of contraceptive provision. Our data demonstrate female adolescents prescribed teratogens receive inadequate contraception provision, which could increase their risk for negative pregnancy outcomes. Although the presence of a federal risk mitigation system appears to improve contraceptive provision, these systems are costly and, in some instances, difficult to implement. Efforts to improve provider practices are needed. Copyright © 2016 by the American Academy of Pediatrics.

  10. A Review of the Teratogenic Factors Effect on Embryo

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    Manzarbanoo Shojaei fard

    2017-02-01

    Full Text Available Background & Objectives: Teratology is a branch of embryology science that studies causes, mechanisms and abnormal pattern development. Embryo growth traumatic factors during pregnancy are called teratogens that some teratogens pass the placental barrier and cause adverse effect during development stages and malformation, however a drug may improve general health of the mother, but it might be poisonous for embryo and cause diverse malformation. Since study of embryo health and risk factor in this stage is important, the aim of this review article was the investigation of some types of teratosgens (such as radiation, infectious agents, heat disorders, maternal conditions and particularly the effect of teratogenic drugs on embryo including some legal drugs (such as acetaminophen, thalidomide, acyclovir, sedatives and anticonvulsants and illegal drugs (such as nicotine, alcohol, cocaine and marijuana. Conclusion: In general, teratogens depending on the type and duration of exposure in pregnancyperiod, adversely affect embryo and cause various disorders. A better understanding of these teratogens can contribute to prevent these defects, since many other drugs with similar effects and lower teratogenicity can be used to improve mothers’ health.

  11. Teratogenicity of recently introduced medications in human pregnancy.

    Science.gov (United States)

    Lo, W Y; Friedman, J M

    2002-09-01

    To determine how long it takes after a new drug is marketed to establish whether or not its use by pregnant women is likely to pose a substantial teratogenic risk. We used standard clinical teratology resources to assess the teratogenic risks in human pregnancy of therapeutic treatment with 468 drugs approved by the US Food and Drug Administration between 1980 and 2000. The teratogenic risk of each treatment was classified using the current online version of TERIS into one of three categories: 1) no risk, minimal risk, or unlikely to produce an increased risk; 2) associated with a small, moderate, or high risk; or 3) risk undetermined. We found that the teratogenic risk in human pregnancy was still undetermined for 91.2% of drug treatments approved in the United States between 1980 and 2000. The proportion of treatments classified as having an "undetermined" teratogenic risk was more than 80% for drugs approved for marketing 0-4, 5-9, 10-14, or 15-20 years ago, but the highest proportion of drugs with an "undetermined" teratogenic risk was found among those approved 15-20 years ago. The agreement between TERIS risk ratings and Food and Drug Administration Use-in-Pregnancy Categories for 163 drugs that had been assessed by both systems was poor (kappa +/- standard error = 0.082 +/- 0.042). We conclude that inadequate information is available for pregnant women and their physicians to determine whether the benefits exceed the teratogenic risks for most drug treatments introduced in the past 20 years.

  12. Teratogenic effects of lead acetate on kidney

    International Nuclear Information System (INIS)

    Jabeen, R.; Tahir, M.; Waqas, S.

    2010-01-01

    Background: Lead remains a considerable occupational and public health problem, which is known to cause a number of adverse effects in both men and women. Conflicting reports have appeared on lead induced nephrotoxicity in experimental studies in the past. There is hardly any work on its teratogenic effects on kidney. Present study was therefore designed to investigate the effects of lead acetate on developing kidney. Methods: Twelve mice were used as experimental model and were divided into two groups of six animals each; group A served as control group and B was used as an experimental group. Lead acetate (10 mg/kg) dissolved in 0.02 ml of distilled water was administered as a single daily dose orally to group B whereas weight related amount of distilled water was given to group A for the entire period of experiment. On 18 day of gestation foetuses were dissected free of uterine wall under the dissecting microscope and were sacrificed; kidneys were removed and fixed in 10% formalin, dehydrated in ascending grades of alcohol, cleared in xylene and infiltrated with filtered paraffin. The paraffin blocks were made and five micron thin sections were obtained using a rotary microtome. The sections were stained with Hematoxylin and eosin and, PAS; these were examined under light microscope. Results: Significant decrease in cortical thickness was observed which varied from 578.6 +- 1.4 mu m in group A to 515.6 +- 5 mu m in group B (p<0.001). Diameter of renal corpuscles varied from 57.7 +- 0.07 mu m in group A to 50.5 +- 0.07 mu m in group B (p<0.001). Moderate cortical tubular atrophy showing thickening of endothelial basement membrane in glomeruli, desquamated epithelium with degenerated nuclei in proximal and distal tubules were observed in group B in contrast to group A. Conclusion: The results of the investigation indicated that lead acetate administration to the dams produced deleterious effects on the developing kidney in mice. (author)

  13. [Leflunomide: assessing teratogenic risk during the first trimester of pregnancy].

    Science.gov (United States)

    Casanova Sorní, C; Romá Sánchez, E; Pelufo Pellicer, A; Poveda Andrés, J L

    2005-01-01

    To assess the teratogenic risk associated with leflunomide during the first quarter of pregnancy, and to establish guidelines to minimize said risk. Literature search using tertiary, secondary, and primary sources related to teratogenicity, including databases (MEDLINE and EMBASE) and specific webs. The information required for assessment, as well as for the establishment of criteria was collected. Leflunomide demonstrated an increased risk of fetal death and teratogenic effects in animals. No major or minor malformation cases have been reported in humans regarding leflunomide, which is classified within category X of fetal risk. A wash-out regimen may possibly reduce the risk for fetal harm. Conception scheduling or early pregnancy detection is required for better clinical counselling and the avoidance of unnecessary risk.

  14. Medical databases in studies of drug teratogenicity: methodological issues

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    Vera Ehrenstein

    2010-03-01

    Full Text Available Vera Ehrenstein1, Henrik T Sørensen1, Leiv S Bakketeig1,2, Lars Pedersen11Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Norwegian Institute of Public Health, Oslo, NorwayAbstract: More than half of all pregnant women take prescription medications, raising concerns about fetal safety. Medical databases routinely collecting data from large populations are potentially valuable resources for cohort studies addressing teratogenicity of drugs. These include electronic medical records, administrative databases, population health registries, and teratogenicity information services. Medical databases allow estimation of prevalences of birth defects with enhanced precision, but systematic error remains a potentially serious problem. In this review, we first provide a brief description of types of North American and European medical databases suitable for studying teratogenicity of drugs and then discuss manifestation of systematic errors in teratogenicity studies based on such databases. Selection bias stems primarily from the inability to ascertain all reproductive outcomes. Information bias (misclassification may be caused by paucity of recorded clinical details or incomplete documentation of medication use. Confounding, particularly confounding by indication, can rarely be ruled out. Bias that either masks teratogenicity or creates false appearance thereof, may have adverse consequences for the health of the child and the mother. Biases should be quantified and their potential impact on the study results should be assessed. Both theory and software are available for such estimation. Provided that methodological problems are understood and effectively handled, computerized medical databases are a valuable source of data for studies of teratogenicity of drugs.Keywords: databases, birth defects, epidemiologic methods, pharmacoepidemiology

  15. Defense mechanisms against radiation induced teratogenic damage in mice

    International Nuclear Information System (INIS)

    Kato, F.; Ootsuyama, A.; Nomoto, S.; Norimura, T.

    2002-01-01

    Experimental studies with mice have established that fetuses at midgestational stage are highly susceptible to malformation at high, but not low, doses of radiation. When DNA damage is produced by a small amount of radiation, it is efficiently eliminated by DNA repair. However, DNA repair is not perfect. There must be defense mechanisms other than DNA repair. In order to elucidate the essential role of p53 gene in apoptotic tissue repair, we compared the incidence of radiation-induced malformations and deaths (deaths after day 10) in wild-type p53 (+/+) mice and null p53 (-/-) mice. For p53 (+/+) mice, an X-ray dose of 2 Gy given at a high dose-rate (450 mGy/min) to fetuses at 9.5 days of gestation was highly lethal and considerably teratogenic whereas it was only slightly lethal but highly teratogenic for p53 (-/-) fetuses. This reciprocal relationship of radiosensitivity to malformations and deaths supports the notion that fetal tissues have a p53 -dependent idguardianln of the tissue that aborts cells bearing radiation-induced teratogenic DNA damage. When an equal dose of 2 Gy given at a 400-fold lower dose-rate (1.2 mGy/min), this dose became not teratogenic for p53 (+/+) fetuses exhibiting p53 -dependent apoptosis, whereas this dose remained teratogenic for p53 (-/-) fetuses unable to carry out apoptosis. Furthermore, when the dose was divided into two equal dose fractions (1+1 Gy) at high dose rate, separated by 24 hours, the incidences of malformations were equal with control level for p53 (+/+), but higher for p53 (-/-) mice. Hence, complete elimination of teratogenic damage from irradiated tissues requires a concerted cooperation of two mechanisms; proficient DNA repair and p53-dependent apoptotic tissue repair

  16. A Study of the Teratogenicity of Butylated Hydroxyanisole on Rabbits

    DEFF Research Database (Denmark)

    Hansen, Ernst; Meyer, Otto A.

    1978-01-01

    A teratogenicity study on butylated hydroxyanisole (BHA) was carried out in SPF New Zealand White rabbits. BHA was given by gavage from day 7–18 of the gestation period in doses of 0, 50, 200 and 400 mg/kg body wt./day. The fetuses were removed on day 28. No effect related to the treatment with BHA...

  17. Teratogenic effect of the water extract of bitter gourd ( Momordica ...

    African Journals Online (AJOL)

    It also showed that 31.2% of all the malformed litters had multiple congenital malformations. It also showed that the experimental rats had nine resorption sites while control had none. This demonstrates that the water extract of Momordica charantia is teratogenic in Sprague Dawley rats and should be used with caution in ...

  18. Teratogenic effects of caffeine and clomipramine on rat fetus

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    Takzare N

    2012-09-01

    Full Text Available Background: Obsessive-compulsive disorders and depression have a high prevalence during pregnancy therefore, pregnant women may take clomipramine and also take other drugs or consume foods that contain caffeine. As investigations about the teratogenic effects of clomipramine and its concurrent administration with caffeine during organogenesis period are scarce, we aimed to study the teratogenicity of simultaneous administration of clomipramine and caffeine in rat fetus.Methods: After dividing 42 pregnant rats to several case and control groups, we injected different doses of caffeine and clomipramine to the animals. All the injections were performed on the eighth until the 15th day of pregnancy. We removed the fetuses on the 17th day of pregnancy and studied the morphological features and apparent anomalies of the fetuses macroscopically. Results: We found a significant rate of mortality, apparent anomalies, abnormal torsion, shrinkage of skin and subcutaneous bleeding in fetuses of rats receiving high doses of caffeine or a combination of caffeine and clomipramine. Statistical analysis of the data revealed a significant increase (P?0.001 in teratogenicity of high doses of caffeine and its combination with clomipramine. Conclusion: This study implies simultaneous intake of high amounts of caffeine and clomipramine lead to teratogenicity. We recommend pregnant women to avoid uncontrolled consumption of foods that contain caffeine or drugs that contain high amounts of this substance. They should not also take clomipramine with caffeine in the first trimester of pregnancy.

  19. Establishing the Embryonic Axes: Prime Time for Teratogenic Insults

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    Thomas W. Sadler

    2017-09-01

    Full Text Available A long standing axiom in the field of teratology states that the teratogenic period, when most birth defects are produced, occurs during the third to eighth weeks of development post-fertilization. Any insults prior to this time are thought to result in a slowing of embryonic growth from which the conceptus recovers or death of the embryo followed by spontaneous abortion. However, new insights into embryonic development during the first two weeks, including formation of the anterior-posterior, dorsal-ventral, and left-right axes, suggests that signaling pathways regulating these processes are prime targets for genetic and toxic insults. Establishment of the left-right (laterality axis is particularly sensitive to disruption at very early stages of development and these perturbations result in a wide variety of congenital malformations, especially heart defects. Thus, the time for teratogenic insults resulting in birth defects should be reset to include the first two weeks of development.

  20. Expert advice in case of exposure to mutagens or teratogens

    International Nuclear Information System (INIS)

    Steuber, E.D.

    1982-01-01

    To answer the question of any induced hazards in progeny by an exogeneous factor it is necessary to differentiate between mutagenic and teratogenic action. Mutations can be caused by ionisizing radiations and chemicals, e.g. cytostatic drugs. After exposure to mutagenic agents a conception should be prevented for a time of 3 months to avoid a fertilization of a germ cell that has been effected during a very sensible phase. In case of conception during mutagenic exposure it is possible to detect chromosome aberrations by prenatal diagnosis after amniocentesis. The spectrum of possible teratogens is extensive and less specific than that of mutagenic agents. Factors established as embryotoxic in man are for instance radiation, several drugs and some virus infections. They have been known to cause malformations in the fetus, if these events take place during a certain critical period of organogenesis. (orig.) [de

  1. The study of teratogenic effect of Cyclosporine in vitro

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    Ostad SN

    2001-07-01

    Full Text Available The use of immunosuppressive medication such as Azathioprine, methoterxate and mercaptopurine in treatment of rheumatic disease in women at childbearing age has some risks of teratogeniesis. Cyclosporine is one of the newer medicines, which has been introduced for this disease but little is known about its teratogenicity. This study was designed to investigate the possible teratogenicity of this drug by using cultured rat limb bud cells, which were obtained from rat embryos 13 days after conception. Cells were incubated in trypsin-EDTA solution for 30 min at 37°C and then filtered through 50 µm nylon filters. The resultant cell suspension was cultivated in 1 ml Dulbecco modified Eagle medium (DMEM containing 10% fetal bovine serum and 445 µg/L L-glutamine at 37°C with 5% CO2. After 8 days of culture the differentiated foci extract were measured by staining with 1% alcian blue. To assess the teratogenic effects of cyclosporine, it was placed in the culture well together with the cells. Results showed that the decrease in the expression of the extracellular matrix at dose of 0.01 molar of cyclosporine is due to limb bud cell toxicity rather than inhibition of cell differentiation.

  2. Teratogenic effect of yogurt in mice fetus (Mus musculus)

    OpenAIRE

    Dwisari Dillasamola; Almahdy A; Amirah Desri; Skunda Diliarosta

    2018-01-01

    Yogurt is one of the dairy products made from lactic acid fermentation by using Lactobacillus bulgaricus and Streptococcus thermophilus. A study on teratogenic effects of yogurt on the white female mice fetus (Mus musculus) has been carried out. Pregnant mice used were 20 which divided into 4 groups : the control group, D1, D2, and D3. The treatments giveThe mice were Distidelled water (control), 0.52 yogurt (D1), 1.04  yogurt (D2), and 2.08 g yogurt (D3). Data were analyzed using one-way ANO...

  3. Teratogens: a public health issue – a Brazilian overview

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    Thiago Mazzu-Nascimento

    2017-05-01

    Full Text Available Abstract Congenital anomalies are already the second cause of infant mortality in Brazil, as in many other middle-income countries in Latin America. Birth defects are a result of both genetic and environmental factors, but a multifactorial etiology has been more frequently observed. Here, we address the environmental causes of birth defects – or teratogens – as a public health issue and present their mechanisms of action, categories and their respective maternal-fetal deleterious effects. We also present a survey from 2008 to 2013 of Brazilian cases involving congenital anomalies (annual average of 20,205, fetal deaths (annual average of 1,530, infant hospitalizations (annual average of 82,452, number of deaths of hospitalized infants (annual average of 2,175, and the average cost of hospitalizations (annual cost of $7,758. Moreover, we report on Brazilian cases of teratogenesis due to the recent Zika virus infection, and to the use of misoprostol, thalidomide, alcohol and illicit drugs. Special attention has been given to the Zika virus infection, now proven to be responsible for the microcephaly outbreak in Brazil, with 8,039 cases under investigation (from October 2015 to June 2016. From those cases, 1,616 were confirmed and 324 deaths occurred due to microcephaly complications or alterations on the central nervous system. Congenital anomalies impact life quality and raise costs in specialized care, justifying the classification of teratogens as a public health issue.

  4. Teratogenic effect of yogurt in mice fetus (Mus musculus

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    Dwisari Dillasamola

    2018-04-01

    Full Text Available Yogurt is one of the dairy products made from lactic acid fermentation by using Lactobacillus bulgaricus and Streptococcus thermophilus. A study on teratogenic effects of yogurt on the white female mice fetus (Mus musculus has been carried out. Pregnant mice used were 20 which divided into 4 groups : the control group, D1, D2, and D3. The treatments giveThe mice were Distidelled water (control, 0.52 yogurt (D1, 1.04  yogurt (D2, and 2.08 g yogurt (D3. Data were analyzed using one-way ANOVA followed by Duncan multiple range test. Results showed that administration of yogurt during pregnancy could affect mother body weight of mice (P 0,05. Observations with Alizarin solution did not show skeletal defects in comparison to the control group. Observations with Bouin’s solution showed defective visceral cleft palate in fetal mice yogurt group D3. This study conclude that yogurt is safe to consume in groups D1 and D2. Yogurt has the potential to cause fetal teratogenic in group D3

  5. Teratogenic interactions between methylmercury and mitomycin-C in mice

    Energy Technology Data Exchange (ETDEWEB)

    Inouye, Minoru; Kajiwara, Yuji

    1988-01-01

    Pregnant mice were given p.o. various nonteratogenic doses (0, 2.5 and 10 mg/kg) of methylmercuric chloride on day 9 of pregnancy, and then injected i.p. with a teratogenic dose (4 mg/kg) of mitomycin-C on day 10. Major malformations produced by mitomycin-C alone were cervical rib and vertebral anomaly, polydactyly of the hindlimb and tail anomaly. Combined treatment significantly increased the incidence of these malformations, showing the dose-effect relationship of methylmercury, whereas methylmercury alone is known not to produce such malformations. When mitomycin-C treatment alone was performed on day 9.5 of pregnancy, only vertebral anomalies increased in incidence. Therefore, mitomycin-C teratogenicity in terms of the manifestation of cervical rib, polydactyly and tail anomaly, but not vertebral anomaly, was suggested to be enhanced by methylmercury. A considerable number of foetuses showed cleft palate involvement following combined treatments, but not by either chemical alone. Cleft palate is known to be a major malformation in mice that is caused by methylmercury, and mitomycin-C also induces cleft palate. Therefore, the two chemicals might have affected foetuses additively and thereby induced cleft palate. (orig.)

  6. Teratogenic effect of Californium-252 irradiation in rats

    International Nuclear Information System (INIS)

    Satow, Yukio; Lee, Juing-Yi; Hori, Hiroshi; Okuda, Hiroe; Tsuchimoto, Shigeo; Sawada, Shozo; Yokoro, Kenjiro

    1989-01-01

    The teratogenicity of Californium-252 (Cf-252) irradiation which generates approximately 70% 2.3 MeV fast neutron and 30% gamma rays was evaluated. A single whole body exposure of Cf-252 at various doses was given to pregnant rats on day 8 or 9 of pregnancy, followed by microscopic autopsy of the fetuses at the terminal stage of pregnancy to search for external and internal malformations. For comparison, pregnant rats were irradiated with various doses of Cobalt-60 (Co-60) standard gamma rays at the same dose rate (1 rad/min.). The doses were 20-120 rad of Cf-252 and 80-220 rad of Co-60. Using frequency of radiation induced malformations observed on day 8 of pregnancy as an index, relative biological effectiveness (RBE) of 2.3-2.7 was obtained from the straight line obtained by modifying by the least squares method the frequency curves of malformed fetuses in total implants and in surviving fetuses. The types of malformations induced by Cf-252 and Co-60 irradiation were alike. Using fetal LD 50 as an index, 2.4 was obtained as RBE when irradiated on day 8 of pregnancy and 3.1 as that when irradiated on day 9. The results showed that Cf-252 had stronger a teratogenic effect than Co-60 gamma rays. (author)

  7. Actions of piperidine alkaloid teratogens at fetal nicotinic acetylcholine receptors.

    Science.gov (United States)

    Green, Benedict T; Lee, Stephen T; Panter, Kip E; Welch, Kevin D; Cook, Daniel; Pfister, James A; Kem, William R

    2010-01-01

    Teratogenic alkaloids are found in many species of plants including Conium maculatum L., Nicotiana glauca, Nicotiana tabaccum, and multiple Lupinus spp. Fetal musculoskeletal defects produced by alkaloids from these plants include arthrogyropisis, scoliosis, torticollis, kyposis, lordosis, and cleft palate. A pharmacodynamic comparison of the alkaloids ammodendrine, anabasine, anabaseine, anagyrine, and coniine in SH-SY5Y cells and TE-671 cells was made. These alkaloids and their enantiomers were more effective in depolarizing TE-671 cells which express the human fetal-muscle type nicotinic acetylcholine receptor (nAChR) relative to SH-SY5Y cells which predominately express autonomic nAChRs. The rank order of potency in TE-671 cells was: anabaseine>(+)-anabasine>(-)-anabasine > (+/-)-anabasine>anagyrine>(-)-coniine > (+/-)-coniine>(+)-coniine>(+/-)-ammodendrine>(+)-ammodendrine. The rank order potency in SH-SY5Y cells was: anabaseine>(+)-anabasine>(-)-coniine>(+)-coniine>(+)-ammodendrine>anagyrine>(-)-anabasine>(+/-)-coniine>(+/-)-anabasine>(-)-ammodendrine. The actions of these alkaloids at nAChRs in both cell lines could be distinguished by their maximum effects in depolarizing cell membrane potential. The teratogenic action of these compounds may be related to their ability to activate and subsequently desensitize nAChRs.

  8. Teratogens: a public health issue – a Brazilian overview

    Science.gov (United States)

    Mazzu-Nascimento, Thiago; Melo, Débora Gusmão; Morbioli, Giorgio Gianini; Carrilho, Emanuel; Vianna, Fernanda Sales Luiz; da Silva, André Anjos; Schuler-Faccini, Lavinia

    2017-01-01

    Abstract Congenital anomalies are already the second cause of infant mortality in Brazil, as in many other middle-income countries in Latin America. Birth defects are a result of both genetic and environmental factors, but a multifactorial etiology has been more frequently observed. Here, we address the environmental causes of birth defects – or teratogens – as a public health issue and present their mechanisms of action, categories and their respective maternal-fetal deleterious effects. We also present a survey from 2008 to 2013 of Brazilian cases involving congenital anomalies (annual average of 20,205), fetal deaths (annual average of 1,530), infant hospitalizations (annual average of 82,452), number of deaths of hospitalized infants (annual average of 2,175), and the average cost of hospitalizations (annual cost of $7,758). Moreover, we report on Brazilian cases of teratogenesis due to the recent Zika virus infection, and to the use of misoprostol, thalidomide, alcohol and illicit drugs. Special attention has been given to the Zika virus infection, now proven to be responsible for the microcephaly outbreak in Brazil, with 8,039 cases under investigation (from October 2015 to June 2016). From those cases, 1,616 were confirmed and 324 deaths occurred due to microcephaly complications or alterations on the central nervous system. Congenital anomalies impact life quality and raise costs in specialized care, justifying the classification of teratogens as a public health issue. PMID:28534929

  9. Methylmercuric chloride toxicity: in vivo evaluation of teratogenicity

    Energy Technology Data Exchange (ETDEWEB)

    Curle, D.C.

    1985-01-01

    Mercury is a major environmental pollutant and a proven teratogen in man and animals. Its teratogenicity and effects on fetal chromosomes were investigated in mice. Various dose levels of methylmercuric chloride (MMC) 1000 ppm (5 mg through 30 mg/kg of body weight) were administered via an intragastric tube to pregnant ICR Swiss/Webster mice on day 9 of gestation. On day 18 of gestation the animals were killed and the fetuses removed. Fetal lung and liver section were processed for light microscopy, electron microscopy and cytogenetic studies. Mercury levels were determined in maternal blood and randomly selected fetuses. A significant increase in embryonic deaths and resorptions were observed at all dose levels. Light microscopy of fetal lungs from MMC treated animals were hypoplastic and retarded in development. The severity of pulmonary changes increased with the dose-level of MMC. Electron microscopy of fetal lung and liver showed degeneration of mitochondria. Vacuolation and lysis of mitochondria increased in severity with the dose-level of MMC. The frequency of sister chromatid exchangers (SCEs) increased significantly as the dosage increased. The frequency of nucleolus organizing regions (NORs) per cell did not change significantly between the treatment groups and the control. Clumping of chromosomes was prevalent and may be due to deactivation of the microtubular proteins following mercury binding.

  10. The acute toxicity and teratogenicity of nickel in pregnant rats

    International Nuclear Information System (INIS)

    Mas, A.; Holt, D.; Webb, M.

    1985-01-01

    The increased susceptibility of the pregnant rat to intraperitoneally administered nickel (Ni) is apparent at 12 and 19 days of pregnancy and cannot be due, therefore, to the increase in total body weight. Teratogenic malformations occur when Ni is administered during organogenesis and are maximal at dose levels that are toxic for the dam. The yolk sac and chorioallantoic placentas accumulate Ni, but this does not prevent the transport of the metal to the embryo or foetus. The Ni concentrations in the conceptuses decrease more slowly with time than those in the maternal organs. In the foetuses, the decrease in concentration is due to the increase in weight, since the content of Ni increases between 4 h and 24 h. Foetal uptake of ( 14 C)thymidine, ( 3 H)leucine and 65 Zn is unaffected at 3 h after the injection of the dam with 4 mg Ni/kg body wt. Incorporation of ( 3 H)leucine into foetal protein, but not the incorporation of ( 14 C)thymidine into DNA, is decreased at this time. A major effect of treatment with this teratogenic dose is an increase in the maternal plasma glucose concentration which, in turn, alters the supply of the sugar to the foetus. The possible relevance of temporary foetal hyperglycaemia to teratogenesis is discussed. (author)

  11. Drugs associated with teratogenic mechanisms. Part II : a literature review of the evidence on human risks

    NARCIS (Netherlands)

    van Gelder, Marleen M. H. J.; de Jong-van den Berg, Lolkje T. W.; Roeleveld, Nel

    What is the current state of knowledge on the human risks of drugs suspected to be associated with teratogenic mechanisms? Evidence for the presence or absence of human risks of birth defects is scarce or non-existent for the majority of drugs associated with teratogenic mechanisms. Medical drugs

  12. The teratogenicity of cadmium-metallothionein in the rat

    International Nuclear Information System (INIS)

    Webb, M.; Holt, D.; Brown, N.; Hard, G.C.

    1988-01-01

    A single dose in the range 0.25-1.9 mg metallothionein-bound cadmium (MT-Cd)/kg body weight, when administered parenterally to the rat between day 8 and day 14 of gestation, is teratogenic. In vitro, the development of the isolated rat conceptus is unaffected by the addition of 1.5 μM MT-Cd to the culture medium whereas the same concentration of ionic Cd (as CdCl 2 ) is lethal. At short times after injection of 0.25 mg MT-Cd/kg body weight on gd 12, the maximal foetal and placental contents of Cd are low in comparison with those after a teratogenic dose of CdCl 2 and are of the same order as those in the embryo and placenta + yolk sac of the rat conceptus, cultured in the presence of the highest no-effect concentration of CdCl 2 . From this evidence, it is concluded that the uptake by the conceptus in vivo of either CdMT, or of Cd liberated therefrom, is unlikely to contribute to the teratogenic response. In the pregnant, as in the non-pregnant rat, the kidney appears to be the only organ that is affected directly by the metalloprotein. All doses in the range 0.25-1.0 mg MT-Cd/kg body weight are nephrotoxic and result in prolonged anorexia in the pregnant animal. While some of the foetal deformities that occur in the CdMT-dosed animal seem to be direct consequences of the renal dysfunction, others apparently are secondary to the maternal anorexia. In rats that are injected i.p on gd 12 with 0.25 mg MT-Cd/kg renal uptake of Cd is slower, but the final concentration is higher than in animals that are given the same dose i.v. At this and the higher dose levels structural and/or functional damage to the kidneys also is greater in i.p.-, than in i.v.-dosed animals. The incidence of foetal malformations, however, is similar in the i.p. and i.v. groups and varies little over the dose range. (orig./MG)

  13. Teratogenicity of ionic cadmium in the Wistar rat

    Energy Technology Data Exchange (ETDEWEB)

    Holt, D.; Webb, M.

    1987-04-01

    In rats of the present (re-derived) Wistar-Porton strain that are dosed either intravenously (i.v.), or intraperitoneally (i.p.) with Cd (1.25 mg/kg body weight) on day 12 of gestation (gd 12), foetal uptake of Cd is at least 6-fold greater than that reported in an earlier study (Webb and Samarawickrama 1981). Higher doses (1.5 and 2.0 mg/kg body weight) are lethal to the maternal animal when administered i.v., but not if given ip. The foetotoxicity of i.p. injected Cd, however, increases with the dose over the range 1.25-2.0 mg Cd/kg body weight. The teratogenic response, which is also wider than that observed previously, is maximal after the injection of 1.25 mg Cd/kg body weight i.v. on gd 10 and i.p. on gd 12. Whilst the incidences of hydrocephalus, urogenital abnormalities, cleft palate and other less common defects are similar after dosing by both routes, the incidence, range and severity of skeletal malformations are greater after i.p. than after i.v. administration of Cd on gd 12. This difference in response is unlikely to be explained by a difference in either foetal, or placental uptake of the metallic ion since, at 4 h after i.p. dosing, the foetal concentration of Cd is not significantly different from that after i.v. injection, whilst the placental concentration is about 33% less. It is suggested that damage to the maternal liver, which is more severe after the i.v. injection of the optimum dose, may be an additional factor that, in conjunction with the inhibition of transport in the placenta and biosynthetic processes in the embryo/foetus, contributes to the teratogenic effects of Cd in the pregnant rat.

  14. Potentiating effects of caffeine on teratogenicity of alkylating agents in mice

    International Nuclear Information System (INIS)

    Fujii, T.; Nakatsuka, T.

    1983-01-01

    Teratogenic to subteratogenic doses of x-ray, mitomycin C, MNNG, thio-TEPA, cyclophosphamide, and chlorambucil were administered to pregnant ICR mice together with caffeine at doses of 12.5, 25, or 50 mg/kg on day 11 of gestation. Fetuses were examined for gross malformations on day 18 of gestation. The teratogenicity of mitomycin C was significantly potentiated by caffeine at a dose as low as 12.5 mg/kg. The teratogenicity of chlorambucil was also significantly potentiated by caffeine at 50 mg/kg, but similar potentiation was not observed for x-ray, MNNG, thio-TEPA, and cyclophosphamide

  15. Teratogenic effects in cattle of Conium maculatum and conium alkaloids and analogs.

    Science.gov (United States)

    Keeler, R F; Balls, L D

    1978-01-01

    The plant Conium maculatum produced congenital defects in calves born to cows gavaged the fresh green plant during days 50-75 of gestation. Both arthrogryposis and spinal curvature were produced and were similar to the defects produced by the piperidine alkaloid coniine. The arthrogrypotic manifestations of the condition markedly increased in severity as the animals aged. Animals gavaged dry plant had either normal or equivocally deformed offspring. A number of chain length and ring saturation analogs of coniine were not teratogenic. No congenital defects arose in offspring from maternal inhalation of either the teratogenic alkaloid coniine, or from the teratogenic green plant.

  16. TERATOGENIC EFFECTS OF DRUGS ON THE ORGANISM OF A FUTURE CHILD DURING FETAL STAGE OF DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    S.A. Sher

    2011-01-01

    Full Text Available Article assesses the impact of adverse factors on intrauterine development of the child, first of all, drugs. The author stresses that the importance of drug safety (D is due to the large number of unintended pregnancies worldwide. A list of the D, providing proven teratogenic effects on a child organism is presenting. It is shown that the D teratogenic effect in humans can not be assessed on the basis of experimental data obtained in animals due to the difference between metabolic and detoxification processes in a different mammals and individuals. Key words: drugs, safety, teratogenic effects, fetal development, the unborn child. (Pediatric pharmacology. — 2011; 8 (6: 57–60.

  17. Exposure to ionizing radiation during pregnancy: Perception of teratogenic risk and outcome

    International Nuclear Information System (INIS)

    Bentur, Y.; Horlatsch, N.; Koren, G.

    1991-01-01

    We quantified the perception of teratogenic risk in women attending the Motherisk program for counseling about diagnostic radiation in pregnancy (n = 50) and compared it with a control group of women exposed to nonteratogenic drugs and chemicals (n = 48). Before receiving known information about the specific exposure, women exposed to radiation assigned themselves a significantly higher teratogenic risk compared with the control group (25.5 +/- 4.3% versus 15.7 +/- 3.0% for major malformations, P less than 0.01). The post-consultation perception of teratogenic risk did not differ between the two groups. Special consideration and attention should be given when counseling pregnant women exposed to low-dose ionizing radiation, as their misperception of teratogenic risk may lead them to unnecessary termination of their pregnancy

  18. Mycophenolate mofetil embryopathy: A newly recognized teratogenic syndrome.

    Science.gov (United States)

    Perez-Aytes, Antonio; Marin-Reina, Purificacion; Boso, Virginia; Ledo, Ana; Carey, John C; Vento, Maximo

    2017-01-01

    Mycophenolate mofetil (MMF) is probably the most common employed immunosuppressant drug in recipients of solid organ transplant and in many autoimmune diseases. In vitro studies, a significant number of single clinical observations and a recent study from a group of different European teratogen information services, have provided very consistent data supporting the existence of a specific MMF embryopathy. The typical malformative pattern of MMF embryopathy includes external ear anomalies ranging from hypoplastic pinna (microtia) to complete absence of pinna (anotia); cleft lip, with or without cleft palate, and ocular anomalies as iris or chorioretinal coloboma and anophthalmia/microphthalmia. Other less frequent features are congenital heart defects, distal limbs anomalies, esophageal atresia, vertebral malformations, diaphragmatic hernia, and kidney and central nervous system anomalies. Neurodevelopmental outcome seems favorable in the small number of patients where information about this issue is available, but neurological deficits have been documented. Physicians in charge of women under MMF therapy should be aware of the potential risk of this drug to cause a specific embryopathy and the need of interrupting the treatment at least six weeks before becoming pregnant. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Predictive teratology: teratogenic risk-hazard identification partnered in the discovery process.

    Science.gov (United States)

    Augustine-Rauch, K A

    2008-11-01

    Unexpected teratogenicity is ranked as one of the most prevalent causes for toxicity-related attrition of drug candidates. Without proactive assessment, the liability tends to be identified relatively late in drug development, following significant investment in compound and engagement in pre clinical and clinical studies. When unexpected teratogenicity occurs in pre-clinical development, three principle questions arise: Can clinical trials that include women of child bearing populations be initiated? Will all compounds in this pharmacological class produce the same liability? Could this effect be related to the chemical structure resulting in undesirable off-target adverse effects? The first question is typically addressed at the time of the unexpected finding and involves considering the nature of the teratogenicity, whether or not maternal toxicity could have had a role in onset, human exposure margins and therapeutic indication. The latter two questions can be addressed proactively, earlier in the discovery process as drug target profiling and lead compound optimization is taking place. Such proactive approaches include thorough assessment of the literature for identification of potential liabilities and follow-up work that can be conducted on the level of target expression and functional characterization using molecular biology and developmental model systems. Developmental model systems can also be applied in the form of in vitro teratogenicity screens, and show potential for effective hazard identification or issue resolution on the level of characterizing teratogenic mechanism. This review discusses approaches that can be applied for proactive assessment of compounds for teratogenic liability.

  20. Teratogenic effects of retinoic acid on neurulation in mice embryos.

    Science.gov (United States)

    Nobakht, M; Zirak, A; Mehdizadeh, M; Tabatabaeei, P

    2006-02-21

    Retinoic acids (RA) are natural chemicals that exert a hormone-like activity and a variety of biological effects on early development of mouse. In this study, the probable teratogenic effects of RA on CNS have been investigated in pregnant mice (n = 20) divided into four groups: (1) untreated controls, (2) controls which received a single dose of DMSO, (3) a group that received 40 mg/kg, and (4) a group that received 60 mg/kg of all-trans RA in DMSO, respectively on the eighth day of gestation. Embryos whose dams had received 40 and 60 mg/kg doses of RA, showed malformations and decreased size. At 40 mg/kg dosage level, 50% of the embryos had closed neural tubes while at 60 mg/kg dosage level the neural tube failed to close. The neuroblast mantle layers were disorganized in the 40 mg/kg and even more in the 60 mg/kg exposed group compared to the controls. In mitosis, the density of chromatin was increased in the 60 mg/kg dose group. Compared to controls the 40 and 60 mg/kg dose groups of RA treated dams decreases in the luminal longitudinal and internal measures were observed. Also the thickness of ventricular, mantle and marginal layers was smaller. Wide intercellular spaces due to the degenerated cells at high doses of RA as well as an accumulation of intercellular fluid were observed. Therefore, the wedge shape of neuroepithelium was abolished, preventing the elevation of the neural wall.

  1. Dose-dependent pharmacokinetics and teratogenic activity of topical retinoids

    International Nuclear Information System (INIS)

    Sharma, R.P.; Willhite, C.C.; Berry, D.L.; Allen, P.V.

    1990-01-01

    Oral retinoid treatment can be teratogenic and topical applications are used to treat acne and smooth wrinkles. A single topical trace (2.5 μg; 191 μCi/kg) or high (1.3 mg; 195 μCi/kg) dose of all-trans-[10, 11- 3 H 2 ] retinoic acid (RA) dissolved in acetone was applied to 4 cm 2 shaved dorsal hamster skin. Peak plasma radioactivity (C max ) occurred at 12 and 36 hr and mean t1/2 values for parent PA absorption were 48 min and 2.8 hr, for trace and high dose, respectively. The dermal RA C max values were only 2% of that after an equivalent oral dose, but plasma AUC after dermal treatment was 63% of the oral value. The mean t1/2 for rapid elimination was shorter for the high (57 min) than for the trace (6.9 hr) dose, but t1/2 values for slow elimination were comparable (t1/2 high = 51.2 hr; t1/2 trace = 36.8 hr). Single topical application of 10-30 mg/kg RA or 5 mg/kg etretinate (Ro 10-9359) to pregnant hamsters (day 8) caused local hyperkeratosis, but failed to induce terata. Similar application of 10-1000 μg/kg arotinoid Ro 13-6298 caused dose-dependent terata, being twice as embryolethal by parenteral as enteric dosing. Skin toxicity and attenuated maternal blood levels limit the amount of retinoids that can reach the embryo

  2. Evaluation of developmental toxicity and teratogenicity of diclofenac using Xenopus embryos.

    Science.gov (United States)

    Chae, Jeong-Pil; Park, Mi Seon; Hwang, Yoo-Seok; Min, Byung-Hwa; Kim, Sang-Hyun; Lee, Hyun-Shik; Park, Mae-Ja

    2015-02-01

    Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) with analgesic and anti-pyretic properties. This compound is therefore used to treat pain, inflammatory disorders, and dysmenorrhea. Due to its multimodal mechanism of action and ability to penetrate placenta, diclofenac is known to have undesirable side effects including teratogenicity. However, limited data exist on its teratogenicity, and a detailed investigation regarding harmful effects of this drug during embryogenesis is warranted. Here, we analyzed the developmental toxic effects of diclofenac using Xenopus embryos according to the Frog Embryo Teratogenesis Assay-Xenopus (FETAX) protocol. Diclofenac treatment exerted a teratogenic effect on Xenopus embryos with a teratogenic index (TI) value of 2.64 TI; if this value is higher than 1.2, the cut-off value indicative of toxicity. In particular, mortality of embryos treated with diclofenac increased in a concentration-dependent manner and a broad spectrum of malformations such as shortening and kinking of the axis, abdominal bulging, and prominent blister formation, was observed. The shape and length of internal organs also differed compared to the control group embryos and show developmental retardation on histological label. However, the expression of major tissue-specific markers did not change when analyzed by reverse transcription-polymerase chain reaction (RT-PCR). In conclusion, diclofenac treatment can promote teratogenicity that results in morphological anomalies, but not disrupt the developmental tissue arrangement during Xenopus embryogenesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Teratogenicity of depleted uranium aerosols: A review from an epidemiological perspective

    Directory of Open Access Journals (Sweden)

    Panikkar Bindu

    2005-08-01

    Full Text Available Abstract Background Depleted uranium is being used increasingly often as a component of munitions in military conflicts. Military personnel, civilians and the DU munitions producers are being exposed to the DU aerosols that are generated. Methods We reviewed toxicological data on both natural and depleted uranium. We included peer reviewed studies and gray literature on birth malformations due to natural and depleted uranium. Our approach was to assess the "weight of evidence" with respect to teratogenicity of depleted uranium. Results Animal studies firmly support the possibility that DU is a teratogen. While the detailed pathways by which environmental DU can be internalized and reach reproductive cells are not yet fully elucidated, again, the evidence supports plausibility. To date, human epidemiological data include case examples, disease registry records, a case-control study and prospective longitudinal studies. Discussion The two most significant challenges to establishing a causal pathway between (human parental DU exposure and the birth of offspring with defects are: i distinguishing the role of DU from that of exposure to other potential teratogens; ii documentation on the individual level of extent of parental DU exposure. Studies that use biomarkers, none yet reported, can help address the latter challenge. Thoughtful triangulation of the results of multiple studies (epidemiological and other of DU teratogenicity contributes to disentangling the roles of various potentially teratogenic parental exposures. This paper is just such an endeavor. Conclusion In aggregate the human epidemiological evidence is consistent with increased risk of birth defects in offspring of persons exposed to DU.

  4. Dithiocarbamates are teratogenic to developing zebrafish through inhibition of lysyl oxidase activity

    International Nuclear Information System (INIS)

    Boxtel, Antonius L. van; Kamstra, Jorke H.; Fluitsma, Donna M.; Legler, Juliette

    2010-01-01

    Dithiocarbamates (DTCs) are a class of compounds that are extensively used in agriculture as pesticides. As such, humans and wildlife are undoubtedly exposed to these chemicals. Although DTCs are thought to be relatively safe due to their short half lives, it is well established that they are teratogenic to vertebrates, especially to fish. In zebrafish, these teratogenic effects are characterized by distorted notochord development and shortened anterior to posterior axis. DTCs are known copper (Cu) chelators but this does not fully explain the observed teratogenic effects. We show here that DTCs cause malformations in zebrafish that highly resemble teratogenic effects observed by direct inhibition of a group of cuproenzymes termed lysyl oxidases (LOX). Additionally, we demonstrate that partial knockdown of three LOX genes, lox, loxl1 and loxl5b, sensitizes the developing embryo to DTC exposure. Finally, we show that DTCs directly inhibit zebrafish LOX activity in an ex vivo amine oxidase assay. Taken together, these results provide the first evidence that DTC induced teratogenic effects are, at least in part, caused by direct inhibition of LOX activity.

  5. Teratogenicity and metabolism of water-soluble forms of vitamin A in the pregnant rat

    International Nuclear Information System (INIS)

    Gunning, D.B.; Barua, A.B.; Olson, J.A.

    1990-01-01

    Retinoyl β-glucuronide, unlike retinoic acid, has been shown to be non-teratogenic when administered orally, even in large doses, to pregnant rats. The degree to which water-solubility is associated with low teratogenicity is not known. Other water-soluble forms of vitamin A have now been synthesized in our laboratory and are being evaluated for teratogenicity. New water-soluble forms of vitamin A were administered orally to pregnant Sprague-Dawley rats in a single dose of 0.35 mmole/kg bw on day 8 of gestation. On day 19, the dams were sacrificed and the litters were examined. Control animals received either vehicle only or an equivalent dose of all-trans retinoic acid. Maternal and fetal tissues were taken and analyzed by HPLC for vitamin A metabolites. In another experiment, a large single oral dose of the radiolabelled water-soluble compound was administered on day 10. At either 30 minutes or 1 hour after the dose, dams were sacrificed and the embryos analyzed both for radioactivity and for specific metabolites. In contrast to retinoyl β-glucuronide, retinoyl β-glucose is highly teratogenic under identical conditions. Thus, water-solubility does not seem to be the determining factor in the teratogenicity of retinoic acid conjugates

  6. The Molecular Mechanisms of Thalidomide Teratogenicity and Implications for Modern Medicine.

    Science.gov (United States)

    Knobloch, J; Jungck, D; Koch, A

    2017-01-01

    Thalidomide is a teratogen that affects many organs but primarily induces limb truncations like phocomelia. Rodents are thalidomide resistant. In the 1950s, this has led to misinterpretations of animal tests and to the fatal assumption that the drug was safe for pregnant women to use against morning sickness. The result was one of the biggest scandals in medical history: 10.000 and more infants with birth defects in Europe. Nonetheless, thalidomide still has its place in modern medicine as it has strong therapeutic potential: it has been approved by the FDA for multiple myeloma and erythema nodosum leprosum, and its anti-inflammatory, immunomodulatory and antiangiogenic activities are considered in many other refractory diseases. The aim is to develop derivatives that are not teratogenic but maintain the therapeutic potential. This requires detailed knowledge about the underlying molecular mechanisms. Much progress has been made in deciphering the teratogenic mechanisms in the last decade. Here, we summarize these mechanisms, explain thalidomide resistance of rodents, and discuss possible mechanisms that could explain why the drug primarily targets the developing limb in the embryo. We also summarize the most important therapeutic mechanisms. Finally, we discuss which therapeutic and teratogenic mechanisms do and do not overlap, and if there is a chance for the development of non-teratogenic thalidomide derivatives with therapeutic potential. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. [Consumption of medications, alcohol and smoking in pregnancy and assessment of teratogenic risks].

    Science.gov (United States)

    Rocha, Rebeca Silveira; Bezerra, Samara Cavalcante; Lima, José Welington de Oliveira; Costa, Fabrício da Silva

    2013-06-01

    Medications, alcohol and smoking can cause fetal damage. A cross-sectional study was conducted with 326 mothers of the Fortaleza General Hospital to evaluate the use of drugs, alcohol and smoking during pregnancy and its relation to teratogenic potential in different population characteristics, between 2006 and 2007. Postpartum women who had their babies in the research site were included and those whose babies were not admitted as hospital inpatients were excluded. Chi-square tests and t-tests were used in the analysis, with a p value drugs/ pregnancy) and self-medication occurred in 11.3% of the cases. Single women took more drugs with high teratogenic potential (p=0.037). 11 cases of fetal malformation were observed, five of them were exposed to high teratogenic risks. Smoking occurred in 11.3% and alcohol use in 16%. Being single was found to be a risk factor for exposure to high teratogenic potential. Quality of prenatal care and other sociodemographic variables weren't related to exposure to teratogenic risks.

  8. Perception of teratogenic and foetotoxic risk by health professionals: a survey in Midi-Pyrenees area.

    Directory of Open Access Journals (Sweden)

    Damase-Michel C

    2008-03-01

    Full Text Available Counselling or prescribing drugs during pregnancy requires health professionals to assess risk/benefit ratio for women and their baby. A misperception of the risk may lead to inappropriate decisions for pregnancy outcomes. The aim of the present study was to assess teratogenic and/or foetotoxic risk perception of common medications by general practitioners (GPs and community pharmacists (CPs from the Midi-Pyrenees area.Methods: 103 GPs and 104 CPs were interviewed. For 21 given drugs, a visual-analogue scale was used to evaluate the risk to give birth to a malformed infant if the mother had taken the drug during first trimester of pregnancy. For 9 drugs, health professionals had to say if they thought there was a potential foetotoxic and/or neonatal risk when drugs were administered during late pregnancy.Results: 97% and 91% of GPs and CPs respectively thought that isotretinoin and thalidomide are teratogenic and more than 80% thought that amoxicillin and acetaminophen are safe in early pregnancy. However, 19% of the GPs and 33% of CPs answered there were no teratogenic risk for valproate. Around 11% of both GPs and CPs said that warfarin was safe during pregnancy. For 22% of GPs and for 13% and 27% of CPs respectively, ibuprofen and enalapril were safe on late pregnancy. For each drug, mean value of perceived teratogenic risk by health professionals was higher than values that can be found in scientific references. Concerning isotretinoin, thalidomide and metoclopramide, perceived teratogenic risk was higher for CPs.Conclusion: These data show that the potential teratogenic and foetotoxic risk of several commonly used drugs is unknown by health professionals. Conversely, GPs and CPs who think that a risk exists, overestimate it. This misperception can lead to inappropriate decisions for pregnancy outcomes.

  9. Strong lethality and teratogenicity of strobilurins on Xenopus tropicalis embryos: Basing on ten agricultural fungicides

    International Nuclear Information System (INIS)

    Li, Dan; Liu, Mengyun; Yang, Yongsheng; Shi, Huahong; Zhou, Junliang; He, Defu

    2016-01-01

    Agricultural chemical inputs have been considered as a risk factor for the global declines in amphibian populations, yet the application of agricultural fungicides has increased dramatically in recent years. Currently little is known about the potential toxicity of fungicides on the embryos of amphibians. We studied the effects of ten commonly used fungicides (four strobilurins, two SDHIs, two triazoles, fludioxonil and folpet) on Xenopus tropicalis embryos. Lethal and teratogenic effects were respectively examined after 48 h exposure. The median lethal concentrations (LC50s) and the median teratogenic concentrations (TC50s) were determined in line with actual exposure concentrations. These fungicides except two triazoles showed obvious lethal effects on embryos; however LC50s of four strobilurins were the lowest and in the range of 6.81–196.59 μg/L. Strobilurins, SDHIs and fludioxonil induced severe malformations in embryos. Among the ten fungicides, the lowest TC50s were observed for four strobilurins in the range of 0.61–84.13 μg/L. The teratogenicity shared similar dose–effect relationship and consistent phenotypes mainly including microcephaly, hypopigmentation, somite segmentation and narrow fins. The findings indicate that the developmental toxicity of currently-used fungicides involved with ecologic risks on amphibians. Especially strobilurins are highly toxic to amphibian embryos at μg/L level, which is close to environmentally relevant concentrations. - Highlights: • Effects of ten agricultural fungicides were tested on Xenopus tropicalis embryos. • Strobilurin fungicides showed strong lethal and teratogenic effects on embryos. • Lowest LC50 and TC50 were observed for strobilurins in ten fungicides. • μg/L level of toxic concentrations for strobilurins was environmentally relevant. • Teratogenicity shared similar dose–effect relationship and main phenotypes. - Strobilurins induced strong lethality and teratogenicity on Xenopus

  10. Drugs associated with teratogenic mechanisms. Part II: a literature review of the evidence on human risks

    NARCIS (Netherlands)

    Gelder, M.M.H.J. van; Jong-van den Berg, L.T. de; Roeleveld, N.

    2014-01-01

    STUDY QUESTION: What is the current state of knowledge on the human risks of drugs suspected to be associated with teratogenic mechanisms? SUMMARY ANSWER: Evidence for the presence or absence of human risks of birth defects is scarce or non-existent for the majority of drugs associated with

  11. Carcinogens, Teratogens and Mutagens: Their Impact on Occupational Health, Particularly for Women in Veterinary Medicine.

    Science.gov (United States)

    Milligan, J. E.; And Others

    1983-01-01

    Pregnant women, especially those working in veterinary medicine, face occupational health/disease risks from mutagens, teratogens, and carcinogens. These hazards can be placed into three categories: physical, chemical, and biological. Each of these hazards is discussed with examples. (Author/JN)

  12. Teratogenic risk and contraceptive counselling in psychiatric practice: analysis of anticonvulsant therapy

    Science.gov (United States)

    2013-01-01

    Background Anticonvulsants have been used to manage psychiatric conditions for over 50 years. It is recognised that some, particularly valproate, carbamazepine and lamotrigine, are human teratogens, while others including topiramate require further investigation. We aimed to appraise the documentation of this risk by psychiatrists and review discussion around contraceptive issues. Methods A retrospective review of prescribing patterns of four anticonvulsants (valproate, carbamazepine, lamotrigine and topiramate) in women of child bearing age was undertaken. Documented evidence of discussion surrounding teratogenicity and contraceptive issues was sought. Results Valproate was most commonly prescribed (n=67). Evidence of teratogenic risk counselling at medication initiation was sub-optimal – 40% of individuals prescribed carbamazepine and 22% of valproate. Documentation surrounding contraceptive issues was also low- 17% of individuals prescribed carbamazepine and 13% of valproate. Conclusion We found both low rates of teratogenic risk counselling and low rates of contraception advice in our cohort. Given the high rates of unplanned pregnancies combined with the relatively high risk of major congenital malformations, it is essential that a detailed appraisal of the risks and benefits associated with anticonvulsant medication occurs and is documented within patients’ psychiatric notes. PMID:24066860

  13. Genotoxic and teratogenic potential of marine sediment extracts investigated with comet assay and zebrafish test

    International Nuclear Information System (INIS)

    Kammann, Ulrike; Biselli, Scarlett; Huehnerfuss, Heinrich; Reineke, Ninja; Theobald, Norbert; Vobach, Michael; Wosniok, Werner

    2004-01-01

    Organic extracts of marine sediments from the North Sea and the Baltic Sea were investigated with two toxicity assays. The comet assay based on the fish cell line Epithelioma papulosum cyprini (EPC) was applied to determine the genotoxic potential; zebrafish embryos (Danio rerio) were used to quantify the teratogenic potential of the samples. EC 50 values were calculated from dose-response curves for both test systems. Highest teratogenic and genotoxic effects normalised to total organic carbon (TOC) content were detected in sediment samples of different origins. Polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) are not likely to be the causes of the observed effects, as demonstrated by a two-step fractionation procedure of selected extracts. The toxic potential was more pronounced in fractions having polarity higher than those possessed by PAHs and PCBs. The suitability of the two in vitro test systems for assessing genotoxic and teratogenic effects of marine sediment extracts could be demonstrated. - Capsule: In vitro toxicity assays are used to assess genotoxic and teratogenic effects of environmental extracts

  14. The unexpected teratogenicity of RXR antagonist UVI3003 via activation of PPARγ in Xenopus tropicalis

    International Nuclear Information System (INIS)

    Zhu, Jingmin; Janesick, Amanda; Wu, Lijiao; Hu, Lingling; Tang, Weiyi; Blumberg, Bruce; Shi, Huahong

    2017-01-01

    The RXR agonist (triphenyltin, TPT) and the RXR antagonist (UVI3003) both show teratogenicity and, unexpectedly, induce similar malformations in Xenopus tropicalis embryos. In the present study, we exposed X. tropicalis embryos to UVI3003 in seven specific developmental windows and identified changes in gene expression. We further measured the ability of UVI3003 to activate Xenopus RXRα (xRXRα) and PPARγ (xPPARγ) in vitro and in vivo. We found that UVI3003 activated xPPARγ either in Cos7 cells (in vitro) or Xenopus embryos (in vivo). UVI3003 did not significantly activate human or mouse PPARγ in vitro; therefore, the activation of Xenopus PPARγ by UVI3003 is novel. The ability of UVI3003 to activate xPPARγ explains why UVI3003 and TPT yield similar phenotypes in Xenopus embryos. Our results indicate that activating PPARγ leads to teratogenic effects in Xenopus embryos. More generally, we infer that chemicals known to specifically modulate mammalian nuclear hormone receptors cannot be assumed to have the same activity in non-mammalian species, such as Xenopus. Rather they must be tested for activity and specificity on receptors of the species in question to avoid making inappropriate conclusions. - Highlights: • UVI3003 is a RXRs antagonist and shows teratogenicity to Xenopus embryos. • UVI3003 activated xPPARγ either in Cos7 cells or Xenopus embryos. • UVI3003 did not activate human or mouse PPARγ in Cos7 cells. • Activating PPARγ leads to teratogenic effects in Xenopus embryos.

  15. Lupines, poison-hemlock and Nicotiana spp: toxicity and teratogenicity in livestock.

    Science.gov (United States)

    Panter, K E; James, L F; Gardner, D R

    1999-02-01

    Many species of lupines contain quinolizidine or piperidine alkaloids known to be toxic or teratogenic to livestock. Poison-hemlock (Conium maculatum) and Nicotiana spp. including N. tabacum and N. glauca contain toxic and teratogenic piperidine alkaloids. The toxic and teratogenic effects from these plant species have distinct similarities including maternal muscular weakness and ataxia and fetal contracture-type skeletal defects and cleft palate. It is believed that the mechanism of action of the piperidine and quinolizidine alkaloid-induced teratogenesis is the same; however, there are some differences in incidence, susceptible gestational periods, and severity between livestock species. Wildlife species have also been poisoned after eating poison-hemlock but no terata have been reported. The most widespread problem for livestock producers in recent times has been lupine-induced "crooked calf disease." Crooked calf disease is characterized as skeletal contracture-type malformations and occasional cleft palate in calves after maternal ingestion of lupines containing the quinolizidine alkaloid anagyrine during gestation days 40-100. Similar malformations have been induced in cattle and goats with lupines containing the piperidine alkaloids ammodendrine, N-methyl ammodendrine, and N-acetyl hystrine and in cattle, sheep, goats, and pigs with poison-hemlock containing predominantly coniine or gamma-coniceine and N. glauca containing anabasine. Toxic and teratogenic effects have been linked to structural aspects of these alkaloids, and the mechanism of action is believed to be associated with an alkaloid-induced inhibition of fetal movement during specific gestational periods. This review presents a historical perspective, description and distribution of lupines, poison-hemlock and Nicotiana spp., toxic and teratogenic effects and management information to reduce losses.

  16. Perception of drug teratogenicity among general practitioners and specialists in obstetrics/gynecology

    DEFF Research Database (Denmark)

    Gils, Charlotte; Pottegård, Anton; Ennis, Zandra Nymand

    2016-01-01

    the perception of the teratogenic risk of 9 commonly and 3 rarely prescribed drugs among general practitioners and specialists in obstetrics/gynecology. METHODS: All 811 general practitioners in the Region of Southern Denmark and all 502 specialist obstetricians/gynecologists in Denmark as a whole were invited...... to participate in the study based on an online questionnaire. Medians and interpercentile ranges of the perceived background risk and perceived risks for each of the drugs were included in the questionnaire. RESULTS: One hundred forty three (18 %) general practitioners and 138 (27 %) obstetricians...... by a dermatologist, and warfarin treatment is only rarely initiated in women of the fertile age without involvement of specialists in internal medicine. Hence, the active knowledge on the teratogenic potential of these drugs is likely to be less accurate among general practitioners and obstetricians...

  17. Teratogenic and embryolethal effects in mice of fission-spectrum neutrons and γ-rays

    International Nuclear Information System (INIS)

    Cairnie, A.B.; Grahn, D.; Rayburn, H.B.; Williamson, F.S.; Brown, R.J.

    1974-01-01

    Fission-spectrum neutrons from the Janus reactor at Argonne National Laboratory were compared with γ-rays in terms of their relative biological effectiveness (RBE) for embryolethal and teratogenic effects in mice. No evidence was found of any processes that were abnormally sensitive to neutrons. The RBE for killing embryos and producing abnormal embryos or specific abnormalities was between 2 and 3. This is close to the values found in other systems for processes involving cell killing. (U.S.)

  18. Discriminative power of an assay for automated in vitro screening of teratogens

    DEFF Research Database (Denmark)

    Walmod, Peter S; Gravemann, Ute; Nau, Heinz

    2004-01-01

    -trans-retinoic acid, pentyl-4-yn-valproic acid, saccharin, salicylic acid and valproic acid. All compounds, with the exception of dimethadione inhibited proliferation in a linear dose-dependent manner, and there were statistically significant compound class-dependent differences between the IC(50)-values...... to teratogenicity were: 5-bromo-2(')-deoxyuridine, 6-aminonicotinamide, acrylamide, boric acid, D-(+)-camphor, dimethadione, dimethyl phthalate, diphenhydramine, hydroxyurea, isobutyl-ethyl-valproic acid, lithium chloride, methyl mercury chloride, methotrexate, methoxyacetic acid, penicillin G, all...

  19. Deprenyl Enhances the Teratogenicity of Hydroxyurea in Organogenesis Stage Mouse Embryos

    Science.gov (United States)

    Schlisser, Ava E.; Hales, Barbara F.

    2013-01-01

    Hydroxyurea, an antineoplastic drug, is a model teratogen. The administration of hydroxyurea to CD1 mice on gestation day 9 induces oxidative stress, increasing the formation of 4-hydroxy-2-nonenal adducts to redox-sensitive proteins such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the caudal region of the embryo. GAPDH catalytic activity is reduced, and its translocation into the nucleus is increased. Because the nuclear translocation of GAPDH is associated with oxidative stress–induced cell death, we hypothesized that this translocation plays a role in mediating the teratogenicity of hydroxyurea. Deprenyl (also known as selegiline), a drug used as a neuroprotectant in Parkinson’s disease, inhibits the nuclear translocation of GAPDH. Hence, timed pregnant CD1 mice were treated with deprenyl (10mg/kg) on gestation day 9 followed by the administration of hydroxyurea (400 or 600mg/kg). Deprenyl treatment significantly decreased the hydroxyurea-induced nuclear translocation of GAPDH in the caudal lumbosacral somites. Deprenyl enhanced hydroxyurea-mediated caudal malformations, inducing specifically limb reduction, digit anomalies, tail defects, and lumbosacral vertebral abnormalities. Deprenyl did not augment the hydroxyurea-induced inhibition of glycolysis or alter the ratio of oxidized to reduced glutathione. However, it did dramatically increase cleaved caspase-3 in embryos. These data suggest that nuclear GAPDH plays an important, region-specific, role in teratogen-exposed embryos. Deprenyl exacerbated the developmental outcome of hydroxyurea exposure by a mechanism that is independent of oxidative stress. Although the administration of deprenyl alone did not affect pregnancy outcome, this drug may have adverse consequences when combined with exposures that increase the risk of malformations. PMID:23696560

  20. Teratogenic effect of calcium edetate (CaEDTA) in rats and the protective effect of zinc.

    Science.gov (United States)

    Brownie, C F; Brownie, C; Noden, D; Krook, L; Haluska, M; Aronson, A L

    1986-03-15

    The calcium chelate of EDTA (CaEDTA) currently is the drug of choice in the treatment of lead intoxication. This study investigated the teratogenic potential of CaEDTA, administered parenterally during periods of organogenesis and determined if incorporating zinc into EDTA would protect against teratogenic effects. Four doses (2, 4, 6, and 8 mmol/m2/day) of CaEDTA, two concentrations (8 and 20 mmol/m2/day) of ZnEDTA and ZnCaEDTA (molar ratio 0.5:0.5:1) were used, and a saline control (0.9% NaCl). Timed-pregnant Long-Evans rats were assigned at random to the treatment groups, 20 per dose for each chelate and 30 to the saline control. Rats were injected with the chelate or saline solution sc, twice daily during the 11th through 15th days of gestation. Pups removed by cesarean section on the 21st day were processed for osseous and visceral examination. Additional animals per treatment group were used for maternal plasma and liver and fetal zinc determinations. Results showed increases in several abnormalities (submucous cleft, cleft palate, adactyly-syndactyly, curly tail, abnormal rib and vertebrae) with increasing amounts of CaEDTA. No malformations were seen with ZnEDTA at either dose or with ZnCaEDTA at 8 mmol/m2/day. However, submucous cleft was seen in 6 of 20 litters from the dams receiving the higher dose of ZnCaEDTA. It was concluded that CaEDTA is teratogenic in rats at concentrations which, except for decreased weight gain, produce no discernible toxicity to the dam, and which are comparable to the recommended therapeutic dosage in humans (1500 mg/m2/day corresponding to 4 mmol/m2/day). Protection is afforded by incorporating zinc in the chelate.

