Sample records for teratogens

  1. Teratogenic evaluation of oxacillin

    DEFF Research Database (Denmark)

    Czeizel, Andrew E.; Rockenbauer, Magda; Sørensen, Henrik Toft


    Teratogenic studies of oxacillin in humans have not been published. The population-based data-set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996 contains 22,865 foetuses or newborns with congenital abnormalities and 38,151 matched control newborns without congen...

  2. Teratogenicity of sodium valproate. (United States)

    Alsdorf, Rachel; Wyszynski, Diego F


    The teratogenicity of the widely popular antiepileptic drug (AED) and mood stabiliser sodium valproate (also known as valproate, VPA) has been evidenced by previous research; however, these findings have often been limited by a small population sample of exposed women and a retrospective study design. Many factors contribute to the teratogenicity of VPA. These include the number of drugs that are co-administered, drug dosage, differences in maternal and/or infant metabolism, the gestational age of the fetus at exposure, and hereditary susceptibility. VPA has been associated with a variety of major and minor malformations, including a 20-fold increase in neural tube defects, cleft lip and palate, cardiovascular abnormalities, genitourinary defects, developmental delay, endocrinological disorders, limb defects, and autism. It has been suggested that polytherapy treatment in epileptic pregnant women increases the risk of teratogenicity in offspring. Furthermore, there is an established relationship between VPA dose and adverse outcome. Large single doses of VPA potentially cause high peak levels in the fetal serum resulting in deleterious effects. Currently there is an increase in the number of national and international pregnancy registries being formed in an effort to better identify the teratogenic effects of AEDs. These efforts hope to enhance our understanding of AEDs and their associated risks by addressing past study limitations.

  3. Teratogene effekter av antiepileptika

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    Bernt A. Engelsen


    Full Text Available  SAMMENDRAGCa. 1 av 200 gravide har epilepsi. Gravide med epilepsi har økt risiko for visse obstetriske komplikasjonerog for å føde barn med medfødte misdannelser. Risikoen for misdannelser synes koblet til bruk avantiepileptika under svangerskapet, og ikke til selve epilepsien. Alle typer misdannelser er økt, men leppeganespalteog nevralrørsdefekter utgjør særlig viktige misdannelser. Årsakene til misdannelsene er multifaktorielle.Bruk av antiepileptika i monoterapi kan sies å gi en individuell risiko for større misdannelser påca. 4-6%. Karbamazepin og natriumvalproat gir hhv. 0,5-1% og 2-3% risiko for nevralrørsdefekt. Samletrisiko for større og mindre anomalier inkludert dysmorfe ansiktstrekk synes ikke å overstige 10%. ENGLISH SUMMARYEngelsen BA. Teratogenic effects of antiepileptic drugs. Nor J Epidemiol 1997; 7 (1: 23-28.Approximately 1 in 200 pregnant women have epilepsy, and 1 in 250 births are to children of mothers whouse antiepleptic drugs (AED. Pregnant women with epilepsy have increased risk for certain obstetricalcomplications, and for giving birth to children with congenital malformations. The increased risk forcongenital malformations seems connected to the use of AED, not to the epileptic syndromes. The etiologyof congenital malformations are multifactorial. Use of AED in monotherapy is associated with anindividual risk of giving birth to a child with a major malformation of 4-6%. The specific risk of spinabifida is 0,5 to 1% for carbamazepine and 2-3% for sodium valproate.

  4. [Thalidomide teratogenicity and its direct target identification]. (United States)

    Ito, Takumi; Ando, Hideki; Handa, Hiroshi


    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.

  5. Teratogenic mechanisms associated with prenatal medication exposure. (United States)

    van Gelder, Marleen M H J; van Rooij, Iris A L M; de Jong-van den Berg, Lolkje T W; Roeleveld, Nel


    Birth defects may originate through multiple mechanisms and may be caused by a variety of possible exposures, including medications in early pregnancy. In this review, we describe six principal teratogenic mechanisms suspected to be associated with medication use: folate antagonism, neural crest cell disruption, endocrine disruption, oxidative stress, vascular disruption, and specific receptor- or enzyme-mediated teratogenesis. Knowledge about these mechanisms, for some of which evidence is mainly derived from animal models, may not only be relevant for etiologic and post-marketing research, but may also have implications for prescribing behavior for women of reproductive age. Since combinations of seemingly unrelated medications may have effects through similar teratogenic mechanisms, the risk of birth defects may be strongly increased in multi-therapy. © 2014 Société Française de Pharmacologie et de Thérapeutique.

  6. Rubella Virus Replication and Links to Teratogenicity


    Lee, Jia-Yee; Bowden, D. Scott


    Rubella virus (RV) is the causative agent of the disease known more popularly as German measles. Rubella is predominantly a childhood disease and is endemic throughout the world. Natural infections of rubella occur only in humans and are generally mild. Complications of rubella infection, most commonly polyarthralgia in adult women, do exist; occasionally more serious sequelae occur. However, the primary public health concern of RV infection is its teratogenicity. RV infection of women during...

  7. Teratogen Screening: State of the Art


    Schumann, Julia


    Due to the number of new substances coming into use every year and the increasing amounts of chemicals, which are introduced into the environment, there is a high demand for a rapid, reliable and cost-effective method for detection of developmental toxicity. To meet this challenge various in vitro techniques have been established additional to in vivo animal testing. This review introduces the techniques in existence at the moment. Requirements on an ideal in vitro teratogenicity test system ...

  8. Teratogenicity and fetotoxicity of the antiepileptics

    Directory of Open Access Journals (Sweden)

    Nikolić Predrag


    Full Text Available Pregnant women with epilepsy have more problems in maintenance of pregnancy and are under higher risk of spontaneous abort ion or occurrence of congenital fetal malformations. Use of antiepileptic drugs during pregnancy is also related to higher risk of congenital fetal malformations. The aim of our study was to determine teratogenicity and fetotoxicity of antiepileptics by performing systematic review of relevant papers. Systematic review was performed using PUBMED and Cochrane Database of Systematic Reviews. Original and review papers that relate to teratogenic effects of antiepileptic drugs were included in the analysis. Fourteen studies were found, out of which there were 7 original papers and 7 review papers. The lowest number of participants in a study was 54 and the highest 3607. Studies followed participants from 5 to 9 years. Antiepileptic drugs were used as monotherapy in 2 studies, while other studies examined both mono- and polytherapy. Doses administered varied from 600 mg (carbamazepine, 100-200 mg (lamotrigine and 600-1000 mg (valproate, depending on kind of administration (mono or polytherapy. Among all examined antiepileptic drugs, valproate has shown the highest relation to occurrence of any degree of mental retardation or congenital malformation. Risk of congenital malformations was correlated with administration of higher drug doses and the use of polytherapy. Carbamazepine was shown to be the safest drug to use during pregnancy. Literature data do not confirm teratogenic effects of antiepileptic drugs with certainty. There are not enough studies that compare drug effects in different stages of pregnancy. Limit of presented studies is also lack of information about the degree of epilepsy and eventual comorbidity.

  9. Valproic Acid Teratogenicity: A Toxicogenomics Approach (United States)

    Kultima, Kim; Nyström, Anna-Maja; Scholz, Birger; Gustafson, Anne-Lee; Dencker, Lennart; Stigson, Michael


    Embryonic development is a highly coordinated set of processes that depend on hierarchies of signaling and gene regulatory networks, and the disruption of such networks may underlie many cases of chemically induced birth defects. The antiepileptic drug valproic acid (VPA) is a potent inducer of neural tube defects (NTDs) in human and mouse embryos. As with many other developmental toxicants however, the mechanism of VPA teratogenicity is unknown. Using microarray analysis, we compared the global gene expression responses to VPA in mouse embryos during the critical stages of teratogen action in vivo with those in cultured P19 embryocarcinoma cells in vitro. Among the identified VPA-responsive genes, some have been associated previously with NTDs or VPA effects [vinculin, metallothioneins 1 and 2 (Mt1, Mt2), keratin 1-18 (Krt1-18)], whereas others provide novel putative VPA targets, some of which are associated with processes relevant to neural tube formation and closure [transgelin 2 (Tagln2), thyroid hormone receptor interacting protein 6, galectin-1 (Lgals1), inhibitor of DNA binding 1 (Idb1), fatty acid synthase (Fasn), annexins A5 and A11 (Anxa5, Anxa11)], or with VPA effects or known molecular actions of VPA (Lgals1, Mt1, Mt2, Id1, Fasn, Anxa5, Anxa11, Krt1-18). A subset of genes with a transcriptional response to VPA that is similar in embryos and the cell model can be evaluated as potential biomarkers for VPA-induced teratogenicity that could be exploited directly in P19 cell–based in vitro assays. As several of the identified genes may be activated or repressed through a pathway of histone deacetylase (HDAC) inhibition and specificity protein 1 activation, our data support a role of HDAC as an important molecular target of VPA action in vivo. PMID:15345369

  10. Teratogenia da vitamina A Vitamin A teratogenicity

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    Maria Helena de Castro Chagas


    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

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

    African Journals Online (AJOL)



    Jun 14, 2012 ... Monosodium glutamate (MSG) has been used as a flavor enhancer for decades. It has various teratogenicity effects on tested animals but has not been examined in zebra fish model to date. This experiment was conducted to study the teratogenic effects of MSG on wild-type zebra fish embryos and.

  12. Propylthiouracil is teratogenic in murine embryos.

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    Valeria C Benavides

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

  13. Perspectives of primary care clinicians on teratogenic risk counseling. (United States)

    Schwarz, Eleanor Bimla; Santucci, Aimee; Borrero, Sonya; Akers, Aletha Y; Nikolajski, Cara; Gold, Melanie A


    Women of childbearing age are commonly prescribed medications by primary care providers (PCPs) that may cause birth defects if used during pregnancy. To identify what PCPs perceive as barriers to and potential facilitators of providing counseling to women of childbearing age when teratogenic medications are prescribed, we conducted eight focus groups with 48 PCPs recruited from four clinical settings in Pittsburgh, Pennsylvania. We explored PCPs' experiences counseling women about teratogenic medications. Each focus group was audio-recorded, transcribed, and coded using a grounded theory approach by three independent coders. PCPs feel responsible for counseling women when they prescribe medications that may cause birth defects, but note difficulties identifying clinically relevant sources of information on teratogenicity. Other barriers to providing counseling include limited visit times and lack of reimbursement for preconception or teratogenic risk counseling. PCPs find it challenging to identify patients who may become pregnant and who therefore need contraceptive and/or teratogenic risk counseling. PCPs expressed a desire for online resources that could be used when explaining medication risks to patients. PCPs feel that the development of patient information materials, electronic decision support tools, clinical care systems that routinely assess patients' pregnancy risk, and changes in the reimbursement structure may facilitate counseling patients about teratogenic risks. PCPs perceive themselves as playing an important role in providing their patients information on risk of medication-induced birth defects. To ensure safe prescription of teratogenic medications, PCPs suggest interventions at both the clinic and healthcare system levels.

  14. A Review of the Teratogenic Factors Effect on Embryo

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    Manzarbanoo Shojaei fard


    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.

  15. Cancer chemotherapeutic agents as human teratogens. (United States)

    Selig, Brady P; Furr, James R; Huey, Ryan W; Moran, Colin; Alluri, Vinod N; Medders, Gregory R; Mumm, Christina D; Hallford, H Gene; Mulvihill, John J


    Cancer is the second leading cause of death among women of reproductive age. Although the coincidence of pregnancy and cancer is rare and treatment may sometimes be safely delayed, the use of chemotherapeutic agents in pregnancy is sometimes unavoidable or inadvertent. We review the literature for the use of antineoplastic agents in single-agent and combination therapy from 1951 through June 2012. We also summarize the evidence relating to teratogenicity of disorder-specific combination chemotherapy treatments for those malignancies frequently encountered in women of childbearing age. Major endpoints were called "adverse pregnancy outcomes" (APOs), to include structural anomalies (congenital malformations), functional defects, blood or electrolyte abnormalities, stillbirths, spontaneous abortions (miscarriages), and fetal, neonatal, or maternal deaths. The registry totals 863 cases. Rates of APOs (and congenital malformations) after any exposure were 33% (16%), 27% (8%), and 25% (6%), for first, second, and third trimesters. Among the groups of cancer drugs, antimetabolites and alkylating agents have the highest rates of APOs. Mitotic inhibitors and antibiotics seem more benign. Mixed results were observed from single-agent exposure, often because of small numbers of exposures. As a whole, the alkylating agents and antimetabolites are more harmful when given as a single agent rather than as part of a regimen. First-trimester exposure poses a more permanent risk to the fetus. Systematic ascertainment of women early in pregnancy, preferably in a population base, is needed for assessment of true risks. Long-term follow-up is needed to rule out neurobehavioral effects. Copyright © 2012 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Vera Ehrenstein


    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

  17. Medicinal plants with teratogenic potential: current considerations

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    Kassiane Cristine da Silva Costa


    Full Text Available The aim of this study was to present the implications of the use of herbs during pregnancy, pointing out those that should be avoided during this condition because of their abortifacient and/or teratogenic potential. We carried out searches in the databases ScienceDirect, Scielo and Google Scholar, adopting as criteria for inclusion: book chapters and/or complete articles (with abstract, available in English, Portuguese or Spanish, published from 1996 to in 2011. After a pre-selection of 83 articles, 49 bibliographies were used in the manufacturing end of the article, where 25 were from the Scielo database, 18 from ScienceDirect and 6 from Google Scholar. From the articles studied, we identified the four most commonly used plants as emmenagogue/abortifacient agents by patients of the Department of Prenatal SUS: senne, arruda, boldo and buchinha-do-norte or cabacinha. Thus, we conclude that people often adhere to the maxim "if it's natural, it does no harm" in their rational use of natural products, without the right guidance, believing that these products are safe to use. This usage is even more worrisome among the elderly, pregnant women and children. Regarding the safety of these products, some information and reliable data are scarce or contradictory.Este trabalho busca as implicações atuais sobre o uso de plantas medicinais durante a gravidez, alertando sobre aquelas que devem ser evitadas nesse período por serem potencialmente abortivas e/ou teratogênicas. Para tanto, foram realizadas buscas nas bases de dados Sciencedirect, Scielo e Google scholar, adotando-se como critérios de inclusão capítulos de livros e/ou artigos completos (com abstract e disponíveis, em português, inglês ou espanhol, publicados de 1996 a 2011. Após uma pré-seleção de 83 artigos, 49 bibliografias foram utilizadas na confecção final do artigo, sendo 25 provenientes da base de dados Scielo, 18 do Sciencedirect e 06 do Google scholar. A partir dos

  18. Histological Studies Of The Teratogenic Effects Of Camphor On The ...

    African Journals Online (AJOL)

    Aims: Since the Kidney is involved in the excretion of many toxic metabolic waste products it would be worthwhile to examine the teratogenic effects of camphor solution on the developing kidneys on adult Wistar rats. Methods: Both adult male and female Wistar rats (n=30) weighing between 150g -180g were randomly ...

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

    African Journals Online (AJOL)



    Dec 3, 2007 ... Teratogenic effect of isotretinoin on the morphology and palate development in rat fetuses. Ofusori, D. A.1*, Adelakun A. E.2, Jimoh, S. A.3, Komolafe A.O4, Falana B. A.4, and Abayomi T. A.4. 1Department of Anatomy, School of Basic Medical Sciences, Igbinedion University, Okada, P.M.B 0006, Benin City, ...

  20. Embryotoxicity and teratogenicity study with γ-cyclodextrin in rats

    NARCIS (Netherlands)

    Waalkens-Berendsen, D.H.; Verhagen, F.J.J.; Bär, A.


    The embryotoxicity/teratogenicity of γ-cyclodextrin (γ-CD) was examined in Wistar Crl:(WI)WU BR rats. γ-CD was fed at dietary concentrations of 0, 1.5, 5, 10, and 20% to groups of 25 pregnant female rats from day 0 to 21 of gestation. A comparison group received a diet with 20% lactose. The

  1. Embryotoxicity and teratogenicity study with α-cyclodextrin in rats

    NARCIS (Netherlands)

    Waalkens-Berendsen, D.H.; Bär, A.


    The embryotoxicity/teratogenicity of α-cyclodextrin (α-CD) was examined in Wistar Crl:(WI)WU BR rats. α-CD was fed at dietary concentrations of 0, 1.5, 5, 10, or 20% to groups of 25 pregnant female rats from day 0 to 21 of gestation. An additional group received a diet with 20% lactose. The

  2. Embryotoxicity and teratogenicity study with y-cyclodextrin in rabbits

    NARCIS (Netherlands)

    Waalkens-Berendsen, D.H.; Smits-van Prooije, A.E.; Bär, A.


    In a standard embryotoxicity/teratogenicity study, γ-cyclodextrin (γ-CD) was administered to groups of 16, artificially inseminated New Zealand White rabbits at dietary concentrations of 0, 5, 10, or 20%. A comparison group received a diet containing 20% lactose. Treatment started on day 0 of

  3. Embryotoxicity and teratogenicity study with neohesperidin dihydrochalcone in rats

    NARCIS (Netherlands)

    Waalkens-Berendsen, D.H.; Kuilman-Wahls, M.E.M.; Bär, A.


    The embryotoxicity/teratogenicity of neohesperidin dihydrochalcone (NHDC) was examined in Wistar Crl:(WI)WU BR rats. NHDC was fed at dietary concentrations of 0, 1.25, 2.5 or 5 to groups of 28 mated female rats from day 0 to 21 of gestation. At Cesarean section 25, 22, 23, and 23 rats were found to

  4. Embryotoxicity and teratogenicity study with erythritol in rats

    NARCIS (Netherlands)

    Smits- Prooije, A.E. van; Waalkens-Berendsen, D.H.; Bär, A.


    The embryotoxicity/teratogenicity of erythritol, a low-calorie polyol sugar substitute, was examined in Wistar Crl:(WI) WU BR rats. Erythritol was fed at dietary concentrations of 0, 2.5, 5, and 10% to groups of 32 female rats from Day 0 to 21 of gestation. The treatment was generally well tolerated

  5. Teratogenic Effects of Caffeine and Clomipramine on Rat Fetus

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    SMA Nabavi


    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.

  6. Morphometric Study Of The Teratogenic Effect Of Artesunate On The ...

    African Journals Online (AJOL)

    The teratogenic influence of maternal administration of artesunate on the morphometry of foetal nervous system was studied. Twenty virgin female Wistar rats weighing between 200g and 230g were used for this study. The animals were divided into 4 groups of 5 rats each. Each group was kept in a separate plastic cage.

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

    DEFF Research Database (Denmark)

    Hansen, Ernst; Meyer, Otto A.


    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...

  8. Histological Studies Of The Teratogenic Effects Of Camphor On The ...

    African Journals Online (AJOL)

    Histological studies of the teratogenic effects of camphor on the developing liver of the wistar rats. Annals Biomedical Sciences 2002;1:88-93.This study, carried out at the Anatomy Department of University of Ilorin between January 2002 and October 2002, involved the oral administration of varying concentrations of ...

  9. Evaluation of the teratogenic potential of chemicals in the rat. (United States)

    Fritz, H; Giese, K


    On the basis of the results of a variety of teratogenicity studies in Sprague-Dawley-derived albino rats, carried out over several years in our laboratory, an appraisal of the principal experimental procedures is set forth. Various categories of chemicals were used for the evaluation of dosage-related teratogenic potency. Salicylate, prednisolone, cyclophosphamide, 5-hydroxytryptamine (serotonin), glycinonitrile, and dimethylformamide have proven to be teratogenic under certain of the experimental conditions used. Particular differences in the embryotropic effects of acetylsalicylic acid were caused by qualitative and quantitative changes of the vehicle. Fetal morphological abnormalities, classified either as 'malformations' or as 'anomalies', may occur independently of overt maternal toxicity and/or embryotoxicity. Further, they may be closely correlated with general inhibitory effects on growth. Drugs may affect developing tissues and organs selectively due to their pharmacological activity and/or specific organ toxicity. The limitation of maternal treatment to a very short period of gestation may disclose a specific susceptibility of developmental stages of the embryo or fetus. Finally, the importance of data collected from a historical control population to the interpretation of teratogenicity data is emphasised.

  10. Embryotoxicity and teratogenicity study with α-cyclodextrin in rabbits

    NARCIS (Netherlands)

    Waalkens-Berendsen, D.H.; Smits-Van Prooije, A.E.; Bär, A.


    In a standard embryotoxicity/teratogenicity study, α-cyclodextrin (α-CD) was administered to groups of sixteen, artificially inseminated New Zealand White rabbits at dietary concentrations of 0, 5, 10, or 20%. An additional group received a diet containing 20% lactose. Treatment started on day 0 of

  11. Retinoid-like activity and teratogenic effects of cyanobacterial exudates. (United States)

    Jonas, Adam; Buranova, Veronika; Scholz, Stefan; Fetter, Eva; Novakova, Katerina; Kohoutek, Jiri; Hilscherova, Klara


    Retinoic acids and their derivatives have been recently identified by chemical analyses in cyanobacteria and algae. Given the essential role of retinoids for vertebrate development this has raised concerns about a potential risk for vertebrates exposed to retinoids during cyanobacterial blooms. Our study focuses on extracellular compounds produced by phytoplankton cells (exudates). In order to address the capacity for the production of retinoids or compounds with retinoid-like activity we compared the exudates of ten cyanobacteria and algae using in vitro reporter gene assay. Exudates of three cyanobacterial species showed retinoid-like activity in the range of 269-2,265 ng retinoid equivalents (REQ)/L, while there was no detectable activity in exudates of the investigated algal species. The exudates of one green alga (Desmodesmus quadricaudus) and the two cyanobacterial species with greatest REQ levels, Microcystis aeruginosa and Cylindrospermopsis raciborskii, were selected for testing of the potential relation of retinoid-like activity to developmental toxicity in zebrafish embryos. The exudates of both cyanobacteria were indeed provoking diverse teratogenic effects (e.g. tail, spine and mouth deformation) and interference with growth in zebrafish embryos, while such effects were not observed for the alga. Fish embryos were also exposed to all-trans retinoic acid (ATRA) in a range equivalent to the REQ concentrations detected in exudates by in vitro bioassays. Both the phenotypes and effective concentrations of exudates corresponded to ATRA equivalents, supporting the hypothesis that the teratogenic effects of cyanobacterial exudates are likely to be associated with retinoid-like activity. The study documents that some cyanobacteria are able to produce and release retinoid-like compounds into the environment at concentrations equivalent to those causing teratogenicity in zebrafish. Hence, the characterization of retinoid-like and teratogenic potency should be

  12. Comparative teratogenicity analysis of valnoctamide, risperidone, and olanzapine in mice. (United States)

    Wlodarczyk, Bogdan J; Ogle, Krystal; Lin, Linda Ying; Bialer, Meir; Finnell, Richard H


    Based on the recent findings from animal studies, it has been proposed that the therapeutic use of valnoctamide, an anxiolytic drug developed in the early 1960s, be extended to treat other neurological disorders such as epilepsy and bipolar disease. Given the scarcity of adequate data on its prenatal toxicity, a comparative teratogenicity study of valnoctamide and two of the most commonly used drugs to treat bipolar disorder, risperidone and olanzapine, was carried out in a mouse model system. Pregnant dams were treated with the aforementioned three drugs at the dose levels calculated as an equal proportion of the respective LD50 values of these drugs. The main reproductive indices examined included the numbers of implantations and resorptions, viable and dead fetuses, and fetal gross, visceral and skeletal abnormalities. The outcomes of the present study indicated that olanzapine was the most teratogenic of the three drugs, inducing maternal-, embryo-, and fetotoxicity. Risperidone also exerted a significant prenatal toxicity, but its adverse effect was less pronounced than that induced by olanzapine. Valnoctamide did not show any teratogenic effect, even when used in relatively higher dosages than olanzapine and risperidone. The observed increased skeletal abnormalities in one of the valnoctamide treatment groups were nonspecific and, as such, signaled a modest developmental delay rather than an indication that the compound could induce structural malformations. Under our experimental conditions, valnoctamide demonstrated the lowest prenatal toxicity of the three tested drugs. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Teratogenic effects of selenium in natural populations of freshwater fish. (United States)

    Lemly, A D


    The prevalence of abnormalities and associated tissue selenium residues were assessed for the fish population of Belews Lake, North Carolina, and two reference lakes in 1975, 1978, 1982, and 1992. Teratogenic defects identified included lordosis, kyphosis, scoliosis, and head, mouth, and fin deformities. Many fish exhibited multiple malformations and some were grossly deformed and distorted in appearance. Other abnormalities observed were edema, exophthalmus, and cataracts. Whole-body tissue residues of selenium in the fishes of Belews Lake were up to 130 times those in the reference lakes and the incidence of abnormalities was some 7 to 70 times greater. Teratogenic defects increased as selenium levels rose between 1975 and 1982 and fell with declining selenium levels between 1982 and 1992 as selenium inputs into Belews Lake were curtailed. The relationship between selenium residues and prevalence of malformations approximated an exponential function (R2 = 0.881, P selenium and 0-70% deformities. This relationship could be useful in evaluating the role of teratogenic effects in warm-water fish populations suspected of having selenium-related reproductive failure. Unique conditions may have existed in Belews Lake which led to the high frequency and persistence of deformities in juvenile and adult fish. In other, less-contaminated locations competition and predation may eliminate malformed individuals in all but the larval life stage. Teratogenesis could be an important, but easily overlooked phenomenon contributing to fishery reproductive failure in selenium-contaminated aquatic habitats.

  14. Inhibition of isotretinoin teratogenicity by acetylsalicylic acid pretreatment in mice. (United States)

    Kubow, S


    Although isotretinoin (ITR) has been suggested to cause malformations via cytopathic effects on embryonic cells, the molecular mechanisms of ITR cytotoxicity in teratogenesis are not clear. Since ITR undergoes metabolism by prostaglandin synthase to a potentially cytotoxic peroxyl free radical, the possible role of prostaglandin synthase metabolism as a modulator of ITR teratogenicity was evaluated. Craniofacial and limb abnormalities were noted in fetuses on day 18.5 of gestation following administration of ITR to pregnant CD-1 mice in a three dose regimen of 100 mg/kg at 4 hr intervals on day 10.5 of gestation (plug day = day 0.5 of gestation). Mice were also treated with acetylsalicylic acid (ASA), an irreversible inhibitor of the cyclooxygenase component of prostaglandin synthase, at doses of 20 and 60 mg/kg body weight 2 hr prior to each ITR dose. ASA pretreatment of mice receiving ITR treatment showed a dose-dependent decrease in the overall incidence of malformations, number of defects per fetus, and the incidence of specific craniofacial and limb defects. Equivalent doses of ASA given to control mice did not cause malformations or alter the incidence of resorptions. These results demonstrate that ASA is able to ameliorate the teratogenic effects of ITR observed in fetal mice near term and indicate that prostaglandin metabolism could play a mechanistic role in ITR teratogenicity.


    Abstract The purine analog 2-chloro-2'-deoxyadenosine (2-CdA, cladribine), an anti-leukemic and immunosuppressive agent, has been found to be teratogenic in the mouse and rabbit, causing ocular and limb defects. The current study examined the teratogenic potential of th...

  16. The teratogenic effects of alprazolam intake on rat fetus

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    Takzare N


    Full Text Available "n 800x600 Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif";} Background: Alprazolam belongs to benzodiazepine family and is increasingly used these days by pregnant women. It should be noticed that alprazolam exposure during pregnancy may have teratogenic effects on the fetus. Till now, limited studies have been conducted on the teratogenic effect of alprazolam. In this study, teratogenicity of alprazolam intake during pregnancy and its effects on fetus development was investigated. "n"nMethods: About 20 virgin rats of known age and weight were selected. After being pregnant, they were divided into four groups which contained five animals in each group: Negative and positive control groups. The case group exposed to 1 to 6 mg/kg/day alprazolam. The fetuses were first studied macroscopically regarding anomalies, and then histologically and histochemically to inspect the defects of tissue organogenesis."n"nResults: Our results show that there was significant difference especially at the dose 6 mg/kg weight and length of the cases compared to the control group. It appeared that at the dose of 6 mg/kg/day, cleft lip and palates were seen in the animals. The highest anomalies of limbs were also seen at the dose of 6 mg/kg/day. The statistical results indicate that alprazolam intake during the second half of pregnancy can lead to irreversible anomalies."n"nConclusion: Our results indicate that alprazolam in doses higher than 4 mg/kg/day might cause teratogenic effect. It seems that benzodiazepine therapy among pregnant woman would be better to avoid during the

  17. Teratogenicity of patulin and patulin adducts formed with cysteine. (United States)

    Ciegler, A; Beckwith, A C; Jackson, L K


    The mean lethal dose of patulin for the chicken embryo injected in the air cell before incubation was determined to be 68.7 mug and that for the 4-day-old embryo was 2.35 mug. Both patulin (1 to 2 mug/egg) and the reaction mixture between patulin and cysteine (15 to 150 mug of patulin equivalents) were teratogenic to the chicken embryo. At least two ninhydrin-negative and four ninhydrin-positive products were formed during the latter reaction. Our explanation of the reaction mechanism remains to be elaborated. PMID:1275488

  18. Systematic procedure for the classification of proven and potential teratogens for use in research. (United States)

    Eltonsy, Sherif; Martin, Brigitte; Ferreira, Ema; Blais, Lucie


    Although there is strong evidence that some medications are teratogenic, the current lists of teratogens to be used in research are outdated. The objective of this study was to develop an updatable and systematic procedure to the classification of medications proven and potentially teratogenic in the first trimester of pregnancy, for use in research. We developed a two-step procedure for teratogen classification. Step 1 includes classifying the medications from Drugs in Pregnancy and Lactation: a Reference Guide to Fetal and Neonatal Risk (9th ed.) into two provisional lists: (1) teratogenic medications, and (2) potentially teratogenic medications. We also searched other references to add other medications. In Step 2, the Teratology Information System (TERIS) database was searched, and the medication was classified as teratogenic or potentially teratogenic according to a newly developed scheme. Expert consensus was used if a medication was not recorded in TERIS. A total of 114 medications were identified in Drugs in Pregnancy and Lactation: a Reference Guide to Fetal and Neonatal Risk, with 57 medications in each provisional list. Seventy-eight medications were identified in other sources. A total of 135 medications were included in Step 2; the TERIS scheme classified 23 medications, and 112 medications required expert opinion. The two experts agreed on 78.6% of the medications (kappa = 0.63). We identified 91 teratogenic and 81 potentially teratogenic medications. Using reliable references, we established a systematic procedure to the classification of medications with evidence of or potential teratogenic risk. These exhaustive lists will be useful in teratology research and related fields. © 2016 Wiley Periodicals, Inc.

  19. Teratogenic efects of injected methylmercury on avian embryos (United States)

    Heinz, Gary H.; Hoffman, David J.; Klimstra, Jon D.; Stebbins, Katherine R.; Kondrad, Shannon L.; Erwin, Carol A.


    Controlled laboratory studies with game farm mallards (Anas platyrhynchos) and chickens (Gallus gallus) have demonstrated that methylmercury can cause teratogenic effects in birds, but studies with wild species of birds are lacking. To address this need, doses of methylmercury chloride were injected into the eggs of 25 species of birds, and the dead embryos and hatched chicks were examined for external deformities. When data for controls were summed across all 25 species tested and across all types of deformities, 24 individuals out of a total of 1,533 (a rate of 1.57%) exhibited at least one deformity. In contrast, when data for all of the mercury treatments and all 25 species were summed, 188 deformed individuals out of a total of 2,292 (8.20%) were found. Some deformities, such as lordosis and scoliosis (twisting of the spine), misshapen heads, shortening or twisting of the neck, and deformities of the wings, were seldom observed in controls but occurred in much greater frequency in Hg-treated individuals. Only 0.59% of individual control dead embryos and hatchlings exhibited multiple deformities versus 3.18% for Hg-dosed dead embryos and hatchlings. Methylmercury seems to have a widespread teratogenic potential across many species of birds.

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

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    Thiago Mazzu-Nascimento


    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.

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

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    Inouye, Minoru; Kajiwara, Yuji


    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.)


    Directory of Open Access Journals (Sweden)

    S.A. Sher


    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.

  3. Inhibition of thalidomide teratogenicity by acetylsalicylic acid: evidence for prostaglandin H synthase-catalyzed bioactivation of thalidomide to a teratogenic reactive intermediate. (United States)

    Arlen, R R; Wells, P G


    Thalidomide is a teratogenic sedative-hypnotic drug that is structurally similar to phenytoin, which is thought to be bioactivated by prostaglandin H synthase (PHS) and other peroxidases to a teratogenic reactive intermediate. The relevance of this mechanism to thalidomide teratogenicity was evaluated in pregnant New Zealand White rabbits treated with thalidomide at 11:00 A.M. on gestational days 8 to 11, with day 0 indicating the time when sperm were observed in the vaginal fluid. Thalidomide (7.5 mg/kg i.v.) produced mainly fetal limb anomalies analogous to those observed in humans. Thalidomide (25-200 mg/kg i.p.), produced a dose-related increase in a spectrum of fetal anomalies, and in postpartum lethality, but did not produce a reliable incidence of limb anomalies. In subsequent studies, pregnant does received the irreversible PHS inhibitor acetylsalicylic acid (ASA), 75 mg/kg i.p., or its vehicle, followed 2 hr later by thalidomide, 7.5 mg/kg i.v., or its vehicle. ASA pretreatment was remarkably embryoprotective, resulting in respective 61.2 and 61.4% decreases in thalidomide-initiated fetal limb anomalies (P = .002) and postpartum fetal lethality (P teratogenicity, suggesting that thalidomide may be bioactivated by PHS to a teratogenic reactive intermediate.

  4. The art and science of teratogen risk communication. (United States)

    Conover, Elizabeth A; Polifka, Janine E


    Despite scientific advances in clinical teratology, exposures during pregnancy still cause great anxiety and misunderstanding. Patients and health care providers are frequently called upon to determine the health implications of scientific studies, which may involve limited and contradictory data. These findings are often conveyed numerically, which is a particularly difficult form of information for both patients and their health providers to understand and interpret. Almost half of the general population (and a substantial minority of physicians) have difficulty with numeracy. Patients with low numeracy tend to interpret information in an absolute manner and ignore uncertainty, have more difficulty using numeric information to inform their choices, and are more easily influenced by emotion and the format used in presenting information. Formats involved in conveying probability include positive or negative framing, use of relative versus absolute risk, and ratios and percentages. Health providers should communicate risk analysis in a fashion that facilitates comprehension and results in informed behavior. This is more likely to be achieved when risks are conceptualized as more than just numbers, and are considered in the context of individuals' life circumstances and values. Most teratogen risk communication is done over the telephone; this presents both advantages and challenges. Strategies are suggested to improve risk communication. These include avoiding the use of relative risk, using a consistent denominator, framing the information in a variety of ways (positive vs. negative), using verbal qualifiers judiciously, and employing visual aids. Copyright © 2011 Wiley-Liss, Inc.

  5. The teratogenic effects of imatinib mesylate on rat fetuses

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    M.M. El Gendy


    Full Text Available Imatinib mesylate, a selective tyrosine kinase inhibitor, is the first line treatment against chronic myelogenous leukemia and gastrointestinal stromal tumors. The aim of the present study is to investigate the effects of imatinib mesylate on the pregnant rats and their fetuses. Pregnant rats were divided into three groups; the first group served as a control group. The second and third groups were orally administered imatinib at doses of 36 mg/kg body weight or 54 mg/kg b.wt. on gestation days (SDs 6 through 13 or SDs 13 through 19, respectively. All animals were sacrificed on the 20th day of gestation. Treatment with imatinib caused a reduction of maternal body weight gain, uterine and placental weights, increased rate of abortion and fetal resorptions. High dose of imatinib caused fetal congenital deformities represented in harelip, contraction of the fore limbs, and paralysis of the hind limbs, exencephaly, encephalocoele and distended abdominal wall, besides occurrence of wavy ribs and absence of other ribs in addition to skeletal growth retardation and lack of ossification of the most skeletal elements. The present work concluded that imatinib is teratogenic when given orally to pregnant rats at 54 mg/kg b.wt. and causes direct maternal or developmental toxicity.

  6. Carcinogenic, mutagenic and teratogenic risks associated with vinyl chloride. (United States)

    Infante, P F; Wagoner, J K; Waxweiler, R J


    The data presented demonstrate clearly that vinyl chloride (VC) is related to a significant excess of mortality from cancer of the liver, lung and brain among workers occupationally exposed to VC. The risk of dying from cancer of the lymphatic and hematopoietic system also appears to increase with an increase in latency. These cancer sites could have been predicted by the animal bioassay conducted by Maltoni. With regard to the liver, even the histophthologic type of cancer (angiosarcoma) was observed first in experimental animals. A study of cancer mortality among populations residing proximate to VC polymerization facilities also demonstrated an increased risk of dying from CNS and lymphatic cancer. These latter findings raise cause for concern about out-plant emmissions of VC, but without further study these cancers obviously cannot be interpreted as being related to out-plant exposure to VC. Various test systems now have elicited a positive mutagenic response to VC. Thus, our observations of a significant excess of fetal mortality among the wives of males, who were occupationally exposed to VC, raise public health concern that VC may be mutagenic in humans. With regard to the teratogenicity of VC, observations of a significant excess of children born with birth defects were reported among populations residing proximate to VC polymerization facilities. Additional epidemiologic study is needed to determine whether a repeated pattern of excessive numbers of children born with birth defects can be observed in other communities with VC polymerization facilities.

  7. Mycophenolate mofetil embryopathy: A newly recognized teratogenic syndrome. (United States)

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


    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.

  8. Teratogenic effects of five anticancer drugs on Xenopus laevis embryos. (United States)

    Isidori, Marina; Piscitelli, Concetta; Russo, Chiara; Smutná, Marie; Bláha, Luděk


    In recent years, the environmental presence of pharmaceuticals - including anticancer drugs - is an emerging issue. Because of the lack of appropriate critical studies about anticancer drug effects in frogs, the aim of the present study was to investigate lethal and teratogenic effects of five anticancer drugs widely used in large quantities, i.e. 5-flourouracil, capecitabine, cisplatin, etoposide, and imatinib, in the embryos of the South African clawed frog, Xenopus laevis, using FETAX - Frog Embryo Teratogenesis Assay in Xenopus. None of the studied anticancer drugs induced statistically significant mortality within the concentrations tested (0.01-50mg/L, depending on the studied compound), and no growth inhibition of embryos after a 96-h exposure was observed. Except for cisplatin, the other pharmaceuticals induced an increase of developmental malformations such as abdominal edema, axial flexure, head, eyes, gut and heart malformations with statistically significant effects observed at the highest concentrations tested (50mg/L for 5-flourouracil; 30mg/L for etoposide and 20mg/L for capecitabine and imatinib). The results indicate that anticancer drugs can affect embryogenesis mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Embryotoxicity and teratogenicity of environmental contaminants to bird eggs (United States)

    Hoffman, D.J.


    First awareness that direct topical application of xenobiotics to bird eggs could be harmful to avian development dates back to the turn of the century. The most widely documented evidence of embryotoxicity following direct exposure comes from petroleum contaminant studies, conducted with at least 10 different avian species. Many petroleum crude oils, refined oils, and waste oils are embryotoxic and moderately teratogenic to different species; LD50s are often less than 5 iL of oil per egg. Toxicity is generally dependent upon the PAH concentration and composition (presence of higher weight PAHs). Five of seven industrial effluents caused significant reduction of embryonic growth in mallards following brief immersion of the eggs. Of the insecticides, organophosphates have been the most widely studied with respect to potential for direct embryotoxicity and teratogenicity following spraying or immersion of eggs. Phenoxy herbicides including 2,4-D and 2,4,5-T have been the most widely studied class of herbicides with respect to potential embryotoxicity of spray application. However, more recent evaluations have indicated that this is not the most toxic class of herbicides. Paraquat was found to be highly toxic in at least three species. Herbicides with LC50s that occurred at ten times the field level of application or less for mallard embryos included bromoxynil with MCPA, methyldiclofop, paraquat, prometon, propanil, and trifluralin. Of different gaseous and particulate air pollutants, ozone and particulates rich in PAH content appeared to be potentially embryotoxic, based on laboratory studies. Environmental contaminants in all classes reviewed have been shown to cause physiological and biochemical disturbances in embryos or hatchlings indicative of contaminant exposure, organ damage, or delayed development. Residue studies have shown the presence of DDT, 2,4-D, 2,4,5-T, decamethrin, petroleum hydrocarbons, and methylmercury after direct exposure of eggs. Ability of

  10. Teratogenic effects of organic extracts from the Pearl River sediments on Xenopus laevis embryos. (United States)

    Zhang, Cong; Liu, Xinhui; Wu, Dan; Liu, Guannan; Tao, Li; Fu, Wenjun; Hou, Jing


    Toxicity of organic extracts from the Pearl River sediments was investigated with Xenopus laevis embryos. The effects of sediment organic extracts on the mortality, body length and malformation of X. laevis embryos were tested by the Frog Embryo Teratogenesis Assay-Xenopus (FETAX). The 96-h LC₅₀ values for X. laevis embryos ranged from 62 to 137 g/L (g extracted sediment per L), and the toxicity effect on body length of larvae was not significant under 20 g/L. However, the teratogenic effects produced by sediment organic extracts were diverse, including edema, hypopigmentation, cardiac and ocular malformations, abdomen recurved and curved spine. The percentage of malformations increased with increasing sediment organic extracts, and even reached almost 100% at 10 and 20 g/L in Guangzhou district. A gradient of pollution in the Pearl River sediments was discerned from the teratogenic toxicity. Guangzhou district showed higher teratogenic toxicity compared with Panyu and Nansha districts as a possible consequence of high levels of PAHs, PCBs, OCPs and NP in the sediments. The teratogenic effects of organic extracts from the Pearl River sediments were successfully assessed which indicated the feasibility of teratogenic potential studies of sediments using X. laevis embryos. Copyright © 2013. Published by Elsevier B.V.

  11. Free radical-mediated oxidative DNA damage in the mechanism of thalidomide teratogenicity. (United States)

    Parman, T; Wiley, M J; Wells, P G


    The sedative drug thalidomide ([+]-alpha-phthalimidoglutarimide), once abandoned for causing birth defects in humans, has found new therapeutic license in leprosy and other diseases, with renewed teratological consequences. Although the mechanism of teratogenesis and determinants of risk remain unclear, related teratogenic xenobiotics are bioactivated by embryonic prostaglandin H synthase (PHS) to a free-radical intermediates that produce reactive oxygen species (ROS), which cause oxidative damage to DNA and other cellular macromolecules. Similarly, thalidomide is bioactivated by horseradish peroxidase, and oxidizes DNA and glutathione, indicating free radical-mediated oxidative stress. Furthermore, thalidomide teratogenicity in rabbits is reduced by the PHS inhibitor acetylsalicylic acid, indicating PHS-catalyzed bioactivation. Here, we show in rabbits that thalidomide initiates embryonic DNA oxidation and teratogenicity, both of which are abolished by pre-treatment with the free radical spin trapping agent alpha-phenyl-N-t-butylnitrone (PBN). In contrast, in mice, a species resistant to thalidomide teratogenicity, thalidomide does not enhance DNA oxidation, even at a dose 300% higher than that used in rabbits, providing insight into an embryonic determinant of species-dependent susceptibility. In addition to their therapeutic implications, these results constitute direct evidence that the teratogenicity of thalidomide may involve free radical-mediated oxidative damage to embryonic cellular macromolecules.

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

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    Panikkar Bindu


    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.

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

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    Damase-Michel C


    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.

  14. Assessing the availability of the teratogenic drug isotretinoin outside the pregnancy prevention programme : a survey of e-pharmacies

    NARCIS (Netherlands)

    Lagan, Briege M.; Dolk, Helen; White, Bronagh; Uges, Donald R. A.; Sinclair, M.

    PurposeThe increase in online purchasing of medications raises safety concerns regarding teratogenic drugs. The use of the teratogenic drug isotretinoin' for women of childbearing age requires strict adherence to the Pregnancy Prevention Programme (PPP), a risk minimisation measure imposed on

  15. Carcinogens, Teratogens and Mutagens: Their Impact on Occupational Health, Particularly for Women in Veterinary Medicine. (United States)

    Milligan, J. E.; And Others


    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)

  16. a morphometric study of the teratogenic effect of artesunate on the ...

    African Journals Online (AJOL)


    Summary: The teratogenic influence of maternal administration of artesunate on the morphometry of foetal nervous system was studied. Twenty virgin female Wistar rats weighing between 200g and 230g were used for this study. The animals were divided into 4 groups of 5 rats each. Each group was kept in a separate ...

  17. Teratogenic effects of antiepileptic drugs : Use of an international database on malformations and drug exposure (MADRE)

    NARCIS (Netherlands)

    Arpino, C; Brescianini, S; Robert, E; Castilla, EE; Cocchi, G; Cornel, MC; de Vigan, C; Lancaster, PAL; Merlob, P; Sumiyoshi, Y; Zampino, G; Renzi, C; Resano, A; Mastroiacovo, P


    Purpose: The study goal was to assess teratogenic effects of antiepileptic drugs (AEDs) through the use of a surveillance system (MADRE) of infants with malformations. Methods: Information on all malformed infants (1990-1996) with maternal first-trimester drug exposure was collected by the

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

    DEFF Research Database (Denmark)

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


    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...

  19. Pharmacological safety during pregnancy: the principles of teratogenesis and teratogenicity of drugs

    Directory of Open Access Journals (Sweden)

    O. V. Reshet’ko


    Full Text Available Drugs used during pregnancy simultaneously have an impact on 2 populations — fetal and maternal. The article is devoted to teratogenic drugs exposition; it points out the need for further research in the field of pharmaceutical safety during pregnancy. Authors analyzed the multiplicity of the congenital disorders in infants, including birth defects cuased by drug application. For ethical reasons, researchers can not conduct any studies on the safety of medicines during pregnancy. Authors suppose that collection of additional information during the marketing phase as a part of the routine pharmacovigilance program and the targeted pharmacoepidemiological trials with the current evaluation of the teratogenic risk of drugs will help to achieve the goals.

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

    DEFF Research Database (Denmark)

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


    -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...

  1. An avian model for the reversal of neurobehavioral teratogenicity with neural stem cells


    Dotan, Sharon; Pinkas, Adi; Slotkin, Theodore A.; Yanai, Joseph


    A fast and simple model which uses lower animals on the evolutionary scale is beneficial for developing procedures for the reversal of neurobehavioral teratogenicity with neural stem cells. Here, we established a procedure for the derivation of chick neural stem cells, establishing embryonic day (E) 10 as optimal for progression to neuronal phenotypes. Cells were obtained from the embryonic cerebral hemispheres and incubated for 5–7 days in enriched medium containing epidermal growth factor (...

  2. Valproic acid increases expression of methylenetetrahydrofolate reductase (MTHFR) and induces lower teratogenicity in MTHFR deficiency


    Roy, Marc; Leclerc, Daniel; Wu, Qing; Gupta, Sapna; Kruger, Warren D.; Rozen, Rima


    Valproate (VPA) treatment in pregnancy leads to congenital anomalies, possibly by disrupting folate or homocysteine metabolism. Since methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of folate interconversion and homocysteine metabolism, we addressed the possibility that VPA might have different teratogenicity in Mthfr+/+ and Mthfr+/− mice and that VPA might interfere with folate metabolism through MTHFR modulation. Mthfr+/+ and Mthfr+/− pregnant mice were injected with VPA on gest...

  3. The teratogenic effects of Lorazepam on the organogenesis of the rat fetus


    Pasbakhsh P; Mehrannia K; Barbarestani M


    Lorazepam has in increasingly being used in our country in recent years. Pharmacologically, lorazepam belongs to the benzodiazepines known for their wide neurotropic properties. There have been several studies on the side effects of the drug as stress disorders, tumors, preconvulsive activities in case of epileptic attacks, overdose, and behavioral problems, but little is known regarding the teratogenicity of the drug and its effects on the craniofascial development. In this study, a group of...

  4. Effect of nitroprusside on furosemide-induced skeletal teratogenicity in rat fetuses

    Directory of Open Access Journals (Sweden)

    Mahmood Khaksary Mahabady


    Full Text Available Background: Furosemide as a loop diuretic can use in treatment of hypertension, renal or heart failures and cirrhosis, when sodium retention is significant. It is known that use of furosemide can be lead congenital abnormalities in humans and animals. Nitroprusside as a NO donor can decrease blood supply complications and constriction of placenta and uterus via vasodilation and improvment blood supply. The aim of this study was preventation or decrease of teratogenicity form furosemide in rat fetuses by sodium nitroprusside. Materials and Methods: This study was performed on 28 pregnant rats that were divided into four groups, the groups consist control, furosemide, sodium nitroprusside and furosemide plus sodium nitroprusside. Drugs were administrated on 14th and 16th day of gestation. Test groups received furosemide (200mg/kg orally, and nitroprusside (0.5 mg/kg intraperitoneally. The rats were euthanized and fetuses were collected at 19th day of gestation, after weight and length determination, they stained by Alizarin red- Alician blue method. Then the skeletal system of the stained fetuses was investigated by stereomicroscope for teratogenicity effects. Results: The results showed the cleft palate, wavy ribs and decreased ossification mean incidence in forelimbs and hindlimbs were 11.11%, 68.88% and 20% in the fetuses of the rats received furosemide, where as it decreased to 7.31%, 21.95% and 12.19% in group which received furosemide plus nitroprusside, respectively. Conclusion: It is concluded that sodium nitroprusside can significantly decrease teratogenicity induced by furosemide.

  5. Teratogenic Effects of Coadministration of Fluoxetine and Olanzapine on Rat Fetuses

    Directory of Open Access Journals (Sweden)

    Azam Bakhtiarian


    Full Text Available Objective. Depression during pregnancy is a relatively common problem. Since little is known about the teratogenic effects of concomitant administration of fluoxetine and olanzapine during the organogenesis period, the aim of the present study was to evaluate the teratogenic effects of coadministration of fluoxetine and olanzapine on rat fetuses. Method. Forty-two pregnant rats were divided into seven groups, randomly. The first group received 0.5 mL of normal saline as the control. The second and third groups received fluoxetine at doses of 9 mg/kg and 18 mg/kg, respectively. Olanzapine was injected at 3 mg/kg and 6 mg/kg to the fourth and fifth groups, respectively. The sixth group received 9 mg/kg fluoxetine and 3 mg/kg olanzapine. Finally, the seventh group was administrated with fluoxetine and olanzapine at 18 mg/kg and 6 mg/kg, respectively. Drugs were injected intraperitoneally between day eight and day 15 of the pregnancy. On the 17th day of pregnancy, the fetuses were removed and micro-/macroscopically studied. Results. Fetuses of rats receiving high doses of these drugs showed a significant rate of cleft palate development, premature eyelid opening and torsion anomalies, compared to the control group (P≤0.01. It is concluded that these drugs can lead to teratogenicity, so their concomitant use during pregnancy should be avoided, or if necessary their doses must be decreased.

  6. Teratogenicity study of N-methylpyrrolidone after dermal application to Sprague-Dawley rats. (United States)

    Becci, P J; Knickerbocker, M J; Reagan, E L; Parent, R A; Burnette, L W


    Teratogenicity studies were performed in rats given N-methylpyrrolidone, a solvent used in chemical processing. Dosages of 75,237 and 750 mg of N-methylpyrrolidone/kg body weight/day were administered dermally to groups of 25 pregnant Sprague-Dawley rats on days 6 through 15 of gestation. Additionally, the study used a positive dermal control. Hexafluoroacetone, was chosen based on its dermal teratogenic activity. An oral positive control, aspirin, was included in order to add significance to the data generated in the experimental positive dermal control group. All animals were killed and subjected to uterine examination on day 20 of gestation. Maternal toxicity was indicated at 750 mg of N-methylpyrrolidone/kg by reduced body weight gain during gestation. Treatment with N-methylpyrrolidone resulted in dose-dependent brightly colored yellow urine and dry skin. Treatment at the high dosage level resulted in fewer live fetuses per dam, an increase in the percentage of resorption sites and skeletal abnormalities. These effects could be the result of maternal toxicity. There was no evidence of teratogenic effects nor effects on the dams at 75 and 237 mg/kg of body weight.

  7. Marshall J. Edwards: discoverer of maternal hyperthermia as a human teratogen. (United States)

    Graham, John M


    In a series of animal studies performed over a career spanning 40 years at the University of Sydney, Professor Marshall J. Edwards investigated the hypothesis that maternal hyperthermia during gestation can be teratogenic to the developing fetus. He is one of few investigators to have discovered a known human teratogen primarily through animal studies. In 1970 he earned his Ph.D. from the University of Sydney, writing a doctoral thesis entitled "A Study of Some Factors Affecting Fertility of Animals with Particular Reference to the Effects of Hyperthermia on Gestation and Prenatal Development of the Guinea-Pig." He went on to prove that hyperthermia-induced malformations in animals involve many organs and structures, particularly the central nervous system. Other defects include craniofacial anomalies, heart defects and hypodactyly, cataracts and coloboma, kyphoscoliosis, renal anomalies, dental agenesis, and abdominal wall defects. In a series of carefully planned and executed experiments, he demonstrated that the type of defect is related to the timing of the hyperthermic insult, and analyzed the underlying mechanisms. Cell death, membrane disruption, vascular disruption, and placental infarction were all implicated in causing embryonic damage. This special article reviews the scientific discoveries and personal philosophy of Marshall J. Edwards, the discoverer of maternal hyperthermia as a human teratogen.

  8. The Dihydroxy Metabolite of the Teratogen Thalidomide Causes Oxidative DNA Damage. (United States)

    Wani, Tasaduq H; Chakrabarty, Anindita; Shibata, Norio; Yamazaki, Hiroshi; Guengerich, F Peter; Chowdhury, Goutam


    Thalidomide [α-(N-phthalimido)glutarimide] (1) is a sedative and antiemetic drug originally introduced into the clinic in the 1950s for the treatment of morning sickness. Although marketed as entirely safe, more than 10 000 babies were born with severe birth defects. Thalidomide was banned and subsequently approved for the treatment of multiple myeloma and complications associated with leprosy. Although known for more than 5 decades, the mechanism of teratogenicity remains to be conclusively understood. Various theories have been proposed in the literature including DNA damage and ROS and inhibition of angiogenesis and cereblon. All of the theories have their merits and limitations. Although the recently proposed cereblon theory has gained wide acceptance, it fails to explain the metabolism and low-dose requirement reported by a number of groups. Recently, we have provided convincing structural evidence in support of the presence of arene oxide and the quinone-reactive intermediates. However, the ability of these reactive intermediates to impart toxicity/teratogenicity needs investigation. Herein we report that the oxidative metabolite of thalidomide, dihydroxythalidomide, is responsible for generating ROS and causing DNA damage. We show, using cell lines, the formation of comet (DNA damage) and ROS. Using DNA-cleavage assays, we also show that catalase, radical scavengers, and desferal are capable of inhibiting DNA damage. A mechanism of teratogenicity is proposed that not only explains the DNA-damaging property but also the metabolism, low concentration, and species-specificity requirements of thalidomide.