  1. A glyphosate micro-emulsion formulation displays teratogenicity in Xenopus laevis.

    Science.gov (United States)

    Bonfanti, Patrizia; Saibene, M; Bacchetta, R; Mantecca, P; Colombo, A

    2018-02-01

    Glyphosate is the active ingredient in broad-spectrum herbicide formulations used in agriculture, domestic area and aquatic weed control worldwide. Its market is growing steadily concurrently with the cultivation of glyphosate-tolerant transgenic crops and emergence of weeds less sensitive to glyphosate. Ephemeral and lentic waters near to agricultural lands, representing favorite habitats for amphibian reproduction and early life-stage development, may thus be contaminated by glyphosate based herbicides (GBHs) residues. Previous studies on larval anuran species highlighted increased mortality and growth effects after exposure to different GBHs in comparison to glyphosate itself, mainly because of the surfactants such as polyethoxylated tallow amine present in the formulations. Nevertheless, these conclusions are not completely fulfilled when the early development, characterized by primary organogenesis events, is considered. In this study, we compare the embryotoxicity of Roundup ® Power 2.0, a new GBH formulation currently authorized in Italy, with that of technical grade glyphosate using the Frog Embryo Teratogenesis Assay-Xenopus (FETAX). Our results evidenced that glyphosate was not embryolethal and only at the highest concentration (50 mg a.e./L) caused edemas. Conversely, Roundup ® Power 2.0 exhibited a 96 h LC50 of 24.78 mg a.e./L and a 96 h EC50 of 7.8 mg a.e./L. A Teratogenic Index of 3.4 was derived, pointing out the high teratogenic potential of the Roundup ® Power 2.0. Specific concentration-dependent abnormal phenotypes, such as craniofacial alterations, microphthalmia, narrow eyes and forebrain regionalization defects were evidenced by gross malformation screening and histopathological analysis. These phenotypes are coherent with those evidenced in Xenopus laevis embryos injected with glyphosate, allowing us to hypothesize that the teratogenicity observed for Roundup ® Power 2.0 may be related to the improved efficacy in delivering

  2. Cell motility is inhibited by the antiepileptic compound, valproic acid and its teratogenic analogues

    DEFF Research Database (Denmark)

    Walmod, P S; Foley, A; Berezin, A

    1998-01-01

    -term recordings and measurements of mean-cell speed, the reduction in the motile behaviour was shown to correlate with the teratogenic potency of the tested compounds. The observed effects of VPA on cell motility was independent of the employed L-cell clone, and could be reproduced in cells containing...... the neuronal marker NCAM and in the neuronal cell line N2a. Furthermore, the observed effect was independent of culture substratum, being observed for L-cells grown on fibronectin as well as on plastic. Immunofluorescence microscopy revealed that VPA-treatment of mouse L-cells caused a redistribution of F...

  3. Teratogenic effects and monetary cost of selenium poisoning of fish in Lake Sutton, North Carolina

    Science.gov (United States)

    A. Dennis Lemly

    2014-01-01

    Selenium pollution from coal ash waste water was investigated in Lake Sutton, NC. This lake has been continuously used as a cooling pond for a coal-fired power plant since 1972. Historic and recent levels of contamination in fish tissues (14–105 µg Se/g dry weight in liver, 24–127 in eggs, 4–23 in muscle,7–38 in whole-body) exceeded toxic thresholds and teratogenic...

  4. Physicians' Perception of Teratogenic Risk and Confidence in Prescribing Drugs in Pregnancy-Influence of Norwegian Drug Information Centers.

    Science.gov (United States)

    Bakkebø, Tina; Widnes, Sofia Frost; Aamlid, Synnøve Stubmo; Schjøtt, Jan

    2016-05-01

    Clinical decision support provided by drug information centers is an intervention that can ensure rational drug therapy for pregnant women. We have examined whether physicians' teratogenic risk perceptions and confidence in prescribing drugs to pregnant women is altered after advice from the Norwegian drug information centers, Regional Medicines and Pharmacovigilance Centres i Norway (RELIS). Physicians who consulted RELIS for advice on patient-specific drug use in pregnancy from November 2013 to April 2014 completed questionnaires before and after receiving the advice. A scale from 1 to 7 was used to rate confidence in prescribing and perception of teratogenic risk. The lower part of the scale represented a low perception of teratogenic risk and a high confidence in prescribing a drug in pregnancy. The data were analyzed using a mixed linear model. A total of 45 physicians participated in the study and they assessed 64 drugs or categories of drugs. Advice from RELIS increased confidence in prescribing, with a statistically significant mean change on the scale from 4.1 to 2.9. The assessment of teratogenic risk was reduced after advice from RELIS, with a mean change from 3.2 to 2.5, though this was not significant. A subgroup of 26 physicians completed questionnaires both before and after advice from RELIS and assessed a total of 32 drugs or categories of drugs. In 94% of these assessments, advice from RELIS altered the physician's confidence in prescribing. Perception of teratogenic risk was altered in 78% of the assessments. Our results show that physicians' perception of teratogenic risk and confidence in prescribing drugs to pregnant women is influenced by advice from Norwegian drug information centers. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  5. Safety of antimicrobial treatment during pregnancy: a current review of resistance, immunomodulation and teratogenicity.

    Science.gov (United States)

    Lamont, Harriet F; Blogg, Henrietta J; Lamont, Ronald F

    2014-12-01

    The extent of antibiotic use in pregnancy remains unknown but may occur in > 40% of pregnant women for various indications, at different gestational ages from different sources. Antibiotic resistance, alterations to the neonatal immune system causing allergy, asthma and atopic disease in later life and teratogenicity. Although teratogenesis is not a major concern, it is important, and ignorance and complacency cast a long shadow. Robust evidence exists to guide clinicians in their choice of a safe agent with respect to teratogenicity. Antibiotic resistance is a major safety concern, and together with decreased research and development of new antibiotic agents, it has required legal initiatives to encourage Big Pharma to search for safe alternatives. New information from culture-independent, molecular-based techniques has resulted in a greater understanding of the adverse effects of antepartum/intrapartum antibiotics on the maternal vaginal microbiome and the neonatal gut microbiome. As this might adversely affect the development of the immature immune system and lead to asthma, allergy and atopic disease in later life, new research merits support in scrutinizing the safety of antibiotic use in pregnancy.

  6. The Teratogenic Effects of Dichlorvos on the Development of Chick Embryos

    Directory of Open Access Journals (Sweden)

    Jantima Roongruangchai, D.D.S., Ph.D.

    2018-01-01

    Full Text Available Objective: The purpose of this study was to elucidate the teratogenic effects of dichlorvos on developing chick embryos. Methods: The fertilized Leghorn hen eggs were divided into two groups: the experimental group which was injected with 0.1 ml of 0.5% and 1% dichlorvos in normal saline and the control group which was injected with 0.1 ml of normal saline after 21 h of incubation. On day 3, 6, and 11, the embryos were collected for studying embryonic dead and abnormalities. Results: The results showed that the mortality rate increased with the increasing concentration of dichlorvos and time of incubation. The total mount of day 3 had only three primary brain vesicles, small and retarded primordial eye, dilated U-shaped heart looping, bifurcation of spinal cord and trunk when compared with the control. The results in the serial section of day 3 and 6 showed several abnormalities especially the retardation of eye and heart. Day 11 embryo revealed morphological anomalies including hematoma and bone deformation. Conclusion: Dichlorvos caused congenital abnormalities in chick embryos in 3 categories, the growth retardation, the malformations and the embryonic death which were predicted to cause the same results in contaminated humans. Dichlorvos exposure increases the risk of malformations and embryonic death. The present study revealed that dichlorvos was a powerful teratogenic compound and therefore its use should be limited and pregnant women should avoid contamination with dichlorvos especially in the first trimester.

  7. Effects of Multivitamins and Known Teratogens on Chick Cardiomyocytes Micromass Culture Assay

    Directory of Open Access Journals (Sweden)

    Samreen Memon

    2013-09-01

    Full Text Available   Objective(s: This study aimed to find out whether the chick cardiomyocyte micromass (MM system could be employed to predict the teratogenecity of common environmental factors. Different multivitamins and over the counter drugs were used in this study.   Materials and Methods: White Leghorn 5-day-old embryo hearts were dissected and trypsinized to produce a cardiomyocyte cell suspension in Dulbecco's Modified Eagle's Medium. The cultures were incubated at 370C in 5% CO2 in air, and observations were made at 24, 48 and 144 hr, for the detection of cell beating. Cellular viability was assessed using the resazurin assay and cell protein content was assessed by the kenacid blue assay. It was observed that while not affecting total cell number folic acid, vitamin C, sodium fluoride and ginseng did not significantly reduced cell activity and beating. However cadmium chloride significantly reduced the beating, cell viability and cell protein content in micromass cultures. Results: The results demonstrate the potential of the chick cardiomyocyte MM culture assay to identify teratogens/embryotoxins that alter morphology and function, which may result in either teratogenic outcome or cytotoxicity. Conclusion: This could form part of a screen for developmental toxicity related to cardiac function

  8. Developmental effects of magnetic field (50 Hz) in combination with ionizing radiation and chemical teratogens.

    Science.gov (United States)

    Pafková, H; Jerábek, J; Tejnorová, I; Bednár, V

    1996-11-01

    The influence of a 50 Hz magnetic field (MF) on avian and mammalian embryogenesis, the MF level and vector, as well as the effect of exposure to MF (50 Hz, 10 mT) in combination with X-rays has been recently reported [2,3]. No significant alterations of chick or rat embryogenesis were found after repeated exposures to 50 Hz MF at 10 mT or 6 microT or with different vectors. However, X-ray chick embryotoxicity was significantly affected by repeated exposures of developing organisms to MF. A strong dependence of effect on the type of interaction was revealed. A decrease of X-ray induced teratogenicity was observed when MF preceded X-ray exposure (indirect interaction), while MF exposure applied immediately after X-ray radiation (direct interaction) non-significantly potentiated adverse developmental effects of ionizing radiation. This study deals with the effects of MF in combination with insulin or tetracycline. Exposure of chick embryos to MF influenced the sensitivity of embryonic morphogenetic systems to the subsequently administered chemical teratogens, insulin and/or tetracycline. A protective effect of MF was detected similarly as in the case of indirect interaction with ionizing radiation.

  9. Brown coal derived humate inhibits contact hypersensitivity; An efficacy, toxicity and teratogenicity study in rats

    Energy Technology Data Exchange (ETDEWEB)

    Van Rensburg, C.E.J.; Snyman, J.R.; Mokoele, T.; Cromarty, A.D. [University of Pretoria, Pretoria (South Africa). Faculty of Health Science

    2007-10-15

    The effects of two humate products were compared to that of prednisolone on a contact hypersensitivity rat model. Rats, sensitized with dinitrofluorobenzene (DNFB), were placed on a daily oral treatment of 61 mg/kg BW of humate derived from either leonardite or bituminous coal or on prednisolone at one mg/kg BW and challenged 6 days later with a topical application of DNFB to the right ear. The inflamed ears were measured daily. In a toxicity study rats were exposed to daily oral treatment of leonardite humate at 1,000 mg/kg BW for 1 month. A teratogenicity study was done where pregnant rats were treated with 500 mg/kg BW on days 5 to 17 of pregnancy. Only the leonardite humate compared favourably with prednisolone in suppressing contact hypersensitivity. No signs of toxicity were observed and weight gain was normal during the 6-day and 1 month treatments and during the teratogenicity study with the leonardite humate. However, the rats on the other two products experienced slower weight gain. The identification of a naturally occurring nontoxic compound with anti-inflammatory activity is exciting and merits further evaluation in the treatment of patients suffering from inflammatory conditions.

  10. Acute embryo toxicity and teratogenicity of three potential biofuels also used as flavor or solvent

    Energy Technology Data Exchange (ETDEWEB)

    Bluhm, Kerstin; Seiler, Thomas-Benjamin [RWTH Aachen University, Institute for Environmental Research, Worringerweg 1, 52074 Aachen (Germany); Anders, Nico [RWTH Aachen University, Aachener Verfahrenstechnik — Enzyme Process Technology, Worringerweg 1, 52074 Aachen (Germany); Klankermayer, Jürgen [RWTH Aachen University, Institut für Technische und Makromolekulare Chemie, Worringerweg 1, 52074 Aachen (Germany); Schaeffer, Andreas [RWTH Aachen University, Institute for Environmental Research, Worringerweg 1, 52074 Aachen (Germany); Chongqing University, College of Resources and Environmental Science, Chongqing 400715 (China); Nanjing University, State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing 210093 (China); Hollert, Henner, E-mail: Henner.Hollert@bio5.rwth-aachen.de [RWTH Aachen University, Institute for Environmental Research, Worringerweg 1, 52074 Aachen (Germany); Chongqing University, College of Resources and Environmental Science, Chongqing 400715 (China); Nanjing University, State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing 210093 (China); Tongji University, College of Environmental Science and Engineering and State Key Laboratory of Pollution Control and Resource Reuse, Shanghai 200092 (China)

    2016-10-01

    The demand for biofuels increases due to concerns regarding greenhouse gas emissions and depletion of fossil oil reserves. Many substances identified as potential biofuels are solvents or already used as flavors or fragrances. Although humans and the environment may be readily exposed little is known regarding their (eco)toxicological effects. In this study, the three potential biofuels ethyl levulinate (EL), 2-methyltetrahydrofuran (2-MTHF) and 2-methylfuran (2-MF) were investigated for their acute embryo toxicity and teratogenicity using the fish embryo toxicity (FET) test to identify unknown hazard potentials and to allow focusing further research on substances with low toxic potentials. In addition, two fossil fuels (diesel and gasoline) and an established biofuel (rapeseed oil methyl ester) were investigated as references. The FET test is widely accepted and used in (eco)toxicology. It was performed using the zebrafish Danio rerio, a model organism useful for the prediction of human teratogenicity. Testing revealed a higher acute toxicity for EL (LC{sub 50}: 83 mg/L) compared to 2-MTHF (LC{sub 50}: 2980 mg/L), 2-MF (LC{sub 50}: 405 mg/L) and water accommodated fractions of the reference fuels including gasoline (LC{sub 50}: 244 mg DOC/L). In addition, EL caused a statistically significant effect on head development resulting in elevated head lengths in zebrafish embryos. Results for EL reduce its likelihood of use as a biofuel since other substances with a lower toxic potential are available. The FET test applied at an early stage of development might be a useful tool to avoid further time and money requiring steps regarding research on unfavorable biofuels. - Highlights: • The demand for biofuels increases but their (eco)toxicological effects are unknown. • Acute fish embryo toxicity and teratogenicity of potential biofuels were evaluated. • Ethyl levulinate induced a higher acute toxicity compared to WAFs of gasoline. • Ethyl levulinate caused

  11. Chemical and HTS Profiling of 63 Cleft Palate Teratogens from ToxCast (FutureTox III)

    Science.gov (United States)

    Cleft palate is a common human birth defect that has been linked to both genetic and environmental factors. To characterize the potential molecular targets and biological processes across mechanistically diverse teratogens that cause cleft palate, we mined the ToxCast high-throug...

  12. The teratogenic effects of low dose 60Co γ-rays on the early pregnant rats

    International Nuclear Information System (INIS)

    Lu Chunlin

    1991-01-01

    The pregnant Wistar rats were exposed to 0.5 Gy and 1.0 Gy 60 Co γ-rays at the 9th day after conception. The results: 60 Co γ-rays at dose of 1.0 Gy could induced many defects: excenphaly, hydrocephalus, gastroschisis, cleft palate and cleft lip, anophthalmia, microphthalmia, shorten tail and absent tail in surviving fetuses. The growth retardation was found from the parameters of fetal weight, height, head circle and development of skeleton. In the group of radiation dose 0.5 Gy, only hydrocephalus, absent tail and growth retardation of skeleton appeared. The results suggest that low-dose exposure in the early pregnant rats can induce fetal defects and growth retardation. The probable mechanism of teratogen and growth retardation was discussed. The cAMP levels of brain and liver of rat fetuses were reported

  13. Evaluation on biosafety in long-term administration, teratogenicity and local toxicity of developed product

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung-Ho; Kim, Jong-Chun; Kim, Se-Ra; Lee, Hae-Jun; Lee, Jin-Hee [Chonnam Nat. Univ., Gwangju (Korea, Republic of)

    2006-01-15

    We performed this study to determine biosafety of developed product in long-term administration and teratogenicity and local toxicity (skin and eye) of developed product (HemoHIM and HemoTonic). It is suggested that long-term administration with the developed products may not exert considerable side effects. It is concluded that the administration of HemoHIM or HemoTonic does not inflict any adverse effect on fetuses of pregnant mice. HemoHIM and HemoTonic could be considered as a no irritating materials to the skin and eye of the test animals. These results indicated that HemoHIM and HemoTonic might be a useful functional food, especially since it is a relatively nontoxic natural product.

  14. Evaluation on biosafety in long-term administration, teratogenicity and local toxicity of developed product

    International Nuclear Information System (INIS)

    Kim, Sung-Ho; Kim, Jong-Chun; Kim, Se-Ra; Lee, Hae-Jun; Lee, Jin-Hee

    2006-01-01

    We performed this study to determine biosafety of developed product in long-term administration and teratogenicity and local toxicity (skin and eye) of developed product (HemoHIM and HemoTonic). It is suggested that long-term administration with the developed products may not exert considerable side effects. It is concluded that the administration of HemoHIM or HemoTonic does not inflict any adverse effect on fetuses of pregnant mice. HemoHIM and HemoTonic could be considered as a no irritating materials to the skin and eye of the test animals. These results indicated that HemoHIM and HemoTonic might be a useful functional food, especially since it is a relatively nontoxic natural product

  15. The Teratogenic Effects of Antiepileptic Drug, Topiramate, on the Development of Chick Embryos

    Directory of Open Access Journals (Sweden)

    Jantima Roongruangchai

    2017-05-01

    Full Text Available Background: Anti-epileptic drugs are known to be the risk of teratogenicity. Topiramate (TPM is a new kind of such drug, for which no research has confirmed the incidence of producing congenital abnormalities. Objective: This study was conducted to study the teratogenic effects of TPM by using chick embryos as an animal model and the results can be compared to the human embryo of the same stage. Methods: Fertilized Leghorn hen eggs were injected in ovo with two concentrations of TPM, which were 10mg, and 20mg, in NSS at a volume of 0.1 ml into the yolk sac at 21 hrs of incubation and repeated injections at 72 hrs at a volume of 0.05 ml. The chick embryos on day 3, 6 and 11 of incubation were sacrificed and all living embryos were processed for total mount and serial section. Results: The mortality rate increased corresponding to the concentrations of TPM, and the embryonic stage. The total mount of day 3 showed major abnormalities of the eye and heart, such as microphthalmia and looser of heart looping. The serial section of day 3 showed opening of the anterior neuropore, ectopia viscerae and multiple malformations of the eye and heart. Day 6 chick embryos showed ectopia cordis and ectopia viscerae. Moreover, there were retardation and abnormalities of several organs such as eye, heart, liver, mesonephros and gonads. Day 11 chick embryos showed ectopia viscerae and several growth retardations, retardation of ossification of both limb bones and skull bones. Conclusion: This study showed that TPM might cause embryonic death, growth retardation and abnormalities of the eye, heart, an opening of the anterior neuropore and ectopia viscerae. This might indicate abnormalities to the baby born from mother with gestational epilepsy who was taking this drug continuously, and it might lead to spontaneous abortion or congenital anomalies of the fetus.

  16. Teratogenic effects of 60Co gamma rays irradiation on rat embryos

    International Nuclear Information System (INIS)

    Lee, Juing-Yi; Okuda, Hiroe; Tutimoto, Sigeo; Satow, Yukio

    1987-01-01

    The teratogenicity of 60 Co gamma rays was evaluated in Donryu rats. The results were compared with those of triterated water (HTO) for determining relative biological effectiveness (RBE) for incidence of malformations and LD 50 in rats. Pregnant rats were irradiated with a 60 Co source at a dose-rate of 0.5 Gy/min or 0.01 Gy/min on day 7, 8, 9, 10 or 11 of gestation with 0.8, 1.0, 1.2, 1.5, 2.0, 2.3, 2.5, 2.8 or 3.0 Gy. HTO was administered intraperitoneal injection to pregnant rats at various doses on day 7, 8, 9, 10 and 11 of gestation. The rats were sacrificed on day 18 and the offspring were examined for external and visceral malformations. Mortality, teratogenicity and effects on fetal growth were day-and dosage-dependent in both radiation groups. Congenital malformations were found most frequently in the 9-day irradiated group and followed by the 8, 11, 10 and 7-day irradiated groups. The incidence of cardiovascular anomalies was highest, especially in the day 9 of gestation group, followed by malformations in the central nervous system, craniofacial system, respiratory system, hind limbs and tail. Beta rays from HTO were found to be more effective than γ rays in inducing congenital malformations. The RBE for incidence of malformations and LD 50 was between 1.3 and 1.5. These studies suggest that simulator of tritium irradiation is urgently needed to investigate the biological effects on rats to estimate the human risks, with respect to RBE of tritium beta rays. (author)

  17. Tissue localization of some teratogens at early and late gestation related to fetal effects

    Energy Technology Data Exchange (ETDEWEB)

    Dencker, L [Uppsala Univ. (Sweden)

    1976-01-01

    A number of teratogens have been studied with regard to their distribution and tissue localization in pregnant rodents. The period from the presomite or early somite stages and up to the last days of gestation has been studied by means of whole body autoradiography. The fetal concentrations have been quantitatively measured from day 12 to day 18 of gestation for some of the teratogens by impulse counting. Cadmium (/sup 109/CdCl/sub 2/), mercury (/sup 203/HgCl/sub 2/), and trypan blue (detected by its colour) accumulated in the visceral yolk sac endoderm and in the embryonic endoderm. After duct closure time none of the substances were detected in the embryo except mercury in late gestation. The herbicide 2,4,5-T (/sup 14/C-2,4,5-T) did not pass to the embryonic tissues up to day 10-11 of gestation. The results obtained with 2,4,5-T show that the visceral yolk sac and chorioallantoic placenta have different characteristics concerning the transport of comparatively small organic molecules. /sup 14/C-salicylic acid reached relatively high concentrations during the entire embryonic-fetal period, proving salicylates fetotoxicity throughout gestation. Mercury, 2,4,5-T and salicylic acid showed an increasing fetal concentration with advancing stage of gestation. Extraembryonic mechanisms must too be considered of importance in inducing fetal damage. Cadmium mercury and trypan blue all accumulated in the placental structures throughout gestation. Zinc (/sup 65/ZnCl/sub 2/), which has been shown to be essential for fetal development probably because of its involvment in DNA synthesis, accumulated in the most rapidly growing embryonic structures. Zinc injected prior to gestation was transported to the embryos and placental structures while only a minor amount of the cadmium injected before gestation was mobilized from the maternal organs.

  18. Embryo-fetal development and its relationship with the responsiveness to teratogens

    International Nuclear Information System (INIS)

    Rios, Hugo

    2001-01-01

    to compensate the failure and the organism will die. Teratogenic agents can be classified according to the developmental mechanism that they affect. Some of these agents act modifying the genomic information or its expression meanwhile others can alter interactions among cells, or between cells and microenvironment. According to the genetic background, the same teratogenic agent might or not establish a malformation. Besides, another external factors modulate the effect of a teratogen or the genetic background, for example: folic acid can prevent abnormalities in the neural tube closure. In conclusion, it is possible to affirm that the development of normal and abnormal phenotypes depend on complex interactions that are far from be understood now and taking part interactions between genes and environment are still obscure. Besides, there are not animal models that could copy either human development or the developmental mechanisms that produce malformations. The solutions to these subjects will arise from a detailed study of prenatal and postnatal developmental biology and genetics, and taking into account the influence of environment on living organisms. (author)

  19. Pulsed magnetic field from video display terminals enhances teratogenic effects of cytosine arabinoside in mice

    Energy Technology Data Exchange (ETDEWEB)

    Chiang, H.; Wu, R.Y.; Shao, B.J.; Fu, Y.D.; Yao, G.D.; Lu, D.J. [Zhejiang Medical Univ. (China)

    1995-05-01

    Eighty-nine Swiss Webster mice were randomly divided into four groups: a control group, a pulsed magnetic field (PMF) group, a cytosine arabinoside (ara-C, a teratogen) group, and a combined PMF + ara-C group. Mice in the PMF and PMF + ara-C groups were irradiated with a PMF (a sawtooth waveform with 52 {mu}s rise time, 12{mu}s decay time, and 15.6 kHz frequency) at a peak magnetic flux density of 40 {mu}T for 4 hours daily on days 6-17 of gestation. The mice in the ara-C and the PMF + ara-C groups were injected intraperitoneally on day 9 of gestation with 10 mg/kg of ara-C. The incidence of resorption and dead fetuses was not affected by PMF but was increased by ara-C injection. The malformation incidence of cleft palate (CP) and/or cleft lip (CL) was significantly higher in all three of the treated groups than in the control group (P < 0.05). If, however, statistical analyses had been done on litters rather than on individual fetuses, they would show that the incidence of CP and/or CL in the PMF group is not significantly greater than that in the control group. A significantly higher incidence of CP and/or CL was found in the PMF + ara-C group (49%) than the ara-C alone group (26.1%). These data suggest that PMF might enhance the development of ara-C-induced CP and/or CL. The incidence of minor variations in skeletal development, including reduction of skeletal calcification and loss of skeleton, was not statistically significant in the PMF group. However, it was higher in the two ara-C-treated groups, and there was no significant difference between the ara-C alone group and the ara-C + PMF group. From these results it is concluded that the very weak embryotoxic effects of PMF exposure may be revealed and enhanced in combination with a teratogenic agent.

  20. Teratogenic study of phenobarbital and levamisole on mouse fetus liver tissue using biospectroscopy.

    Science.gov (United States)

    Ashtarinezhad, Azadeh; Panahyab, Ataollah; Shaterzadeh-Oskouei, Shahrzad; Khoshniat, Hessam; Mohamadzadehasl, Baharak; Shirazi, Farshad H

    2016-09-05

    Biospectroscopic investigations have attracted attention of both the clinicians and basic sciences researchers in recent years. Scientists are discovering new areas for FTIR biospectroscopy applications in medicine. The aim of this study was to measure the possibility of FTIR-MSP application for the recognition and detection of fetus abnormalities after exposure of pregnant mouse to phenobarbital (PB) and levamisole (LEV) alone or in combination. PB is one of the most widely used antiepileptic drugs (AEDs), with sedative and hypnotic effects. When used by pregnant women, it is known to be a teratogenic agent. LEV is an antihelminthic drug with some applications in immune-deficiency as well as colon cancer therapy. Four groups of ten pregnant mice were selected for the experiments as follows: one control group received only standard diet, one group was injected with 120mg/kg of BP, one group was injected with 10mg/kg of LEV, and the last group was treated simultaneously with both BP and LEV at the above mentioned doses. Drugs administration was performed on gestation day 9 and fetuses were dissected on pregnancy day 15. Each dissected fetus was fixed, dehydrated and embedded in paraffin. Sections of liver (10μm) were prepared from control and treated groups by microtome and deparaffinized with xylene. The spectra were taken by FTIR-MSP in the region of 4000-400cm(-1). All the spectra were normalized based on amide II band (1545cm(-1)) after baseline correction of the entire spectrum, followed by classification using PCA, ANN and SVM. Both morphological and spectral changes were shown in the treated fetuses as compared to the fetuses in the control group. While cleft palate and C-R elongation were seen in PB injected fetuses, developmental retardation was mostly seen in the LEV injected group. Biospectroscopy revealed that both drugs mainly affected the cellular lipids and proteins, with LEV causing more changes in amide I and lipid regions than PB. Application of

  1. Immunomodulatory drugs disrupt the cereblon-CD147-MCT1 axis to exert antitumor activity and teratogenicity.

    Science.gov (United States)

    Eichner, Ruth; Heider, Michael; Fernández-Sáiz, Vanesa; van Bebber, Frauke; Garz, Anne-Kathrin; Lemeer, Simone; Rudelius, Martina; Targosz, Bianca-Sabrina; Jacobs, Laura; Knorn, Anna-Maria; Slawska, Jolanta; Platzbecker, Uwe; Germing, Ulrich; Langer, Christian; Knop, Stefan; Einsele, Herrmann; Peschel, Christian; Haass, Christian; Keller, Ulrich; Schmid, Bettina; Götze, Katharina S; Kuster, Bernhard; Bassermann, Florian

    2016-07-01

    Immunomodulatory drugs (IMiDs), such as thalidomide and its derivatives lenalidomide and pomalidomide, are key treatment modalities for hematologic malignancies, particularly multiple myeloma (MM) and del(5q) myelodysplastic syndrome (MDS). Cereblon (CRBN), a substrate receptor of the CRL4 ubiquitin ligase complex, is the primary target by which IMiDs mediate anticancer and teratogenic effects. Here we identify a ubiquitin-independent physiological chaperone-like function of CRBN that promotes maturation of the basigin (BSG; also known as CD147) and solute carrier family 16 member 1 (SLC16A1; also known as MCT1) proteins. This process allows for the formation and activation of the CD147-MCT1 transmembrane complex, which promotes various biological functions, including angiogenesis, proliferation, invasion and lactate export. We found that IMiDs outcompete CRBN for binding to CD147 and MCT1, leading to destabilization of the CD147-MCT1 complex. Accordingly, IMiD-sensitive MM cells lose CD147 and MCT1 expression after being exposed to IMiDs, whereas IMiD-resistant cells retain their expression. Furthermore, del(5q) MDS cells have elevated CD147 expression, which is attenuated after IMiD treatment. Finally, we show that BSG (CD147) knockdown phenocopies the teratogenic effects of thalidomide exposure in zebrafish. These findings provide a common mechanistic framework to explain both the teratogenic and pleiotropic antitumor effects of IMiDs.

  2. The Role of Clomipramine in Potentiating the Teratogenic Effects of Caffeine in Pregnant Rats: A Histopathological Study

    Directory of Open Access Journals (Sweden)

    Vahid Nikoui

    2013-01-01

    Full Text Available Since little is known about the teratogenic effects of clomipramine used concurrently with caffeine during the organogenesis period, the aim of this study was to test the teratogenic effects of a coadministration of caffeine and clomipramine on rat fetuses. We divided 42 pregnant rats into seven groups, randomly. The first group (control received 0.5 mL of normal saline. Clomipramine was injected at 40 mg/kg and 80 mg/kg to the second and third groups, respectively. The fourth and fifth groups received caffeine in doses of 60 mg/kg and 120 mg/kg, respectively. The sixth group received a combination of 40 mg/kg clomipramine and 60 mg/kg caffeine, and the seventh group was given clomipramine and caffeine at 80 mg/kg and 120 mg/kg, respectively. The fetuses were removed on the 17th day of pregnancy and studied in terms of microscopic and macroscopic morphological features. Fetuses of rats receiving high doses of caffeine or combinations of caffeine and clomipramine showed a significant rate of cleft palate development, open eyelids, mortality, torsion anomalies, shrinkage of skin, and subcutaneous haemorrhage (P≤0.001. This study concludes that caffeine in high doses or the simultaneous administration of caffeine and clomipramine leads to teratogenicity.

  3. Valnoctamide, which reduces rat brain arachidonic acid turnover, is a potential non-teratogenic valproate substitute to treat bipolar disorder.

    Science.gov (United States)

    Modi, Hiren R; Ma, Kaizong; Chang, Lisa; Chen, Mei; Rapoport, Stanley I

    2017-08-01

    Valproic acid (VPA), used for treating bipolar disorder (BD), is teratogenic by inhibiting histone deacetylase. In unanaesthetized rats, chronic VPA, like other mood stabilizers, reduces arachidonic acid (AA) turnover in brain phospholipids, and inhibits AA activation to AA-CoA by recombinant acyl-CoA synthetase-4 (Acsl-4) in vitro. Valnoctamide (VCD), a non-teratogenic constitutional isomer of VPA amide, reported effective in BD, also inhibits recombinant Acsl-4 in vitro. VCD like VPA will reduce brain AA turnover in unanaesthetized rats. A therapeutically relevant (50mg/kg i.p.) dose of VCD or vehicle was administered daily for 30 days to male rats. AA turnover and related parameters were determined using our kinetic model, following intravenous [1- 14 C]AA in unanaesthetized rats for 10min, and measuring labeled and unlabeled lipids in plasma and high-energy microwaved brain. VCD, compared with vehicle, increased λ, the ratio of brain AA-CoA to unesterified plasma AA specific activities; and decreased turnover of AA in individual and total brain phospholipids. VCD's ability like VPA to reduce rat brain AA turnover and inhibit recombinant Acsl-4, and its efficacy in BD, suggest that VCD be further considered as a non-teratogenic VPA substitute for treating BD. Published by Elsevier B.V.

  4. Assessment of Cytotoxicity, Fetotoxicity, and Teratogenicity of Plathymenia reticulata Benth Barks Aqueous Extract

    Directory of Open Access Journals (Sweden)

    Lia de Barros Leite Albuquerque

    2013-01-01

    Full Text Available Scientific assessment of harmful interactions of chemicals over the entire reproductive cycle are divided into three segments based on the period: from premating and mating to implantation (I, from implantation to major organogenesis (II, and late pregnancy and postnatal development (III. We combined the segments I and II to assess Plathymenia reticulata aqueous extract safety. In order to investigate reproductive toxicity (segment I, pregnant rats received orally 0.5 or 1.0 g/kg of extract, daily, during 18 days. These concentrations were determined by a preliminary in vitro LD50 test in CHO-k1 cells. A control group received deionized water. The offspring was removed at the 19th day, by caesarean, and a teratology study (segment II was carried out. The corpora lutea, implants, resorptions, live, and dead fetuses were then counted. Placenta and fetuses were weighted. External and visceral morphology were provided by the fixation of fetuses in Bouin, whereas skeletal analysis was carried out on the diaphanizated ones. The increase in the weights of placenta and fetuses was the only abnormality observed. Since there was no sign of alteration on reproduction parameters at our experimental conditions, we conclude that P. reticulata aqueous extract is safe at 0.5 to 1.0 g/kg and is not considered teratogenic.

  5. Boric acid inhibits embryonic histone deacetylases: A suggested mechanism to explain boric acid-related teratogenicity

    International Nuclear Information System (INIS)

    Di Renzo, Francesca; Cappelletti, Graziella; Broccia, Maria L.; Giavini, Erminio; Menegola, Elena

    2007-01-01

    Histone deacetylases (HDAC) control gene expression by changing histonic as well as non histonic protein conformation. HDAC inhibitors (HDACi) are considered to be among the most promising drugs for epigenetic treatment for cancer. Recently a strict relationship between histone hyperacetylation in specific tissues of mouse embryos exposed to two HDACi (valproic acid and trichostatin A) and specific axial skeleton malformations has been demonstrated. The aim of this study is to verify if boric acid (BA), that induces in rodents malformations similar to those valproic acid and trichostatin A-related, acts through similar mechanisms: HDAC inhibition and histone hyperacetylation. Pregnant mice were treated intraperitoneally with a teratogenic dose of BA (1000 mg/kg, day 8 of gestation). Western blot analysis and immunostaining were performed with anti hyperacetylated histone 4 (H4) antibody on embryos explanted 1, 3 or 4 h after treatment and revealed H4 hyperacetylation at the level of somites. HDAC enzyme assay was performed on embryonic nuclear extracts. A significant HDAC inhibition activity (compatible with a mixed type partial inhibition mechanism) was evident with BA. Kinetic analyses indicate that BA modifies substrate affinity by a factor α = 0.51 and maximum velocity by a factor β = 0.70. This work provides the first evidence for HDAC inhibition by BA and suggests such a molecular mechanism for the induction of BA-related malformations

  6. An Exploratory Analysis of Stream Teratogenicity and Human Health Using Zebrafish Whole-Sediment Toxicity Test

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    Matthew Dellinger

    2014-02-01

    Full Text Available This study demonstrates a novel application of effect-based toxicity testing for streams that may provide indications of co-perturbation to ecological and human health. For this study, a sediment contact assay using zebrafish (Danio rerio embryos was adapted to serve as an indicator of teratogenic stress within river sediments. Sediment samples were collected from Lake Michigan tributary watersheds. Sediment contact assay responses were then compared to prevalence of congenital heart disease (CHD and vital statistic birth indicators aggregated from civil divisions associated with the watersheds. Significant risk relationships were detected between variation in early life-stage (ELS endpoints of zebrafish embryos 72 h post-fertilization and the birth prevalence of human congenital heart disease, low birthweight and infant mortality. Examination of principal components of ELS endpoints suggests that variance related to embryo heart and circulatory malformations is most closely associated with human CHD prevalence. Though toxicity assays are sometimes used prospectively, this form of investigation can only be conducted retrospectively. These results support the hypothesis that bioassays normally used for ecological screening can be useful as indicators of environmental stress to humans and expand our understanding of environmental–human health linkages.

  7. The Teratogenicity and the Action Mechanism of Gallic Acid Relating with Brain and Cervical Muscles

    Science.gov (United States)

    Hsieh, Chiu Lan; Lin, Chien-Hong; Chen, Kuan Chou; Peng, Chiung-Chi; Peng, Robert Y.

    2015-01-01

    Gallic acid (3,4,5-trihydroxybenzoic acid) (GA) and other flavanoids are extensively used in nutraceuticals because of their antioxidant and antiinflammatory properties. While examining whether GA is effective in alleviating valproic-acid-induced teratogenesis in a chicken embryo model (CEM), we observed embryo hemorrhage and liposis in the musculi longissimus cervicis. We conducted this study to determine whether GA is inherently teratogenic and the extent to which the risk can be transferred to fetuses. A CEM was used to administer GA at 2, 6, 10, and 14 μM. GA at 2 μM did not exhibit cytotoxicity. At 6, 10, and 14 μM, GA caused severe decreases in body and liver weights, causing -5.6%, -21.3%, and -27.5% body weights and 4.0, 3.8, and 3.2-g, liver weights, respectively, in day-1 chicks. The optimal alive birth rate (or damaging rate) reached 33.3%, 39.4%, and 29.2% at 6, 10, and 14 μM GA, respectively. The damaged tissue was primarily cervical muscle (musculi longissimus cervicis), as evidenced by liposis, Zenker’s necrosis, and hemolysis. The erythrocyte, hemoglobin, eosinophil, lymphocyte, and monocyte counts were severely reduced and PPAR-α was downregulated, whereas the Ras/Raf/JAK/STAT pathway was upregulated. The GA dose required to induce teratogenesis was ≥ 6 μM (1.02 mg/kg), which can be easily consumed by pregnant women in typical teas such as Chinese Pu-’Er and Chinese black teas, indicating a potential risk to human fetuses. GA at doses ≥ 1.02 mg/kg of body weight potentially causes characteristic cerebral hemolysis and liposis in the musculi longissimus cervicis. The mechanism of action of GA is multidisciplinary: The liposis can be ascribed to downregulation of PPAR-α; the erythrocyte hemolysis can be attributed to its unique autooxidative and prooxidant behavior and the inhibition of carbonic anhydrase; and the proliferation and differentiation deficits can be attributed to the upregulation of the Ras/Raf/JAK/STAT pathway. PMID

  8. Cadmium-induced teratogenicity: Association with ROS-mediated endoplasmic reticulum stress in placenta

    International Nuclear Information System (INIS)

    Wang, Zhen; Wang, Hua; Xu, Zhong Mei; Ji, Yan-Li; Chen, Yuan-Hua; Zhang, Zhi-Hui; Zhang, Cheng; Meng, Xiu-Hong; Zhao, Mei; Xu, De-Xiang

    2012-01-01

    The placenta is essential for sustaining the growth of the fetus. An increased endoplasmic reticulum (ER) stress has been associated with the impaired placental and fetal development. Cadmium (Cd) is a potent teratogen that caused fetal malformation and growth restriction. The present study investigated the effects of maternal Cd exposure on placental and fetal development. The pregnant mice were intraperitoneally injected with CdCl 2 (4.5 mg/kg) on gestational day 9. As expected, maternal Cd exposure during early limb development significantly increased the incidences of forelimb ectrodactyly in fetuses. An obvious impairment in the labyrinth, a highly developed tissue of blood vessels, was observed in placenta of mice treated with CdCl 2 . In addition, maternal Cd exposure markedly repressed cell proliferation and increased apoptosis in placenta. An additional experiment showed that maternal Cd exposure significantly upregulated the expression of GRP78, an ER chaperone. Moreover, maternal Cd exposure induced the phosphorylation of placental eIF2α, a downstream molecule of PERK signaling. In addition, maternal Cd exposure significantly increased the level of placental CHOP, another target of PERK signaling, indicating that the unfolded protein response (UPR) signaling was activated in placenta of mice treated with CdCl 2 . Interestingly, alpha-phenyl-N-t-butylnitrone, a free radical spin-trapping agent, significantly alleviated Cd-induced placental ER stress and UPR. Taken together, these results suggest that reactive oxygen species (ROS)-mediated ER stress might be involved in Cd-induced impairment on placental and fetal development. Antioxidants may be used as pharmacological agents to protect against Cd-induced fetal malformation and growth restriction. -- Highlights: ► Cd induces fetal malformation and growth restriction. ► Cd induced placental ER stress and UPR. ► PBN alleviates Cd-induced ER stress and UPR in placenta. ► ROS-mediated ER stress might

  9. Acute and sub-lethal exposure to copper oxide nanoparticles causes oxidative stress and teratogenicity in zebrafish embryos.

    Science.gov (United States)

    Ganesan, Santhanamari; Anaimalai Thirumurthi, Naveenkumar; Raghunath, Azhwar; Vijayakumar, Savitha; Perumal, Ekambaram

    2016-04-01

    Nano-copper oxides are a versatile inorganic material. As a result of their versatility, the immense applications and usage end up in the environment causing a concern for the lifespan of various beings. The ambiguities surround globally on the toxic effects of copper oxide nanoparticles (CuO-NPs). Hence, the present study endeavored to study the sub-lethal acute exposure effects on the developing zebrafish embryos. The 48 hpf LC50 value was about 64 ppm. Therefore, we have chosen the sub-lethal dose of 40 and 60 ppm for the study. Accumulation of CuO-NPs was evidenced from the SEM-EDS and AAS analyzes. The alterations in the AChE and Na(+)/K(+)-ATPase activities disrupted the development process. An increment in the levels of oxidants with a concomitant decrease in the antioxidant enzymes confirmed the induction of oxidative stress. Oxidative stress triggered apoptosis in the exposed embryos. Developmental anomalies were observed with CuO-NPs exposure in addition to oxidative stress in the developing embryos. Decreased heart rate and hatching delay hindered the normal developmental processes. Our work has offered valuable data on the connection between oxidative stress and teratogenicity leading to lethality caused by CuO-NPs. A further molecular mechanism unraveling the uncharted connection between oxidative stress and teratogenicity will aid in the safe use of CuO-NPs. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Allopurinol Use during Pregnancy - Outcome of 31 Prospectively Ascertained Cases and a Phenotype Possibly Indicative for Teratogenicity.

    Directory of Open Access Journals (Sweden)

    Maria Hoeltzenbein

    Full Text Available Allopurinol is a purine analogue that inhibits xanthine oxidase. It is mainly used for the treatment of hyperuricemia in patients with gout or tumor lysis syndrome. Experience with allopurinol in pregnancy is scarce. In 2011, Kozenko et al. reported on a child with multiple malformations after maternal treatment with allopurinol throughout pregnancy. Possible teratogenicity of allopurinol was proposed due to the similarity of the pattern of malformations in children with mycophenolate embryopathy. A possible common mechanism of both drugs, i.e. disruption of purine synthesis, was discussed. We report on the outcome of 31 prospectively ascertained pregnancies with allopurinol exposure at least during first trimester. Pregnancy outcomes were 2 spontaneous abortions, 2 elective terminations of pregnancy and 27 live born children. The overall rate of major malformations (3.7% and of spontaneous abortions (cumulative incidence 11%, 95%-CI 3-40 were both within the normal range. However, there was one child with severe malformations including microphthalmia, cleft lip and palate, renal hypoplasia, low-set ears, hearing deficit, bilateral cryptorchidism, and micropenis. The striking similarity of the anomalies in this child and the case described by Kozenko et al. might be considered as a signal for teratogenicity. Thus, we would recommend caution with allopurinol treatment in the first trimester, until further data are available.

  11. Potential teratogenicity of methimazole: exposure of zebrafish embryos to methimazole causes similar developmental anomalies to human methimazole embryopathy.

    Science.gov (United States)

    Komoike, Yuta; Matsuoka, Masato; Kosaki, Kenjiro

    2013-06-01

    While methimazole (MMI) is widely used in the therapy for hyperthyroidism, several groups have reported that maternal exposure to MMI results in a variety of congenital anomalies, including choanal and esophageal atresia, iridic and retinal coloboma, and delayed neurodevelopment. Thus, adverse effects of maternal exposure to MMI on fetal development have long been suggested; however, direct evidence for the teratogenicity of MMI has not been presented. Therefore, we studied the effects of MMI on early development by using zebrafish as a model organism. The fertilized eggs of zebrafish were collected immediately after spawning and grown in egg culture water containing MMI at various concentrations. External observation of the embryos revealed that exposure to high concentrations of MMI resulted in loss of pigmentation, hypoplastic hindbrain, turbid tissue in the forebrain, swelling of the notochord, and curly trunk. Furthermore, these effects occurred in a dose-dependent manner. Precise observation of the serial cross-sections of MMI-exposed embryos elucidated delayed development and hypoplasia of the whole brain and spinal cord, narrowing of the pharynx and esophagus, severe disruption of the retina, and aberrant structure of the notochord. These neuronal, pharyngeal, esophageal, and retinal anomalous morphologies have a direct analogy to the congenital anomalies observed in children exposed to MMI in utero. Here, we show the teratogenic effects of MMI on the development of zebrafish and provide the first experimental evidence for the connection between exposure to MMI and human MMI embryopathy. © 2013 Wiley Periodicals, Inc.

  12. A Modified Murine Embryonic Stem Cell Test for Evaluating the Teratogenic Effects of Drugs on Early Embryogenesis.

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    Ruoxing Yu

    Full Text Available Mammalian fetal development is easily disrupted by exogenous agents, making it essential to test new drug candidates for embryotoxicity and teratogenicity. To standardize the testing of drugs that might be used to treat pregnant women, the U.S. Food and Drug Administration (FDA formulated special grade categories, labeled A, B, C, D and X, that define the level of risk associated with the use of a specific drug during pregnancy. Drugs in categories (Cat. D and X are those with embryotoxic and/or teratogenic effects on humans and animals. However, which stages of pregnancy are affected by these agents and their molecular mechanisms are unknown. We describe here an embryonic stem cell test (EST that classifies FDA pregnancy Cat.D and Cat.X drugs into 4 classes based on their differing effects on primitive streak formation. We show that ~84% of Cat.D and Cat.X drugs target this period of embryogenesis. Our results demonstrate that our modified EST can identify how a drug affects early embryogenesis, when it acts, and its molecular mechanism. Our test may thus be a useful addition to the drug safety testing armamentarium.

  13. Study of the teratogenic potential of FD & C Yellow No. 5 when given by gavage to rats.

    Science.gov (United States)

    Collins, T F; Black, T N; Brown, L H; Bulhack, P

    1990-12-01

    FD & C Yellow No. 5 (tartrazine) was given to Osborne-Mendel rats by gavage at dose levels of 0, 60, 100, 200, 400, 600 or 1000 mg/kg body weight/day on days 0-19 of gestation. No maternal or developmental toxicity was observed when the rats were killed on day 20. The mean daily food consumption for the entire period of gestation was significantly greater in the females given 1000 mg/kg body weight/day than in the controls, but maternal body-weight gain was not affected. No dose-related effects were observed in implantations, foetal viability or external foetal development. Foetal skeletal and visceral development was similar among foetuses from all groups. At the doses given, FD & C Yellow No. 5 was neither toxic nor teratogenic.

  14. Comparison of a teratogenic transcriptome-based predictive test based on human embryonic versus inducible pluripotent stem cells.

    Science.gov (United States)

    Shinde, Vaibhav; Perumal Srinivasan, Sureshkumar; Henry, Margit; Rotshteyn, Tamara; Hescheler, Jürgen; Rahnenführer, Jörg; Grinberg, Marianna; Meisig, Johannes; Blüthgen, Nils; Waldmann, Tanja; Leist, Marcel; Hengstler, Jan Georg; Sachinidis, Agapios

    2016-12-30

    Human embryonic stem cells (hESCs) partially recapitulate early embryonic three germ layer development, allowing testing of potential teratogenic hazards. Because use of hESCs is ethically debated, we investigated the potential for human induced pluripotent stem cells (hiPSCs) to replace hESCs in such tests. Three cell lines, comprising hiPSCs (foreskin and IMR90) and hESCs (H9) were differentiated for 14 days. Their transcriptome profiles were obtained on day 0 and day 14 and analyzed by comprehensive bioinformatics tools. The transcriptomes on day 14 showed that more than 70% of the "developmental genes" (regulated genes with > 2-fold change on day 14 compared to day 0) exhibited variability among cell lines. The developmental genes belonging to all three cell lines captured biological processes and KEGG pathways related to all three germ layer embryonic development. In addition, transcriptome profiles were obtained after 14 days of exposure to teratogenic valproic acid (VPA) during differentiation. Although the differentially regulated genes between treated and untreated samples showed more than 90% variability among cell lines, VPA clearly antagonized the expression of developmental genes in all cell lines: suppressing upregulated developmental genes, while inducing downregulated ones. To quantify VPA-disturbed development based on developmental genes, we estimated the "developmental potency" (D p ) and "developmental index" (D i ). Despite differences in genes deregulated by VPA, uniform D i values were obtained for all three cell lines. Given that the D i values for VPA were similar for hESCs and hiPSCs, D i can be used for robust hazard identification, irrespective of whether hESCs or hiPSCs are used in the test systems.

  15. Can we ensure the safe use of known human teratogens? Introduction of generic isotretinoin in the US as an example.

    Science.gov (United States)

    Honein, Margaret A; Moore, Cynthia A; Erickson, J David

    2004-01-01

    The prescription of known teratogenic medications requires a careful balance between allowing women access to medications that they might need and avoiding unnecessary exposure to these medications during pregnancy because of their devastating fetal effects. Isotretinoin, a potent human teratogen, is of particular concern because of its widespread use among reproductive-aged women and the dramatic increase in use from 1992 through 2000. A revised risk management system was implemented in 2002 because of concerns about the continued occurrence of isotretinoin-exposed pregnancies. However, the recent approval of three generic versions of isotretinoin in the US has further complicated risk management and raises concerns that use might increase further if the lower cost of generics serves to increase accessibility. There are now four separate isotretinoin risk management systems in the US, each with its own distinct packaging, though the requirements for and substance of each are identical. Some additional concrete steps could be taken to minimise any unnecessary use of isotretinoin and help allow an adequate assessment of the current risk management systems. In addition to being familiar with and following all aspects of the current risk management system, physicians could choose to limit the use of isotretinoin to those who meet the labelled indications in order to reduce the number of exposed pregnancies. All four companies currently marketing isotretinoin in the US could jointly and voluntarily establish a consolidated, mandatory registration and follow-up of all women of reproductive potential who receive an isotretinoin prescription. Mandatory registration has many challenges, but it could allow a clear accounting of the total number of women for whom follow-up information is and is not available. Although the companies cannot be legally compelled to use a consolidated approach, the use of a single registry for the originator's product and all generic brands

  16. In vitro cytotoxic and teratogenic potential of sediment extracts from Skadar Lake using fish cell line RTL-W1 and Danio rerio embryos

    Directory of Open Access Journals (Sweden)

    Perović Andrej

    2013-01-01

    Full Text Available As a part of Sediment Quality Triad (SQT, organic extracts of sediment from Skadar Lake (a Mediterranean lake and the largest freshwater reservoir in southeastern Europe were investigated in order to evaluate possible ecotoxicological contamination by organic pollutants and to obtain a comprehensive insight into the ecotoxicological hazard. Sediments were investigated for toxicity by two different bioassays. Acute cytotoxicity was investigated using the fibroblast-like cell line RTL-W1 (Oncorhynchus mykiss in combination with the neutral red retention assay. The embryos of zebrafish (Danio rerio were used to assess the toxic and teratogenic potential of organic extracts of the sediment. Preliminary results point to the presence of a cytotoxic and teratogenic potential in Skadar Lake sediment extracts in certain locations.

  17. Evidence for cell-replacement repair of X-ray-induced teratogenic damage in male genital imaginal discs of Drosophila melanogaster

    International Nuclear Information System (INIS)

    Fukunaga, Akihiro; Kondo, Sohei

    1985-01-01

    Male genital imaginal discs from old (late-third-instar) larvae of Drosophila that had been X-irradiated with appropriate doses developed into severely damaged adult genitalia when implanted into old larvae, but they developed into completely normal adult genitalia when transplanted into 2-day-younger larvae. Complete repair of X-ray-induced teratogenic damage in the genital discs on transplantation into young host larvae was similar in the wild-type and mei-9sup(a) strains. The results are discussed in relation to the hypothesis that repair of X-ray-induced teratogenic damage depends not on DNA repair but on replacement of damage-bearing primordial cells by healthy ones after suicidal elimination of the former. (Auth.)

  18. The effects of green tea extract on teratogenicity induced by low frequency electromagnetic field on bone marrow Balb/C mice embryo

    Directory of Open Access Journals (Sweden)

    Baharara Javad

    2014-01-01

    Full Text Available Introduction: Electromagnetic fields produce free radicals which might be teratogen. Camellia sinensis is rich in natural antioxidants and antioxidants can neutralize free radicals effects. In present research the effect of C. sinensis extract in reduction of teratogenicity induced by electromagnetic field with 50 gauss intensity was studied on bone marrow of Balb/C mice fetuses. Methods: In this experimental study, 24 Balb/C pregnant mice were randomly divided into four groups: control, sham exposed (off position, experimental 1 (electromagnetic field with 50-gauss intensity and experimental 2 (treatment by C. sinensis extract + electromagnetic field with 50-gauss intensity. After treatment period, the bone marrow aspirates of Balb/C mice embryos were prepared and studied by Giemsa. The quantitative data were analyzed by Kruskal-Wallis and Kolmogorov- Smirnov using SPSS16 software at the level of p<0.05. Results: The mean number of promyelocytes, myelocytes, erythrocytes, necrotic and apoptotic cells in experimental group1 compared with sham exposed embryos showed significant increase but the mean number of eosinophils in experimental group 1 compared with sham exposed embryos showed significant decrease. The mean number of promyelocyte and erythrocyte in experimental group 2 compared with experimental group 1 showed significant decrease. The mean of necrotic and apoptotic cells, in experimental group 2 compared with experimental group 1 showed significant increase. Conclusion: Usage of C. sinensis can decrease the damage due to teratogenicity induced by low frequency electromagnetic field in some cells.

  19. A descriptive study to provide evidence of the teratogenic and cellular effects of sibutramine and ephedrine on cardiac- and liver-tissue of chick embryos.

    Science.gov (United States)

    Oberholzer, Hester Magdalena; Van Der Schoor, Ciska; Taute, Helena; Bester, Megan Jean

    2015-08-01

    Exposure to drugs during pregnancy is a major concern, as some teratogenic compounds can influence normal foetal development. Although the use of drugs during pregnancy should generally be avoided, exposure of the developing foetus to teratogens may occur unknowingly since these compounds may be hidden in products that are being marketed as "all natural." The aim of the current study was to investigate the possible teratogenic and cellular effects of sibutramine-a serotonin-norepinephrine reuptake inhibitor used in the treatment of obesity-on the heart and liver tissue of chick embryos. Ephedrine was used as a positive control. The chick embryo model was chosen because it has been used in studying developmental and experimental biology and teratology with great success. The embryos were exposed to three different concentrations of sibutramine and ephedrine respectively. The results obtained revealed that both compounds exhibited embryotoxicity when compared to the control groups. Liver and heart tissue of the exposed embryos was severely affected by these compounds in a dose-related manner. Morphology similar to that of muscle dystrophy was observed in the heart, where the muscle tissue was infiltrated by adipose and connective tissue. Severe liver steatosis was also noted. A more in-depth investigation into the molecular pathways involved might provide more information on the exact mechanism of toxicity of these products influencing embryonic development. © 2015 Wiley Periodicals, Inc.

  20. Congenital bladder exstrophy associated with Duogynon hormonal pregnancy tests-signal for teratogenicity or consumer report bias?

    Science.gov (United States)

    Tümmler, Gregor; Rißmann, Anke; Meister, Reinhard; Schaefer, Christof

    2014-06-01

    A combination of ethinylestradiol and 10mg norethisterone under the brand names of Duogynon (Germany) or Primodos (UK) was used as a pregnancy test until the 1970s. Until very recently there was continuing public concern about the safety of these drugs and legal proceedings were instituted against the medicinal authorization holder. Given the lack of epidemiological studies focusing on Duogynon/Primodos, the present study evaluates 296 consumer reports of the German Duogynon database and compares the reported birth defects with data from a population based birth registry. The most striking result is an increase of bladder exstrophy (OR=37.27; 95%-CI 14.56-95.28). Neural tube defects (OR=2.99; 95%-CI 1.85-4.84) and renal agenesis (OR=2.53; 95%-CI 1.17-5.45) were also significantly increased. Bladder exstrophy may be a yet undetected teratogenic effect of Duogynon, but may also represent a reporting bias. The present study highlights the difficulties of evaluating consumer reports which may be influenced by public media. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Determination and occurrence of retinoids in a eutrophic lake (Taihu Lake, China): cyanobacteria blooms produce teratogenic retinal.

    Science.gov (United States)

    Wu, Xiaoqin; Jiang, Jieqiong; Hu, Jianying

    2013-01-15

    Besides retinoic acids (RAs), some retinoids such as retinal (RAL) and retinol (ROH), which are considered as RA precursors in vertebrates, are also reported to be teratogenic agents. In this study we investigated four RA precursors including RAL, ROH, retinyl palmitate, and β-carotene in the eutrophic Taihu Lake, China, by developing a sensitive analytical method. RAL and β-carotene were widely detected in natural cyanobacteria blooms and lake water. Intracellular concentrations of RAL and β-carotene in blooms were 9.4 to 6.9 × 10(3) and 3.4 to 1.8 × 10(5) ng L(-1), respectively, and their concentrations in lake water were up to 1.4 × 10 ng L(-1) (RAL) and 9.8 × 10(2) ng L(-1) (β-carotene). The good correlation between intracellular concentrations of RAL and RAs implied that RAL was involved in the production of RAs by cyanobacteria blooms. Further examination of 39 cyanobacteria and algae species revealed that most species could produce RAL and β-carotene. The greatest amount of RAL was found in Chlamydomonas sp. (FACHB-715; 1.9 × 10(3) ng g(-1) dry weight). As the main cyanobacteria in Taihu Lake, many Microcystis species could produce high amounts of RAL and were thought to greatly contribute to the production of RAL measured in the blooms. Productions of RAL and β-carotene by cyanobacteria were associated with species, origin location, and growth stage. The results in this study present the existence of a potential risk to aquatic animals living in a eutrophic environment from a high concentration of RAL in cyanobacteria blooms and also provide a clue for further investigating the mechanism underlying the biosynthetic pathway of RAs in cyanobacteria and algae.

  2. Modulation of phenytoin teratogenicity and embryonic covalent binding by acetylsalicylic acid, caffeic acid, and alpha-phenyl-N-t-butylnitrone: implications for bioactivation by prostaglandin synthetase

    International Nuclear Information System (INIS)

    Wells, P.G.; Zubovits, J.T.; Wong, S.T.; Molinari, L.M.; Ali, S.

    1989-01-01

    Teratogenicity of the anticonvulsant drug phenytoin is thought to involve its bioactivation by cytochromes P-450 to a reactive arene oxide intermediate. We hypothesized that phenytoin also may be bioactivated to a teratogenic free radical intermediate by another enzymatic system, prostaglandin synthetase. To evaluate the teratogenic contribution of this latter pathway, an irreversible inhibitor of prostaglandin synthetase, acetylsalicylic acid (ASA), 10 mg/kg intraperitoneally (ip), was administered to pregnant CD-1 mice at 9:00 AM on Gestational Days 12 and 13, 2 hr before phenytoin, 65 mg/kg ip. Other groups were pretreated 2 hr prior to phenytoin administration with either the antioxidant caffeic acid or the free radical spin trapping agent alpha-phenyl-N-t-butylnitrone (PBN). Caffeic acid and PBN were given ip in doses that respectively were up to 1.0 to 0.05 molar equivalents to the dose of phenytoin. Dams were killed on Day 19 and the fetuses were assessed for teratologic anomalies. A similar study evaluated the effect of ASA on the in vivo covalent binding of radiolabeled phenytoin administered on Day 12, in which case dams were killed 24 hr later on Day 13. ASA pretreatment produced a 50% reduction in the incidence of fetal cleft palates induced by phenytoin (p less than 0.05), without significantly altering the incidence of resorptions or mean fetal body weight. Pretreatment with either caffeic acid or PBN resulted in dose-related decreases in the incidence of fetal cleft palates produced by phenytoin, with maximal respective reductions of 71 and 82% at the highest doses of caffeic acid and PBN (p less than 0.05)

  3. Nanosecond pulsed electric field incorporation technique to predict molecular mechanisms of teratogenicity and developmental toxicity of estradiol-17β on medaka embryos.

    Science.gov (United States)

    Yamaguchi, Akemi; Ishibashi, Hiroshi; Kono, Susumu; Iida, Midori; Uchida, Masaya; Arizono, Koji; Tominaga, Nobuaki

    2018-05-01

    Herein, we propose using a nanosecond pulsed electric field (nsPEF) technique to assess teratogenicity and embryonic developmental toxicity of estradiol-17β (E 2 ) and predict the molecular mechanisms of teratogenicity and embryonic developmental defects caused by E 2 on medaka (Oryzias latipes). The 5 hour post-fertilization embryos were exposed to co-treatment with 10 μm E 2 and nsPEF for 2 hours and then continuously cultured under non-E 2 and nsPEF conditions until hatching. Results documented that the time to hatching of embryos was significantly delayed in comparison to the control group and that typical abnormal embryo development, such as the delay of blood vessel formation, was observed. For DNA microarray analysis, 6 day post-fertilization embryos that had been continuously cultured under the non-E 2 and nsPEF condition after 2 hour co-treatments were used. DNA microarray analysis identified 542 upregulated genes and one downregulated gene in the 6 day post-fertilization embryos. Furthermore, bioinformatic analyses using differentially expressed genes revealed that E 2 exposure affected various gene ontology terms, such as response to hormone stimulus. The network analysis also documented that the estrogen receptor α in the mitogen-activated protein kinase signaling pathway may be involved in regulating several transcription factors, such as FOX, AKT1 and epidermal growth factor receptor. These results suggest that our nsPEF technique is a powerful tool for assessing teratogenicity and embryonic developmental toxicity of E 2 and predict their molecular mechanisms in medaka embryos. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Effects of exposing rat embryos in utero to physical or chemical teratogens are expressed later as enhanced induction of heat-shock proteins when embryonic hearts are cultured in vitro

    International Nuclear Information System (INIS)

    Higo, H.; Higo, K.; Lee, J.Y.; Hori, H.; Satow, Y.