  9. Evaluation on Genotoxicity and Teratogenicity of Aqueous Extract from Cyclocarya paliurus Leaves

    Directory of Open Access Journals (Sweden)

    Lihong Deng


    Full Text Available Tremendous attentions have been attracted to the foods labeled with natural, green, organic, and nuisanceless conception of healthy diet. Therefore, it is of great significance to establish relative defining guidance for safe assessment of botanicals. Cyclocarya paliurus (Batal. Iljinsk (family Cyclocaryaceae, called sweet tea tree, is a well-known edible and medicinal plant, which has been widely used in China as drug formulation for the treatment of hypertension and diabetes. Despite its benefits, no reports have been described on the safe assessment of C. paliurus leaves aqueous extract. In this study, we have conducted the genotoxicity assay (including Ames test, bone marrow polychromatic erythrocyte micronucleus test, and sperm abnormality test in mice and traditional teratogenicity assay in rats (maternal toxicity, embryo toxicity, and teratogenicity test to assess the genetic and teratogenic safety of aqueous extracts from C. paliurus leaves. Results of each assay show that the highest dose of C. paliurus leaves aqueous extract is considered relatively nonmutagenic and nonteratogenic, revealing that C. paliurus leaves possess safety and quality as a functional additional ingredient in food.

  10. Evaluation of acute toxicity and teratogenic effects of plant growth regulators by Daphnia magna embryo assay. (United States)

    Wang, Kai-Sung; Lu, Chi-Yuan; Chang, Shih-Hsien


    This study selected common plant growth regulators (Atonik, Cytokinin, Ethephon, Gibberellic acid and Paclobutrazol) to investigate their biological toxicity to the waters of the important biological indicator Daphnia magna. The methods used in this study included traditional neonate acute toxicity test, new Daphnia embryo toxicity test, and teratogenic embryo test. The study concluded that the acute toxicity of the five PGRs to Daphnia neonate had EC(50) value range of 1.9-130.5 mg l(-1), while acute toxicity of PGRs on Daphnia embryo had EC(50) value range of 0.2-125 mg l(-1); the Daphnia embryos' LOEC values (0.05-48 mg l(-1)) for the five PGRs were lower than embryo EC(50) values. The toxic ratios of 48 h EC(50) (neonate)/48 h LOEC (embryo) for 5 PGRs were 19-512 times. The study found that teratogenic effects of Paclobutrazol and Cytokinin induced in embryo were higher than those of most other PGRs. Microscopic observation of the teratogenic effects showed that all 5 PGRs induced malformations of the second antenna, rostrum, Malpighian tube, sensory bristles, and tail spine as well as function loss and death. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. A comparison of the teratogenicity of methylmercury and selenomethionine injected into bird eggs (United States)

    Heinz, Gary H.; Hoffman, David J.; Klimstra, Jon D.; Stebbins, Katherine R.


    Methylmercury chloride and seleno-L-methionine were injected separately or in combinations into the fertile eggs of mallards (Anas platyrhynchos), chickens (Gallus gallus), and double-crested cormorants (Phalacrocorax auritus), and the incidence and types of teratogenic effects were recorded. For all three species,selenomethionine alone caused more deformities than did methylmercury alone. When mallard eggs were injected with the lowest dose of selenium (Se) alone (0.1 μg/g), 28 of 44 embryos and hatchlings were deformed, whereas when eggs were injected with the lowest dose of mercury (Hg) alone (0.2 μg/g), only 1 of 56 embryos or hatchlings was deformed. Mallard embryos seemed to be more sensitive to the teratogenic effects of Se than chicken embryos:0 of 15 chicken embryos or hatchlings from eggs injected with 0.1 μg/g Se exhibited deformities. Sample sizes were small with double-crested cormorant eggs, but they also seemed to be less sensitive to the teratogenic effects of Se than mallard eggs. There were no obvious differences among species regarding Hg-induced deformities. Overall, few interactions were apparent between methylmercury and selenomethionine with respect to the types of deformities observed. However, the deformities spina bifida and craniorachischisis were observed only when Hg and Se were injected in combination. One paradoxical finding was that some doses of methylmercury seemed to counteract the negative effect selenomethionine had on hatching of eggs while at the same time enhancing the negative effect selenomethionine had on creating deformities. When either methylmercury or selenomethionine is injected into avian eggs, deformities start to occur at much lower concentrations than when the Hg or Se is deposited naturally in the egg by the mother.

  12. Common increase of GATA-3 level in PC-12 cells by three teratogens causing autism spectrum disorders. (United States)

    Rout, Ujjwal K; Clausen, Pete


    Autism spectrum disorder (ASD) is a disease of neuro-developmental origin of uncertain etiology. The current understanding is that both genetic and environmental factors contribute to the development of ASD. Exposure to valproate, thalidomide and alcohol during gestation are amongst the environmental triggers that are associated with the development of ASD. These teratogens may disturb the ontogeny of the brain by altering the expression pattern of genes that regulate the normal development of the brain. In this study, a neuron-like PC-12 cell model was used to examine the effects of these compounds on the binding potential of 50 different transcription factors to understand the molecular mechanism/s that may be involved in the teratogenesis caused by these agents. Cells in culture were treated with low or high concentrations of teratogens within a range that are reported in the blood of individuals. A pronounced increase in GATA transcription factor binding was observed for all three teratogens. Furthermore, Western blot analysis showed that GATA-3 level in the nuclear fractions was enhanced by each of the three teratogens. Results suggest that altered gene expression pattern due to heightened GATA-3 activities in the fetral brains following exposure to these teratogens may contribute to the development of ASD.

  13. Teratogenic effects and monetary cost of selenium poisoning of fish in Lake Sutton, North Carolina (United States)

    A. Dennis. Lemly


    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...

  14. A glyphosate micro-emulsion formulation displays teratogenicity in Xenopus laevis. (United States)

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


    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

  15. The use of ultrasonography to study teratogenicity in ruminants: evaluation of Ipomoea carnea in goats. (United States)

    Gotardo, André T; Schumaher, Breno H; Pfister, James A; Traldi, Anneliese S; Maiorka, Paulo C; Spinosa, Helenice S; Górniak, Silvana L


    Ipomoea carnea (I. carnea) is a poisonous plant found in Brazil and other tropical countries that often poison livestock. The plant contains the alkaloids calystegines and mainly swainsonine, which inhibit cellular enzymes and cause systematic cell death. The objective of this study was to evaluate the perinatal effects of I. carnea in goats. Forty-seven pregnant goats were randomly allocated into 5 treatment groups and given the following doses (g/kg BW) of I. carnea: 0 (IC0), 1.0 (IC1), 3.0 (IC3), 5.0 (IC5) and 7.5 (IC7). The treatment animals were given fresh I. carnea from day 27 of gestation to parturition. Weight gains and serum biochemistry were evaluated. Fetuses were evaluated using ultrasonographic measurements. Goats from the IC7 group showed clinical signs of poisoning. Ultrasound examination revealed that I. carnea feeding in all treatment groups reduced fetal movement compared to the controls. There was an increase in the total number of birth defects (retrognathia and arthrogyposis) in the IC7 and IC5 groups compared to the controls. The results show that I. carnea has teratogenic potential in goats. In addition, ultrasounds were useful in evaluating fetotoxicity and teratogenicity. © 2012 Wiley Periodicals, Inc.

  16. The role of teratology information services in screening for teratogenic exposures: challenges and opportunities. (United States)

    Chambers, Christina


    Teratology Information Services (TIS) located throughout the world have long played a key role in screening for potential new human teratogens. Using a basic prospective cohort study design, TIS recruit pregnant women from among callers to the Services who have had an exposure of interest and at the same time identify an unexposed comparison group from the same pool of callers. Women in both groups are followed to pregnancy outcome and a range of adverse outcomes including major congenital anomalies, birth size, pregnancy loss, and preterm delivery are evaluated, while controlling for potential confounding. Particularly for rare exposures or newly marketed medications, TIS may be uniquely suited to gathering this information in a timely and efficient fashion. The primary limitation of these studies is the unknown representativeness of the volunteer sample, and the typical small to moderate sample sizes. Methods to increase the proportion of exposed pregnancies that are recruited should be developed. However, small sample size TIS studies, especially when considering new or rare exposures, often fulfill the important function of providing some reassurance to women who have already had the exposure of interest by ruling out major risks for teratogenicity, that is, on the order of thalidomide. Collaborations across TIS nationally and internationally help to address the sample size challenges. A formal collaboration between the TIS cohort study model with a case-control study design is also underway and will provide complementary strengths. Copyright © 2011 Wiley-Liss, Inc.

  17. Evaluation of the teratogenic potential and reproductive toxicity of coal-derived naphtha. (United States)

    McKee, R H; Hinz, J P; Traul, K A


    Liquids which are derived from coal liquefaction processes and boil above approximately 250 degrees C have induced terata in rats. However, few studies have addressed the teratogenic potential of coal liquids which boil below 250 degrees C. The present studies evaluated the reproductive and teratogenic potential of EDS hydrotreated naphtha, a refined coal liquid boiling below 177 degrees C. These studies were conducted by inhalation exposures with Sprague-Dawley rats at target vapor concentrations of 0.2, 1.0, and 5.0 g/m3. The first study assessed teratogenesis. There was no evidence that inhalation exposures for 6 hr per day between Days 6 and 19 of gestation induced maternal toxicity, fetal toxicity, or malformation. In a second study, rats were exposed for 6 hr per day, 5 days per week for 13 weeks, and then mated to assess reproductive toxicity. There was little evidence that inhalation exposure to EDS hydrotreated naphtha adversely affected reproductive performance or fetal development in Sprague-Dawley rats. A low incidence of malformations was observed in treated groups, but these malformations were probably not treatment related.

  18. Teratogenic risk perception and confidence in use of medicines in pairs of pregnant women and general practitioners based on patient information leaflets. (United States)

    Widnes, Sofia Frost; Schjøtt, Jan; Eide, Geir Egil; Granas, Anne Gerd


    The aim of this study was to examine teratogenic risk perceptions and confidence in the use of medicines in pairs of pregnant women and general practitioners (GPs) through assessments of medicines information texts from patient information leaflets (PILs). A questionnaire was handed out to women attending regular ultrasound examination in week 17-19 of pregnancy. The women stated name and address of their GP and questionnaires were sent to the GPs' clinic. The questionnaires contained texts regarding pregnancy from PILs for pivmecillinam, metoclopramide, paracetamol, escitalopram, Valeriana officinalis and dexchlorpheniramine. For each PIL, teratogenic risk (scale from 0: never teratogenic to 10: always teratogenic), confidence in use of medicines (yes or no) and clarity of the text (scale from 0: exceptionally clear to 3: exceptionally unclear) were assessed. In total, 171 pregnant women and 74 GPs participated, of which 98 pairs were identified. Pregnant women had significantly higher perceptions of teratogenic risks and lower confidence in use of medicines compared to GPs. Differences in teratogenic risk perceptions and confidence in use were highest for escitalopram and lowest for dexchlorpheniramine, representing texts with different phrasing and length. Neither pregnant women nor GPs were confident in using Valeriana officinalis. Perceptions of teratogenic risks and confidence in use of medicines during pregnancy differ within pairs of pregnant women and their GP when they assess PILs. Phrasing of medicines information texts can influence teratogenic risk perceptions and thereby prescribing of medicines and adherence.

  19. 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: [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)


    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

  20. Teratogenicity studies with methotrexate, aminopterin, and acetylsalicylic acid in domestic cats. (United States)

    Khera, K S


    Pregnancy was timed in cats following induced ovulation. Methotrexate, (0.5 mg/kg), aminopterin, (0.1 mg/kg), and acetylsalicylic acid, (25 or 50 mg/kg) were administered orally in gelatin capsules in single daily doses on different days of gestation, methotrexate (MTX) on days 11-14, 14-17, or 17-20, aminopterin on day 12, 14, or 16, and acetylsalicylic acid (ASA) on days 10-15 or 15-20. Maternal toxicity was produced only by MTX. MTX given on days 11-14 and 14-17 produced high frequencies of malformations including umbilical hernia. Aminopterin caused no conclusive teratogenic response. An overall increased frequency of anomalies occurred after 50 mg/kg ASA but no single anomaly predominated.

  1. 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)


    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.

  2. Endocrine disrupting, mutagenic, and teratogenic effects of upper Danube River sediments using effect-directed analysis. (United States)

    Higley, Eric; Grund, Stefanie; Jones, Paul D; Schulze, Tobias; Seiler, Thomas-B; Lübcke-von Varel, Urte; Brack, Werner; Wölz, Jan; Zielke, Hanno; Giesy, John P; Hollert, Henner; Hecker, Markus


    Effect-directed analysis (EDA) can be useful in identifying and evaluating potential toxic chemicals in matrixes. Previous investigations of extracts of sediments from the upper Danube River in Germany revealed acute nonspecific and mechanism-specific toxicity as determined by several bioassays. In the present study, EDA was used to further characterize these sediments and identify groups of potentially toxic chemicals. Four extracts of sediments were subjected to a novel fractionation scheme coupled with identification of chemicals to characterize their ability to disrupt steroidogenesis or cause mutagenic and/or teratogenic effects. All four whole extracts of sediment caused significant alteration of steroidogenesis and were mutagenic as well as teratogenic. The whole extracts of sediments were separated into 18 fractions and these fractions were then subjected to the same bioassays as the whole extracts. Fractions 7 to 15 of all four extracts were consistently more potent in both the Ames fluctuation and H295R assays. Much of this toxicity could be attributed to polycyclic aromatic hydrocarbons, sterols, and in fraction 7-naphthoic acids. Because the fraction containing polychlorinated biphenyls, polychlorodibenzodioxin/furan, dichlorodiphenyltrichloroethane, and several organophosphates did not cause any observable effects on hormone production or a mutagenic response, or were not detected in any of the samples, these compounds could be eliminated as causative agents for the observed effects. These results demonstrate the value of using EDA, which uses multiple bioassays and new fractionation techniques to assess toxicity. Furthermore, to our knowledge this is the first study using the recently developed H295R assay within EDA strategies. Copyright © 2012 SETAC.

  3. [Study of embryo toxicity and the teratogenicity of 2, 4-dinitroanisole in rats]. (United States)

    Gao, Junhong; Zhang, Panhong; Liu, Zhiyong; Wang, Hong; Yue, Hong; Lu, Qin; Dang, Jun


    To detect the embryo toxicity and the teratogenicity of DNAN in rats and provide basic data to occupational protection. 120 adult female SD rats and 60 male rats are mating for 1: 1, and the pregnant rats were randomly divided into five groups by the pregnant time. The negative control group are gavaged with 4% starch, and the three experiment groups are gavaged with DNAN suspension with the dose of 5 mg/kg, 15 mg/kg and 45 mg/kg respectively, while the positive control give aspirin of 280 mg/kg. All rats of the five groups are administrated gavage from gestation day 5 (GD5) to GD19 continuously. The rats are dislocated in GD20, and the toxicity of embryo and toetus are detected. The net weight growth in all three dose group are less than that of negative group, while the dead foetus in high dose group is more than negative group. Moreover, the body weight, body lenghth, tail lenghth and the anal genital distance of foetus rats in high dose group are all less than that of negative group. The foetus external malformations of three dose groups appear no significant compared with negative group.However, the prevalences of skeleton malformation in high dose group and the internal organs malformation in the median and high dose group appear significant higher than that of negative group. There are significantly maternal reproductive toxicity, embryo toxicity and toetus toxicity in positive group. DNAN can induced maternal reproductive toxicity, embryo toxicity and the teratogenicity to rats.

  4. Teratogen exposure and congenital ocular abnormalities in Brazilian patients with Möbius sequence

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    Camila V. Ventura


    Full Text Available Purpose: To assess the sociodemographic profiles, teratogen exposures, and ocular congenital abnormalities in Brazilian patients with Möbius sequence. Method: Forty-four patients were recruited from the Brazilian Möbius Sequence Society. This cross-section comprised 41 patients (age, mean ± standard deviation, 9.0 ± 5.5 years who fulfilled the inclusion criteria. The parent or caregiver answered a questionnaire regarding sociodemographic data and pregnancy history. Patients underwent ophthalmological assessments. They were subdivided into groups according to misoprostol exposure during pregnancy, and the two groups were compared. Results: Mothers/caregivers reported unplanned pregnancies in 36 (88% cases. Of these, 19 (53% used misoprostol during their first trimesters. A stable marital status tended to be more frequent in the unexposed group (P=0.051. Incomplete elementary school education was reported by two (11% mothers in the exposed group and by three (14% mothers in the unexposed group (P=0.538. The mothers' gestational exposures to cocaine, marijuana, alcohol, and cigarettes were similar in both groups (P=0.297, P=0.297, P=0.428, and P=0.444, respectively. One (5% case of Rubella infection during pregnancy was found in the unexposed group. The main malformations in the exposed and unexposed groups were the following: strabismus (72% and 77%, respectively, lack of emotional tearing (47% and 36%, respectively, and lagophthalmos (32% and 41%, respectively. Conclusion: Stable marital statuses tended to be more frequent among mothers that did not take misoprostol during pregnancy. Exposures to other teratogens and the main ocular abnormalities were similar in both groups.

  5. Interpretation of recurring weak associations obtained from epidemiologic studies of suspected human teratogens. (United States)

    Khoury, M J; James, L M; Flanders, W D; Erickson, J D


    Epidemiological studies of suspected human teratogens not infrequently lead to recurring weak or moderate associations (relative risks or odds ratios ranging from greater than 1 to 3 for adverse effects and from 1/3 to less than 1 for protective effects) between specific defects and prenatal exposures. Examples of such associations include cigarette smoking and oral clefts (odds ratios between 1 and 2) and periconceptional multivitamin/folic acid supplementation and neural tube defects (odds ratios from 1/3 to 1). In this paper, we illustrate that low relative risk recurring in well-designed studies may reflect underlying biologic mechanisms and should not be readily dismissed. Low relative risks could be the result of a combination of the following factors: 1) unmeasured confounding, 2) exposure misclassification (often related to the inability to pinpoint relevant dose and timing), 3) outcome misclassification (related to the etiologic heterogeneity of birth defects), 4) biologic interactions (related to teratogenic effects in population subgroups defined by genetic susceptibility or the presence of other exposures), and 5) differential prenatal survival (related to the combined impact of the exposure and the defect on prenatal survival). These issues can be addressed in epidemiologic studies by using biological markers of exposure and susceptibility, dysmorphologic evaluation of affected infants, subgroup analysis for etiologic heterogeneity, a search for biologic interactions, and the use of prospective cohort studies. Finally, low relative risks in the face of common exposures can reflect an important public health contribution of the exposure to the occurrence of the defect in the population.

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

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    Jantima Roongruangchai


    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.

  7. Potential teratogenic and neurodevelopmental consequences of coffee and caffeine exposure: a review on human and animal data. (United States)

    Nehlig, A; Debry, G


    The teratogenic effect of caffeine has been clearly demonstrated in rodents. The sensitivity of different animals species is variable. Malformations have been demonstrated in mice at 50-75 mg/kg of caffeine, whereas the lowest dose usually needed to induce malformations is 80 mg/kg in rats. However, when caffeine is administered in fractioned amounts during the day, 330 mg/kg/day are necessary to reach teratogenicity in rats. In rodents, the most frequently observed malformations are those of the limbs and digits, ectrodactyly, craniofacial malformations (labial and palatal clefts) and delays in ossification of limbs, jaw and sternum. Nevertheless, even in rodents, caffeine can be considered as a weak teratogenic agent, given the quite large quantities of caffeine necessary to induce malformations and the small number of animals affected. In humans, caffeine does not present any teratogenic risk. The increased risk of the most common congenital malformations entailed by moderate consumption of caffeine is very slight. However, caffeine potentiates the teratogenic effect of other substances, such as tobacco, alcohol, and acts synergistically with ergotamine and propranolol to induce materno-fetal vasoconstrictions leading to malformations induced by ischemia. Therefore, even though caffeine does not seem to be harmful to the human fetus when intake is moderate and spread out over the day, some associations, especially with alcohol, tobacco, and vasoconstrictive or anti-migraine medications should be avoided. Maternal consumption of caffeine affects brain composition, especially in case of a low-protein diet and also seems to interfere with zinc fixation in brain. Maternal exposure to caffeine induces also long-term consequences on sleep, locomotion, learning abilities, emotivity, and anxiety in rat offspring, whereas in humans, more studies are needed to ascertain long-term behavioral effects of caffeine ingestion by pregnant mothers.

  8. The Hydra regeneration assay reveals ecological risks in running waters: a new proposal to detect environmental teratogenic threats. (United States)

    Traversetti, Lorenzo; Del Grosso, Floriano; Malafoglia, Valentina; Colasanti, Marco; Ceschin, Simona; Larsen, Stefano; Scalici, Massimiliano


    The regenerative ability of Hydra vulgaris was tested as potential biomarker for the development of a new eco-toxicological index. The test is based on the regeneration rate and the aberration frequency of the columna (body and adhesive foot) after separation from head and tentacles by a bistoury. Particularly, 45 columnae were submerged in the rearing solution (that is Hydra medium) to have control, and 285 in potential contaminated waters to have treatments, collected from 19 sites along 10 rivers in central Italy. ANCOVA and chi-square tests were used to compare values from each site to a laboratory control. Subsequently the values on regeneration rate and aberration frequency were inserted in a double entry matrix, where the match of the two entries in the matrix provides the score of the proposed Teratogenic Risk Index (TRI). Each score corresponded to one of the 5 teratogenic risk classes, to which a risk level was associated: from 1 (no risk) to 5 (very high risk). On the whole, 32% of the studied sites were classified as no teratogenic risk while the remaining showed a variable risk level from low to very high. This study proposed for the first time an early warning system to detect the presence of teratogens in running waters, providing a rapid and cost-effective evaluation method. Therefore, TRI may contribute to initiate adequate measures to manage riverine habitats, and to monitor the running water teratogenic status. Specifically, this index may provide the opportunity to identify the disturbance sources and then to drive the decisions, together with competent authorities, on the catchment and landscape management and on the possible use of waters for urban, agricultural, and industrial activities, since they may show significant effects on the human health.

  9. Teratogenic study of phenobarbital and levamisole on mouse fetus liver tissue using biospectroscopy. (United States)

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


    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

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

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


    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.

  11. Distribution, teratogenicity, and embryonic delivered dose of retinoid Ro 23-9223. (United States)

    Willhite, C C; Lovey, A; Eckhoff, C


    Ro 23-9223 is a highly lipophilic aromatic retinoid with antiproliferative and sebum supressive effects in preclinical disease models of acne. To investigate the relation between Ro 23-9223 developmental toxicity, drug distribution, and transplacental transfer, groups of pregnant hamsters were given oral doses of 50-500 mg/kg Ro 23-9223 on days 8 and 9 of gestation. The teratogenic phenotype induced at doses greater than 125 mg/kg per day was similar to that found after exposure to doses of 13-cis-retinoic acid (isotretinoin, Accutane) greater than 37.5 mg/kg per day. Oral bioavailability of Ro 23-9223 was very low compared to 13-cis-retinoic acid. The highest concentrations of Ro 23-9223 were found in maternal liver, lung, adipose tissue, cardiac muscle, and placenta, whereas only little of the compound crossed the blood-brain barrier. Based on embryo AUC, Ro 23-9223 had a 30- to 50-fold greater embryo:maternal concentration ratio than 13-cis-retinoic acid plus its bioactive metabolites following similar doses of the two retinoids. In preclinical pharmacology studies, oral doses of Ro 23-9223 (5 mg/kg per day) and 13-cis-retinoic acid (10 mg/kg per day) produced comparable gland size reductions in the hamster ear sebaceous gland reduction assay. Under these conditions, Ro 23-9223 plasma AUC was 40 times smaller than that of 13-cis-retinoic acid plus its bioactive metabolites. Assuming that the near linear dose-exposure relationship of Ro 23-9223 extends beyond the dose range of this study, embryo AUCs of Ro 23-9223 and 13-cis-retinoic acid (plus metabolites) would be near identical following pharmacologically equivalent doses. A comparison of embryo retinoid AUCs suggests a 4-fold lower teratogenic potency of Ro 23-9223 compared to with 13-cis-retinoic acid. Despite high embryo levels in hamsters, the data suggest an improved therapeutic index for Ro 23-9223 compared with 13-cis-retinoic acid in a preclinical acne disease model. Copyright 2000 Academic Press.

  12. The Teratogenic Potencies of Valproic Acid Derivatives and Their Effects on Biological End-points are Related to Changes in Histone Deacetylase and Erk1/2 Activities

    DEFF Research Database (Denmark)

    Gotfryd, Kamil; Hansen, Maria; Kawa, Anna


    Valproic acid (VPA) is a known teratogen. In the present study, the effects of VPA and seven VPA derivatives with different teratogenic potencies (isobutyl-, 5-methyl-, ethyl-, propyl-, butyl-, pentyl- and hexyl-4-yn-VPA) were investigated in L929 cells in vitro. Evaluated end-points included...... associated with the teratogenic potencies of the VPA derivatives. However, in contrast to changes in Erk1/2 phosphorylation and H3 acetylation, significant changes in GSK-3ß phosphorylation could only be obtained in response to prolonged incubation at high drug concentration. There was an association between...... changes in H3 acetylation and GSK-3ß-Tyr216 phosphorylation, whereas none of these end-points were associated with changes in Erk1/2 phosphorylation. These results suggest that the teratogenic potencies of VPA and VPA derivatives are related to effects on both Erk1/2 and histone deacetylase activities...

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

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    Vahid Nikoui


    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.

  14. Apoptosis May Explain the Pharmacological Mode of Action and Adverse Effects of Isotretinoin, Including Teratogenicity. (United States)

    Melnik, Bodo C


    Isotretinoin (13-cis retinoic acid) is the most effective sebum-suppressive drug for the treatment of severe acne. Its effect depends on sebocyte apoptosis, which results from isotretinoin-induced expression of the apoptotic protein tumour necrosis factor-related apoptosis-inducing ligand, insulin-like growth factor-binding protein-3 and neutrophil gelatinase-associated lipocalin. This review proposes that the pharmacological mode of action of isotretinoin in the treatment of severe acne, acute promyelocytic leukaemia, and neuroblastoma results from apoptosis. Furthermore, apoptosis may be the underlying and unifying mechanism of the adverse effects of isotretinoin on neural crest cells (teratogenicity), hippocampal neurones (depression), epidermal keratinocytes and mucosa cells (mucocutaneous side-effects), hair follicle cells (telogen effluvium), intestinal epithelial cells (inflammatory bowel disease), skeletal muscle cells (myalgia and release of creatine kinase), and hepatocytes (release of transaminases and very low-density lipoproteins). Genetic variants of components of the apoptotic signalling cascade, such as RARA polymorphisms, might explain variations in the magnitude of isotretinoin-induced apoptotic signalling and apparently identify subgroups of patients who experience either stronger adverse effects with isotretinoin therapy or resistance to treatment.

  15. Exploring the Caffeine-Induced Teratogenicity on Neurodevelopment Using Early Chick Embryo (United States)

    Wang, Guang; Li, Xiao-di; He, Rong-rong; Chuai, Manli; Kurihara, Hiroshi; Yang, Xuesong


    Caffeine consumption is worldwide. It has been part of our diet for many centuries; indwelled in our foods, drinks, and medicines. It is often perceived as a “legal drug”, and though it is known to have detrimental effects on our health, more specifically, disrupt the normal fetal development following excessive maternal intake, much ambiguity still surrounds the precise mechanisms and consequences of caffeine-induced toxicity. Here, we employed early chick embryos as a developmental model to assess the effects of caffeine on the development of the fetal nervous system. We found that administration of caffeine led to defective neural tube closures and expression of several abnormal morphological phenotypes, which included thickening of the cephalic mesenchymal tissues and scattering of somites. Immunocytochemistry of caffeine-treated embryos using neural crest cell markers also demonstrated uncharacteristic features; HNK1 labeled migratory crest cells exhibited an incontinuous dorsal-ventral migration trajectory, though Pax7 positive cells of the caffeine-treated groups were comparatively similar to the control. Furthermore, the number of neurons expressing neurofilament and the degree of neuronal branching were both significantly reduced following caffeine administration. The extent of these effects was dose-dependent. In conclusion, caffeine exposure can result in malformations of the neural tube and induce other teratogenic effects on neurodevelopment, although the exact mechanism of these effects requires further investigation. PMID:22470550

  16. Chemical and toxicological characterization of residential oil burner emissions. II. Mutagenic, tumorigenic, and potential teratogenic activity

    Energy Technology Data Exchange (ETDEWEB)

    Braun, A.G.; Busby, W.F. Jr.; Liber, H.L.; Thilly, W.G.


    Extracts of effluents from a modern residential oil burner have been evaluated in several toxicological assay systems. Bacterial mutagens were detected in extracts from both the particulate and vapor phase emissions. Effluents from continuous operation were an order of magnitude less mutagenic than those from cyclic (5 min on, 10 min off) operations. No difference in the yield of bacterial mutagens per gram of fuel burned was found between cyclic operation under low and moderate sooting conditions. On the basis of elution behavior from alumina it appeared that the bacterial mutagens collected from high sooting effluents were more polar than those from low sooting effluent. An extract that was mutagenic in bacteria did not induce a significant increase in mutation frequency to human lymphoblasts. No evidence of tumorigenicity was observed in a limited number of newborn mice after IP injection of effluent extract when compared to historical control data. Putative nonmutagenic teratogens were detected in effluent using an attachment inhibition assay. The level of these agents was reduced in effluents from continuous oil burner operation.

  17. Lack of teratogenicity after combined exposure of pregnant mice to CDMA and WCDMA radiofrequency electromagnetic fields. (United States)

    Lee, Hae-June; Lee, Jae-Seon; Pack, Jeong-Ki; Choi, Hyung-Do; Kim, Nam; Kim, Sung-Ho; Lee, Yun-Sil


    Concern about the possible adverse effects of radiofrequency (RF)-field exposure on public health has increased because of the extensive use of wireless mobile phones and other telecommunication devices in daily life. The murine fetus is a very sensitive indicator of the effects of stress or stimuli in the environment. Therefore, we investigated the teratogenic effects of multi-signal radiofrequency electromagnetic fields (RF EMFs) on mouse fetuses. Pregnant mice were simultaneously exposed to two types of RF signals, single code division multiple access (CDMA) and wideband code division multiple access (WCDMA). Mice received two 45-min RF-field exposures, separated by a 15-min interval, daily throughout the entire gestation period. The whole-body average specific absorption rate (SAR) of CDMA or WCDMA was 2.0 W/kg. The animals were killed humanely on the 18th day of gestation and fetuses were examined for mortality, growth retardation, changes in head size and other morphological abnormalities. From the results, we report for the first time that simultaneous experimental exposure to CDMA and WCDMA RF EMFs did not cause any observable adverse effects on mouse fetuses.

  18. Exploring the caffeine-induced teratogenicity on neurodevelopment using early chick embryo.

    Directory of Open Access Journals (Sweden)

    Zheng-lai Ma

    Full Text Available Caffeine consumption is worldwide. It has been part of our diet for many centuries; indwelled in our foods, drinks, and medicines. It is often perceived as a "legal drug", and though it is known to have detrimental effects on our health, more specifically, disrupt the normal fetal development following excessive maternal intake, much ambiguity still surrounds the precise mechanisms and consequences of caffeine-induced toxicity. Here, we employed early chick embryos as a developmental model to assess the effects of caffeine on the development of the fetal nervous system. We found that administration of caffeine led to defective neural tube closures and expression of several abnormal morphological phenotypes, which included thickening of the cephalic mesenchymal tissues and scattering of somites. Immunocytochemistry of caffeine-treated embryos using neural crest cell markers also demonstrated uncharacteristic features; HNK1 labeled migratory crest cells exhibited an incontinuous dorsal-ventral migration trajectory, though Pax7 positive cells of the caffeine-treated groups were comparatively similar to the control. Furthermore, the number of neurons expressing neurofilament and the degree of neuronal branching were both significantly reduced following caffeine administration. The extent of these effects was dose-dependent. In conclusion, caffeine exposure can result in malformations of the neural tube and induce other teratogenic effects on neurodevelopment, although the exact mechanism of these effects requires further investigation.

  19. Teratogenicity study of the dihydroorotate-dehydrogenase inhibitor and protein tyrosine kinase inhibitor Leflunomide in mice. (United States)

    Fukushima, Ryou; Kanamori, Susumu; Hirashiba, Masahiro; Hishikawa, Atsuko; Muranaka, Ri-Ich; Kaneto, Masako; Nakamura, Kazuichi; Kato, Ikuo


    Leflunomide is an immunosuppressive agent that inhibits de novo synthesis of pyrimidine nucleotides and the activity of protein tyrosine kinase. This study examined the teratogenicity of Leflunomide in mice. Pregnant mice were treated orally with Leflunomide at a dose of 10, 30 or 70 mg/kg/day from day 6 to 15 of pregnancy. At 70 mg/kg, all embryos were resorbed and no live fetuses were detected. At 30 mg/kg, Leflunomide reduced fetal viability, and increased the incidence of multiple external, skeletal and visceral malformations. Characteristic external malformations were neural tube defects, cleft palate and tail deformities. Limb malformations were observed in a small number of fetuses. Skeletal examinations revealed malformations of cervical to sacral vertebrae, ribs and sternebrae. In the viscerae, the main anomalies were membranous ventricular septum defect and persistent truncus arteriosus. The results of this study indicate that Leflunomide administered at 30 mg/kg on days 6 to 15 of pregnancy can induce craniofacial malformations and deformities of the axial skeleton, heart and great vessels in mice.

  20. Fate of the teratogenic and carcinogenic ochratoxin A in human perfused placenta. (United States)

    Woo, Chit Shing Jackson; Partanen, Heidi; Myllynen, Päivi; Vähäkangas, Kirsi; El-Nezami, Hani


    Ochratoxin A (OTA) is one of the most frequent mycotoxins detected in human blood worldwide. Apart from its well known nephrotoxicity, OTA-induced teratogenicity and carcinogenicity proven in animals are potential effects also in humans. Pregnant women have been exposed to this food contaminant via dietary exposure in a continuous and widespread manner. Although the transplacental transfer of OTA has been demonstrated in laboratory animals and the presence of OTA in human fetal samples has been reported, little is known about the role of human placenta in OTA toxicokinetics. In this study, human perfused placenta was used to reveal the actual placental toxicokinetics of OTA using concentrations found in serum of pregnant women. Moreover, the effect of protein concentration and biological significance of placental transporters on the OTA transfer in human placenta were also determined. Our study is the first to pursue the transfer of OTA through perfused human placenta. The transfer of OTA through term human placenta was barely detectable in all perfusions. Inhibitors of neither ABCG2 nor ABCC2 increased the transport of OTA to fetal circulation in placental perfusion, and thus these transporters apparently do not have biological significance in inhibiting transplacental transfer of OTA. Human albumin has inhibited OTA transfer through a tight monolayer of BeWo b30 cells. Finding from this study clearly contradict the existing epidemiological studies reporting higher OTA levels in fetal than in maternal circulation in vivo. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. 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


    analysis, and it was found that VPA and selected VPA-analogues inhibited individual cell motility of L-cells in a dose-dependent manner. The compounds caused a decrease in the root-mean-square speed, S, and in the rate of diffusion, R, but an increase in the time of persistence in direction, P. Using short......Valproic acid (VPA) is an established human teratogen that causes neural tube defects in 1-2% of human foetuses exposed to the drug during early pregnancy. In this study, individual cell motility was evaluated using short- and long-term time-lapse video-recording and computer assisted image...... 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...

  2. An avian model for the reversal of neurobehavioral teratogenicity with neural stem cells. (United States)

    Dotan, Sharon; Pinkas, Adi; Slotkin, Theodore A; Yanai, Joseph


    A fast and simple model which uses lower animals on the evolutionary scale is beneficial for developing procedures for the reversal of neurobehavioral teratogenicity with neural stem cells. Here, we established a procedure for the derivation of chick neural stem cells, establishing embryonic day (E) 10 as optimal for progression to neuronal phenotypes. Cells were obtained from the embryonic cerebral hemispheres and incubated for 5-7 days in enriched medium containing epidermal growth factor (EGF) and basic fibroblast growth factor (FGF2) according to a procedure originally developed for mice. A small percentage of the cells survived, proliferated and formed nestin-positive neurospheres. After removal of the growth factors to allow differentiation (5 days), 74% of the cells differentiated into all major lineages of the nervous system, including neurons (Beta III tubulin-positive, 54% of the total number of differentiated cells), astrocytes (GFAP-positive, 26%), and oligodendrocytes (O4-positive, 20%). These findings demonstrate that the cells were indeed neural stem cells. Next, the cells were transplanted in two allograft chick models; (1) direct cerebral transplantation to 24-h-old chicks, followed by post-transplantation cell tracking at 24 h, 6 days and 14 days, and (2) intravenous transplantation to chick embryos on E13, followed by cell tracking on E19. With both methods, transplanted cells were found in the brain. The chick embryo provides a convenient, precisely-timed and unlimited supply of neural progenitors for therapy by transplantation, as well as constituting a fast and simple model in which to evaluate the ability of neural stem cell transplantation to repair neural damage, steps that are critical for progress toward therapeutic applications. Copyright 2010 Elsevier Inc. All rights reserved.

  3. The teratogenic effects of Lorazepam on the organogenesis of the rat fetus

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    Pasbakhsh P


    Full Text Available Lorazepam has in increasingly being used in our country in recent years. Pharmacologically, lorazepam belongs to the benzodiazepines known for their wide neurotropic properties. There have been several studies on the side effects of the drug as stress disorders, tumors, preconvulsive activities in case of epileptic attacks, overdose, and behavioral problems, but little is known regarding the teratogenicity of the drug and its effects on the craniofascial development. In this study, a group of adult wistar rats of definite average of age and weight were selected and exposed to 2 mg/kg/day to 20 mg/kg day of lorazepam after conception (during the organogenesis in the days 9 to 18 in case and control groups. The fetuses were first studied macroscopically regarding gross anomalies, and then histologically and histochemically to exactly inspect the defects of tissue organogenesis. According to the results obtained, there was significant difference in the weight and length of the cases compared to the control group. Several anomalies of the eyes and ears (Coloboma of the eyelids with protruded globes and absence of the auricle and external auditory meatus, anomalies of the skull (Acrocephaly, and large rhombencephalon were found. The craniofascial organs such as the nasal epithelium, tongue, salivary glands and the palates were also affected. According to the final analysis, there is a significant difference between the case and control groups. It was also found that taking the drug in the second half of pregnancy could affect the migration of the neural crest cells (being very sensitive and change the mesenchymal structure of the neural crests. It also promotes the synthesis of proteins like growth hormone and growth factors. The fast, uncontrolled growth, defects the normal maturing process of the tissues during organogenesis, which ends in irreversible malformations.

  4. Teratogen update: evaluation of the reproductive and developmental risks of caffeine. (United States)

    Christian, M S; Brent, R L


    plasma level that could never be obtained from consuming caffeine containing products. More recent animal studies have demonstrated, that depending on the method of administration and species, the developmental NOEL in rodents is approximately 30 mg/kg per day, the teratogenic NOEL is 8,100 mg/kg per day, and the reproductive NOEL approximately 80-120 mg/kg per day. Lack of biological plausibility to support the concept that caffeine has been responsible for human malformations is another important part of this analysis. For example, no one has described the Caffeine "teratogenic syndrome," a cluster of malformations associated with caffeine ingestion. Proven human teratogens have an identifiable syndrome. The malformations described in the animal studies at very high doses fit the description of vascular disruptive types of malformations. (ABSTRACT TRUNCATED)

  5. Inhibition of trimethadione and dimethadione teratogenicity by the cyclooxygenase inhibitor acetylsalicylic acid: a unifying hypothesis for the teratologic effects of hydantoin anticonvulsants and structurally related compounds. (United States)

    Wells, P G; Nagai, M K; Greco, G S


    Teratogenicity of the anticonvulsant phenytoin may be due in part to its bioactivation by prostaglandin synthetase, forming a reactive free radical intermediate. We examined whether teratogenicity of the structurally similar oxazolidinedione anticonvulsants, trimethadione and its N-demethylated metabolite dimethadione, could be inhibited by the prostaglandin synthetase inhibitor acetylsalicylic acid (ASA). Trimethadione, 700 or 1000 mg/kg intraperitoneally (ip), was given to pregnant CD-1 mice during (Gestational Days 12 and 13) or before (Days 11 and 12) the critical period of susceptibility to phenytoin-induced fetal cleft palates. Dimethadione was given similarly on Days 11 and 12, or 12 and 13, in a dose (900 mg/kg ip) that was equimolar to 1000 mg/kg of trimethadione. ASA, 10 or 1 mg/kg ip, was given 2 hr before trimethadione or dimethadione on Days 11 and 12, and before trimethadione on Day 11 only. Dams were killed on Day 19 and fetuses were examined for anomalies. Either dose of trimethadione given on Days 12 and 13 was negligibly teratogenic, as evidenced by a non-dose-related, 1.1% mean incidence of fetal cleft palates. However, when given earlier on Days 11 and 12, trimethadione 1000 mg/kg caused an 8.9% incidence of cleft palates (p less than 0.05). Similarly, dimethadione caused a 3.9-fold higher incidence of cleft palates when given earlier on Days 11 and 12 (17.3-34.9%) than on Days 12 and 13 (4.4%) (p less than 0.05). At equimolar doses, dimethadione caused a 1.9- to 3.9-fold higher incidence of cleft palates compared to trimethadione (p less than 0.05), suggesting that dimethadione may be the proximate teratogen. Either dose of ASA given on both days before trimethadione totally prevented cleft palates, and ASA 10 mg/kg given only on Day 11 reduced the incidence of trimethadione-induced cleft palates to 1.1% (p less than 0.05). ASA reduced the incidence of cleft palates caused by dimethadione given on Days 11 and 12 from 34.9 to 20.3% (p less than

  6. The Teratogenic Effect of The Mindi (Melia azedarach L Leaves Ethanol Extract on Mice (Mus musculus Fetus

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    Adisti Erlina Sutomo


    Full Text Available Background: Mindi leaves (Melia azeradach L. were used by Indonesians as a traditional medicine for pregnant women because it was considered to be safe. Mindi leaves contain several active compounds and one of them is suspected as a teratogen and can disrupt fetus growth in gestation. This research aims to know about the teratogenic effect of ethanol extract of Mindi leaves by using mice. Methods: This was a laboratory experimental study using 27 pregnant female mice (Mus musculus of Swiss Webster strain which were randomly assigned to 3 groups (n=9 controlled (Carboxymethyl cellulose 1% for day 1–18 of pregnancy, group I (mindi leaves ethanol extract 3.22 mg+Carboxymethyl cellulose 1% day 1–5 of pregnancy, and group II (mindi leaves ethanol extract 3.22 mg+Carboxymethyl cellulose 1% day 6–18 of pregnancy. Observation was done to see total amount of fetus, live normal fetus count, length and weight of fetus, abnormal fetus count consisting of dead fetus count with normal and abnormal external morphology, and resorbed fetus count. This research was done from October to November 2012 in Pharmacological laboratory of Faculty of Medicine Universitas Padjajdjaran. Data analysis utilized unpaired t-test. Results: The result showed a significant difference (p<0.05, seen from live normal fetus count and abnormal fetus count consisting of dead fetus count with normal and abnormal external morphology, and resorpted fetus count. Conclusions: Administration of Mindi leaves extract during pregnancy of mices can cause teratogenic effect.

  7. Effects of maternal administration of vitamins C and E on ethanol neurobehavioral teratogenicity in the guinea pig. (United States)

    Nash, Christopher M; Ibram, Ferda; Dringenberg, Hans C; Reynolds, James N; Brien, James F


    Consumption of ethanol during human pregnancy can produce a wide spectrum of teratogenic effects, including neurobehavioral dysfunction. This study, in the guinea pig, tested the hypothesis that chronic maternal administration of antioxidant vitamins C plus E, together with ethanol, mitigates ethanol neurobehavioral teratogenicity. Pregnant guinea pigs received one of the following four chronic oral regimens: ethanol and vitamins C plus E; ethanol and vitamin vehicle; isocaloric-sucrose/pair-feeding and vitamins C plus E; or isocaloric-sucrose/pair-feeding and vehicle. Vitamins C (250 mg) plus E (100mg) or vehicle were given daily, and ethanol (4 g/kg maternal body weight/day) (E) or isocaloric-sucrose/pair-feeding was given for 5 consecutive days followed by 2 days of no treatment each week throughout gestation. One neonate from selected litters was studied on postnatal day (PD) 0. Neurobehavioral function was determined by measuring task acquisition and task retention using an 8-day moving-platform version of the Morris water-maze task, starting on PD 45. Thereafter, in vivo electrophysiologic assessment of changes in hippocampal synaptic plasticity was conducted. There was an ethanol-induced decrease in neonatal brain weight compared with sucrose. The vitamins C plus E regimen protected hippocampal weight relative to brain weight in ethanol offspring, and mitigated the ethanol-induced deficit in the task-retention component of the water-maze task. However, in the sucrose group, this Vit regimen produced deficits in both task acquisition and task retention. The vitamins C plus E regimen did not mitigate the ethanol-induced impairment of hippocampal long-term potentiation. These results indicate that maternal administration of this high-dose vitamins C plus E regimen throughout gestation has limited efficacy and potential adverse effects as a therapeutic intervention for E neurobehavioral teratogenicity.

  8. Health care providers' requests to Teratogen Information Services on medication use during pregnancy and lactation. (United States)

    Gendron, Marie-Pierre; Martin, Brigitte; Oraichi, Driss; Bérard, Anick


    Medication use during pregnancy and lactation is prevalent. However, current knowledge of the risks and benefits of medication use during pregnancy and lactation is incomplete as the best available evidence has been obtained from cohort studies of inadvertent exposures and registries. This situation may partly explain health care providers' (HCP) risk perceptions and thus the increasing number of calls to Teratogen Information Services (TIS). The objectives of this study were (1) to identify the medication classes for which HCP are seeking counseling from the IMAGe center, a Quebec TIS; (2) to identify the medical conditions for which medication classes were used during pregnancy and lactation; (3) to identify and quantify predictors of medication information requests during pregnancy and lactation. A retrospective analysis of data was conducted within the population served by the IMAGe center, a TIS based at CHU Ste-Justine in Montreal, Quebec, Canada, that serves the French population of Canada. To be included, calls had to be received between January 1, 2004 and April 30, 2007, and the subject of the call had to be directly associated with the exposure, or not, of a pregnant or breastfeeding woman to medication. Multivariate generalized estimating equation (GEE) regression models were performed to identify the predictors of medication requests. A total of 11, 076 requests regarding medication exposure during pregnancy, 12 055 requests regarding pregnant women before the exposure took place, and 13, 364 requests regarding lactation were included for analyses. Pregnant women were most frequently exposed to antidepressants (17.3), antibiotics (6.3%), and benzodiazepines (5.3%). Prior to drug exposure, the most frequent inquiries by HCP were on antibiotics (11.0%), anti-inflammatory drugs (6.0%), and antiemetics (5.1%). Inquiries concerning lactating women most frequently requested information on the drug classes of antidepressants (10.8%), antibiotics (9.1%), and

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

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    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, E-mail:


    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{sub 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{sub 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{sub 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

  10. Teratogenic effects of bis-diamine on early embryonic rat heart: an in vitro study. (United States)

    Nishijima, S; Nakagawa, M; Fujino, H; Hanato, T; Okamoto, N; Shimada, M


    Bis-diamine induces cardiac defects, including conotruncal anomalies in rat embryos when the agent is administered to the mother. To evaluate the teratogenic effects and mechanism of bis-diamine, we performed morphological and immunohistochemical analyses of early rat embryos cultured in medium containing bis-diamine. The embryos were removed from mother rats on gestational day 10.5 and cultured in medium containing 1 mg of bis-diamine for 6 hr. The embryos were then cultured in medium only for another 6, 12, 18, and 42 hr, corresponding to embryonic day (ED) 11.0, 11.25, 11.5, and 12.5, respectively. Some embryos from the same mothers were used as controls and were cultured in medium only for the corresponding periods to the embryos exposed to bis-diamine. Some mother rats were given a single oral dose of 200 mg of bis-diamine on gestational day 10.5. Embryos from these pregnant rats were removed 6 hr after the oral administration of bis-diamine, and were also cultured in medium only for 6, 12, 18, and 42 hr. No cardiac abnormalities were detected in the controls at any stage of development. Thirty-three of 51 (65%) embryos exposed to bis-diamine and 15 of 20 (75%) embryos removed from bis-diamine-administered mothers showed abnormal cardiac development, including dilated ventricle, elongation of outflow tract, and pericardial defect on ED 11.5. Four of six (67%) embryos exposed to bis-diamine, and five of seven (71%) removed from bis-diamine-administered mothers also presented almost the same cardiac abnormalities on ED 12.5. No cardiac abnormalities were detected in bis-diamine-treated embryos before ED 11.5. In addition, the expression of neural cell adhesion molecule (N-CAM) was examined using immunohistochemical methods. Fewer N-CAM immunoreactive cells were detected in the third and fourth aortic arches in the bis-diamine-treated embryos than in controls on ED 11.5. However, more N-CAM immunoreactive cells were detected in the bis-diamine-treated embryos

  11. Teratogenicity of Australian Simbu serogroup and some other Bunyaviridae viruses: the embryonated chicken egg as a model. (United States)

    McPhee, D A; Parsonson, I M; Della-Porta, A J; Jarrett, R G


    The use of embryonated chicken eggs as a model for assessing the teratogenic potential of animal viruses was investigated with 12 members of the Bunyaviridae family. Infection of 4-day-old embryonated chicken eggs via the yolk sac with 10 of the viruses resulted in deaths or congenital deformities that were similar to those observed in Akabane virus infections of fetal ruminants and included arthrogryposis, scoliosis, mandible defects, and retarded development. Statistical analysis showed that the viruses fell into three main groupings, namely, those that caused both death and deformities (Akabane, Aino, Tinaroo, and Belmont viruses), those that mainly caused death (Peaton, Thimiri, and Facey's Paddock viruses), and those that required very high doses to cause either death or deformities (Douglas and CSIR0296 viruses). In addition, two viruses (Kowanyama and Mapputta viruses) caused neither death nor deformities. A difference in the pathogenic potential between two Akabane isolates (B8935 and CSIR016) in the embryonated chicken egg model was found to correlate with differences previously observed in experimentally infected sheep; Akabane CSIR016 was the more pathogenic. It is concluded that the embryonated chicken egg model should also be of value in assessing the teratogenic potential of other Bunyaviridae and attenuated vaccine viruses, although it does not assess the ability of the virus to cross the placenta.

  12. Acute and sub-lethal exposure to copper oxide nanoparticles causes oxidative stress and teratogenicity in zebrafish embryos. (United States)

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


    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.

  13. A Bmp Reporter Transgene Mouse Embryonic Stem Cell Model as a Tool to Identify and Characterize Chemical Teratogens. (United States)

    Kugler, Josephine; Tharmann, Julian; Chuva de Sousa Lopes, Susana M; Kemler, Rolf; Luch, Andreas; Oelgeschläger, Michael


    Embryonic stem cells (ESCs) were first isolated from mouse embryos more than 30 years ago. They have proven invaluable not only in generating genetically modified mice that allow for analysis of gene function in tissue development and homeostasis but also as models for genetic disease. In addition, ESCs in vitro are finding inroads in pharmaceutical and toxicological testing, including the identification of teratogenic compounds. Here, we describe the use of a bone morphogenetic protein (Bmp)-reporter ESC line, isolated from a well-characterized transgenic mouse line, as a new tool for the identification of chemical teratogens. The Bmp-mediated expression of the green fluorescent protein enabled the quantification of dose- and time-dependent effects of valproic acid as well as retinoic acid. Significant effects were detectable at concentrations that were comparable to the ones observed in the classical embryonic stem cell test, despite the fact that the reporter gene is expressed in distinct cell types, including endothelial and endodermal cells. Thus these cells provide a valuable new tool for the identification and characterization of relevant mechanisms of embryonic toxicity. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail:

  14. Potential teratogenicity of methimazole: exposure of zebrafish embryos to methimazole causes similar developmental anomalies to human methimazole embryopathy. (United States)

    Komoike, Yuta; Matsuoka, Masato; Kosaki, Kenjiro


    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.

  15. 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.

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

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    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.

  17. Free radical intermediates of phenytoin and related teratogens. Prostaglandin H synthase-catalyzed bioactivation, electron paramagnetic resonance spectrometry, and photochemical product analysis. (United States)

    Parman, T; Chen, G; Wells, P G


    Phenytoin and related xenobiotics can be bioactivated by embryonic prostaglandin H synthase (PHS) to a teratogenic free radical intermediate. The mechanism of free radical formation was evaluated using photolytic oxidation with sodium persulfate and by EPR spectrometry. Characterization of the products by mass spectrometry suggested that phenytoin photolyzes to a nitrogen-centered radical that rapidly undergoes ring opening to form a carbon-centered radical. PHS-1 was incubated with teratogen (phenytoin, mephenytoin, trimethadione, phenobarbital, and major metabolites) or its vehicle and the free radical spin trap alpha-phenyl-N-t-butylnitrone, and incubations were analyzed by EPR spectrometry. There was no alpha-phenyl-N-t-butylnitrone radical adduct in control incubations. For phenytoin, a putative unstable nitrogen-centered radical adduct and a stable carbon-centered radical adduct were detected. Free radical spin adducts also were detected for all other teratogens and metabolites except carbamazepine. The PHS inhibitor eicosatetraynoic acid abolished the free radical EPR signal. Incubation of 2'-deoxyguanosine with phenytoin and PHS-1 resulted in a 5-fold increase in its oxidation to 8-hydroxy-2'-deoxyguanosine. This is the first direct chemical evidence for PHS-catalyzed bioactivation of phenytoin and related teratogens to a free radical intermediate that initiates DNA oxidation, which may constitute a common molecular mechanism of teratologic initiation.

  18. The effect of body condition on serum concentrations of two teratogenic alkaloids (anagyrine and ammodendrine) from Lupines (Lupinus spp.) that cause crooked calf disease. (United States)

    Several species of lupine (Lupinus spp.) are toxic to livestock, causing death losses in sheep and cattle but more commonly “crooked calf disease” in pregnant range cows. The major toxic alkaloids in lupine are of the quinolizidine alkaloid group and include the teratogen anagyrine, which is primari...