    1988-01-01

    In order to get more insight into the effects of teratogens on developing embryos, we investigated the protein synthesis patterns of the target organs isolated from teratogen-treated embryos. Rat embryos were either irradiated in utero with either 252Cf fission neutrons or 60Co gamma rays on day 8 of gestation or treated in utero with a bis(dichloroacetyl)diamine (a chemical teratogen) on days 9 and 10. Hearts were removed from the embryos on day 12 and were incubated in vitro at 37 degrees C in the presence of [35S]methionine for up to 8 hr. The newly synthesized labeled proteins were then analyzed qualitatively by two-dimensional polyacrylamide gel electrophoresis. Enhanced and prolonged induction of a family of heat-shock (stress) proteins with a molecular weight of about 70,000 (SP70s) was observed as compared with those of controls. Among the teratogen-treated hearts, those with gross malformations already detectable at this early stage showed especially higher inductions of SP70s than did the others. The abnormal expression of SP70s observed in the present study appears to be a reflection of persisting cellular (tissue) damage inflicted by the teratogens, and the extent of the induction may be indicative of the degree and/or type of the damage. Such persisting defects in surviving cells, manifested by abnormal induction of SP70s in the present study, might be related to malformation of embryonic hearts

  5. Comparing attitudes about legal sanctions and teratogenic effects for cocaine, alcohol, tobacco and caffeine: A randomized, independent samples design

    Directory of Open Access Journals (Sweden)

    Alanis Kelly L

    2006-02-01

    than for the non-exposed teen beyond .0001 alpha level. The positive media program closed estimated grade point average differences and risks of later problems to a non-statistically significant margin, p >.05. Conclusion Ratings for prenatal cocaine were more negative than comparable ratings for alcohol, nicotine or caffeine exposure. Stereotypes can be reduced, showing viewers that positive postnatal environments ameliorate potential teratogenic effects of cocaine. Reducing negative stereotypes for crack babies may be a requisite for substantive changes in current policy.

  6. Dose-Related Effects of Acetylsalicylic acid (ASA) on Gamma Radiation-Induced Teratogenicity in Pregnant Albino Rats

    International Nuclear Information System (INIS)

    Ibrahim, M.F.

    2013-01-01

    radiation induced variations in the craniofacial measurements and segments of fore and hind limbs. Consistent with expectations, the 200 mg/kg body wt. ASA has strongly potentiated the radiation induced teratogenesis as monitored by high intrauterine lethality, incomplete fetal development showing apparent signs of maceration (Group 6). Thus it can be deliberated that considerable low doses of ASA appear to possess a beneficial effect during pregnancy as perits evident radioprotective ability even when manipulated during the serious gestational period of organ formation. However, at this period, caution must be assessed when taking high repeated daily doses of ASA due to its known undesirable effects and its recorded enhancing radiation teratogenic potential

  7. European medicinal and edible plants associated with subacute and chronic toxicity part I: Plants with carcinogenic, teratogenic and endocrine-disrupting effects.

    Science.gov (United States)

    Kristanc, Luka; Kreft, Samo

    2016-06-01

    In recent decades, the use of herbal medicines and food products has been widely embraced in many developed countries. These products are generally highly accepted by consumers who often believe that "natural" equals "safe". This is, however, an oversimplification because several botanicals have been found to contain toxic compounds in concentrations harmful to human health. Acutely toxic plants are in most cases already recognised as dangerous as a result of their traditional use, but plants with subacute and chronic toxicity are difficult or even impossible to detect by traditional use or by clinical research studies. In this review, we systematically address major issues including the carcinogenicity, teratogenicity and endocrine-disrupting effects associated with the use of herbal preparations with a strong focus on plant species that either grow natively or are cultivated in Europe. The basic information regarding the molecular mechanisms of the individual subtypes of plant-induced non-acute toxicity is given, which is followed by a discussion of the pathophysiological and clinical characteristics. We describe the genotoxic and carcinogenic effects of alkenylbenzenes, pyrrolizidine alkaloids and bracken fern ptaquiloside, the teratogenicity issues regarding anthraquinone glycosides and specific alkaloids, and discuss the human health concerns regarding the phytoestrogens and licorice consumption in detail. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Embryo-fetal development and its relationship with the responsiveness to teratogens; Etapas del desarrollo embriofetal y su relacion con la sensibilidad a los agentes teratogenos

    Energy Technology Data Exchange (ETDEWEB)

    Rios, Hugo [Buenos Aires Univ. (Argentina). Facultad de Medicina

    2001-07-01

    to compensate the failure and the organism will die. Teratogenic agents can be classified according to the developmental mechanism that they affect. Some of these agents act modifying the genomic information or its expression meanwhile others can alter interactions among cells, or between cells and microenvironment. According to the genetic background, the same teratogenic agent might or not establish a malformation. Besides, another external factors modulate the effect of a teratogen or the genetic background, for example: folic acid can prevent abnormalities in the neural tube closure. In conclusion, it is possible to affirm that the development of normal and abnormal phenotypes depend on complex interactions that are far from be understood now and taking part interactions between genes and environment are still obscure. Besides, there are not animal models that could copy either human development or the developmental mechanisms that produce malformations. The solutions to these subjects will arise from a detailed study of prenatal and postnatal developmental biology and genetics, and taking into account the influence of environment on living organisms. (author)

  9. Efeito embriotóxico, teratogênico e abortivo de plantas medicinais Embryotoxic, teratogenic and abortive effects of medicinal plants

    Directory of Open Access Journals (Sweden)

    H.G. Rodrigues

    2011-01-01

    Full Text Available O uso milenar de plantas medicinais mostrou ao longo dos anos, que determinadas plantas apresentam substâncias potencialmente perigosas. Do ponto de vista científico, algumas pesquisas mostraram que muitas dessas plantas possuem substâncias agressivas e por essa razão devem ser utilizadas com cuidado, respeitando seus riscos toxicológicos. Os efeitos mais preocupantes do uso indiscriminado de plantas medicinais são embriotóxico, teratogênico e abortivo, uma vez, que os constituintes da planta podem atravessar a placenta, chegar ao feto e gerar um desses efeitos. Este estudo objetiva fornecer uma listagem das principais plantas medicinais que tenham efeitos embriotóxicos, teratogênicos e abortivos comprovados, conhecendo as partes da planta utilizadas e seus respectivos nomes científicos, com a finalidade de alertar gestantes quanto aos riscos de seu uso. Realizou-se buscas nas bases eletrônicas de dados SciELO, PubMed, MEDLINE, LILACS, CAPES e Google acadêmico. Nos resultados encontrados, plantas como Arnica (Arnica montana, Artemísia (Artemisia vulgaris, Arruda (Ruta chalepensis/ Ruta graveolens, Barbatimão (Stryphnodendron polyphyllum, Boldo (Vernonia condensata dentre outras, podem vir a gerar um desses efeitos. A partir deste estudo comprova-se que para a maioria das plantas medicinais não há dados a respeito da segurança de seu uso durante a gravidez.The ancient use of medicinal plants has shown over the years that certain plants have potentially dangerous substances. From a scientific point of view, some studies have shown that many of these plants contain aggressive substances and therefore should be used with caution, respecting their toxicological risks. The most important effects of the indiscriminate use of medicinal plants are embryotoxic, teratogenic and abortifacient since the plant constituents can cross the placenta, reaching the fetus and leading to one of these effects. This study aimed to provide a list of

  10. Bioindication of total toxicity and teratogenicity of bottom deposits and soils from regions with different degree of the influence of the Chernobyl NPP accident using the developing embryos of grey sea urchins

    International Nuclear Information System (INIS)

    Grishchenko, O.M.; Chumak, V.K.; Grishchenko, S.O.; Rachins'kij, V.N.; Grishchenko, N.O.

    1992-01-01

    The changes (for 1983-90) in total toxicity and teratogenicity of bottom deposits in the Dnieper cascade and soil from some regions of the Ukraine with unequal degree of the influence of the Chernobyl NPP accident have been comparatively studied using developing embryos and larvae of grey sea urchins which are very sensitive to the unfavourable effect of radionuclides, many chemical technogenic factors. (author)

  11. MiR-153 targets the nuclear factor-1 family and protects against teratogenic effects of ethanol exposure in fetal neural stem cells

    Directory of Open Access Journals (Sweden)

    Pai-Chi Tsai

    2014-07-01

    Full Text Available Ethanol exposure during pregnancy is an established cause of birth defects, including neurodevelopmental defects. Most adult neurons are produced during the second trimester-equivalent period. The fetal neural stem cells (NSCs that generate these neurons are an important but poorly understood target for teratogenesis. A cohort of miRNAs, including miR-153, may serve as mediators of teratogenesis. We previously showed that ethanol decreased, while nicotine increased miR-153 expression in NSCs. To understand the role of miR-153 in the etiology of teratology, we first screened fetal cortical NSCs cultured ex vivo, by microarray and quantitative RT-PCR analyses, to identify cell-signaling mRNAs and gene networks as important miR-153 targets. Moreover, miR-153 over-expression prevented neuronal differentiation without altering neuroepithelial cell survival or proliferation. Analysis of 3′UTRs and in utero over-expression of pre-miR-153 in fetal mouse brain identified Nfia (nuclear factor-1A and its paralog, Nfib, as direct targets of miR-153. In utero ethanol exposure resulted in a predicted expansion of Nfia and Nfib expression in the fetal telencephalon. In turn, miR-153 over-expression prevented, and partly reversed, the effects of ethanol exposure on miR-153 target transcripts. Varenicline, a partial nicotinic acetylcholine receptor agonist that, like nicotine, induces miR-153 expression, also prevented and reversed the effects of ethanol exposure. These data collectively provide evidence for a role for miR-153 in preventing premature NSC differentiation. Moreover, they provide the first evidence in a preclinical model that direct or pharmacological manipulation of miRNAs have the potential to prevent or even reverse effects of a teratogen like ethanol on fetal development.

  12. EXAMINATION OF THE SUNGKAI’S YOUNG LEAF EXTRACT (Peronema canescens AS AN ANTIPIRETIC, IMMUNITY, ANTIPLASMODIUM AND TERATOGENITY IN MICE (Mus.muculus

    Directory of Open Access Journals (Sweden)

    Agus Martono Hadi Putranto

    2014-05-01

    Full Text Available The research of examination extract sungkai’s young leafs as an antipyretic, immunity, anti plasmodium and teratogenity in mice (Mus. Muculus has been done. The aims of this research is examinations in infusa effectiveness extract of the young leafs in mice (Mus. Muculus. The object of this research used 50 males Webster’s species mice has 7 – 8 week olds, averages 30 gram in weight. Mice are divided into 5 groups in examination for antipyretic. Mice has been introduced the DPT-HB fever before. The first group as a negative control treated a pure water, second group as a positive control treated a paracetamol 1.08 mg/Kg w/w and rest of groups treated a young sungkai’s extract leafs in the concentration of 0.186 mg/Kg w/w, 0.375 mg/Kg w/w and 0.5625 mg/Kg w/w respectively. Measurements of the temperature toke in the duration of 30, 60, 90 and 120 minutes. Furthermore, in the immunity examination, mice also divided into 5 groups, first as a negative control treated a pure water, second group as a positive control treated 0.07 mg/Kg imunos w/w and respectively for the rest groups treated with young sungkai’s extract leafs in the concentration of 0.186 mg/Kg w/w, 0.375 mg/Kg w/w and 0.5625 mg/Kg w/w. These treatments held in gavage system with the duration at 24 hours. In examination amount of the leukocyte number, toke from the tail of the mice, has a result the dosage in 0.5625 mg/Kg w/w extract’s young leafs of sungkai could be decrease the temperature 29%, it is better than paracetamol treatment which could be decreased only 26% of temperature. In addition, for the immunity examination, the best dosage of the young sungkai’s extract leafs is 0.567 mg/Kg w/w, which It can increase 36% amount of the leukocyte number. This dosage is better than the positive control by using Imunos, which is can increase only 23% of the temperature.

  13. Avaliação de teratógenos potenciais na população brasileira Evaluation of potential teratogens in Brazilian population

    Directory of Open Access Journals (Sweden)

    Lavínia Schüler-Faccini

    2002-01-01

    Full Text Available O fato de agentes ambientais, nomeadamente fármacos, infecções maternas, e agentes químicos ou físicos poderem causar danos ao embrião ou feto em desenvolvimento é um problema reconhecido principalmente a partir do século 20. Nos países em desenvolvimento, existem características especiais que podem tornar esse problema mais agudo. Essas características incluem níveis educacionais e econômicos baixos da população, alta incidência de doenças infecciosas e carenciais, escassos recursos para saúde e pesquisa, prática freqüente e sem controle de automedicação, facilidade de obtenção de medicações que deveriam estar submetidas à prescrição médica e, finalmente, proibição legal de interrupção da gestação. Além disso, pode somar-se uma qualidade ambiental precária ou mesmo condições de trabalho insalubres durante a gravidez. No presente trabalho apresentamos as principais metodologias para detecção e monitorização de potenciais teratógenos, com ênfase especial nos programas desenvolvidos no Brasil e América Latina.The fact that environmental agents, namely drugs, maternal infections, other chemical or physical agents could harm the developing embryo or fetus is a problem recognized specially since the XXth century. In developing countries there are some special characteristics that can make this problem more severe. These include low educational and economical level of the population, high incidence of infectious and carential diseases, habits of self-medication associated to easy ways to obtain prescription drugs and, finally no legal permission for pregnancy termination. More than that, sometimes there are also bad environmental conditions or unhealthy working conditions during pregnancy. In this article we present the main methodologies to detect and to monitorize potential teratogens, with special emphasis in present programs going on in Brazil and Latin America.

  14. Manifestaciones cutáneas como parámetro de teratogenicidad en la intoxicación con metales pesados Cutaneous signs as parameter in teratogenicity by heavy metal intoxication

    Directory of Open Access Journals (Sweden)

    N L Pauza

    2007-03-01

    Full Text Available Se estudiaron los efectos teratogénicos de metales pesados (acetatos de Cd2+ y Pb2+ y sulfato de Cu2+, en embriones de pollo en desarrollo, después de la administración de una monodosis del metal. Los huevos embrionados fueron inyectados en la yema en el día 12 de incubación. Las concentraciones de los iones fueron (nmoles/g huevo: Cd2+: Dosis 1 (D1: 0,16 y Dosis 2 (D2: 0,32; Pb2+: D1: 8,0 y D2: 16,0 y Cu2+: D1: 1,7 y D2: 3,3. Los resultados se evaluaron después de continuar la incubación in ovo durante 12 y 60 hs Cu2+ y Pb2+ no aumentaron la mortalidad de los embriones, en cambio, la presencia de Cd2+ produjo entre 30 y 86 % de mortalidad de los embriones, con efectos dosis y tiempo dependientes. Los embriones intoxicados con la D2 de Cd2+ durante 60 hs fueron los únicos ejemplares que presentaron disminución en su peso promedio, respecto de los ejemplares de control. La administración de Cd2+ causó efectos teratogénicos más severos que los tratamientos con Cu2+ y Pb2+. Se puede concluir que los metales pesados son embriotóxicos e inducen teratogenia en embriones de pollo en desarrollo. Se sugiere que los mejores parámetros para evaluar la teratogenicidad producida por la intoxicación Cd2+, Cu2+ y Pb2+ son los derrames cutáneos y hepáticos.Teratogenic effects of heavy metals (Cd2+- and Pb2+- acetates and Cu2+- suphate were studied on chick embryos, after the administration as a single dose. Test materials were injected into the yolk on day 12 of incubation. Tested concentrations were (nmole/g egg: Cd2+ Dose 1 (D1: 0.16 and Dose 2 (D2: 0.32; Pb2+: D1: 8.0 and D2: 16.0 and Cu2+: D1: 1.7 and D2: 3.3. Evaluations were performed after in ovo incubation for 12 and 60 hours. Embryonic mortality did not increase at the two dose levels of Cu2+ and Pb2+, while Cd2+ caused 30 and 86% of mortality, showing dose and time responses. Eggs treated with D2 of Cd2+ for 60 hs, significantly decreased the average of body mass embryo, when

  15. Pharmacogenetic evaluation of ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase polymorphisms in teratogenicity of anti-epileptic drugs in women with epilepsy

    Directory of Open Access Journals (Sweden)

    Manna Jose

    2014-01-01

    Full Text Available Aim: Pregnancy in women with epilepsy (WWE who are on anti-epileptic drugs (AEDs has two- to three-fold increased risk of fetal malformations. AEDs are mostly metabolized by Cyp2C9, Cyp2C19 and Cyp3A4 and transported by ABCB1. Patients on AED therapy can have folate deficiency. We hypothesize that the polymorphisms in ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase (MTHFR might result in differential expression resulting in differential drug transport, drug metabolism and folate metabolism, which in turn may contribute to the teratogenic impact of AEDs. Materials and Methods: The ABCB1, Cyp2C9, Cyp2C19 and MTHFR polymorphisms were genotyped for their role in teratogenic potential and the nature of teratogenecity in response to AED treatment in WWE. The allelic, genotypic associations were tested in 266 WWE comprising of 143 WWE who had given birth to babies with WWE-malformation (WWE-M and 123 WWE who had normal offsprings (WWE-N. Results: In WWE-M, CC genotype of Ex07 + 139C/T was overrepresented (P = 0.0032 whereas the poor metabolizer allele FNx012 and FNx012 FNx012 genotype of CYP2C219 was significantly higher in comparison to WWE-N group (P = 0.007 and P = 0.005, respectively. All these observations were independent of the nature of malformation (cardiac vs. non cardiac malformations. Conclusion: Our study indicates the possibility that ABCB1 and Cyp2C19 may play a pivotal role in the AED induced teratogenesis, which is independent of nature of malformation. This is one of the first reports indicating the pharmacogenetic role of Cyp2C19 and ABCB1 in teratogenesis of AED in pregnant WWE.

  16. Efecto teratogénico y toxico de ácidos grasos de cadena corta insaturados, en Rhodnius prolixus Teratogenic and toxic effect of unsaturated fatty acids of short chain, in Rhodnius prolixus

    Directory of Open Access Journals (Sweden)

    Ivonne Gomez

    1985-12-01

    Full Text Available Se estudia el papel teratogénico de dos ácidos grasos insaturados de cadena corta, ácido octinoico y ácido undecilénico, sobre insectos de metamorfosis hemimetábola, Rhodnius prolixus (Hemiptera. La penetración de los ácidos, se realiza a través de la cutícula del abdomen y de los tarsos, se presenta como una acción independiente del grado de distensión de la misma, ya que sus efectos se registran tanto en los insectos repletos, como en los hambrientos; tanto en los tratados tópicamente como en aquellos donde la droga se aplicó al papel de soporte. Los ácidos estudiados aparentemente no afectan la formación de la cutícula, ni la melanización, como tampoco afecta el proceso de la muda. Los daños inducidos por estos ácidos se presentam al azar tanto en los apéndices locomotores como en los cefálicos, observándose un desplazamiento a la proboscide a medida que se incrementa la dosis. De las malformaciones en la proboscide, es el labio el mas dramáticamente dañado, aunque también se presentan daños en los otros apéndices bucales, aisladamente o junto con el daño del labio. El daño en los apéndices locomotores está frecuentemente desplazado al segundo y tercer par de patas, mientras que el par, fue el menos afectado. El ácido octinoico se comportó como teratogénico en las dosis que fueron letales para el insecto con el ácido undecilénico.The teratogenic role of two short-chain unsaturated fatty acids, octinoic acid and undecylenic acid on the hemimetabolic metamorphosis of the insect Rhodnius prolixus (Hemipter is studied. The acids penetrate through the cuticle of the abdomen and tarsi, independently of the amount of distention. The effects are registered equally in satiated or hungry insects, in those treated topically or in those where the treatment was applied to the support paper. The acids apparently do not affect the formation of the cuticle, melanization, nor the metamorphic process. The damage induced by

  17. TERATOGENIC EFFECTS OF SILVER NANOPARTICLES: GROSS ANOMALIES

    OpenAIRE

    Jyoti Prakash; Rajniti; Deepika; Royana

    2015-01-01

    BACK GROUND: Prenatal exposure of AgNPs can induces devastative and detrimental effect in the organogenesis period of the developing embryos and foetuses. Organogenesis period is highly condemnatory and persuadable. Any injury to embryo during this period leads to dysmorphogenesis or even death AIM: The present study means to evaluate the gross anomalies on developing f o etus subsequent to silver nanoparticle ingestion during the gestational period. ...

  18. Influence of Methionine Supplementation on Nicotine Teratogenicity ...

    African Journals Online (AJOL)

    Human and animal studies have shown that maternal tobacco smoking during pregnancy adversely affects pre and postnatal growth and increases the risk of fetal mortality. The aim of the present study was to determine the toxicity of nicotine and protective effect of methionine on the toxic effects of nicotine. Pregnant ...

  19. Teratogenic effects of x-rays

    International Nuclear Information System (INIS)

    Faisal, Arif

    1981-01-01

    The application of x-rays in the medical field has positive and negative effects. The effects of x-ray radiation to the intrauterine embryo and foetus depend on the period of gestation. In the first trimester the embryo may be resorbed and aborted and may also be born with serious defects. In the late trimester radiation may cause less serious defects and it may disturb the function of organs. Many defects involve nerve tissues and are associated with symptoms of mental retardation. To prevent radiation exposure to embryo and foetus, it is necessary to observe the ''ten-day rule'', when x-ray examination is performed. The threshold doses for embryo and foetus are still unknown. (author)

  20. Retinoic acid in developmental toxicology: Teratogen, morphogen and biomarker.

    NARCIS (Netherlands)

    Piersma, Aldert H; Hessel, Ellen V; Staal, Yvonne C

    This review explores the usefulness retinoic acid (RA) related physiological factors as possible biomarkers of embryotoxicity. RA is involved in the morphogenesis of the early embryo as well as in the development and maturation of a wide variety of organ anlagen. The region-specific homeostasis of

  1. Teratogenic effect of isotretinoin on the morphology and palate ...

    African Journals Online (AJOL)

    SERVER

    2007-12-03

    Dec 3, 2007 ... 4Department of Anatomy and Cell Biology, Faculty of Basic Medical Sciences, Obafemi Awolowo University, Ile-Ife,. Osun State. ... that certain stages of embryonic development are more ... period of human development of the eyes, ears and heart. ..... germ and palate development in mouse embryos. Braz.

  2. CASTING A BROAD NETWORK: FISHING FOR MECHANISMS OF RETINOID TERATOGENICITY

    Science.gov (United States)

    This is a short essay that serves to introduce a featured paper for an issue of Toxicological Sciences. The paper being introduced describes a study of mechanisms of retinoid induced abnormal limb development in mice. The paper was notable because the authors used gene expressi...

  3. Teratogenic assessment of 'Winniecure' in pregnant Wistar rats ...

    African Journals Online (AJOL)

    Journal of Pharmacy & Bioresources. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 10, No 2 (2013) >. Log in or Register to get access to full text downloads.

  4. Dose-dependent teratogenicity of valproate in mono- and polytherapy

    DEFF Research Database (Denmark)

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio

    2015-01-01

    OBJECTIVE: To assess the risk of major congenital malformations (MCMs) in association with maternal use of valproic acid (VPA) in monotherapy or adjunctive therapy, and its relationship with dose. METHODS: The analysis was based on prospectively acquired data from EURAP, a registry enrolling women...... treated with antiepileptic drugs (AEDs) in early pregnancy, in which the primary outcome is presence of MCMs at 1 year after birth. Exposure was defined as type and dose of AEDs at time of conception. A comparison was made among 3 exposure types: (1) VPA monotherapy (n = 1,224); (2) VPA combined...... with lamotrigine (LTG) (n = 159); and (3) VPA combined with another AED but not LTG (n = 205). RESULTS: The frequency of MCMs at 1 year after birth was 10.0% for VPA monotherapy, 11.3% for exposures to VPA and LTG, and 11.7% for exposures to VPA + another (non-LTG) AED. Regardless of exposure group, the frequency...

  5. Neurobehavioral teratogenic effects of clomipramine and alpha-methyldopa

    NARCIS (Netherlands)

    Mirmiran, M; Van Haaren, F; Louwerse, A; van de Poll, N E; de Boer, Sietse

    1989-01-01

    Neonatal treatment of rats with centrally acting drugs such as clomipramine was shown to affect adult body and brain weight, behavior and sleep. We made a further study of the effects of clomipramine and tested one dose of alpha-methyldopa. Male rats were treated twice daily with saline, 7.5 or 15

  6. Teratogenic effects of Khat (Catha edulis in New Zealand rabbit

    Directory of Open Access Journals (Sweden)

    Aref Saleh Abdul-Mughni

    2018-03-01

    Conclusion: Prenatal exposure of Khat in rabbit induces harmful effects in defferent visceral organs including liver, kidney, brain, spinal cord, spleen, intestine, heart and lung. [J Adv Vet Anim Res 2018; 5(1.000: 25-36

  7. Studies on tritium (tritiated water) mutagenicity and teratogenicity in rats

    International Nuclear Information System (INIS)

    Yagova, A.Kh.

    1979-01-01

    Single parental exposures to a range of tritium (tritiated water) activities, injecterd intraperitoneally, were used to study induction of genetic damage and effects on prenatal development in rats. In the male, treatment of postmeiotic stages of spermatogenesis was found to produce genetic damage, as judged by the dominant lethality test, at activity levels of the order of 1.0 microcurie/g body weight and above; when treating spermatogonia, no genetic damage was detected by this test. In the female, induced dominant lethality was observed after exposing oocytes in growing follicles to a tritium activity level of 10 microcurie/g b.w. Cytogenetic analysis of spermatocytes in meiosis disclosed increased frequency of reciprocal translocations after exposure of premeiotic cells (spermatogonia) to activities above 7 microcurie/g b.w., the effect tending to rise with increase in activity aministered per gram of body weight. Maternal treatment during early pregnancy was shown to raise prenatal death rate only at activities above 0.1 microcurie/g b.w; with such low activities, no discernible effects on postnatal development were noted, judging by postnatal death rate and increase in offspring body weight with time. In conclusion, experimental evidence was obthained that a tritiated water activity level of 0.1 microcurie per gram body weight (which is one order of magnitude above the annual limit of intake of tritiated water for members of the public) appears to produce no mutagenic effect and exert no influence upon the embryo

  8. Interpretation of Controversial Teratogenic Findings of Drugs Such As Phenobarbital

    OpenAIRE

    Czeizel, Andrew E.; Dudás, Istvan; Bánhidy, Ferenc

    2011-01-01

    Objective. To check the debated association between phenobarbital treatment during pregnancy and risk for congenital abnormalities (CAs) in their children. Study Design. It is a comparison of phenobarbital treatment in the mothers of cases with CA and matched controls without CAs in the Hungarian Case-Control Surveillance System of Congenital Abnormalities. Results. Of 22,843 cases with CA, 149 (0.65%) had mothers with phenobarbital treatment, while of 38,151 control newborn infants without C...

  9. Teratogenic impact of dioxin-activated AHR in laboratory animals

    Science.gov (United States)

    AHR and ARNT are expressed in mouse and human palatal shelves and in the urinary tract of the mouse fetus. AHR expression, translocation to the nucleus, binding to DRE, and activation are required for mediation of TCDD-induction of CP and HN. Although the human palate requires a ...

  10. Drug utilization and teratogenicity risk categories during pregnancy.

    Science.gov (United States)

    Basgül, Alin; Akici, Ahmet; Uzuner, Arzu; Kalaça, Sibel; Kavak, Zehra N; Tural, Alper; Oktay, Sule

    2007-01-01

    A limited number of studies have investigated in detail the use of drugs during pregnancy. Researchers in the present study investigated the details of drug utilization in pregnant women during the month before pregnancy, at the time that they became aware of the pregnancy, and during the first trimester. Face-to-face interviews were conducted with 359 pregnant women who were admitted to the fetal medicine unit at a university hospital for diagnosis and follow-up. A questionnaire was used to document sociodemographic characteristics and details of drug use. Drugs were categorized according to the US Food and Drug Administration fetal risk classification. Mean maternal age was 29.9+/-5.1 y, and mean gestational age was 19.6+/-9.5 wk. Many of the pregnant women studied (46.6%) were university graduates, and most (61.9%) had a relatively high annual income. Mean gestational age when participants first learned of their pregnancy was 39.8+/-16.4 d. One hundred seventeen participants (32.6%) used drugs during the month before conception, 54 (15%) at the time when they learned of their pregnancy, 180 (50.1%) at the time of the interview, and 289 (80.5%) during the first trimester. The percentages of drugs in categories D and X used by these subjects were 14%, 13.5%, 2.9%, and 5.9%, respectively. Most of the drugs were hormones. The total rate of drug utilization was not high before and during the first trimester of pregnancy. A considerable number of women were using drugs from the D and X categories; however, these numbers decreased significantly when women learned of their pregnancies. Intake of folic acid, vitamins, and iron was very low during the preconception period and was not high enough during the first trimester; this suggests that particular attention should be paid to the use of beneficial "safe" drugs during the preconception and early pregnancy periods.

  11. Role of folic acid in chlorpyrifos induced teratogenicity in mice ...

    African Journals Online (AJOL)

    Folic acid is known to reduce the incidence of neural tube defects, in animal experiments however, it has not been effective in reducing the congenital anomalies caused by antiepileptics and many other chemicals. Pesticides of organophosphate group such as chlorpyrifos are widely used in agriculture and household, and ...

  12. Toxicity and teratogenicity evaluation of fenproporex in mice fetuses descending from parents that were exposed to this drug during intrauterine life Avaliação da toxicidade e da teratogenicidade do femproporex em fetos de camundongos provenientes de pais expostos à droga durante a vida intra-uterina

    Directory of Open Access Journals (Sweden)

    Camila Queiroz Moreira

    2007-10-01

    Full Text Available Fenproporex is an anorectic drug that is transformed into amphetamine in the organism. The use of amphetaminic compounds during pregnancy increases the risk of exencephaly, cleft palate and cardiac malformations. The aim of this study was to evaluate embryo-fetal development, embryotoxicity and possible teratogenic effects in mice fetuses descending from parents that were exposed to fenproporex duringintra-uterine development. Pregnant females were treated daily, by gavage, with 15 mg/kg of fenproporex during all the gestation. When the off springs reached the adult age, they were mated with integral mice, obtaining the2nd generation. On the 18th gestational day, female mice were killed. It was observed that fenproporex did not alter significantly placent weight, fetuses length, rate of postimplantation loss, visceral and skeletal analysis. This may have occurred due to the decrease of the amphetamine effects on the 2nd generation. However, there was statistically significant difference in relation to the fetuses weight. The reduction of fetal weight is used as parameter to evidence toxic effects of asubstance. Therefore, the results suggest that fenproporex presented fetaltoxicity in the tested experimental conditions. Femproporex é um anorexígeno que se transforma em anfetamina no organismo. O uso de compostos anfetamínicos durante a gravidez aumenta o risco de exencefalia, de fenda palatina e de malformações cardíacas. O objetivo deste estudo foi avaliar o desenvolvimento embriofetal, a embriotoxicidade e possíveis efeitos teratogênicos em fetos de camundongos provenientes de pais que foram expostos ao femproporex durante o desenvolvimento intra-uterino. As fêmeas prenhes foram tratadas diariamente, via gavage, com 15 mg/kg de femproporex, durante toda a gestação. Quando as progênies atingiram a idade adulta, foram acasaladas com camundongos íntegros, obtendo-se a 2ª geração. No 18º dia de prenhez, as fêmeas foram mortas

  13. Meta-analysis of toxicity and teratogenicity of 133 chemicals from zebrafish developmental toxicity studies

    Science.gov (United States)

    Zebrafish developmental toxicity testing is an emerging field, which faces considerable challenges regarding data meta-analysis and the establishment of standardized test protocols. Here, we present an initial correlation study on toxicity of 133 chemicals based on data in the li...

  14. Teratogenicity following inhalation exposure of rats to a high-boiling coal liquid

    Energy Technology Data Exchange (ETDEWEB)

    Springer, D.L.; Poston, K.A.; Mahlum, D.D.; Sikov, M.R.

    1982-01-01

    On days 12 to 16 of gestation pregnant rats were exposed to heavy distillate (hd), the highest-boiling material derived from the solvent refined coal-II (SRC-II) process, and the litters were examined at day 21. Adverse biological effects were observed in the group of animals exposed to an aerosol concentration of 0.66 mg 1/sup -1/ (1.8 ..mu..m, mass medium aerodynamic diameter); groups of animals exposed to lower aerosol concentrations (0.084 and 0.017 mg 1/sup -1/) were largely unaffected. Embryolethality during mid- and late gestation appeared attributable to the coal liquid exposure. Fetuses from pregnant rats in the high exposure group were smaller in weight and length than fetuses from control animals, and skeletal ossification was reduced. Increased incidences of small lungs and cleft palate were observed in fetuses from the high exposure group. Pregnant rats in the high-exposure group gained less weight than controls during gestation; the reduced weight gain was accounted for by the reduced size of the fetuses and placentas. Even though maternal body weight (exclusive of the products of conception) was unaffected by the exposure, the weights of the maternal thymus, lung and spleen were altered in the high exposure group.

  15. Teratogenicity following inhalation exposure of rats to a high-boiling coal liquid

    Energy Technology Data Exchange (ETDEWEB)

    Springer, D.L.; Poston, K.A.; Mahlum, D.D.; Sikov, M.R.

    1982-01-01

    On days 12-16 of gestation pregnant rats were exposed to heavy distillate (HD), the highest-boiling material derived from the solvent refined coal-II (SRC-II) process, and the litters were examined at day 21. Adverse biological effects were observed in the group of animals exposed to an aerosol concentration of 0.66 mg 1/sup -1/ (1.8 ..mu..m, mass medium aerodynamic diameter (MMAD)); groups of animals exposed to lower aerosol concentrations (0.084 and 0.017 mg 1/sup -1/) were largely unaffected. Embryolethality during mid- and late gestation appeared attributable to the coal liquid exposure. Fetuses from pregnant rats in the high exposure group were smaller in weight and length than fetuses from control animals, and skeletal ossification was reduced. Increased incidences of small lungs and cleft palate were observed in fetuses from the high exposure group. Pregnant rats in the high-exposure group gained less weight than controls during gestation; the reduced weight gain was accounted for by the reduced size of the fetuses and placentas. Even though maternal body weight (exclusive of the products of conception) was unaffected by the exposure, the weights of the maternal thymus, lung and spleen were altered in the high exposure group.

  16. Teratogenic processes in an embryo without gills and low yolk absorption of Zapteryx brevirostris (Elasmobranchii: Rhinobatidae

    Directory of Open Access Journals (Sweden)

    Wanessa Priscila David do Carmo

    2015-12-01

    Full Text Available Abstract This is the first report of morphological anomaly in embryos of Zapteryx brevirostris (Lesser guitarfish, a very common species in Brazil. The gills were absent, and the pectoral fins were not fully formed nor were they completely fused to the head. They were asymmetrical, with the larger left pectoral fin projecting more toward the head (almost at the height of the eyes. The pelvic fin was absent, making sexing impossible. The cause of the morphological deformity is uncertain, although a nutritional problem of the embryo is evoked.

  17. Environmental impact of a teratogenic actinide: a case study of americium-241

    Energy Technology Data Exchange (ETDEWEB)

    Wang, J.; Yang, J.Y.

    1985-10-16

    Americium-241 is widely used as a radiation source, but it also has some potential risk if taken into the body. Although the radiotoxicity of americium-241 is small compared to other transuranic actinides, its effects on the reproductive system and on development of the placenta are more damaging than the effects of plutonium-239. A previous report based on a worst-case scenario involving a hypothetical fire accident in a contaminated facility indicated that there could have been a significant impact on nearby residents from a unit release of americium-241 via atmospheric dispersion. However, because the facility is located in a rural region where most drinking water supplies are drawn from private wells, it is believed that deposition of americium-241 from the atmosphere might also have impacts via the groundwater pathway by infiltration of rainwater. In this analysis, a three-dimensional analytical mathematical model is used to assess several aspects of americium-241 contamination of groundwater, including radioactive transformation, advection, dispersion, and soil sorption. Simulation results indicate that no significant radiological impacts would occur to the nearby residents via the groundwater pathway. 15 refs., 2 figs., 2 tabs.

  18. Anticonvulsants Teratogenic Mechanism Involves Alteration of Bioelectrically-controlled Processes in the Embryo. A hypothesis

    Science.gov (United States)

    Hernández-Díaz, Sonia; Levin, Michael

    2014-01-01

    Maternal use of anticonvulsants during the first trimester of pregnancy has been associated with an elevated risk of major congenital malformations in the offspring. Whether the increased risk is caused by the specific pharmacological mechanisms of certain anticonvulsants, the underlying epilepsy, or common genetic or environmental risk factors shared by epilepsy and malformations is controversial. We hypothesize that anticonvulsant therapies during pregnancy that attain more successful inhibition of neurotransmission might lead to both better seizure control in the mother and stronger alteration of bioelectrically-controlled processes in the embryo that result in structural malformations. If our theory were correct, development of pharmaceuticals that do not alter cell resting transmembrane voltage levels could result in safer drugs. PMID:24815983

  19. Alteration of bioelectrically-controlled processes in the embryo: a teratogenic mechanism for anticonvulsants.

    Science.gov (United States)

    Hernández-Díaz, Sonia; Levin, Michael

    2014-08-01

    Maternal use of anticonvulsants during the first trimester of pregnancy has been associated with an elevated risk of major congenital malformations in the offspring. Whether the increased risk is caused by the specific pharmacological mechanisms of certain anticonvulsants, the underlying epilepsy, or common genetic or environmental risk factors shared by epilepsy and malformations has been controversial. We hypothesize that anticonvulsant therapies during pregnancy that attain more successful inhibition of neurotransmission might lead to both better seizure control in the mother and stronger alteration of bioelectrically-controlled processes in the embryo that result in structural malformations. We propose that development of pharmaceuticals that do not alter cell resting transmembrane voltage levels could result in safer drugs. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Teratogenic Effects of Diatom Metabolites on Sea Urchin Paracentrotus lividus Embryos

    Directory of Open Access Journals (Sweden)

    Giovanna Romano

    2010-03-01

    Full Text Available The diatom-derived polyunsaturated aldehydes (PUAs, 2-trans,4-trans-decadienal, 2-trans,4-trans-octadienal, 2-trans,4-trans,7-octatrienal, 2-trans,4-trans-heptadienal, as well as tridecanal were tested on early and later larval development in the sea urchin Paracentrotus lividus. We also tested the effect of some of the more abundant diatom polyunsaturated fatty acids (PUFAs on development, in particular 5,8,11,14,17-eicosapentaenoic acid (EPA, one of the main precursors of diatom PUAs, as well as 4,7,10,13,16,19-docosahexaenoic acid (DHA, 6,9,12,15-octadecatetraenoic acid (stearidonic acid, 6,9,12-octadecatrienoic acid (γ-linolenic acid and 9,12-octadecadienoic acid (linoleic acid. PUAs blocked sea urchin cell cleavage in a dose dependent manner and with increasing chain length from C7 to C10 PUAs, with arrest occurring at 27.27 µM with heptadienal, 16.13 µM with octadienal, 11.47 µM with octatrienal and 5.26 mM with decadienal. Of the PUFAs tested, only EPA and stearidonic acid blocked cleavage, but at much higher concentrations compared to PUAs (331 μM for EPA and 181 μM for stearidonic acid. Sub-lethal concentrations of decadienal (1.32–5.26 μM delayed development of embryos and larvae which showed various degrees of malformations depending on the concentrations tested. Sub-lethal concentrations also increased the proportion of TUNEL-positive cells indicating imminent death in embryos and larvae. Using decadienal as a model PUA, we show that this aldehyde can be detected spectrophotometrically for up to 14 days in f/2 medium.

  1. Embryotoxic and teratogenic effects of petroleum hydrocarbons in mallards (Anas platyrhynchos)

    Science.gov (United States)

    Hoffman, D.J.

    1979-01-01

    Egg surface applications of microliter quantities of crude and refined oils of high aromatic content are embryotoxic to mallards (Anas platyrhynchos) and other avian species; applications of aliphatic hydrocarbons have virtually no effect. Mallard eggs at 72 h of development were exposed to a mixture of aromatic hydrocarbons or to aromatic compounds representative to those present in crude oil to assess their toxicity. The class composition of the mixture was similar to that of South Louisiana crude oil, an American Petroleum Institute reference oil. Application of 20 microliter of the mixture reduced embryonic survival by nearly 70%. The temporal pattern of embryonic death was similar to that after exposure to South Louisiana crude oil. Embryonic growth was stunted, as reflected by weight, crown-rump length, and bill length, and there was a significant increase in the incidence of abnormal survivors. When individual classes of aromatic hydrocarbons were tested, tetracyclics caused some embryonic death at the concentrations in the mixture. When classes were tested in all possible combinations of two, no combination appeared to be as toxic as the entire mixture. Addition of the tetracyclic compound chrysene to the aromatic mixture considerably enhanced embryotoxicity, but could not completely account for the toxicity of the crude oil. The presence of additional unidentified polycyclic aromatic hydrocarbons as well as methylated derivatives of polycyclic aromatic compounds such as chrysene may further account for the embryotoxicity of the crude oil.

  2. Embryotoxic and Teratogenic Effects of Nickel in Swiss Albino Mice during Organogenetic Period

    Directory of Open Access Journals (Sweden)

    Shivi Saini

    2013-01-01

    Full Text Available The present study evaluates potential hazardous of nickel (Ni+2 as NiCl2·6H2O to Swiss albino mice fetus. Ni was administered orally on body weight base from days 6 to 13 of gestation period. Based on LD50, Ni doses (46.125, 92.25, and 184.5 mg Ni/kg b.wt. were used. On day 18 of gestation, uteri of the sacrificed dams were examined. A dose-dependent decrease ( in the body weight of the pregnant females and fetuses during the gestation period was observed. Number of implant sites and placental weight at all the three dose levels was lower compared with their respective control groups. Average number of live fetuses/dams reduced significantly ( at 184.5 mg Ni/kg b.wt. with concomitant increase in the percentage of postimplantation death and percentage of resorbed, macerated, and dead fetuses, respectively. Exposure increased the fetal malformations, namely, hydrocephaly, open eyelids, microphthalmia, exophthalmia, club foot, umbilical hernia, and skeletal anomalies. Reduced ossification of nasal, frontal, parietal, intraparietal, and supraoccipital bones, absence/gap between the ribs, reduced/fused sternebrae, vertebral centra, and caudal vertebrae, reduced pelvic elements, absence of carpals, metacarpals, tarsals, metatarsals, and phalanges were distinct. This indicates vulnerability of the mice fetus to nickel during prenatal exposure.

  3. Environmental impact of a teratogenic actinide: a case study of americium-241

    International Nuclear Information System (INIS)

    Wang, J.; Yang, J.Y.

    1985-01-01

    Americium-241 is widely used as a radiation source, but it also has some potential risk if taken into the body. Although the radiotoxicity of americium-241 is small compared to other transuranic actinides, its effects on the reproductive system and on development of the placenta are more damaging than the effects of plutonium-239. A previous report based on a worst-case scenario involving a hypothetical fire accident in a contaminated facility indicated that there could have been a significant impact on nearby residents from a unit release of americium-241 via atmospheric dispersion. However, because the facility is located in a rural region where most drinking water supplies are drawn from private wells, it is believed that deposition of americium-241 from the atmosphere might also have impacts via the groundwater pathway by infiltration of rainwater. In this analysis, a three-dimensional analytical mathematical model is used to assess several aspects of americium-241 contamination of groundwater, including radioactive transformation, advection, dispersion, and soil sorption. Simulation results indicate that no significant radiological impacts would occur to the nearby residents via the groundwater pathway. 15 refs., 2 figs., 2 tabs

  4. Teratogenic radiation effects: Phenomena, dose-response relationships and risk levels

    International Nuclear Information System (INIS)

    Konermann, G.

    1991-01-01

    The report in hand informs about a study performed within the framework of the research project 'Animal experiments with albino mice for establishing a model for the detection and assessment of radiation-induced, developmental risks in man due to low-dose irradiation'. The subjects investigated in this study are: (1) Dose-response relationships for postnatal developmental disturbances of the brain as a result of prenatal X-ray treatment. (2) Biokinetics, distribution patterns and effects of inorganically and organically bonded radioiodine (I-125) during the phase of development of the brain. For investigation of the first-mentioned subject, computerized microphotograph analysis was applied for detecting and assessing disturbances of the alignment of axons, as well as deviations from normal cross-sectional data of the Cortex layer, and cerebral commissures as final locations of neurogenetic damage. With all parameters studied, the slope of the relevant curves was found to decrease as a function of age of the fetus at the time of exposure. In addition, time factor effects were investigated. For the parameter cross-sectional area of the Cortex, a clear decrease of effect was found, but for all other parameters, reactions were ambiguous. The study into the second subject was done with cell cultures, showing that the I-125 bonded to the cell nucleus has a much stronger radiotoxic effect than I-125 bonded to the cytoplasma. This difference in effect was studied in mice after incorporation of equal doses administered by way of (I-125)-sodium iodide or (I-125)-iododesoxyuridine. Long-term effects on Cortex cross-sectional areas, cerebral commissures or the texture of axons were quantified by microphotograph analysis. Acute cell death and initial disturbances of the neuronal cell growth were evident after incorporation of (I-125)-IdUR, but not detectable after administration of (I-125)-NaI. (orig./MG) [de

  5. [Study of the radioprotective effects of TMG on teratogenic malformations in irradiated mice].

    Science.gov (United States)

    Gu, Y; Hasegawa, T; Kim, H; Suzuki, I; Mori, T; Yamamoto, Y

    2000-12-01

    ICR mice fetuses in the organogenesis stage were used to clarify experimentally the mechanism of the protective effect of vitamin E derivant (TMG: 2-(alpha-D-Glucopyranosyl) methyl-2, -5, -7, -8-Teramethylchorman-6-working woman) on the effects of radiation. The authors paid careful attention to radiation, and the radioprotective effects of TMG on the induction of malformations was examined. Radiation is an important consideration because of its widespread use in the areas of medicine, nuclear energy, and industry. Malformations induced by radiation at the organogenesis stage, skeletal malformations, and the effects at the cellular level of embryos were examined in this research. Further, the mechanism of the protection effect of TMG against radiation-induced malformations was analyzed and observed experimentally. Thus, this study was done to provide fundamental data on the radioprotective agent TMG. It was clear that TMG exerted radioprotective effects against embryonic death and the rate of teratogenesis when administered before exposure. Such effects were also exerted against skeletal malformations and fetal body weight. In summary, radioprotective effects were observed at the whole-body level as well as at the cellular level.

  6. Dithiocarbamates are teratogenic to developing zebrafish through inhibition of lysyl oxidase activity

    NARCIS (Netherlands)

    van Boxtel, A.L.; Kamstra, J.H.; Fluitsma, D.M.; Legler, J.

    2010-01-01

    Dithiocarbamates (DTCs) are a class of compounds that are extensively used in agriculture as pesticides. As such, humans and wildlife are undoubtedly exposed to these chemicals. Although DTCs are thought to be relatively safe due to their short half lives, it is well established that they are

  7. Study of the radioprotective effects of TMG on teratogenic malformations in irradiated mice

    International Nuclear Information System (INIS)

    Gu, Yeunhwa; Hasegawa, Takeo; Suzuki, Ikukatsu; Mori, Takehiko; Yamamoto, Youichi; Kim, Hwakon

    2000-01-01

    ICR mice fetuses in the organogenesis stage were used to clarify experimentally the mechanism of the protective effect of vitamin E derivant (TMG: 2- (α-D-Glucopyranosyl) methyl-2, -5, -7, -8-Teramethylchorman-6-working woman) on the effects of radiation. The authors paid careful attention to radiation, and the radioprotective effects of TMG on the induction of malformations was examined. Radiation is an important consideration because of its widespread use in the areas of medicine, nuclear energy, and industry. Malformations induced by radiation at the organogenesis stage, skeletal malformations, and the effects at the cellular level of embryos were examined in this research. Further, the mechanism of the protection effect of TMG against radiation-induced malformations was analyzed and observed experimentally. Thus, this study was done to provide fundamental data on the radioprotective agent TMG. It was clear that TMG exerted radioprotective effects against embryonic death and the rate of teratogenesis when administered before exposure. Such effects were also exerted against skeletal malformations and fetal body weight. In summary, radioprotective effects were observed at the whole-body level as well as at the cellular level. (author)

  8. Histochemical characterization of CNS development in mice: A methodological contribution for evaluation of teratogenic effects

    International Nuclear Information System (INIS)

    Plendl, J.; Schmahl, W.

    1986-01-01

    In the NMRI-mouse strain Dolichos biflorus agglutinin (DBA) showed an outstanding histochemical affinity to some newly developed neuro-glial cells on gestation day 13 and in front of all to the vessel endothelium from gestation day 8 on. The latter affinity pattern, however, was not homogenously distributed within the embryo, but clearly showed varying intensities with advancing cell differentiation. The latter finding was intensely studied at the embryonal central nervous system during the late organogenesis stage (days 10 to 13). Two hours after X-irradiation with 1.0 Gy some irregular DBA-positive patches were found on the surface of neuronal cells which otherwise seemed to be still unaffected. The DBA-affinity of these cells was intensified until 6 hours post irradiation. Simultaneously it was evident that these cells were pre-necrotic. After phagocytotic elimination of these cells the remaining nervous structures were completely DBA-negative. These findings indicate to a possible use of DBA for evaluation of an early lesion pattern in neuroteratological studies. (orig.)

  9. Marginal Biotin Deficiency Is Teratogenic in ICR Mice1,2

    OpenAIRE

    Mock, Donald M.; Mock, Nell I.; Stewart, Christopher W.; LaBorde, James B.; Hansen, Deborah K.

    2003-01-01

    The incidence of marginal biotin deficiency in normal human gestation is approximately one in three. In ICR mice, maternal biotin deficiency results in cleft palate, micrognathia, microglossia and limb hypoplasia. However, the relationships among the severity of maternal biotin deficiency, fetal biotin status and malformations have not been reported. This study utilized validated indices of biotin status to investigate the relationships among maternal biotin status, fetal biotin status and th...

  10. The use of ultrasonography to study teratogenicity in ruminants: Evaluation of Ipomoea carnea in goats

    Science.gov (United States)

    Ipomoea carnea (I. carnea) is a poisonous plant found in Brazil and other tropical countries that often poison livestock. The plant contains calystegines and swainsonine, which inhibit cellular enzymes and cause systematic cell death. The objective of this study was to evaluate the perinatal effects...

  11. Antiepileptic teratogen valproic acid (VPA) modulates organisation and dynamics of the actin cytoskeleton

    DEFF Research Database (Denmark)

    Walmod, P S; Skladchikova, G; Kawa, A

    1999-01-01

    for the VPA mediated inhibition of motility. In addition it is shown that the actomyosin cytoskeleton of VPA-treated cells was capable of contraction upon exposure to ATP, indicating that the reduced motility of VPA-treated cells was not caused by an inhibition of actomyosin contraction. On the other hand...... state. These findings indicate that VPA affects cell morphology and motility through interference with the dynamics of the actin cytoskeleton....

  12. EXPOSURE-DISEASE CONTINUUM FOR 2-CHLORO-2'-DEOXYADENOSINE (2CDA), A PROTOTYPE OCULAR TERATOGEN. 1. DOSE-RESPONSE ANALYSIS

    Science.gov (United States)

    Treatment of pregnant mice with 2-chloro-2'-deoxyadenosine (2CdA) on day 8 of gestation induces coloboma, microphthalmia and anophthalmia through a mechanism coupled to the effects of the p53 tumor suppressor gene (Wubah et al.'96). The present study defines the dosimetry for 2Cd...

  13. Studies of the teratogenic potential of exposure of rats to 6000-MHz microwave radiation. II. Postnatal psychophysiologic evaluations

    International Nuclear Information System (INIS)

    Jensh, R.P.

    1984-01-01

    Wistar rats (36) were exposed daily throughout pregnancy to a power density level of 35 mW/cm 2 of 6000-MHz microwave radiation (11), sham irradiated (10), or used as control animals (15). Litters were culled to a maximum of eight F 1 /sub a/ offspring/litter (total = 124) on Postnatal Day 1 and subjected to a series of reflex tests beginning Day 3. Mothers were rebred 10 days after weaning. Teratologic evaluations were completed on 263 F 1 /sub b/ offspring. Weekly weights were recorded for 298 F 1 /sub a/ offspring. At 60 days, behavioral testing was initiated on 121 offspring. At 90 days, offspring were bred within/across groups. Teratologic evaluations were completed on 659 F 2 term fetuses. Organ weight analyses were completed on 17 mothers and 181 F 1 /sub a/ adult offspring, and blood analyses on 21 mothers and 131 offspring. Sex differences within groups were observed in four behavioral tests and in blood data. Significant differences between groups were observed for: F 1 /sub b/ term fetal weight; F 1 /sub a/ eye opening, postnatal growth to the fifth week, water T-maze and open field test results; and several organ/body weight ratios. These results indicate that exposure to 6000-MHz radiation at this power density level may result in subtle long-term neurophysiologic alterations not detectable at term using conventional morphologic teratologic procedures

  14. Studies of the teratogenic potential of exposure of rats to 6000-MHz microwave radiation. II. Postnatal phychophysiologic evaluations

    International Nuclear Information System (INIS)

    Jensh, R.P.

    1984-01-01

    Wistar rats (36) were exposed daily throughout pregnancy to a power density level of 35 mW/cm 2 of 6000-MHz microwave radiation (11), sham irradiated (10), or used as control animals (15). Litters were culled to a maximum of eight F 1 /sub a/ offspring/litter (total = 124) on Postnatal Day 1 and subjected to a series of reflex tests beginning Day 3. Mothers were rebred 10 days after weaning. Teratologic evaluations were completed on 263 F 1 /sub b/ offspring. Weekly weights were recorded for 298 F 1 /sub a/ offspring. At 60 days, behavioral testing was initiated on 121 offspring. At 90 days, offspring were bred within/across groups. Teratologic evaluations were completed on 659 F 2 term fetuses. Organ weight analyses were completed on 17 mothers and 181 F 1 /sub a/ adult offspring, and blood analyses on 21 mothers and 131 offspring. Sex differences within groups were observed in four behavioral tests and in blood data. Significant differences between groups were observed for: F 1 /sub b/ term fetal weight; F 1 /sub a/ eye opening, postnatal growth to the fifth week, water T-maze and open field test results; and several organ/body weight ratios. These results indicate that exposure to 6000-MHz radiation at this power density level may result in subtle long-term neurophysiologic alterations not detectable at term using conventional morphologic teratologic procedures

  15. Studies of the teratogenic potential of exposure of rats to 6000-MHz microwave radiation. I. Morphologic analysis at term

    International Nuclear Information System (INIS)

    Jensh, R.P.

    1984-01-01

    Thirty-six pregnant Wistar strain albino rats were exposed throughout pregnancy to 6000-MHz microwave radiation at a power density level of 35 mW/cm 2 or were used as controls. The irradiation did not cause a significant increase in maternal body temperature as measured by a rectal thermocouple. The rats were randomly assigned to one of four groups: home cage control (5), anechoic chamber control (10), sham-irradiated concurrent control (10), and irradiated (11). All animals were killed on the 22nd day of gestation, and maternal tissues were removed and weighed and maternal blood samples were taken. The 384 resultant fetuses and their placentas were individually weighed, fixed, and dissected to determine normality. Teratologic evaluation included the following parameters: maternal weight and weight gain; mean litter size; maternal organ weight and organ weight/body weight ratios; body weight ratios of brain, liver, kidneys, and ovaries; maternal peripheral blood parameters including hematocrit, hemoglobin, and white cell counts; number of resorptions and resorption rate; number of abnormalities and abnormality rate; mean term fetal weight. The irradiated fetuses exhibited slight but statistically significant growth retardation at term. Term maternal monocyte count was also significantly depressed. No other parameters differed between the control groups and the irradiated group

  16. Lethal and teratogenic effects after exposure to X-rays at various times of early murine gestation

    International Nuclear Information System (INIS)

    Mueller, W.U.S.; Streffer, C.

    1990-01-01

    Various well-defined stages during completion of the second meiotic division and early organogenesis of mouse embryos were X-irradiated with doses of 1-4 Gy (100-400 rad). The major risk was prenatal mortality with radiation sensitivity changing markedly with dependence on the developmental stage irradiated; in the case of day 1 even within hours. The surviving fetuses did show a significantly enhanced frequency of malformations on day 19 of gestation (mostly gastroschisis and some exencephalies). This was true for all stages between days 1 and 8; only sensitivity again changed considerably. The radiation doses used in this study are markedly higher than doses that can be expected from radiation diagnostics, but exposure is in a range comparable to doses that can occur in radiation therapy (e.g., Morbus Hodgkin)

  17. Teratogenicity, Mutagenicity, and Effects of Grade 2 Diesel Fuel on Reproduction in a Single Generation of Rats.

    Science.gov (United States)

    1987-10-01

    nation. The first had a distorted cranium and short body. The second had divided cranial plates, cervical vetebra, and upper thoracic vertebra (Figure...intestine and fat. A fourth fetus in this litter was examined viscerally and had adiaphramatic hernia , and a fifth fetus had greatly distended ventricles...cranium and short body, the bottom fetus has divided cranium, cervical vertebra, and upper thorax vertebra. 14 0DI ~ -:% % Lac ’ ’L apparent cranial

  18. EXPOSURE-DISEASE CONTINUUM FOR 2-CHLORO-2'-DEOXYADENOSINE, A PROTOTYPE OCULAR TERATOGEN. 3. INTERVENTION WITH PK11195. (R827445)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  19. Immunomodulatory drugs disrupt the cereblon-CD147-MCT1 axis to exert antitumor activity and teratogenicity

    NARCIS (Netherlands)

    Eichner, Ruth; Heider, Michael; Fernández-Sáiz, Vanesa; van Bebber, Frauke; Garz, Anne-Kathrin; Lemeer, Simone|info:eu-repo/dai/nl/311474683; Rudelius, Martina; Targosz, Bianca-Sabrina; Jacobs, Laura; Knorn, Anna-Maria; Slawska, Jolanta; Platzbecker, Uwe; Germing, Ulrich; Langer, Christian; Knop, Stefan; Einsele, Herrmann; Peschel, Christian; Haass, Christian; Keller, Ulrich; Schmid, Bettina; Götze, Katharina S; Kuster, Bernhard; Bassermann, Florian

    Immunomodulatory drugs (IMiDs), such as thalidomide and its derivatives lenalidomide and pomalidomide, are key treatment modalities for hematologic malignancies, particularly multiple myeloma (MM) and del(5q) myelodysplastic syndrome (MDS). Cereblon (CRBN), a substrate receptor of the CRL4 ubiquitin

  20. The ribosome-inactivating, antiproliferative and teratogenic activities and immunoreactivities of a protein from seeds of Luffa aegyptiaca (Cucurbitaceae).

    Science.gov (United States)

    Ng, T B; Chan, W Y; Yeung, H W

    1993-05-01

    1. The protein isolated from Luffa aegyptiaca seeds was capable of inhibiting protein synthesis in a rabbit reticulocyte lysate system and [3H]thymidine uptake by mouse melanoma (B16) cells. 2. It also adversely affected the development of mouse embryos in culture. 3. In enzyme-linked immunosorbent assay it reacted with antisera raised against other ribosome-inactivating proteins.

  1. Detection in chick embryo of fetoproteins not recognized by the dam's immune system and of soluble alloantigens. Presumptive teratogenic and abortogenic capacity of their specific IgY

    Directory of Open Access Journals (Sweden)

    Rodríguez-Burgos Antonio

    2003-06-01

    Full Text Available Abstract Background The aim of this work was to detect antigens, non-self to the dam, potentially present in chick embryo prior to organogenesis with a view to establishing the consequences of their neutralization on chick development. To this end, hens were immunized with the extract from embryos incubated for 53 h. Their eggs were either used to isolate immunoglobulins for dot and blot tests or incubated for variable lengths of time. Results Immunoblot tests, using adsorbed primary and secondary antibodies against paternal serum, revealed the presence of at least four antigens of 32, 34, 70 and 200 kDa that can be classified as soluble alloantigens. The same antibodies against chick embryo extracts (between 53 h and 9 showed at least five aged antigens of 34, 52, 90, 200 and 250 kDa, not detected in cock serum, that can thus be considered as soluble, foreign to the immunized hens and transitory antigens. The abnormalities observed included arrested development and fetal death, as well as minor functional damage in the few chicks that were born alive. The ratio of abnormal to normal embryos was 2.85 in the experimental group and 0.43 in the control group. With regard to congenital anomalies it must be said that of the 81 eggs incubated only four chicks were born alive, and of these, only one had a healthy birth and subsequent growth. The other three showed a transitory ataxia and one of them presented adult lumbar scoliosis and asymmetric pelvis. Conclusions The problem of recurrent spontaneous abortions is revisited in the light of these results. Some recent data suggest that soluble alloantigens may be candidates for a new etiological entity in recurrent spontaneous abortions. They can also be the cause of some congenital anomalies. The soluble, foreign, transitory antigens may have a similar effect although there is no supportive data in the literature.

  2. International practices in the provision of teratology information: a survey of international teratogen information programmes and comparisons with the North American model.

    Science.gov (United States)

    Hancock, Rebecca L; Ungar, Wendy J; Einarson, Adrienne; Koren, Gideon

    2010-10-01

    Teratology Information Services (TIS) provide health care professionals and the public with information regarding the safety and/or risk of exposures during pregnancy and lactation, mainly via telephone consultations. An international comparison of clinical practices at TIS has never been conducted. The survey objective was to compare international TIS to North American TIS, with an aim to identify strengths and challenges that can lead to service improvement. Twenty-two international TIS were approached for participation during an international conference. TIS were surveyed on information in six categories: services, staffing, operations, data collection, knowledge transfer activities and additional information. Data were summarized using descriptive statistics. Statistical tests were conducted using SPSS®. Sixteen TIS from 12 countries participated. Survey results were compared with previously reported results from a similar survey of North American TIS (16 US, two Canadian). TIS exist in a variety of departments and settings, but most commonly are in university hospitals. Pregnant women were the most commonly counselled group worldwide. International TIS spent significantly more time fielding inquiries regarding medications, while North American TIS had a wider variety of inquiry categories. All TIS could improve budget tracking. Overall, service practices and goals were similar, although international TIS conducted more follow-up with service users than North American TIS. This report offers TIS the first ever opportunity to compare practices. Increased dialogue between TIS encourages sharing of best practices and improves the ability of these important public health programmes to support women and health care providers. © 2010 Blackwell Publishing Ltd.

  3. QSAR model for human pregnane X receptor (PXR) binding: Screening of environmental chemicals and correlations with genotoxicity, endocrine disruption and teratogenicity

    DEFF Research Database (Denmark)

    Dybdahl, Marianne; Nikolov, Nikolai G.; Wedebye, Eva Bay

    2012-01-01

    The pregnane X receptor (PXR) has a key role in regulating the metabolism and transport of structurally diverse endogenous and exogenous compounds. Activation of PXR has the potential to initiate adverse effects, causing drug–drug interactions, and perturbing normal physiological functions...

  4. Teratogenicity Induced By 13-Cis-Retinoic Acid and/or Gamma Irradiation on Bone of Fetuses and Placenta of Pregnant Albino Rats

    International Nuclear Information System (INIS)

    Ramadan, F.L.; Ismail, N.H.