  19. Assessing the availability of the teratogenic drug isotretinoin outside the pregnancy prevention programme: a survey of e-pharmacies. (United States)

    Lagan, Briege M; Dolk, Helen; White, Bronagh; Uges, Donald R A; Sinclair, M


    The increase in online purchasing of medications raises safety concerns regarding teratogenic drugs. The use of the teratogenic drug 'isotretinoin' for women of childbearing age requires strict adherence to the Pregnancy Prevention Programme (PPP), a risk minimisation measure imposed on prescribers and users. We sought to determine how readily consumers can purchase isotretinoin online and the associated safety procedures and information. A descriptive cross-sectional survey was conducted of 50 e-pharmacies identified from commonly used search engines. E-pharmacy characteristics and isotretinoin PPP specific criteria were evaluated. Purchases of isotretinoin from seven e-pharmacies not bearing authentication logos and not requiring a prescription were assessed for PPP policy adherence, purchasing procedures and compound quality. Forty-three (86%) of the e-pharmacies did not have an authentication seal/logo. Isotretinoin could be purchased from 42 sites without a valid prescription. Information on isotretinoin causing birth defects was lacking in 25 of the 50 sites, on not taking isotretinoin in pregnancy in 24 sites and not taking isotretinoin if planning or at risk of a pregnancy in 33 sites. Of the eight attempted purchases, seven arrived, all without any patient information leaflet. All were verified as isotretinoin. The Internet provides a loophole for purchasing of medications known to cause congenital abnormalities, which needs to be addressed by medicines regulatory agencies worldwide. The current PPP for isotretinoin may be failing to protect mothers and babies from preventable harm-clinicians need to be aware of this, and the public needs to be educated about the potential risks. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

  20. Assessing the availability of the teratogenic drug isotretinoin outside the pregnancy prevention programme: a survey of e-pharmacies† (United States)

    Lagan, Briege M; Dolk, Helen; White, Bronagh; Uges, Donald R A; Sinclair, M


    Purpose The increase in online purchasing of medications raises safety concerns regarding teratogenic drugs. The use of the teratogenic drug ‘isotretinoin’ for women of childbearing age requires strict adherence to the Pregnancy Prevention Programme (PPP), a risk minimisation measure imposed on prescribers and users. We sought to determine how readily consumers can purchase isotretinoin online and the associated safety procedures and information. Methods A descriptive cross-sectional survey was conducted of 50 e-pharmacies identified from commonly used search engines. E-pharmacy characteristics and isotretinoin PPP specific criteria were evaluated. Purchases of isotretinoin from seven e-pharmacies not bearing authentication logos and not requiring a prescription were assessed for PPP policy adherence, purchasing procedures and compound quality. Results Forty-three (86%) of the e-pharmacies did not have an authentication seal/logo. Isotretinoin could be purchased from 42 sites without a valid prescription. Information on isotretinoin causing birth defects was lacking in 25 of the 50 sites, on not taking isotretinoin in pregnancy in 24 sites and not taking isotretinoin if planning or at risk of a pregnancy in 33 sites. Of the eight attempted purchases, seven arrived, all without any patient information leaflet. All were verified as isotretinoin. Conclusion The Internet provides a loophole for purchasing of medications known to cause congenital abnormalities, which needs to be addressed by medicines regulatory agencies worldwide. The current PPP for isotretinoin may be failing to protect mothers and babies from preventable harm—clinicians need to be aware of this, and the public needs to be educated about the potential risks. PMID:24493556

  1. Editor's Highlight: Identification and Characterization of Teratogenic Chemicals Using Embryonic Stem Cells Isolated From a Wnt/β-Catenin-Reporter Transgenic Mouse Line. (United States)

    Kugler, Josephine; Kemler, Rolf; Luch, Andreas; Oelgeschläger, Michael


    Embryonic stem cells (ESCs) are commonly used for the analysis of gene function in embryonic development and provide valuable models for human diseases. In recent years, ESCs have also become an attractive tool for toxicological testing, in particular for the identification of teratogenic compounds. We have recently described a Bmp-reporter ESC line as a new tool to identify teratogenic compounds and to characterize the molecular mechanisms mediating embryonic toxicity. Here we describe the use of a Wnt/β-Catenin-reporter ESC line isolated from a previously described mouse line that carries the LacZ reporter gene under the control of a β-Catenin responsive promoter. The reporter ESC line stably differentiates into cardiomyocytes within 12 days. The reporter was endogenously induced between day 3-5 of differentiation reminiscent of its expression in vivo, in which strong LacZ activity is detected around gastrulation. Subsequently its expression becomes restricted to mesodermal cells and cells undergoing an epithelial to mesenchymal transition. The Wnt/β-Catenin-dependent expression of the reporter protein allowed quantification of dose- and time-dependent effects of teratogenic chemicals. In particular, valproic acid reduced reporter activity on day 7 whereas retinoic acid induced reporter activity on day 5 at concentrations comparable to the ones inhibiting the formation of functional cardiomyocytes, the classical read-out of the embryonic stem cell test (EST). In addition, we were also able to show distinct effects of teratogenic chemicals on the Wnt/β-Catenin-reporter compared with the previously described Bmp-reporter ESCs. Thus, different reporter cell lines provide complementary tools for the identification and analysis of potentially teratogenic compounds. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail:

  2. Antifungal triazole alcohols: A comparative analysis of structure-activity, structure-teratogenicity and structure-therapeutic index relationships using the Multiple Computer-Automated Structure Evaluation (Multi-CASE) methodology (United States)

    Klopman, Gilles; Ptchelintsev, Dmitri


    An increase in the opportunistic fungal infections necessitates a design of new more effective and safer antifungal agnets. Triazole alcohols are effective antifungals, but have a risk of teratogenicity associated with them. Therefore, successful design of drugs from this class depends on understanding the structure-activity and structure-teratogenicity relationships in conjunction. To this end, we applied the Multiple Computer-Automated Structure Evaluation (Multi-CASE) methodology to a study of the relationships between the structures of 71 triazole alcohols and their in vitro antifungal activity, teratogenicity, and therapeutic index. For each end point, several relevant structural descriptors were identified. A comparative analysis of the Multi-CASE results indicates that cyano, methoxy groups, and ortho-difluorination on the aromatic ring decrease antifungal activity, but not the therapeutic index because of the concomitant negative contribution to teratogenicity. Metabolically deactivating para-substitution in the benzene ring is beneficial for the therapeutic index in agreement with the idea of metabolically induced teratogenicity. Fluorinated para-alkyl substituents are most preferable. The pattern of ortho-substitution in the benzene ring affects both antifungal and teratogenic activity. This suggests that the relative orientation of the benzene ring with respect to the rest of the molecule may play a modulating role. The Multi-CASE model could correctly predict, a priori, the teratogenicity and antifungal potency of SCH 39304 and ICI 156,066 and be used to optimize the structure and therapeutic index of the latter.

  3. Anticonvulsant profile and teratogenicity of 3,3-dimethylbutanoylurea: a potential for a second generation drug to valproic acid. (United States)

    Shimshoni, Jakob Avi; Yagen, Boris; Pessah, Neta; Wlodarczyk, Bogdan; Finnell, Richard H; Bialer, Meir


    The purpose of this study was to evaluate the anticonvulsant activity and teratogenic potential of branched aliphatic acylureas represented by isovaleroylurea (IVU), pivaloylurea (PVU) and 3,3-dimethylbutanoylurea (DBU), as potential second-generation drugs to valproic acid (VPA). The anticonvulsant activity of IVU, PVU, and DBU was determined in mice and rats utilizing the maximal electroshock seizure (MES) and the pentylenetetrazole (scMet) tests. The ability of DBU to block electrical-, or chemical-induced seizures was further examined in three acute seizure models: the psychomotor 6 Hz model, the bicuculline and picrotoxin models and one model of chronic epilepsy (i.e., the hippocampal kindled rat model). The induction of neural tube defects (NTDs) by IVU, PVU, and DBU was evaluated after i.p. administration at day 8.5 of gestation to a mouse strain highly susceptible to VPA-induced teratogenicity. The pharmacokinetics of DBU was studied following i.v. administration to rats. DBU emerged as the most potent compound having an MES-ED(50)of 186 mg/kg (mice) and 64 mg/kg (rats) and an scMet-ED(50)of 66 mg/kg (mice) and 26 mg/kg (rats). DBU underwent further evaluation in the hippocampal kindled rat (ED(50)= 35 mg/kg), the psychomotor 6 Hz mouse model (ED(50)= 80 mg/kg at 32 mA and ED(50)= 133 mg/kg at 44 mA), the bicuculline- and picrotoxin-induced seizure mouse model (ED(50)= 205 mg/kg and 167 mg/kg, respectively). In contrast to VPA, DBU, IVU, and PVU did not induce a significant increase in NTDs as compared to control. DBU was eliminated by metabolism with a half-life of 4.5 h. DBU's broad spectrum and potent anticonvulsant activity, along with its high safety margin and favorable pharmacokinetic profile, make it an attractive candidate to become a new, potent, and safe AED.

  4. Sensitivity of modified Biel-maze task, compared with Y-maze task, to measure spatial learning and memory deficits of ethanol teratogenicity in the guinea pig. (United States)

    Dobson, Christine C; Mongillo, Daniel L; Poklewska-Koziell, Margo; Winterborn, Andrew; Brien, James F; Reynolds, James N


    Ethanol consumption during pregnancy can produce a variety of teratogenic effects in offspring, termed Fetal Alcohol Spectrum Disorders (FASD). The most debilitating and permanent consequence of chronic prenatal ethanol exposure (CPEE) is neurobehavioral teratogenicity, which often manifests as cognitive and behavioral impairments, including deficits in spatial learning and memory. This study tested the hypothesis that a modified dry-land version of the multi-choice Biel-maze task is more sensitive than the rewarded-alternation Y-maze task for the determination of spatial learning and memory deficits of ethanol teratogenicity. Pregnant guinea pigs received ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding (control) for 5days/week throughout gestation. CPEE resulted in ethanol neurobehavioral teratogenicity in offspring, as demonstrated by increased spontaneous locomotor activity at postnatal day (PD) 10 and decreased brain weight at euthanasia (PD 150-200). On PD 21, offspring were randomly assigned to one of two tasks to assess spatial learning and memory performance: a dry-land version of the Biel maze or a rewarded-alternation Y-maze. Animals were habituated to the environment of their assigned task and performance of each CPEE or control offspring was measured. In the modified Biel maze, CPEE and control offspring were not different for percent completed trials or time to complete a trial. However, CPEE offspring made more errors (reversals and entering dead ends) in the Biel maze, demonstrating impaired spatial learning and memory. In contrast, CPEE offspring did not have impaired performance of the rewarded-alternation Y-maze task. Therefore, the modified dry-land version of the Biel-maze task, which measures cognitive performance using a complex multi-choice design, is more sensitive in demonstrating CPEE-induced spatial learning and memory deficits compared with a simple, rewarded-alternation Y-maze task. Copyright © 2012

  5. Congenital bladder exstrophy associated with Duogynon hormonal pregnancy tests-signal for teratogenicity or consumer report bias? (United States)

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


    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.

  6. Fertility, developmental toxicity and teratogenicity in albino rats treated with methanol sub-fraction of Carica papaya seeds. (United States)

    Shrivastava, S; Ansari, A S; Lohiya, N K


    To evaluate the status of fertility, developmental stages during gestation and teratological changes, if any, following oral administration of methanol sub-fraction (MSF) of the benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya in rats. The MSF was administered at the doses of 50 mg contraceptive dose (CD), 100 mg (2× CD), 250 mg (5× CD) and 500 mg (10× CD)/kg body wt/day along with vehicle-treated control using 10 male and 20 female Wistar rats in each group. Necropsies were performed one day before the expected parturition. Status of gravid/non-gravid uterus, the number of corpora lutea in the ovary, implantation status, fetal wellbeing, fetal resorption, fetal body weight, external, visceral and skeletal malformations were recorded. Pregnancies were recorded in vehicle-treated control animals and in the animals treated with 50 mg/kg body wt/day. The animals treated with 2× CD, 5× CD and 10× CD did not get pregnant. The fetuses and the status of the ovary, uterus and implantation, fetal body weight, soft tissues and skeletal structures were recorded normal. Data were comparable to those of control. The results suggest that the test substance had no developmental toxicity and teratogenicity which could affect pregnancy, implantation and gestation.

  7. [Experimental model for the study of the teratogenic interaction of chemical agents and drugs (toluene and acetylsalicylic acid)]. (United States)

    Tátrai, E; Hudák, A; Ungváry, G


    On the 10th-13th days of pregnancy toluene (3600 mg/m3) by inhalation) and on 12th day acetylsalicylic acid (500 mg/kg of body weight per os) were administered to CFY rats and the common effect of these agents was studied. It was established that: 1. the maternal toxicity increased, i.e. increased the mortality rate, decreased the consumption of the food and the gain of weight, increased the relative weight of the liver; 2. the foetal toxicity increased, i.e. increased the mortality rate of foetuses, the rate of the loss of the body weight, the number of the anomalies of the sternum and the incidence of the supernumerary ribs. It is believed, that the non-teratogenic toluene rises the utilization of the glycine and the level of the free salicylic-acid, consequently the embryotoxic effect of the acetylsalicylic-acid. The danger of the occurrence of malformations as an effect of interaction of chemical agents and drugs taken in therapeutic doses is stressed.

  8. Depletion of retinoic acid receptors initiates a novel positive feedback mechanism that promotes teratogenic increases in retinoic acid.

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    Enrico D'Aniello

    Full Text Available Normal embryonic development and tissue homeostasis require precise levels of retinoic acid (RA signaling. Despite the importance of appropriate embryonic RA signaling levels, the mechanisms underlying congenital defects due to perturbations of RA signaling are not completely understood. Here, we report that zebrafish embryos deficient for RA receptor αb1 (RARαb1, a conserved RAR splice variant, have enlarged hearts with increased cardiomyocyte (CM specification, which are surprisingly the consequence of increased RA signaling. Importantly, depletion of RARαb2 or concurrent depletion of RARαb1 and RARαb2 also results in increased RA signaling, suggesting this effect is a broader consequence of RAR depletion. Concurrent depletion of RARαb1 and Cyp26a1, an enzyme that facilitates degradation of RA, and employment of a novel transgenic RA sensor line support the hypothesis that the increases in RA signaling in RAR deficient embryos are the result of increased embryonic RA coupled with compensatory RAR expression. Our results support an intriguing novel mechanism by which depletion of RARs elicits a previously unrecognized positive feedback loop that can result in developmental defects due to teratogenic increases in embryonic RA.

  9. Low- and high-frequency transcutaneous electrical nerve stimulation have no deleterious or teratogenic effects on pregnant mice. (United States)

    Yokoyama, L M; Pires, L A; Ferreira, E A Gonçalves; Casarotto, R A


    To evaluate the effects of application of transcutaneous electrical nerve stimulation (TENS) at low and high frequencies to the abdomens of Swiss mice throughout pregnancy. Experimental animal study. Research laboratory. Thirty Swiss mice received TENS throughout pregnancy. They were divided into three groups (n=10): placebo, low-frequency TENS (LF group) and high-frequency TENS (HF group). In the placebo group, the electrodes were applied to the abdominal region without any electrical current. In the LF group, the frequency was 10 Hz, pulse duration was 200 μs and intensity started at 2 mA. In the HF group, the same parameters were applied and the frequency was 150 Hz. All stimulation protocols were applied for 20 min/day from Day 0 until Day 20. The pregnant mice were weighed on Days 0, 7, 14 and 20 to verify weekly weight gain by two-way analysis of variance. The numbers of fetuses, placentas, implantations, resorptions and major external fetal malformations on Day 20 were analysed using the Kruskal-Wallis test. No significant differences were found between the placebo and TENS groups (P>0.05). Application of low- and high-frequency TENS to the abdomens of pregnant mice did not cause any deleterious or major teratogenic effects. Copyright © 2014 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  10. Efficacy of Spirulina platensis in improvement of the reproductive performance and easing teratogenicity in hyperglycemic albino mice (United States)

    Pankaj, Pranay Punj


    Objectives: The present study evaluates the therapeutic efficacy of cell suspension of Spirulina platensis (SP) on estrous cycle, fetal development and embryopathy in alloxan (AXN) induced hyperglycemic mice. Materials and Methods: Diabetes was induced by intra-peritoneal administration of AXN. Mice with blood glucose level above 200 mg/dl were divided into Group I (control), Group II (diabetic control), Group III (diabetic control mice fed with SP), and Group IV (control mice fed with SP). Litter counts, estrous cycles, percent survival of litter, and gestation length were recorded. Results: In hyperglycemic mice, a significant (P < 0.05) increase in duration of diestrus (14.48%), estrus (84.21%), and metestrus (164.15%) with concomitant decrease in proestrus phase by 26.13% was recorded when compared with control. Reduction in litter count and survival of litter was 68.67% and 88.38%, respectively, whereas gestation length increased to 14.51% day in diabetic mice, but recovery in these parameters was observed (P < 0.05) when subjected to SP treatment. SP resulted in increased fertility rate from 77.5% to 82.5% and dropped off resorption of the fetus to 33.73% while the survival rate of offspring of diabetic mice went up to 88.89% from 83.61%. Conclusions: These findings suggest that SP is effective in improving the reproductive performance and easing teratogenic effects in diabetic mice and hence warrants further detailed dose-dependent studies to understand its mechanism of action. PMID:26285837

  11. CD24 expression identifies teratogen-sensitive fetal neural stem cell subpopulations: evidence from developmental ethanol exposure and orthotopic cell transfer models. (United States)

    Tingling, Joseph D; Bake, Shameena; Holgate, Rhonda; Rawlings, Jeremy; Nagsuk, Phillips P; Chandrasekharan, Jayashree; Schneider, Sarah L; Miranda, Rajesh C


    Ethanol is a potent teratogen. Its adverse neural effects are partly mediated by disrupting fetal neurogenesis. The teratogenic process is poorly understood, and vulnerable neurogenic stages have not been identified. Identifying these is a prerequisite for therapeutic interventions to mitigate effects of teratogen exposures. We used flow cytometry and qRT-PCR to screen fetal mouse-derived neurosphere cultures for ethanol-sensitive neural stem cell (NSC) subpopulations, to study NSC renewal and differentiation. The identity of vulnerable NSC populations was validated in vivo, using a maternal ethanol exposure model. Finally, the effect of ethanol exposure on the ability of vulnerable NSC subpopulations to integrate into the fetal neurogenic environment was assessed following ultrasound guided, adoptive transfer. Ethanol decreased NSC mRNAs for c-kit, Musashi-1and GFAP. The CD24(+) NSC population, specifically the CD24(+)CD15(+) double-positive subpopulation, was selectively decreased by ethanol. Maternal ethanol exposure also resulted in decreased fetal forebrain CD24 expression. Ethanol pre-exposed CD24(+) cells exhibited increased proliferation, and deficits in cell-autonomous and cue-directed neuronal differentiation, and following orthotopic transplantation into naïve fetuses, were unable to integrate into neurogenic niches. CD24(depleted) cells retained neurosphere regeneration capacity, but following ethanol exposure, generated increased numbers of CD24(+) cells relative to controls. Neuronal lineage committed CD24(+) cells exhibit specific vulnerability, and ethanol exposure persistently impairs this population's cell-autonomous differentiation capacity. CD24(+) cells may additionally serve as quorum sensors within neurogenic niches; their loss, leading to compensatory NSC activation, perhaps depleting renewal capacity. These data collectively advance a mechanistic hypothesis for teratogenesis leading to microencephaly.

  12. Nanosecond pulsed electric field incorporation technique to predict molecular mechanisms of teratogenicity and developmental toxicity of estradiol-17β on medaka embryos. (United States)

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


    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.

  13. 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

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


    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).

  14. Potentiation of the teratogenic effects induced by coadministration of retinoic acid or phytanic acid/phytol with synthetic retinoid receptor ligands. (United States)

    Elmazar, M M A; Nau, H


    Previous studies in our laboratory identified retinoid-induced defects that are mediated by RAR-RXR heterodimerization using interaction of synthetic ligands selective for the retinoid receptors RAR and RXR in mice (Elmazar et al. 1997, Toxicol Appl Pharmacol 146:21-28; Elmazar et al. 2001, Toxicol Appl Pharmacol 170:2-9; Nau and Elmazar 1999, Handbook of experimental pharmacology, vol 139, Retinoids, Springer-Verlag, pp 465-487). The present study was designed to investigate whether these RAR-RXR heterodimer-mediated defects can be also induced by interactions of natural and synthetic ligands for retinoid receptors. A non-teratogenic dose of the natural RXR agonist phytanic acid (100 mg/kg orally) or its precursor phytol (500 mg/kg orally) was coadministered with a synthetic RARalpha-agonist (Am580; 5 mg/kg orally) to NMRI mice on day 8.25 of gestation (GD8.25). Furthermore, a non-teratogenic dose of the synthetic RXR agonist LGD1069 (20 mg/kg orally) was also coadministered with the natural RAR agonist, all- trans-retinoic acid (atRA, 20 mg/kg orally) or its precursor retinol (ROH, 50 mg/kg orally) to NMRI mice on GD8.25. The teratogenic outcome was scored in day-18 fetuses. The incidence of Am580-induced resorptions, spina bifida aperta, micrognathia, anotia, kidney hypoplasia, dilated bladder, undescended testis, atresia ani, short and absent tail, fused ribs and fetal weight retardation were potentiated by coadministration of phytanic acid or its precursor phytol. Am580-induced exencephaly and cleft palate, which were not potentiated by coadministration with the synthetic RXR agonists, were also not potentiated by coadministration with either phytanic acid or its precursor phytol. LGD1069 potentiated atRA- and ROH-induced resorption, exencephaly, spina bifida, aperta, ear anotia and microtia, macroglossia, kidney hypoplasia, undescended testis, atresia ani, tail defects and fetal weight retardation, but not cleft palate. These results suggest that synergistic

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

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    Alanis Kelly L


    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.

  16. Comparing attitudes about legal sanctions and teratogenic effects for cocaine, alcohol, tobacco and caffeine: A randomized, independent samples design (United States)

    Ginsburg, Harvey J; Raffeld, Paul; Alanis, Kelly L; Boyce, Angela S


    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. PMID:16722564

  17. Evaluation of the perinatal, postnatal and teratogenic effects of cocoa powder and theobromine in Sprague-Dawley/CD rats. (United States)

    Tarka, S M; Applebaum, R S; Borzelleca, J F


    Studies were conducted to evaluate the effects of cocoa powder (CP) and theobromine (TBR) on perinatal and postnatal parameters and to assess their potential teratogenicity in the rat. In the peri/postnatal study, CP was given at 0, 2.5, 5.0 or 7.5% in the diet throughout gestation and lactation (postnatal day 21). In the teratology study, rats were given diets containing 0, 2.5 or 5.0% CP or 0.0675 or 0.135% TBR on days 6-19 of gestation. The CP-treated dams in the peri/postnatal study consumed significantly more food than did the controls during gestation. Weight gain was increased only in the 5.0 and 7.5% CP groups during lactation. Litter size was reduced slightly at 7.5% CP and pup survival was slightly decreased at 5.0 and 7.5% CP but none of these reductions was statistically significant. However, small but statistically significant decreases in pup body weights were noted in all treatment groups throughout lactation. In the teratology studies, rats given 2.5 or 5.0% CP or 0.0675 or 0.135% TBR consumed significantly more food than did the controls and the CP-treated dams gained significantly more weight. The percentage of pregnant dams and the mean number of corpora lutea were not affected by either CP or TBR. Foetuses exposed to 0.135 TBR had a significantly higher incidence of incompletely ossified or absent sternebrae and pubic bones, indicating a delay in osteogenesis. On the basis of the survival of treated offspring in the peri/postnatal study, these effects were not considered to be deleterious to either growth or survival. The effects are similar to those that have been reported elsewhere and been considered to indicate potential maternal or foetal toxicity that is unrelated to a specific compound/treatment. We conclude that any variations observed in these studies may be attributed to this non-specific maternal toxicity and are not related to the ingestion of either CP or TBR. The major methylxanthine found in the serum after CP or TBR ingestion was

  18. Teratogenic and toxic effects of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (W.Curt.:Fr.) P. Karst. (higher Basidiomycetes), on zebrafish embryo as model. (United States)

    Dulay, Rich Milton R; Kalaw, Sofronio P; Reyes, Renato G; Alfonso, Noel F; Eguchi, Fumio


    This paper highlights the teratogenic and toxic effects of Ganoderma lucidum (Lingzhi or Reishi mushroom) extract on zebrafish embryos. Hatchability, malformations, and lethality rate of zebrafish embryos were assessed to provide valuable information regarding the potential teratogenic activity of G. lucidum. Hatching was completed 48 h post treatment application (hpta) at 1% or lower concentrations of extract and embryo water. The hatching rate of embryos treated with 5% or higher concentrations was significantly lower (p> 0.05) than the control. Tail malformation was the most marked morphological abnormality in embryos at 72 hpta, which was obviously caused by 1% extract (55.56% tail malformation) and was observed in all embryos exposed to 5% of extract. Growth retardation was evident in embryos exposed to 5%, 10%, and 20%. However, lethal effect of extract of G. lucidum was dependent on dose and time of exposure. Mortality rates of embryos treated with 5% (44.44%) or higher concentrations of the extract was significantly higher (p > 0.05) than that of the control embryos at 72 hpta. These results suggest that G. lucidum extract has lethal and sub-lethal effects on zebrafish embryos.

  19. European medicinal and edible plants associated with subacute and chronic toxicity part I: Plants with carcinogenic, teratogenic and endocrine-disrupting effects. (United States)

    Kristanc, Luka; Kreft, Samo


    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.

  20. Teratogenic effects of the interaction acetylsalicylic acid (ASA) and ethanol: morphologic and morphometric evaluation of the lingual epithelium in rat fetuses. (United States)

    Marinho, S A; Sala, M A; Lopes, R A; de Moraes Grisi, M F; Novaes, A B; de Souza, S L S; Taba, M


    The objective of the present work was to evaluate the teratogenic effects of the interaction between acetylsalicylic acid (ASA) and ethanol on the epithelium of the lingual mucosa in rat fetuses. On the 10th pregnancy day, a single intraperitoneal ethanol dose (2.96 g/kg body weight) (Group I), ASA (200 mg/kg body weight) (Group II) and ASA plus ethanol, in the same doses (Group III), or saline (Group IV - control), were administrated. The epithelial alterations were assessed by means of histological and morphometric methods, on posterior dorsal, anterior dorsal and ventral regions of the tongue. ASA reduced, in rat fetuses, the ethanol deleterious effects on nuclear size in the epithelial prickle cell of the lingual mucosa. On the other hand, ASA did not influence the effects of ethanol in both epithelial layers of the lingual mucosa, when the nuclear shape, cell volume or epithelial layers thickness were evaluated.

  1. Teratogenic Effects of Crude Ethanolic Root Bark and Leaf Extracts of Rauwolfia vomitoria (Apocynaceae on the Femur of Albino Wistar Rat Fetuses

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    Mokutima A. Eluwa


    Full Text Available Introduction. Rauwolfia vomitoria is a plant used as a sedative and in the treatment of psychotic tendency. This study was on the teratogenic effects of its root bark and leaf extracts on Wistar rat’s fetal femurs. Materials and Methods. Twenty-five female rats weighing between 180 and 200 g were divided into 5 groups, of 5 rats each. Group A was the control, while Groups B, C, D, and E were the experimental. The female rats were mated with mature male rats to allow for pregnancy. Groups B and C animals received orally 150 mg/kg each of the root bark and leaf extracts of Rauwolfia vomitoria, respectively, while Groups D and E animals received 250 mg/kg bodyweight each of the root bark and leaf extracts of Rauwolfia vomitoria, respectively, from day 7 to day 11 of gestation. On day 20 of gestation, the rats were sacrificed, the fetuses were examined, and their femurs were dissected out and preserved, decalcified, and routinely processed using the Haematoxylin and Eosin staining method. Results. Histological observations of the fetal femur bones showed numerous osteoblast and osteoclast, hypertrophy, and hyperplasia of bone cells compared with the control. Conclusion. Ethanolic root bark and leaf extracts of Rauwolfia vomitoria may lead to advanced skeletal development.

  2. Acute Toxicity, Teratogenic, and Estrogenic Effects of Bisphenol A and Its Alternative Replacements Bisphenol S, Bisphenol F, and Bisphenol AF in Zebrafish Embryo-Larvae. (United States)

    Moreman, John; Lee, Okhyun; Trznadel, Maciej; David, Arthur; Kudoh, Tetsuhiro; Tyler, Charles R


    Bisphenol A (BPA), a chemical incorporated into plastics and resins, has estrogenic activity and is associated with adverse health effects in humans and wildlife. Similarly structured BPA analogues are widely used but far less is known about their potential toxicity or estrogenic activity in vivo. We undertook the first comprehensive analysis on the toxicity and teratogenic effects of the bisphenols BPA, BPS, BPF, and BPAF in zebrafish embryo-larvae and an assessment on their estrogenic mechanisms in an estrogen-responsive transgenic fish Tg(ERE:Gal4ff)(UAS:GFP). The rank order for toxicity was BPAF > BPA > BPF > BPS. Developmental deformities for larval exposures included cardiac edema, spinal malformation, and craniofacial deformities and there were distinct differences in the effects and potencies between the different bisphenol chemicals. These effects, however, occurred only at concentrations between 1.0 and 200 mg/L which exceed those in most environments. All bisphenol compounds induced estrogenic responses in Tg(ERE:Gal4ff)(UAS:GFP) zebrafish that were inhibited by coexposure with ICI 182 780, demonstrating an estrogen receptor dependent mechanism. Target tissues included the heart, liver, somite muscle, fins, and corpuscles of Stannius. The rank order for estrogenicity was BPAF > BPA = BPF > BPS. Bioconcentration factors were 4.5, 17.8, 5.3, and 0.067 for exposure concentrations of 1.0, 1.0, 0.10, and 50 mg/L for BPA, BPF, BPAF, and BPS, respectively. We thus show that these BPA alternatives induce similar toxic and estrogenic effects to BPA and that BPAF is more potent than BPA, further highlighting health concerns regarding the use of BPA alternatives.