    2011-01-01

    Isotretinoin (13-cis retinoic acid) has revolutionized the management of severe treatment-resistant acne and it has been widely used for a range of dermatological conditions. During pregnancy, high incidence of developmental anomalies were occurred in pregnant rats given isotretinion and/or exposed to gamma irradiation on specific days during organogenesis. The objective of this study was to evaluate the side effects of isotretinoin administration and/or exposure to gamma radiation on the placenta of pregnant rats, vertebrae and neural spine of their fetuses. Isotretinoin at the dose level 70 mg/kg was daily administered via an oral stomach tube to pregnant adult albino rats from the 11th to 15th days of pregnancy while mothers were subjected to gamma radiation 1.5 Gy as fractionated dose (0.5 Gy/3 times) on the 11th, 12th and 13th day of gestation. The experimental investigations carried out one day prior to parturition (the 20 th day of gestation) have demonstrated that isotretinoin intake from the 11th-15th days of gestation induced embryological, biochemical, histochemical and histopathological disorders in irradiated mothers and their fetuses. The data obtained revealed that isotretinoin administration and/or gamma irradiation caused significant elevation in alkaline phosphatase accompanied by a decline in total protein and DNA in the placenta tissues and vertebrae bone. In addition, histopathological results showed different distortions in the placenta which varied from necrotic nuclei of giant cells, haemorrhage and pyknotic nuclei in trophoblast. Moreover, ill-shaped vertebrae with degenerated osteogenic layers and reduced number of chondrocytes together with severe damage in spine neural arch were viewed. In conclusion, isotretinoin is a serious and powerful drug and should be used with great caution, therefore, it is recommended that radiation workers especially females have to be careful toward isotretinoin intake during pregnancy.

  5. In Utero Exposure to a Cardiac Teratogen Causes Reversible Deficits in Postnatal Cardiovascular Function, But Altered Adaptation to the Burden of Pregnancy.

    Science.gov (United States)

    Aasa, Kristiina L; Maciver, Rebecca D; Ramchandani, Shyamlal; Adams, Michael A; Ozolinš, Terence R S

    2015-11-01

    Congenital heart defects (CHD) are the most common birth anomaly and while many resolve spontaneously by 1 year of age, the lifelong burden on survivors is poorly understood. Using a rat model of chemically induced CHD that resolve postnatally, we sought to characterize the postnatal changes in cardiac function, and to investigate whether resolved CHD affects the ability to adapt to the increased the cardiovascular (CV) burden of pregnancy. To generate rats with resolved CHD, pregnant rats were administered distilled water or dimethadione (DMO) [300 mg/kg b.i.d. on gestation day (gd) 9 and 10] and pups delivered naturally. To characterize structural and functional changes in the heart, treated and control offspring were scanned by echocardiography on postnatal day 4, 21, and 10-12 weeks. Radiotelemeters were implanted for continuous monitoring of hemodynamics. Females were mated and scanned by echocardiography on gd12 and gd18 during pregnancy. On gd18, maternal hearts were collected for structural and molecular assessment. Postnatal echocardiography revealed numerous structural and functional differences in treated offspring compared with control; however, these resolved by 10-12 weeks of age. The CV demand of pregnancy revealed differences between treated and control offspring with respect to mean arterial pressure, CV function, cardiac strain, and left ventricular gene expression. In utero exposure to DMO also affected the subsequent generation. Gd18 fetal and placental weights were increased in treated F2 offspring. This study demonstrates that in utero chemical exposure may permanently alter the capacity of the postnatal heart to adapt to pregnancy and this may have transgenerational effects. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Carcinogenicity and teratogenicity vs. psychogenicity: Psychological characteristics associated with self-reported Agent Orange exposure among Vietnam combat veterans who seek treatment for substance abuse

    Energy Technology Data Exchange (ETDEWEB)

    Robinowitz, R.; Roberts, W.R.; Dolan, M.P.; Patterson, E.T.; Charles, H.L.; Atkins, H.G.; Penk, W.E. (Univ. of Texas Health Science Center, Dallas (USA))

    1989-09-01

    This study asked, What are the psychological characteristics of Vietnam combat veterans who claim Agent Orange exposure when compared with combat-experienced cohorts who do not report such contamination The question was researched among 153 heroin addicts, polydrug abusers, and chronic alcoholics who were seeking treatment: 58 reported moderate to high defoliant exposure while in combat; 95 reported minimal to no exposure while in Vietnam. The null hypothesis was accepted for measures of childhood and present family social climate, premilitary backgrounds, reasons for seeking treatment, patterns and types of illicit drug and alcohol use, interpersonal problems, intellectual functioning, and short-term memory. The null hypothesis was rejected for personality differences, however, those who self-reported high Agent Orange exposure scored significantly higher on MMPI scales F, Hypochondriasis, Depression, Paranoia, Psychasthenia, Schizophrenia, Mania, and Social interoversion. The results suggest that clinicians carefully assess attributional processing of those who report traumatic experience.

  7. Avaliação de riscos teratogênicos em gestações expostas ao misoprostol Evaluation of the teratogenic risks in gestations exposed to misoprostol

    Directory of Open Access Journals (Sweden)

    Emérita Sátiro Opaleye

    2010-01-01

    Full Text Available OBJETIVOS: a tentativa de aborto mal sucedida com o uso do misoprostol (Cytotec® sem indicação médica tem sido associada a malformações congênitas. Este estudo teve por objetivo identificar, em recém-nascidos malformados e controles normais, a frequência de exposição ao misoprostol e o espectro de malformações associadas. MÉTODOS: estudo de caso-controle desenvolvido em 2005 nas quatro principais maternidades públicas de Fortaleza (CE. Através de busca ativa diária, foram identificados recém-nascidos com diagnóstico de malformação fetal (caso e controles saudáveis de mesmo sexo nascidos em seguida na mesma maternidade (pareamento 1:1. A amostra foi de 252 parturientes entrevistadas por equipe treinada utilizando questionário estruturado com base no Estudo Colaborativo Latino-Americano de Malformações Congênitas (ECLAMC. Além de abordar questões sociodemográficas e histórico familiar de malformação, o questionário objetivou identificar exposições diversas durante a gestação, incluindo o misoprostol. A análise bivariada com teste do χ2 comparou os grupos quanto às características e fatores associados à malformação e foi calculada a Odds Ratio para verificar a razão de chances de o Grupo Caso apresentar malformação em relação ao Grupo Controle com relação à exposição ao misoprostol. RESULTADOS: não houve diferenças significativas entre os grupos caso e controle quanto à maioria dos fatores de riscos investigados para malformações. O relato de tentativa de aborto foi de 6,8%, havendo uma maior exposição ao misoprostol durante a gestação em neonatos malformados comparados a saudáveis, Odds Ratio (OR=3,65 (IC95%=0,74-17,91. O espectro de malformações encontradas entre os recém-nascidos expostos ao misoprostol foi compatível com a literatura, como os decorrentes de defeitos do tubo neural e disrupção vascular. CONCLUSÕES: os achados deste estudo, apesar de não apresentarem significância estatística, sugerem que os fetos expostos ao misoprostol apresentam uma tendência a maior risco de defeitos congênitos comparados aos não-expostos. Outras investigações devem ser incentivadas para que se identifique melhor o dano causado pela utilização indevida do misoprostol, principalmente em países onde o controle de medicamentos é ineficaz.PURPOSE: failed attempted abortions with the use of misoprostol (Cytotec® without medical indication have been associated with the occurrence of congenital malformations. The objective of the present study was to identify, in newborns with malformations and in normal controls, the frequency of exposure to misoprostol and the spectrum of associated malformations. METHODS: this was a case-control study involving a daily survey at four public maternities in Fortaleza (CE for the identification of newborns with malformations and paired controls (1:1 during the period from July to November 2005. The sample comprised 252 parturients interviewed by a trained team by means of a structured questionnaire based on the Latin American Collaborative Study of Congenital Malformations (Estudo Colaborativo Latino-Americano de Malformações Congênitas, ECLAMC. The questionnaire was used to obtain sociodemographic data and a family history of malformations, as well as to identify diverse forms of exposure during pregnancy, including misoprostol. Bivariate analysis and the chi-square test were used to compare cases and controls regarding their characteristics and factors associated with malformation, and the Odds Ratio was calculated to determine the chance of the Case Group to present malformations as compared to the Control Group after exposure to misoprostol. RESULTS: there were no significant differences between groups regarding most of the risk factors for malformations investigated. Attempted abortion was reported by 6.8% of the mothers, with a higher exposure to misoprostol during pregnancy resulting in a greater proportion of malformed newborns, Odds Ratio (OR=3.65 (95%CI=0.74-17.91. The spectrum of congenital defects encountered with exposure to misoprostol included defects of the central nervous, musculoskeletal, urogenital and cardiovascular systems, in agreement with literature data. CONCLUSION: the findings of this study suggest that fetuses exposed to misoprostol tend to be at higher risk of developing congenital malformations in comparison to non-exposed fetuses. Other studies should be encouraged for a better identification of the damage caused by the improper use of misoprostol, especially in countries where the control of medication is inadequate.

  8. Teratogenic effect of retinoic acid in swiss mice Efeito teratogênico do ácido retinóico em camundongo swiss

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Veiga Quemelo

    2007-12-01

    Full Text Available PURPOSE: To identify the types of malformations resulting from the administration of retinoic acid (RA to Swiss mice on different days of pregnancy. METHODS: Twenty-four pregnant Swiss mice were divided into 4 groups of 6 animals each. The experimental groups received a single intraperitoneal injection of RA (70 mg/kg on gestational days 7, 8 and 9 (D7, D8 and D9, while control animals (C received only saline solution. RESULTS: Were obtained: exencephaly (C:0; D7:16.1%; D8:25.4%; D9:0, myelomeningocele (C:0; D7:25.8%, D8:30.9%, D9:0, spina bifida occulta (C:0, D7:29%, D8:41.8%, D90, gastroschisis (C:0, D7:6.4% D8:5.4%, D9:0, omphalocele (C:0, D7:6.4%, D8:14.5%, D9:0, lower limb alterations (C:0, D7:74.1%, D8:80%, D9:0, imperforated anus (C:0, D7:100%, D8:100%, D9:100%, and tail agenesis/alteration (C: D7:100%, D8:100%, D9:100%. CONCLUSION: The experimental model using Swiss mice proved to be efficient in the induction of the different types of defects, with the eighth gestational day being the one that most favored the induction of neural tube defect, omphalocele, gastroschisis, lower limb defects, imperforated anus and tail agenesis/alteration. On this basis, this is a useful model for future investigation of neural development and of the formation of the appendicular skeleton.OBJETIVO: Identificar os tipos de malformação resultantes da administração do ácido retinóico (AR a camundongos Swiss em diferentes dias gestacionais. MÉTODOS: Foram utilizados 24 camundongos fêmeas, linhagem Swiss, prenhes, divididos em 4 grupos com 6 animais cada. Os grupos experimentais receberam uma única injeção intraperitoneal de AR (70mg/Kg nos dias gestacionais 7, 8 e 9 (D7, D8 e D9, enquanto que os animais do grupo controle (C receberam apenas solução salina. RESULTADOS: Foram encontrados: exencefalia (C:0; D7:16.1%; D8:25.4%; D9:0; mielomeningocele (C:0; D7:25.8%; D8:30.9%; D9:0; Espina Bífida Oculta (C:0; D7:29%; D8:41.8%; D90; gastrosquise (C:0; D7:6.4% D8:5.4%; D9:0; onfalocele (C:0; D7:6.4%; D8:14.5%; D9:0; alterações do membro inferior (C:0; D7:74.1%; D8:80%; D9:0; imperfuração anal (C:0; D7:100%; D8:100%; D9:100% e agenesia/alteração de cauda (C: D7:100%; D8:100%; D9:100%. CONCLUSÕES: O modelo experimental utilizando camundongo Swiss mostrou-se eficiente na indução dos diferentes tipos de defeitos, sendo o oitavo dia gestacional o mais propicio na indução de DFTN, onfalocele, gastrosquise, defeitos de membro inferior, imperfuração anal e agenesia/alteração de cauda, tornando este um modelo útil para futuras investigações do desenvolvimento neural e no processo de formação do esqueleto apendicular.

  9. PSK, a biological response modifier, modifies p53 expression, mitosis and apoptosis in X-ray irradiated mouse embryos. Possible cellular mechanism of the anti-teratogenic effect

    International Nuclear Information System (INIS)

    Kagohashi, Yukiko; Naora, Hiroyuki; Otani, Hiroki

    2002-01-01

    We previously showed that PSK, a biological response modifier, suppressed X-ray irradiation induced ocular anomalies in mouse embryos. In the present study, in mouse embryos irradiated at E7.5, PSK, when administered immediately after irradiation, suppressed mitosis and increased apoptosis as compared with embryos not treated with PSK at 12 hrs after irradiation. In the irradiated embryos, p53, which is normally expressed at a high level in early embryos, increased at 6 hrs and decreased at 12 hrs after irradiation. In the irradiated and PSK-treated embryos, the p53 level did not change at 6 hrs, increased at 12 hrs and decreased at 24 hrs after irradiation. This timing of PSK-induced delayed increase of p53 coincided with that of the PSK-induced decrease in mitosis and increase in apoptosis. These results suggested that PSK modified the p53 level and affected cell proliferation and apoptosis, which might contribute to the suppression of teratogenesis. (author)

  10. Sublethal effects of tritium on aquatic systems. Ecological effects of lithium and beryllium on important aquatic organisms and associted communities. Teratogenic effects of low-level magnetic fields

    International Nuclear Information System (INIS)

    Strand, J.A.; Emery, R.M.

    1980-01-01

    Continuing studies of the sublethal effects of tritium on freshwater species emphasize the potential for genetic transmission of suppressed immune competence in offspring of parental rainbow trout (Salmo gairdneri) exposed to tritium (0, 0.04, 0.4, 40.0 rads) during embryogenesis. We plan to determine the relative biological effectiveness of tritium beta irradiation when compared to 60 Co gamma irradiation using the relatively radiosensitive immune process of rainbow trout. During FY 1979, we concluded genetic effects studies and prepared a manuscript for open literature publication summarizing FY 1977 and FY 1978 studies on the permanence of suppression of the primary immune response in rainbow trout sublethally irradiated during embryogenesis. We are also studying the potential effects of beryllium and lithium on aquatic systems. Because of mining and refining subsequent to the use of these metals in the construction of fusion reactors, increased levels of each are likely to be encountered in surface waters. Studies included an evaluation of potential toxicity of lithium on embryological life stages of rainbow trout and an assessment of fate and effects in artificial stream habitats. Levels of lithium necessary to cause an observed effect would have to be at least three orders of magnitude above observed background. Studies initiated in FY 1978 include evaluation of effects of low-level magnetic fields on embryologic development of rainbow trout. The objective of these studies to provide data useful in assessing potentially harmful effects of low-level magnetic fields encountered by attendant personnel working in the transport and hot cell areas of fusion reactors. This approach is less costly than using mammalian systems, provides large numbers of experimental organisms for meaningful statistical analysis and permits examination of potential latent effects in a representative vertebrate

  11. Uso de medicamentos durante el embarazo y su posible efecto teratogénico Use of drugs during pregnancy and its possible teratogenic effect

    Directory of Open Access Journals (Sweden)

    Noel Taboada Lugo

    2004-08-01

    Full Text Available Se realizó un estudio descriptivo en el área de salud Esperanza, del municipio Ranchuelo, provincia Villa Clara. Se incluyeron 82 embarazadas captadas entre los meses de octubre de 2002 y marzo de 2003. Nos propusimos describir los problemas de salud más frecuentes en las gestantes, la prescripción de medicamentos en ellas y su posible relación con la presencia de defectos congénitos en la descendencia. Las infecciones respiratorias altas y la anemia fueron los problemas de salud más frecuentes. Los medicamentos que con mayor frecuencia se prescribieron durante el embarazo fueron las tabletas prenatales, el fumarato ferroso, el ácido ascórbico, el ácido fólico y el toxoide tetánico. El mayor número de prescripciones fueron realizadas por los Médicos de Familia y el nivel de automedicación resultó bajo en las embarazadas estudiadas. No se comprobó relación alguna entre los medicamentos usados en la gestación y la aparición de defectos congénitos en la descendencia.A descriptive study was conducted at Esperanza health area, Ranchuelo muncipality, Villa Clara province. 82 pregnant women recruited between October 2002 and March 2003 were included. Our purpose was to describe the most frequent health problems in pregnant women, as well as drug prescription and its possible relation to the presence of congenital defects in the offspring. Upper respiratory infections and anemia were the commonest health problems. The most frequently prescribed drugs were prenatal pills, ferrous fumarate, ascorbic acid, folic acid and tetanus toxoid. Most of the prescriptions were made by family physicians and the selfmedication level was low in the studied pregnant women. No relation was found between the drugs used during pregnancy and the appareance of congenital defects in the descendants.

  12. Methods for detection of environmental agents that produce congenital defects

    Energy Technology Data Exchange (ETDEWEB)

    Shepard, T.H.; Miller, J.R.; Marois, M. (eds.)

    1975-01-01

    Some topics discussed are as follows: current methods for teratogenicity testing in animals and suggestion for improvement; use of zebra fish for screening of teratogens; chemical structure and teratogenic mechanism of action; somatic cell genetics and teratogenesis; studies on mammalian embryos during organogenesis; infectious agents as teratogens; and pharmacogenetics and teratogenesis. (HLW)

  13. Teratogenic potency of 2,3,4,7,8-pentachlorodibenzofuran and of three mixtures of polychlorinated dibenzo-p-dioxins and dibenzofurans in mice. Problems with risk assessment using TCDD toxic-equivalency factors

    Energy Technology Data Exchange (ETDEWEB)

    Nagao, Tetsuji (Inst. fuer Toxikologie und Embryopharmakologie, Freie Univ. Berlin (Germany)); Golor, G. (Inst. fuer Toxikologie und Embryopharmakologie, Freie Univ. Berlin (Germany)); Hagenmaier, H. (Inst. fuer Organische Chemie, Univ. Tuebingen (Germany)); Neubert, D. (Inst. fuer Toxikologie und Embryopharmakologie, Freie Univ. Berlin (Germany))

    1993-11-01

    The potency of 2,3,4,7,8-pentachlorodibenzofuran (P5CDF) and of three defined 2,3,7,8-TCDD-free mixtures of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/PCDFs) to induce cleft palates in NMRI mice was studied. The data were compared with a dose-response curve for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The slope of the dose-response curve for P5CDF was the same as for TCDD. However, application of the International-TCDD-Toxic-Equivalency (I-TE) factor (NATO/CCMS 1988) of 0.5 overestimated the potency of the pentachlorinated congener about 2.5-fold under these experimental conditions, suggesting 0.2 as a TE factor. When assessing the cleft palate frequency on the basis of I-TEs and the weight of the substances, the potencies of the two PCDF mixtures studied were also clearly overestimated. This result was not substantially changed when using the TE factor of 0.2 for P5CDF. For the PCDD mixture studied, the cleft palate-inducing potency found largely agreed with the prediction when applying the I-TE factors. According to our data, the use of TE factors as calculated by the UBA/BGA (1985) or the NATO/CCMS (1988) are both conservative when attempting to assess the cleft palate incidence induced by PCDF mixtures in mice. (orig.)

  14. Sublethal effects of tritium on aquatic systems, effects of low-level chronic irradiation on embryonic development, effects of beryllium and lithium on aquatic systems, and teratogenic effects of low-level magnetic fields

    International Nuclear Information System (INIS)

    Strand, J.A.; Roesijadi, G.; Emery, R.M.

    1978-01-01

    It is conceivable, and possible, that with increasing applications of nuclear energy, greater quantities of potentially harmful radionuclides will be released to the environment. This may be particularly true for advanced reactor designs such as the fusion reactor where radionuclides, principally tritium, may be expected to escape from the plant both in gaseous and liquid effluents in quantities significantly greater than for present PWR or BWR designs. Foreseeing such contingencies, the research programs described herein are in response to the need to measure the potential radiation effects of tritium releases on individuals, and ultimately populations and biotic communities. As a first approach, our efforts are directed to determine effects of low-level chronic exposures on developing embryo and larval stages, clearly the most radiosensitive. The anticipated increase in the release of beryllium and lithium from mining, refining, and fabrication of materials used during construction of fusion reactors has also caused concern as to potential adverse effects on the environment. Accordingly, FY-78 fusion related research will include efforts to study the metabolism of each metal in the living organism, and to determine at what levels toxicity may be expected. Fusion related research will also include preliminary experiments on the effects of low-level magnetic fields. It is conceivable that magnetic fields of 70 to 450 gauss will be encountered by attendant personnel working in the transport and hot cell areas of fusion reactors. Also, those personnel assigned to the areas immediately surrounding the reactor may be exposed

  15. Mal-Development of the Penis and Loss of Fertility in Male Rats Treated Neonatally with Female Contraceptive 17α-Ethinyl Estradiol: A Dose-Response Study and a Comparative Study with a Known Estrogenic Teratogen Diethylstilbestrol

    Science.gov (United States)

    Mathews, Ensa; Braden, Tim D.; Williams, Carol S.; Williams, John W.; Bolden-Tiller, Olga; Goyal, Hari O.

    2009-01-01

    The objectives of this study were to find a minimal dose of 17α-ethinyl estradiol (EE) that is detrimental to the developing penis and fertility and to compare estrogenic effects between EE and diethylstilbestrol (DES). Neonatal rats received EE at 10 ng (1 μg/kg), 100 ng, 1 μg, or 10 μg per pup on alternate days from postnatal days 1 to 11 (dose-response study) or received EE or DES at 100 ng per pup daily from postnatal days 1 to 6 (comparative study). Effects of EE were dose dependent, with ≥ 100-ng dose inducing significant (p penis was malformed, characterized by underdeveloped os penis and accumulation of fat cells. Fertility was 0% in the ≥ 1-μg groups, in contrast to 60% in the 100-ng group and 100% in the 10-ng and control groups. Animals treated with ≥ 10 ng had significant reductions in the weight of bulbospongious muscle, testis, seminal vesicle, epididymal fat pad, and in epididymal sperm numbers. A comparison of EE and DES effects showed similar reductions in penile weight and length and the weight of bulbospongiosus muscle, testis, seminal vesicle, epididymis, and epididymal fat pad in both adolescent and adult rats. While 5/6 control males sired, only 1/6 in the EE group and 0/6 in the DES group sired. Hence, neonatal exposure to EE at 10 ng (environmentally relevant dose) adversely affects male reproductive organs. A dose ten times higher than this leads to permanently mal-developed penis and infertility. Furthermore, EE and DES exposures show similar level of toxicity to male reproductive organs. PMID:19729556

  16. Manifestaciones cutáneas como parámetro de teratogenicidad en la intoxicación con metales pesados Cutaneous signs as parameter in teratogenicity by heavy metal intoxication

    OpenAIRE

    N L Pauza; M J Pérez Cotti; M L Godar; Y Sopena; A M Ferramola de Sancovich; H A Sancovich

    2007-01-01

    Se estudiaron los efectos teratogénicos de metales pesados (acetatos de Cd2+ y Pb2+ y sulfato de Cu2+), en embriones de pollo en desarrollo, después de la administración de una monodosis del metal. Los huevos embrionados fueron inyectados en la yema en el día 12 de incubación. Las concentraciones de los iones fueron (nmoles/g huevo): Cd2+: Dosis 1 (D1): 0,16 y Dosis 2 (D2): 0,32; Pb2+: D1: 8,0 y D2: 16,0 y Cu2+: D1: 1,7 y D2: 3,3. Los resultados se evaluaron después de continuar la incubación...

  17. Drogy s teratogenními účinky

    OpenAIRE

    Łuńská, Rut

    2017-01-01

    Charles University, Faculty of Pharmacy, Hradec Králové Department: Department of Pharmacognosy Head of thesis: doc. PharmDr. Lenka T mová, Csc. Student: Bc. Rut Łu ská Title of the thesis: Teratogenic drugs The aim of this diploma thesis is to give an overview of teratogenic drugs. The work approaches the problems of teratogenesis, factors affecting teratogenicity, distribution of teratogens, classification of medication in pregnancy and methods of teratogenicity study. An overview of terato...

  18. Clinical teratology

    International Nuclear Information System (INIS)

    McCormack, M.K.

    1983-01-01

    Of particular importance in teratogenesis is the time of exposure to the offending environmental agent, route of exposure, and genotype of the embryo and the mother. The major teratogens include irradiation, maternal infections, other illnesses in pregnancy (diabetes, thyroid disease, maternal phenylketonuria, virilizing diseases), a host of pharmacologic agents and environmental contaminants. Teratogen exposure carries the potential for cancer in later life. Several sources of information on teratogens are now available

  19. Clinical teratology

    Energy Technology Data Exchange (ETDEWEB)

    McCormack, M.K.

    1983-12-01

    Of particular importance in teratogenesis is the time of exposure to the offending environmental agent, route of exposure, and genotype of the embryo and the mother. The major teratogens include irradiation, maternal infections, other illnesses in pregnancy (diabetes, thyroid disease, maternal phenylketonuria, virilizing diseases), a host of pharmacologic agents and environmental contaminants. Teratogen exposure carries the potential for cancer in later life. Several sources of information on teratogens are now available.

  20. Behavioral Teratology Comes to the Classroom.

    Science.gov (United States)

    Brackbill, Yvonne

    1987-01-01

    The article discusses types of teratogenic agents, (behavioral defects caused by toxic agents) behavioral targets, organismic vulnerability during growth spurts, teratogenic "routing" (path to the brain), exposure, and duration of effects. Lead is used as a paradigm of chemical neurotoxins known to affect cognitive and noncognitive…

  1. SELECTIVE VULNERABILITY OF EMBRYONIC CELL POPULATIONS TO ETHANOL-INDUCED APOPTOSIS: IMPLICATIONS FOR ALCOHOL RELATED BIRTH DEFECTS AND NEURODEVELOPMENTAL DISORDER

    Science.gov (United States)

    The locations of cell death and resulting malformations in embryos following teratogen exposure vary depending on the teratogen used, the genotype of the conceptus, and the developmental stage of the embryo at time of exposure. To date, ethanol-induced cell death has been charac...

  2. Morphologic and Immunologic effects in the rat after prenatal exposure to Cyclophosphamide

    NARCIS (Netherlands)

    Hessel EM; Verhoef A; van Loveren H; Piersma AH

    1993-01-01

    Several teratogens have been shown to alter postnatal immune function after prenatal exposure. Until now, relatively little is known about the perinatal maturation of the immune system and about the effects of teratogens on this process. Therefore, further research is necessary into the field of

  3. Activation and desensitization of peripheral muscle and neuronal nicotinic acetylcholine receptors by selected, naturally-occurring pyridine alkaloids

    Science.gov (United States)

    Teratogenic alkaloids can cause developmental defects due to inhibition of fetal movement that results from desensitization of fetal muscletype nicotinic acetylcholine receptors (nAChRs). We investigated the ability of two known teratogens, the piperidinyl-pyridine anabasine and its 1,2-dehydropiper...

  4. Predicting human developmental toxicity of pharmaceuticals using human embryonic stem cells and metabolomics

    International Nuclear Information System (INIS)

    West, Paul R.; Weir, April M.; Smith, Alan M.; Donley, Elizabeth L.R.; Cezar, Gabriela G.

    2010-01-01

    Teratogens, substances that may cause fetal abnormalities during development, are responsible for a significant number of birth defects. Animal models used to predict teratogenicity often do not faithfully correlate to human response. Here, we seek to develop a more predictive developmental toxicity model based on an in vitro method that utilizes both human embryonic stem (hES) cells and metabolomics to discover biomarkers of developmental toxicity. We developed a method where hES cells were dosed with several drugs of known teratogenicity then LC-MS analysis was performed to measure changes in abundance levels of small molecules in response to drug dosing. Statistical analysis was employed to select for specific mass features that can provide a prediction of the developmental toxicity of a substance. These molecules can serve as biomarkers of developmental toxicity, leading to better prediction of teratogenicity. In particular, our work shows a correlation between teratogenicity and changes of greater than 10% in the ratio of arginine to asymmetric dimethylarginine levels. In addition, this study resulted in the establishment of a predictive model based on the most informative mass features. This model was subsequently tested for its predictive accuracy in two blinded studies using eight drugs of known teratogenicity, where it correctly predicted the teratogenicity for seven of the eight drugs. Thus, our initial data shows that this platform is a robust alternative to animal and other in vitro models for the prediction of the developmental toxicity of chemicals that may also provide invaluable information about the underlying biochemical pathways.

  5. Counselling pregnant women at the crossroads of Europe and Asia: effect of Teratology Information Service in Turkey.

    Science.gov (United States)

    Kaplan, Yusuf Cem; Karadaş, Barış; Küçüksolak, Gözde; Ediz, Bartu; Demir, Ömer; Sozmen, Kaan; Nordeng, Hedvig

    2017-08-01

    Background Previous studies from western countries demonstrated the effectiveness of Teratology Information Service (TIS) counselling in reducing the teratogenic risk perception of pregnant women. Objective To assess whether TIS counselling would be effective in reducing the teratogenic risk perception of the Turkish pregnant women. Setting A TIS (Terafar) operating in a university hospital in Turkey. Methods A cross-sectional survey study. Pregnant women with non-teratogenic medication exposures were asked to assign scores on visual analogue scales (VAS) in response to the questions aiming to measure their teratogenic risk perception. The mean score before and after counselling were compared and the associations with maternal socio-demographic characteristics were analysed using SPSS (Version 20.0). Main outcome measures The differences in the mean scores of the perception regarding the baseline risk of pregnancy, own teratogenic risk and the likelihood of termination of pregnancy before and after counselling and their possible associations with maternal socio-demographic characteristics. Results 102 pregnant women participated in the study. The counselling significantly reduced the mean own teratogenic risk perception score and the mean score for the likelihood of termination of pregnancy whereas the mean baseline risk perception score was not significantly changed. Pregnancy week <8 and the exposed number of active ingredients <3 were significantly associated with the difference in the mean score for the likelihood of termination of pregnancy. Conclusions TIS counselling lowers the teratogenic risk perception of Turkish pregnant women and increases their likelihood to continue the pregnancy as it does in the western countries.

  6. Development of a new screening assay to identify proteratogenic substances using zebrafish danio rerio embryo combined with an exogenous mammalian metabolic activation system (mDarT).

    Science.gov (United States)

    Busquet, François; Nagel, Roland; von Landenberg, Friedrich; Mueller, Stefan O; Huebler, Nicole; Broschard, Thomas H

    2008-07-01

    The assessment of teratogenic effects of chemicals is generally performed using in vivo teratogenicity assays, for example, in rats or rabbits. We have developed an in vitro teratogenicity assay using the zebrafish Danio rerio embryo combined with an exogenous mammalian metabolic activation system (MAS), able to biotransform proteratogenic compounds. Cyclophosphamide (CPA) and ethanol were used as proteratogens to test the efficiency of this assay. Briefly, the zebrafish embryos were cocultured at 2 hpf (hours postfertilization) with the test material at varying concentrations, induced male rat liver microsomes and nicotinamide adenine dinucleotide phosphate (reduced) for 60 min at 32 degrees C under moderate agitation in Tris-buffer. The negative control (test material alone) and the MAS control (MAS alone) were incubated in parallel. For each test group, 20 eggs were used for statistical robustness. Afterward fish embryos were transferred individually into 24-well plates filled with fish medium for 48 h at 26 degrees C with a 12-h light cycle. Teratogenicity was scored after 24 and 48 hpf using morphological endpoints. No teratogenic effects were observed in fish embryos exposed to the proteratogens alone, that is, without metabolic activation. In contrast, CPA and ethanol induced abnormalities in fish embryos when coincubated with microsomes. The severity of malformations increased with increasing concentrations of the proteratogens. We conclude that the application of microsomes will improve and refine the D. rerio teratogenicity assay as a predictive and valuable alternative method to screen teratogenic substances.

  7. LSD and Genetic Damage

    Science.gov (United States)

    Dishotsky, Norman I.; And Others

    1971-01-01

    Reviews studies of the effects of lysergic acid diethylamide (LSD) on man and other organisms. Concludes that pure LSD injected in moderate doses does not cause chromosome or detectable genetic damage and is not a teratogen or carcinogen. (JM)

  8. Does topical isotretinoin exposure during pregnancy increase the risk of congenital malformations?

    Directory of Open Access Journals (Sweden)

    İsmail Yılmaz

    2015-06-01

    Full Text Available A 34-year-old patient learned that she was 7 weeks pregnant while she was using topical isotretinoin + erythromycin gel for acne treatment and referred to Izmir Katip Celebi University Teratology Information Service for information regarding the risk of teratogenicity. Systemic use of isotretinoin is well-known for its teratogenic effects and case reports suggesting possible teratogenic effects regarding topical exposure to retinoids in pregnancy exist in the literature. However, findings reported in four prospective controlled studies do not suggest an increased congenital malformation risk in case of inadvertent exposure during pregnancy. This manuscript aims to give a summary and evaluation of available data for counseling pregnant patients regarding the possible teratogenic risk of inadvertent topical isotretinoin exposure during pregnancy. It also aims to emphasize the importance of increasing communication between pregnant patients, clinicians and teratology information services for the benefit of mother and unborn.

  9. MEMS based impedimetric sensing of phthalates

    KAUST Repository

    Zia, Asif I.; Mohd. Syaifudin, A. R.; Mukhopadhyay, Subhas Chandra; Al-Bahadly, Ibrahim H.; Yu, Paklam; Gooneratne, Chinthaka Pasan; Kosel, Jü rgen; Liao, Taishan

    2013-01-01

    Phthalate esters are known ubiquitous teratogenic and carcinogenic environmental and food pollutants. Their detection and quantification is strictly laboratory based, time consuming, expensive and professionally handled procedure. Presented research

  10. Analysis of Lethality and Malformations During Zebrafish (Danio rerio) Development.

    Science.gov (United States)

    Raghunath, Azhwar; Perumal, Ekambaram

    2018-01-01

    The versatility offered by zebrafish (Danio rerio) makes it a powerful and an attractive vertebrate model in developmental toxicity and teratogenicity assays. Apart from the newly introduced chemicals as drugs, xenobiotics also induce abnormal developmental abnormalities and congenital malformations in living organisms. Over the recent decades, zebrafish embryo/larva has emerged as a potential tool to test teratogenicity potential of these chemicals. Zebrafish responds to compounds as mammals do as they share similarities in their development, metabolism, physiology, and signaling pathways with that of mammals. The methodology used by the different scientists varies enormously in the zebrafish embryotoxicity test. In this chapter, we present methods to assess lethality and malformations during zebrafish development. We propose two major malformations scoring systems: binomial and relative morphological scoring systems to assess the malformations in zebrafish embryos/larvae. Based on the scoring of the malformations, the test compound can be classified as a teratogen or a nonteratogen and its teratogenic potential is evaluated.

  11. Preventing foetal alcohol syndrome with motivational interviewing

    African Journals Online (AJOL)

    2012-10-14

    Oct 14, 2012 ... Alcohol is widely established as a teratogenic drug that is capable of ... interviewing (MI) with cognitive behavioural therapy (CBT) practice, borrowed from health ... certain families, heritability, linked to genetically determined.

  12. Technique for rapid detection of phthalates in water and beverages

    KAUST Repository

    Zia, Asif I.; Rahman, Mohammed Syaifudin Abdul; Mukhopadhyay, Subhas Chandra; Yu, Paklam; Al-Bahadly, Ibrahim H.; Gooneratne, Chinthaka Pasan; Kosel, Jü rgen; Liao, Taishan

    2013-01-01

    The teratogenic and carcinogenic effects of phthalate esters on living beings are proven in toxicology studies. These ubiquitous food and environmental pollutants pose a great danger to the human race due to their extraordinary use as a plasticizer

  13. PCB126 induces deformities during pectoral fin development in little skate

    Science.gov (United States)

    Polychlorinated biphenyls (PCBs) are ubiquitous legacy chemicals found throughout the environment, which can accumulate in humans, domestic animals, and wildlife. Some PCBs are agonists of the aryl hydrocarbon receptor (AHR) and are potent teratogens in bony fish. Leucoraja erina...

  14. (GAGs) in normal and ethanol-induced chick embryo during neural

    African Journals Online (AJOL)

    Administrator

    2011-09-14

    Sep 14, 2011 ... Alcohol as a teratogenic agent inhibits cell growth, function, proliferation and migration by affecting .... formed along the right and left side of the neural tube .... of neurons by harming the developing brain and also can.

  15. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    Manifestation of Aflaxoxicosis in Poultry in Southwest, Nigeria ... Aflatoxin remains the most studied mycotoxin with aflatoxin B1 making up 66 to ... resulting from its hepatocarcinogenic, mutagenic, teratogenic and immunosuppressive effects.

  16. Long term effects of radiation in man

    International Nuclear Information System (INIS)

    Tso Chih Ping; Idris Besar

    1984-01-01

    An overview of the long term effects of radiation in man is presented, categorizing into somatic effects, genetic effects and teratogenic effects, and including an indication of the problems that arise in their determination. (author)

  17. Use of hierarchical models to analyze European trends in congenital anomaly prevalence

    DEFF Research Database (Denmark)

    Cavadino, Alana; Prieto-Merino, David; Addor, Marie-Claude

    2016-01-01

    BACKGROUND: Surveillance of congenital anomalies is important to identify potential teratogens. Despite known associations between different anomalies, current surveillance methods examine trends within each subgroup separately. We aimed to evaluate whether hierarchical statistical methods that c...

  18. Cardiovascular Ultrasound of Neonatal Long Evans Rats Exposed Prenatally to Trichloroacetic Acid: Effects on Heart Rate, Ejection Fraction, and Cardiac Output

    Science.gov (United States)

    This abstract describes the use of a relatively new technology, cardiovascular ultrasound (echocardiography) for evaluating developmental toxicity affecting heart development. The abstract describes the effects of two known cardiac teratogens, trichloroacetic acid and dimethadio...

  19. Pharmacogenetics of drug-induced birth defects : What is known so far?

    NARCIS (Netherlands)

    Wilffert, Bob; Altena, Judith; Tijink, Laurien; van Gelder, Marleen M. H. J.; de Jong-van den Berg, Lolkje T. W.

    A literature review was performed to collect information on the role of pharmacogenetics in six proposed teratogenic mechanisms associated with drug use during pregnancy: folate antagonism, oxidative stress, angiotensin-converting enzyme inhibition and angiotensin II receptor antagonism,

  20. Evaluation of the knowledge and practices of pregnant Yemeni ...

    African Journals Online (AJOL)

    Keywords: Knowledge, Practices, Teratogens, Pregnant Yemeni women, Folic acid deficiency. Tropical Journal of ..... United Arab Emirates (UAE) have published rates of awareness .... emphasis on good hygiene in the American population.

  1. Congenital and Genetic Disease in Domestic Animals

    Science.gov (United States)

    Mulvihill, John J.

    1972-01-01

    Reviews observations on domestic animals that have led to the identification of environmental teratogens, and have provided insight into the pathogenesis of congenital defects and genetic diseases in man." (Author/AL)

  2. Oral phenoxymethylpenicillin treatment during pregnancy

    DEFF Research Database (Denmark)

    Czeizel, A.E.; Rockenbauer, M.; Olsen, Jørn

    2000-01-01

    The objective of the study was to examine the human teratogenic potential of oral penicillin V: phenoxymethylpenicillin treatment during pregnancy in the large population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980–1996. The dataset included 22......, i.e. in the critical period for most major congenital abnormalities in case-matched control pairs. Thus, treatment with oral phenoxymethylpenicillin during pregnancy presents very little if any teratogenic risk to the fetus....

  3. Quantifying the risks and benefits of efavirenz use in HIV-infected women of childbearing age in the USA.

    Science.gov (United States)

    Hsu, H E; Rydzak, C E; Cotich, K L; Wang, B; Sax, P E; Losina, E; Freedberg, K A; Goldie, S J; Lu, Z; Walensky, R P

    2011-02-01

    The aim of the study was to quantify the benefits (life expectancy gains) and risks (efavirenz-related teratogenicity) associated with using efavirenz in HIV-infected women of childbearing age in the USA. We used data from the Women's Interagency HIV Study in an HIV disease simulation model to estimate life expectancy in women who receive an efavirenz-based initial antiretroviral regimen compared with those who delay efavirenz use and receive a boosted protease inhibitor-based initial regimen. To estimate excess risk of teratogenic events with and without efavirenz exposure per 100,000 women, we incorporated literature-based rates of pregnancy, live births, and teratogenic events into a decision analytic model. We assumed a teratogenicity risk of 2.90 events/100 live births in women exposed to efavirenz during pregnancy and 2.68/100 live births in unexposed women. Survival for HIV-infected women who received an efavirenz-based initial antiretroviral therapy (ART) regimen was 0.89 years greater than for women receiving non-efavirenz-based initial therapy (28.91 vs. 28.02 years). The rate of teratogenic events was 77.26/100,000 exposed women, compared with 72.46/100,000 unexposed women. Survival estimates were sensitive to variations in treatment efficacy and AIDS-related mortality. Estimates of excess teratogenic events were most sensitive to pregnancy rates and number of teratogenic events/100 live births in efavirenz-exposed women. Use of non-efavirenz-based initial ART in HIV-infected women of childbearing age may reduce life expectancy gains from antiretroviral treatment, but may also prevent teratogenic events. Decision-making regarding efavirenz use presents a trade-off between these two risks; this study can inform discussions between patients and health care providers.

  4. Quantifying the risks and benefits of efavirenz use in HIV-infected women of childbearing age in the United States

    Science.gov (United States)

    Hsu, HE; Rydzak, CE; Cotich, KL; Wang, B; Sax, PE; Losina, E; Freedberg, KA; Goldie, SJ; Lu, Z; Walensky, RP

    2010-01-01

    Objectives We quantified the benefits (life expectancy gains) and harms (efavirenz-related teratogenicity) associated with using efavirenz in HIV-infected women of childbearing age in the United States. Methods We used data from the Women’s Interagency HIV Study in an HIV disease simulation model to estimate life expectancy in women who receive an efavirenz-based initial antiretroviral regimen compared with those who delay efavirenz use and receive a boosted protease inhibitor-based initial regimen. To estimate excess risk of teratogenic events with and without efavirenz exposure per 100,000 women, we incorporated literature-based rates of pregnancy, live births, and teratogenic events into a decision analytic model. We assumed a teratogenicity risk of 2.90 events/100 live births in women exposed to efavirenz during pregnancy and 2.68/100 live births in unexposed women. Results Survival for HIV-infected women who received an efavirenz-based initial antiretroviral therapy regimen was 0.89 years greater than for women receiving non-efavirenz-based initial therapy (28.91 vs. 28.02 years). The rate of teratogenic events was 77.26/100,000 exposed women, compared with 72.46/100,000 unexposed women. Survival estimates were sensitive to variations in treatment efficacy and AIDS-related mortality. Estimates of excess teratogenic events were most sensitive to pregnancy rates and number of teratogenic events/100 live births in efavirenz-exposed women. Conclusions Use of non-efavirenz-based initial antiretroviral therapy in HIV-infected women of childbearing age may reduce life expectancy gains from antiretroviral treatment, but may also prevent teratogenic events. Decision-making regarding efavirenz use presents a tradeoff between these two risks; this study can inform discussions between patients and health care providers. PMID:20561082

  5. Prevention of Fetal Congenital Malformations with Allowance for the Pharmacogenetic Features of the Metabolism of Antiepileptic Drugs and Hereditary Abnormalities in the Folate Cycle

    Directory of Open Access Journals (Sweden)

    D. V. Dmitrenko

    2014-01-01

    Full Text Available Fetal congenital malformations are among the most dangerous complications of pregnancy in women with epilepsy taking antiepileptic drugs. Valproic acid and phenobarbital have the greatest risk of teratogenic effects. Insights into the current mechanisms of teratogenic effect of antiepileptic drugs, pharmacogenetic features of the metabolism of valproates and hereditary abnormalities in the folate cycle enables prevention of fetal congenital malformations. 

  6. Behavioral Teratogenesis in Drosophila melanogaster.

    Science.gov (United States)

    Mishra, Monalisa; Barik, Bedanta Kumar

    2018-01-01

    Developmental biology is a fascinating branch of science which helps us to understand the mechanism of development, thus the findings are used in various therapeutic approach. Drosophila melanogaster served as a model to find the key molecules that initiate and regulate the mechanism of development. Various genes, transcription factors, and signaling pathways helping in development are identified in Drosophila. Many toxic compounds, which can affect the development, are also recognized using Drosophila model. These compounds, which can affect the development, are named as a teratogen. Many teratogens identified using Drosophila may also act as a teratogen for a human being since 75% of conservation exist between the disease genes present in Drosophila and human. There are certain teratogens, which do not cause developmental defect if exposed during pregnancy, however; behavioral defect appears in later part of development. Such compounds are named as a behavioral teratogen. Thus, it is worthy to identify the potential behavioral teratogen using Drosophila model. Drosophila behavior is well studied in various developmental stages. This chapter describes various methods which can be employed to test behavioral teratogenesis in Drosophila.

  7. In Vitro Developmental Toxicology Screens: A Report on the Progress of the Methodology and Future Applications.

    Science.gov (United States)

    Zhang, Cindy; Ball, Jonathan; Panzica-Kelly, Julie; Augustine-Rauch, Karen

    2016-04-18

    There has been increasing focus on generation and assessment of in vitro developmental toxicology models for assessing teratogenic liability of chemicals. The driver for this focus has been to find reliable in vitro assays that will reduce or replace the use of in vivo tests for assessing teratogenicity. Such efforts may be eventually applied in testing pharmaceutical agents where a developmental toxicology assay or battery of assays may be incorporated into regulatory testing to replace one of the two species currently used in teratogenic assessment. Such assays may be eventually applied in testing a broader spectrum of chemicals, supporting efforts aligned with Tox21 strategies and responding to REACH legislation. This review describes the developmental toxicology assays that are of focus in these assessments: rodent whole embryo culture, zebrafish embryo assays, and embryonic stem cell assays. Progress on assay development as well as future directions of how these assays are envisioned to be applied for broader safety testing of chemicals are discussed. Altogether, the developmental model systems described in this review provide rich biological systems that can be utilized in better understanding teratogenic mechanisms of action of chemotypes and are promising in providing proactive safety assessment related to developmental toxicity. Continual advancements in refining/optimizing these in vitro assays are anticipated to provide a robust data set to provide thoughtful assessment of how whole animal teratogenicity evaluations can be reduced/refined in the future.

  8. Embryo yolk sac membrane kynurenine formamidase of l-tryptophan to NAD+ pathway as a primary target for organophosphorus insecticides (OPI) in OPI-induced NAD-associated avian teratogenesis.

    Science.gov (United States)

    Seifert, Josef

    2017-10-01

    The objective of this study was to provide in ovo evidence for the proposed role of kynurenine formamidase of l-tryptophan to NAD + pathway in embryo yolk sac membranes as a primary target for organophosphorus insecticide (OPI) teratogens in OPI-induced NAD-associated avian teratogenesis. Slices prepared from yolk sac membranes or embryo livers of chicken eggs treated with the OPI dicrotophos and/or methyl parathion were incubated with l-tryptophan. Yolk sac membrane slices metabolized l-tryptophan in the pathway to NAD + before that function was established in livers. OPI interfered in ovo with the second step of l-tryptophan to NAD + biosynthesis by inhibiting kynurenine formamidase. Its inhibition due to the teratogen dicrotophos occurred in yolk sac membranes during the period of embryo highest susceptibility to OPI teratogens in contrast to delayed and lower inhibition caused by the nonteratogen methyl parathion. Both OPI affected liver kynurenine formamidase in a similar manner. The onsets of liver enzyme inhibition, however, were delayed by about two days and occurred at the time of the reduced embryo susceptibility to teratogens. The early disruption of l-tryptophan metabolism and higher inhibition of kynurenine formamidase in yolk sac membranes may be the factors that determine action of OPI as teratogens in chicken embryos. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Nitrofurantoin and congenital abnormalities

    DEFF Research Database (Denmark)

    Czeizel, A.E.; Rockenbauer, M.; Sørensen, Henrik Toft

    2001-01-01

    or fetuses with Down’s syndrome (patient controls), 23 (2.8%) pregnant women were treated with nitrofurantoin. The above differences between population controls and cases may be connected with recall bias, because the case-control pair analysis did not indicate a teratogenic potential of nitrofurantoin use......Objective: To study human teratogenic potential of oral nitrofurantoin treatment during pregnancy. Materials and Methods: Pair analysis of cases with congenital abnormalities and matched population controls in the population-based dataset of the Hungarian Case-Control Surveillance of Congenital...... during the second and the third months of gestation, i.e. in the critical period for major congenital abnormalities. Conclusion: Treatment with nitrofurantoin during pregnancy does not present detectable teratogenic risk to the fetus....

  10. Congenital skeletal malformations induced by maternal ingestion of Conium maculatum (poison hemlock) in newborn pigs.

    Science.gov (United States)

    Panter, K E; Keeler, R F; Buck, W B

    1985-10-01

    Skeletal malformations were induced in newborn pigs from gilts fed Conium maculatum seed or plant during gestation days 43 through 53 and 51 through 61. The teratogenic effects in groups dosed during gestation days 43 through 53 were more severe than those in groups dosed during the later period, with many newborn pigs showing arthrogryposis and twisted and malaligned bones in the limbs and with 1 pig showing scoliosis and deformity of the thoracic cage. The pigs born to gilts given C maculatum during gestation days 51 through 61 had excessive flexure primarily in the carpal joints, without scoliosis or bone malalignment in the limbs. The teratogenicity of poison hemlock depends on the alkaloid concentration and content. Based on the data presented, we speculate that gamma-coniceine is the teratogenic alkaloid in the poison hemlock fed to the gilts.

  11. A population-based case-control teratologic study of furazidine, a nitrofuran-derivative treatment during pregnancy.

    Science.gov (United States)

    Czeizel, A E; Rockenbauer, M; Sørensen, H T; Olsen, J

    2000-04-01

    To study human teratogenic potential of furazidine treatment during pregnancy. Pair analysis of cases with congenital abnormalities and matched population controls. The Hungarian Case-Control Surveillance of Congenital Abnormalities. 38,151 pregnant women who had newborn infants without any defects (population control group) and 22,865 pregnant women who had newborns or fetuses with congenital abnormalities between 1980 and 1996. In the case group, 157 (0.7%) and in the control group, 254 (0.7%) pregnant women were treated with furazidine. The case-control pair analysis did not indicate a teratogenic potential of furazidine use during the second to third months of gestation, i.e. in the critical period for major congenital abnormalities. Treatment with furazidine during pregnancy did not show teratogenic risk to the fetus.

  12. [Gynecological and obstetrical management of rheumatic diseases in reproductive age].

    Science.gov (United States)

    Pepe, Franco; Stracquadanio, Mariagrazia; Privitera, Agata; Ciotta, Lilliana; DE Luca, Francesco

    2018-04-01

    The gynecologist's role in the management of rheumatic patients is complex: it includes the prevention of damage caused by drugs, the counseling about contraception to avoid pregnancy while taking teratogen drugs, the scheduling of pregnancy during the quiescent phase of the specific disease, the replacement of teratogen drugs and a competent management of the pregnancy. The task is carried out as part of a multidisciplinary team with a focus on the differential diagnosis between specific complications of pregnancy and the complications of the rheumatic disease. This is the right way to allow a conscious reproduction, with reduced risks and acceptable maternal-fetal outcomes, to this kind of patients considered at high risk.

  13. [Wilson's principles--a base of modern teratology].

    Science.gov (United States)

    Burdan, Franciszek; Bełzek, Artur; Szumiło, Justyna; Dudka, Jarosław; Korobowicz, Agnieszka; Tokarska, Edyta; Klepacz, Lidia; Bełzek, Marta; Klepacz, Robert

    2006-03-01

    Wilson's principles were formulated after thalidomide tragedy. They become a fundamental for teratological studies with drugs and other factors that may disturb fetal development. It is postulated that susceptibility to teratogen depends on the genotype and developmental stage of the conceptus. Teratogenic agents act in specific manner on developing cells and tissues. The exposition depends on the agent's nature and availability. Manifestations of deviant development depends on the dosage and exposure frequency. In case of abnormal development the final manifestations include death of embryo or fetus, malformation, growth retardation and functional disorder.

  14. Occupational radiation hazards during pregnancy

    International Nuclear Information System (INIS)

    Devik, F.

    1979-01-01

    The general principles in teratology are discussed and it is pointed out that ionising radiation is only one of many agents with teratogenic effects. Human experience with radiation induced congenital malformations is insufficient to warrant conclusions about dose and effect. The teratogenic effects are then discussed in more detail and indications of radiation doses said to produce these are given. The question of a threshold dose is briefly discussed, as is the possibility of carcinogenesis. Finally precautions to be taken and the recommendations of the ICRP and the CEC are presented. (JIW)

  15. Perinatal Influences of Valproate on Brain and Behaviour: An Animal Model for Autism.

    Science.gov (United States)

    Ranger, Peter; Ellenbroek, Bart A

    Valproic acid or valproate (VPA) is an anti-convulsant and mood stabiliser effective in treating epilepsy and bipolar disorders. Although in adults VPA is well tolerated and safe, there is convincing evidence that it has teratogenic properties, ranging from mild neurodevelopmental changes to severe congenital malformations. In particular, studies involving humans and other animals have shown that prenatal exposure to VPA can induce developmental abnormalities reminiscent of autism spectrum disorder (ASD). In this chapter, we discuss the connection between VPA and ASD, evaluate the VPA animal model of ASD, and describe the possible molecular mechanisms underlying VPA's teratogenic properties.

  16. EVIDENCE FOR EGFR PATHWAY MEDIATION OF CLEFT PALATE INDUCTION BY TCDD

    Science.gov (United States)

    EVIDENCE FOR EGFR PATHWAY MEDIATION OF CLEFT PALATE INDUCTION BY TCDD. B D Abbott, A R Buckalew, and K E Leffler. RTD, NHEERL, ORD,US EPA, RTP, NC, USA.2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is teratogenic in C57BL/6J mice, producing cleft palate (CP) after exposure...

  17. Probabilistic record linkage for monitoring the safety of artemisinin-based combination therapy in the first trimester of pregnancy in Senegal

    NARCIS (Netherlands)

    Dellicour, Stephanie; Brasseur, Philippe; Thorn, Per; Gaye, Oumar; Olliaro, Piero; Badiane, Malik; Stergachis, Andy; ter Kuile, Feiko O.

    2013-01-01

    There are insufficient data on the safety in early pregnancy of the artemisinins, a new class of antimalarials. Assessment of drug teratogenicity requires large sample sizes for an adequate risk-benefit assessment. There is currently limited pharmacovigilance infrastructure in malaria-endemic

  18. The Effects of Palm wine on the Morphometry and Femur Histology ...

    African Journals Online (AJOL)

    Background: Palm-wine as an alcoholic beverage plays an important role in the social life of many people in Nigeria especially those in the southern part of the country. The aim of this study was to evaluate the possible teratogenic effects of palm wine on wistar rat foetuses. Methodology: Female rats were caged with mature ...

  19. Lead and radiation induced hepatic lesions in Swiss albino mice and their inhibition by vitamin E

    International Nuclear Information System (INIS)

    Gajawat, Sunita; Goyal, P.K.

    2002-01-01

    The present study has been carried out to access the protective role of vitamin E against hepato-toxicity induced by lead and radiation. The present study demonstrates that the application of vitamin E prior to lead and gamma radiation exposure is quite potential to provide protection against hepatic lesions induced by such teratogens

  20. BOOK REVIEWS BOEKBESPREKINGS

    African Journals Online (AJOL)

    The Problems of Species Difference alld Srarisrics in Toxi- cology. Vol. XI. Proceedings of the European Society for the ... metabolism enzymes in rats, rabbits and mice. Various aspects of teratogenic drugs also receive attention and the ... Respiratory Diseases. Deur J. Crofton, M.A., (Cantab),. F.R.C.P. (Edin. & Lond.) ...

  1. Levels of micronutrients and heavy metals in cord blood and ...

    African Journals Online (AJOL)

    The basis of the impact of HAP on maternal and fetal health was assessed by determining the levels of teratogenic heavy metals [Lead (Pb), Mercury (Hg)] and micronutrients associated with DNA methylation [Zinc (Zn), Iodine (I), vitamins B6 and B12, folic acid and homocysteine] in cord blood of babies and maternal blood ...

  2. Mechanism of nitrofen teratogenesis

    International Nuclear Information System (INIS)

    Manson, J.M.

    1986-01-01

    Nitrofen (2,4-dichloro-4'-nitrodiphenyl ether) is an herbicide with potent teratogenic activity in rats. When administered at doses as low as 0.15 mg/kg/day during organogenesis, abnormal development of the heart, kidneys, diaphragm, and lung occurs. The specific pattern of visceral malformations produced in the absence of overt maternal toxicity or embryolethality/cytotoxicity suggest that the compound perturbs processes unique or highly selective for embryonic differentiation. Despite findings of metabolic activation to mutagenic intermediates and carcinogenic activity in adult rodents, several lines of evidence indicate that teratogenicity is not based on mutagenic insult to the embryo. Rather, evidence is accumulating that nitrofen exerts a teratogenic effect via alterations in thyroid hormone status. The premature and pharmacologic exposure of the embryo to a nitrofen-derived thyromimetic challenge is believed to be the cause of abnormal morphogenesis of the heart, lungs, kidneys, and diaphragm. The parent compound itself could directly bind to embryonic nuclear receptors for T 3 , leading to altered differentiation of target organs. Alternatively, increased availability and placental transport of free thyroid hormones in the maternal compartment could be the source of thyromimetric challenge to the embryo. Overall, these studies indicate that, in the case of nitrofen, the mode of teratogenic activity is uniquely different from the mode of adult toxicity

  3. Paper 5: Surveillance of multiple congenital anomalies: implementation of a computer algorithm in European registers for classification of cases

    DEFF Research Database (Denmark)

    Garne, Ester; Dolk, Helen; Loane, Maria

    2011-01-01

    Surveillance of multiple congenital anomalies is considered to be more sensitive for the detection of new teratogens than surveillance of all or isolated congenital anomalies. Current literature proposes the manual review of all cases for classification into isolated or multiple congenital anomal...

  4. Augmentin treatment during pregnancy and the prevalence of congenital abnormalities

    DEFF Research Database (Denmark)

    Czeizel, A.E.; Rockenbauer, M.; Sørensen, Henrik T

    2001-01-01

    Objective: To study the human teratogenic potential of augmentin (amoxicillin+clavulanic acid) treatment during pregnancy. Materials and methods: Pair analysis of cases with different congenital abnormalities and their matched controls in the population-based dataset of the Hungarian Case-Control...

  5. Fetal Alcohol Syndrome: A Behavioral Teratology.

    Science.gov (United States)

    Kavale, Kenneth A.; Karge, Belinda D.

    1986-01-01

    The review examines the literature on the behaviorally teratogenic aspects of Fetal Alcohol Syndrome, including: (1) prevalence of alcohol abuse among women, (2) acute and chronic effects of alcohol on the fetus, (3) genetic susceptibility, (4) neuropathology, (5) correlative conditions, and (6) animal studies. (Author/DB)

  6. An Overview of Teratology.

    Science.gov (United States)

    Calado, Ana M; Dos Anjos Pires, Maria

    2018-01-01

    In this chapter, we provide an overview of the basic principles of teratology, beginning with its definition, the critical point for teratogenesis to occur and the most evident etiological agents to improve the understanding of this science.Teratology is a recent science that began in the early twentieth century, and has greatly improved over the recent years with the advancements in molecular biology, toxicology, animal laboratory science, and genetics, as well as the improvement on the knowledge of the environmental influences.Nevertheless, more work is required to reduce the influence of hazardous products that could be deleterious during pregnancy, thus reducing teratogenic defects in the newborn. While some teratogenic defects are attributed to their agents with certainty, the same for a lot of other such defects is lacking, necessitating consistent studies to decipher the influence of various teratogenic agents on their corresponding teratogenic defects. It is here that the laboratory animal science is of great importance both in the present and in the future.

  7. Drug use by pregnant women and comparable non-pregnant women in The Netherlands with reference to the Australian classification system

    NARCIS (Netherlands)

    Schirm, Eric; Meijer, W.M.; Tobi, H; de Jong-van den Berg, Lolkje Theodora Wilhelmina

    2004-01-01

    Objective: To describe drug use in pregnancy, and compare drug use of pregnant women with non-pregnant women with respect to possible teratogenicity. Study design: A cross-sectional study based on pharmacy records from 1997 to 2001 was performed. Pregnant women and matched non-pregnant women (same

  8. Polydactyly in the central pacific gecko, Lepidodactylus sp. (Squamata: Gekkonidae)

    Science.gov (United States)

    Bauer, A.M.; Hathaway, S.A.; Fisher, R.N.

    2009-01-01

    We report the first known case of naturally occurring polydactyly in a gekkotan lizard. A single individual from Palmyra Atoll exhibited a triplication of digit III of the m hand. No obvious teratogenic sources are present on the atoll and the causal factors of polydactyly in Lepidodactylus sp. remain unknown.

  9. Cyclopamine: From cyclops lambs to cancer treatment

    Science.gov (United States)

    In the late 1960’s, the steroidal alkaloid, cyclopamine, was isolated from the plant Veratrum californicum and identified as the teratogen responsible for craniofacial birth defects including cyclops in the offspring of sheep grazing on mountain ranges in the western United States. Cyclopamine was f...

  10. Cardiovascular Ultrasound of Neonatal Long Evans Rats ...

    Science.gov (United States)

    This abstract describes the use of a relatively new technology, cardiovascular ultrasound (echocardiography) for evaluating developmental toxicity affecting heart development. The abstract describes the effects of two known cardiac teratogens, trichloroacetic acid and dimethadione, and their effects as determined by echocardiography. This abstract describes the use and development of a relatively new technology, cardiovascular ultrasound (echocardiography) for evaluating developmental toxicity affecting heart development.

  11. A monoclonal antibody-based ELISA for the hedgehog inhibitors cyclopamine and cyclopamine derivatives

    Science.gov (United States)

    In the late 1960’s cyclopamine was isolated from the plant Veratrum californicum and identified as the teratogen responsible for craniofacial birth defects including cyclops in the offspring of sheep grazing on mountain ranges in the western United States. More recently, cyclopamine was found to inh...

  12. Toxcast Profiling in a Human Stem Cell Assay for Developmental Toxicity (SOT)

    Science.gov (United States)

    We correlated the ToxCast library in a metabolic biomarker-based in vitro assay (Stemina devTOXqP) utilizing human embryonic stem (hES) cells (H9 line). This assay identifies the concentration of a chemical that disrupts cellular metabolism in a manner indicative of teratogenic...

  13. Effects of 5HPP-33,an antiangiogenic thalidomide analog, in mouse whole embryo culture

    Science.gov (United States)

    Thalidomide is a well-known example of a teratogen which has been shown to have an inhibitory effect on angiogenesis. As a result of its targeted effect on immature blood vessels, anti-angiogenic specific chemical analogs were developed to maximize this mechanism of thalidomide e...

  14. The Fetal Alcohol Syndrome Public Awareness Campaign, 1979: Progress Report Concerning the Advance Notice of Proposed Rulemaking on Warning Labels on Containers of Alcoholic Beverages and Addendum.

    Science.gov (United States)

    Department of the Treasury, Washington, DC.

    This report provides expert opinion on the problems of fetal alcohol syndrome (FAS) and ways to inform the public of teratogenic risk of alcohol consumption during pregnancy. In the absence of firm evidence that moderate drinking of alcoholic beverages leads to FAS and uncertainty concerning the effectiveness of labeling of alcoholic beverages, a…

  15. Toxicology and metabolism of nickel compounds: comprehensive report of overall activities during the three-year period from December 1, 1977 to November 30, 1980

    Energy Technology Data Exchange (ETDEWEB)

    Sunderman, Jr, F W

    1980-08-15

    The main research accomplishments during the past three years are summarized. The principle areas of investigation are: 1. embryotoxicity, teratogenicity, and mutagenicity of nickel carbonyl; 2. metabolism, detoxification, and excretion of nickel compounds; 3. studies of nickel carcinogenesis; 4. nickel analysis in body fluids and tissues to monitor occupational exposures; 5. nephrotoxicity of nickel compounds; and 6. hematological effects of nickel compounds. (ACR)

  16. Occurrence of aflatoxin contamination in maize kernels and ...

    African Journals Online (AJOL)

    Aflatoxins are toxic metabolites produced mainly by Aspergillus flavus and Aspergillus parasiticus. Aflatoxin B1 (AFB1) is a potent carcinogen, teratogen and mutagen. 660 pre- and post- harvest maize samples were collected from major maize growing areas in Tamil Nadu, India. Aflatoxin contamination was observed in ...

  17. Towards Building an AOP-based Prenatal Developmental Toxicity Ontology (SOT)

    Science.gov (United States)

    Retinoid signaling plays an important role in embryo-fetal development and its disruption is broadly teratogenic. The retinoic acid (RA) pathway includes elements in retinoid metabolism and nuclear receptor (RAR, RXR) activation and thus serves as an excellent prototype for adver...

  18. Mood-Stabilizing Anticonvulsants, Spina Bifida, and Folate Supplementation: Commentary.

    Science.gov (United States)

    Patel, Neil; Viguera, Adele C; Baldessarini, Ross J

    2018-02-01

    High risks of neural tube defects and other teratogenic effects are associated with exposure in early pregnancy to some anticonvulsants, including in women with bipolar disorder. Based on a semistructured review of recent literature, we summarized findings pertaining to this topic. Valproate and carbamazepine are commonly used empirically (off-label) for putative long-term mood-stabilizing effects. Both anticonvulsants have high risks of teratogenic effects during pregnancy. Risks of neural tube defects (especially spina bifida) and other major malformations are especially great with valproate and can arise even before pregnancy is diagnosed. Standard supplementation of folic acid during pregnancy can reduce risk of spontaneous spina bifida, but not that associated with valproate or carbamazepine. In contrast, lamotrigine has regulatory approval for long-term use in bipolar disorder and appears not to have teratogenic effects in humans. Lack of protective effects against anticonvulsant-associated neural tube defects by folic acid supplements in anticipation of and during pregnancy is not widely recognized. This limitation and high risks of neural tube and other major teratogenic effects, especially of valproate, indicate the need for great caution in the use of valproate and carbamazepine to treat bipolar disorder in women of child-bearing age.

  19. The Violation of Childhood: A Review of Possible Effects on Development of Toxic Chemical and Nuclear Waste.

    Science.gov (United States)

    Evans, Roy

    Emphasizing that for any known teratogen no safe dosage level exists, this case-illustrated review identifies the bases for current concern about the pollution of the environment, reflects on the promise and complexities of the emerging disciplines of behavioral toxicology and behavioral teratology, and describes existing evidence of teratogenic…

  20. Fetal-muscle type nicotinic acetylcholine receptor activation in TE-671 cells, and inhibition of fetal movement in a day 40 pregnant goat model by optical isomers of the piperidine alkaloid coniine

    Science.gov (United States)

    Coniine is an optically active toxic piperidine alkaloid and nicotinic acetylcholine receptor (nAChR) agonist found in poison hemlock (Conium maculatum L.). Coniine teratogenicity is hypothesized to be due to the binding, activation, and prolonged desensitization of fetal muscle-type nAChR which re...

  1. Assay for the developmental toxicity of safflower (Carthamus tinctorius L. to zebrafish embryos/larvae

    Directory of Open Access Journals (Sweden)

    Qing Xia

    2017-01-01

    Conclusion: Safflower exhibits developmental toxicity for zebrafish embryos/larvae. The developing heart was speculated as the target organ of toxicity. Oxidative stress and increased apoptosis have roles in the developmental toxicity of safflower. This article provides a novel method to research the teratogenicity and possible mechanisms of toxicity of traditional Chinese medicines that are prohibited or contraindicated in pregnant women.

  2. Selection of controls in case-control studies on maternal medication use and risk of birth defects

    NARCIS (Netherlands)

    Bakker, M.K.; de Walle, H.E.; Dequito, A.; van den Berg, P.B.; de Jong-van den Berg, L.T.

    BACKGROUND:: In case-control studies on teratogenic risks of maternal drug use during pregnancy, the use of normal or malformed controls may lead to recall-bias or selection bias. This can be avoided by using controls with a genetic disorder. However, researchers are hesitant to use these as

  3. A toxicity signature for species-specific disruption of embryonic vasculogenesis derived from ToxCast in vitro profiling data

    Science.gov (United States)

    Blood vessel formation is crucial for normal embryo development and is sensitive to disruption by diverse teratogens. Recent studies have begun to reveal the cell signaling networks underlying vasculogenesis and angiogenesis and how these pathways might be perturbed by specific c...

  4. Proteins in growth regulation during early development. Comprehensive three year report, 1974--1977

    Energy Technology Data Exchange (ETDEWEB)

    Klein, N.W.

    1977-08-01

    Progress is reported on the following research projects: response of embryo regions to nutrition; synthesis of serum proteins by the yolk-sac; serum protein synthesis in relation to protein nutrition, protease secretion, teratogenic agents, genetic abnormalities, yolk-sac cell cultures, and cell free systems; and effects of serum proteins on rat embryos, chick embryos without yolk-sacs, and isolated brains. (HLW)

  5. EFFECTS OF EPIDERMAL GROWTH FACTOR (EGF), TRANSFORMING GROWTH FACTOR- (TGF), AND 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN ON FUSION OF EMBRYONIC PALATES IN SERUM-FREE ORGAN CULTURE USING WILD-TYPE, EGF KNOCKOUT, AND TGF KNOCKOUT MOUSE STRAINS

    Science.gov (United States)

    Backround: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is teratogenic in mice, producing cleft palate (CP). TCDD exposure disrupts expression of epidermal growth factor (EGF) receptor, EGF, and transforming growth factor- (TGF) in the palate and affects proliferation and different...

  6. Omalizumab use during pregnancy for CIU: a tertiary care experience.

    Science.gov (United States)

    Cuervo-Pardo, L; Barcena-Blanch, M; Radojicic, C

    2016-07-01

    The treatment of antihistamine and steroid resistant Chronic Idiopathic Urticaria (CIU) during pregnancy poses a challenge due to teratogenicity of immunosuppressants. Omalizumab is a recently FDA approved therapy for CIU and is classified as pregnancy category B. We present an initial series of subjects treated at a tertiary care center for antihistamine and steroid resistant CIU with omalizumab who became pregnant during therapy.

  7. Antipsykotika i graviditeten--skades barnet?

    DEFF Research Database (Denmark)

    Dehn, Camilla; Dalhoff, Kim P

    2007-01-01

    of teratogenicity. Use of antipsychotic drugs should, however, be avoided during the first 3 months of pregnancy. If this is not possible, it is recommended to use the lowest dose possible for as short a period as possible. In addition, an obstetrician should follow the pregnant woman very closely, and the pregnant...

  8. Congenital malformations in mice induced by addiction to alcohol ...

    African Journals Online (AJOL)

    Objective: To study the teratogenic effect of either alcohol alone, cocaine alone, or a combination of both alcohol and cocaine on mice foetuses. Design: Eighty pregnant mice were divided into four equal groups. In the first (alcohol) group, the pregnant females were given absolute ethanol at 2.5gm/100 gm twice daily by ...

  9. Safety assessment of lactate esters

    NARCIS (Netherlands)

    Clary, J.J.; Feron, V.J.; Velthuijsen, J.A. van

    1998-01-01

    Lactate eaters have an oral LD50 greater than 2000 mg/kg and the inhalation LC50 is generally above 5000 mg/m3 and they may be potential eye and skin irritants, but not skin sensitizers. No evidence of teratogenicity or maternal toxicity was observed in an inhalation (2-ethylhexyl-L-lactate) or

  10. Development of a monoclonal antibody-based ELISA for the hedgehog inhibitors cyclopamine and cyclopamine-KAAD

    Science.gov (United States)

    Cyclopamine was isolated from Veratrum californicum and identified as the teratogen responsible for severe craniofacial birth defects including cyclops in the offspring of sheep grazing on mountain ranges in central Idaho. More recently, cyclopamine was found to inhibit the hedgehog (Hh) signaling ...

  11. Kinetiek en teratogeniteit van vitamine A. Een literatuurstudie

    NARCIS (Netherlands)

    Olling M; Bode W; Bruil M; Groen K; Piersma AH

    1992-01-01

    This report describes a literature study of the kinetics of vitamin A in different animal species. The goal of this study was to collect data to develop a model for risk assessment of the teratogenic effects of vitamin A. In the diet vitamin A is present as esters of retinol and as carotenoids. In

  12. Mutagenesis and teratogenesis as end points in health impact assessment

    International Nuclear Information System (INIS)

    Bender, M.A.

    1976-01-01

    The genetic and teratogenic effects of agents released to the environment as a consequence of energy production are exceedingly difficult to evaluate. Nevertheless, these effects on human health may be very costly in the context of cost-benefit analysis. In fact, the procedures required to limit mutagenic or teratogenic agents to the levels considered acceptable by regulatory bodies may constitute a major fraction of the cost of energy, especially where prudence dictates that a lack of empirical data requires extremely conservative regulations. Experience with ionizing radiation and with regulation of nuclear power installations illustrates the difficulty of genetic and teratogenic health impact assessment and the great uncertainties involved, as well as the influence of these impacts on the regulatory process and the consequent increased cost of power from this source. Data on genetic and teratogenic impacts on human health from chemical agents released to the environment by other energy technologies are much less complete, and, because of the large number of potentially active agents involved, it is evident that generic solutions to health impact assessment will be required to evaluate these energy alternatives

  13. National legislation, international conventions and exposure to harmful chemicals

    CSIR Research Space (South Africa)

    Hietkamp, S

    2006-06-01

    Full Text Available to be teratogenic in rats and rabbits at low doses according to the information available to Canada at the time. It is used in orchards and greenhouses to control mites on apples, pears, peaches, nectarines, strawberries, hops, non- bearing raspberries...

  14. CONTAMINANT-INDUCED ENDOCRINE DISRUPTION IN WILDLIFE

    Science.gov (United States)

    Environmental contaminants have posed a threat to the health of wildlife since the onset of the industrial age. Over the last four decades, much concern has focused on the lethal, carcinogenic and/or extreme teratogenic manifestations of environmental pollution. During the last d...

  15. Inhibitory effect of essential oil on aflatoxin activities | Alpsoy ...

    African Journals Online (AJOL)

    Aflatoxins, which are well-known to be mutagenic, carcinogenic, teratogenic, hepatotoxic and immunosuppressive, also inhibit several metabolic systems. Aflatoxins are biologically active secondary metabolites produced by certain strains of Aspergillus parasiticus, Aspergillus nominus and Aspergillus flavus. Many different ...

  16. Evaluation of medicated feeds with antiparasitical and immune-enhanced Chinese herbal medicines against Ichthyophthirius multifiliis in grass carp (Ctenopharyngodon idellus)

    Science.gov (United States)

    Ichthyophthirius multifiliis (Ich) is a widespread ciliated ectoparasite and results in severe economic loss in the aquaculture industry. Since malachite green was banned for using in food fish due to its carcinogenic and teratogenic effects on human, the search of alternative drug to treat I. multi...

  17. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry

    DEFF Research Database (Denmark)

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio

    2011-01-01

    Prenatal exposure to antiepileptic drugs is associated with a greater risk of major congenital malformations, but there is inadequate information on the comparative teratogenicity of individual antiepileptic drugs and the association with dose. We aimed to establish the risks of major congenital ...

  18. Separation and Measurement of Plant Alkaloid Enantiomers by RP-HPLC Analysis of their Fmoc-Alanine Analogs

    Science.gov (United States)

    Plants often synthesize secondary metabolites that are enantiomers. Enantiomers can cause very different physiological responses. Ammodendrine (1) and anabasine (2) are teratogens that can cause congenital malformations in livestock and enantiomeric forms of each have been found in Lupinus spp. an...

  19. Dose rate effectiveness in radiation-induced teratogenesis in mice

    International Nuclear Information System (INIS)

    Kato, F.; Ootsuyama, A.; Norimura, T.

    2000-01-01

    To investigate the role of p53 gene in tissue repair of teratogenic injury, we compared incidence of radiation-induced malformations in homozygous p53(-/-) mice, heterozygous p53(+/-) mice and wild-type p53(+/+) mice. After X-irradiation with 2 Gy at high dose rate on 9.5 days of gestation, p53(-/-) mice showed higher incidences of anomalies and higher resistance to prenatal deaths than p53(+/+) mice. This reciprocal relationship of radiosensitivity to anomalies and deaths supports the notion that embryos or fetuses have a p53-dependent 'guardian' that aborts cells bearing radiation-induced teratogenic DNA damage. In fact, after X-irradiation, the number of apoptotic cells was greatly increased in p53(+/+) fetuses but not in p53(-/-) fetuses. The same dose of γ-ray exposure at low dose rate on 9.5-10.5 day of gestation produced significant reduction of radiation-induced malformation in p53(+/+) and p53(+/-) mice, remained teratogenic for p53(-/-) mice. These results suggest that complete elimination of teratogenic damage from irradiated tissues requires the concerted cooperation of two mechanisms; proficient DNA repair and the p53-dependent apoptotic tissue repair. When concerted DNA repair and apoptosis functions efficiently, there is a threshold dose-rate for radiation-induced malformations. (author)

  20. Risks versus benefits of medication use during pregnancy : What do women perceive?

    NARCIS (Netherlands)

    Mulder, Bianca; Schuiling-Veninga, Nynke C.M.; Morssink, Leonard P.; Bijlsma, Maarten J.; Van Puijenbroek, Eugene; Aarnoudse, Jan G.; Hak, Eelko; De Vries, Tjalling W.

    2014-01-01

    Background: Understanding risk perception is essential in designing good risk communication strategies. It has been reported that women overestimate the teratogenic risk of medication use, but these studies didn't include perceived benefits and major concerns of pregnant women regarding medication

  1. Incidence of nevirapine-associated hepatitis in an antenatal clinic

    African Journals Online (AJOL)

    2008-01-22

    Jan 22, 2008 ... together with a non-nucleoside reverse transcriptase inhibitor, either efavirenz or nevirapine.1 As efavirenz is thought to be a teratogen and is classified as a Food and Drug Administration. (FDA) category D drug, nevirapine is the preferred agent for use in pregnant women, for women planning a pregnancy ...

  2. Anomalous Origin of the Subclavian Artery Associated with ...

    African Journals Online (AJOL)

    Thallium, insulin, sulphonamides and other compounds as well as lack of riboflavine produce phocomelia-like malformations in experimental animals while maternal infection such as rubella is teratogenic in humans, but evidence that it causes phocomelia is not well established. Fig. 3. Arteriogram with injection of contrast ...

  3. Biological assays for aquatic toxicity testing

    CSIR Research Space (South Africa)

    Slabbert, JL

    1999-10-01

    Full Text Available and management purposes of effluents. If receiving water is used for drinking water purposes, the Ames Salmonella mutagenicity and toad embryo teratogenicity tests should be included in the battery of tests. Some of the rapid microbiotests, the petrozoan oxygen...

  4. Selective Cognitive Deficits in Adult Rats after Prenatal Exposure to Inhaled Ethanol

    Science.gov (United States)

    Increased use of ethanol blends in gasoline suggests a need to assess the potential public health risks of exposure to these fuels. Ethanol consumed during pregnancy is a teratogen. However, little is known about the potential developmental neurotoxicity of ethanol delivered by i...

  5. Author Details

    African Journals Online (AJOL)

    Enaibe, BU. Vol 7, No 1-2 (2008) - Articles Histological Studies Of The Teratogenic Effects Of Camphor On The Developing Kidney Of The Wistar Rats Abstract. ISSN: 1596-6569. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners ...

  6. Author Details

    African Journals Online (AJOL)

    Enaibe, B U. Vol 1, No 2 (2002) - Articles Histological Studies Of The Teratogenic Effects Of Camphor On The Developing Liver Of The Wistar Rats Abstract · Vol 2, No 2 (2003) - Articles Histological Studies Of The Effects Of Oral Administration Of Damiana (Turnera Diffusa) On The Liver Of Mature Wistar Rats Abstract.

  7. Author Details

    African Journals Online (AJOL)

    Histological Studies Of The Teratogenic Effects Of Camphor On The Developing Kidney Of The Wistar Rats Abstract · Vol 7, No 1-2 (2008) - Articles Histological Studies Of The Effects Of Oral Administration Of Artesunate On The Lateral Geniculate Body Of Adult Wistar Rats Abstract · Vol 9, No 1 (2010) - Articles Histological ...

  8. The effect of intermittent dosing of Nicotiana glauca on teratogenesis in goats

    Science.gov (United States)

    Sustained inhibition of fetal movement in livestock species, induced by several poisonous plants, can result in numerous skeletal-contracture malformations. Lupines are responsible for a condition in cattle referred to as “crooked calf syndrome” that occurs when pregnant cattle graze teratogenic lup...

  9. Concentration-dependent actions of piperidine alkaloids on the inhibition of fetal movement in day 40 pregnant goats and comparison to cell-based models

    Science.gov (United States)

    Anabasine and anabaseine are potent and effective agonists at nicotinic acetylcholine receptors (nAChR). Anabasine in livestock species is teratogenic and has been shown to cause developmental defects that include arthrogyrposis, kyposis, lordosis, scoliosis, and torticollis. We have postulated that...

  10. Health Risk Assessment Approach for 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (Draft)

    Science.gov (United States)

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most toxic and environmentally stable pollutants. In addition to various toxic effects, TCDD has been found to cause teratogenic, fetocidal, reproductive and carcinogenic effects in animals. In humans it adversely affects v...

  11. 76 FR 34706 - Privacy Act of 1974; System of Records

    Science.gov (United States)

    2011-06-14

    ... female) and teratogenic agents; (8) bio-accumulating non-carcinogen agents; (9) chronic vascular disease- causing agents; and (10) ionizing radiation. Also included are those individuals in the general population... retrieve records required to reconstruct radiation doses and to enable NIOSH to evaluate petitions for...

  12. Behavioural Outcomes of Four-Year-Old Children Prenatally Exposed to Methadone or Buprenorphine: A Test of Three Risk Models

    Science.gov (United States)

    Konijnenberg, Carolien; Lund, Ingunn Olea; Melinder, Annika

    2015-01-01

    It is still under debate whether the reported effects of opioid maintenance therapy (OMT) on child behaviour are a direct effect of prenatal exposure, or whether other factors are involved. This prospective cohort study investigated three models: the teratogenic risk model, the maternal risk model, and a combined risk model in a group of 35…

  13. O renascimento de um fármaco: talidomida The rebirth of a drug: thalidomide

    Directory of Open Access Journals (Sweden)

    Lídia Moreira Lima

    2001-10-01

    Full Text Available Thalidomide, first synthesized in 1953, was widely prescribed for morning sickness of pregnant women from 1957 to 1961, when it was found to be seriously teratogenic, having caused serious birth defect. Nowadays, a quarter of a century later, it appears that it may be a miracle drug for such diseases as leprosy, AIDS, cancer and tuberculosis.

  14. Exposure to candesartan during the first trimester of pregnancy in type 1 diabetes: experience from the placebo-controlled diabetic retinopathy candesartan trials

    DEFF Research Database (Denmark)

    Porta, M; Hainer, J W; Jansson, S-O

    2011-01-01

    AIMS/HYPOTHESIS: The teratogenic consequences of angiotensin-converting enzyme inhibitors angiotensin receptor blockers (ARBs) during the second and third trimesters of pregnancy are well described. However, the consequences of exposure during the first trimester are unclear, especially in diabet...

  15. Anagyrine desensitization of peripheral nicotinic acetylcholine receptors. A potential biomarker of quinolizidine alkaloid teratogenesis in cattle.

    Science.gov (United States)

    Anagyrine, a teratogenic quinolizidine alkaloid found in certain Lupinus spp., has been proposed to undergo metabolism by pregnant cattle to a piperidine alkaloid which acts inhibit fetal movement, the putative mechanism behind crooked calf syndrome. The objective of this study was to test the hypot...

  16. Agonist mediated fetal muscle-type nicotinic acetylcholine receptor desensitization

    Science.gov (United States)

    The exposure of a developing embryo or fetus to teratogenic alkaloids from plants has the potential to cause developmental defects in livestock due to the inhibition of fetal movement by alkaloids. The mechanism behind the inhibition of fetal movement is the desensitization of fetal muscle-type nico...

  17. Safety evaluation of synthetic β-carotene

    NARCIS (Netherlands)

    Woutersen, R.A.; Wolterbeek, A.P.M.; Appel, M.J.; Berg, H. van den; Goldbohm, R.A.; Feron, V.J.

    1999-01-01

    The safety of β-carotene was reassessed by evaluating the relevant literature on the beneficial and adverse effects of β-carotene on cancer and, in particular, by evaluating the results of toxicity studies. β- Carotene appeared neither genotoxic nor reprotoxic or teratogenic, and no signs of organ

  18. Genetic and environmental risk factors in congenital heart disease functionally converge in protein networks driving heart development

    DEFF Research Database (Denmark)

    Hansen, Kasper Lage; Greenway, Steven C.; Rosenfeld, Jill A.

    2012-01-01

    Congenital heart disease (CHD) occurs in ∼1% of newborns. CHD arises from many distinct etiologies, ranging from genetic or genomic variation to exposure to teratogens, which elicit diverse cell and molecular responses during cardiac development. To systematically explore the relationships between...

  19. Psychiatry Trainees' Training and Experience in Fetal Alcohol Spectrum Disorders

    Science.gov (United States)

    Eyal, Roy; O'Connor, Mary J.

    2011-01-01

    Background/Objective: Alcohol is a teratogen. Fetal alcohol spectrum disorders (FASDs) affect about 1% of live births, causing severe impairment. Individuals affected by FASDs are overrepresented in psychiatric settings. This study reports on the education and experience of psychiatry trainees in approaching FASDs. Method: Data were collected from…

  20. Public Attitudes to and Awareness of Fetal Alcohol Syndrome in Young Adults.

    Science.gov (United States)

    Oei, Tian P. S.; And Others

    1986-01-01

    Assessed public attitude toward, and awareness of possible problems and risks associated with, the consumption of alcohol during pregnancy. Results indicated a high awareness of the problem, knowledge of the specific effects to the offspring, and of quantities and frequency of consumption of alcohol which would have teratogenic effects were…

  1. Oxidative-stress-mediated teratogenesis and the role of folate

    NARCIS (Netherlands)

    Tran, Y.H.; Bergman, J.; Bakker, M.; Groen, H.; Wilffert, B.

    2016-01-01

    Background: Oxidative stress (OS) is one of the underlying teratogenic mechanisms of medical drugs. Folate is indirectly involved in OS because of its role in the methylation steps in the detoxification of xenobiotics and in the repair of OS-induced DNA damage. Our study was to explore the

  2. Lewisite: its chemistry, toxicology, and biological effects.

    Science.gov (United States)

    Goldman, M; Dacre, J C

    1989-01-01

    Lewisite is an organic arsenical war gas which is a vesicant with attendant toxicities due to its ability to combine with thiol groups which are essential for activity of a variety of enzymes. Although Lewisite has been designated as a "suspected carcinogen," the indictment is not supported by the available scientific evidence. Indeed, the unwarranted conclusion is based on one specific case history of a former German soldier whose lower right leg was exposed to liquid Lewisite in 1940 with subsequent development of intraepidermal squamous cell carcinoma, and the examination of death certificates of former workers at a Japanese factory that manufactured a variety of war gases including mustard gas, hydrocyanic acid, chloracetophenome, phosgene, diphenylcyanarsine and Lewisite. It is difficult to comprehend why Lewisite was selected out of this group of toxic chemicals as one of those responsible for respiratory cancer in these workers. It would appear to be a difficult task, indeed, to disengage a specific worker from one of the other of several gases at the workplace and assign a specific gas-induced death. The evidence that organic arsenicals are carcinogenic is weak. Although the weight of evidence is such that inorganic arsenical derivatives are considered weak mutagens, the evidence that organic arsenicals are mutagenic is poor. Recent examination of the mutagenic potential of Lewisite using the Ames test has shown that Lewisite is not mutagenic under these circumstances. While oral administration of arsenical compounds, whether inorganic or organic, does not induce teratogenicity except at very high dose levels which are associated with some degree of maternal toxicity, parenteral administration has been associated with teratogenicity but information of maternal toxicity has not always been available. Indeed, maternal toxicity should be considered as an important diagnostic tool in assessing whether a chemical is teratogenic. The significance of parenteral

  3. Clinical trial considerations on male contraception and collection of pregnancy information from female partners

    Directory of Open Access Journals (Sweden)

    Banholzer Maria

    2012-06-01

    Full Text Available Abstract Background There is little guidance regarding the risk of exposure of pregnant women/ women of childbearing potential to genotoxic or teratogenic compounds via vaginal dose delivered through seminal fluid during sexual intercourse. Method We summarize current thinking and provide clinical trial considerations for a consistent approach to contraception for males exposed to genotoxic and/or teratogenic compounds or to compounds of unknown teratogenicity, and for collection of pregnancy data from their female partners. Results Where toxicity testing demonstrates genotoxic potential, condom use is required during exposure and for 5 terminal plasma half-lives plus 74 days (one human spermatogenesis cycle to avoid conception. For non-genotoxic small molecules and immunoglobulins with unknown teratogenic potential or without a no observed adverse effect level (NOAEL from embryo-fetal development (EFD studies and no minimal anticipated biological effect level (MABEL, condom use is recommended for males with pregnant partner/female partner of childbearing potential. For teratogenic small molecules with estimated seminal fluid concentration and a margin between projected maternal area under the curve (AUC and NOAEL AUC from EFD studies of ≥300 (≥100 for immunoglobulins or in the absence of a NOAEL with a margin between MABEL plasma concentration and maternal Cmax of ≥300 (≥10 for immunoglobulins, condom use is not required. However, condom use is required for margins below the thresholds previously indicated. For small molecules with available seminal fluid concentrations, condom use is required if margins are Pregnancy data should be proactively collected if pregnancy occurs during the condom use period required for males exposed to first-in-class molecules or to molecules with a target/class shown to be teratogenic, embryotoxic or fetotoxic in human or preclinical experiments. Conclusion These recommendations, based on a precaution

  4. Improvements in Clinical Trials Information Will Improve the Reproductive Health and Fertility of Cancer Patients.

    Science.gov (United States)

    Dauti, Angela; Gerstl, Brigitte; Chong, Serena; Chisholm, Orin; Anazodo, Antoinette

    2017-06-01

    There are a number of barriers that result in cancer patients not being referred for oncofertility care, which include knowledge about reproductive risks of antineoplastic agents. Without this information, clinicians do not always make recommendations for oncofertility care. The objective of this study was to describe the level of reproductive information and recommendations that clinicians have available in clinical trial protocols regarding oncofertility management and follow-up, and the information that patients may receive in clinical trials patient information sheets or consent forms. A literature review of the 71 antineoplastic drugs included in the 68 clinical trial protocols showed that 68% of the antineoplastic drugs had gonadotoxic animal data, 32% had gonadotoxic human data, 83% had teratogenic animal data, and 32% had teratogenic human data. When the clinical trial protocols were reviewed, only 22% of the protocols reported the teratogenic risks and 32% of the protocols reported the gonadotoxic risk. Only 56% of phase 3 protocols had gonadotoxic information and 13% of phase 3 protocols had teratogenic information. Nine percent of the protocols provided fertility preservation recommendations and 4% provided reproductive information in the follow-up and survivorship period. Twenty-six percent had a section in the clinical trials protocol, which identified oncofertility information easily. When gonadotoxic and teratogenic effects of treatment were known, they were not consistently included in the clinical trial protocols and the lack of data for new drugs was not reported. Very few protocols gave recommendations for oncofertility management and follow-up following the completion of cancer treatment. The research team proposes a number of recommendations that should be required for clinicians and pharmaceutical companies developing new trials.

  5. Comparing three novel endpoints for developmental osteotoxicity in the embryonic stem cell test

    International Nuclear Information System (INIS)

    Nieden, Nicole I. zur; Davis, Lesley A.; Rancourt, Derrick E.

    2010-01-01

    Birth defects belong to the most serious side effects of pharmaceutical compounds or environmental chemicals. In vivo, teratogens most often affect the normal development of bones, causing growth retardation, limb defects or craniofacial malformations. The embryonic stem cell test (EST) is one of the most promising models that allow the in vitro prediction of embryotoxicity, with one of its endpoints being bone tissue development. The present study was designed to describe three novel inexpensive endpoints to assess developmental osteotoxicity using the model compounds penicillin G (non-teratogenic), 5-fluorouracil (strong teratogen) and all-trans retinoic acid (bone teratogen). These three endpoints were: quantification of matrix incorporated calcium by (1) morphometric analysis and (2) measurement of calcium levels as well as (3) activity of alkaline phosphatase, an enzyme involved in matrix calcification. To evaluate our data, we have compared the concentration curves and resulting ID 50 s of the new endpoints with mRNA expression for osteocalcin. Osteocalcin is an exclusive marker found only in mineralized tissues, is regulated upon compound treatment and reliably predicts the potential of a chemical entity acting as a bone teratogen. By comparing the new endpoints to quantitative expression of osteocalcin, which we previously identified as suitable to detect developmental osteotoxicity, we were ultimately able to illustrate IMAGE analysis and Ca 2+ deposition assays as two reliable novel endpoints for the EST. This is of particular importance for routine industrial assessment of novel compounds as these two new endpoints may substitute previously used molecular read-out methods, which are often costly and time-consuming.

  6. A role for glutathione, independent of oxidative stress, in the developmental toxicity of methanol

    International Nuclear Information System (INIS)

    Siu, Michelle T.; Shapiro, Aaron M.; Wiley, Michael J.; Wells, Peter G.

    2013-01-01

    Oxidative stress and reactive oxygen species (ROS) have been implicated in the teratogenicity of methanol (MeOH) in rodents, both in vivo and in embryo culture. We explored the ROS hypothesis further in vivo in pregnant C57BL/6J mice. Following maternal treatment with a teratogenic dose of MeOH, 4 g/kg via intraperitoneal (ip) injection on gestational day (GD) 12, there was no increase 6 h later in embryonic ROS formation, measured by 2′,7′-dichlorodihydrofluorescin diacetate (DCFH-DA) fluorescence, despite an increase observed with the positive control ethanol (EtOH), nor was there an increase in embryonic oxidatively damaged DNA, quantified as 8-oxo-2′-deoxyguanosine (8-oxodG) formation. MeOH teratogenicity (primarily ophthalmic anomalies, cleft palate) also was not altered by pre- and post-treatment with varying doses of the free radical spin trapping agent alpha-phenyl-N-tert-butylnitrone (PBN). In contrast, pretreatment with L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, depleted maternal hepatic and embryonic GSH, and enhanced some new anomalies (micrognathia, agnathia, short snout, fused digits, cleft lip, low set ears), but not the most common teratogenic effects of MeOH (ophthalmic anomalies, cleft palate) in this strain. These results suggest that ROS did not contribute to the teratogenic effects of MeOH in this in vivo mouse model, in contrast to results in embryo culture from our laboratory, and that the protective effect of GSH in this model may arise from its role as a cofactor for formaldehyde dehydrogenase in the detoxification of formaldehyde. - Highlights: • In vivo, a free radical scavenger did not block methanol (MeOH) teratogenesis. • MeOH did not increase embryonic reactive oxygen species formation or DNA oxidation. • MeOH teratogenesis was enhanced by glutathione (GSH) depletion. • GSH may protect as the cofactor for formaldehyde dehydrogenase (ADH3). • Formaldehyde may be a ROS

  7. A role for glutathione, independent of oxidative stress, in the developmental toxicity of methanol

    Energy Technology Data Exchange (ETDEWEB)

    Siu, Michelle T.; Shapiro, Aaron M. [Division of Biomolecular Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario (Canada); Wiley, Michael J. [Division of Anatomy, Faculty of Medicine, University of Toronto, Toronto, Ontario (Canada); Wells, Peter G., E-mail: pg.wells@utoronto.ca [Division of Biomolecular Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario (Canada); Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario (Canada)

    2013-12-15

    Oxidative stress and reactive oxygen species (ROS) have been implicated in the teratogenicity of methanol (MeOH) in rodents, both in vivo and in embryo culture. We explored the ROS hypothesis further in vivo in pregnant C57BL/6J mice. Following maternal treatment with a teratogenic dose of MeOH, 4 g/kg via intraperitoneal (ip) injection on gestational day (GD) 12, there was no increase 6 h later in embryonic ROS formation, measured by 2′,7′-dichlorodihydrofluorescin diacetate (DCFH-DA) fluorescence, despite an increase observed with the positive control ethanol (EtOH), nor was there an increase in embryonic oxidatively damaged DNA, quantified as 8-oxo-2′-deoxyguanosine (8-oxodG) formation. MeOH teratogenicity (primarily ophthalmic anomalies, cleft palate) also was not altered by pre- and post-treatment with varying doses of the free radical spin trapping agent alpha-phenyl-N-tert-butylnitrone (PBN). In contrast, pretreatment with L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, depleted maternal hepatic and embryonic GSH, and enhanced some new anomalies (micrognathia, agnathia, short snout, fused digits, cleft lip, low set ears), but not the most common teratogenic effects of MeOH (ophthalmic anomalies, cleft palate) in this strain. These results suggest that ROS did not contribute to the teratogenic effects of MeOH in this in vivo mouse model, in contrast to results in embryo culture from our laboratory, and that the protective effect of GSH in this model may arise from its role as a cofactor for formaldehyde dehydrogenase in the detoxification of formaldehyde. - Highlights: • In vivo, a free radical scavenger did not block methanol (MeOH) teratogenesis. • MeOH did not increase embryonic reactive oxygen species formation or DNA oxidation. • MeOH teratogenesis was enhanced by glutathione (GSH) depletion. • GSH may protect as the cofactor for formaldehyde dehydrogenase (ADH3). • Formaldehyde may be a ROS

  8. Risk factors for congenital heart diseases in Alexandria, Egypt

    International Nuclear Information System (INIS)

    Bassili, A.; Mokhtar, S.A.; Dabous, N.I.; Zaher, S.R.; Mokhtar, M.M.; Zaki, A.

    2000-01-01

    A matched case control study has been conducted in the children's hospitals in Alexandria, Egypt, during 2 years-period, aiming at investigating the risk factors for the occurrence of congenital heart diseases. Our results showed that the significant risk factors for developing any type of congenital heart disease and ventricular septal defects were: older paternal age at birth, positive consanguinity, positive family history, female sex hormones, irradiation, hazardous maternal occupation, diabetes mellitus and suburban or rural residence. However, some environmental/teratogenic factors were not implicated in the etiology of atrial septal defects or pulmonary stenosis. These findings strongly suggest that environmental factors vary according to the specific type of congenital heart disease. This study emphasizes on the need to instruct the public about the importance of pre-marital counselling and the deleterious effects of various teratogens in the environment

  9. Summary of safety evaluation toxicity studies of glufosinate ammonium.

    Science.gov (United States)

    Ebert, E; Leist, K H; Mayer, D

    1990-05-01

    This article reviews the results of toxicity studies to evaluate the safety of the herbicide glufosinate ammonium (GLA) and its formulation (200 g/litre) in laboratory animals. The data show that GLA and its formulation are slightly toxic following oral exposure. In addition, the formulation induced GLA and its formulation are slightly toxic following oral exposure. In addition, the formulation induced slight dermal toxicity and eye irritation. Testing for teratogenicity in rats and rabbits indicated no teratogenic potential, and numerous mutagenicity tests showed GLA to be non-genotoxic. Chronic toxicity testing in rats and dogs yielded no-observable-effect levels of 2 and 5 mg/kg body weight/day, respectively. Oncogenicity studies in rats and mice revealed no carcinogenic potential. On the basis of these toxicity data it is concluded that this herbicide is safe under conditions of recommended use.

  10. Mullerian agenesis associated with in-utero thalidomide exposure: A case report

    Directory of Open Access Journals (Sweden)

    Sarah Dotters-Katz

    2013-09-01

    Full Text Available Thalidomide is a well-known teratogen, which is experiencing resurgence as new uses are identified. Exposure is classically associated with limb deformities, such as: dysmelia, phocomelia, preaxial hypoplasia and polydactyly, in addition to visceral anomalies that have been documented as well. We report a case of a 38 year-old nulligravid female, who was previously evaluated for primary amenorrhea, and given the presumptive false diagnosis of an imperforate hymen. On magnetic resonance imaging (MRI exam, she was noted to have uterovaginal agenesis. The implications of thalidomide on women’s health extend beyond external birth defects. Although, most commonly associated with limb deformities, there may also be gynecologic implications of in utero exposure. As this medication is increasingly used for various medical conditions, obstetricians/gynecologists need to remain aware of this potential mullerian teratogenic effect.

  11. MORFOLOGI FETUS MENCIT (MUS MUSCULUS L. SETELAH PEMBERIAN EKSTRAK DAUN SAMBILOTO (ANDROGRAPHIS PANICULATA NEES

    Directory of Open Access Journals (Sweden)

    IRIANI SETYAWATI

    2014-08-01

    Full Text Available This experiment was performed to examine the effects of Andrographis paniculata Nees leaves extract on foetus morphology if given during organogenesis period. Thirty pregnant mice were randomly divided into 5 groups for teratogenic effects. Extract was given orally by gavage with 0 (as control; 0,004 (equal to one time dose to human; 7,5; 15; and 22,5 g/g body weight/ day. Treatment was given from day 6 to day 13 of gestation (organogenesis period. Foetus were removed on day 18 of gestation by caesarean section. Quantitative data were analyzed with Anova and Duncan's Multiple Range Test. The results showed that teratogenic effects increased in dose-related manner by causing foetus death and resorption, hemorrhage and clubfoot.

  12. The rat whole embryo culture assay using the Dysmorphology Score system.

    Science.gov (United States)

    Zhang, Cindy; Panzica-Kelly, Julie; Augustine-Rauch, Karen

    2013-01-01

    The rat whole embryo culture (WEC) system has been used extensively for characterizing teratogenic properties of test chemicals. In this chapter, we describe the methodology for culturing rat embryos as well as a new morphological score system, the Dysmorphology Score (DMS) system for assessing morphology of mid gestation (gestational day 11) rat embryos. In contrast to the developmental stage focused scoring associated with the Brown and Fabro score system, this new score system assesses the respective degree of severity of dysmorphology, which delineates normal from abnormal morphology of specific embryonic structures and organ systems. This score system generates an approach that allows rapid identification and quantification of adverse developmental findings, making it conducive for characterization of compounds for teratogenic properties and screening activities.

  13. Human malformations induced by environmental noxae

    International Nuclear Information System (INIS)

    Hecker, W.C.; Angerpointner, T.A.

    1980-01-01

    The paper reviews congenital malformations in humans and presents possible causes. 60% of all malformations are a result of environmental and other factors; i.e. not hereditary or caused by a disease of the mother. The teratogenic effects of ionizing radiation, drugs, alcohol, polyvinyl chloride and trichlorophenol are discussed as well as the effect of the mother's working in certain fields, e.g. clinical laboratories or printing offices; in the latter case the teratogenic noxae are still unknown. Efficient research requires centralized storage of all data on children born with malformations and on the mother's health situation during pregnancy, and the legislator is asked to do so while observing the law on data protection. Foundation of a German Institute of Teratology is recommended. In order to intensify research, it is suggested to set up groups or departments for research on malformations in some major paediatric hospitals. (MG) [de

  14. Ethylene glycol and propylene glycol ethers – Reproductive and developmental toxicity

    Directory of Open Access Journals (Sweden)

    Beata Starek-Świechowicz

    2015-10-01

    Full Text Available Both ethylene and propylene glycol alkyl ethers (EGAEs and PGAEs, respectively are widely used, mainly as solvents, in industrial and household products. Some EGAEs demonstrate gonadotoxic, embriotoxic, fetotoxic and teratogenic effects in both humans and experimental animals. Due to the noxious impact of these ethers on reproduction and development of organisms EGAEs are replaced for considerably less toxic PGAEs. The data on the mechanisms of testicular, embriotoxic, fetotoxic and teratogenic effects of EGAEs are presented in this paper. Our particular attention was focused on the metabolism of some EGAEs and their organ-specific toxicities, apoptosis of spermatocytes associated with changes in the expression of various genes that code for oxidative stress factors, protein kinases and nuclear hormone receptors. Med Pr 2015;66(5:725–737

  15. Induction of cleft palate in newborn pigs by maternal ingestion of poison hemlock (Conium maculatum).

    Science.gov (United States)

    Panter, K E; Keeler, R F; Buck, W B

    1985-06-01

    Cleft palates were induced in newborn pigs of gilts fed Conium maculatum seed or plant during gestation days 30 through 45. Twelve of 23 newborn pigs born to 3 gilts given Utah-grown C maculatum seed and 9 of 12 newborn pigs born to a single gilt given the fresh Utah spring-growth C maculatum plant had cleft palates. The cleft palates ranged from a unilateral cleft, involving only 1 side of the palate, to a full bilateral cleft. Brachygnathia was also observed in some of these newborn pigs with cleft palate. Other malformations were not observed. Chemical analysis of seed and plant samples indicated that gamma-coniceine was the responsible teratogenic alkaloid. A daily dose of plant or seed that provided greater than or equal to 1.07 mg of gamma-coniceine/kg of body weight fed to gilts during the 30th through the 45th day of pregnancy resulted in teratogenic effects.

  16. Splenogonadal fusion with limb deficiency and micrognathia.

    Science.gov (United States)

    Moore, P J; Hawkins, E P; Galliani, C A; Guerry-Force, M L

    1997-11-01

    Splenogonadal fusion (SGF) is a rare abnormality with two known types. In the continuous type, the spleen is connected to the gonad, and there are often limb defects, micrognathia, or other congenital malformations such as ventricular septal defect, anal atresia, microgastria, spina bifida, craniosynostosis, thoracopagus, diaphragmatic hernia, hypoplastic lung and abnormal lung fissures, polymicrogyria, deficient coccyx, and bifid spine C6-T3. The discontinuous type is usually not associated with congenital defects, and the gonad that fused with an accessory spleen has no connection with the native spleen. The etiology of SGF is not known. Conceivably, a teratogenic insult occurring between 5 weeks' and 8 weeks' gestation could interfere with the normal development of the spleen, gonads, and limb buds. We describe a case of splenogonadal fusion in a stillborn black boy with associated micrognathia and limb deformities. Also, we review the possible teratogenic etiologies and embryonic basis of SGF.

  17. Severe malformations of eelpout (Zoarces viviparus) fry are induced by maternal estrogenic exposure during early embryogenesis

    DEFF Research Database (Denmark)

    Morthorst, Jane Ebsen; Korsgaard, Bodil; Bjerregaard, Poul

    2016-01-01

    Pregnant eelpout were exposed via the water to known endocrine disrupting compounds (EDCs) to clarify if EDCs could be causing the increased eelpout fry malformation frequencies observed in coastal areas receiving high anthropogenic input. The presence of a teratogenic window for estrogen...... induced by EE2 (5.7 and 17.8 ng/L) but not by 4-t-OP and pyrene. A critical period for estrogen-induced fry malformations was identified and closed between 14 and 22 days post fertilization (dpf). Exposure to 17β-estradiol (E2) between 0 and 14 dpf caused severe malformations and severity increased...... the closer exposure start was to fertilization, whereas malformations were absent by exposure starting later than 14 dpf. Data on ovarian fluid volume and larval length supported the suggested teratogenic window. Larval mortality also increased when exposure started right after fertilization....

  18. First-Trimester Maternal Alcohol Consumption and the Risk of Infant Oral Clefts in Norway: A Population-based Case-Control Study

    OpenAIRE

    DeRoo, Lisa A.; Wilcox, Allen J.; Drevon, Christian A.; Lie, Rolv Terje

    2008-01-01

    Although alcohol is a recognized teratogen, evidence is limited on alcohol intake and oral cleft risk. The authors examined the association between maternal alcohol consumption and oral clefts in a national, population-based case-control study of infants born in 1996–2001 in Norway. Participants were 377 infants with cleft lip with or without cleft palate, 196 with cleft palate only, and 763 controls. Mothers reported first-trimester alcohol consumption in self-administered questionnaires com...

  19. Aberrant twinning (diprosopus) associated with anencephaly.

    Science.gov (United States)

    Moerman, P; Fryns, J P; Goddeeris, P; Lauweryns, J M; Van Assche, A

    1983-10-01

    A case of Monocephalus diprosopus, associated with craniorachischisis and duplication of most of the foregut derivates is presented. The major part of the cardiovascular system remained single but the heart exhibited severe defects, including a complete persistent atrioventricular canal, transposition of the great arteries and atresia of the pulmonary valve. This report further supports the hypothesis that certain-types of incomplete twinning and neural tube defects may be caused by a single teratogenic mechanism.

  20. Use of Herbal Medicine Among Pregnant Women on Antenatal Care at Nekemte Hospital, Western Ethiopia

    OpenAIRE

    Bayisa, Bodena; Tatiparthi, Ramanjireddy; Mulisa, Eshetu

    2014-01-01

    Background: Investigations across the world confirm dramatic increment in the use of complementary and alternative medicine in pregnant women. The most important aspect is lack of awareness of pregnant women about potential effects of using traditional medicine on fetus; some herbal products may be teratogenic in human and animal models. In this area, so far, no research has been conducted in Ethiopia to assess traditional medicine use in pregnant women. Objectives: Therefore, the main object...

  1. The Mustard Consortium’s Elucidation of the Pathophysiology of Sulfur Mustard and Antidote Development

    Science.gov (United States)

    2006-09-01

    fibrosis is well documented (4). Not unexpectedly, HD is radiomimetic, teratogenic and mutagenic (5,6). Currently, there is no effective therapy ...available. The long term goals are to further define the mode of action of mustard gas and to develop a therapy using liposomes containing both lipid...unilamellar antioxidant liposomes containing 6.6 mole percent RRR-alpha- tocopherol (as well as 66.6, 26.5 and 0.66 mole percent of soy lecithin

  2. RISK FACTORS IN CHILD CONGENITAL MALFORMATIONS

    OpenAIRE

    Alina-Costina LUCA; Mirabela SUBOTNICU

    2015-01-01

    Congenital heart malformations are among the most common congenital malformations. Congenital heart malformations occur due to genetic and environmental factors during embryonic morphogenesis period of the heart. About 25% of these malformations are severe, requiring intervention immediately after birth or in infancy. Abnormalities of structure and function of the heart and great vessels are the consequence of teratogenic factors occurring between day 19 and 45 of gestation. (Yagel et al...

  3. Phocomelia: Report of Three Cases

    Science.gov (United States)

    Coodin, Fischel J.; Uchida, Irene A.; Murphy, Claude H.

    1962-01-01

    Three infants were born with phocomelia in Winnipeg during the period from May 1961 to May 1962. In one case thalidomide had been administered to the mother early in the pregnancy. No etiological agent was discovered in the other two, both of whom died. Known teratogenic agents capable of causing phocomelia are reviewed, but no clear association with the two cases described in this report is evident. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5 PMID:14022756

  4. Influence of beryllium chloride and oxide on the sexual function in female rats and development of offspring

    International Nuclear Information System (INIS)

    Selivanova, L.N.; Savinova, T.B.

    1989-11-01

    A translation is given of a Russian article on the influence of beryllium chloride and oxide on the sexual cycle in female rats and on their capacity to conceive; another aim was to identify any embryotoxic and teratogenic effect of these compounds and to identify the exposure period values for pregnant females and the capacity of beryllium to penetrate the placenta and to accumulate in the foetus. (UK)

  5. The plausibility of maternal nutritional status being a contributing factor to the risk for fetal alcohol spectrum disorders: the potential influence of zinc status as an example.

    Science.gov (United States)

    Keen, Carl L; Uriu-Adams, Janet Y; Skalny, Anatoly; Grabeklis, Andrei; Grabeklis, Sevil; Green, Kerri; Yevtushok, Lyubov; Wertelecki, Wladimir W; Chambers, Christina D

    2010-01-01

    There is increasing evidence that human pregnancy outcome can be significantly compromised by suboptimal maternal nutritional status. Poor diet results in a maternal-fetal environment in which the teratogenicity of other insults such as alcohol might be amplified. As an example, there is evidence that zinc (Zn) can interact with maternal alcohol exposure to influence the risk for fetal alcohol spectrum disorders (FASD). Studies with experimental animals have shown that the teratogenicity of alcohol is increased under conditions of Zn deficiency, whereas its teratogenicity is lessened when animals are given Zn-supplemented diets or Zn injections before the alcohol exposure. Alcohol can precipitate an acute-phase response, resulting in a subsequent increase in maternal liver metallothionein, which can sequester Zn and lead to decreased Zn transfer to the fetus. Importantly, the teratogenicity of acute alcohol exposure is reduced in metallothionein knockout mice, which can have improved Zn transfer to the conceptus relative to wild-type mice. Consistent with the above, Zn status has been reported to be low in alcoholic women at delivery. Preliminary data from two basic science and clinical nutritional studies that are ongoing as part of the international Collaborative Initiative on Fetal Alcohol Spectrum Disorders support the potential role of Zn, among other nutritional factors, relative to risk for FASD. Importantly, the nutrient levels being examined in these studies are relevant to general clinical populations and represent suboptimal levels rather than severe deficiencies. These data suggest that moderate deficiencies in single nutrients can act as permissive factors for FASD, and that adequate nutritional status or intervention through supplementation may provide protection from some of the adverse effects of prenatal alcohol exposure.

  6. The teratology testing of cosmetics.

    Science.gov (United States)

    Spézia, François; Barrow, Paul C

    2013-01-01

    In Europe, the developmental toxicity testing (including teratogenicity) of new cosmetic ingredients is performed according to the Cosmetics Directive 76/768/EEC: only alternatives leading to full replacement of animal experiments should be used. This chapter presents the three scientifically validated animal alternative methods for the assessment of embryotoxicity: the embryonic stem cell test (EST), the micromass (MM) assay, and the whole embryo culture (WEC) assay.

  7. Fetal behavioral teratology.

    Science.gov (United States)

    Visser, Gerard H A; Mulder, Eduard J H; Tessa Ververs, F F

    2010-10-01

    Ultrasound studies of fetal motor behavior provide direct – in vivo – insight in the functioning of the motor component of the fetal central nervous system. In this article, studies are reviewed showing changes in the first timetable of appearance of fetal movements, changes in quality and/or quantity of movements and disturbances in the development of fetal behavioral states in case of endogenous malfunctions, maternal diseases and exogenous behavioral teratogens.

  8. Caudal Regression Syndrome with Partial Agenesis of the Corpus callosum and Partial Lobar Holoprosencephaly

    Science.gov (United States)

    Hashami, Hilal Al; Bataclan, Maria F; Mathew, Mariam; Krishnan, Lalitha

    2010-01-01

    Caudal regression syndrome is a rare fetal condition of diabetic pregnancy. Although the exact mechanism is not known, hyperglycaemia during embryogenesis seems to act as a teratogen. Independently, caudal regression syndrome (CRS), agenesis of the corpus callosum (ACC) and partial lobar holoprosencephaly (HPE) have been reported in infants of diabetic mothers. To our knowledge, a combination of all these three conditions has not been reported so far. PMID:21509087

  9. Caudal Regression Syndrome with Partial Agenesis of the Corpus callosum and Partial Lobar Holoprosencephaly: Case report.

    Science.gov (United States)

    Hashami, Hilal Al; Bataclan, Maria F; Mathew, Mariam; Krishnan, Lalitha

    2010-04-01

    Caudal regression syndrome is a rare fetal condition of diabetic pregnancy. Although the exact mechanism is not known, hyperglycaemia during embryogenesis seems to act as a teratogen. Independently, caudal regression syndrome (CRS), agenesis of the corpus callosum (ACC) and partial lobar holoprosencephaly (HPE) have been reported in infants of diabetic mothers. To our knowledge, a combination of all these three conditions has not been reported so far.

  10. Monitoring nitrosamines in large water distribution systems and their removal using cyclodextrin polyurethanes

    OpenAIRE

    2010-01-01

    M.Sc. The disinfection of drinking water is an important step in the water treatment process. However, toxic (unwanted) disinfection by-products (DBPs) are often produced during the disinfection of drinking water. One such group of DBPs are the nitrosamines such as N-Nitrosodimethylamine (NDMA). Nitrosamines, particularly NDMA, are highly carcinogenic, mutagenic and teratogenic. The US Environmental Protection Agency (USEPA) placed these compounds into the group B2, which indicates compoun...

  11. Recall bias in a case-control surveillance system on the use of medicine during pregnancy

    DEFF Research Database (Denmark)

    Rockenbauer, M.; Olsen, Jørn; Czeizel, A.E.

    2001-01-01

    It is important to study possible teratogenic effects of drugs used during pregnancy. Many studies of this type rely upon case-control designs in which drug intake is recalled by the mothers after having given birth. Recall bias in this situation may lead to spurious associations. We looked...... study. A case-control surveillance system of this type may frequently cause spurious associations, with biased odds ratios up to a factor of 1.9....

  12. Polyphasic approach including maldi-tof mass spectrometry to characterise aflatoxigenic species of aspergillus section flavi

    OpenAIRE

    Rodrigues, Paula; Santos, Cledir; Kozakiewicz, Zofia; Venâncio, Armando; Lima, Nelson

    2009-01-01

    Aflatoxins are toxic compounds which are produced as secondary metabolites by the fungi Aspergillus flavus, A. parasiticus and A. nomius growing on a variety of food products and are known to be carcinogenic, mutagenic, teratogenic and immunosuppressive1,2. Aspergillus is a large genus, with a complex taxonomy. The genus is easily identified by its characteristic conidiophore, but species identification and differentiation is complex, mainly because it is traditionally based on a range of mor...

  13. QSAR models for reproductive toxicity and endocrine disruption in regulatory use – a preliminary investigation

    DEFF Research Database (Denmark)

    Jensen, Gunde Egeskov; Niemelä, Jay Russell; Wedebye, Eva Bay

    2008-01-01

    the new legislation. This article focuses on a screening exercise by use of our own and commercial QSAR models for identification of possible reproductive toxicants. Three QSAR models were used for reproductive toxicity for the endpoints teratogenic risk to humans (based on animal tests, clinical data...... for humans owing to possible developmental toxic effects: Xn (Harmful) and R63 (Possible risk of harm to the unborn child). The chemicals were also screened in three models for endocrine disruption....

  14. Growth of colonies and hyphal ultrastructure of filamentous fungi grown on dibutyl phthalate and di(2-ethylhexyl)phthalate

    OpenAIRE

    Suárez-Segundo, J.L.; Vázquez-López, D.; Torres-García, J.L.; Ahuactzin-Perez, M.; Montiel-Martínez, N.; Tlecuitl-Beristain, S.; Sánchez, C.

    2013-01-01

    Phthalates are compounds that give fl exnbíüty to the plastics and are considered mutagens and teratogens. Mycelial growth rate, biomass production and hyphal diameter of the young and mature zones of colonies of Fusarium oxysporum, Mortierella alpina, Pleurotuspulmonarius, two strains of Pleurotus ostreatus (Po 37 and Po 83) and one strain of Pleurotus florida grown on glucose, di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate were studied. F oxysporum had the highest mycelial growth r...

  15. Evaluation of developmental toxicity of coniine to rats and rabbits.

    Science.gov (United States)

    Forsyth, C S; Frank, A A

    1993-07-01

    Conium maculatum (poison hemlock, CM) is teratogenic in several domestic species, presumably due to its piperidine alkaloids, including coniine, which has been verified to be teratogenic in cattle. Coniine/CM teratogenicity culminates in production of arthrogryposis. The purpose of this study was to evaluate coniine-induced teratogenicity in two laboratory animal species, Sprague-Dawley rats and New Zealand white rabbits. Pregnant rats were given coniine (25 mg/kg body weight) by oral gavage at 8-hour intervals on gestation days 16-18. Pregnant rabbits were given coniine (40 mg/kg body weight) by oral gavage at 8-hour intervals on gestation days 20-24. Rats were killed on day 19 and rabbits on day 29. Fetuses were immediately removed, weighed, and examined for external abnormalities. Alternate fetuses were either stained for skeletal examinations with alizarin red-S or fixed in Bouin's solution for visceral examination. Symptoms of maternal intoxication due to coniine administration were observed in both the rat and the rabbit, and higher doses were uniformly lethal. Rabbits treated with coniine appeared to lose more weight and eat less than controls, but there was no statistically significant difference between groups. Fetal weights were significantly lower in coniine-exposed rat and rabbit fetuses indicating fetotoxicity. The only statistically significant treatment-related visceral or skeletal malformation was a reduction of cranial ossification of rabbit fetuses, probably related to maternal toxicity. Coniine-exposed rabbit litters tended to be affected by arthrogryposis (no bony deformities noted on skeletal exam) more than controls (2/6 vs. 0/9).

  16. Health-related biological effects of electric, magnetic, and electro-magnetic fields with special reference to nonthermal effects

    International Nuclear Information System (INIS)

    Stevenson, A.F.G.

    1993-02-01

    This expert report is a supplement to the report by L. von Klitzing (The actions and effects of electric, magnetic, and electro-magnetic fields in man with special reference to athermal effects) and concerns in particular the biological effects on cationic homeostasis and cell regulation with special reference to calcium and the effects on the pineal gland. The report concludes with statements on teratogenicity, concerogenicity, mutagenicity and a bibliography of literature. (VHE) [de

  17. Pregnancy outcome following gestational exposure to azithromycin

    Directory of Open Access Journals (Sweden)

    Woodland C Cindy

    2006-05-01

    Full Text Available Abstract Background Azithromycin is an azalide antibiotic with an extensive range of indications and has become a common treatment option due to its convenient dosing regimen and therapeutic advantages. Human studies addressing gestational use of azithromycin have primarily focused on antibiotic efficacy rather than fetal safety. Our primary objective was to evaluate the possibility of teratogenic risk following gestational exposure to azithromycin. Methods There were 3 groups of pregnant women enrolled in our study: 1 women who took azithromycin. 2 women exposed to non-teratogenic antibiotics for similar indications, and 3 women exposed to non-teratogenic agents. They were matched for gestational age at time of call, maternal age, cigarette and alcohol consumption. Rates of major malformations and other endpoints of interest were compared among the three groups. Results Pregnancy outcome of 123 women in each group was ascertained. There were no statistically significant differences among the three groups in the rates of major malformations; 3.4% (exposed versus 2.3% (disease matched and 3.4% (non teratogen or any other endpoints that were examined. In the azithromycin group, 88 (71.6% women took the drug during the first trimester Conclusion Results suggest that gestational exposure to azithromycin is not associated with an increase in the rate of major malformations above the baseline of 1–3%. Our data adds to previous research showing that macrolide antibiotics, as a group, are generally safe in pregnancy and provides an evidence-based option for health professionals caring for populations with chlamydia.

  18. Behandling med valproat under graviditet: beskrivelse af fire cases med føtalt valproatsyndrom

    DEFF Research Database (Denmark)

    Sabers, Anne; Larsen, Katja; Blichfeldt, Susanne

    2009-01-01

    INTRODUCTION: Treatment with valproate is associated with an increased risk of teratogenicity compared to other antiepileptic drugs and can cause a complex of serious symptoms usually referred to as "foetal valproate symdrome" which is characterised by major and minor malformations in association...... are born of mothers with epilepsy. The 677C-T mutation does not seem to be a useful genetic marker of this syndrome. Udgivelsesdato: 2009-Jan...

  19. Sirenomelia after phenobarbital and carbamazepine therapy in pregnancy.

    Science.gov (United States)

    Tica, Oana Sorina; Tica, Andrei Adrian; Brailoiu, Cristina Gabriela; Cernea, Nicolae; Tica, Vlad Iustin

    2013-06-01

    Epilepsy still remains a serious challenge for any obstetrician due to the potential teratogenicity of all antiepileptics. However, without appropriate maternal therapy the seizures can reappear, with direct negative impact on fetus. Currently, sirenomelia is the most severe caudal pole dysgenesis, consequent to an abnormal vascular supply development in the fetal lower body. We report a stillborn, GA/LMP = 37 weeks, delivered by an epileptic woman, who received in the first four months of pregnancy phenobarbital (PH) 0.1 g/day and carbamazepine (CMZ) 0.4 g/day, followed only by PH 0.1 g/day, until delivery. The stillborn, weighing 2200 g, presented sirenomelia type II, with some of its "classic" features: oligohydramnios, absence of kidneys, bladder, rectum, uterus, and a single umbilical artery. Some other "particularities" included: no Potter's facies and no significant cardio-pulmonary abnormalities. Since PH and CMZ alone are responsible, commonly, for mild abnormalities, we hypothesized that combined therapy with PH and CMZ (both strong enzyme-inductors, especially PH) potentiated their teratogenicity, by producing supplementary quantities of epoxides and/or other oxides, which accumulated in the fetal tissues. Except for sirenomelia, all other mild abnormalities, theoretically associated with "fetal CMZ and/or PH syndrome," are rarely observed, fact which demonstrates the drug-drug interactions between the two antiepileptics. This report highlights the possibility that PH/CBZ therapy during fetal organogenesis can induce sirenomelia, by a synergistic teratogenic effect and support the recommendation to use only one drug in pregnant epileptic women. A careful ultrasound monitoring of these patients is mandatory due to the teratogenic risk of both seizures and therapy. Copyright © 2013 Wiley Periodicals, Inc.

  20. Health consequences of Chernobyl. 25 years after the reactor catastrophy; Gesundheitliche Folgen von Tschernobyl. 25 Jahre nach der Reaktorkatastrophe

    Energy Technology Data Exchange (ETDEWEB)

    Pflugbeil, Sebastian; Schmitz-Feuerhake, Inge [Gesellschaft fuer Strahlenschutz e.V., Berlin (Germany); Paulitz, Henrik; Claussen, Angelika [Internationale Aerzte fuer die Verhuetung des Atomkrieges, Aerzte in sozialer Verantwortung e.V. (IPPNW), Berlin (Germany). Deutsche Sektion

    2011-04-15

    The report is an evaluation of studies indicating health effects as a consequence of the reactor catastrophe in Chernobyl. The most exposed population include the cleaning personnel (liquidators), the population evacuated from the 30 km zone, the populations in highly contaminated regions in Russia, Belarus and Ukraine, the European population in lass contaminated regions. The following issues are discussed: the liquidators, infant mortality, genetic and teratogenic damages, thyroid carcinoma and other thyroid diseases, carcinogenic diseases and leukemia, other diseases following the Chernobyl catastrophe.