  3. Prevalence of periconceptional folic acid use and perceived barriers to the postgestation continuance of supplemental folic acid: survey results from a Teratogen Information Service. (United States)

    Goldberg, Beck B; Alvarado, Sonia; Chavez, Carmen; Chen, Brian H; Dick, Lyn M; Felix, Robert J; Kao, Kelly K; Chambers, Christina D


    Fewer than 40% of U.S. women are taking folic acid supplements periconceptionally at a time when the risk of neural tube defects (NTDs) can be reduced by supplementation. A better understanding of the vitamin-taking habits of childbearing-age women and effective methods for improving periconceptional supplement use are needed. A telephone survey conducted through the California Teratogen Information Service (TIS) between August 2003 and January 2004 assessed the prevalence and characteristics of pregnant callers who did not use folic acid supplements in the periconceptional period, and explored attitudes toward advice to continue vitamin use following pregnancy in order to be protected in a future pregnancy. A total of 327 pregnant women who called the TIS for information agreed to participate in the survey. More than half (53.2%) were not taking folic acid-containing supplements in the periconceptional period. Predictors of lack of use included a higher prepregnancy body mass index, younger maternal age, non-white race/ethnicity, lower education level, and unplanned pregnancy. One-quarter of the women said they would be willing to continue taking vitamins after the pregnancy if advised to do so by a physician. The remainder identified obstacles to following that advice--notably, not planning to become pregnant again and the belief that enough folate is derived from diet alone. More than half of the callers to the TIS were not compliant with recommendations regarding periconceptional folic acid supplementation. This represents an opportunity for TIS specialists and physicians to intervene in a current pregnancy to encourage maintenance of supplement use in the subsequent interpregnancy interval. Copyright 2006 Wiley-Liss, Inc.

  4. DNA oxidation as a potential molecular mechanism mediating drug-induced birth defects: phenytoin and structurally related teratogens initiate the formation of 8-hydroxy-2'-deoxyguanosine in vitro and in vivo in murine maternal hepatic and embryonic tissues. (United States)

    Liu, L; Wells, P G


    A considerable number of teratogens, including the anticonvulsant drug phenytoin and structurally related drugs and environmental chemicals, may be bioactivated by peroxidases, such as prostaglandin H synthase (PHS) and lipoxygenases (LPOs), to a reactive free radical intermediate that initiates birth defects. However, the molecular targets of the reactive free radical intermediates mediating chemical teratogenesis, and hence the fundamental determinants of susceptibility, are poorly understood. In these studies, a teratogenic dose of phenytoin (65 mg/kg), when injected into pregnant CD-1 mice during organogenesis on gestational day 12, initiated the oxidation of DNA in maternal hepatic and embryonic nuclei, forming 8-hydroxy-2'-deoxyguanosine. Significant maternal and embryonic DNA oxidation occurred at 6 and 3 h, respectively, suggesting relative embryonic deficiencies in free radical-related cytoprotective enzymes, although the rates appeared similar. Maximal DNA oxidation in both maternal and embryonic tissues occurred at 6 h, presumably reflecting the balance of DNA oxidation and repair, the latter of which appeared similar in both tissues. Inhibition of phenytoin-initiated embryonic DNA oxidation by the free radical spin trapping agent alpha-phenyl-N-t-butylnitrone (41.5 mg/kg), and by acetylsalicylic acid (10 mg/kg), an inhibitor of the cyclooxygenase component of PHS, was consistent with the previously reported reduction by these inhibitors of phenytoin-initiated murine birth defects. In vitro studies using a horseradish peroxidase (0.5 mg/ml)-H2O2 (5.45 micrograms/ml) bioactivating system for drug-initiated oxidation of 2'-deoxyguanosine (3.74 mM), indicated that the potency of xenobiotic-initiated formation of 8-hydroxy-2'-deoxyguanosine for the structurally related drugs and metabolites phenytoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin, trimethadione, dimethadione, l-mephenytoin, l-nirvanol, d-nirvanol (80 microM each), or thalidomide (64 micro

  5. The teratogenicity of anticonvulsant drugs. (United States)

    Holmes, L B; Harvey, E A; Coull, B A; Huntington, K B; Khoshbin, S; Hayes, A M; Ryan, L M


    The frequency of major malformations, growth retardation, and hypoplasia of the midface and fingers, known as the anticonvulsant embryopathy, is increased in infants exposed to anticonvulsant drugs in utero. However, whether the abnormalities are caused by the maternal epilepsy itself or by exposure to anticonvulsant drugs is not known. We screened 128,049 pregnant women at delivery to identify three groups of infants: those exposed to anticonvulsant drugs, those unexposed to anticonvulsant drugs but with a maternal history of seizures, and those unexposed to anticonvulsant drugs with no maternal history of seizures (control group). The infants were examined systematically for the presence of major malformations, signs of hypoplasia of the midface and fingers, microcephaly, and small body size. The combined frequency of anticonvulsant embryopathy was higher in 223 infants exposed to one anticonvulsant drug than in 508 control infants (20.6 percent vs. 8.5 percent; odds ratio, 2.8; 95 percent confidence interval, 1.1 to 9.7). The frequency was also higher in 93 infants exposed to two or more anticonvulsant drugs than in the controls (28.0 percent vs. 8.5 percent; odds ratio, 4.2; 95 percent confidence interval, 1.1 to 5.1). The 98 infants whose mothers had a history of epilepsy but took no anticonvulsant drugs during the pregnancy did not have a higher frequency of those abnormalities than the control infants. A distinctive pattern of physical abnormalities in infants of mothers with epilepsy is associated with the use of anticonvulsant drugs during pregnancy, rather than with epilepsy itself.

  6. 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


    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

  7. Evaluation of the teratogenic potential of N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-α-aspartyl]-L-phenylalanine 1-methyl ester, monohydrate (advantame) in the rat and rabbit. (United States)

    Otabe, A; Fujieda, T; Masuyama, T


    To assess its teratogenic potential, advantame (N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-α-aspartyl]-L-phenylalanine 1-methyl ester, monohydrate) was administered to mated rats (22/group) in the diet at 0, 5000, 15,000, and 50,000 ppm (providing approximately 465, 1418, and 4828 mg/kg body weight/day), and to mated rabbits (24/group) via oral gavage at 0, 500, 1000, and 2000 mg/kg body weight/day throughout gestation. Shortly before delivery (rats: day 20; rabbits: day 29), animals were killed and subjected to a detailed necropsy. Fetuses were examined for external, visceral, and skeletal alterations. Atypical coloration of the feces and cage liners seen with test diets in both rats and rabbits was attributed to excretion of test material/metabolites in the feces and urine. Advantame had no adverse effect on rat offspring survival or development. The no-observed-adverse-effect level (NOAEL) for both maternal and developmental toxicity in rats was 50,000 ppm, the highest dietary concentration tested. Due to adverse effects associated with reduced food intake and fecal output, approximately 20% of mated rabbits receiving 200 0mg/kg body weight/day and 1 animal at 1000 mg/kg body weight/day had to be terminated before scheduled necropsy. A NOAEL of 500 mg/kg body weight/day was established for maternal toxicity in rabbits. No teratogenic effects were observed in any animals, and based on a slightly increased incidence of fetal deaths at 2000 mg/kg body weight/day, a finding that was considered to be indirectly related to advantame treatment, 1000 mg/kg body weight/day was considered the NOAEL for developmental toxicity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. 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


    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.

  9. EFECTOS TERATOGÉNICOS DE ALGUNOS FÁRMACOS QUE PUEDEN PRODUCIR CARDIOPATÍAS CONGÉNITAS Y OTRAS ANOMALÍAS / Teratogenic effects of some drugs that can cause congenital heart disease and other abnormalities

    Directory of Open Access Journals (Sweden)

    Lissett Batista Santos


    Full Text Available Resumen Muchas de las malformaciones o anomalías de carácter anatómico o funcional provocadas en el feto se deben a la utilización de medicamentos por la madre, durante la gestación. Estos trastornos pueden detectarse en la vida intrauterina, inmediatamente después del nacimiento o, en ocasiones, muchos años después; pero generalmente se diagnostican tempranamente y en determinadas circunstancias pueden comprometer la vida del enfermo. En este artículo se exponen, de forma general, los principales efectos teratogénicos de algunos fármacos que pueden predisponer a cardiopatías y otras anomalías congénitas. El ambiente de una gestante se encuentra cargado de sustancias agresivas para el futuro producto de la gestación. La mayoría de las malformaciones más importantes son producidas durante el período teratogénico que comprende de la tercera a la octava semana de la gestación. Las medidas de prevención secundaria se sustentan en el diagnóstico prenatal y el asesoramiento genético. / Abstract Many of the malformations or abnormalities of anatomical or functional character provoked in the fetus are due to drug use by the mother during gestation. These disorders can be detected during intrauterine life, immediately after birth or at times, many years later, but they are generally diagnosed early and in certain circumstances they can compromise the life of the newborn. The main teratogenic effects of some drugs that can predispose to heart diseases and other congenital abnormalities are set out in this article in a general way. The environment of a pregnant woman is loaded with aggressive substances for the future product of gestation. The majority of the most relevant malformations are produced during the teratogenic period, which comprises weeks third to eigth of gestation. Secondary prevention measures are based on prenatal diagnosis and genetic counseling.

  10. 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


    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

  11. Nitric oxide rescues thalidomide mediated teratogenicity (United States)

    Siamwala, Jamila H.; Veeriah, Vimal; Priya, M. Krishna; Rajendran, Saranya; Saran, Uttara; Sinha, Swaraj; Nagarajan, Shunmugam; T, Pradeep; Chatterjee, Suvro


    Thalidomide, a sedative drug given to pregnant women, unfortunately caused limb deformities in thousands of babies. Recently the drug was revived because of its therapeutic potential; however the search is still ongoing for an antidote against thalidomide induced limb deformities. In the current study we found that nitric oxide (NO) rescues thalidomide affected chick (Gallus gallus) and zebrafish (Danio rerio) embryos. This study confirms that NO reduced the number of thalidomide mediated limb deformities by 94% and 80% in chick and zebrafish embryos respectively. NO prevents limb deformities by promoting angiogenesis, reducing oxidative stress and inactivating caspase-3 dependent apoptosis. We conclude that NO secures angiogenesis in the thalidomide treated embryos to protect them from deformities. PMID:22997553

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

    African Journals Online (AJOL)

    Pregnant Sprague-Dawley rats were treated from day 9 through 12 of gestation with either nicotine alone (6 mg/kg/day nicotine osmotic minipump or nicotine plus methionine (200 mg/kg) by gavage. Fetuses and embryos were recovered on gestational day-20 or day-12, respectively and were quantitatively and qualitatively ...

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

    African Journals Online (AJOL)

    Hatching and survival decreased in all treatments with significant difference (p < 0.05) at 50 and 100 μg/ml concentrations with control. Stunted skeletal structure was observed at 100 μg/ml treatment. At 96 hpf, MSG induced enhanced green fluorescence protein (EGFP) expression in the olfactory bulb at 100 μg/ml treatment ...

  14. Drug safety in pregnancy : studying and communicating teratogenic risks

    NARCIS (Netherlands)

    Meijer, Willemijn Marieke


    In dit proefschrift worden verschillende relaties tussen (genees)middelgebruik en aangeboren afwijkingen bestudeerd. Omdat deze relaties zeldzaam zijn, en dus de power om een relatie te onderzoeken vaak laag is, wordt tevens de mogelijkheid bestudeerd om dergelijke studies in een database uit te

  15. Studies on the teratogenic effects of deltamethrin in rats. (United States)

    Abdel-Khalik, M M; Hanafy, M S; Abdel-Aziz, M I


    Deltamethrin is a pyrethroid insecticide used to eradicate external parasites on farm animals. Residues of this pesticide were shown to be present in food from animal origin which encouraged us to investigate the effects of deltamethrin on foetuses of pregnant rats. Literature search shows that previous research was focused on organochlorine and organophosphate pesticides whereas little attention was given to the newer pyrethroid insecticides. Four groups of pregnant rats (20 rats each) were given either the vehicle (control) or doses of 1, 2.5 or 5 mg/kg b. w. of deltamethrin orally from day 6 to day 15 of pregnancy which was terminated by killing the animals on the 19th day for foetal examinations. The incidence of early embryonic deaths was higher in deltamethrin-treated rats than in control females. Deltamethrin caused retardation of growth, hypoplasia of the lungs, dilatation of the renal pelvis and increase in placental weight. No skeletal changes were observed in foetuses recovered from deltamethrin-treated females. Although deltamethrin is relatively safe, however its effects on the foetus should be considered when used on pregnant animals or in environments where pregnant animals and women live.

  16. 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


    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


    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...

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

    African Journals Online (AJOL)

    The effect of isotretinoin currently used in dermatological treatments was investigated on the morphology and palate development during organogenesis in rat fetuses. This was in an attempt to evaluate the morphological implications associated with isotretinoin consumption. The animals were randomly divided into groups: ...

  19. 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.

  20. Teratogenic effects of Origanum Vulgare extract in mice fetals

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    Iraj Ragerdi Kashani


    Full Text Available Background: A number of studies on reproduction have mentioned Origanum Vulgare extract’s ability to reduce mortality rates and improve fertility rates. However, other studies have suggested that it is possible to use Origanum Vulgare extract to induce abortion. The aim of this study was to investigate the effect of different doses of Origanum Vulgare on embryo survival and macroscopic abnormalities in mice.Methods: In this study, 24 mice Balb/c female weighting approximately 25-30 g were divided into 4 groups. Origanum Vulgare extract was prepared; different concentrations (2.5, 12.5, and 25 mg in 0.25 ml distilled water were administered, by oral gavage, to three experimental groups of mice between day 6 (starting gastrulation until day 15 of pregnancy (end of organogenesis. The control group consisted of six mice that received 0.25 ml of distilled water daily. On day 16 of study, pregnant mice were anesthetized by chloroform and fetuses were removed and stained with Alcian Blue, Alizarin Red s and microwave irradiation. Morphological and skeletal abnormalities were investigated by light and stereomicroscopes.Results: The results of this study showed that high doses of the Origanum Vulgare extract significantly decreased the mean number of embryos (100.5, P>0.05, mean number of live embryos (70.5, P>0.05 in each mouse and resulted in significant reduction in mean weight(11848 mg, P>0.05 and crown-rump length(11.90.23 mm, P>0.05 and the overall size of fetuses compared to control group, whereas there was no significant difference between the groups receiving low dose of Origanum Vulgare extract with control group. In addition, under the effect of the Origanum Vulgare extract the subcutaneous bleeding seemed (20.1, P>0.05 significantly more frequent compared to the control group. Conclusion: Origanum Vulgare extract did not have any positive effect on fetal development; and high dosages led to an increased incidence rate of abortion and fetal malformations in the fetuses of women who received it.

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

    DEFF Research Database (Denmark)

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio


    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 wome...

  2. Teratogenicity and the Threshold of Toxicological Concern concept

    NARCIS (Netherlands)

    Schothorst F van; Piersma AH; TOX


    The Threshold of Toxicological Concern (TTC) is a principle that refers to the possibility of establishing a human exposure threshold value for all chemicals below which there is no significant risk to human health. The threshold value is primarily based on carcinogenesis data. For

  3. Teratogenicity and the Threshold of Toxicological Concern concept

    NARCIS (Netherlands)

    van Schothorst F; Piersma AH; TOX


    Het principe van de Threshold of Toxicological Concern (TTC) verwijst naar de mogelijkheid om voor alle chemische stoffen een humane blootstellinggrens te bepalen, waaronder geen noemenswaardig risico optreedt voor de gezondheid van de mens. Deze grenswaarde is in de eerste plaats gebaseerd op

  4. Paving ways for personalizing drug therapy during pregnancy : A focus on the risk of drug teratogenicity

    NARCIS (Netherlands)

    Daud, Nur


    Medication use during pregnancy is very common, but can potentially harm the unborn child. Many studies have evaluated the safety of certain medications, but data are still lacking. The level of medication exposure of the unborn child also differs because of differences between individual mothers

  5. Teratogenic Potential of Ethylene Thiourea (ETU), A Positive Control in Sprague-Dawley Rats. (United States)


    hernia 1 0 Short forelimb 1 0 Short paw digits 1 0 Forepaw digits long and separate 116 38 Forepaw one digit long, others short 20 6 Syndactyly 152 49...Diaphragmatic hernia 1 *Percent calculated with number of male fetuses - 69. tPercent calculated with n,,mher of female fetuses - 79. 6** Coppes 15 a...mandible 6 4 1 1 Short mandible 13 8 Cleft palate 26 16 Kyphosis 70 44 Scoliosis 5 3 Missing lumbar vertebrae 3 2 Missing ribs 4 2 Branched or fused ribs 42

  6. Concentration-response relationship for teratogenic effect of 17β-oestradiol in eelpout Zoarces viviparus

    DEFF Research Database (Denmark)

    Brande-Lavridsen, Nanna; Morthorst, Jane Ebsen; Korsgaard, Bodil

    arrested development and spinal axis deformities. Moreover, it was observed that the amount of ovarian fluid was significantly reduced (P=0.001) in the highest exposure group. The study further showed that delaying the onset of exposure to the highest dose of E2 by approximately three weeks reduced...

  7. Teratogenic effect of cadmium on the foetal development of albino rats

    African Journals Online (AJOL)

    Foetus of pregnant rats exposed to single intraperitoneal injection of 2 mg/kg body weight cadmium sulphate on eighth gestational days; were compared with control (saline injected) fetuses to assess the effects of cadmium sulphate on foetal growth and ossification. Cadmium sulphate caused significant reduction in body ...

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

  9. Assembly, maturation and three-dimensional helical structure of the teratogenic rubella virus.

    Directory of Open Access Journals (Sweden)

    Vidya Mangala Prasad


    Full Text Available Viral infections during pregnancy are a significant cause of infant morbidity and mortality. Of these, rubella virus infection is a well-substantiated example that leads to miscarriages or severe fetal defects. However, structural information about the rubella virus has been lacking due to the pleomorphic nature of the virions. Here we report a helical structure of rubella virions using cryo-electron tomography. Sub-tomogram averaging of the surface spikes established the relative positions of the viral glycoproteins, which differed from the earlier icosahedral models of the virus. Tomographic analyses of in vitro assembled nucleocapsids and virions provide a template for viral assembly. Comparisons of immature and mature virions show large rearrangements in the glycoproteins that may be essential for forming the infectious virions. These results present the first known example of a helical membrane-enveloped virus, while also providing a structural basis for its assembly and maturation pathway.

  10. Assembly, maturation and three-dimensional helical structure of the teratogenic rubella virus. (United States)

    Mangala Prasad, Vidya; Klose, Thomas; Rossmann, Michael G


    Viral infections during pregnancy are a significant cause of infant morbidity and mortality. Of these, rubella virus infection is a well-substantiated example that leads to miscarriages or severe fetal defects. However, structural information about the rubella virus has been lacking due to the pleomorphic nature of the virions. Here we report a helical structure of rubella virions using cryo-electron tomography. Sub-tomogram averaging of the surface spikes established the relative positions of the viral glycoproteins, which differed from the earlier icosahedral models of the virus. Tomographic analyses of in vitro assembled nucleocapsids and virions provide a template for viral assembly. Comparisons of immature and mature virions show large rearrangements in the glycoproteins that may be essential for forming the infectious virions. These results present the first known example of a helical membrane-enveloped virus, while also providing a structural basis for its assembly and maturation pathway.

  11. Teratogenic and genotoxic responses of larval Chironomus (Diptera) to contaminated sediments

    Energy Technology Data Exchange (ETDEWEB)

    Hudson, L.A.; Muir, K.; Ciborowski, J.J.H. [Univ. of Windsor, Ontario (Canada)


    Sediment-associated contaminants can produce developmental or genotoxic stresses independently of their cytotoxic effects. In the laboratory, the authors exposed Chironomus larvae to mixtures of polluted (either Detroit R., MI, or cadmium or benzo-[a]-pyrene-spiked) sediment diluted with uncontaminated, formulated sediment. Second-instar Chironomus nr. salinarius were grown to 4th star in water filled 1-L jars containing 300 mL of contaminated:formulated sediment mixture in ratios of 1:0, 1:1, 1:3, 1:7, 1:15 or 0:1. Surviving larvae were preserved in Carnoy`s solution. Each larva`s head was slide-mounted and examined for deformities of the mentum. Polytene chromosome preparations were made from salivary glands of the same animals using acid fuschin staining and examined for reduced relative size of the nuclear organizer (NO) indicative of inhibition of RNA synthesis activity. Incidence of chironomid deformities from control (0:1) sediments ({plus_minus}I SE) was 7.9 {plus_minus} 1.6% (N = 268): 4.0 {plus_minus} 1.5% of 178 control larvae examined displayed NO reduction. Incidence of mentum deformities and of NO reduction increased linearly with each doubling of Detroit R. concentration at 1:0 for deformities; 12.2 {plus_minus} 3.5% (N = 149) for NO reductions. Reduction of NO in a larva was unrelated to mentum condition, indicating that these are independent responses to contaminant stress. Equivalent results were obtained for exposure to single-compound sediments. This is the first documentation of controlled dose-response effects of contaminants on chironomid deformities.

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

    DEFF Research Database (Denmark)

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


    of control cells and cells treated with VPA, indicating that VPA affected the cytoskeletal determinants of cell morphology. Furthermore, VPA treatment induced an increase of F-actin, and of FAK, paxillin, vinculin, and phosphotyrosine in focal adhesion complexes. These changes were accompanied by increased...

  13. Embryotoxic and teratogenic effects of styrene derivatives on sea urchin development. (United States)

    Pagano, G; Esposito, A; Giordano, G G; Hagström, B E


    The effects of styrene and some of its derivatives on the fertilization and differentiation of sea urchins was investigated. When one of the gametes was pretreated for a few minutes, it was ascertained that the test substances act on the haploid nucleus, producing specific changes in the differentiation of the embryo. By this test system directly acting, weak mutagens may be detected.

  14. Ecotoxicological impact of MSW landfills: assessment of teratogenic effects by means of an adapted FETAX assay. (United States)

    de Lapuente, J; González-Linares, J; Pique, E; Borràs, M


    The introduction of chemical products into the environment can cause long-term effects on the ecosystems. Increasing efforts are being made to determine the extent of contamination in particularly affected areas using diverse methods to assess the ecotoxicological impact. We used a modified Frog Embrio Toxicity Assay-Xenopus method to determine the extent of toxicological load in different sample soils obtained near three municipal solid waste landfills in Catalonia (Spain). The results show that the Garraf landfill facility produces more embryotoxic damage to the surroundings, than the others ones: Can Mata landfill and Montferrer-Castellbó landfill. The aim of this work is to demonstrate how different management of complex sources of contamination as the controlled dumping sites can modulate the presence of toxics in the environment and their effects and through this, help determine the safer way to treat these wastes. To this effect some conceptual modifications have been made on the established American Society for Testing and Materials protocol. The validity of the new model, both as to model of calculation as to protocol, has been demonstrated in three different sites with complex sources of contamination.

  15. Evaluation of mutagenic, teratogenic, and immunomodulatory effects of Annona nutans hydromethanolic fraction on pregnant mice. (United States)

    Gonçalves, C A; Silva, N L; Mauro, M O; David, N; Cunha-Laura, A L; Auharek, S A; Monreal, A C D; Vieira, M C; Silva, D B; Santos, F J L; Siqueira, J M; Oliveira, R J


    Plants such as Annona nutans used in folk medicine have a large number of biologically active compounds with pharmacological and/or toxic potential. Moreover, pregnant women use these plants indiscriminately, mainly in the form of teas, without being aware of the harm that they could cause to the health of the embryo/fetus. Therefore, it is necessary to analyze the potential toxic effects of medicinal plants during gestation. The present study aimed to evaluate the effects of A. nutans hydromethanolic fraction leaves (ANHMF) on mutagenic and immunomodulatory activity, reproductive performance, and embryo-fetal development in pregnant female mice. The animals (N=50 female and 25 male) were divided into 5 groups: Control, Pre-treatment, Organogenesis, Gestational, and Pre+Gestational. The results indicate that ANHMF mainly contains flavonoid and other phenolic derivatives. It was found that it does not exhibit any mutagenic or immunomodulatory activity, and it does not cause embryo-fetal toxicity. Based on the protocols used in the present studies, our analyses confirm that it is safe to use ANHMF during pregnancy.

  16. 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.


    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

  17. In vitro teratogenicity of acetylsalicylic acid on rat embryos: studies with various culture conditions. (United States)

    Cicurel, L; Schmid, B


    Rat embryos taken at day 9.5 of gestation were exposed in vitro to acetylsalicylic acid (aspirin) using various culture conditions. It was observed that embryos were sensitive to aspirin emulsified in olive oil at concentrations greater than or equal to 150 micrograms/ml. Between 43% and 66% of the embryos exhibited multiple malformations depending on the culture medium, 100% homologous rat serum or Waymouth medium supplemented with 50% rat serum, respectively. At concentrations greater than or equal to 400 micrograms/ml aspirin induced further toxic effects on embryo growth and differentiation. When gelatin was used as the drug-delivery system, aspirin at concentrations of greater than or equal to 150 micrograms/ml induced some malformations (mainly irregular somite shapes) in 57% of the embryos cultured in Waymouth medium, but in only 13% of the embryos grown in 100% serum. At concentrations which were greater than or equal to 400 micrograms/ml aspirin induced dysmorphogenic effects in all embryos, without any concomittant toxicity.

  18. Teratogenic Effect of Verbascoside, Main Constituent of Lippia citriodora Leaves, in Mice. (United States)

    Etemad, Leila; Zafari, Reza; Moallem, Seyed Adel; Vahdati-Mashhadian, Naser; Skouei Shirvan, Zahra; Hosseinzadeh, Hossein


    Verbascoside (acteoside), a phenyl propanoid glycoside, comprises 0.5 to 3.5 % dry weight of Lippia citriodora leaves. A wide range of biological activities are attributed to verbascoside including anti-inflammatory, antioxidant, anti-bacterial, anti-tumor, anti-fungal, photoprotective as well as chelating effects. The objective of this study is to evaluate the effect of verbascoside on pregnancy outcome in mice. Timed-pregnant mice received doses of 1g/kg/day verbascoside or the vehicle control during organogenesis, intraperitoneally. Maternal body weights were measured throughout pregnancy. The litters were examined for external malformations and skeletal abnormalities. Then they were stained with Alizarin red S and Alcian blue. Maternal exposure to verbascoside throughout pregnancy did not influence the mean of maternal weight gain. Statistically significant difference was not found in mean number of implantation sites, live and resorbed fetuses between control and experiment groups. Our data demonstrate that the main component of L. citriodora, verbascoside using during organogenesis possesses no risk to fetuses. However, more research projects are needed to confirm these findings and determine the exact effects of verbascoside on human embryo development.

  19. Transcriptome Profiling Identifies Ribosome Biogenesis as a Target of Alcohol Teratogenicity and Vulnerability during Early Embryogenesis.

    Directory of Open Access Journals (Sweden)

    Mark E Berres

    Full Text Available Fetal alcohol spectrum disorder (FASD is a leading cause of neurodevelopmental disability. Individuals with FASD may exhibit a characteristic facial appearance that has diagnostic utility. The mechanism by which alcohol disrupts craniofacial development is incompletely understood, as are the genetic factors that can modify individual alcohol vulnerability. Using an established avian model, we characterized the cranial transcriptome in response to alcohol to inform the mechanism underlying these cells' vulnerability. Gallus gallus embryos having 3-6 somites were exposed to 52 mM alcohol and the cranial transcriptomes were sequenced thereafter. A total of 3422 genes had significantly differential expression. The KEGG pathways with the greatest enrichment of differentially expressed gene clusters were Ribosome (P = 1.2 x 10-17, 67 genes, Oxidative Phosphorylation (P = 4.8 x 10-12, 60 genes, RNA Polymerase (P = 2.2 x 10-3, 15 genes and Spliceosome (P = 2.6 x 10-2, 39 genes. The preponderance of transcripts in these pathways were repressed in response to alcohol. These same gene clusters also had the greatest altered representation in our previous comparison of neural crest populations having differential vulnerability to alcohol-induced apoptosis. Comparison of differentially expressed genes in alcohol-exposed (3422 and untreated, alcohol-vulnerable (1201 transcriptomes identified 525 overlapping genes of which 257 have the same direction of transcriptional change. These included 36 ribosomal, 25 oxidative phosphorylation and 7 spliceosome genes. Using a functional approach in zebrafish, partial knockdown of ribosomal proteins zrpl11, zrpl5a, and zrps3a individually heightened vulnerability to alcohol-induced craniofacial deficits and increased apoptosis. In humans, haploinsufficiency of several of the identified ribosomal proteins are causative in craniofacial dysmorphologies such as Treacher Collins Syndrome and Diamond-Blackfan Anemia. This work suggests ribosome biogenesis may be a novel target mediating alcohol's damage to developing neural crest. Our findings are consistent with observations that gene-environment interactions contribute to vulnerability in FASD.

  20. Teratogenic effects of 17β-estradiol and other environmental chemicals in eelpout Zoarces viviparus

    DEFF Research Database (Denmark)

    Morthorst, Jane Ebsen; Brande-Lavridsen, Nanna; Korsgaard, Bodil

    . The specific chemicals or group of chemicals causing the malformations observed in nature are not known, but similar malformations upon exposure of pregnant eelpout to octylphenol (OP) and 17β-estradiol (E2) in high concentrations have recently been observed in the laboratory. In the current two experiments...... the abundance of larvae malformations and the amount of ovarian fluid was signicficantly reduced. Plasma levels of E2 and vitellogenin increased with increasing E2 exposure. Similar endpoints were investigated in the experiment with OP, pyrene and EE2. The results also indicate that there is a sensitive window...

  1. Abrupt discontinuation of psychotropic drugs during pregnancy: fear of teratogenic risk and impact of counselling. (United States)

    Einarson, A; Selby, P; Koren, G


    To assess the consequences to mother and baby of abruptly discontinuing antidepressant or benzodiazepine medication during pregnancy and to assess the impact of our counselling. All women who consulted the Motherisk Program between November 1996 and December 1997 and who stopped taking antidepressant or benzodiazepine medication when pregnancy was confirmed agreed to participate in the study. Subjects were interviewed, received counselling, and completed a questionnaire 1 month after their initial call and after the birth of their baby. Of 36 women who completed the study, 34 discontinued their medication abruptly for fear of harming the fetus, 28 on the advice of their physician; 26 (70.3%) women reported physical and psychological adverse effects, 11 reported psychological effects only, and 11 reported suicidal ideation (4 were admitted to hospital). After counselling, 22 of 36 (61.1%) women resumed taking their medication, and 4 found that they no longer required it. One woman had a therapeutic abortion and 2 experienced spontaneous abortions; there were therefore 35 healthy babies (including 2 sets of twins) born to 33 women; 14 of 21 mothers breast-fed their babies while taking their psychotropic medication, with no adverse effects reported. When assessing the risks and benefits of taking psychotropic medication during pregnancy, women and their physicians should be aware that the abrupt discontinuation of psychotropic drugs can lead to serious adverse effects. Counselling is effective in reassuring women to adhere to therapy.

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


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


    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...

  3. Molecular epidemiological analyses of the teratogenic Aino virus based on the sequences of a small RNA segment. (United States)

    Yamakawa, Makoto; Yanase, Tohru; Kato, Tomoko; Tsuda, Tomoyuki


    The sequences of a small RNA segment of Aino virus isolates were analyzed to define the molecular epidemiology and genetic relationships to other species in the genus Orthobunyavirus in the family Bunyaviridae. The nucleotide and amino acid sequences of the segment were highly conserved among strains isolated from 1964 to 2002 in Japan. These Japanese isolates were segregated into two distinct lineages, one containing the prototype strain JaNAr28 isolated in 1964 and the other containing strains isolated after 1986, by phylogenetic analysis based on the nucleocapsid gene sequences. Japanese strains isolated after 1986 were rather more closely related to Kaikalur virus isolated in India in 1971 than to strain JaNAr28. On the other hand, an Australian strain, B7974, was closely related to Peaton virus. The B7974 strain might have been generated by inter-serotype genetic reassortment between Aino and Peaton viruses in Australia during their evolution. However, recent Aino virus strains isolated in Japan appear to be genetically stable.

  4. Determination of trace thiophanate-methyl and its metabolite carbendazim with teratogenic risk in red bell pepper (Capsicumannuum L.) by surface-enhanced Raman imaging technique. (United States)

    Li, Jiang-Lin; Sun, Da-Wen; Pu, Hongbin; Jayas, Digvir S


    Surface-enhanced Raman scattering (SERS) imaging coupling with multivariate analysis in spectral region of 200 to 1800cm-1 was developed to quantify and visualize thiophanate-methyl (TM) and its metabolite carbendazim residues in red bell pepper (Capsicum annuum L.). Least squares support vector machines (LS-SVM) and support vector machines (SVM) models based on seven optimized characteristic peaks that showed SERS effects of TM and its metabolite carbendazim residues were employed to establish prediction models. SERS spectra with first derivative (1st) and second derivative (2nd) method were subsequently compared and the optimized model of 1st-LS-SVM acquired showed the best performance (RPD=6.08, R2P=0.986 and RMSEP=0.473). The results demonstrated that SERS imaging with multivariate analysis had the potential for rapid determination and visualization of the trace TM and its metabolite carbendazim residues in complex food matrices. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. 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


    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.

  6. 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


    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. There...

  7. Effects of gestational exposure to 1.95-GHz W-CDMA signals for IMT-2000 cellular phones: Lack of embryotoxicity and teratogenicity in rats. (United States)

    Ogawa, Kumiko; Nabae, Kyoko; Wang, Jianqing; Wake, Kanako; Watanabe, So-ichi; Kawabe, Mayumi; Fujiwara, Osamu; Takahashi, Satoru; Ichihara, Toshio; Tamano, Seiko; Shirai, Tomoyuki


    The present study was designed to evaluate whether gestational exposure to an EMF targeting the head region, similar to that from cellular phones, might affect embryogenesis in rats. A 1.95-GHz wide-band code division multiple access (W-CDMA) signal, which is one applied for the International Mobile Telecommunication 2000 (IMT-2000) system and used for the freedom of mobile multimedia access (FOMA), was employed for exposure to the heads of four groups of pregnant CD(SD) IGS rats (20 per group) for gestational days 7-17. The exposure was performed for 90 min/day in the morning. The spatial average specific absorption rate (SAR) for individual brains was designed to be 0.67 and 2.0 W/kg with peak brain SARs of 3.1 and 7.0 W/kg for low (group 3) and high (group 4) exposures, respectively, and a whole-body average SAR less than 0.4 W/kg so as not to cause thermal effects due to temperature elevation. Control and sham exposure groups were also included. At gestational day 20, all dams were killed and fetuses were taken out by cesarean section. There were no differences in maternal body weight gain. No adverse effects of EMF exposure were observed on any reproductive and embryotoxic parameters such as number of live (243-271 fetuses), dead or resorbed embryos, placental weights, sex ratios, weights or external, visceral or skeletal abnormalities of live fetuses. (c) 2008 Wiley-Liss, Inc.

  8. 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

    Energy Technology Data Exchange (ETDEWEB)

    Kagohashi, Yukiko; Naora, Hiroyuki; Otani, Hiroki [Shimane Medical Univ., Izumo (Japan)


    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)

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

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    Paulo Roberto Veiga Quemelo


    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.

  10. 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


    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.

  11. 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

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    Rodríguez-Burgos Antonio


    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.

  12. Exposure of the eggs to 17{alpha}-methyl testosterone reduced hatching success and growth and elicited teratogenic effects in postembryonic life stages of crayfish

    Energy Technology Data Exchange (ETDEWEB)

    Vogt, Guenter [Zoological Institute and Museum, University of Greifswald, Johann-Sebastian-Bach-Strasse 11/12, D-17487 Greifswald (Germany)], E-mail:


    Testosterone is regularly found in the tissues of decapod crustaceans. Although this vertebrate-type sex hormone is not the principal factor of sex differentiation in crustaceans, it was shown to be capable of acting on the reproductive organs of shrimps and crabs. In the present study I have exposed developing eggs and stage 5 juveniles of the parthenogenetic all female marbled crayfish to 17{alpha}-methyl testosterone in order to test whether in freshwater crayfish sex can be changed from female to male by this androgen. MT did not elicit sex change, neither when administered during embryonic development nor during juvenile stage 5, the main period of proliferation of the oocytes. However, exposure to 100 {mu}g/L MT from 64% to 84% embryonic development resulted in prolonged embryonic development, reduced hatching success, reduced growth of the juveniles, and severe malformations of the appendages in the juveniles. The marbled crayfish is recommended to be considered for toxicity tests due to its easy culture in the laboratory and its genotypical uniformity.

  13. 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))


    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.

  14. Teratogenic and behavioral anomalies induced by acute exposure of mice to ethanol and their possible relation to fetal brain DNA synthesis. (United States)

    Ciociola, A A; Gautieri, R F


    Physical and behavioral anomalies of fetal alcohol syndrome were studied after the i.p. administration of a single 3- or 6-g/kg dose of ethanol (25%, v/v) to gravid mice on either day 15 or day 18 of gestation. The physical effects of ethanol administered on either day 8, day 10, or day 12 of gestation (N = 6/group) were also examined and compared to the saline-administered controls. The identification of these anomalies and the effect of ethanol on the rate of fetal brain DNA synthesis were investigated. The physical anomalies were identified by standard procedures. Behavioral anomalies were measured as the inhibition of the development of various neonatal reflexes (N = 6-13/group) as compared to the saline-administered controls. The possible mechanism for these ethanol-induced abnormalities was identified by using [3H]thymidine to measure the rate of DNA synthesis (N = 6/group) in fetal mouse brains. Blood alcohol concentrations (N = 6/group) ranged from 410.2 mg/dl at 30 min to 25.8 mg/dl at 4.5 hr following the dosage of 3 g/kg of ethanol. Concentrations following the dosage of 6 g/kg of ethanol ranged from 753.7 mg/dl at 15 min to 127.1 mg/dl at 10.5 hr postinjection. Fetal and maternal weight gains were significantly inhibited compared to those of the controls. Various cranial facial, urogenital, skeletal, and cardiovascular anomalies were observed (P less than or equal to 0.05). Delays in the onset of the air and surface righting, visual placing, and negative geotaxis reflexes were observed for the ethanol-treated neonates, as compared to control values.(ABSTRACT TRUNCATED AT 250 WORDS)

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


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


    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...

  16. Cholinergic synaptic signaling mechanisms underlying behavioral teratogenicity : Effects of nicotine, chlorpyrifos, and heroin converge on protein kinase C translocation in the intermedial part of the hyperstriatum ventrale and on imprinting behavior in an avian model

    NARCIS (Netherlands)

    Izrael, M; Van der Zee, EA; Slotkin, TA; Yanai, J; Slotkin, Theodore A.


    A wide variety of otherwise unrelated neuroteratogens elicit a common set of behavioral defects centering around cholinergic contributions to cognitive function. We utilized the developing chick to overcome confounds related to maternal effects and compared the actions of nicotine, chlorpyrifos, and

  17. 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 (United States)

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


    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

  18. Cholinergic synaptic signaling mechanisms underlying behavioral teratogenicity: effects of nicotine, chlorpyrifos, and heroin converge on protein kinase C translocation in the intermedial part of the hyperstriatum ventrale and on imprinting behavior in an avian model. (United States)

    Izrael, Michal; Van der Zee, Eddy A; Slotkin, Theodore A; Yanai, Joseph


    A wide variety of otherwise unrelated neuroteratogens elicit a common set of behavioral defects centering around cholinergic contributions to cognitive function. We utilized the developing chick to overcome confounds related to maternal effects and compared the actions of nicotine, chlorpyrifos, and heroin on cholinergic signaling in the intermedial part of the hyperstriatum ventrale (IMHV), which controls imprinting behavior. Chicken eggs were injected with nicotine (10 mg/kg of egg), chlorpyrifos (10 mg/kg of egg), or heroin (20 mg/kg of egg; all doses below the threshold for dysmorphology) on incubation days (ID) 0 and 5, and then tests were conducted posthatching. All three compounds elicited significant deficits in imprinting behavior. We also found defects in cholinergic synaptic signaling specifically involving the muscarinic receptor-mediated membrane translocation of protein kinase C (PKC)-gamma and in the basal levels of both PKCgamma and PKCbetaII, the two isoforms known to be relevant to behavioral performance. In contrast, there were no alterations in the response of PKCalpha, an isoform that does not contribute to the behavior, nor were cytosolic levels of any of the isoforms affected. Taken together with similar results obtained in rodents, our findings suggest that disparate neuroteratogens all involve signaling defects centering on the ability of cholinergic receptors to elicit PKCgamma translocation/activation and that this effect is direct, i.e., not mediated by maternal confounds. The chick thus provides a suitable model for the rapid screening of neuroteratogens and elucidation of the mechanisms underlying behavioral anomalies.

  19. Effects induced by feeding organochlorine-contaminated carp from Saginaw Bay, Lake Huron, to laying white leghorn hens: I. Effects on health of adult hens, egg production, and fertility: II. Embryotoxic and teratogenic effects (United States)

    US Fish and Wildlife Service, Department of the Interior — The objectives of the study summarized in this report are as follows: I. This study was conducted to determine the effects of consumption of halogenated hydrocarbon...


    African Journals Online (AJOL)


    resulting from its hepatocarcinogenic, mutagenic, teratogenic and immunosuppressive effects. ... should be abolished by concerned government agencies. ... It has been reported to have hepatocarcinogenic, mutagenic, teratogenic and immunosuppressive effects (CAST, 2003). The immunosuppressive damage by aflatoxin ...

  1. The Effects of Quercetin and Retinoic acid on Skeletal System of Rat Embryos in Prenatal Period


    Nahid Gohari-Behbahani; Mahmood Khaksary-Mahabady; Reza Ranjbar; Hossein Najafzadeh-Varzi; Babak Mohammadian3. Department of Pathology, Faculty of Veterinary Medicine, Shahid Cha


    Background: Prenatal rat embryo exposure to retinoid induces some malformations in various organs, the most active and teratogenic metablolite is all-trans-retinoic acid (atRA). The teratogenic effects of some drugs can be prevented by the application of antioxidant drugs and stimulation of the maternal immune system. Also, quercetin, a naturally occurring flavonoid has excellent antioxidant properties. Therefore, in this study, the prophylactic effect of quercetin on teratogenic effects of a...

  2. Eye conditions and blindness in children: priorities for research, programs, and policy with a focus on childhood cataract

    National Research Council Canada - National Science Library

    Gilbert, Clare; Muhit, Mohammed


    The major causes of blindness in children encompass intrauterine and acquired infectious diseases, teratogens and developmental and molecular genetics, nutritional factors, the consequences of preterm birth, and tumors...

  3. 75 FR 20942 - Hazardous Waste Management System; Identification and Listing of Hazardous Waste; Removal of... (United States)


    ... shown in scientific studies to have toxic, carcinogenic, mutagenic or teratogenic effects on humans or... toxic, carcinogenic, mutagenic, or teratogenic effects on humans or other life forms, and included... saccharin as a sweetening agent. Nor does the listing apply to manufacturing process wastes that may contain...

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

    African Journals Online (AJOL)

    Abstract. Purpose: To investigate the knowledge and practice of pregnant women with regards to teratogens. Methods: A month-long ... Keywords: Knowledge, Practices, Teratogens, Pregnant Yemeni women, Folic acid deficiency. Tropical Journal of ..... that less than 15 % of Japanese women were aware of a link between ...


    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...

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

  7. Fetal valproate syndrome in a 14-month-old child: A case report

    African Journals Online (AJOL)

    developmental delay. However, he had no features suggestive of autism, Asperger's syndrome or autistic spectrum disorder, although these are frequently associated with FVS. There is still uncertainty about the mechanism of teratogenicity of VPA. It has been suggested that the accumulated epoxides may act as teratogen.

  8. Cyclopia and maternal ingestion of salicylates. (United States)

    Agapitos, M; Georgiou-Theodoropoulou, M; Koutselinis, A; Papacharalampus, N


    Salicylates are teratogens in animals, but their teratogenicity in man remains controverted. The possibility that massive oral intake in the first 3 months of pregnancy may induce malformations has not been eliminated. We report a second case of cyclopia associated with daily maternal ingestion of up to 4 g of acetylsalicylic acid in the first trimester.

  9. Browse Title Index

    African Journals Online (AJOL)

    Vol 6, No 23 (2007), Teratogenic effect of isotretinoin on the morphology and palate development in rat fetuses, Abstract PDF. DA Ofusori, AE Adelakun, SA Jimoh, AO Komolafe, BA Falana, TA Abayomi. Vol 11, No 48 (2012), Teratogenicity and brain aromatase-induction of monosodium glutamate in estrogen-responsive ...

  10. Browse Title Index - African Journals Online (AJOL)

    African Journals Online (AJOL)

    Vol 6, No 23 (2007), Teratogenic effect of isotretinoin on the morphology and palate development in rat fetuses, Abstract PDF. DA Ofusori, AE Adelakun, SA Jimoh, AO Komolafe, BA Falana, TA Abayomi. Vol 11, No 48 (2012), Teratogenicity and brain aromatase-induction of monosodium glutamate in estrogen-responsive ...

  11. Use of the cricket embryo (Acheta domesticus) as an invertebrate teratology model

    Energy Technology Data Exchange (ETDEWEB)

    Walton, B.T.


    Embryos of the cricket Acheta domesticus (L.) have been shown by bioassay to develop gross morphological abnormalities after exposure to a number of complex organic mixtures as well as to display a critical period of teratogen sensitivity and an ability to metabolize xenobiotics during development. Because the assay is simple, inexpensive, short-term (less than two weeks), and objective, it could be useful as an in vivo screen in an hierarchical approach to teratogen detection. Further investigation of cricket embryo responses to known teratogens is needed to establish the predictive value of this assay. 25 references, 1 figure, 2 tables.

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

    Directory of Open Access Journals (Sweden)

    İsmail Yılmaz


    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.

  13. 21 CFR 180.22 - Acrylonitrile copolymers. (United States)


    ... 212 °F using 3 percent acetic acid as the hydrolic agent. Acrylonitrile monomer levels, acrylonitrile... oral administration of the test material, (3) assessment of teratogenic and mutagenic potentials, (4...

  14. Embryo culture in teratological surveillance and serum proteins in development. Progress report, 1979-1980

    Energy Technology Data Exchange (ETDEWEB)

    Klein, N.W.


    Research progress for the period 1979-1980 is reported. The feasibility of using rat embryo cultures to test the teratogenic activity of serum was studied. The mechanisms regulating the synthesis of serum proteins were investigated. (ACR)

  15. PCB126 induces deformities during pectoral fin development in little skate (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...

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

    DEFF Research Database (Denmark)

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


    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...

  17. Fetal malformations and early embryonic gene expression response in cynomolgus monkeys maternally exposed to thalidomide (United States)

    The present study was performed to determine experimental conditions for thalidomide induction of fetal malformations and to understand the molecular mechanisms underlying thalidomide teratogenicity in cynomolgus monkeys. Cynomolgus monkeys were orally administered (±)-thalidomid...

  18. Cadmium in the Umtata River and the associated health impact of on rural communities who are primary users of water from the river

    CSIR Research Space (South Africa)

    Fatoki, OS


    Full Text Available suspected of having mutagenic, carcinogenic and teratogenic effects (Fischer, 1987; Kazantzis, 1987) and recently it has been classified as an endocrine disruptor. Studies have also shown that the offspring of animals exposed to Cd during pregnancy...

  19. LSD and Genetic Damage (United States)

    Dishotsky, Norman I.; And Others


    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)

  20. Developmental effects of methyl benzimidazolecarbamate following exposure during early pregnancy (United States)

    Methyl 2-benzimidazolecarbamate (MBC) and its parent compound benomyl are used as agricultural fungicides. Both chemicals are embryotoxic if administered during organogenesis, and benomyl is teratogenic. Based on a previous study indicating a lack of maternal effects of MBC follo...

  1. Organizer formation in Hydra is disrupted by thalidomide treatment

    National Research Council Canada - National Science Library

    Brooun, Maria; Manoukian, Armen; Shimizu, Hiroshi; Bode, Hans R; McNeill, Helen


    .... Surprisingly, thalidomide does not have teratogenic effects on mouse development. We investigated the effect of thalidomide on patterning in hydra, an early metazoan with a very simple axial symmetry...

  2. A Case of Suspected Isotretinoin-Induced Malformation in a Baby of a Mother Who Became Pregnant One Month after Discontinuation of the Drug (United States)

    Lee, Soon Min; Kim, He Min; Lee, Jun Seok; Yoon, Choon Sik; Park, Kook In; Namgung, Ran; Lee, Chul


    Isotretinoin is a known human teratogen that can cause multiple malformations. At present, women who conceive one cycle after discontinuing isotretinoin are told that their teratogenic risk is not higher than baseline. We present a case of both ear malformation in a newborn whose mother had taken isotretinoin for 2 years until one month prior to the time when she became pregnant. We suggest that further studies of pharmacokinetics and malformation of isotreinoin are needed. PMID:19568610

  3. Toxicity of the Alternaria metabolites alternariol, alternariol methyl ether, altenuene, and tenuazonic acid in the chicken embryo assay.


    Griffin, G F; Chu, F S


    The effects in the chicken embryo assay of four Alternaria metabolites (alternariol [AOH], alternariol methyl ether [AME], altenuene [ALT], and tenuazonic acid [TA]) were investigated. Administered to 7-day-old chicken embryos by yolk sac injection, AOH, AME, and ALT caused no mortality or teratogenic effect at doses up to 1,000, 500, and 1,000 micrograms per egg, respectively. TA exhibited a calculated 50% lethal dose of 548 micrograms per egg, with no teratogenic effect observed at either l...

  4. 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


    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. 

  5. Oral phenoxymethylpenicillin treatment during pregnancy

    DEFF Research Database (Denmark)

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


    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....

  6. [Isotretinoin embryopathy. Report of one case]. (United States)

    Troncoso Sch, Mónica; Rojas H, Carla; Bravo C, Eduardo


    Retinoic acid is a widely used drug in the treatment of cystic acne. It has teratogenic effects that depend on the gestational period in which it is used. We report a seven months old female whose mother was exposed to retinoic acid in both pre-gestational and gestational periods. She had a retardation of psychomotor development and a brain MRI showed frontal atrophy and a malformation of the posterior fossa. We discuss the mechanisms of the teratogenic effects of retinoic acid.

  7. Thalidomide-induced limb abnormalities in a humanized CYP3A mouse model. (United States)

    Kazuki, Yasuhiro; Akita, Masaharu; Kobayashi, Kaoru; Osaki, Mitsuhiko; Satoh, Daisuke; Ohta, Ryo; Abe, Satoshi; Takehara, Shoko; Kazuki, Kanako; Yamazaki, Hiroshi; Kamataki, Tetsuya; Oshimura, Mitsuo


    Thalidomide is a teratogen in humans but not in rodents. It causes multiple birth defects including malformations of limbs, ears, and other organs. However, the species-specific mechanism of thalidomide teratogenicity is not completely understood. Reproduction of the human teratogenicity of thalidomide in rodents has previously failed because of the lack of a model reflecting human drug metabolism. In addition, because the maternal metabolic effect cannot be eliminated, the migration of unchanged thalidomide to embryos is suppressed, and the metabolic activation is insufficient to develop teratogenicity. Previously, we generated transchromosomic mice containing a human cytochrome P450 (CYP) 3A cluster in which the endogenous mouse Cyp3a genes were deleted. Here, we determined whether human CYP3A or mouse Cyp3a enzyme expression was related to the species difference in a whole embryo culture system using humanized CYP3A mouse embryos. Thalidomide-treated embryos with the human CYP3A gene cluster showed limb abnormalities, and human CYP3A was expressed in the placenta, suggesting that human CYP3A in the placenta may contribute to the teratogenicity of thalidomide. These data suggest that the humanized CYP3A mouse is a useful model to predict embryonic toxicity in humans.

  8. Toxicity of the Alternaria metabolites alternariol, alternariol methyl ether, altenuene, and tenuazonic acid in the chicken embryo assay. (United States)

    Griffin, G F; Chu, F S


    The effects in the chicken embryo assay of four Alternaria metabolites (alternariol [AOH], alternariol methyl ether [AME], altenuene [ALT], and tenuazonic acid [TA]) were investigated. Administered to 7-day-old chicken embryos by yolk sac injection, AOH, AME, and ALT caused no mortality or teratogenic effect at doses up to 1,000, 500, and 1,000 micrograms per egg, respectively. TA exhibited a calculated 50% lethal dose of 548 micrograms per egg, with no teratogenic effect observed at either lethal or sublethal doses.

  9. Pregnancy under treatment of imatinib and successful labor in a patient with chronic myelogenous leukemia (CML). Outcome of discontinuation of imatinib therapy after achieving a molecular remission. (United States)

    Ali, Ridvan; Ozkalemkaş, Fahir; Ozçelik, Tülay; Ozkocaman, Vildan; Ozan, Ulkü; Kimya, Yalçin; Köksal, Nilgün; Gülten, Tuna; Yakut, Tahsin; Tunali, Ahmet


    Because of the teratogenicity data in rats, it is recommended that women treated with imatinib should be aware of the potential teratogenicity of imatinib and effective contraception should be used during imatinib therapy to prevent pregnancy. We describe successful pregnancy and delivery, without any congenital anomaly, in a patient with CML under treatment of imatinib. The fetus had been exposed to imatinib for 8 weeks. The patient remained off treatment during gestation and cytogenetic relapse of CML (5 months after discontinuation of imatinib therapy) developed at seventh month of gestation.

  10. Use of proton pump inhibitors during pregnancy and breastfeeding. (United States)

    Nava-Ocampo, Alejandro A; Velázquez-Armenta, Elvia Y; Han, Jung-Yeol; Koren, Gideon


    A 36-year-old pregnant patient has symptoms of peptic disease. Treatment with diet and lifestyle modifications and also antacids has given her little relief. If she were not pregnant, I would prescribe a proton pump inhibitor (PPI) for her. She is now 4 weeks pregnant, and I need to determine whether PPIs are safe during pregnancy. Data currently available suggest that omeprazole is not teratogenic in humans. While information on other PPIs is limited, a systematic review of the evidence suggests that they are also not teratogenic.

  11. Cardiovascular Ultrasound of Neonatal Long Evans Rats ... (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.

  12. Author Details

    African Journals Online (AJOL)

    Histological Studies Of The Effects Of Monosodium Glutamate On The Stomach Of Adult Wistar Rats Abstract · Vol 7, No 1-2 (2008) - Articles 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 ...