  1. Early life programming as a target for prevention of child and adolescent mental disorders

    OpenAIRE

    Lewis, Andrew James; Galbally, Megan; Gannon, Tara; Symeonides, Christos

    2014-01-01

    This paper concerns future policy development and programs of research for the prevention of mental disorders based on research emerging from fetal and early life programming. The current review offers an overview of findings on pregnancy exposures such as maternal mental health, lifestyle factors, and potential teratogenic and neurotoxic exposures on child outcomes. Outcomes of interest are common child and adolescent mental disorders including hyperactive, behavioral and emotional disorders...

  2. Somatic and genetic effects

    International Nuclear Information System (INIS)

    Broerse, J.J.; Barendsen, G.W.; Kal, H.B.; Kogel, A.J. van der

    1983-01-01

    This book contains the extended abstracts of the contributions of the poster workshop sessions on somatic and genetic effects of the 7th international congress of radiation research. They cover the following main topics: haematopoietic and immune systems, mechanisms of late effects in various tissues, endogenous and exogenous factors in radiation carcinogenesis, teratogenic effects, genetic effects, in vitro transformation, tumour induction in different tissues, carcinogenesis in incorporated tissues, cancer epidemology and risk assessment. refs.; figs.; tabs

  3. Thalidomide Induces Limb Anomalies by PTEN Stabilization, Akt Suppression, and Stimulation of Caspase-Dependent Cell Death▿

    OpenAIRE

    Knobloch, Jürgen; Schmitz, Ingo; Götz, Katrin; Schulze-Osthoff, Klaus; Rüther, Ulrich

    2007-01-01

    Thalidomide, a drug used for the treatment of multiple myeloma and inflammatory diseases, is also a teratogen that causes birth defects, such as limb truncations and microphthalmia, in humans. Thalidomide-induced limb truncations result from increased cell death during embryonic limb development and consequential disturbance of limb outgrowth. Here we demonstrate in primary human embryonic cells and in the chicken embryo that thalidomide-induced signaling through bone morphogenetic proteins (...

  4. Modulators of Fish Immune Responses. Volume 1. Models for Environmental Toxicology/Biomarkers Immunostimulators

    Science.gov (United States)

    1994-01-01

    I.W., McNamee, R.B. and E.L. Jones (1989). Immunization against Trypanosoma cruzi: adjuvant effect of glucan. Int. J. Immnunopharmacol. 11: 403-410...Feder et al. 1992), teratogenicity assessment using frog embryos (Bantle etal., 1991; American Society for Testing and Materials, 1991), carcinogenic...maintenance of the fish use,; in these studies. REFERENCES American Society for Testing and Materials (1991). Standard guide for conducting the frog

  5. Monitoring Maternal Beta Carotene and Retinol Consumption May Decrease the Incidence of Neurodevelopmental Disorders in Offspring

    Directory of Open Access Journals (Sweden)

    Joel S. Goldberg

    2012-01-01

    Full Text Available Retinoic acids (13-cis and 13-trans are known teratogens, and their precursor is retinol, a form of vitamin A. In 1995, Rothman et al demonstrated an association between excessive vitamin A, > 10,000 IU/day, during the first trimester of pregnancy and teratogenic effects, particularly in the central nervous system. However, vitamin A deficiency has long been known to be deleterious to the mother and fetus. Therefore, there may be a narrow therapeutic ratio for vitamin A during pregnancy that has not previously been fully appreciated. Neurodevelopmental disorders may not be apparent by macroscopic brain examination or imaging, and proving the existence of a behavioral teratogen is not straightforward. However, an excess of retinoic acid and some neurodevelopmental disorders are both associated with abnormalities in cerebellar morphology. Physical and chemical evidence strongly supports the notion that beta carotene crosses the placenta and is metabolized to retinol. Only very limited amounts of beta carotene are stored in fetal fat cells as evidenced by the fact that maternal fat is yellow from beta carotene, whereas non-brown neonatal fat is white. Furthermore, newborns of carotenemic mothers do not share the yellow complexion of their mothers. The excess 13-trans retinoic acid derived from metabolized beta carotene in the fetus increases the concentration of the more teratogenic 13-cis retinoic acid since the isomerization equilibrium is shifted to the left. Therefore, this paper proposes that consideration be given to monitoring all potential sources of fetal 13-cis and 13-trans retinoic acid, including nutritional supplements, dietary retinol, and beta carotene, particularly in the first trimester of pregnancy.

  6. Congenital diplopodia

    International Nuclear Information System (INIS)

    Brower, Jason S.; Wootton-Gorges, Sandra L.; Costouros, John G.; Boakes, Jennette; Greenspan, Adam

    2003-01-01

    Diplopodia, or duplicated foot, is a rare congenital anomaly. It differs from polydactyly in that supernumerary metatarsal and tarsal bones are present as well as extra digits. Only a few cases of this anomaly have been reported in the literature to date. We present a newborn male without intrauterine teratogen exposure who was born with a duplicate foot of the left lower extremity and imperforate anus. (orig.)

  7. Medico-biological factors of speech and language development in young children (part 1

    Directory of Open Access Journals (Sweden)

    Chernov D.N.

    2015-03-01

    Full Text Available The article analyzed the main results of medico-biological directions in the study of the factors of children's speech and language. It shows that a variety of pre-, peri-and neonatal developmental factors (teratogenic effects, prematurity, low birth weight, maternal diseases during pregnancy, and chronic diseases of the child had a negative impact on the child-parent relationship that has a lasting influence on child speech and language development.

  8. ORIGINAL ARTICLES

    African Journals Online (AJOL)

    It is of public health importance largely owing to the teratogenic effects ... Information on the epidemiology of rubella in South Africa is .... interval(%). 93.33 - 96.88. 95.45 - 98.79. 94.96 - 99.45. 95.30 - 97.47. The age-stratified results from each district are shown in. Table II. Combining the results from the 4 districts, a total of.

  9. Behandling med valproat under graviditet: beskrivelse af fire cases med føtalt valproatsyndrom

    DEFF Research Database (Denmark)

    Sabers, Anne; Larsen, Katja; Blichfeldt, Susanne

    2009-01-01

    INTRODUCTION: Treatment with valproate is associated with an increased risk of teratogenicity compared to other antiepileptic drugs and can cause a complex of serious symptoms usually referred to as "foetal valproate symdrome" which is characterised by major and minor malformations in association...... are born of mothers with epilepsy. The 677C-T mutation does not seem to be a useful genetic marker of this syndrome. Udgivelsesdato: 2009-Jan-19...

  10. Biological radiation effects

    International Nuclear Information System (INIS)

    Kiefer, J.

    1989-01-01

    The book covers all aspects of biological radiation effects. The physical basis is dealt with in some detail, and the effects at the subcellular and the cellular level are discussed, taking into account modern developments and techniques. The effects on the human organism are reviewed, both from the point of view of applications in medicine as well as with regard to radiation hazards (teratogenic, gonadal and carcinogenic effects)

  11. Wholesomeness study of irradiated salted and dried mackerel in rats

    International Nuclear Information System (INIS)

    Anukarahanonta, T.; Temcharoen, P.; Nagara, B.N.; Chudhabuddhi, C.; Bhamarapravati, N.

    1981-01-01

    A long-term multigeneration study was performed of the wholesomeness of irradiated salted and dried mackerel fed to the rats of Wistar strain and revealed no significant evidence that would impose a hazard attributable to irradiation with respect to the longevity, carcinogenecity, teratogenicity, dominant lethal, reproductive function and biophysiological function. Some abnormalities that were noted could be explained on the basis of differences in food quality due to the addition of fish protein and minerals rather than the irradiation effect

  12. Monitoring of Aflatoxins in Peanuts

    OpenAIRE

    UÇKUN, Okşan; VAR, Işıl

    2014-01-01

    Peanuts (Arachis hypogaea L.) are one of the most important oilseed crops and snack foods in the world Agro-food trade market. The major producers/exporters of peanuts are the United States, China, Argentina, Sudan, Senegal, and Brazil. Peanuts are a perishable commodity, easily spoiled by fungi. Aflatoxins are a group of natural compounds mainly produced by Aspergillus flavus and Aspergillus parasiticus. They have been found to be carcinogenic, teratogenic, and mutagenic to humans and animal...

  13. Subcutaneous Injection of Oxyfluorfen Herbicide to the Forearm: Case Report

    OpenAIRE

    Couceiro, José; Garcia-Portal, Gonzalo; Garcia, Olga

    2017-01-01

    Background  Oxyfluorfen, a commercially available pesticide, commonly used for weed control in crop production, has been studied in terms of its toxicity, its carcinogenic properties, and its teratogenicity. We have found no reports, however, of the effects produced by an oxyfluorfen injection to the upper limb. Methods  We present the case of a 40 years old psychiatric patient, who reportedly injected her forearm accidentally while fumigating her garden. She was treated with irrigation and o...

  14. Pregnant women and non-steroidal anti-inflammatory drugs: Knowledge, perception and drug consumption pattern during pregnancy in Ethiopia

    OpenAIRE

    Chalelgn Kassaw; Nasir Tajure Wabe

    2012-01-01

    Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the widely used drugs and are often used by pregnant women. However, they can have significant teratogenic effects. The aim of the study was to investigate pregnant women′s knowledge about NSAIDs use during pregnancy and their perception and consumption pattern. Materials and Methods: The study was a cross sectional study on women waiting for a consultation in the selected maternity hospitals in Addis Ababa, Ethiopia. The pr...

  15. Drug prescribing during pregnancy in a central region of Italy, 2008-2012.

    Science.gov (United States)

    Ventura, Martina; Maraschini, Alice; D'Aloja, Paola; Kirchmayer, Ursula; Lega, Ilaria; Davoli, Marina; Donati, Serena

    2018-05-15

    Drug consumption during pregnancy is a matter of concern, especially regarding drugs known or suspected to be teratogens. Little is known about drug use in pregnant women in Italy. The present study is aimed at examining the prevalence, and to detect potential inappropriateness of drug prescribing among pregnant women in Latium, a region of central Italy. This retrospective study was conducted on a cohort of women aged 18-45 years who delivered between 2008 and 2012 in public hospitals. Women were enrolled through the Regional Birth Register. After linking the regional Health Information Systems and the Regional Drug Claims Register, women's clinical data and prescribed medications were analyzed. Italian Medicine Agency (AIFA) and US Food and Drug Administration (FDA) evidence were used to investigate inappropriate prescribing and teratogenic risk. Excluding vitamins and minerals, 80.6% (n = 153,079) of the women were prescribed at least one drug during pregnancy, with an average of 4.6 medications per pregnancy. Drugs for blood and hematopoietic organs were the most commonly prescribed (53.0%,), followed by anti-infectives for systemic use (50.7%). Among the inappropriate prescriptions, progestogen supplementation was given in 20.1% of pregnancies; teratogen drugs were prescribed in 0.8%, mostly angiotensin co-enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) (0.3%). In Latium, drugs are widely used in pregnancy. Prescriptions of inappropriate drugs are observed in more than a fifth of pregnancies, and teratogens are still used, despite their known risk. Continuous updates of information provided to practitioners and an increased availability of information to women might reduce inappropriate prescribing.

  16. Fever in pregnancy and the risk of congenital malformations

    DEFF Research Database (Denmark)

    Sass, L; Urhoj, S K; Kjærgaard, J

    2017-01-01

    Background: In a variety of animal species, hyperthermia in pregnancy has been recognized as teratogenic. Hyperthermia interferes with protein synthesis via heat-shock proteins, which can entail membrane disruption, cell death, vascular disruption, and placental infarction. This can induce severe....... Congenital malformations within the first three and a half years of life were categorized according to EUROCAT's classification criteria. Logistic regression models were used to estimate the associations between fever in first trimester and overall congenital malformations and congenital malformations...

  17. The effects of ionizing radiations on in utero development

    International Nuclear Information System (INIS)

    Lallemand, J.

    1984-01-01

    Following a reminder of embryology and methodology, a review is made of the main teratogenic effects related to radiation exposure, i.e. lethal effects, radioinduced malformations, maldevelopment and cancers. The sensitivity of the embryo and foetus to radiation seems to last during the whole gestation. Howewer, the latest investigations indicate that the main damage is mental retardation. This review concludes on practical considerations of radiation protection in the field of radiographic examinations of pregnant women [fr

  18. DNA damage and repair in mouse embryos following treatment transplacentally with methylnitrosourea and methylmethanesulfonate

    International Nuclear Information System (INIS)

    Jirakulsomchok, S.; Yielding, K.L.

    1984-01-01

    Mouse embryos were labeled in vivo at 10 1/2-12 1/2 days of gestation with [ 3 H]-thymidine and subjected to DNA damage using x-ray, methylmethanesulfonate, or methylnitrosourea. DNA damage and its repair were assessed in specific cell preparations from embryos isolated at intervals thereafter using the highly sensitive method of nucleoid sedimentation, which evaluates the supercoiled state of the DNA. Repair of x-ray damage was demonstrated using trypsin-dispersed cells from whole embryos and from homogenized embryonic liver to show the validity of the analytical approach. The effects of the highly teratogenic methylnitrosourea and the much less teratogenic methylmethanesulfonate were compared in the targeted limb buds using equitoxic doses of the two alkylating agents. DNA supercoiling was fully restored after 24 hr in limb bud cells damaged with methylmethanesulfonate, while as much as 48 hr were required for full repair of methylnitrosourea damage. These results demonstrated the feasibility of studying DNA repair in embryonic tissues after damage in vivo and suggest that the potency of methylnitrosourea as a teratogen may be correlated with a prolonged period required for complete repair of DNA

  19. Excess caffeine exposure impairs eye development during chick embryogenesis

    Science.gov (United States)

    Ma, Zheng-lai; Wang, Guang; Cheng, Xin; Chuai, Manli; Kurihara, Hiroshi; Lee, Kenneth Ka Ho; Yang, Xuesong

    2014-01-01

    Caffeine has been an integral component of our diet and medicines for centuries. It is now known that over consumption of caffeine has detrimental effects on our health, and also disrupts normal foetal development in pregnant mothers. In this study, we investigated the potential teratogenic effect of caffeine over-exposure on eye development in the early chick embryo. Firstly, we demonstrated that caffeine exposure caused chick embryos to develop asymmetrical microphthalmia and induced the orbital bone to develop abnormally. Secondly, caffeine exposure perturbed Pax6 expression in the retina of the developing eye. In addition, it perturbed the migration of HNK-1+ cranial neural crest cells. Pax6 is an important gene that regulates eye development, so altering the expression of this gene might be the cause for the abnormal eye development. Thirdly, we found that reactive oxygen species (ROS) production was significantly increased in eye tissues following caffeine treatment, and that the addition of anti-oxidant vitamin C could rescue the eyes from developing abnormally in the presence of caffeine. This suggests that excess ROS induced by caffeine is one of the mechanisms involved in the teratogenic alterations observed in the eye during embryogenesis. In sum, our experiments in the chick embryo demonstrated that caffeine is a potential teratogen. It causes asymmetrical microphthalmia to develop by increasing ROS production and perturbs Pax6 expression. PMID:24636305

  20. Birth defects and aplastic anemia: differences in polycyclic hydrocarbon toxicity associated with the Ah locus. [Mice

    Energy Technology Data Exchange (ETDEWEB)

    Nebert, D.W.; Levitt, R.C.; Jensen, N.M.; Lambert, G.H.; Felton, J.S.

    1977-01-01

    The balance between cytochrome(s) P/sub 1/-450 and other forms of P-450 in the liver, and probably many nonhepatic tissues as well, appears to be important in the toxicity, carcinogenicity, mutagenicity, and teratogenicity of numerous compounds. Thus, allelic differences in a single gene--the Ah locus-- can have profound effects on the susceptibility of mice to drug toxicity and cancer. There is evidence for the Ah lous in the human. Striking increases in the incidence of stillborns, reorptions,and malformations caused by 3-methylcholanthrene or 7,12-dimethylbenz(a)anthracene were observed in the aromatic hydrocarbon responsive C57BL/6N,C3H/HeN, and BALB/cAnN inbred strains, compared with the genetically nonresponsive AKR/N. These data suggest that an association exists between the Ah locus and teratogenesis. Although numerous teratogenic differences among inbred mouse strains have been previously reported, this study is unique in that the genetic differences in teratogenicity observed were predicted in advance, on the basis of known differences in polycyclic hydrocarbon metabolism regulated by the Ah locus.

  1. Congenital malformations caused by Stryphnodendron fissuratum (Leg. Mimosoideae) in guinea pigs (Cavia porcellus).

    Science.gov (United States)

    Macedo, Josenaldo S; Rocha, Brena P; Colodel, Edson M; Freitas, Sílvio H; Dória, Renata G S; Riet-Correa, Franklin; Evêncio-Neto, Joaquim; Mendonça, Fábio S

    2015-11-01

    The aim of this study was to evaluate the toxicity of Stryphnodendron fissuratum pods in guinea pigs (Cavia porcellus) and test the hypothesis that this plant has teratogenic effects. Thus, sixteen guinea pigs were randomly divided into four groups of four animals each. Groups 10, 20 and 40 consisted of guinea pigs that received commercial food that contained crushed pods of S. fissuratum at concentrations of 10, 20 and 40 g/kg, respectively, during the period of organogenesis. Control group consisted of guinea pigs under the same management conditions that did not receive crushed pods of S. fissuratum in their food. In all experimental groups, the main clinical signs of poisoning consisted of anorexia, prostration, absence of vocalizations, alopecia, diarrhea, and abortions within the adult guinea pigs. Those that did not abort gave birth to weak, malnourished pups, some of which had fetal malformations. The main teratogenic changes consisted of eventration, arthrogryposis, amelia of the forelimbs, anophthalmia, microphthalmia, anotia and agnathia. The reductions in the number of offspring and the malformations observed in the experimental groups suggest that S. fissuratum affects fetal development and is teratogenic. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Risk of Ionizing Radiation in Women of Childbearing Age undergoing Radiofrequency Ablation

    International Nuclear Information System (INIS)

    Lima, Gustavo Glotz de; Gomes, Daniel Garcia; Gensas, Caroline Saltz; Simão, Mariana Fernandez; Rios, Matheus N.; Pires, Leonardo Martins; Kruse, Marcelo Lapa; Leiria, Tiago Luiz Luz

    2013-01-01

    The International Commission of Radiology recommends a pregnancy screening test to all female patients of childbearing age who will undergo a radiological study. Radiation is known to be teratogenic and its effect is cumulative. The teratogenic potential starts at doses close to those used during these procedures. The prevalence of positive pregnancy tests in patients undergoing electrophysiological studies and/or catheter ablation in our midst is unknown. To evaluate the prevalence of positive pregnancy tests in female patients referred for electrophysiological study and/or radiofrequency ablation. Cross-sectional study analyzing 2,966 patients undergoing electrophysiological study and/or catheter ablation, from June 1997 to February 2013, in the Institute of Cardiology of Rio Grande do Sul. A total of 1490 procedures were performed in women, of whom 769 were of childbearing age. All patients were screened with a pregnancy test on the day before the procedure. Three patients tested positive, and were therefore unable to undergo the procedure. The prevalence observed was 3.9 cases per 1,000 women of childbearing age. Because of their safety and low cost, pregnancy screening tests are indicated for all women of childbearing age undergoing radiological studies, since the degree of ionizing radiation needed for these procedures is very close to the threshold for teratogenicity, especially in the first trimester, when the signs of pregnancy are not evident

  3. Risk of Ionizing Radiation in Women of Childbearing Age undergoing Radiofrequency Ablation

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Gustavo Glotz de, E-mail: gglima.pesquisa@gmail.com; Gomes, Daniel Garcia; Gensas, Caroline Saltz; Simão, Mariana Fernandez; Rios, Matheus N.; Pires, Leonardo Martins; Kruse, Marcelo Lapa; Leiria, Tiago Luiz Luz [Instituto de Cardiologia, Fundação Universitária de Cardiologia, Porto Alegre, RS (Brazil)

    2013-11-15

    The International Commission of Radiology recommends a pregnancy screening test to all female patients of childbearing age who will undergo a radiological study. Radiation is known to be teratogenic and its effect is cumulative. The teratogenic potential starts at doses close to those used during these procedures. The prevalence of positive pregnancy tests in patients undergoing electrophysiological studies and/or catheter ablation in our midst is unknown. To evaluate the prevalence of positive pregnancy tests in female patients referred for electrophysiological study and/or radiofrequency ablation. Cross-sectional study analyzing 2,966 patients undergoing electrophysiological study and/or catheter ablation, from June 1997 to February 2013, in the Institute of Cardiology of Rio Grande do Sul. A total of 1490 procedures were performed in women, of whom 769 were of childbearing age. All patients were screened with a pregnancy test on the day before the procedure. Three patients tested positive, and were therefore unable to undergo the procedure. The prevalence observed was 3.9 cases per 1,000 women of childbearing age. Because of their safety and low cost, pregnancy screening tests are indicated for all women of childbearing age undergoing radiological studies, since the degree of ionizing radiation needed for these procedures is very close to the threshold for teratogenicity, especially in the first trimester, when the signs of pregnancy are not evident.

  4. Lower limits of radiosensitivity in organisms, excluding man

    International Nuclear Information System (INIS)

    Rose, K.S.B.

    1992-01-01

    Published literature has been reviewed to determine the lowest acute and chronic exposures at which certain radiation-induced changes have been detected in organisms. Three broad categories of change are considered: death, behavioural or developmental, teratogenic or genetic. The lowest chronic exposure found that resulted in death is 3.6Gy/year for several species of American rodents. For acute exposures, the lowest dose is 0.8 Gy, which leads to the death of a small proportion of young Douglas fir trees. The lowest chronic exposure found that produces a detectable change in behaviour or development is about 10 -2 Gy/year: this dose rate can be detected by planarium worms and mud snails. For acute exposures a dose of only 10 -6 Gy causes a transient reduction in the growth rate of a slime mould and can be visually detected by cockroaches whose eyes have adjusted to the dark. The lowest chronic exposure found that produces a reliable teratogenic or genetic change is 3 x 10 -3 Gy/year; this dose rate reduces the birth mass and increases the brain mass of laboratory rats irradiated as foetuses during their final third period of intrauterine life. For acute exposures, a dose of 10 -2 Gy to pregnant rats impairs the reflexes of their offspring. While the doses required to produce death are greater than those for humans in nearly all organisms, teratogenic or genetic effects have been recorded in many species below the lethal threshold. (author)

  5. Lower limits of radiosensitivity in organisms, excluding man

    Energy Technology Data Exchange (ETDEWEB)

    Rose, K.S.B. (AEA Environment and Energy, Harwell (United Kingdom))

    1992-01-01

    Published literature has been reviewed to determine the lowest acute and chronic exposures at which certain radiation-induced changes have been detected in organisms. Three broad categories of change are considered: death, behavioural or developmental, teratogenic or genetic. The lowest chronic exposure found that resulted in death is 3.6Gy/year for several species of American rodents. For acute exposures, the lowest dose is 0.8 Gy, which leads to the death of a small proportion of young Douglas fir trees. The lowest chronic exposure found that produces a detectable change in behaviour or development is about 10{sup -2}Gy/year: this dose rate can be detected by planarium worms and mud snails. For acute exposures a dose of only 10{sup -6}Gy causes a transient reduction in the growth rate of a slime mould and can be visually detected by cockroaches whose eyes have adjusted to the dark. The lowest chronic exposure found that produces a reliable teratogenic or genetic change is 3 x 10{sup -3}Gy/year; this dose rate reduces the birth mass and increases the brain mass of laboratory rats irradiated as foetuses during their final third period of intrauterine life. For acute exposures, a dose of 10{sup -2}Gy to pregnant rats impairs the reflexes of their offspring. While the doses required to produce death are greater than those for humans in nearly all organisms, teratogenic or genetic effects have been recorded in many species below the lethal threshold. (author).

  6. Ionizing radiation effect on human reproduction

    International Nuclear Information System (INIS)

    Jirous, J.

    1987-01-01

    A review is presented of the existing knowledge on the adverse effects of ionizing radiation on human reproduction. Some interesting findings have been obtained by interapolating the results of studies in mouse embryos to humans, important knowledge has been obtained in studies involving the population of Hiroshima and Nagasaki. The review summarizes the knowledge in the following conclusions: (1) prior to the blastocyst stage, the mammalian embryo is insensitive to teratogenic and growth retarding radiation effects but is highly sensitive to the lethal radiation effect; (2) in the early organogenesis, the embryo is very sensitive to growth retarding, teratogenic and lethal radiation effects. It can, however, partly offset growth retardation in the post-natal period; (3) in the early fetal development stage, the fetus shows reduced sensitivity to teratogenic damage of many organs; sensitivity of the central nervous system and growth retardation remain which can only be compensated post-natally with difficulties; (4) in the late stage of pregnancy the fetus is not significantly deformed as a result of irradiation but permanent cellular depletion can result in various organs and tissues post-natally if radiation doses are high. (L.O.). 22 refs

  7. Effect of allyl isothiocyanate on developmental toxicity in exposed Xenopus laevis embryos

    Directory of Open Access Journals (Sweden)

    John Russell Williams

    2015-01-01

    Full Text Available The pungent natural compound allyl isothiocyanate isolated from the seeds of Cruciferous (Brassica plants such as mustard is reported to exhibit numerous beneficial health-promoting antimicrobial, antifungal, anticarcinogenic, cardioprotective, and neuroprotective properties. Because it is also reported to damage DNA and is toxic to aquatic organisms, the objective of the present study was to determine whether it possesses teratogenic properties. The frog embryo teratogenesis assay-Xenopus (FETAX was used to determine the following measures of developmental toxicity of the allyl isothiocyanate: (a 96-h LC50, defined as the median concentration causing 50% embryo lethality; (b 96-h EC50, defined as the median concentration causing 50% malformations of the surviving embryos; and (c teratogenic malformation index (TI, equal to 96-h LC50/96-h EC50. The quantitative results and the photographs of embryos before and after exposure suggest that allyl isothiocyanate seems to exhibit moderate teratogenic properties. The results also indicate differences in the toxicity of allyl isothiocyanate toward exposed embryos observed in the present study compared to reported adverse effects of allyl isothiocyanate in fish, rodents, and humans. The significance of the results for food safety and possible approaches to protect against adverse effects of allyl isothiocyanate are discussed.

  8. Zebrafish on a chip: a novel platform for real-time monitoring of drug-induced developmental toxicity.

    Directory of Open Access Journals (Sweden)

    Yinbao Li

    Full Text Available Pharmaceutical safety testing requires a cheap, fast and highly efficient platform for real-time evaluation of drug toxicity and secondary effects. In this study, we have developed a microfluidic system for phenotype-based evaluation of toxic and teratogenic effects of drugs using zebrafish (Danio rerio embryos and larvae as the model organism. The microfluidic chip is composed of two independent functional units, enabling the assessment of zebrafish embryos and larvae. Each unit consists of a fluidic concentration gradient generator and a row of seven culture chambers to accommodate zebrafish. To test the accuracy of this new chip platform, we examined the toxicity and teratogenicity of an anti-asthmatic agent-aminophylline (Apl on 210 embryos and 210 larvae (10 individuals per chamber. The effect of Apl on zebrafish embryonic development was quantitatively assessed by recording a series of physiological indicators such as heart rate, survival rate, body length and hatch rate. Most importantly, a new index called clonic convulsion rate, combined with mortality was used to evaluate the toxicities of Apl on zebrafish larvae. We found that Apl can induce deformity and cardiovascular toxicity in both zebrafish embryos and larvae. This microdevice is a multiplexed testing apparatus that allows for the examination of indexes beyond toxicity and teratogenicity at the sub-organ and cellular levels and provides a potentially cost-effective and rapid pharmaceutical safety assessment tool.

  9. Species differences in methanol and formic acid pharmacokinetics in mice, rabbits and primates

    International Nuclear Information System (INIS)

    Sweeting, J. Nicole; Siu, Michelle; McCallum, Gordon P.; Miller, Lutfiya; Wells, Peter G.

    2010-01-01

    Methanol (MeOH) is metabolized primarily by alcohol dehydrogenase in humans, but by catalase in rodents, with species variations in the pharmacokinetics of its formic acid (FA) metabolite. The teratogenic potential of MeOH in humans is unknown, and its teratogenicity in rodents may not accurately reflect human developmental risk due to differential species metabolism, as for some other teratogens. To determine if human MeOH metabolism might be better reflected in rabbits than rodents, the plasma pharmacokinetics of MeOH and FA were compared in male CD-1 mice, New Zealand white rabbits and cynomolgus monkeys over time (24, 48 and 6 h, respectively) following a single intraperitoneal injection of 0.5 or 2 g/kg MeOH or its saline vehicle. Following the high dose, MeOH exhibited saturated elimination kinetics in all 3 species, with similar peak concentrations and a 2.5-fold higher clearance in mice than rabbits. FA accumulation within 6 h in primates was 5-fold and 43-fold higher than in rabbits and mice respectively, with accumulation being 10-fold higher in rabbits than mice. Over 48 h, FA accumulation was nearly 5-fold higher in rabbits than mice. Low-dose MeOH in mice and rabbits resulted in similarly saturated MeOH elimination in both species, but with approximately 2-fold higher clearance rates in mice. FA accumulation was 3.8-fold higher in rabbits than mice. Rabbits more closely than mice reflected primates for in vivo MeOH metabolism, and particularly FA accumulation, suggesting that developmental studies in rabbits may be useful for assessing potential human teratological risk.

  10. Dose-response relationship of cadmium or radiation-induced embryotoxicity in mouse whole embryo culture

    International Nuclear Information System (INIS)

    Nakashima, Kiyohito; Kawamata, Akitoshi; Matsuoka, Masato; Wakisaka, Takashi; Fujiki, Yoshishige

    1988-01-01

    Mouse embryos of B6C3F 1 strain were exposed in vitro to 1.2 to 2.2 μM cadmium chloride (Cd) or to 100 to 320 R x-rays, and the effects of the exposure on development were examined after 39 h of culture. Development of embryos was assessed from lethality, formation of the neural tube defect, diameter and protein of yolk sac, crown-rump and head lengths, embryonic protein, and number of somites. Incidence of the neural tube defect increased from 3.4 to 100% by 1.2 to 2.0 μM Cd, while embryo deaths increased from 13.8 to 93.3% by 2.0 to 2.2 μM Cd. Embryonic protein was significantly reduced at the teratogenic range, but the number of somites was only affected by 1.6 to 2.0 μM Cd. X-irradiation at 100 to 320 R induced the neural tube defect in 2.9 to 72.7% of the embryos. An embryolethal effect was observed only at the 320 R dose. Crown-rump and head lengths and embryonic protein were significantly affected at the teratogenic range, but the diameter and protein of yolk sac and number of somites were hardly affected. Cadmium- or radiation-induced response data of both teratogenicity and endpoints indicating inhibition of embryonic development were acceptably fitted to a linear log-probit regression. These regressions suggest that as an estimation of interference in development of embryos, embryonic protein and head length are sensitive endpoints while the number of somites is an insensitive criterion. (author)

  11. Thalidomide induces apoptosis in undifferentiated human induced pluripotent stem cells.

    Science.gov (United States)

    Tachikawa, Saoko; Nishimura, Toshinobu; Nakauchi, Hiromitsu; Ohnuma, Kiyoshi

    2017-10-01

    Thalidomide, which was formerly available commercially to control the symptoms of morning sickness, is a strong teratogen that causes fetal abnormalities. However, the mechanism of thalidomide teratogenicity is not fully understood; thalidomide toxicity is not apparent in rodents, and the use of human embryos is ethically and technically untenable. In this study, we designed an experimental system featuring human-induced pluripotent stem cells (hiPSCs) to investigate the effects of thalidomide. These cells exhibit the same characteristics as those of epiblasts originating from implanted fertilized ova, which give rise to the fetus. Therefore, theoretically, thalidomide exposure during hiPSC differentiation is equivalent to that in the human fetus. We examined the effects of thalidomide on undifferentiated hiPSCs and early-differentiated hiPSCs cultured in media containing bone morphogenetic protein-4, which correspond, respectively, to epiblast (future fetus) and trophoblast (future extra-embryonic tissue). We found that only the number of undifferentiated cells was reduced. In undifferentiated cells, application of thalidomide increased the number of apoptotic and dead cells at day 2 but not day 4. Application of thalidomide did not affect the cell cycle. Furthermore, immunostaining and flow cytometric analysis revealed that thalidomide exposure had no effect on the expression of specific markers of undifferentiated and early trophectodermal differentiated cells. These results suggest that the effect of thalidomide was successfully detected in our experimental system and that thalidomide eliminated a subpopulation of undifferentiated hiPSCs. This study may help to elucidate the mechanisms underlying thalidomide teratogenicity and reveal potential strategies for safely prescribing this drug to pregnant women.

  12. Cartilage and bone malformations in the head of zebrafish (Danio rerio) embryos following exposure to disulfiram and acetic acid hydrazide

    Energy Technology Data Exchange (ETDEWEB)

    Strecker, Ruben, E-mail: Ruben.Strecker@cos.uni-heidelberg.de [Aquatic Ecology and Toxicology Section, Center for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg (Germany); Weigt, Stefan, E-mail: stefan.weigt@merckgroup.com [Institute of Toxicology, Merck KGaA, 64293 Darmstadt (Germany); Braunbeck, Thomas, E-mail: braunbeck@uni-hd.de [Aquatic Ecology and Toxicology Section, Center for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg (Germany)

    2013-04-15

    In order to investigate teratogenic effects, especially on cartilage and bone formation, zebrafish embryos were exposed for 144 h to the dithiocarbamate pesticide disulfiram (20–320 μg/L) and acetic acid hydrazide (0.375–12 g/L), a degradation product of isoniazid. After fixation and full-mount staining, disulfiram could be shown to induce strong cartilage malformations after exposure to ≥ 80 μg/L, whereas acetic acid hydrazide caused cartilage alterations only from 1.5 g/L. Undulating notochords occurred after exposure to disulfiram even at the lowest test concentration of 20 μg/L, whereas at the two lowest concentrations of acetic acid hydrazide (0.375 and 0.75 g/L) mainly fractures of the notochord were observed. Concentrations of acetic acid hydrazide ≥ 1.5 g/L resulted in undulated notochords similar to disulfiram. Cartilages and ossifications of the cranium, including the cleithrum, were individually analyzed assessing the severity of malformation and the degree of ossification in a semi-quantitative approach. Cartilages of the neurocranium such as the ethmoid plate proved to be more stable than cartilages of the pharyngeal skeleton such as Meckel's cartilage. Hence, ossification proved significantly more susceptible than cartilage. The alterations induced in the notochord as well as in the cranium might well be of ecological relevance, since notochord malformation is likely to result in impaired swimming and cranial malformation might compromise regular food uptake. - Highlights: ► Disulfiram and acetic acid hydrazide as notochord, cartilage and bone teratogens ► Zebrafish embryos to model effects on single cartilages and bones in the head ► LC50 calculation and head length measurements after six days post-fertilization ► Lethality, head length and teratogenic effects are dose-dependent. ► Cartilages of the neurocranium are the most stable elements in the head.

  13. Developmental toxicity of prenatal exposure to toluene.

    Science.gov (United States)

    Bowen, Scott E; Hannigan, John H

    2006-01-01

    Organic solvents have become ubiquitous in our environment and are essential for industry. Many women of reproductive age are increasingly exposed to solvents such as toluene in occupational settings (ie, long-term, low-concentration exposures) or through inhalant abuse (eg, episodic, binge exposures to high concentrations). The risk for teratogenic outcome is much less with low to moderate occupational solvent exposure compared with the greater potential for adverse pregnancy outcomes, developmental delays, and neurobehavioral problems in children born to women exposed to high concentrations of abused organic solvents such as toluene, 1,1,1-trichloroethane, xylenes, and nitrous oxide. Yet the teratogenic effects of abuse patterns of exposure to toluene and other inhalants remain understudied. We briefly review how animal models can aid substantially in clarifying the developmental risk of exposure to solvents for adverse biobehavioral outcomes following abuse patterns of use and in the absence of associated health problems and co-drug abuse (eg, alcohol). Our studies also begin to establish the importance of dose (concentration) and critical perinatal periods of exposure to specific outcomes. The present results with our clinically relevant animal model of repeated, brief, high-concentration binge prenatal toluene exposure demonstrate the dose-dependent effect of toluene on prenatal development, early postnatal maturation, spontaneous exploration, and amphetamine-induced locomotor activity. The results imply that abuse patterns of toluene exposure may be more deleterious than typical occupational exposure on fetal development and suggest that animal models are effective in studying the mechanisms and risk factors of organic solvent teratogenicity.

  14. Cartilage and bone malformations in the head of zebrafish (Danio rerio) embryos following exposure to disulfiram and acetic acid hydrazide

    International Nuclear Information System (INIS)

    Strecker, Ruben; Weigt, Stefan; Braunbeck, Thomas

    2013-01-01

    In order to investigate teratogenic effects, especially on cartilage and bone formation, zebrafish embryos were exposed for 144 h to the dithiocarbamate pesticide disulfiram (20–320 μg/L) and acetic acid hydrazide (0.375–12 g/L), a degradation product of isoniazid. After fixation and full-mount staining, disulfiram could be shown to induce strong cartilage malformations after exposure to ≥ 80 μg/L, whereas acetic acid hydrazide caused cartilage alterations only from 1.5 g/L. Undulating notochords occurred after exposure to disulfiram even at the lowest test concentration of 20 μg/L, whereas at the two lowest concentrations of acetic acid hydrazide (0.375 and 0.75 g/L) mainly fractures of the notochord were observed. Concentrations of acetic acid hydrazide ≥ 1.5 g/L resulted in undulated notochords similar to disulfiram. Cartilages and ossifications of the cranium, including the cleithrum, were individually analyzed assessing the severity of malformation and the degree of ossification in a semi-quantitative approach. Cartilages of the neurocranium such as the ethmoid plate proved to be more stable than cartilages of the pharyngeal skeleton such as Meckel's cartilage. Hence, ossification proved significantly more susceptible than cartilage. The alterations induced in the notochord as well as in the cranium might well be of ecological relevance, since notochord malformation is likely to result in impaired swimming and cranial malformation might compromise regular food uptake. - Highlights: ► Disulfiram and acetic acid hydrazide as notochord, cartilage and bone teratogens ► Zebrafish embryos to model effects on single cartilages and bones in the head ► LC50 calculation and head length measurements after six days post-fertilization ► Lethality, head length and teratogenic effects are dose-dependent. ► Cartilages of the neurocranium are the most stable elements in the head

  15. Effect of coniine on the developing chick embryo.

    Science.gov (United States)

    Forsyth, C S; Frank, A A; Watrous, B J; Bohn, A A

    1994-04-01

    Coniine, an alkaloid from Conium maculatum (poison hemlock), has been shown to be teratogenic in livestock. The major teratogenic outcome is arthrogryposis, presumably due to nicotinic receptor blockade. However, coniine has failed to produce arthrogryposis in rats or mice and is only weakly teratogenic in rabbits. The purpose of this study was to evaluate and compare the effects of coniine and nicotine in the developing chick. Concentrations of coniine and nicotine sulfate were 0.015%, 0.03%, 0.075%, 0.15%, 0.75%, 1.5%, 3%, and 6% and 1%, 5%, and 10%, respectively. Both compounds caused deformations and lethality in a dose-dependent manner. All concentrations of nicotine sulfate caused some lethality but a no effect level for coniine lethality was 0.75%. The deformations caused by both coniine and nicotine sulfate were excessive flexion or extension of one or more toes. No histopathological alterations or differences in bone formation were seen in the limbs or toes of any chicks from any group; however, extensive cranial hemorrhage occurred in all nicotine sulfate-treated chicks. There was a statistically significant (P < or = 0.01) decrease in movement in coniine and nicotine sulfate treated chicks as determined by ultrasound. Control chicks were in motion an average of 33.67% of the time, while coniine-treated chicks were only moving 8.95% of a 5-min interval, and no movement was observed for nicotine sulfate treated chicks. In summary, the chick embryo provides a reliable and simple experimental animal model of coniine-induced arthrogryposis. Data from this model support a mechanism involving nicotinic receptor blockade with subsequent decreased fetal movement.

  16. Potential protective effect of L-cysteine against the toxicity of acrylamide and furan in exposed Xenopus laevis embryos: an interaction study.

    Science.gov (United States)

    Williams, John Russell; Rayburn, James R; Cline, George R; Sauterer, Roger; Friedman, Mendel

    2014-08-06

    The embryo toxicities of two food-processing-induced toxic compounds, acrylamide and furan, with and without added L-cysteine were examined individually and in mixtures using the frog embryo teratogenesis assay-Xenopus (FETAX). The following measures of developmental toxicity were used: (a) 96 h LC50, the median concentration causing 50% embryo lethality; (b) 96 h EC50, the median concentration causing 50% malformations of the surviving embryos; and (c) teratogenic index (96 h LC50/96 h EC50), an estimate of teratogenic risk. Calculations of toxic units (TU) were used to assess possible antagonism, synergism, or response addition of several mixtures. The evaluated compounds demonstrated counterintuitive effects. Furan had lower than expected toxicity in Xenopus embryos and, unlike acrylamide, does not seem to be teratogenic. However, the short duration of the tests may not show the full effects of furan if it is truly primarily genotoxic and carcinogenic. L-Cysteine showed unexpected properties in the delay of hatching of the embryos. The results from the interaction studies between combination of two or three components (acrylamide plus L-cysteine; furan plus L-cysteine; acrylamide plus furan; acrylamide plus furan and L-cysteine) show that furan and acrylamide seem to have less than response addition at 1:1 toxic unit ratio in lethality. Acrylamide and L-cysteine show severe antagonism even at low 19 acrylamide/1 L-cysteine TU ratios. Data from the mixture of acrylamide, furan, and L-cysteine show a slight antagonism, less than would have been expected from binary mixture exposures. Bioalkylation mechanisms and their prevention are discussed. There is a need to study the toxicological properties of mixtures of acrylamide and furan concurrently formed in heat-processed food.

  17. Protective role of vitamin C and E against sodium arsenate induced changes in developing kidney of albino mice

    International Nuclear Information System (INIS)

    Qureshi, F.; Tahir, M.; Sami, W.

    2009-01-01

    Background: Arsenic is a teratogenic agent present in the environment as oxides and arsenate and humans are exposed to it through contaminated drinking water, food, soil and air. This investigation was undertaken to evaluate protective role of Vitamin C and E against teratogenic injury produced by sodium arsenate in developing kidney of the mouse. Methods: Twenty-four pregnant albino mice of BALB/c strain, were randomly divided into 4 groups of 6 each: A1, A2, A3 and A4. Group A1 served as the control and received weight related distilled water by intra-peritoneal (I/P) injection, group A2 was given a single doses of 35 mg/kg on 8 GD whereas groups A3 and A4 were treated with Vitamin C and E by IP injection, 9 mg/kg/day and 15 mg/kg/day respectively, starting from 8 day and continued for the rest of the pregnancy period. The foetal kidneys were weighed and histological studies carried out including micrometry on different components of nephron. Results: Sodium arsenate toxicity manifested as an increase in weight of the kidneys, wider nephrogenic zone and significant reduction in the mean of number of mature renal corpuscles as compared to the control group (p<0.000). There were moderate to severe necrotic and degenerative changes in proximal and distal convoluted tubules; glomeruli were hyper cellular, the Bowman's spaces were obliterated. There was a statistically significant difference in mean diameter of renal corpuscles of group A2 when compared with groups A1, A3 and A4, (p<0.000). Conclusions: The findings implied that groups receiving Vitamin C and E along with sodium arsenate showed an overall improvement in all parameters, indicating the protective role of Vitamin C and E against arsenic induced teratogenicity in developing kidney and are safe to use during pregnancy without deleterious effect on human conspectuses in arsenic exposed areas. (author)

  18. Arsenate-induced maternal glucose intolerance and neural tube defects in a mouse model

    International Nuclear Information System (INIS)

    Hill, Denise S.; Wlodarczyk, Bogdan J.; Mitchell, Laura E.; Finnell, Richard H.

    2009-01-01

    Background: Epidemiological studies have linked environmental arsenic (As) exposure to increased type 2 diabetes risk. Periconceptional hyperglycemia is a significant risk factor for neural tube defects (NTDs), the second most common structural birth defect. A suspected teratogen, arsenic (As) induces NTDs in laboratory animals. Objectives: We investigated whether maternal glucose homeostasis disruption was responsible for arsenate-induced NTDs in a well-established dosing regimen used in studies of arsenic's teratogenicity in early neurodevelopment. Methods: We evaluated maternal intraperitoneal (IP) exposure to As 9.6 mg/kg (as sodium arsenate) in LM/Bc/Fnn mice for teratogenicity and disruption of maternal plasma glucose and insulin levels. Selected compounds (insulin pellet, sodium selenate (SS), N-acetyl cysteine (NAC), L-methionine (L-Met), N-tert-Butyl-α-phenylnitrone (PBN)) were investigated for their potential to mitigate arsenate's effects. Results: Arsenate caused significant glucose elevation during an IP glucose tolerance test (IPGTT). Insulin levels were not different between arsenate and control dams before (arsenate, 0.55 ng/dl; control, 0.48 ng/dl) or after glucose challenge (arsenate, 1.09 ng/dl; control, 0.81 ng/dl). HOMA-IR index was higher for arsenate (3.9) vs control (2.5) dams (p = 0.0260). Arsenate caused NTDs (100%, p < 0.0001). Insulin pellet and NAC were the most successful rescue agents, reducing NTD rates to 45% and 35%. Conclusions: IPGTT, insulin assay, and HOMA-IR results suggest a modest failure of glucose stimulated insulin secretion and insulin resistance characteristic of glucose intolerance. Insulin's success in preventing arsenate-induced NTDs provides evidence that these arsenate-induced NTDs are secondary to elevated maternal glucose. The NAC rescue, which did not restore maternal glucose or insulin levels, suggests oxidative disruption plays a role.

  19. Maternal Stress Combined with Terbutaline Leads to Comorbid Autistic-Like Behavior and Epilepsy in a Rat Model.

    Science.gov (United States)

    Bercum, Florencia M; Rodgers, Krista M; Benison, Alex M; Smith, Zachariah Z; Taylor, Jeremy; Kornreich, Elise; Grabenstatter, Heidi L; Dudek, F Edward; Barth, Daniel S

    2015-12-02

    Human autism is comorbid with epilepsy, yet, little is known about the causes or risk factors leading to this combined neurological syndrome. Although genetic predisposition can play a substantial role, our objective was to investigate whether maternal environmental factors alone could be sufficient. We examined the independent and combined effects of maternal stress and terbutaline (used to arrest preterm labor), autism risk factors in humans, on measures of both autistic-like behavior and epilepsy in Sprague-Dawley rats. Pregnant dams were exposed to mild stress (foot shocks at 1 week intervals) throughout pregnancy. Pups were injected with terbutaline on postnatal days 2-5. Either maternal stress or terbutaline resulted in autistic-like behaviors in offspring (stereotyped/repetitive behaviors and deficits in social interaction or communication), but neither resulted in epilepsy. However, their combination resulted in severe behavioral symptoms, as well as spontaneous recurrent convulsive seizures in 45% and epileptiform spikes in 100%, of the rats. Hippocampal gliosis (GFAP reactivity) was correlated with both abnormal behavior and spontaneous seizures. We conclude that prenatal insults alone can cause comorbid autism and epilepsy but it requires a combination of teratogens to achieve this; testing single teratogens independently and not examining combinatorial effects may fail to reveal key risk factors in humans. Moreover, astrogliosis may be common to both teratogens. This new animal model of combined autism and epilepsy permits the experimental investigation of both the cellular mechanisms and potential intervention strategies for this debilitating comorbid syndrome. Copyright © 2015 the authors 0270-6474/15/3515894-09$15.00/0.

  20. Prescription drug use during pregnancy in France: a study from the national health insurance permanent sample.

    Science.gov (United States)

    Demailly, Romain; Escolano, Sylvie; Quantin, Catherine; Tubert-Bitter, Pascale; Ahmed, Ismaïl

    2017-09-01

    To provide an up-to-date account of drug prescription during pregnancy in France from 2011 to 2014 using the permanent sample of the French national computerized healthcare database and with a focus on recommended supplementations, fetotoxic drugs and teratogenic drugs. All pregnancies identified by the International Classification of Diseases, 10th Revision codes list in the hospitalization database, lasting more than 9 weeks of amenorrhea and whose delivery occurred between 01/01/2011 and 12/31/2014, were included. Drugs delivered between the trimester before and until the end of the pregnancy were included. Drug exposure prevalence was calculated for each year and according to pregnancy trimesters. The study included 28,491 pregnancies with a median number of 9 [5-13] (median [IQ range]) drugs delivered. The most prescribed drug class was antianemia (in 72.5% of exposed). The prescription rate of recommended vitamins (B9 and D) increased over the study period (+10%). Influenza vaccination also increased but remained at a low rate (1%). Exposure to fetotoxic drugs decreased as pregnancy advanced. Exposure to the main teratogenic antiepileptics was stable over the study period. Low-income pregnant women had a higher average drug consumption except for recommended vitamins. Pregnant French women are among the largest consumers of prescription medications worldwide. Overall, the dispensation trends observed in this study are in line with the recommendations of the French National College of Gynecologists and Obstetricians. Nevertheless, while being low, exposure to fetotoxic drugs, teratogenic drugs or those under safety alerts still occurred. Supplementations and vaccines in low-income pregnant women should also be increased. Copyright © 2017 John Wiley & Sons, Ltd.

  1. Use of TNF-inhibitors and ustekinumab for psoriasis during pregnancy

    DEFF Research Database (Denmark)

    Lund, Tamara; Thomsen, Simon Francis

    2017-01-01

    From 2002 to 2016 a total of seven women with severe refractory psoriasis were exposed to the TNF-inhibitors infliximab and adalimumab or to the IL12/23 inhibitor ustekinumab during one or more pregnancies. Maternal, fetal or teratogenic toxicity were not detected during pregnancy and puerperium....... All pregnancies were uneventful and resulted in delivery of 10 healthy children in total, one of the women is due February 2017. Postpartum, five of the women were lactating, but none of the women or newborns developed adverse reactions. Data on safety of treatment during breastfeeding are sparse...

  2. Mutagenesis and Teratogenesis Section

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    Progress is reported in the following areas of research: studies on chromosome damage and indirect indicators of genetic damage; cytogenetic, embryological, and biochemical studies of mutants in mammals; studies on mammalian gonads in relation to mutagenic effects; systems for detecting mutagenic effects of chemicals; processes in repair of damage to DNA; methods for detecting mutations that result in proteins with altered amino acid sequences; recombination in Drosophila; DNA repair processes in bacteria; development of a sensitive teratological prescreen; teratogenic end points in amphibians; and development of a method for long-term culture of Xenopus oocytes

  3. Health effects of low-level ionising radiation: biological basis for risk assessment

    International Nuclear Information System (INIS)

    Upton, A.C.

    1987-01-01

    The biological basis for risk assessment is discussed. The risks of carcinogenic effects, teratogenic effects, and genetic (heritable) effects are estimated to vary in proportion with the dose of radiation in the low-dose domain; however, the risks also appear to vary with the LET of the radiation, age at the time of irradiation, and other variables. Although the data suffice to place the risks in perspective with other hazards of modern life, further research to refine the reliability of the risk assessment is called for. (author)

  4. Congenital deformity in calves induced by the maternal consumption of lupin

    Energy Technology Data Exchange (ETDEWEB)

    Shupe, J.L.; Binns, W.; James, L.F.; Keeler, R.F.

    1968-01-01

    A congenital skeletal deformity called crooked calf syndrome occurs in many of the beef cattle-producing areas of the western United States. This deformity is characterized by arthrogryposis, torticollis, scoliosis, and cleft palate. The condition is non-hereditary, and is due to the consumption of lupin by the dam. The most severe and characteristic deformities are produced between the 40th and 70th days of gestation. Experimental analyses were performed to ascertain the teratogenic effect of lupin plants, lupin and lead, and lead alone upon cattle.

  5. Hazard of Sulfonamides and Detection Technology Research Progress

    Science.gov (United States)

    Jiang, Jiahui; Wang, Guangyu

    2017-12-01

    As a kind of widely used antibiotic with typical characteristics, sulfonamides have been greatly applied in clinical medicine for long time. It can’t be effectively treated by pollutant disposal system during pharmaceutical process and utilization and will be discharged into natural environment to be one of the antibiotics with great effect. This kind of substance is difficult to be biodegraded and will be easy to accumulate in the environment, generating huge eco-toxicological effect with significant mutagenicity and teratogenic effect. It is the severe threat for ecological balance, human health and drinking water safety. Its environmental behavior and detection technology attract extensive attention home and abroad.

  6. Management of an infant with cleft lip and palate with phocomelia in dental practice.

    Science.gov (United States)

    Muthu, M S

    2000-12-01

    Cleft lip and palate is a severe birth defect occurring approximately one in 800-1000 newborn infants. The incidence varies widely among races. Cleft lip and palate together account for approximately 50% of all cases whereas isolated cleft lip and isolated cleft palate occur in about 25% of cases. Many of these congenital anomalies appear to be genetically determined though the majority are of unknown causes or teratogenic influences. Presented here is a 3 day old infant with bilateral cleft lip and palate and phocomelia for whom a feeding obturator was made and delivered to facilitate feeding.

  7. Histological aspects of arterial abnormalities produced by X-irradiation of the aortic and branchial arches in the chick embryo

    International Nuclear Information System (INIS)

    Fischer, J.-L.

    1976-01-01

    Low dose X irradiations centred on one or two aortic and branchial arches of 3-day chick embryos result in teratogenic effects on the arteries (21-92%) and in low mortality (4-12%). Histological studies of abnormal arteries show different structural malformations of the arterial wall: inorganized arterial fibres, abnormal intima, newly formed arterial tissue in arterial lumen, coalescence of two arteries. It is suggested that a disturbance at the aortic differentiation level results under experimental conditions in the observed arterial abnormalities

  8. Review of PAH contamination in food products and their health hazards.

    Science.gov (United States)

    Bansal, Vasudha; Kim, Ki-Hyun

    2015-11-01

    Public concern over the deleterious effects of polycyclic aromatic hydrocarbons (PAHs) has grown rapidly due to recognition of their toxicity, carcinogenicity, and teratogenicity. The aim of this review is to describe the status of PAH pollution among different food types, the route of dietary intake, measures for its reduction, and legislative approaches to control PAH. To this end, a comprehensive review is outlined to evaluate the status of PAH contamination in many important food categories along with dietary recommendations. Our discussion is also extended to describe preventive measures to reduce PAH in food products to help reduce the risks associated with human intake. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. An acute episode of rhabdomyolysis associated with everolimus and cabergoline intake in a postpartum kidney recipient

    Directory of Open Access Journals (Sweden)

    B. I. Yaremin

    2017-01-01

    Full Text Available Kidney transplantation is one of the most promising ways to ensure the onset and successful maintenance of pregnancy in patients with end-stage chronic renal disease. A multicomponent drug therapy in such patients creates risks for fetal development, primarily due to the teratogenicity of mTOR receptor inhibitors and mycophenolate. Moreover, the inhibitors of the proliferative signal may have potential drug interactions, which can result in additional complications.Rhabdomyolysis is one of them. The paper describes the clinical case of an acute episode of reversible rhabdomyolysis in a patient on everolimus therapy.

  10. Prenatal exposition on ionizing radiations

    International Nuclear Information System (INIS)

    2001-01-01

    The Sessions on Prenatal Exposition on Ionizing Radiations was organized by the Argentine Radioprotection Society, in Buenos Aires, between 8 and 9, November 2001. In this event, were presented papers on: biological effects of ionizing radiation; the radiation protection and the pregnant woman; embryo fetal development and its relationship with the responsiveness to teratogens; radioinduced delayed mental; neonatal irradiation: neurotoxicity and modulation of pharmacological response; pre implanted mouse embryos as a model of uranium toxicity studies; hereditary effects of the radiation and new advances from the UNSCEAR 2001; doses estimation in embryo

  11. Distruption of retinoid and CYP systems and embryo development in marine organisms: a potential model for humans

    DEFF Research Database (Denmark)

    Tairova, Zhanna; Strand, Jakob; Jørgensen, Eva Cecilie Bonefeld

    Some environmental persistent organic pollutants (POPs) can be highly toxic and pose risk for both natural fauna populations and humans. POPs can disrupt an array of molecular and cellular mechanisms causing endocrine disruptions, cancer and teratogenic effects. Potentially, POPs can interfere...... with embryo development and reproduction. At present, there is only limited knowledge of the potential effects of dioxin-like compounds and polycyclic aromatic hydrocarbons in the Danish environment. The Ph.D. project is expected to link exposure to POPs such as dioxin-like compounds and PAHs to effects...... to a better integrated exposure assessment for aquatic organisms as well as for humans....

  12. Determination of metal ion contents of two antiemetic clays use in Geophagy

    Directory of Open Access Journals (Sweden)

    Solomon E. Owumi

    2015-01-01

    Specifically, our result indicates unacceptably high levels of aluminum in Eko and Omumu (>10-fold greater than the highest desirable levels set by the USEPA. The aluminum concentrations were influenced by the pH condition in which the samples were digested. Dietary exposure to aluminum at such high levels may be deleterious to maternal health and fetal development. Therefore consumption of Eko and Omumu as an antidote to reduce nausea during pregnancy should be discouraged. Future studies are planned to investigate specific impacts on fetal and maternal health and likely teratogenicity in rodent models.

  13. RDT&E for Emerging Contaminants

    Science.gov (United States)

    2010-06-01

    Perchlorate ● NDMA ● 1,4-Dioxane ● PFCs 8 Perchlorate Issue ● Broad Use & Occurrence  DoD - Rocket propellant - Insensitive munitions  Pyrotechnics and...and 18O -20 -15 -10 -5.0 0.0 5.0 -30 -25 -20 -15 -10 -5 0 5 10 Laboratory Military Natural Herbicides Gunpowder Road Flares Taiwan 3 7 C l 18 O 27 NDMA ...Toxicology  NDMA is a potent mutagen, teratogen, & carcinogen.  EPA 10-6 Lifetime Cancer Risk = 0.7 ng/L.  California DHS; 10 ng/L Action

  14. Copper hazards to fish, wildlife and invertebrates: a synoptic review

    Science.gov (United States)

    Eisler, Ronald

    1998-01-01

    Selective review and synthesis of the technical literature on copper and copper salts in the environment and their effects primarily on fishes, birds, mammals, terrestrial and aquatic invertebrates, and other natural resources. The subtopics include copper sources and uses; chemical and biochemical properties; concentrations of copper in field collections of abiotic materials and living organisms; effects of copper deficiency; lethal and sublethal effects on terrestrial plants and invertebrates, aquatic organisms, birds and mammals, including effects on survival, growth, reproduction, behavior, metabolism, carcinogenicity, matagenicity, and teratogenicity; proposed criteria for the protection of human health and sensitive natural resources; and recommendations for additional research.

  15. Immunosuppression by hypoxic cell radiosensitizers: a phenomenon of potential clinical importance

    International Nuclear Information System (INIS)

    Rockwell, S.; Kapp, D.S.

    1982-01-01

    The nitroimidazoles metronidazole, misonidazol, and desmethyl misonidazole are currently undergoing clinical trials as possible adjuncts to radiotherapy. Ongoing clinical trials are evaluating the effectiveness of these agents and also documenting the pharmacokinetics and toxicities of radiosensitizing doses of these drugs in man. A variety of toxic effects have been noted in man, including anorexia, nausea and vomiting, peripheral neuropathy, central nervous system symptoms, ototoxicity, allergy, and fear. Laboratory studies have also suggested that these agents have potential to be mutagenic, carcinogenic, and teratogenic. In the editorial presented, the author attempts to draw attention to an additional toxic effect of nitroimidazoles - the inhibition of cell-mediated immune responses

  16. ISSUES OF FETUS DRUG SAFETY

    Directory of Open Access Journals (Sweden)

    A.V. Ostrovskaya

    2010-01-01

    Full Text Available The article is focused on the issue of fetus drug safety. Development of a child’s health depends both on hereditary information and environment factors. The reason for deviation from the process of normal prenatal development could be any xenobiotics, physical factors and some medications having a pathogenic effect during pregnancy on the embryo and fetus. Due to that, the physician’s preventive work based on the knowledge of embryogenesis processes and critical development periods. Key words: teratogenic action, medications, prenatal development, congenital malformation, newborns, children.(Pediatric Pharmacology. – 2010; 7(1:25-28

  17. Radioiodine treatment of Graves' disease. An assessment of its potential risks

    International Nuclear Information System (INIS)

    Graham, G.D.; Burman, K.D.

    1986-01-01

    Concern about the side effects of radiation exposure has deterred physicians from using radioiodine treatment for Graves' disease, although the efficacy and safety of this treatment have been established in the 35 years since its introduction. In that time, no significant side effects have been discovered. We believe iodine-131 should be considered the treatment of choice in most patients with Graves' disease. This article reviews the current understanding of the risks in radioiodine treatment of Graves' disease, including the risks for teratogenicity, genetic damage, carcinogenesis, and cellular dysfunction

  18. Elevated human chorionic gonadotropin levels in patients with chronic kidney disease: Case series and review of literature

    Directory of Open Access Journals (Sweden)

    S Soni

    2013-01-01

    Full Text Available Women are often subjected to serum human chorionic gonadotropin (HCG testing prior to diagnostic and therapeutic interventions. A positive result leads to further testing to rule out pregnancy and avoid possible fetal teratogenicity. The impact of chronic kidney disease (CKD on HCG testing has not been studied. We report a series of 5 women out of 62 with CKD, who had a positive HCG test on routine pre-transplant screening at a single transplant center. We analyzed their case records retrospectively. Despite aggressive investigation, their elevated HCG levels remained unexplained. The positive test contributed to delays in transplantation and increased overall cost of treatment.

  19. Risks to the offspring from parental occupational exposures

    International Nuclear Information System (INIS)

    Haas, J.F.; Schottenfeld, D.

    1979-01-01

    Risks to the offspring of workers with occupational chemical exposures may derive from mutagenic, teratogenic or carcinogenic effects of industrial agents to which the parents are exposed. Evidence for impaired pregnancies and hazards to the offspring of working populations with chemical exposures is, however, very limited. Evidence is reviewed for hazards to the offspring resulting from parental occupational exposure to vinyl chloride, benzene, chloroprene, radiation and petroleum-derived hydrocarbons. Other environmental and behavioral factors with major effects on pregnancy outcome are considered. These include smoking, alcohol, and drug exposures. An approach to surveillance for chromosomal abnormalities in offspring of occupationally exposed parents is outlined

  20. Phthalates biodegradation in the environment.

    Science.gov (United States)

    Liang, Da-Wei; Zhang, Tong; Fang, Herbert H P; He, Jianzhong

    2008-08-01

    Phthalates are synthesized in massive amounts to produce various plastics and have become widespread in environments following their release as a result of extensive usage and production. This has been of an environmental concern because phthalates are hepatotoxic, teratogenic, and carcinogenic by nature. Numerous studies indicated that phthalates can be degraded by bacteria and fungi under aerobic, anoxic, and anaerobic conditions. This paper gives a review on the biodegradation of phthalates and includes the following aspects: (1) the relationship between the chemical structure of phthalates and their biodegradability, (2) the biodegradation of phthalates by pure/mixed cultures, (3) the biodegradation of phthalates under various environments, and (4) the biodegradation pathways of phthalates.

  1. Programmed cell death for defense against anomaly and tumor formation

    International Nuclear Information System (INIS)

    Kondo, Sohei; Norimura, Toshiyuki; Nomura, Taisei

    1995-01-01

    Cell death after exposure to low-level radiation is often considered evidence that radiation is poisonous, however small the dose. Evidence has been accumulating to support the notion that cell death after low-level exposure to radiation results from activation of suicidal genes open-quote programmed cell death close-quote or open-quote apoptosis close-quote - for the health of the whole body. This paper gives experimental evidence that embryos of fruit flies and mouse fetuses have potent defense mechanisms against teratogenic or tumorigenic injury caused by radiation and carcinogens, which function through programmed cell death

  2. Valproic Acid in Women and Girls of Childbearing Age.

    Science.gov (United States)

    Gotlib, Dorothy; Ramaswamy, Rachel; Kurlander, Jacob E; DeRiggi, Alana; Riba, Michelle

    2017-09-01

    The aim of this paper is to evaluate recent literature on valproic acid (VPA) in women and girls of childbearing age and to emphasize new findings. Recent research confirms VPAs teratogenicity and risk of hormone disruption. VPA exposure in utero increases the risk for a variety of major congenital malformations (MCMs), reduced IQ and behavioral problems. In girls and women, VPA increases the risk of hormone abnormalities, obesity, and polycystic ovarian syndrome (PCOS). Despite guidelines recommending caution, VPA use continues to be prescribed to reproductive-aged women and girls. Despite significant and well-documented risk, adherence to guidelines in VPA use in reproductive-aged girls and women remains low.

  3. [The child from families with type 1 diabetes].

    Science.gov (United States)

    Wasikowa, Renata; Suchańska, Dorota; Suchańska, Danuta; Basiak, Aleksander; Noczyńska, Anna; Stasińska, Teresa

    2005-01-01

    Diabetes type 1 is observed in individuals with a genetic predisposition to the disease. Observed is a 3-5 fold risk for congenital defects, therefore diabetes type 1 is one of the highest known teratogenic risk factor. The main factor responsible for the development of congenital defects is hyperglycemia. Observed are congenital defects of the central nervous system, the bones, urinary and digestive tract. Characteristic is macrosomia. Observed are hypocalcemia, hypomagnesemia, polycythemia, hyperbilirubinemia, hypertrophic cardiomyopathy, respiratory disturbances. Children from families with diabetes type 1 are at high risk for the development of the disease in the newborn period, additional diseases. They must be in permanent medical control.

  4. Can exposure to electromagnetic radiation in diathermy operators be estimated from interview data A pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, A.I.; Skotte, J. (Central Hospital, Esbjerg (Denmark))

    1991-01-01

    As preparation for a case-control study dealing with possible teratogenic property of short waves, a pilot study was conducted in order to compare exposure assessment from different sources. In 11 physiotherapy clinics, exposure assessments based on interviews within 1 week among the exposed physiotherapists were compared with exposure assessments based on observations including measurements. It was possible to discriminate between recent high and low peak exposure. Furthermore, an interview index reflecting the duration of the exposure correlated to some extent with the corresponding measurements.

  5. Current approach for urinary system stone disease in pregnant women

    Directory of Open Access Journals (Sweden)

    Orcun Celik

    2016-01-01

    Full Text Available Urinary system stones can be classified according to size, location, X-ray characteristics, aetiology of formation, composition, and risk of recurrence. Especially urolithiasis during pregnancy is a diagnostic and therapeutic challenge. In most cases, it becomes symptomatic in the second or third trimester. Diagnostic options in pregnant women are limited due to the possible teratogenic, carcinogenic, and mutagenic risk of foetal radiation exposure. Clinical management of a pregnant urolithiasis patient is complex and demands close collaboration between patient, obstetrician and urologist. We would like to review current diagnosis and treatment modalities of stone disease of pregnant woman.

  6. Embryotoxicity induced by alkylating agents. Some methodological aspects of DNA alkylation studies in murine embryos using ethylmethanesulfonate.

    Science.gov (United States)

    Platzek, T; Bochert, G; Rahm, U; Neubert, D

    1987-05-01

    Synthesis and spectroscopic analysis of some alkylated DNA purine bases are described. HPLC separation methods are developed for the determination of DNA alkylation rates in mammalian embryonic tissues. Following treatment of pregnant mice with the ethylating agent ethylmethanesulfonate (EMS), an appreciable amount of alkylation (ethylation and methylation) was found in the nuclear DNA of the embryos during organogenesis. The results are discussed in context of our thesis that a certain amount of DNA alkylation in the embryos is correlated to the teratogenic potential of alkylating agents.

  7. [Biochemical changes in the placenta of white rats treated with basfungin].

    Science.gov (United States)

    Markova, E

    1976-01-01

    The author carried out experiments on white rats and discussed the role of the placental insufficiency in the perinatal pathology under the action of fungicide basfugine. After administration of the preparation singly at the critical 13th day of embriogenesis and repeatedly during the course of the gestation the author examined biochemically the activity of the following enzymes: glucose-6-phosphatdehydrogenase, lactatdehydrogenase and thermostable alkaline phosphatase. Basfungine, administered in effective teratogenic doses, inhibited the activity of the indicated enzymes in the placenta, manifesting in this way its functional insufficiency, which was most probably the substantial moment in the pathogenesis of the induced anamaly in the fetal development.

  8. Safety of Contrast Material Use During Pregnancy and Lactation.

    Science.gov (United States)

    Puac, Paulo; Rodríguez, Andrés; Vallejo, Carina; Zamora, Carlos A; Castillo, Mauricio

    2017-11-01

    The use of contrast media to image patients who are pregnant has increased during the past decades worldwide. Their use in pregnancy and in patients who are lactating remains a challenging issue for radiologists and other physicians. This article addresses the different types of contrast media that may be used in such patients according to the imaging modality (iodinated contrast media, barium, gadolinium-based, and ultrasound contrast agents), focusing on their adverse effects, potential teratogenic effects, strategies to minimize risks, and current clinical recommendation. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Use of cephalosporins during pregnancy and in the presence of congenital abnormalities: a population-based, case-control study

    DEFF Research Database (Denmark)

    Czeizel, A.E.; Rockenbauer, M.; Sørensen, Henrik Toft

    2001-01-01

    of cephalosporins, mainly oral cephalexin, in the case and patient control groups was explained by recall bias. The comparison of the occurrence of medically documented cephalosporin treatments during the second to third months of gestation (ie, the critical period for major congenital abnormalities) in different...... congenital abnormality groups with the referent data of the total population control group and the patient control group did not indicate a detectable human teratogenic potential of the studied drug. Conclusion: Treatment with the studied cephalosporins during pregnancy does not seem to present a detectable...

  10. Effects of toxic chemicals on the reproductive system. Council on Scientific Affairs.

    Science.gov (United States)

    1985-06-21

    In an effort to make physicians more aware of the hazards of the workplace to pregnant workers, the Council on Scientific Affairs' Advisory Panel on Reproductive Hazards in the Workplace prepared this third and final report reviewing the effects of chemical exposure. A total of 120 chemicals were considered for reviews based on an estimation of their imminent hazard, ie, widespread use and/or inherent toxicity. Following a brief introduction, which sets out general principles, clinical applications, and aids to the recognition of a human teratogen, the report presents reviews and opinions for three representative chemicals. Information concerning the remaining 117 compounds is available upon request.

  11. Elevated NMDA receptor levels and enhanced postsynaptic long-term potentiation induced by prenatal exposure to valproic acid

    DEFF Research Database (Denmark)

    Rinaldi, Tania; Kulangara, Karina; Antoniello, Katia

    2007-01-01

    as the commonly linked kinase calcium/calmodulin-dependent protein kinase II. Synaptic plasticity experiments between pairs of pyramidal neurons revealed an augmented postsynaptic form of long-term potentiation. These results indicate that VPA significantly enhances NMDA receptor-mediated transmission and causes......Valproic acid (VPA) is a powerful teratogen causing birth defects in humans, including autism spectrum disorder (ASD), if exposure occurs during the first trimester of embryogenesis. Learning and memory alterations are common symptoms of ASD, but underlying molecular and synaptic alterations remain...

  12. Long-term feeding studies in mice fed a diet containing irradiated fish. I

    International Nuclear Information System (INIS)

    Petten, L.E. van; Calkins, J.E.; McConnell, R.F.; Gottschalk, H.M.; Elias, P.S.

    1980-01-01

    A wholesomeness feeding study was carried out in mice fed equal amounts of cod or redfish, comprising 45% of the diet. Three groups of animals received either irradiated [1.75 kGy (175 krad)] fish, non-irradiated fish or stock ration. A 90-day subchronic study, a multigeneration reproduction, a dominant lethality and a teratology study were carried out together with an 80-week oncogenic study on the F 1 generation. No adverse effects were noted on growth, reproduction and litter behaviour, in relation to dominant lethality, teratogenicity or oncogenicity. (Auth.)

  13. Mood disturbance and pregnancy: pros and cons of pharmacologic treatment

    Directory of Open Access Journals (Sweden)

    Soares Claudio N

    2001-01-01

    Full Text Available The management of psychiatric disturbances during pregnancy, particularly depression and bipolar disorders, is complex. This article reviews the existing data regarding the impact of an untreated psychiatric illness on the infant's development. In addition, the potential risks to the fetus due to prenatal exposure to different psychotropic agents, including antidepressants, mood stabilizers, antipsychotics, and benzodiazepines, are summarized. Moreover, this article emphasizes that no decision is risk-free, and the ultimate goal is to reduce the exposure to both the illness and the potential teratogenic effects of the treatment. Therefore, clinicians should seek a treatment strategy, which poses the least risk for both mother and infant.

  14. How many breaks do we need to CATCH on 22q11?

    Energy Technology Data Exchange (ETDEWEB)

    Dallapiccola, B.; Pizzuti, A.; Novelli, G. [Univ. of Rome, Rome (Italy)]|[Univ. of Milan (Italy)]|[CSS IRCCS Hospital, San Giovanni Rotondo (Italy)

    1996-07-01

    The major clinical manifestations of DiGeorge syndrome (DGS; MIM 188400), which reflect developmental abnormalities of the 3d and 4th pharyngeal pouch derivatives, include thymus- and parathyroid-gland aplasia or hypoplasia and conotruncal cardiac malformations. The additional dysmorphic facial features, such as hypertelorism, cleft lip and palate, bifid uvula, and small/low-set ears, which are also common, presumably reflect the same defect. The DGS phenotype has been associated with chromosome abnormalities and, sometimes, is the effect of teratogenic agents such as retinoic acid and alcohol. 53 refs., 1 fig.

  15. Fetal Valproate Syndrome with Limb Defects: An Indian Case Report

    Directory of Open Access Journals (Sweden)

    Manisha Goyal

    2016-01-01

    Full Text Available Epilepsy is a common disorder and exposure to antiepileptic drugs during pregnancy increases the risk of teratogenicity. Older AEDs such as valproate and phenobarbital are associated with a higher risk of major malformations in the fetus than newer AEDs like lamotrigine and levetiracetam. Exposure to valproic acid during first trimester can result in fetal valproate syndrome (FVS, comprising typical facial features, developmental delay, and a variety of malformations such as neural tube defects, cardiac and genitourinary malformations, and limb defects. We are presenting an Indian case of FVS with major limb defects.

  16. 30 years life with Chernobyl, 5 years life with Fukushima. Health consequences of the nuclear catastrophes of Chernobyl and Fukushima; 30 Jahre Leben mit Tschernobyl, 5 Jahre Leben mit Fukushima. Gesundheitliche Folgen der Atomkatastrophen von Tschernobyl und Fukushima

    Energy Technology Data Exchange (ETDEWEB)

    Claussen, Angelika; Rosen, Alex

    2016-02-15

    The IPPNW report on health consequences of the nuclear catastrophes of Chernobyl and Fukushima covers the following issues: Part.: 30 years life with Chernobyl: Summarized consequences of Chernobyl, the accident progression, basic data of the catastrophe, estimation of health hazards as a consequence of the severe accident of Chernobyl, health consequences for the liquidators, health consequences for the contaminated population, mutagenic and teratogenic effects. Part B: 5 years life with Fukushima: The start of the nuclear catastrophe, emissions and contamination, consequences of the nuclear catastrophe on human health, thyroid surveys in the prefecture Fukushima, consequences of the nuclear catastrophe on the ecosystem, outlook.

  17. In vitro evaluation of cytotoxicity and oxidative damage induced by ochratoxin A and aflatoxin B1: protective role of antioxidants

    Directory of Open Access Journals (Sweden)

    F. Cheli

    2011-03-01

    Full Text Available In animal nutrition, mycotoxins are important feed contaminants. Among them, ochratoxins (OTA and aflatoxins (AF have several biological activities, including acute toxicity, teratogenicity, mutagenicity, immunotoxicity and carcinogenicity (Creepy, 2002. Obviously, toxicity of mycotoxins is a risk factor not only for animals but for humans, too (Hussein et al., 2001. Deficiencies of certain nutritional factors e.g. micronutrients may predispose or enhance individuals to the toxic effects of mycotoxins (Atroshi et al., 2002. It is well known that antioxidants like vitamin E, protect cellular membranes from oxidative damage.........

  18. Brain’s DNA Repair Response to Neurotoxicants

    Science.gov (United States)

    2007-01-01

    Creppy et al., 1983b; Haubeck et al., 1981; Lea et al., 1989; Stormer and Lea, 1995), teratogenic (Arora et al., 1983; Fukui et al., 1992; Szczech and Hood...aminoacyl-tRNA synthetases and on the growth and protein synthesis of hepatoma cells. Toxicol Lett 1983a;19:217–24. Creppy EE, Stormer FC, Roschenthaler R...1989;2:179–248. Lea T, Steien K, Stormer FC. Mechanism of ochratoxin A-induced immuno- suppression. Mycopathologia 1989;107:153–9. Lebrun S, Follmann W

  19. Reproductive toxicity of the glycol ethers.

    Science.gov (United States)

    Hardin, B D

    1983-06-01

    The glycol ethers are an important and widely used class of solvents. Recent studies have demonstrated that ethylene glycol monomethyl ether (EGME), ethylene glycol dimethyl ether (EGdiME), ethylene glycol monoethyl ether (EGEE), and ethylene glycol monoethyl ether acetate (EGEEA) are teratogenic. Other studies have demonstrated that testicular atrophy or infertility follow treatment of males with EGME, ethylene glycol monomethyl ether acetate (EGMEA), EGEE, EGEEA, diethylene glycol dimethyl ether (diEGdiME), and diethylene glycol monoethyl ether (diEGEE). Experimental data are reviewed and structure-activity relationships are speculated upon.

  20. Major congenital anomalies in a Danish region

    DEFF Research Database (Denmark)

    Garne, Ester; Hansen, Anne Vinkel; Birkelund, Anne Sofie

    2014-01-01

    INTRODUCTION: This study describes the prevalence of congenital anomalies and changes over time in birth outcome, mortality and chronic maternal diseases. MATERIAL AND METHODS: This study was based on population data from the EUROCAT registry covering the Funen County, Denmark, 1995...... mortality decreased significantly over time for cases with major congenital anomalies (p congenital anomaly cases, 8% had a registration of one of these chronic maternal diseases......: diabetes, epilepsy, mental disorder, thyroid disease, asthma, or inflammatory bowel disease. Medication for these conditions accounted for 46% of maternal drug use. CONCLUSION: Maternal morbidity and use of potentially teratogenic medication have increased among congenital anomaly cases. Foetal and infant...

  1. Reproductive studies with the anti-inflammatory agent, piroxicam: modification of classical protocols.

    Science.gov (United States)

    Perraud, J; Stadler, J; Kessedjian, M J; Monro, A M

    1984-02-14

    Reproductive toxicology studies were conducted in rabbits and rats given piroxicam, a non-steroidal anti-inflammatory agent (NSAI), orally at 2, 5 and 10 mg/kg/day. In teratology studies there was neither drug-related embryotoxicity nor teratogenicity. As piroxicam, like other NSAI, affects parturition in rats and leads to a progressive toxicity in lactating females, standard protocols were modified: dams of the female fertility study were treated from 2 weeks prior to mating until day 6 of gestation and females of the post-natal toxicity study were treated from parturition until day 12 of lactation. No other adverse effects on reproduction, fertility and postnatal development were observed.

  2. Discovery of the target for immunomodulatory drugs (IMiDs).

    Science.gov (United States)

    Ito, Takumi; Ando, Hideki; Handa, Hiroshi

    2016-05-01

    Half a century ago, the sedative thalidomide caused a serious drug disaster because of its teratogenicity and was withdrawn from the market. However, thalidomide, which has returned to the market, is now used for the treatment of leprosy and multiple myeloma (MM) under strict control. The mechanism of thalidomide action had been a long-standing question. We developed a new affinity bead technology and identified cereblon (CRBN) as a thalidomide-binding protein. We found that CRBN functions as a substrate receptor of an E3 cullin-Ring ligase complex 4 (CRL4) and is a primary target of thalidomide teratogenicity. Recently, new thalidomide derivatives, called immunomodulatory drugs (IMiDs), have been developed by Celgene. Among them, lenalidomide (Len) and pomalidomide (Pom) were shown to exert strong therapeutic effects against MM. It was found that Len and Pom both bind CRBN-CRL4 and recruit neomorphic substrates (Ikaros and Aiolos). More recently it was reported that casein kinase 1a (Ck1a) was identified as a substrate for CRBN-CRL4 in the presence of Len, but not Pom. Ck1a breakdown explains why Len is specifically effective for myelodysplastic syndrome with 5q deletion. It is now proposed that binding of IMiDs to CRBN appears to alter the substrate specificity of CRBN-CRL4. In this review, we introduce recent findings on IMiDs.

  3. Approach to Investigating Congenital Skeletal Abnormalities in Livestock.

    Science.gov (United States)

    Dittmer, K E; Thompson, K G

    2015-09-01

    Congenital skeletal abnormalities may be genetic, teratogenic, or nutritional in origin; distinguishing among these different causes is essential in the management of the disease but may be challenging. In some cases, teratogenic or nutritional causes of skeletal abnormalities may appear very similar to genetic causes. For example, chondrodysplasia associated with intrauterine zinc or manganese deficiency and mild forms of hereditary chondrodysplasia have very similar clinical features and histologic lesions. Therefore, historical data are essential in any attempt to distinguish genetic and acquired causes of skeletal lesions; as many animals as possible should be examined; and samples should be collected for future analysis, such as genetic testing. Acquired causes of defects often show substantial variation in presentation and may improve with time, while genetic causes frequently have a consistent presentation. If a disease is determined to be of genetic origin, a number of approaches may be used to detect mutations, each with advantages and disadvantages. These approaches include sequencing candidate genes, single-nucleotide polymorphism array with genomewide association studies, and exome or whole genome sequencing. Despite advances in technology and increased cost-effectiveness of these techniques, a good clinical history and description of the pathology and a reliable diagnosis are still key components of any investigation. © The Author(s) 2015.

  4. Multiple effects of pentyl-4-yn-VPA enantiomers: from toxicity to short-term memory enhancement

    DEFF Research Database (Denmark)

    Gotfryd, Kamil; Owczarek, Sylwia; Hoffmann, Katrin

    2006-01-01

    and migration, neuronal differentiation and survival, intracellular signal transduction, synaptic plasticity and maturation, and short-term memory as determined by the social recognition test. The results show that the enantiomers of PE-4-yn-VPA largely had similar effects in vitro. However, in all in vitro......-differentiating properties. Moreover, the less teratogenic enantiomer, R-PE-4-yn-VPA, was recently shown to improve learning and memory. We here present a detailed investigation of the enantioselective properties of PE-4-yn-VPA using a range of in vitro and in vivo assays including measurements of cellular growth...... experiments the more teratogenic enantiomer, S-PE-4-yn-VPA, exhibited a stronger potency than R-PE-4-yn-VPA, and only S-PE-4-yn-VPA had a detrimental effect on cell survival. Interestingly, both the R- and S-enantiomer improved learning and memory. In contrast, the beneficial effect of S-PE-4-yn-VPA on memory...

  5. The role of diclofenack on inducing of aplasia cutis congenita: a case report.

    Science.gov (United States)

    Pajaziti, Laura; Rexhepi, Syzana; Shatri-Muça, Ylfete; Ferizi, Mybera

    2009-10-12

    Aplasia cutis congenita is a disorder where e newborn child is missing skin from certain areas. It is a rare condition with no particular race or sex more at risk. May occur by itself or be associated with other physical syndromes or disorders. A classification system exists for aplasia cutis congenital consisting of 9 groups, based on the number and location of the skin defects and the presence or absence of other malformations. Causes of aplasia congenital could be heredity, teratogenic substances, placental infarcts, intrauterine infections, ectodermal dysplasias etc. Diagnosis is made based on the clinical findings. Prognosis depends of the other organs malfunction level and lesions size. Our case was an 22 months old Albanian girl, who was recommended to dermatology for a consultation by a pediatric surgeon because of the changes she had on her parietal part of the scalp with missing hair areas. The child has stenosis congenita ani and to her was installed stoma. In order to investigate other accompanied anomalies of the disease, there are made specific consults by neurologist, orthopedist, cardiologist, nephrologists and citogenetics. It was found out a minor visual discoordination, Sy Floppy, Digiti V superductus pedis bill. Laxitas articularum generalisata. It was a great challenge for us to find out that during the first trimester of the pregnancy (unplanned pregnancy), her mother used Diclofenac. Since there is limited information regarding to teratogenic effects of diclofenac, we considered it interesting to present this case.

  6. Phytol in a pharma-medico-stance.

    Science.gov (United States)

    Islam, Md Torequl; de Alencar, Marcus Vinícius Oliveira Barros; da Conceição Machado, Katia; da Conceição Machado, Keylla; de Carvalho Melo-Cavalcante, Ana Amélia; de Sousa, Damiao Pergentino; de Freitas, Rivelilson Mendes

    2015-10-05

    This study aims to review phytol (PYT), through published articles, periodicals, magazines and patents, which were retrieved from the PM, SD, WS, SP; DII, WIPO, CIPO, USPTO and INPI databases. Among the 149 articles and 62 patents, 27.52% articles and 87.09% patients were found on the searched topic, PYT and its sources and synthesis and metabolism; then followed by 15.44% and 14.77% articles on PYT in cytotoxicity/cancer/mutagenicity/teratogenicity and PYT in neurological diseases, respectively. In the pharma-medico viewpoint, PYT and its derivatives have been evident to have antimicrobial, cytotoxic, antitumorous, antimutagenic, anti-teratogenic, antibiotic-chemotherapeutic, antidiabetic, lipid lowering, antispasmodic, anticonvulsant, antinociceptive, antioxidant, anti-inflammatory, anxiolytic, antidepressant, immunoadjuvancy, hair growth facilitator, hair fall defense and antidandruff activities. Otherwise, the important biometebolite of PYT is phytanic acid (PA). Evidence shows PA to have cytotoxic, anticancer, antidiabetic, lipid lowering and aniteratogenic activities. In addition, it may be considered as an important biomarker for some diseases such as Refsum's Disease (RD), Sjögren Larsson syndrome (SLS), rhizomelic chondrodysplasia punctata (RZCP), chronic polyneuropathy (CP), Zellweger's disease hyperpipecolic academia (ZDHA) and related diseases. Thus, phytol may be considered as a new drug candidate. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Epilepsy during pregnancy: focus on management strategies

    Directory of Open Access Journals (Sweden)

    Borgelt LM

    2016-09-01

    Full Text Available Laura M Borgelt,1 Felecia M Hart,2 Jacquelyn L Bainbridge2 1Departments of Clinical Pharmacy and Family Medicine, 2Departments of Clinical Pharmacy and Neurology, University of Colorado Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA Abstract: In the US, more than one million women with epilepsy are of childbearing age and have over 20,000 babies each year. Patients with epilepsy who become pregnant are at risk of complications, including changes in seizure frequency, maternal morbidity and mortality, and congenital anomalies due to antiepileptic drug exposure. Appropriate management of epilepsy during pregnancy may involve frequent monitoring of antiepileptic drug serum concentrations, potential preconception switching of antiepileptic medications, making dose adjustments, minimizing peak drug concentration with more frequent dosing, and avoiding potentially teratogenic medications. Ideally, preconception planning will be done to minimize risks to both the mother and fetus during pregnancy. It is important to recognize benefits and risks of current and emerging therapies, especially with revised pregnancy labeling in prescription drug product information. This review will outline risks for epilepsy during pregnancy, review various recommendations from leading organizations, and provide an evidence-based approach for managing patients with epilepsy before, during, and after pregnancy. Keywords: epilepsy, teratogens, anticonvulsants, medication therapy management

  8. [Influence of valproic acid (depakine I.V.) on human placenta metabolism--experimental model].

    Science.gov (United States)

    Semczuk-Sikora, Anna; Rogowska, Wanda; Semczuk, Marian

    2003-08-01

    The pregnancy in women with epilepsy is associated with an increased incidence of congenital malformations in offspring. Currently, anti-epileptic drugs (AEDs) are concerned to be a major etiologic factor of abnormal fetal development but the pathomechanism of teratogenicity of AEDs is complex and not well understood. The purpose of this study was to evaluate an influence of one of the AED-valproic acid (VPA) on placental metabolism (glucose consumption and lactate production). Term human placental cotyledons were perfused in vitro using a recycling perfusion of maternal and fetal circulations. A total 18 placentas were perfused either with 75 micrograms/ml of VPA (therapeutic dose) or with 225 micrograms/ml of VPA (toxic dose). Eight placentas were perfused with a medium without VPA and served as controls. During 2.5 h of experiment, both maternal and fetal glucose consumption and lactate production were measured every 30 minutes. The introduction of different concentrations of VPA into the perfusion system did not effect placental glucose consumption and lactate production rates in both maternal and fetal compartments. The teratogenic effect of valproic acid is not associated with metabolic disturbances of glucose or lactate in the placental tissue.

  9. Fetal and juvenile radiotoxicity

    International Nuclear Information System (INIS)

    Sikov, M.R.

    1985-01-01

    This project is directed at obtaining detailed comparative information on the deposition, distribution, retention, and toxicity of radionuclides in the prenatal and juvenile mammal. Because quantitative data cannot necessarily be extrapolated to man, emphasis is also directed toward establishing patterns, phenomenologic interactions, and relationships which will be useful in determining appropriate exposure levels for rapidly growing infants or children and for pregnant women. Further dosimetry for an experiment to evaluate the effects of foster-rearing of newborn rats on the lifetime effects of 239 Pu exposure has demonstrated that most of the lifetime burden is derived from prenatal exposure and that milk contributes little in addition. Other measurements have confirmed a tentative observation that the lifetime burden in offspring is greater with near-term exposure than with exposure earlier in gestation. Additional results from a comparison of the embryotoxicity of 239 Pu and 241 Am have confirmed that, on the basis of dose administered to the dam, the former has a greater effect on the conceptus. Pilot studies indicate that 233 U is teratogenic, acting as a chemical rather than as a radiological teratogen. Studies with 239 Pu-exposed pregnant rabbits have shown that maternal distribution differs from that in rodents; concentration patterns in the placenta and membranes also differed. 4 figures, 1 table

  10. Prenatal choline supplementation mitigates behavioral alterations associated with prenatal alcohol exposure in rats.

    Science.gov (United States)

    Thomas, Jennifer D; Idrus, Nirelia M; Monk, Bradley R; Dominguez, Hector D

    2010-10-01

    Prenatal alcohol exposure can alter physical and behavioral development, leading to a range of fetal alcohol spectrum disorders. Despite warning labels, pregnant women continue to drink alcohol, creating a need to identify effective interventions to reduce the severity of alcohol's teratogenic effects. Choline is an essential nutrient that influences brain and behavioral development. Recent studies indicate that choline supplementation can reduce the teratogenic effects of developmental alcohol exposure. The present study examined whether choline supplementation during prenatal ethanol treatment could mitigate the adverse effects of ethanol on behavioral development. Pregnant Sprague-Dawley rats were intubated with 6 g/kg/day ethanol in a binge-like manner from gestational days 5-20; pair-fed and ad libitum chow controls were included. During treatment, subjects from each group were intubated with either 250 mg/kg/day choline chloride or vehicle. Spontaneous alternation, parallel bar motor coordination, Morris water maze, and spatial working memory were assessed in male and female offspring. Subjects prenatally exposed to alcohol exhibited delayed development of spontaneous alternation behavior and deficits on the working memory version of the Morris water maze during adulthood, effects that were mitigated with prenatal choline supplementation. Neither alcohol nor choline influenced performance on the motor coordination task. These data indicate that choline supplementation during prenatal alcohol exposure may reduce the severity of fetal alcohol effects, particularly on alterations in tasks that require behavioral flexibility. These findings have important implications for children of women who drink alcohol during pregnancy. © 2010 Wiley-Liss, Inc.

  11. A comparative review of the isotretinoin pregnancy risk management programs across four continents.

    Science.gov (United States)

    Kovitwanichkanont, Tom; Driscoll, Tim

    2018-03-06

    Isotretinoin has revolutionized the treatment of severe acne vulgaris, a condition which if left untreated may result in significant socio-psychological implications for those affected. Timely access to isotretinoin therapy is important to avoid the risks of potential physical and emotional scarring. However, due to its high risks of teratogenicity, isotretinoin must be used with care in females of childbearing potential. Since isotretinoin's introduction, numerous risk management programs have been implemented across the world in an attempt to prevent isotretinoin use in pregnancy. This paper aims to provide an evidence-based review of the risk management programs for isotretinoin in Australia, Europe, Singapore, New Zealand, and the United States of America. The effectiveness of these programs and the factors leading to isotretinoin exposure in pregnancy are critically analyzed in an effort to inform the future direction with respect to designing the ideal regulatory program. Stringent risk management programs, such as the iPLEDGE in the US and Pregnancy Prevention Program (PPP) in Europe, may not be effective in reducing the risks of fetal exposure to isotretinoin when used alone. There is evidence that such strenuous regulation results in increased fear of teratogenic risks but does not translate into a reduced rate of pregnancies exposed to isotretinoin. A successful program must prioritize education about effective contraception, while minimizing any extraneous requirements, to ensure that women are not inadvertently undertreated for acne. © 2018 The International Society of Dermatology.

  12. Association between risk of birth defects occurring level and arsenic concentrations in soils of Lvliang, Shanxi province of China

    International Nuclear Information System (INIS)

    Wu, Jilei; Zhang, Chaosheng; Pei, Lijun; Chen, Gong; Zheng, Xiaoying

    2014-01-01

    The risk of birth defects is generally accredited with genetic factors, environmental causes, but the contribution of environmental factors to birth defects is still inconclusive. With the hypothesis of associations of geochemical features distribution and birth defects risk, we collected birth records and measured the chemical components in soil samples from a high prevalence area of birth defects in Shanxi province, China. The relative risk levels among villages were estimated with conditional spatial autoregressive model and the relationships between the risk levels of the villages and the 15 types of chemical elements concentration in the cropland and woodland soils were explored. The results revealed that the arsenic levels in cropland soil showed a significant association with birth defects occurring risk in this area, which is consistent with existing evidences of arsenic as a teratogen and warrants further investigation on arsenic exposure routine to birth defect occurring risk. - Highlights: • Association between soil geochemical components and birth defects risk was proposed. • The relative risk difference among villages were estimated with CAR model. • Arsenic levels in cropland showed a significant association to birth defect risk. • The finding warrants further investigation on arsenic as a teratogen. - The difference of risk levels estimate by spatial statistics to birth defect significantly associated with arsenic levels in cropland soils warrants further investigation

  13. Pyruvate remediation of cell stress and genotoxicity induced by haloacetic acid drinking water disinfection by-products.

    Science.gov (United States)

    Dad, Azra; Jeong, Clara H; Pals, Justin A; Wagner, Elizabeth D; Plewa, Michael J

    2013-10-01

    Monohaloacetic acids (monoHAAs) are a major class of drinking water disinfection by-products (DBPs) and are cytotoxic, genotoxic, mutagenic, and teratogenic. We propose a model of toxic action based on monoHAA-mediated inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a target cytosolic enzyme. This model predicts that GAPDH inhibition by the monoHAAs will lead to a severe reduction of cellular ATP levels and repress the generation of pyruvate. A loss of pyruvate will lead to mitochondrial stress and genomic DNA damage. We found a concentration-dependent reduction of ATP in Chinese hamster ovary cells after monoHAA treatment. ATP reduction per pmol monoHAA followed the pattern of iodoacetic acid (IAA) > bromoacetic acid (BAA) > chloroacetic acid (CAA), which is the pattern of potency observed with many toxicological endpoints. Exogenous supplementation with pyruvate enhanced ATP levels and attenuated monoHAA-induced genomic DNA damage as measured with single cell gel electrophoresis. These data were highly correlated with the SN 2 alkylating potentials of the monoHAAs and with the induction of toxicity. The results from this study strongly support the hypothesis that GAPDH inhibition and the possible subsequent generation of reactive oxygen species is linked with the cytotoxicity, genotoxicity, teratogenicity, and neurotoxicity of these DBPs. Copyright © 2013 Wiley Periodicals, Inc.

  14. The role of the open-quotes stress protein responseclose quotes in hormesis

    International Nuclear Information System (INIS)

    Smith-Sonneborn, J.

    1992-01-01

    Hormesis refers to the phenomenon of induction of beneficial effects by low doses of otherwise harmful physical or chemical agents: 'a little bit of bad can be good for you.' That the hormetic response may operate by a common mechanism has already been proposed, but this review is the first to propose the hypothesis that the common pathway is a heat shock-like response. The heat shock response is a model for a more general phenomenon, called the stress response. The stress response is characterized by increased synthesis of a family of stressor specific proteins with concomitant reduction of synthesis of most of the proteins transcribed prior to the exposure to the toxic agent. The stress response has been characterized using heat, radiation, heavy metals, and oxidizing agents as the stressors. This chapter includes: Identification of agents known to induce both the stress response and hormetic phenomena; A description of the unique and common pathways in the stress response to three stressors - heat, DNA-damaging agents, and teratogens; The stress response as a model for teratogen-induced damage; A theory explaining the paradoxical beneficial response to low doses of an otherwise harmful agent via a stress-response pathway

  15. Aggregation patterns of fetal rat brain cells following exposure to X-irradiation

    International Nuclear Information System (INIS)

    Shoji, R.; Suzuki, K.; Lee, I.P.

    1980-01-01

    In our search for a simplified in vitro test system to assess the teratogenic effects of physical factors, we studied the effects of total maternal body X-irradiation on aggregation patterns of enzymatically isolated fetal rat brain cells and on ultrastructural aggregate changes. The fetal brain cells were derived from day 14 gestation fetuses of pregnant Sprague-Dawley (CD strain) rats exposed to X-irradiation (25 - 200 R) one hour prior to sacrifice. Notable changes in the cell aggregates following X-irradiation included a reduction in cell aggregate size and an increase in number. The frequency of cell aggregates was higher in the treated than in the control group, and the mean diameter of cell aggregates was inversely related to increasing X-irradiation doses. Transmission electron microscopy revealed in isolated cells features of degenerative process which were similar to those found in intact fetal brain lesions caused by maternal X-irradiation. Furthermore, scanning electron microscopy revealed that inhibition of cell aggregation following X-irradiation could probably be attributed to inhibition of membrane filopodia development and a consequent failure of cell aggregates to fuse into a greater cell aggregate mass. These results suggest that the membrane factors which influence cell aggregation may be a useful parameter to assess early effects of X-irradiation-induced brain deformity. Presently, the cell aggregation culture system is being further evaluated as a short term test system for environmental teratogens

  16. KEAMANAN STEVIA HASIL BUDIDAYA B2P2TO2T DALAM ASPEK TERATOGENITAS

    Directory of Open Access Journals (Sweden)

    Lucie Widowati

    2012-07-01

    Full Text Available Teratogenic test has been performed on sweet stevia as product of B2P2TO2T cultivation at  rats (Rattus novergicus pregnant female  Wistar. Stevia sweet was administered orally at a dose of 360, 120 and 40 mg/kg bw, volume 1 ml/100g bw per day during organogenesis period, on the day of pregnancy to the 6th until 15th. During the test, test animals were observed two times daily with the distance of six hours against the toxicity symptoms such as changes in skin, hair, eyes and mucous membranes, bleeding. Animals that experienced abortion, premature birth or death during the trial period were sacrificed and observed immediately with microscopic technic. At 20th day of pregnancy all of the pregnant rat dissected, and put out the fetuses  from the mother's and observated the health conditions in general and  the whole of mothers reproductive systems of fetuses, the outer fetal malformation and soft tissue system of fetal. The conclusion were  sweet stevia  of B2P2TO2T  no worse effect on the mother rats, fetal body weight and morphology of mother rats and the fetus, does not affect the process of development of fetal soft tissue, and does not affect the development of fetal skeleton. Generally the B2P2TO2T stevia sweet substances safe for used, does not cause teratogenic effects.

  17. Concern over Zika virus outbreak: another alarming global threat

    Directory of Open Access Journals (Sweden)

    Hafiz MY

    2016-06-01

    Full Text Available Muhammad Yusuf Hafiz,1 Syed Uzair Mahmood,2 Maria Shoaib,1 Farah Hafiz Yusuf1 1Dow Medical College, Dow University of Health Sciences, 2Sindh Medical College, Jinnah Sindh Medical University, Karachi, Pakistan Abstract: Zika virus, as highlighted by the World Health Organization in February 2016, has emerged as a public health emergency of international concern. Zika virus is enveloped and icosahedral, and has a nonsegmented, single-stranded, positive-sense RNA genome. It belongs to Flaviviridae family. Aedes aegypticus mosquito is the known vector. Transmission is anthroponotic (human to vector to human during outbreaks, or occurs perinatally in utero, sexually, and via transfusion of infected blood. Zika virus is turning out to be a major public health concern. Not only has it shown dramatic teratogenic association and caused serious neurological concerns but it has also spread around the globe. Countries that have not yet been affected by Zika virus should adopt proper preventive methods to limit its spread in the population. Keywords: Zika virus, global spread, teratogenic, neurological anomalies, public health emergency

  18. Does maternal exposure to benzene and PM10 during pregnancy increase the risk of congenital anomalies? A population-based case-control study

    Science.gov (United States)

    Vinceti, Marco; Malagoli, Carlotta; Malavolti, Marcella; Cherubini, Andrea; Maffeis, Giuseppe; Rodolfi, Rossella; Heck, Julia E.; Astolfi, Gianni; Calzolari, Elisa; Nicolini, Fausto

    2015-01-01

    A few studies have suggested an association between maternal exposure to ambient air pollution from vehicular traffic and risk of congenital anomalies in the offspring, but epidemiologic evidence is neither strong nor entirely consistent. In a population-based case-control study in a Northern Italy community encompassing 228 cases of birth defects and 228 referent newborns, we investigated if maternal exposure to PM10 and benzene from vehicular traffic during early pregnancy, as estimated through a dispersion model, was associated with excess teratogenic risk. In conditional logistic regression analysis, and with adjustment for the other pollutant, we found that higher exposure to PM10 but not benzene was associated with increased risk of birth defects overall. Anomaly categories showing the strongest dose-response relation with PM10 exposure were musculoskeletal and chromosomal abnormalities but not cardiovascular defects, with Down syndrome being among the specific abnormalities showing the strongest association, though risk estimates particularly for the less frequent defects were statistically very unstable. Further adjustment in the regression model for potential confounders did not considerably alter the results. All the associations were stronger for average levels of PM10 than for their maximal level. Findings of this study give some support for an excess teratogenic risk following maternal exposure during pregnancy to PM10, but not benzene. Such association appears to be limited to some birth defect categories. PMID:26410719

  19. Retinaldehyde dehydrogenase 2 as a molecular adjuvant for enhancement of mucosal immunity during DNA vaccination.

    Science.gov (United States)

    Holechek, Susan A; McAfee, Megan S; Nieves, Lizbeth M; Guzman, Vanessa P; Manhas, Kavita; Fouts, Timothy; Bagley, Kenneth; Blattman, Joseph N

    2016-11-04

    In order for vaccines to induce efficacious immune responses against mucosally transmitted pathogens, such as HIV-1, activated lymphocytes must efficiently migrate to and enter targeted mucosal sites. We have previously shown that all-trans retinoic acid (ATRA) can be used as a vaccine adjuvant to enhance mucosal CD8 + T cell responses during vaccination and improve protection against mucosal viral challenge. However, the ATRA formulation is incompatible with most recombinant vaccines, and the teratogenic potential of ATRA at high doses limits its usage in many clinical settings. We hypothesized that increasing in vivo production of retinoic acid (RA) during vaccination with a DNA vector expressing retinaldehyde dehydrogenase 2 (RALDH2), the rate-limiting enzyme in RA biosynthesis, could similarly provide enhanced programming of mucosal homing to T cell responses while avoiding teratogenic effects. Administration of a RALDH2- expressing plasmid during immunization with a HIVgag DNA vaccine resulted in increased systemic and mucosal CD8 + T cell numbers with an increase in both effector and central memory T cells. Moreover, mice that received RALDH2 plasmid during DNA vaccination were more resistant to intravaginal challenge with a recombinant vaccinia virus expressing the same HIVgag antigen (VACVgag). Thus, RALDH2 can be used as an alternative adjuvant to ATRA during DNA vaccination leading to an increase in both systemic and mucosal T cell immunity and better protection from viral infection at mucosal sites. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Accumulation of polyunsaturated aldehydes in the gonads of the copepod Acartia tonsa revealed by tailored fluorescent probes.

    Science.gov (United States)

    Wolfram, Stefanie; Nejstgaard, Jens C; Pohnert, Georg

    2014-01-01

    Polyunsaturated aldehydes (PUAs) are released by several diatom species during predation. Besides other attributed activities, these oxylipins can interfere with the reproduction of copepods, important predators of diatoms. While intensive research has been carried out to document the effects of PUAs on copepod reproduction, little is known about the underlying mechanistic aspects of PUA action. Especially PUA uptake and accumulation in copepods has not been addressed to date. To investigate how PUAs are taken up and interfere with the reproduction in copepods we developed a fluorescent probe containing the α,β,γ,δ-unsaturated aldehyde structure element that is essential for the activity of PUAs as well as a set of control probes. We developed incubation and monitoring procedures for adult females of the calanoid copepod Acartia tonsa and show that the PUA derived fluorescent molecular probe selectively accumulates in the gonads of this copepod. In contrast, a saturated aldehyde derived probe of an inactive parent molecule was enriched in the lipid sac. This leads to a model for PUAs' teratogenic mode of action involving accumulation and covalent interaction with nucleophilic moieties in the copepod reproductive tissue. The teratogenic effect of PUAs can therefore be explained by a selective targeting of the molecules into the reproductive tissue of the herbivores, while more lipophilic but otherwise strongly related structures end up in lipid bodies.

  1. Accumulation of polyunsaturated aldehydes in the gonads of the copepod Acartia tonsa revealed by tailored fluorescent probes.

    Directory of Open Access Journals (Sweden)

    Stefanie Wolfram

    Full Text Available Polyunsaturated aldehydes (PUAs are released by several diatom species during predation. Besides other attributed activities, these oxylipins can interfere with the reproduction of copepods, important predators of diatoms. While intensive research has been carried out to document the effects of PUAs on copepod reproduction, little is known about the underlying mechanistic aspects of PUA action. Especially PUA uptake and accumulation in copepods has not been addressed to date. To investigate how PUAs are taken up and interfere with the reproduction in copepods we developed a fluorescent probe containing the α,β,γ,δ-unsaturated aldehyde structure element that is essential for the activity of PUAs as well as a set of control probes. We developed incubation and monitoring procedures for adult females of the calanoid copepod Acartia tonsa and show that the PUA derived fluorescent molecular probe selectively accumulates in the gonads of this copepod. In contrast, a saturated aldehyde derived probe of an inactive parent molecule was enriched in the lipid sac. This leads to a model for PUAs' teratogenic mode of action involving accumulation and covalent interaction with nucleophilic moieties in the copepod reproductive tissue. The teratogenic effect of PUAs can therefore be explained by a selective targeting of the molecules into the reproductive tissue of the herbivores, while more lipophilic but otherwise strongly related structures end up in lipid bodies.

  2. Radioprotection effects of TMG to radical scavenger effect of the mice in radiation

    International Nuclear Information System (INIS)

    Gu, Yeunhwa; Hasegawa, Takeo; Oshima, Masami

    2002-01-01

    Now there is many it, and the radiotherapy that is one of cancer therapy is used by single or anticancer drug and combination. A chemical material has been used as radioprotector, but the use is limited conventionally by a serious side effect. Vitamin E derivative[TMG 2- (α - D-Glucopyranosyl) Methyl-2,5,7,8-Teramethyl -chorman-6-OL] which we are water-soluble, And is the nature material as well for the fetal teratogenicity that I use ICR mouse used for a malformed experiment frequently in this study, and sensibility for radiation is the highest, we studied radiation protection effect of TMG. As a result, as for the fetal malformed incidence, it was admitted that it fell in shifts and changes by administering TMG before radiation exposure. Decrease depression of degradation of a skeletal malformation rate in particular and fetal weight was recognized, and an individual level made radiation protection indication of TMG clear. In addition, that there was radioprotection effect for embryonic death by radiation was made clear by premedication doing TMG equally, and that there was protection effect for radiation exposure in a cell level same as an individual level was proved, and TMG showed the potency that it was it in radioprotector promising in the future. Furthermore, by what we reviewed about congenital defect for radiation, effect for skeletal malformation incidence and sensibility of embryonic cell level in organogenesis, we analyzed mechanism of protection effect of TMG for fetal teratogenicity by radiation experimentally

  3. Radioprotection effects of TMG to radical scavenger effect of the mice in radiation

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Yeunhwa; Hasegawa, Takeo; Oshima, Masami [Suzuka Univ. of Medical Science, Suzuka (Japan)] [and others

    2002-07-01

    Now there is many it, and the radiotherapy that is one of cancer therapy is used by single or anticancer drug and combination. A chemical material has been used as radioprotector, but the use is limited conventionally by a serious side effect. Vitamin E derivative[TMG 2- ({alpha} - D-Glucopyranosyl) Methyl-2,5,7,8-Teramethyl -chorman-6-OL] which we are water-soluble, And is the nature material as well for the fetal teratogenicity that I use ICR mouse used for a malformed experiment frequently in this study, and sensibility for radiation is the highest, we studied radiation protection effect of TMG. As a result, as for the fetal malformed incidence, it was admitted that it fell in shifts and changes by administering TMG before radiation exposure. Decrease depression of degradation of a skeletal malformation rate in particular and fetal weight was recognized, and an individual level made radiation protection indication of TMG clear. In addition, that there was radioprotection effect for embryonic death by radiation was made clear by premedication doing TMG equally, and that there was protection effect for radiation exposure in a cell level same as an individual level was proved, and TMG showed the potency that it was it in radioprotector promising in the future. Furthermore, by what we reviewed about congenital defect for radiation, effect for skeletal malformation incidence and sensibility of embryonic cell level in organogenesis, we analyzed mechanism of protection effect of TMG for fetal teratogenicity by radiation experimentally.

  4. Developmental exposure to fenproporex: reproductive and morphological evaluation.

    Science.gov (United States)

    Moreira, C Q; Faria, M J S S; Baroneza, J E; Oliveira, R J; Moreira, E G

    2005-08-01

    This study was designed to evaluate the maternal toxicity and teratogenicity of fenproporex, one of the most widely-used anorectic drugs in many countries, including Brazil. Three periods of exposure were evaluated: (a) 30 days before mating; (b) from gestational day (GD) 0 to 14; and (c) 30 days before mating and during pregnancy, until GD 14. Female mice from experimental groups received, by gavage, 15 mg/kg of fenproporex. Treatment with fenproporex increased ambulation of dams in the open-field test and did not influence the mobility in the forced-swimming test. There was no significant difference in maternal weight gain between the controls and fenproporex-treated groups, although fenproporex treatment reduced the gravid uterus weight. No significant difference was observed in postimplantation loss, fetal viability and sex ratio. In addition, this compound did not impair intra-uterine growth. The reduction in the number of implantations in the groups receiving fenproporex indicates that this drug may have an adverse effect on implantation. Fenproporex treatment also increased the number of fetuses presenting small kidneys and cervical ribs. The present results indicate that fenproporex, in the dose and exposure periods tested, appears to exhibit a low maternal toxicity and teratogenic potential in mice.

  5. Experimental methods in behavioral teratology

    Energy Technology Data Exchange (ETDEWEB)

    Zbinden, G.

    1981-09-01

    Efforts are made to develop toxicological techniques with which new behavioral teratogens can be recognized. The review describes the most important experimental methods which are presently explored, and which are based on a rich body of knowledge accumulated by experimental psychologists. Most of the tests were developed with small animals, mostly with rats. They range from the rather straightforward determination of various reflexes to complex behavioral situations involving mechanical devices, operant conditioning techniques and procedures evaluating social behavior. In applying these methods in routine toxicology, it is important to remember, that many behavioral effects determined in newborn and adult animals are subtle. Moreover, they are influenced by a large variety of environmental factors affecting the health and the behavior of the mothers and of the offspring in the early and later phases of development. Therefore, the experiments must be conducted under highly standardized conditions and must be controlled rigorously. It is concluded that the best experimental strategy for the evaluation of potential behavioral teratogens is not yet established. Therefore, it would be premature to decide on a fixed protocol to be included in routine animal safety experiments for drugs and other chemical substances.

  6. Russian Register of Pregnancy and Epilepsy

    Directory of Open Access Journals (Sweden)

    D. V. Dmitrenko

    2017-01-01

    Full Text Available The use of antiepileptic drugs (AEDs during pregnancy is associated with an increased risk of congenital malformations (CMF. Information on the teratogenicity of AEDs is contradictory. The potential negative effects of new-generation AEDs are less well known. Many physicians and patients face difficulties in establishing a balance between the risk of seizures during pregnancy and that of teratogenicity in the use of AEDs. In most foreign countries, there are national and international pregnancy and epilepsy registries that make possible to centralize and systematize information on the safety of AEDs and to also give a true picture of the state of the problem.The Russian pregnancy and epilepsy register (RPER has been launched since 2017. RPER is a Russian national prospective and retrospective observational study, without interfering with the antiepileptic therapy prescribed by an attending physician to childbearing-aged patients living in the subjects of the Russian Federation. RPER is an independent research initiative and is implemented by neurologists and psychiatrists who provide assistance to women with epilepsy. The main goal of the RPER is to compare the risk of serious CMFs following the maternal intake of various AEDs and their combinations in different regions of the Russian Federation and to develop strategies for preventing CMFs. 

  7. Metabolic profiles of pomalidomide in human plasma simulated with pharmacokinetic data in control and humanized-liver mice.

    Science.gov (United States)

    Shimizu, Makiko; Suemizu, Hiroshi; Mitsui, Marina; Shibata, Norio; Guengerich, F Peter; Yamazaki, Hiroshi

    2017-10-01

    1. Pomalidomide has been shown to be potentially teratogenic in thalidomide-sensitive animal species such as rabbits. Screening for thalidomide analogs devoid of teratogenicity/toxicity - attributable to metabolites formed by cytochrome P450 enzymes - but having immunomodulatory properties is a strategic pathway towards development of new anticancer drugs. 2. In this study, plasma concentrations of pomalidomide, its primary 5-hydroxylated metabolite, and its glucuronide conjugate(s) were investigated in control and humanized-liver mice. Following oral administration of pomalidomide (100 mg/kg), plasma concentrations of 7-hydroxypomalidomide and 5-hydroxypomalidomide glucuronide were slightly higher in humanized-liver mice than in control mice. 3. Simulations of human plasma concentrations of pomalidomide were achieved with simplified physiologically-based pharmacokinetic models in both groups of mice in accordance with reported pomalidomide concentrations after low dose administration in humans. 4. The results indicate that pharmacokinetic profiles of pomalidomide were roughly similar between control mice and humanized-liver mice and that control and humanized-liver mice mediated pomalidomide 5-hydroxylation in vivo. Introducing one aromatic amino group into thalidomide resulted in less species differences in in vivo pharmacokinetics in control and humanized-liver mice.

  8. A scale out approach towards neural induction of human induced pluripotent stem cells for neurodevelopmental toxicity studies.

    Science.gov (United States)

    Miranda, Cláudia C; Fernandes, Tiago G; Pinto, Sandra N; Prieto, Manuel; Diogo, M Margarida; Cabral, Joaquim M S

    2018-05-21

    Stem cell's unique properties confer them a multitude of potential applications in the fields of cellular therapy, disease modelling and drug screening fields. In particular, the ability to differentiate neural progenitors (NP) from human induced pluripotent stem cells (hiPSCs) using chemically-defined conditions provides an opportunity to create a simple and straightforward culture platform for application in these fields. Here, we demonstrated that hiPSCs are capable of undergoing neural commitment inside microwells, forming characteristic neural structures resembling neural rosettes and further give rise to glial and neuronal cells. Furthermore, this platform can be applied towards the study of the effect of neurotoxic molecules that impair normal embryonic development. As a proof of concept, the neural teratogenic potential of the antiepileptic drug valproic acid (VPA) was analyzed. It was verified that exposure to VPA, close to typical dosage values (0.3 to 0.75 mM), led to a prevalence of NP structures over neuronal differentiation, as confirmed by analysis of the expression of neural cell adhesion molecule, as well as neural rosette number and morphology assessment. The methodology proposed herein for the generation and neural differentiation of hiPSC aggregates can potentially complement current toxicity tests such as the humanized embryonic stem cell test for the detection of teratogenic compounds that can interfere with normal embryonic development. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Chronic toxicology of cannabis.

    Science.gov (United States)

    Reece, Albert Stuart

    2009-07-01

    Cannabis is the most widely used illicit drug worldwide. As societies reconsider the legal status of cannabis, policy makers and clinicians require sound knowledge of the acute and chronic effects of cannabis. This review focuses on the latter. A systematic review of Medline, PubMed, PsychInfo, and Google Scholar using the search terms "cannabis," "marijuana," "marihuana," "toxicity," "complications," and "mechanisms" identified 5,198 papers. This list was screened by hand, and papers describing mechanisms and those published in more recent years were chosen preferentially for inclusion in this review. There is evidence of psychiatric, respiratory, cardiovascular, and bone toxicity associated with chronic cannabis use. Cannabis has now been implicated in the etiology of many major long-term psychiatric conditions including depression, anxiety, psychosis, bipolar disorder, and an amotivational state. Respiratory conditions linked with cannabis include reduced lung density, lung cysts, and chronic bronchitis. Cannabis has been linked in a dose-dependent manner with elevated rates of myocardial infarction and cardiac arrythmias. It is known to affect bone metabolism and also has teratogenic effects on the developing brain following perinatal exposure. Cannabis has been linked to cancers at eight sites, including children after in utero maternal exposure, and multiple molecular pathways to oncogenesis exist. Chronic cannabis use is associated with psychiatric, respiratory, cardiovascular, and bone effects. It also has oncogenic, teratogenic, and mutagenic effects all of which depend upon dose and duration of use.

  10. Effects of white phosphorus on mallard reproduction

    Science.gov (United States)

    Vann, S.I.; Sparling, D.W.; Ottinger, M.A.

    2000-01-01

    Extensive waterfowl mortality involving thousands of ducks, geese, and swans has occurred annually at Eagle River Flats, Alaska since at least 1982. The primary agent for this mortality has been identified as white phosphorus. Although acute and subacute lethality have been described, sublethal effects are less well known. This study reports on the effects of white phosphorus on reproductive function in the mallard (Anas platyrhynchos) in captivity. Fertility, hatching success, teratogenicity, and egg laying frequency were examined in 70 adult female mallards who received up to 7 daily doses of 0, 0.5, 1.0, and 2.0 mg/kg of white phosphorus. Measurements of fertility and hatchability were reduced by the white phosphorus. Teratogenic effects were observed in embryos from hens dosed at all treatment levels. Egg laying frequency was reduced even at the lowest treatment level; treated hens required a greater number of days to lay a clutch of 12 eggs than control hens. After two doses at 2.0 mg/kg, all females stopped laying completely for a minimum of 10 days and laying frequency was depressed for at least 45 days. Fertility of 10 adult male mallards dosed with 1.0 mg/kg of white phosphorus did not differ from 10 controls, but plasma testosterone levels were significantly (p free-ranging mallards may be impaired if they are exposed to white phosphorus at typical field levels.

  11. Double-blind trial of the efficacy of pentoxifylline vs thalidomide for the treatment of type II reaction in leprosy

    Directory of Open Access Journals (Sweden)

    A.M. Sales

    2007-02-01

    Full Text Available Type II reaction in leprosy, or erythema nodosum leprosum (ENL, is often characterized by severe clinical symptoms together with nerve function impairment leading to permanent disabilities. Thalidomide has been shown to be a highly effective drug for the treatment of ENL. It is, however, contraindicated for women of childbearing age due to its teratogenicity. On the other hand, pentoxifylline, used to treat hypercoagulable states, is not teratogenic and, like thalidomide, can inhibit the synthesis of tumor necrosis factor-a and other cytokines. In the present randomized double-blind clinical study we compared the effectiveness of orally administered pentoxifylline vs thalidomide in treating type II reaction in 44 patients. Daily doses of 300 mg thalidomide or 1.2 g pentoxifylline were administered for 30 days to multibacillary leprosy patients undergoing type II reaction. Randomly chosen patients were included in the study before, during, and after specific multidrug therapy. Clinical evaluations were performed on the 1st, 7th, 14th, 21st, and 30th days of treatment and laboratory tests were carried out on the 1st and 30th days. As expected, overall, thalidomide proved to be more effective in the treatment of type II leprosy reaction. Nevertheless, continuous treatment with pentoxifylline was effective in relieving the clinical signs of ENL, especially limb edema and systemic symptoms, in 62.5% of the patients.

  12. Talidomida: indicações em Dermatologia Thalidomide: indications in Dermatology

    Directory of Open Access Journals (Sweden)

    Rubem David Azulay

    2004-10-01

    Full Text Available A talidomida, descoberta na Alemanha Oriental, em 1954, mostrou vários efeitos terapêuticos: antiemético, sedativo e hipnótico. De 1959 a 1961, foram descritas cerca de 12.000 crianças nascidas com defeitos teratogênicos. Seu uso foi, conseqüentemente, suspenso. Sheskin, entretanto, recomeçou a usar a droga e verificou efeito benéfico no eritema nodoso leprótico. A talidomida é derivada do ácido glutâmico. Sua eliminação urinária é mínima (1%. Tem ações: antiinflamatória, imunomoduladora e antiangiogênica. Tem sido usada, com certo êxito terapêutico, em algumas entidades mais adiante estudadas. O principal efeito adverso é teratogênico: alterações nos membros, orelhas, olhos e órgãos internos. Supõe-se que esses efeitos teratogênicos decorram da ação antiangiogênica. Outros efeitos adversos: cefaléia, secura da pele e da mucosa da boca, prurido, erupção cutânea, aumento de peso, hipotireoidismo, neutropenia, bradicardia ou taquicardia e hipotensão. Interage com outros fármacos: barbitúrico, clorpromazina, reserpina, álcool, acetaminofen, histamina, serotonina e prostaglandina.Thalidomide was discovered in East Germany in 1954. It presented with several therapeutic effects: antiemetic, sedative and hypnotic. From 1959 to 1961, roughly 12,000 children born with teratogenic defects were described. Its use was consequently halted. Sheskin started using the drug again and observed its beneficial effect on erythema nodosa leprosum. Thalidomide is derived from glutamic acid. Its urinary elimination is minimal (1%. It has the following actions: anti-inflammatory, immunomodulary and antiangiogenic. It has been used with a successful therapeutic outcome on some entities, which have been studied further. The main side effect is teratogenic: limb alterations, ears, eyes and internal organs. The teratogenic effects are assumed to result from antiangiogenic action. Other side effects are cephalea, dry skin and mouth

  13. Assessing the Risk of Birth Defects Associated with Exposure to Fixed-Dose Combined Antituberculous Agents during Pregnancy in Rats

    Directory of Open Access Journals (Sweden)

    O. Awodele

    2012-01-01

    Full Text Available Due to the risks of disease progression and transmission to the newborn, treatment of tuberculosis is often pursued during pregnancy and fixed-dose combined antituberculous agents have been found to be beneficial. Unfortunately, there is paucity of data on the safety of the fixed-dose combined antituberculous drugs during pregnancy. This study intends to assess the teratogenic effect of fixed-dose combined antituberculous drugs on the organogenesis stage of fetal development and also investigate the possible roles of vitamin C in modulating the teratogenic effects of these agents on the fetus using animal model. Pregnant rats were divided into 3 groups with 12 animals per group: group 1 received distilled water (10 mL/kg orally; group 2 received 51.4 mg/kg/day of fixed-dose combined antituberculous agents orally; group 3 received 51.4 mg/kg/day of fixed-dose combined antituberculous agents plus vitamin C (10 mg/kg/day orally. Six rats in each group were randomly selected and sacrificed on day 20 by cervical dislocation prior to day 21 of gestation, and the foetuses were harvested through abdominal incision for physical examination. Blood samples were collected from the 1st filial rats of the remaining six animals for biochemical and hematological examination. The liver, kidney, heart, and brain of all the sacrificed animals were used for histopathological examination. There were significant (≤0.05 low birth weights of the foetuses of the animals that were treated with fixed-dose combined antituberculous agents. The haematological parameters also revealed a reduction in the platelets counts and neutrophiles at the first filial generation. Significant (≤0.05 elevations in the levels of aspartate aminotransferase (AST and alkaline phosphatase (ALP in the foetuses of the animals treated with fixed-dose combined antituberculous agents were also observed. However, the combination of vitamin C with fixed-dose combined antituberculous agents

  14. Acute toxic responses of the freshwater planarian, Dugesia dorotocephala, to methylmercury

    Energy Technology Data Exchange (ETDEWEB)

    Best, J.B.; Morita, M.; Ragin, J.; Best, J. Jr.

    1981-07-01

    Toxic responses of planaria to various aquatic habitat concentrations of methylmercury chloride (MMC) were investigated. One hundred percent lethality occurred within 5 h in 2 ppM MMC, 24 h in 1 ppM MMC, and 5 days in 0.5 ppM MMC. No deaths occurred in 0.2 ppM MMC over a 10 day period, however, non-lethal toxic responses were observed. Varying degrees of head resorption, progressing caudally from the snout were observed. With continuing exposure, partial head regeneration and recovery toward more normal appearance occurred by 10 days. Teratogenic effects were observed in surgical decapitation experiments. Head regeneration was retarded in 0.1 and 0.2 ppM MMC. Malformations, visible lesions, or gross behavioral abnormalities were produced by 2 week exposure of planaria to concentrations of 20 ppB MMC or lower. (RJC)

  15. Report of the twenty-first session, London, 18-22 February 1991

    International Nuclear Information System (INIS)

    1991-01-01

    The Joint Group of Experts on the Scientific Aspects of Marine Pollution (GESAMP) held its twenty-first session at the Headquarters of the International Maritime Organization (IMO), London, from 18 to 22 February 1991. Marine pollution is primarily linked to coastal development. The most serious problems are those associated with inadequately controlled coastal development and intensive human settlement of the coastal zone. GESAMP emphasizes the importance of the following problems and issues: State of the marine environment; comprehensive framework for the assessment and regulation of waste disposal in the marine environment; information on preparations for the United Nations Conference on Environment and Development; review of potentially harmful substances: 1. Carcinogenic substances. 2. Mutagenic substances. 3. Teratogenic substances. 4. Organochlorine compounds. 5. Oil, and other hydrocarbons including used lubricating oils, oil spill dispersants and chemicals used in offshore oil exploration and exploitation; environmental impacts of coastal aquaculture; global change and the air/sea exchange of chemicals; future work programme

  16. Potential hazards of diagnostic radiation

    Energy Technology Data Exchange (ETDEWEB)

    Houston, C S; Shokeir, M H

    1977-03-01

    There are no precise data for determining the extent of somatic damage from small doses of radiation used in diagnostic radiology. Diagnostic radiation given to pregnant women, knowingly or unknowingly, should rarely reach teratogenic levels causing brain and eye abnormalities. Evidence suggests that it does increase the risk of childhood malignancy, especially leukemia. Although rapidly growing tissues seem most susceptible, all radiation probably carries a very small risk of carcinogenesis. Genetic damage is equally difficult to estimate. Diagnostic radiation of females, even in childhood, may be related to an increased incidence of Down's syndrome in older mothers. Radiation also causes point mutations, which may explain the increase of some genetic abnormalities in progeny of older fathers. Whenever an abdominal or pelvic radiograph is ordered before the end of the reproductive period, there must be a potential benefit to balance the small risk involved.

  17. Study on modification of radiation effects in mammalian fetuses

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Kiyoto; Kawamata, Akitoshi; Goto, Toshifumi (Asahi Univ., Hozumi, Gifu (Japan). School of Dentistry) (and others)

    1990-10-01

    In searches for the potential application of mouse whole-embryo culture, combined effects of x radiation and cadmium or hyperthermia were examined with cultures of 8-day and 11-day mouse embryos. Combination of x radiation and cadmium had synergistic action on both in vitro and in vivo teratogenesis of mouse embryos. When irradiation was given 30 minutes before and after the administration of cadmium in 11-day mouse embryos, interaction factor values for cleft palate were 8.53 and 9.09, respectively. This revealed that the order of giving radiation and cadmium was independent of synergistic action. When low doses of radiation was combined with non-teratogenic hyperthermia, synergistic action occurred in vitro. This was more noticeable when combined with lower doses of x radiation. Low doses of x radiation are of great concern to human embryos or fetuses who may sustain potential exposures to them. (N.K.) 96 refs.

  18. BIFID UVULAE PREVALENCE IN ISFAHAN ELEMENTARY SCHOOL CHILDREN

    Directory of Open Access Journals (Sweden)

    M OMRANI FARD

    2000-06-01

    Full Text Available Introduction. Bifid uvulae is a silent abnormality in children which can almost exist without clinical problems but in some instances it is accompanied with either sub mucosal cleft and hypernasality.
    Methods. In a cross sectional study, the examiners carried out oral examination of 3000 children and the structure of the uvulae was evaluated as normal or bifid.
    Results. The prevalence of bifid uvula was 0.8 percent (25 children. Positive family history, familial marriage and positive teratogen exposure history were detected in four, twenty and eight percent of bifid uvalae cases, respectively.
    Discussion. Bifid uvulue prevalence in European and American children was reported more than our findings. This gap may be due to different cultural habits as well as environmental factors.

  19. Removal of Reactive Red 198 by Nanoparticle Zero Valent Iron in the Presence of Hydrogen Peroxide

    Directory of Open Access Journals (Sweden)

    Siroos Shojaei

    2017-04-01

    Full Text Available Although dyes are widely used in textile industries, they are carcinogenic, teratogenic and mutagenic. Industries discharge their wastewater containing a variety of colors into water resources and make harmful effect on the environment. The present study aims to Evaluate removal of reactive red 198 by nanoparticle zero valent iron (NZVI in the presence of hydrogen peroxide from aqueous solution. The effective parameters on the removal of dye such as the hydrogen peroxide concentration of NZVI, contact time, pH and dye concentration were investigated and optimized. According to the results, the combination of NZVI with hydrogen peroxide is more effective than single hydrogen peroxide. At pH = 4, contact time= 40 min, 200 M of hydrogen peroxide, dye concentration= 75 mg/L and concentration of NZVI 2g/L, color removal was achieved 91% approximately. Based on the results of experiments, using hydrogen peroxide- NZVI has high efficiency in removal of azo dye type.

  20. The metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea are not influenced by ethanol

    DEFF Research Database (Denmark)

    Grønhøj Larsen, F; Jakobsen, P; Grønhøj Larsen, C

    2009-01-01

    BACKGROUND: Isotretinoin is effective in the treatment of severe acne and rosacea. Both parent drug and its main metabolite 4-oxo-isotretinoin are potentially teratogenic compounds and contain a carboxylic acid moiety. In the presence of ethanol, naturally occurring as well as synthetic retinoids......-RA), and other possible metabolites in the presence or absence of ethanol are converted to their corresponding ethyl derivatives in patients with severe acne or rosacea after multiple isotretinoin dosing. In addition, pharmacokinetic parameters of the parent drug and its 4-oxo metabolite were determined....... PATIENTS/METHODS: Eleven patients with severe acne or rosacea were treated with isotretinoin daily for 3 months and investigated pharmacokinetically during 24 h after 1 month of treatment and for up to 28 days after discontinuation of therapy. A possible influence of ethanol was evaluated using a simple...

  1. Report of the nineteenth session, Athens, 8-12 May 1989

    International Nuclear Information System (INIS)

    1989-01-01

    The Joint Group of Experts on the Scientific Aspects of Marine Pollution (GESAMP) held its nineteenth session at UNEP's Co-ordinating Unit of the Mediterranean Action Plan in Athens, from 8 to 12 May 1989. The following subjects were discussed at the meeting: Review of the potentially harmful substances (carcinogenic, mutagenic and teratogenic substances; chlorinated hydrocarbons; oil and oil spill dispersants and chemicals), interchange of pollutants between the atmosphere and the oceans, coastal modelling, state of the marine environment and long-term ecological consequences of low-level contamination of the marine environment. The future works in marine environmental protection and management as well as assessment and regulation of waste disposal in the marine environment were also planned

  2. The Danish (Q)SAR Database Update Project

    DEFF Research Database (Denmark)

    Nikolov, Nikolai Georgiev; Dybdahl, Marianne; Abildgaard Rosenberg, Sine

    2013-01-01

    The Danish (Q)SAR Database is a collection of predictions from quantitative structure–activity relationship ((Q)SAR) models for over 70 environmental and human health-related endpoints (covering biodegradation, metabolism, allergy, irritation, endocrine disruption, teratogenicity, mutagenicity......, carcinogenicity and others), each of them available for 185,000 organic substances. The database has been available online since 2005 (http://qsar.food.dtu.dk). A major update project for the Danish (Q)SAR database is under way, with a new online release planned in the beginning of 2015. The updated version...... will contain more than 600,000 discrete organic structures and new, more precise predictions for all endpoints, derived by consensus algorithms from a number of state-of-the-art individual predictions. Copyright © 2013 Published by Elsevier Ireland Ltd....

  3. Frequency changes of inherited anomalies in the Republic of Belarus after the Chernobyl accident

    Energy Technology Data Exchange (ETDEWEB)

    Lazjuk, G.I.; Kirillova, I.A.; Nikolaev, D.L.; Novikova, I.V.; Fomina, Z.N.; Khmel, R.D. [Belarus Institute for Hereditary Diseases, Minsk (Belarus)

    1995-12-31

    Complex cytogenetic, embryologic and clinical studies of possible genetic consequences of the Chernobyl nuclear accident for the population of Belarus have been carried out. They showed that groups of the population (pregnant women, fetuses, school children) had received biologically significant doses of radiation, as assessed by the registration of ring and dicentric chromosomes in blood lymphocytes. The study of more than 22,000 embryos and fetuses, and of 4090 neonates with compulsory registered congenital malformations, showed a considerable increase of anomalies of intrauterine origin since 1987. They correlated with the level of {sup 137}Cs contamination in the areas, but did not correlate with the preconception dose to the mother from the same radionuclide. Teratogenic effects of the Chernobyl pollution have not been conclusively idenitifed. The increase of embryonal anomalies was mainly due to the group of multifactorial defects, and to the anomalies with a large contribution from dominant mutations. The Down`s syndrome incidence showed to increase. (Author).

  4. Fetal alcohol spectrum disorders: experimental treatments and strategies for intervention.

    Science.gov (United States)

    Idrus, Nirelia M; Thomas, Jennifer D

    2011-01-01

    Despite the known damaging effects of prenatal alcohol exposure, women continue to drink during pregnancy, creating a need for effective interventions and treatments for fetal alcohol spectrum disorders (FASD). Experimental models can be useful in identifying potential treatments, and this article describes the spectrum of experimental therapeutics that currently are being investigated, including pharmacological, nutritional, and environmental/behavioral interventions. Some treatments target the underlying mechanisms that contribute to alcohol-induced damage, protecting against alcohol's teratogenic effects, whereas other treatments may enhance central nervous system plasticity either during alcohol exposure or long after alcohol exposure has ceased. The insights gained to date from experimental models offer several candidates for attenuating the deficits associated with FASD.

  5. Biodegradação de alcoóis, ftalatos e adipatos em um solo tropical contaminado Biodegradation of alcohol, phthalates and adipates in a tropical soil

    Directory of Open Access Journals (Sweden)

    Ieda Domingues Ferreira

    2010-01-01

    Full Text Available The adipic and phthalic acid esters are plasticizers, have low water solubility, high partition octanol/water coefficients (Kow and accumulate in soil and sediments. These compounds are considered teratogenic, carcinogenic and endocrine disruptors chemicals. This study evaluated the bioremediation of tropical soil contaminated with plasticizers process wastes, in aerobic conditions, with and without introduction of acclimated bacteria. It was selected 200 kg of contaminated tropical soil for the biodegradation study. The plasticizers concentrations in soil ranged between 153 mgDOA/kg up to 15552 mgDIDP/kg and after 90 days of biodegradation, the lower removal efficiencies were 72% with a 1-2 log simultaneous bacterial growth.

  6. Identification of Metabolism and Excretion Differences of Procymidone between Rats and Humans Using Chimeric Mice: Implications for Differential Developmental Toxicity.

    Science.gov (United States)

    Abe, Jun; Tomigahara, Yoshitaka; Tarui, Hirokazu; Omori, Rie; Kawamura, Satoshi

    2018-02-28

    A metabolite of procymidone, hydroxylated-PCM, causes rat-specific developmental toxicity due to higher exposure to it in rats than in rabbits or monkeys. When procymidone was administered to chimeric mice with rat or human hepatocytes, the plasma level of hydroxylated-PCM was higher than that of procymidone in rat chimeric mice, and the metabolic profile of procymidone in intact rats was well reproduced in rat chimeric mice. In human chimeric mice, the plasma level of hydroxylated-PCM was less, resulting in a much lower exposure. The main excretion route of hydroxylated-PCM-glucuronide was bile (the point that hydroxylated-PCM enters the enterohepatic circulation) in rat chimeric mice, and urine in human chimeric mice. These data suggest that humans, in contrast to rats, extensively form the glucuronide and excrete it in urine, as do rabbits and monkeys. Overall, procymidone's potential for causing teratogenicity in humans must be low compared to that in rats.

  7. Antibodies 'green' against aflatoxins for consumer protection

    International Nuclear Information System (INIS)

    Capodicasa, Cristina; Catellani, Marcello

    2015-01-01

    Among the natural toxins that can contaminate products food or feed intended for animal, a particular concern is aroused by mycotoxins. They are toxic substances produced as secondary metabolites, in appropriate conditions micro climate, mainly by members of fungi the genera Aspergillus, Penicillium and Fusarium. The attention paid to these contaminants is justified from the serious effects (teratogenic, carcinogenic, estrogen, neurotoxic and immunosuppression) on health of humans and animals resulting from their intake through food. The Laboratory of Biotechnology Biotechnology Division and agro-industry, at the Research Center Casaccia, has been engaged for years in antibody production in alternative systems to animal cells, such as plants for various applications, the biomedical field to the food industry. Me.Di.T.A. the project under (Methodologies Diagnostic and Advanced Technologies for the quality and the safety of food of the South of Italy), in particular, they have been isolated antibody to develop a diagnostic assay for quantification of aflatoxins in food matrices. [it

  8. Oak Ridge National Laboratory review: Volume 20, No. 2, 1987

    Energy Technology Data Exchange (ETDEWEB)

    Krause, C.; Zucker, A.; Corrill, L. (eds.)

    1987-01-01

    After a brief statement on the 1986 state of the laboratory, science highlights in collaborative research are presented: an attempt to recreate the first moments of the Big Bang, surface modification techniques in electronics, assessing home radon levels in five states, managing international integrated forest study, US-Japan joint breeder reprocessing project, optical components for SDI, evaluating the Chernobyl reactor accident, fusion superconducting magnet and fueling, scanning tunneling microscope, laser-processed solar cells, explosive trace detector, parallel computer processing algorithms, risk of fertilized egg to teratogens, trees for biomass energy, toxic waste leaching test, corn fermentation, and electricity distribution automation at Athens, TN. Milestones, other programs, the HFIR situation, book publications, and news are finally given. (DLC)

  9. Antidepressant exposure during early pregnancy and congenital malformations

    DEFF Research Database (Denmark)

    Pedersen, Lars Henning

    are reassuring, however, an association with heart malformations has been suggested for e.g. paroxetine. A potential biological explanation will be reviewed. The potential teratogenic potential of antidepressants needs to be balanced against the obvious problems associated with under-treated maternal depression......Pharmacological treatment of pregnant women with depression is hampered by concerns for the developing fetus. The presentation will summarize existing knowledge on the potential association between antidepressants and congenital malformations, elaborate on the scientific background, and discuss...... the clinical significance. Most information on malformations in humans is derived from epidemiological studies. The strengths and limitations of the different designs need careful consideration, including issues of confounding by indication, recall bias, and power. For most antidepressants existing data...

  10. Fetal and neonatal abnormalities due to congenital rubella syndrome: a review of literature.

    Science.gov (United States)

    Yazigi, Alexandre; De Pecoulas, Aurelia Eldin; Vauloup-Fellous, Christelle; Grangeot-Keros, Liliane; Ayoubi, Jean-Marc; Picone, Olivier

    2017-02-01

    Rubella virus infection during the first trimester of pregnancy can cause congenital rubella syndrome (CRS). We aimed to describe the abnormalities in order to define the ultrasound features to look for when performing prenatal scans. The goal of this review is to focus specifically on the signs of CRS accessible to prenatal diagnosis. We analyzed every case of CRS described before and/or after birth that we identified in the Pubmed database and classified them as accessible or not to prenatal diagnosis. The most frequently reported malformations accessible to prenatal diagnosis were: cardiac septal defects, pulmonary artery stenosis, microcephaly, cataract, microphtalmia, and hepatosplenomegaly. This extensive literature review shows that the ultrasound features of CRS are not well known, even though rubella was the first teratogenic virus described. This review will help clinicians in the management of rubella during pregnancy by clarifying the findings to be sought.

  11. Developmental effects of irradiation on the brain of the embryo and fetus

    International Nuclear Information System (INIS)

    Anon.

    1987-01-01

    This publication represents an evaluation of the data relating to radiation-induced effects on the central nervous system, especially radiation-induced mental retardation;assesses the gestational age at risk and the quantitative risk at low doses;analyses these effects in the light of what is known about cell survival, proliferation, repopulation and differentiation in the development of the fetal rain;and identifies the needs for future research. Contents: Preface;Introduction;Prenatal development of the primate brain and cerebral adnexa;Developmental disorders of the central nervous system;Ionizing radiation as a central nervous system teratogen;Periods of maximum sensitivity;Risk estimates in humans;Research needs;References

  12. Occurrence of toxigenic Aspergillus flavus in commercial Bulgur wheat

    Directory of Open Access Journals (Sweden)

    Carla Bertechini FARIA

    Full Text Available Abstract Aflatoxins are mutagenic, carcinogenic, and teratogenic mycotoxins. The objective of this work was to study the presence of aflatoxigenic Aspergillus in commercial Bulgur wheat in the city of Maringá, Paraná, Brazil. Thirty samples of commercial Bulgur wheat, acquired in the period of August 2011 to January 2012, were evaluated. The enumeration analysis showed that samples had up to 273.3 CFU of molds and 133.3 CFU of aflatoxigenic Aspergillus per gram of wheat. Forty-two monosporic isolates were obtained and identified as Aspergillus flavus. The isolates were analyzed regarding their aflatoxigenic potential by culture in coconut milk agar; hydroxide vapor exposure; chromatography; and polymerase chain reaction (PCR targeting genes that code enzymes of the aflatoxins synthesis pathway. Some of the isolates were confirmed to be aflatoxin producers and several of them presented a genetic profile of aflatoxin synthesis. The obtained results demonstrated that Bulgur wheat A. flavus contamination is concerning.

  13. Prenatal VPA exposure and changes in sensory processing by the superior colliculus

    Directory of Open Access Journals (Sweden)

    Georgia eDendrinos

    2011-10-01

    Full Text Available Disorders involving dysfunctional sensory processing are characterized by an inability to filter sensory information, particularly simultaneously arriving multimodal inputs. We examined the effects of prenatal exposure to valproic acid (VPA, a teratogen linked to sensory dysfunction, on the behavior of juvenile and adult rats, and on the anatomy of the superior colliculus, a critical multisensory integration center in the brain. VPA-exposed rats showed deficits in colliculus-dependent behaviors including startle response, prepulse inhibition and nociceptive responses. Some deficits reversed with age. Stereological analyses revealed that colliculi of VPA-treated rats had significantly fewer parvalbumin-positive neurons, a subset of GABAergic cells. These results suggest that prenatal VPA treatment affects the development of the superior colliculus and leads to persistent anatomical changes evidenced by aberrant behavior in tasks that require sensory processing.

  14. Late morphological and functional changes caused by ionizing radiation in eggs of Japanese quail

    Energy Technology Data Exchange (ETDEWEB)

    Baumgartner, J; Grom, A; Csuka, J; Stasko, J; Kindlova, L [Vyskumny Ustav Chovu a Slachtenia Hydiny, Ivanka pri Dunaji (Czechoslovakia)

    1976-01-01

    Eggs of Japanese quail (Coturnix coturnix japonica) were irradiated before incubation with doses of 300, 500, 800, 1500, 2000 and 2500 R of /sup 60/Co gamma rays at a dose rate of 187 R/min. The parameters of hatchability, embryonic morphology in the last phases of development, growth changes, viability, sex ratio and production of eggs in the control and experimental groups were followed. Embryonic mortality was proportional to the dose, irradiation weakened the embryos, at doses of 800 R and more the radiation evoked various teratogenic changes and slightly lengthened the incubation period. For the period of embryonic development, LD/sub 50/ approximately equal to 800 R and LD/sub 100/=2500 R was determined. Radiation slightly suppressed growth, viability in the postembryonic stage was influenced very slightly. Irradiation of eggs did not influence the sex ratio; the production of eggs was significantly reduced only at a dose of 1500 R and more.

  15. Somatic Treatments in Treatment of Depression During Pregnancy

    Directory of Open Access Journals (Sweden)

    Eylem Ozten

    2015-09-01

    Full Text Available Although some psychotropic drugs are known to be teratogenic no psychotropic drug is of proven safety for treatment of depression during pregnancy. Untreated mood disorders during pregnancy pose significant risks for mother and the newborn. This review focuses on the use of somatic tretments of depression during pregnancy.Electroconvulsive therapy, bright light therapy, transcranial magnetic stimulation and vagal nerve stimulation are relatively safe and effective treatments during pregnancy if steps are taken to decrease potential risks. A clear information related to the somatic treatment should be given to the patient and informed consent should be obtained. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(3.000: 244-254

  16. Review of NCRP radiation dose limit for embryo and fetus in occupationally-exposed women

    International Nuclear Information System (INIS)

    Anon.

    1977-01-01

    On the basis of the current review, the NCRP has decided to make no change in the current recommendation of its radiation dose limit to the unborn. The NCRP recommendation is restated here as follows: During the entire gestation period, the maximum permissible dose equivalent to the embryo-fetus from occupational exposure of the expectant mother should be 0.5 rem. Since the preparation of the 1971 report there has been no new evidence concerning teratogenic or carcinogenic effects of irradiation of the embryo-fetus that would justify a change in the limit in either direction. It is implicit in this position and recommendation that women who can reasonably be expected to be pregnant should not, in certain instances, be exposed to the same radiation environment as women who are not considered fertile or as men. This applies particularly to conditions where radiation workers can receive dose equivalents of 0.5 rem or more in short periods

  17. Review of NCRP radiation dose limit for embryo and fetus in occupationally-exposed women - approved 1977

    International Nuclear Information System (INIS)

    Anon.

    1978-01-01

    On the basis of the current review, the NCRP has decided to make no change in the current recommendation of its radiation dose limit to the unborn. The NCRP recommendation is restated here as follows: During the entire gestation period, the maximum permissible dose equivalent to the embryo-fetus from occupational exposure of the expectant mother should be 0.5 rem. Since the preparation of the 1971 report there has been no new evidence concerning teratogenic or carcinogenic effects of irradiation of the embryo-fetus that would justify a change in the limit in either direction. It is implicit in this position and recommendation that women who can reasonably be expected to be pregnant should not, in certain instances, be exposed to the same radiation environment as women who are not considered fertile or as men. This applies particularly to conditions where radiation workers can receive dose equivalents of 0.5 rem or more in short periods

  18. Biomagnification of bioassay derived 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents

    Science.gov (United States)

    Jones, P.D.; Ankley, G.T.; Best, D. A.; Crawford, R.; DeGalan, N.; Giesy, J.P.; Kubiak, T.J.; Ludwig, J. P.; Newsted, J.L.; Tillitt, D. E.; Verbrugge, D.A.

    1993-01-01

    In recent years contamination of the Great Lakes ecosystem with planar chlorinated hydrocarbons (PCHs) has attracted considerable concern due to their known reproductive and teratogenic effects. The H4IIE bioassay has been standardized as a means of measuring the biological potency of a PCH mixture as 2,3,7,8-tetrachloro-p-dibenzodioxin equivalents (TCDD-EQ). Using this bioassay we have investigated the biomagnification of TCDD-EQ in a semi-closed ecosystem. The biomagnification of TCDD-EQ is demonstrated and results indicate that the food chain is the major pathway for TCDD-EQ through this ecosystem. The H4IIE assay system is demonstrated to be a viable integrative measure of the total concentration of TCDD-EQ in different trophic levels.

  19. Pacman dysplasia: a lethal skeletal dysplasia with variable radiographic features

    Energy Technology Data Exchange (ETDEWEB)

    Miller, S.F. [Dept. of Radiology, Children' s Hospital of the King' s Daughters, Norfolk (United States); Proud, V.K. [Dept. of Genetics, Children' s Hospital of the King' s Daughters, Norfolk (United States); Werner, A.L. [Dept. of Pathology, Children' s Hospital of the King' s Daughters, Norfolk (United States); Field, F.M.; Wilcox, W.F.; Lachman, R.S.; Rimoin, D.L. [International Skeletal Dysplasia Registry, Cedars-Sinai Medical Center, Los Angeles (United States)

    2003-04-01

    Background: Punctate or stippled cartilaginous calcifications are associated with many conditions, including chromosomal, infectious, endocrine, and teratogenic etiologies. Some of these conditions are clinically mild, while others are lethal. Accurate diagnosis can prove instrumental in clinical management and in genetic counseling. Objective: To describe the diagnostic radiographic features seen in Pacman dysplasia, a distinct autosomal recessive, lethal skeletal dysplasia. Materials and methods: We present the fourth reported case of Pacman dysplasia and compare the findings seen in our patient with the three previously described patients. Results: Invariable and variable radiographic findings were seen in all four cases of histologically proven Pacman dysplasia. Conclusion: Pacman dysplasia presents both constant and variable diagnostic radiographic features. (orig.)

  20. Teratology studies in the rat.

    Science.gov (United States)

    Leroy, Mariline; Allais, Linda

    2013-01-01

    The rat is the rodent species of choice for the regulatory safety testing of xenobiotics, such as medicinal products, food additives, and other chemicals. Many decades of experience and extensive data have accumulated for both general and developmental toxicology investigations in this species. The high fertility and large litter size of the rat are advantages for teratogenicity testing. The study designs are well defined in the regulatory guidelines and are relatively standardized between testing laboratories across the world. Teratology studies address maternal- and embryo-toxicity following exposure during the period of organogenesis. This chapter describes the design and conduct of a teratology study in the rat in compliance with the regulatory guidelines. The procedures for the handling and housing of the pregnant animals, the caesarean examinations and the sampling of fetuses for morphological examinations are described. The utility and design of preliminary studies and the inclusion of satellite animals in the main study for toxicokinetic sampling are discussed.

  1. The teratology testing of food additives.

    Science.gov (United States)

    Barrow, Paul C; Spézia, François

    2013-01-01

    The developmental and reproductive toxicity testing (including teratogenicity) of new foods and food additives is performed worldwide according to the guidelines given in the FDA Redbook. These studies are not required for substances that are generally recognized as safe, according to the FDA inventory. The anticipated cumulated human exposure level above which developmental or reproduction studies are required depends on the structure-alert category. For food additives of concern, both developmental (prenatal) and reproduction (multigeneration) studies are required. The developmental studies are performed in two species, usually the rat and the rabbit. The reproduction study is generally performed in the rat. The two rat studies are preferably combined into a single experimental design, if possible. The test methods described in the FDA Redbook are similar to those specified by the OECD for the reproductive toxicity testing of chemicals.

  2. Teratology studies in the rabbit.

    Science.gov (United States)

    Allais, Linda; Reynaud, Lucie

    2013-01-01

    The rabbit is generally the non-rodent species or second species after the rat recommended by the regulatory authorities and is part of the package of regulatory reproductive studies for the detection of potential embryotoxic and/or teratogenic effects of pharmaceuticals, chemicals, food additives, and other compounds, including vaccines (see Chapters 1-7).Its availability, practicality in housing and in mating as well as its large size makes the rabbit the preferred choice as a non-rodent species. The study protocols are essentially similar to those established for the rat (Chapter 9), with some particularities. The study designs are well defined in guidelines and are relatively standardized between testing laboratories across the world.As for the rat, large litter sizes and extensive background data in the rabbit are valuable criteria for an optimal assessment of in utero development of the embryo or fetus and for the detection of potential external or internal fetal malformations.

  3. Pregnancy in epileptic patients: comparison between well-established therapeutic strategies and opportunities coming from new drugs

    Directory of Open Access Journals (Sweden)

    Francesca Pizzo

    2013-12-01

    Full Text Available Treating women affected by epilepsy during pregnancy is challenging.  Clinicians have to consider both the teratogenic effects of Antiepileptic Drugs (AEDs and the risk of seizure recurrence. Pharmacokinetic changes during pregnancy are rapid and conspicuous so that the serum concentration of drugs can be modified and the effectiveness of AEDs cannot be guaranteed. The aim of this study is to evaluate the risk of Major Congenital Malformation (MCM associated with AEDs treatment during the first trimester of pregnancy. We collected data from 338 patients who contacted the Teratology Information Services of XXX University Hospital and we found that only the variable monotherapy vs politherapy had statistical significance for MCM. More studies are needed to assess the efficacy and safety of newer AEDs.

  4. Paternal exposure and counselling: experience of a Teratology Information Service.

    Science.gov (United States)

    De Santis, Marco; Cesari, Elena; Cavaliere, Annafranca; Ligato, Maria Serena; Nobili, Elena; Visconti, Daniela; Caruso, Alessandro

    2008-09-01

    We describe paternal exposure and counselling in a selected population calling to an Italian Teratology Information Service (TIS). The majority of callers asked for paternal drug exposure (76%, drugs except chemotherapy) and treatment for cancer (17%, chemotherapy and/or radiotherapy). Others asked for exposure to diagnostic radiations (4%), recreational drugs (2%) and occupational chemicals (1%). Among paternal drugs neurological compounds, immunosuppressive drugs and antiviral agents were the main reasons for calling. In humans, there are no evidences of birth defects after paternal exposures, but to minimize any possible risk, counselling in men exposed to radio and chemotherapy should recommend delaying conception for at least 3 months after the end of the therapy. Male patients treated with drugs, whose teratogenic potential has been well assessed or suspected for maternal exposure, should be advised to practice effective birth control during therapy and up to one or two cycles of spermatogenesis and to avoid semen contact with vaginal walls during first trimester of pregnancy.

  5. Regulatory aspects of teratology: role of the Food and Drug Administration

    International Nuclear Information System (INIS)

    Kelsey, F.O.

    1982-01-01

    The Food and Drug Administration is a scientific regulatory agency whose consumer protection activities cover a wide range of products including foods and additives, and pesticide residues on foods; drugs; cosmetics; medical devices; and radiation-emitting electronic products. Amongst its concerns is the possible teratogen effects of regulated products to which the pregnant woman is exposed. The policies and programs of the agency directed toward reducing such risks to the unborn are reviewed. These measures include guidelines for animal reproduction studies and for clinical trials involving women to childbearing potential; labeling of products to disclose known or possible harm to the fetus or embryo; surveillance procedures designed to detect previously unsuspected adverse effects of marketed products; research activities designed to develop better understanding of developmental toxicology and improved techniques for detecting embryocidal and embryotoxic effects; and educational efforts directed both to professionals and the public regarding hazards to the unborn of agency-regulated products

  6. Depression and Anxiety During Pregnancy: Evaluating the Literature in Support of Clinical Risk-Benefit Decision-Making.

    Science.gov (United States)

    Dalke, Katharine Baratz; Wenzel, Amy; Kim, Deborah R

    2016-06-01

    Depression and anxiety during pregnancy are common, and patients and providers are faced with complex decisions regarding various treatment modalities. A structured discussion of the risks and benefits of options with the patient and her support team is recommended to facilitate the decision-making process. This clinically focused review, with emphasis on the last 3 years of published study data, evaluates the major risk categories of medication treatments, namely pregnancy loss, physical malformations, growth impairment, behavioral teratogenicity, and neonatal toxicity. Nonpharmacological treatment options, including neuromodulation and psychotherapy, are also briefly reviewed. Specific recommendations, drawn from the literature and the authors' clinical experience, are also offered to help guide the clinician in decision-making.

  7. Further evidence of a relationship between the retinoic acid receptor alpha locus and nonsyndromic cleft lip with or without cleft palate (CL [+-] P)

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, D.; Field, L. (Univ. of Calgary (Canada)); Ray, A. (Univ. of Toronto (Canada)); Marazita, M. (Medical College of Virginia, Richmond, VA (United States))

    1993-11-01

    Chenevix-Trench et al. (1992) reported a significant difference between nonsyndromic cleft lip with or without cleft palate (CL [+-] P) cases and unrelated controls in the frequency of alleles at the retinoic acid receptor alpha (RARA) PstI RFLP located at 17q21.1. They also observed borderline significant (P = .055) differences between allele frequencies in subjects with cleft lip and palate (CL + P) compared with those with cleft lip only (CL). Retinoic acid (RA) is a known teratogen capable of producing cleft palate in rodents (Abbott and Birnbaum 1990). Chenevix-Tench et al. (1992) hypothesized that variation in susceptibility to the effects of RA in humans may result from alterations at the RARA locus. We have investigated association and linkage between CL [+-] P and a microsatellite marker (D17S579) located at 17q21 (Hall et al. 1992), selected for its proximity to RARA, in 14 extended multiplex families from rural West Bengal, India.

  8. Hereditary effects of low and chronic radiation exposure: a case-control study of mental retardation and cleft lip/palate in the monazite bearing coastal areas of Southern Kerala

    International Nuclear Information System (INIS)

    Koya, P.K.M.; Cheriyan, V.D.; Chougaonkar, M.P.; Mayya, Y.S.; Jojo, P.J.; Predeep, P.; Seshadri, M.

    2010-01-01

    The high level natural radiation (HLNR) areas of Kerala in the south west coast of Kerala is suitable for direct human studies to assess the genetic and teratogenic effect of low and chronic radiation exposures. The radiation level in the region (about 55 km long and 0.5 km wide belt) range from ≤1.0 mGy to 45.0 mGy per year and is due to natural deposit of monazite sand containing Thorium (8-10%), Uranium (0.3%) and corresponding decay products. A population based case-control study was carried out in the area to assess the role, if any, of HLNR as a causative factor in the etiology of two relatively frequent and easily identifiable congenital malformations, viz., mental retardation (MR) and cleft lip/palate (CLP). Findings from the study are discussed in this paper

  9. Removal of polycyclic aromatic hydrocarbons in aqueous environment by chemical treatments: a review.

    Science.gov (United States)

    Rubio-Clemente, Ainhoa; Torres-Palma, Ricardo A; Peñuela, Gustavo A

    2014-04-15

    Due to their carcinogenic, mutagenic and teratogenic potential, the removal of polycyclic aromatic hydrocarbons (PAHs) from aqueous environment using physical, biological and chemical processes has been studied by several researchers. This paper reviews the current state of knowledge concerning PAHs including their physico-chemical properties, input sources, occurrence, adverse effects and conventional and alternative chemical processes applied for their removal from water. The mechanisms and reactions involved in each treatment method are reported, and the effects of various variables on the PAH degradation rate as well as the extent of degradation are also discussed. Extensive literature analysis has shown that an effective way to perform the conversion and mineralization of this type of substances is the application of advanced oxidation processes (AOPs). Furthermore, combined processes, particularly AOPs coupled with biological treatments, seem to be one of the best solutions for the treatment of effluents containing PAHs. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Genetic effects of organic mercury compounds

    Energy Technology Data Exchange (ETDEWEB)

    Ramel, C

    1967-01-01

    Organic mercury compounds have a c-mitotic effect on plant cells that cause polyploidi. Studies were performed on Allium root cells. These investigations involved methyl mercury dicyandiamide, methyl mercury hydroxide, and phenyl mercury hydroxide. The lowest concentration necessary for a cytologically observable effect was about 0.05 ppM Hg for the methyl compounds. For the phenyl compound, the value was lower. Experiments were performed on Drosophila melanogaster. The question was whether the mercury would reach the gonads. Experimental data with mercury treated larvae indicated a chromosome disjunction. Data indicated a preferential segregation at the meiotic division might be involved. Experiments are being performed on mice inbred (CBA) in order to investigate teratogenic effects and dominant lethality caused by organic mercury compounds. The mutagenic effects of these compounds are studied on Neurospora Drosophila. No conclusive data is now available.

  11. Nail bed expansion: A new technique for correction of multiple isolated congenital micronychia

    Directory of Open Access Journals (Sweden)

    Gholamhossein Ghaffarpour

    2014-01-01

    Full Text Available Congenital micronychia may involve big toes or may involve other nails. The etiology of micronychia is not clear but amniotic bands, teratogens (drugs, alcohol, Nail Patella Syndrome etc. A 44-year-old woman with multiple isolated congenital micronychia over her hands and feet was selected. The major affected nails were thumbs and Index fingers. Surgical method were done step by step: Anesthesia of the area, extraction of short nail, elevation of nail bed, longitudinal nail bed incisions, suturing the lateral nail bed to the nail wall, covering the nail bed by a splint of plastic suction tube, bandage with gauze Vaseline. Finally, we hypnotized that in congenital micronychia, the main pathology is in nail bed; through this theory by nail bed expansion better outcomes are coming.

  12. Shift work, fetal development and course of pregnancy.

    Science.gov (United States)

    Nurminen, T

    1989-12-01

    Information on 1475 mothers of infants with selected structural malformations and an equal number of mothers of "normal" babies was analyzed for a possible relationship between shift work and adverse pregnancy outcome or a complicated course of pregnancy. The primary data were obtained from the Finnish Register of Congenital Malformations supplemented by special interviews on the mothers' work conditions. No signs of a teratogenic risk were observed. The relationship between course of pregnancy and outcomes other than malformations was determined from the noncase mothers' experience. Threatened abortion and pregnancy-induced hypertension were not associated with rotating shift work alone, but in a noisy work environment moderate risks could not be ruled out. Rotating shift work was associated with a slight excess of babies small for their gestational age independently of noise exposure. The results suggest that further studies on the effects of different work schedules on pregnancy are worth consideration.

  13. ATTENTION FUNCTIONING IN CHILDREN WITH PRENATAL DRUG EXPOSURE.

    Science.gov (United States)

    Jaeger, Dominique A; Suchan, Boris; Schölmerich, Axel; Schneider, Dominik T; Gawehn, Nina

    2015-01-01

    Children born to drug abusers are exposed to teratogenic influences on intrauterine brain development and undergo postnatal withdrawal. We investigated the interplay of different domains and levels of attention functioning in 24 prenatally exposed and 25 nonexposed children who were 5 to 6 years old. Assessment included parent ratings and neuropsychological and electrophysiological methods. Exposed children had a higher prevalence of attention deficit hyperactivity symptoms, tended to have poorer performance in an attention test battery, and showed EEG alterations in P3 and N2c. Findings suggest long-term effects of prenatal drug exposure on specific domains and on different levels of attention functioning. © 2015 Michigan Association for Infant Mental Health.

  14. The clinical geneticist and the evaluation of failure to thrive versus failure to feed.

    Science.gov (United States)

    Rabago, Jillian; Marra, Kayt; Allmendinger, Nikki; Shur, Natasha

    2015-12-01

    Common clinical genetic referrals for the pediatric patient include a single major or multiple minor anomalies, dysmorphic features, especially when accompanied by developmental delay or intellectual disability, and failure to thrive (FTT). This review provides pediatric definitions of FTT and the genetic differential for FTT, which includes chromosomal disorders, microdeletion/duplication syndromes, uniparental disomy/methylation disorder, disorders of DNA repair, teratogens, metabolic syndromes, and skeletal dysplasias. Three clinical genetics cases highlight challenges in deciphering the cause of FTT. The review concludes with a ten-step approach that might improve diagnostic ability in differentiating FTT cases (those with genetic or other metabolic causes) from "failure to feed," in other words FTT as the direct result of neglect and/or child abuse. © 2015 Wiley Periodicals, Inc.

  15. Mechanisms involved in the neurotoxic and cognitive effects of developmental methamphetamine exposure.

    Science.gov (United States)

    Jablonski, Sarah A; Williams, Michael T; Vorhees, Charles V

    2016-06-01

    Methamphetamine exposure in utero leads to a variety of higher-order cognitive deficits, such as decreased attention and working, and spatial memory impairments in exposed children (Piper et al., 2011; Roussotte et al., 2011; Kiblawi et al., 2011). As with other teratogens, the timing of methamphetamine exposure greatly determines its effects on both neuroanatomical and behavioral outcomes. Methamphetamine exposure in rodents during the third trimester human equivalent period of brain development results in distinct and long-lasting route-based and spatial navigation deficits (Williams et al., 2003; Vorhees et al., 2005, 2008, 2009;). Here, we examine the impact of neonatal methamphetamine-induced neurotoxicity on behavioral outcomes, neurotransmission, receptor changes, plasticity proteins, and DNA damage. Birth Defects Research (Part C) 108:131-141, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Effects of tributyltin on metamorphosis and gonadal differentiation of Xenopus laevis at environmentally relevant concentrations.

    Science.gov (United States)

    Shi, Huahong; Zhu, Pan; Guo, Suzhen

    2014-05-01

    Tributyltin (TBT), a well known endocrine disruptor, has high teratogenicity to embryos of amphibian (Xenopus tropicalis). An amphibian metamorphosis assay (AMA) and a complete AMA (CAMA) were conducted for TBT. In AMA, the body weight, the snout-to-vent length and the hind limb length of X. laevis tadpoles were decreased in tributyltin chloride (TBTCl; 12.5-200 ng/L) treatment groups after 7 days exposure. TBT greatly retarded the development of tadpoles, decreased the number of follicle and induced thyroid follicle cell hyperplasia after 19 days exposure. In CAMA, 10 and 100 ng/L TBTCl led to various malformations of gonad, including intersex, segmental aplasia and multiple ovary cavities of X. laevis following exposure from stages 46 to stage 66. The sex ratio was male-biased in TBT treatment groups. These results suggest that TBT delayed the metamorphosis, inhibited the growth of tadpoles and disrupted the gonadal differentiation of X. laevis at environmentally relevant concentrations.

  17. Role of microRNAs in Alcohol-Induced Multi-Organ Injury

    Directory of Open Access Journals (Sweden)

    Sathish Kumar Natarajan

    2015-11-01

    Full Text Available Alcohol consumption and its abuse is a major health problem resulting in significant healthcare cost in the United States. Chronic alcoholism results in damage to most of the vital organs in the human body. Among the alcohol-induced injuries, alcoholic liver disease is one of the most prevalent in the United States. Remarkably, ethanol alters expression of a wide variety of microRNAs that can regulate alcohol-induced complications or dysfunctions. In this review, we will discuss the role of microRNAs in alcoholic pancreatitis, alcohol-induced liver damage, intestinal epithelial barrier dysfunction, and brain damage including altered hippocampus structure and function, and neuronal loss, alcoholic cardiomyopathy, and muscle damage. Further, we have reviewed the role of altered microRNAs in the circulation, teratogenic effects of alcohol, and during maternal or paternal alcohol consumption.

  18. Evidence of Some Natural Products with Antigenotoxic Effects. Part 1: Fruits and Polysaccharides

    Science.gov (United States)

    Izquierdo-Vega, Jeannett Alejandra; Morales-González, José Antonio; Sánchez-Gutiérrez, Manuel; Betanzos-Cabrera, Gabriel; Sosa-Delgado, Sara M.; Sumaya-Martínez, María Teresa; Morales-González, Ángel; Paniagua-Pérez, Rogelio; Madrigal-Bujaidar, Eduardo; Madrigal-Santillán, Eduardo

    2017-01-01

    Cancer is one of the leading causes of deaths worldwide. The agents capable of causing damage to genetic material are known as genotoxins and, according to their mode of action, are classified into mutagens, carcinogens or teratogens. Genotoxins are involved in the pathogenesis of several chronic degenerative diseases including hepatic, neurodegenerative and cardiovascular disorders, diabetes, arthritis, cancer, chronic inflammation and ageing. In recent decades, researchers have found novel bioactive phytocompounds able to counteract the effects of physical and chemical mutagens. Several studies have shown potential antigenotoxicity in a variety of fruits. In this review (Part 1), we present an overview of research conducted on some fruits (grapefruit, cranberries, pomegranate, guava, pineapple, and mango) which are frequently consumed by humans, as well as the analysis of some phytochemicals extracted from fruits and yeasts which have demonstrated antigenotoxic capacity in various tests, including the Ames assay, sister chromatid exchange, chromosomal aberrations, micronucleus and comet assay. PMID:28157162

  19. The transformation suppressor gene Reck is required for postaxial patterning in mouse forelimbs

    Directory of Open Access Journals (Sweden)

    Mako Yamamoto

    2012-03-01

    The membrane-anchored metalloproteinase-regulator RECK has been characterized as a tumor suppressor. Here we report that mice with reduced Reck-expression show limb abnormalities including right-dominant, forelimb-specific defects in postaxial skeletal elements. The forelimb buds of low-Reck mutants have an altered dorsal ectoderm with reduced Wnt7a and Igf2 expression, and hypotrophy in two signaling centers (i.e., ZPA and AER that are essential for limb outgrowth and patterning. Reck is abundantly expressed in the anterior mesenchyme in normal limb buds; mesenchyme-specific Reck inactivation recapitulates the low-Reck phenotype; and some teratogens downregulate Reck in mesenchymal cells. Our findings illustrate a role for Reck in the mesenchymal-epithelial interactions essential for mammalian development.

  20. Review of the quantification techniques for polycyclic aromatic hydrocarbons (PAHs) in food products.

    Science.gov (United States)

    Bansal, Vasudha; Kumar, Pawan; Kwon, Eilhann E; Kim, Ki-Hyun

    2017-10-13

    There is a growing need for accurate detection of trace-level PAHs in food products due to the numerous detrimental effects caused by their contamination (e.g., toxicity, carcinogenicity, and teratogenicity). This review aims to discuss the up-to-date knowledge on the measurement techniques available for PAHs contained in food or its related products. This article aims to provide a comprehensive outline on the measurement techniques of PAHs in food to help reduce their deleterious impacts on human health based on the accurate quantification. The main part of this review is dedicated to the opportunities and practical options for the treatment of various food samples and for accurate quantification of PAHs contained in those samples. Basic information regarding all available analytical measurement techniques for PAHs in food samples is also evaluated with respect to their performance in terms of quality assurance.

  1. Pregnancy and Evans´ syndrome: case report

    Directory of Open Access Journals (Sweden)

    Santiago Artucio

    2015-12-01

    Full Text Available Evans´ syndrome is the coexistence of autoimmune thrombocytopenia with autoimmune hemolytic anemia. It is rarely found during the course of a pregnancy. This makes treatment options more difficult, since some therapeutic drugs are teratogenic. The effects of Evans´ syndrome in the fetus and newborn are unknown given the low number of reported cases. We report the case of a patient with preconceptional diagnosis of Evans´ syndrome, who develops a hemolytic crisis during the course of a pregnancy, and diagnosis of intrauterine growth restriction (IUGR, treated at Clínica Ginecotocológica “A” at the Pereira Rossell Hospital Center, in Montevideo, Uruguay. Treatment options and evolution are analyzed, as well as previous reports.

  2. Congenital skeletal malformations and cleft palate induced in goats by ingestion of Lupinus, Conium and Nicotiana species.

    Science.gov (United States)

    Panter, K E; Keeler, R F; Bunch, T D; Callan, R J

    1990-01-01

    Three piperidine alkaloid containing plants, Conium maculatum (poison-hemlock), Nicotiana glauca (tree tobacco) and Lupinus formosus (lunara lupine), induced multiple congenital contractures (MCC) and palatoschisis in goat kids when their dams were gavaged with the plant during gestation days 30-60. The skeletal abnormalities included fixed extension or flexure of the carpal, tarsal, and fetlock joints, scoliosis, lordosis, torticollis and rib cage abnormalities. Clinical signs of toxicity included those reported in sheep, cattle and pigs--ataxia, incoordination, muscular weakness, prostration and death. One quinolizidine alkaloid containing plant, Lupinus caudatus (tailcup lupine), on the other hand, which is also known to cause MCC in cows, caused only slight signs of toxicity in pregnant goats and no teratogenic effects in their offspring.

  3. Radiographic, MR or ultrasound contrast media in pregnant or breast-feeding women. What are the key issues?

    International Nuclear Information System (INIS)

    Froehlich, J.M.; Kubik-Huch, Rahel A.

    2013-01-01

    The use and the safety of radiographic, MR- or ultrasound contrast media in the diagnostic work-up of pregnant or lactating patients is a frequently discussed question. As only sparse clinical data is available, a careful benefit-risk assessment must contain physico-chemical properties, preclinical data including teratogeneity and embryotoxicity, as well as maternal and foetal exposure. With consideration to the individual risks, iodinated contrast media, macrocyclic MR contrast media with increased stability or sulphur hexafluoride ultrasound contrast media may, if clinically justified, be administered in the smallest possible doses throughout pregnancy. After parental administration of an iodinated contrast medium after the 12th week of pregnancy, the neonate's thyroidal function should be checked during the first week after birth. After parental administration of iodinated, stable macrocyclic, gadolinium or ultrasound contrast media, lactation can be continued normally. In any case, contrast media should be used with caution and only if the benefits outweigh the risk. (orig.)

  4. The toxic effects of ionizing radiations

    International Nuclear Information System (INIS)

    Draghita Payet, A.C.

    2006-06-01

    The sources of radiations to which the human body is subjected are of natural or artificial origin and the irradiation of the human body can take place either by internal or external way. The ionizing radiations act at several levels of the human body, the main thing being the molecule of DNA. The ionizing radiations have no specificity, the effects on the human body can be: somatic, genetic or hereditary, teratogen. In the case of a human being irradiation, we proceed to the diagnosis and to the treatment of the irradiated person, however, to decrease the incidence of injuries we use the radiation protection. The treatment if necessary will be established according to the irradiation type. (N.C.)

  5. Sirenomelia and VACTERL association in the offspring of a woman with diabetes.

    Science.gov (United States)

    Castori, Marco; Silvestri, Evelina; Cappellacci, Sandra; Binni, Francesco; Sforzolini, Giovanna Scassellati; Grammatico, Paola

    2010-07-01

    Sirenomelia and VACTERL association are defects of blastogenesis of unknown cause. Although they appear clinically distinct, some epidemiological and experimental studies suggest a common pathogenetic mechanism. We report on the reproductive history of a 28-year-old obese, diabetic mother who had three pregnancies. The first resulted in the birth of a sirenomelic child, the second in a miscarriage, while the third was terminated for fetal malformations, diagnosed post-mortem as VACTERL association. This observation supports the relationship between sirenomelia and VACTERL, which probably represent the two ends of the same phenotypic spectrum. Their occurrence in the same sibship also indicates a possible common cause. The coexistence with maternal diabetes seems more than a chance occurrence and the constellation of malformations observed in the present family may be explained as the pleiotropic effect of the same teratogenic agent interacting with genetic predisposition to diabetes and/or obesity. (c) 2010 Wiley-Liss, Inc.

  6. Inhibitory effects of silver zeolite on in vitro growth of fish egg pathogen, Saprolegnia sp.

    Directory of Open Access Journals (Sweden)

    Seyed Ali Johari

    2014-05-01

    Full Text Available Objective: To investigate the effects of powdered silver zeolite (SZ on the in vitro growth of the fish pathogen Saprolegnia sp. Methods: The antifungal activity of SZ was evaluated by determining the minimum inhibitory concentrations using two-fold serial dilutions of powdered SZ in a glucose yeast extract agar at 22 °C. The growth of Saprolegnia sp. on the SZ agar treatments was compared to that on SZ-free agar controls. Results: The results showed that SZ had an inhibitory effect on the in vitro growth of the tested fungi. The minimum inhibitory concentration of SZ for Saprolegnia sp. was also calculated at 600 mg/L, which is equal to 0.06 percent. Conclusions: SZ is a potential good candidate to replace teratogenic and toxic agents, such as malachite green in aquaculture systems.

  7. Early life programming as a target for prevention of child and adolescent mental disorders

    Science.gov (United States)

    2014-01-01

    This paper concerns future policy development and programs of research for the prevention of mental disorders based on research emerging from fetal and early life programming. The current review offers an overview of findings on pregnancy exposures such as maternal mental health, lifestyle factors, and potential teratogenic and neurotoxic exposures on child outcomes. Outcomes of interest are common child and adolescent mental disorders including hyperactive, behavioral and emotional disorders. This literature suggests that the preconception and perinatal periods offer important opportunities for the prevention of deleterious fetal exposures. As such, the perinatal period is a critical period where future mental health prevention efforts should be focused and prevention models developed. Interventions grounded in evidence-based recommendations for the perinatal period could take the form of public health, universal and more targeted interventions. If successful, such interventions are likely to have lifelong effects on (mental) health. PMID:24559477

  8. Radiation teratogenesis

    International Nuclear Information System (INIS)

    Miller, R.W.

    1987-01-01

    Although small head size and metal retardation (MR) were first recognized as teratogenic effects of ionizing radiation in the 1920s, new information continues to emerge about these effects. Early studies of the Japanese atomic-bomb survivors showed that small head size was induced by doses as low as 10-19 rad in air. The next steps are to relate the effects to the new (1985) dosimetry, and to seek lesser effects on the brain by new tests to detect such clinical deficits as inability to sequence ideas, comprehend complex syntax, or pay attention. Although an array of congenital anomalies has been induced by prenatal radiation exposures of animals, only small head size and MR have occured excessively in the human

  9. Late morphological and functional changes caused by ionizing radiation in eggs of Japanese quail

    International Nuclear Information System (INIS)

    Baumgartner, J.; Grom, A.; Csuka, J.; Stasko, J.; Kindlova, L.

    1976-01-01

    Eggs of Japanese quail (Coturnix coturnix japonica) were irradiated before incubation with doses of 300, 500, 800, 1500, 2000 and 2500 R of 60 Co gamma rays at a dose rate of 187 R/min. The parameters of hatchability, embryonic morphology in the last phases of development, growth changes, viability, sex ratio and production of eggs in the control and experimental groups were followed. Embryonic mortality was proportional to the dose, irradiation weakened the embryos, at doses of 800 R and more the radiation evoked various teratogenic changes and slightly lengthened the incubation period. For the period of embryonic development, LD 50 approximately equal to 800 R and LD 100 =2500 R was determined. Radiation slightly suppressed growth, viability in the postembryonic stage was influenced very slightly. Irradiation of eggs did not influence the sex ratio; the production of eggs was significantly reduced only at a dose of 1500 R and more. (author)

  10. Early appearance and possible roles of non-neuromuscular cholinesterases.

    Directory of Open Access Journals (Sweden)

    Carla eFalugi

    2012-04-01

    Full Text Available The biological function of the cholinesterase (ChE enzymes is well known and has been studied since the beginning of the XXth century; in particular, acetylcholinesterase (AChE, E.C. 3.1.1.7 is an enzyme playing a key role in the modulation of neuromuscular impulse transmission. However, in the past decades, there has been increasing interest concerning its role in regulating non-neuromuscular cell-to-cell interactions mediated by intracellular ion concentration changes, like the ones occurring during gamete interaction and embryonic development. An understanding of the mechanisms of the cholinergic regulation of these events can help us foresee the possible impact on environmental and human health, including gamete efficiency and possible teratogenic effects on different models, and help elucidate the extent to which exposure to ChE inhibitors may affect human health.

  11. A case of fetal valproate syndrome with new features expanding the phenotype

    International Nuclear Information System (INIS)

    Seidahmed, Mohammed Z.; Miqdad, Abeer M.; AlDohami, Hessa S.; Shareefi, Osama M.

    2009-01-01

    Fetal valproate syndrome (FVS) is a well-recognized constellation of dysmorphic features, and neurodevelopmental retardation that results from prenatal exposure to the anticonvulsant valproic acid. In this report, we describe a case with typical features of FVS. A 23-year-old lady with post-traumatic epilepsy controlled by sodium valproate (Depakene) 500 mg twice daily throughout pregnancy as monotherapy, gave birth to a female baby with facial features characteristic of FVS, and severe radial ray reduction. She also had wide-spaced nipples and short neck, features not described before. Sodium valproate, a widely used anticonvulsant and mood regulator, is a well-recognized teratogen that can result in severe limb deformities, craniosynostosis, neural tube defects and neurodevelopmental retardation. Therefore, we recommend that valproic acid must be avoided during pregnancy, as new generation of anticonvulsant drugs have emerged into the market. (author)

  12. Effect of valproic acid on 65Zn distribution in the pregnant rat

    International Nuclear Information System (INIS)

    Keen, C.L.; Peters, J.M.; Hurley, L.S.

    1989-01-01

    The effect of valproic acid on the distribution of gavaged 65 Zn in maternal and embryonic tissue of Sprague-Dawley rats was examined 24 h after gavaging of the drug on d 13 of pregnancy. Valproic acid treatment resulted in a significantly higher retention of 65 Zn in maternal liver and lower amounts in uterus, placenta and embryos than in controls. Compared to controls, gel chromatography of maternal liver from valproic acid-treated dams showed higher 65 Zn counts associated with a protein peak of molecular weight of 6,500, the approximate molecular weight of the Zn-binding protein metallothionein. These results support the idea that the teratogenicity of valproic acid is in part due to an induction of embryonic Zn deficiency secondary to a drug-induced sequestering of Zn into maternal liver that results in a decrease in maternal plasma Zn and subsequent reduction in embryonic Zn uptake

  13. Assessment and management of risk to wildlife from cadmium

    International Nuclear Information System (INIS)

    Burger, Joanna

    2008-01-01

    Cadmium, a nonessential heavy metal that comes from natural and anthropogenic sources, is a teratogen, carcinogen, and a possible mutagen. Assessment of potential risk from cadmium requires understanding environmental exposure, mainly from ingestion, although there is some local exposure through inhalation. Chronic exposure is more problematic than acute exposure for wildlife. There is evidence for bioaccumulation, particularly in freshwater organisms, but evidence for biomagnification up the food chain is inconsistent; in some bird studies, cadmium levels were higher in species that are higher on the food chain than those that are lower. Some freshwater and marine invertebrates are more adversely affected by cadmium exposure than are birds and mammals. There is very little experimental laboratory research on the effects of cadmium in amphibians, birds and reptiles, and almost no data from studies of wildlife in nature. Managing the risk from cadmium to wildlife involves assessment (including ecological risk assessment), biomonitoring, setting benchmarks of effects, regulations and enforcement, and source reduction

  14. Assessment and management of risk to wildlife from cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Burger, Joanna [Division of Life Sciences, Environmental and Occupational Health Sciences Institute, Consortium for Risk Evaluation with Stakeholder Participation, Rutgers University, Piscataway, New Jersey, 08854-8082 (United States)], E-mail: burger@biology.rutgers.edu

    2008-01-15

    Cadmium, a nonessential heavy metal that comes from natural and anthropogenic sources, is a teratogen, carcinogen, and a possible mutagen. Assessment of potential risk from cadmium requires understanding environmental exposure, mainly from ingestion, although there is some local exposure through inhalation. Chronic exposure is more problematic than acute exposure for wildlife. There is evidence for bioaccumulation, particularly in freshwater organisms, but evidence for biomagnification up the food chain is inconsistent; in some bird studies, cadmium levels were higher in species that are higher on the food chain than those that are lower. Some freshwater and marine invertebrates are more adversely affected by cadmium exposure than are birds and mammals. There is very little experimental laboratory research on the effects of cadmium in amphibians, birds and reptiles, and almost no data from studies of wildlife in nature. Managing the risk from cadmium to wildlife involves assessment (including ecological risk assessment), biomonitoring, setting benchmarks of effects, regulations and enforcement, and source reduction.

  15. Challenges and opportunities in the phytoremediation of heavy metals contaminated soils: A review.

    Science.gov (United States)

    Mahar, Amanullah; Wang, Ping; Ali, Amjad; Awasthi, Mukesh Kumar; Lahori, Altaf Hussain; Wang, Quan; Li, Ronghua; Zhang, Zengqiang

    2016-04-01

    Mining operations, industrial production and domestic and agricultural use of metal and metal containing compound have resulted in the release of toxic metals into the environment. Metal pollution has serious implications for the human health and the environment. Few heavy metals are toxic and lethal in trace concentrations and can be teratogenic, mutagenic, endocrine disruptors while others can cause behavioral and neurological disorders among infants and children. Therefore, remediation of heavy metals contaminated soil could be the only effective option to reduce the negative effects on ecosystem health. Thus, keeping in view the above facts, an attempt has been made in this article to review the current status, challenges and opportunities in the phytoremediation for remediating heavy metals from contaminated soils. The prime focus is given to phytoextraction and phytostabilization as the most promising and alternative methods for soil reclamation. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Endoscopy in pregnancy.

    LENUS (Irish Health Repository)

    O'mahony, Seamus

    2012-02-03

    Endoscopy is rarely required during pregnancy. The potential risks of endoscopy during pregnancy include foetal hypoxia due to sedative drugs and exposure to radiation. There is no evidence that endoscopy precipitates premature labour, and studies in this area have concluded that endoscopy during pregnancy is generally safe. There should be a strong indication for the procedure, which should be deferred whenever possible to the second trimester. Procedures should be performed without any sedation, or with the lowest dose of sedative medication. Radiation exposure should be kept to a minimum. Support should be obtained from specialists in obstetrics and anaesthesia. Indications for endoscopy during pregnancy are as follows: (1) gastroscopy: upper gastrointestinal bleeding, dysphagia, uncontrolled nausea\\/vomiting; (2) sigmoidoscopy\\/colonoscopy: rectal bleeding, diarrhoea; and (3) ERCP: choledocholithiasis, biliary pancreatitis. Sedative drugs, such as midazolam appear to be safe if used carefully. Radiation exposure during ERCP can be kept well below the danger level for teratogenicity.

  17. Report on results of seventeen years in consultations of radiation exposed pregnant women

    International Nuclear Information System (INIS)

    Bruening, L.; Arndt, D.; Laude, G.

    1992-01-01

    In a survey it will be given results of consultations of pregnant women exposed during the pregnancy in the period of 1976 to 1992 formerly in the National Board of Atomic Safety and Radiation Protection of the GDR and since 1990 in the Clinic-diagnostical Division of the Federal Health Office. The report includes dose estimations of the embryo and medical assessments of 430 pregnant women. The radiation exposure were mainly received by X-ray diagnostic (n = 406 cases) and the others by applications of radiation in nuclear medicine, research and vocational training (n = 24 cases). Results of dose and risk estimation were summarized in tables. Women having incurred fetal doses in excess of 100 mGy were recommended to interrupt pregnancy. A fetal dose above 100 mGy occured in 9 cases. The anatomico-pathological and embryological findings of the embryo or fetus showed only in one case a reference of teratogenic radiation damage. (orig.) [de

  18. High vulnerability of the developing fetal brain to ionizing radiation and hyperthermia

    International Nuclear Information System (INIS)

    Kameyama, Yoshiro

    1989-01-01

    The developing brain is one of the fetal structures most susceptible to environmental teratogenic insults, because of its long-lasting sensitive period extending from the beginning of embryonic organogenesis to the postnatal infantile period, the great vulnerability of undifferentiated neural cells to a wide range of environmental agents, and the lack of further reproductive capacity of neurons. Among the environmental agents which affect the developing brain, ionizing radiation and hyperthermia are regarded as the most important physical agents. The most prevalent disorders of the brain produced are histogenetic ones such as a deficit of cortical neurons, disorganized cortical architecture, and poor dendritic arborization of the cortical neurons. In this review, emphasis is given to a review of studies on the critical development stage for the induction of histogenetic disorders of the cerebral cortex and on the high vulnerability of developing neuronal cells to the two physical environmental agents mentioned. (author) 59 refs

  19. Prediabetes and Pregnancy

    Science.gov (United States)

    Barnes, P. H.

    1963-01-01

    In a prospective study of perinatal losses associated with prediabetes, 105 pregnancies were followed in women showing mild abnormalities of glucose tolerance. Hypoglycemic agents were not administered in the absence of frank diabetes. All patients were attended at delivery by interns or residents. Only two perinatal losses (1.5%) occurred in complicated cases, one of which might have been avoided. Perinatal losses in unrecognized prediabetics are largely due to associated obstetric factors, and in uncomplicated prediabetes should not differ from nondiabetic pregnancies. Recognition of the prediabetic state allows subsequent complications to be anticipated and treated early. In the absence of frank diabetes, hypoglycemic agents would not improve the immediate fetal salvage. Their value for reducing the incidence of recognized complications or in promoting the remote welfare of the fetus (preventing the ultimate development of diabetes) has not been established. The administration of hypoglycemic agents to the pregnant prediabetic is not recommended in view of the possible teratogenic effect. PMID:13969369

  20. A population-based case-control study of the safety of oral anti-tuberculosis drug treatment during pregnancy

    DEFF Research Database (Denmark)

    Czeizel, A.E.; Rockenbauer, M.; Olsen, J.

    2001-01-01

    OUTCOME MEASURES: Congenital abnormalities in newborn infants and fetuses diagnosed prenatally during the second and third trimesters, and postnatally from birth to the age of one year. RESULTS: Of 38,151 controls, 29 (0.08%) were exposed to anti-tuberculosis drug treatment during pregnancy......OBJECTIVE: To study the human teratogenic potential of isoniazid and other anti-tuberculosis drug treatment during pregnancy. DESIGN AND SETTING: Cases from a large population-based dataset at the Hungarian Case-Control Surveillance of Congenital Abnormalities, and controls from the National Birth...... Registry, between 1980 and 1996. Information on all oral anti-tuberculosis drug treatments during pregnancy was medically recorded. STUDY PARTICIPANTS: Women who had newborns or fetuses with congenital abnormalities (case group), and women who had babies with no congenital abnormality (control group). MAIN...