  13. African Journal of Biotechnology - Vol 11, No 48 (2012)

    African Journals Online (AJOL)

    Teratogenicity and brain aromatase-induction of monosodium glutamate in estrogen-responsive mosaic transgenic zebra fish Danio rerio · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Tamer Said Abdelkader, Chang Seo-Na, Kim Tae-Hyun, Song Juha, Kim ...

  14. African Journal of Biotechnology - Vol 6, No 23 (2007)

    African Journals Online (AJOL)

    Teratogenic effect of isotretinoin on the morphology and palate development in rat fetuses · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. DA Ofusori, AE Adelakun, SA Jimoh, AO Komolafe, BA Falana, TA Abayomi ...

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

  16. 76 FR 34706 - Privacy Act of 1974; System of Records (United States)


    ...) inorganic carcinogens; (3) mucosal or dermal irritants; (4) fibrogenic materials; (5) acute toxic agents including sensitizing agents; (6) neurotoxic agents; (7) mutagenic (male and female) and teratogenic agents... by the system: That segment of the population exposed to physical and/or chemical agents or other...

  17. 75 FR 78918 - Hazardous Waste Management System; Identification and Listing of Hazardous Waste; Removal of... (United States)


    ...., discarded products that contain saccharin as a sweetening agent. Nor does the listing apply to manufacturing... risk of causing toxic, carcinogenic, mutagenic or teratogenic effects on humans or other life forms... effect mechanisms that are not relevant to humans; and (3) are not reasonably expected to be mutagenic or...

  18. 78 FR 64735 - Current Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for... (United States)


    ... necessary by APHIS because of the possibility of cross contamination with the BSE agent. Subsequently, on... does not address drug residues and agents that cause BSE and other transmissible spongiform... toxic, carcinogenic, mutagenic, teratogenic, or otherwise deleterious to animals, humans, or both...

  19. 76 FR 31211 - Privacy Act of 1974; System of Records (United States)


    ... irritants; (4) fibrogenic materials; (5) acute toxic agents including sensitizing agents; (6) neurotoxic agents; (7) mutagenic (male and female) and teratogenic agents; (8) bio-accumulating non-carcinogen... to physical and/or chemical agents or other workplace hazards that may damage the human body in any...

  20. Teratogeniteit van ethanol en aceetaldehyde. Literatuurstudie en in vitro onderzoek bij de rat

    NARCIS (Netherlands)

    Zeilmaker MJ; Verhoef A; Peters PWJ


    In dit rapport wordt verslag gedaan van een in vitro onderzoek naar de teratogene werking van ethanol en zijn primaire metaboliet aceetaldehyde in het ratte-embryo tijdens de organogenese. Aanleiding tot dit onderzoek is het bij de mens voorkomen van het Foetaal Alcohol Syndroom (FAS), een patroon

  1. The Safety of Artemisinin Derivatives for the Treatment of Malaria in the 2nd or 3rd Trimester of Pregnancy: A Systematic Review and Meta-Analysis

    NARCIS (Netherlands)

    Kovacs, Stephanie D.; van Eijk, Anna Maria; Sevene, Esperanca; Dellicour, Stephanie; Weiss, Noel S.; Emerson, Scott; Steketee, Richard; ter Kuile, Feiko O.; Stergachis, Andy


    Given the high morbidity for mother and fetus associated with malaria in pregnancy, safe and efficacious drugs are needed for treatment. Artemisinin derivatives are the most effective antimalarials, but are associated with teratogenic and embryotoxic effects in animal models when used in early

  2. Inhibitory effect of essential oil on aflatoxin activities

    African Journals Online (AJOL)



    Apr 19, 2010 ... grains, milk, cheese, meat, nut products, fruit juice and numerous other agricultural commodities (Bullerman,. 1986). Aflatoxins have been shown to be hepatotoxic, carcino- genic, mutagenic and teratogenic to different species of animals (Wogan et al., 1974; Eaton and Gallagher, 1994;. Abdel-Wahhab et ...

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

    African Journals Online (AJOL)



    Sep 14, 2011 ... Alcohol as a teratogenic agent inhibits cell growth, function, proliferation and migration by affecting ..... related with the closure of the NT, migration of neural .... Toole B (1991). Proteoglycans and hyaluronan in morphogenesis and differentiation. In: Hay E. (Ed). Cell Biology of extracellular matrix 2nd edn.

  4. Prenatal exposure to cigarette smoke or alcohol and cerebellum volume in attention-deficit/hyperactivity disorder and typical development

    NARCIS (Netherlands)

    Zeeuw, P. de; Zwart, F.S.; Schrama, R.; Engeland, H. van; Durston, S.


    Prenatal exposure to teratogenic substances, such as nicotine or alcohol, increases the risk of developing attention-deficit/hyperactivity disorder (ADHD). To date, studies examining this relationship have used symptom scales as outcome measures to assess the effect of prenatal exposure, and have

  5. Gutiérrez et al., Afr J Tradit Complement Altern Med. (2014) 11(3 ...

    African Journals Online (AJOL)


    livestock and poultries (Papavisiliu and Heliakis, 1947; Castorena et al., 1987; Sims et al., 1999; Mizrachi et al., 2000; Schep et al., 2009; Botha et al., 2011; Semmler et al., 2012). Also, teratogenic activity has been attributed to this alkaloid (Keeler et al., 1981; Green et al., 2012). However, no intoxication after external ...

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

  7. Safety assessment of lactate esters

    NARCIS (Netherlands)

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


    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

  8. Antiretroviral treatment of maternal HIV infection.


    Talaie, Haleh; Nava-Ocampo, Alejandro A.; Koren, Gideon


    QUESTION: One of my pregnant patients tested positive for human immunodeficiency virus. Will HIV therapy put her pregnancy outcome at risk? ANSWER: The biggest risk is vertical transmission of HIV to her baby. She should be treated with combination therapy; triple therapy is required to reduce vertical transmission. Zidovudine is not teratogenic in humans, but information on other antiretroviral drugs is incomplete.

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

  10. Spirulina (arthrospira) protects against valproic acid-induced neural tube defects in mice. (United States)

    Escalona-Cardoso, Gerardo N; Paniagua-Castro, Norma; Pérez-Pastén, Ricardo; Chamorro-Cevallos, Germán


    Valproic acid (VPA) is a potent inducer of neural tube defects in human and mouse, its teratogenicity is associated with its potential to generation of free radicals and increase oxidative stress. Furthermore, spirulina (SP) has shown pharmacological properties against teratogenicity, which are attributed to its antioxidant potential. Accordingly, the present study was performed to investigate the influence of SP on the teratogenicity of VPA in imprinting control region mice and the possible mechanisms of action. VPA (sodium valproate) was administered intraperitoneally to mice on gestation day (GD) 8 at a dose of 600 mg/kg. SP was given orally at 125, 250, and 500 mg/kg daily from GD0 through GD18. The most common finding in fetuses with VPA exposure was exencephaly. SP decreased the incidence of this and other malformations and increased levels of superoxide dismutase, catalase, and glutathione peroxidase. In conclusion, these results illustrate the protective action of SP through its antioxidant activity against VPA-induced teratogenicity.

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

    Directory of Open Access Journals (Sweden)

    Qing Xia


    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.

  12. Maternal genes and facial clefts in offspring

    DEFF Research Database (Denmark)

    Jugessur, Astanand; Shi, Min; Gjessing, Håkon Kristian


    -to-offspring and father-to-offspring recurrence of clefts in these two populations. It is likely that fetal genes make the major genetic contribution to clefting risk in these populations, but we cannot rule out the possibility that maternal genes can affect risk through interactions with specific teratogens or fetal...


    African Journals Online (AJOL)

    immunoassay during October 2004. Rubella virus is a common cause of childhood fever and rash. It is of public health importance largely owing to the teratogenic effects of primary or secondary rubella infection in the first trimester of pregnancy.' Rubella acquired in the first 12 weeks of pregnancy is associated with a nearly ...

  14. Biological assays for aquatic toxicity testing

    CSIR Research Space (South Africa)

    Slabbert, JL


    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...

  15. A case of partial sirenomelia and possible vitamin A teratogenesis. (United States)

    Von Lennep, E; El Khazen, N; De Pierreux, G; Amy, J J; Rodesch, F; Van Regemorter, N


    Prenatal echographical findings of a partial sirenomelic fetus are described. An attempt was made to terminate pregnancy by administration of prostaglandin F2 alpha, but uterine rupture occurred. The teratogenic role of vitamin A ingested by the mother in the periconceptional period is discussed.

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

  17. Fever in pregnancy and risk of fetal death: a cohort study

    DEFF Research Database (Denmark)

    Andersen, Anne-Marie Nybo; Vastrup, Pernille; Wohlfahrt, Jan


    Hyperthermia acts as a teratogen in some animals where it can induce resorption of the fetus and fetal death. Fever during pregnancy, especially in the period of embryogenesis, is also suspected as being a risk factor for fetal death in human beings. We did a large cohort study in Denmark...

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

  19. Rational dispensing and use of artemether-lumefantrine during ...

    African Journals Online (AJOL)

    effects of artemisinin and its derivatives in animals, including primates, with risk being confined to a defined ... The teratogenic effect is thought to involve red blood cells production, which implies the human sensitive period would ..... on the evolution of chloroquine resistance in an area of East Africa receiving intermittent.

  20. 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

  1. Space Propulsion Hazards Analysis Manual (SPHAM). Volume 1 (United States)


    include asphyxiants, poisons, carcinogens/teratogens/ mutagens , and acidic or caustic conditions. There are three major areas of concern involving the...1, loss of ;,; tPm . >,,v,.,.t iurv is defined as injury requiring hospitalization. 7-1,i (r -vstem damage is defined as extensive performance

  2. Air National Guard Installation Restoration Program Site Investigation Report, 185th Tactical Fighter Group, Iowa Air National Guard, Sioux Gateway Airport, Sergeant Bluff, Iowa (United States)


    toxic, carcinogenic, mutagenic , and/or teratogenic to many species. PNAs have demonstrated toxicity via the oral and dermal routes, indicating that...2125-04 matrix: Water Water Water3 TPM (mg/kg) ... ...-- . ....- ~~gca arteswater Water Water DATE ANALYZED ... .. ... 1 ross Aloa--U rossBj Footnotes

  3. [The effect of meclofenoxate on the growth, fertility and number of offspring in Wistar rats]. (United States)

    Neumann, H J


    In experiments with rats concerning teratological aspects of meclofenoxate it was demonstrated that this drug reduces the teratogenicity in Wistar rats. Meclofenoxate leads in the fetuses of rats to a significant increase of the weight when the dams were treated prenatally with the ester. Besides, meclofenoxate causes in continuous series of generations an increase of fertility which results in a higher number of offsprings.

  4. Traditional Tongan cures for morning sickness and their mutagenic/toxicological evaluations. (United States)

    Ostraff, M; Anitoni, K; Nicholson, A; Booth, G M


    Every year millions of women become pregnant, and more than 60% of them will develop some form of morning sickness. Yet drugs like Thalidomide, Bendectin and other possibly potent teratogens administered for pre-partum nausea have severely limited any medicinal intervention. In Tonga, women have been treated for morning sickness for hundreds of years. Two types of traditional treatments exist, the first one consists of an infusion of fresh leaves, commonly called vai momoko. The second type of treatment is called vai haka, which is made from the boiled bark of several trees. In this paper we describe the results of 6 months of intensive interviews in Tonga regarding the second type of treatment called vai haka. In addition, we tested vai haka for mutagenic and teratogenic effects. Data from the Ames TA-98 mutagenic bioassay clearly indicate that vai haka is not mutagenic with or without S-9 activation. Twenty-six experimental CD-1 white mice were gavaged with 0.1 ml of vai haka (at 540xthe human dose) while the control group of 17 mice were gavaged with 0.1 ml of water to determine teratogenic and developmental effects of the vai haka. No significant teratogenic or developmental anomalies occurred in the mice dosed with vai haka compared to the controls.

  5. Hyperconnectivity of local neocortical microcircuitry induced by prenatal exposure to valproic acid

    DEFF Research Database (Denmark)

    Rinaldi, Tania; Silberberg, Gilad; Markram, Henry


    Exposure to valproic acid (VPA) during embryogenesis can cause several teratogenic effects, including developmental delays and in particular autism in humans if exposure occurs during the third week of gestation. We examined the postnatal effects of embryonic exposure to VPA on microcircuit...

  6. Lupine-Induced 'Crooked Calf Disease' in Washington and Oregon: Identification of the alkaloid profiles of Lupinus sericeus, Lupinus sulphureus, and Lupinus leucophyllus (United States)

    Lupines are common plants found on the rangelands in the western United States. Lupines are known to contain alkaloids that can be toxic and teratogenic causing congenital birth defects (crooked calf disease). Lupine-induced crooked calf disease cases are documented in North-eastern Oregon and the...

  7. Velvet lupine (Lupinus leucophyllis) population cycles with climate (United States)

    Velvet lupine (Lupinus leucophyllis Dougl. ex Lindl) contains the teratogenic alkaloid anagyrine that causes a crooked calf syndrome when a cow ingests lupine between the 40-100 day of gestation. An outbreak of crooked calves occurred in the Scabland region of eastern Washington in 1997 following t...

  8. The Alkaloid Profiles of Lupinus sulphureus (United States)

    Lupines are common plants found on the rangelands in the western United States. Lupines are known to contain alkaloids that can be toxic and teratogenic causing congenital birth defects (crooked calf disease). One such lupine, Lupinus sulphureus, occurs in parts of Oregon, Washington, and British ...

  9. Phylogenetic examination of two chemotypes of Lupinus leucophyllus (United States)

    Lupines (Lupinus spp.) are a common legume found on western U.S. rangelands. Lupinus spp. may contain quinolizidine and or piperidine alkaloids that could be toxic and or teratogenic to grazing livestock. Lupinus leucohyllus and Lupinus polyphyllus represent important species in the rangelands of ...

  10. 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.


    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Klein, N.W.


    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)

  12. 78 FR 14241 - Acetonitrile; Community Right-to-Know Toxic Chemical Release Reporting (United States)


    ... in humans-- (i) cancer or teratogenic effects, or (ii) serious or irreversible- (I) reproductive...,000 milligrams/kilogram (mg/kg)) (Ref. 9). Symptoms exhibited by poisoning victims include anxiety... thymus weight, increases in absolute and/or relative liver and kidney weight, and decreases and increases...

  13. Isotretinoin use and compliance with the Dutch Pregnancy Prevention Programme: a retrospective cohort study in females of reproductive age using pharmacy dispensing data.

    NARCIS (Netherlands)

    Teichert, M.; Visser, L.E.; Dufour, M.; Rodenburg, E.; Straus, S.M.; Smet, P.A.G.M. de; Stricker, B.H.C.


    BACKGROUND: Isotretinoin is very effective in the treatment of severe acne. However, because of the teratogenic properties of this agent an isotretinoin Pregnancy Prevention Programme (PPP) was implemented in the Netherlands to guarantee that treatment is contraindicated in women of reproductive age

  14. Serotonin reuptake inhibitors (SRIs) and the risk of fetal congenital heart anomalies (CHA) : An exploratory pharmacogenetics study

    NARCIS (Netherlands)

    Daud, Aizati Nur; Frederikse, Wilhelmina; Bergman, JEH; van der Vlies, P.; Hak, Eelko; Berger, Rudolf; Groen, Henk; Wilffert, Berend


    Introduction: Several studies reported the risk of CHA associated with prenatal use of SRIs, but the results have been inconsistent. Objective: To explore whether pharmacogenetics play a role in this teratogenicity using a gene-environment interaction study. Patients and methods: A total of 33

  15. Holoprosencephaly: report of four cases and genotype–phenotype ...

    Indian Academy of Sciences (India)


    Apr 2, 2013 ... congenital malformations or other disorders, no exposure to alcohol, teratogenic agents, irradiation, or infectious diseases were reported. During the ultrasonographic examination at. 13th week, the presence of omphalocele was confirmed. Nor- mal auxological and nuchal translucency (NT) parameters.

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

    Directory of Open Access Journals (Sweden)

    Lídia Moreira Lima


    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.


    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...

  18. Safety of Tioguanine During Pregnancy in Inflammatory Bowel Disease

    NARCIS (Netherlands)

    Berg, S.A. van den; Boer, M. de; Meulen-Jong, A.E. van der; Jansen, J.M.; Hoentjen, F.; Russel, M.G.; Mahmmod, N.; Bodegraven, A.A. van; Woude, C.J. van der; Mulder, C.J.; Boer, N.K. de


    BACKGROUND AND AIMS: Conventional thiopurine [azathioprine and mercaptopurine] treatment during pregnancy in patients with inflammatory bowel disease [IBD] is considered to be safe; however data on the safety and teratogenicity of the non-conventional thiopurine tioguanine [TG] in pregnant IBD

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

    DEFF Research Database (Denmark)

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


    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...

  20. 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.


    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

  1. 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


    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 ...

  2. The Pesticide Malathion Disrupts "Xenopus" and Zebrafish Embryogenesis: An Investigative Laboratory Exercise in Developmental Toxicology (United States)

    Chemotti, Diana C.; Davis, Sarah N.; Cook, Leslie W.; Willoughby, Ian R.; Paradise, Christopher J.; Lom, Barbara


    Malathion is an organophosphorus insecticide, which is often sprayed to control mosquitoes. When applied to aquatic habitats, malathion can also influence the embryogenesis of non-target organisms such as frogs and fish. We modified the frog embryo teratogen assay in "Xenopus" (FETAX), a standard toxicological assay, into an investigative…

  3. 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


    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....

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

  5. What can we learn from the thalidomide experience: an ophthalmologic perspective (United States)

    Miller, Marilyn T.; Strömland, Kerstin K.


    Purpose of review The thalidomide tragedy of the early 1960s resulted in a great number of studies and reports involving many specialties of medicine. Because of the estimated large number of affected children (5000+) worldwide exposed to this potent teratogen, and the many informative cases in which the exposure time was known, a teratogenic timetable was constructed relating affected structures to the time of exposure. This demonstrated that thalidomide had a teratogenic effect between approximately 20 to 36 days after fertilization. Recent findings We found that Duane syndrome and its variants were prominent in individuals who were exposed to thalidomide early in the sensitive period (days 20 to 26±). Other anomalies associated with this early effect were aberrant tearing, facial nerve palsy, ear malformations, and autism. Structural eye malformations were less frequent in this early phase, appearing slightly later in the sensitive period. Summary This study summarizes the ophthalmologic findings from a number of studies and compares them with respect to the implications of time of exposure. Because the timing of anomalies such as external ear and limb malformations are well established in the thalidomide literature, correlation with associated eye anomalies gives insight into the approximate timing of the causative teratogen exposure. PMID:21825994

  6. Tail-like Congenital Duplication of Lower Extremity (Extra Leg or ...

    African Journals Online (AJOL)


    Jan 1, 2018 ... extremities, and to access the vascular supply of the tail like soft tissue growth . Her mother died after giving birth to this child. History from close relative remarked no similar congenital abnormality among the members of her family. There was no known maternal history of diabetes or teratogenic drug usage ...

  7. Assessment of organochlorine pesticides residues in fish sold in ...

    African Journals Online (AJOL)

    Contamination of foods by pesticides can give rise to carcinogenic, mutagenic and teratogenic effects. Pesticides are also accountable for toxic effects on the nervous, immune, reproductive, renal, hepatic and hematopoietic systems. For the present ... The fishing port of Vridi was the most contaminated site. The species ...

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

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


    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. Dithiocarbamates Induce Craniofacial Abnormalities and Downregulate sox9a during Zebrafish Development

    NARCIS (Netherlands)

    van Boxtel, A.L.; Pieterse, B.; Cenijn, P.; Kamstra, J.H.; Brouwer, A.M.; van Wieringen, W.N.; de Boer, J.; Legler, J.


    Dithiocarbamates (DTCs) have a wide variety of applications in diverse fields ranging from agriculture to medicine. DTCs are teratogenic to vertebrates but the mechanisms by which they exert these effects are poorly understood. Here, we show that low nanomolar exposure to three DTCs,

  10. The serum concentrations of lupine alkaloids in orally-dosed Holstein cattle (United States)

    Teratogenic alkaloid-containing Lupinus spp. cause significant losses to the cattle industry. Previous research has suggested that Holstein cattle clear toxic Delphinium alkaloids from their serum at a greater rate than beef cattle. The toxicokinetics of lupine alkaloids in Holsteins are not known...

  11. Behavioural Outcomes of Four-Year-Old Children Prenatally Exposed to Methadone or Buprenorphine: A Test of Three Risk Models (United States)

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


    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…

  12. 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


    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...... anomalies....





    In suitablemoisture and temperature conditions some fungus such as Aspergillus,Penicillium, Fusarium, Alternaria, Claviceps synthesis the mycotoxins whichhave toxic and carcinogenic properties are fungal metabolites that have lowmolecular weights. Aflatoxin, ochratoxin, trichothecene, zearalenone, patulinand fumonisin are the most common mycotoxins. Aflatoxins, one ofthe mostimportant mycotoxins, are heat- resistant, toxic, immunosuppressive, mutagenic,teratogenic secondary metabolic products...

  14. Alcohol effects on embryonal bone growth | Adebisi | Nigerian ...

    African Journals Online (AJOL)

    Background:The possible teratogenic and lethal potencies of ethanol on the developing foetal bones especially when ingested during pregnancy is now well established; but the actual mechanisms of these actions are yet elusive and this had since stimulated unending interests and numerous researches particularly in the ...

  15. Rubella IgG Antibody among Nigerian Pregnant Women without ...

    African Journals Online (AJOL)

    Rubella is a vaccine-preventable viral infection, its aetiologic agent; rubella virus was identified as human teratogen capable of causing a spectrum of birth defects described as congenital rubella syndrome (CRS). Despite the availability of safe and effective vaccines, significant proportion of the population remains ...

  16. Zizyphus spina-Christi Extract Protects Against Aflatoxin B1 ...

    African Journals Online (AJOL)

    Aflatoxins (AF), a group of closely related, extremely toxic mycotoxins, produced by Aspergillus flavus and A. parasiticus can occur as natural contaminants of foods and feeds. Aflatoxins have been shown to be hepatotoxic, carcinogenic, mutagenic, and teratogenic to different animal species. Zizyphus spina-Christi L. extract ...

  17. Delayed effects of environmentally relevant concentrations of 3,3',4,4'-tetrachlorobiphenyl (PCB-77) and non-polar sediment extracts detected in the prolonged-FETAX

    NARCIS (Netherlands)

    Gutleb, A.C.; Mossink, L.; Schriks, M.; Berg, van den J.H.J.; Murk, A.J.


    In the prolonged-FETAX (prolonged-Frog Embryo Teratogenic Assay-Xenopus) tadpoles are allowed to develop until metamorphosis after an initial 4 day early life-stage exposure (FETAX). PCB 77 (3,4,3¿,4¿-tetrachlorobiphenyl) and sediment extracts were used in the presented experiments. Concentrations

  18. Ochratoxin A Producing Fungi, Biosynthetic Pathway and Regulatory Mechanisms


    Wang, Yan; Wang, Liuqing; Liu, Fei; Wang, Qi; Selvaraj, Jonathan Nimal; Xing, Fuguo; Zhao, Yueju; Liu, Yang


    Ochratoxin A (OTA), mainly produced by Aspergillus and Penicillum species, is one of the most important mycotoxin contaminants in agricultural products. It is detrimental to human health because of its nephrotoxicity, hepatotoxicity, carcinogenicity, teratogenicity, and immunosuppression. OTA structurally consists of adihydrocoumarin moiety linked with l-phenylalanine via an amide bond. OTA biosynthesis has been putatively hypothesized, although several contradictions exist on some processes ...

  19. 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 ...

  20. Evaluation of the effect of the use of vitamin supplements on vitamin A intake among (potentially) pregnant women in relation to the consumption of liver and liver products

    NARCIS (Netherlands)

    Berg, H. van den; Hulshof, K.F.A.M.; Deslypere, J.P.


    Objective: To assess the distribution of dietary vitamin A intake among Dutch women aged 16-50 and among pregnant women, and to evaluate the effect of the use of a vitamin A (1200 RE) containing multivitamin supplement in terms of nutritional and teratogenic risk. Study design: Data from the 2nd

  1. Produciton and biological activity of patulin and citrinin from Penicillium expansum. (United States)

    Ciegler, A; Vesonder, R F; Jackson, L K


    Penicillium expansum isolated from meat and apples produced both patulin and citrinin. Toxin identity was confirmed by spectroscopic and physical methods. The mean lethal dose in chicken embryos was determined for toxins administered both singly and in various ratios. Data from simultaneous administration of mycotoxin combinations plotted as isobolograms showed and additive effect. Both toxins were teratogenic in chicken embryos. Images PMID:559470

  2. P-Glycoprotein-Mediated Drug Interactions in Pregnancy and Changes in the Risk of Congenital Anomalies : A Case-Reference Study

    NARCIS (Netherlands)

    Daud, Aizati N.A.; Bergman, Jorieke E.H.; Bakker, Marian K.; Wang, Hao; Kerstjens-Frederikse, Wilhelmina S.; de Walle, Hermien E.K.; Groen, Henk; Bos, Jens H. J.; Hak, Eelko; Wilffert, Bob


    INTRODUCTION: Drug use in pregnancy is very common but may cause harm to the fetus. The teratogenic effect of a drug is partly dependent on the drug level in the fetal circulation, which is associated with the transport across the placenta. Many drugs are substrates of P-glycoprotein (P-gp), an

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

    DEFF Research Database (Denmark)

    Sabers, Anne; Larsen, Katja; Blichfeldt, Susanne


    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...

  4. 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.


    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...

  5. 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


    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

  6. Severe limb defects and craniofacial anomalies in a fetus conceived during acitretin therapy

    NARCIS (Netherlands)

    deDieSmulders, CEM; Sturkenboom, MCJM; Veraart, J; vanKatwijk, G; Sastrowijoto, P; VanderLinden, E


    We describe a 20-week-old fetus with multiple congenital anomalies exposed to acitretin in the first trimester of pregnancy. Acitretin and its ethylester etretinate are both vitamin A congeners; drugs of this group are well-known teratogenic agents. Since the marketing of acitretin only one report

  7. The status of diabetic embryopathy


    Eriksson, Ulf J.; Wentzel, Parri


    Diabetic embryopathy is a theoretical enigma and a clinical challenge. Both type 1 and type 2 diabetic pregnancy carry a significant risk for fetal maldevelopment, and the precise reasons for the diabetes induced teratogenicity are not clearly identified. The experimental work in this field has revealed a partial, however complex, answer to the teratological question, and we will review some of the latest suggestions.

  8. Fetal Alcohol Syndrome: A Behavioral Teratology. (United States)

    Kavale, Kenneth A.; Karge, Belinda D.


    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)

  9. Animal Models of Fetal Alcohol Spectrum Disorders: Impact of the Social Environment (United States)

    Kelly, Sandra J.; Goodlett, Charles R.; Hannigan, John H.


    Animal models of fetal alcohol spectrum disorder (FASD) have been used to demonstrate the specificity of alcohol's teratogenic effects and some of the underlying changes in the central nervous system (CNS) and, more recently, to explore ways to ameliorate the effects of alcohol. The main point of this review is to highlight research findings from…

  10. Internet Journal of Medical Update

    African Journals Online (AJOL)


    milestones were normal as per the age. There was no teratogenic exposure or consanguinity. Ambulation was delayed until 3 year of age but other developmental milestones were normal. Bowing of the lower extremities was noted at the age of 5 years. There had been no fractures or other significant medical history. The.

  11. Histochemical Study Of The Effect Of Ethanol On Alkaline ...

    African Journals Online (AJOL)

    The teratogenic effects of ethanol include the assaults of the various developmental processes of tissues exposed in utero, and particularly the mineralisation of bones. An experimental investigation of the mechanisms of action of this toxic agent was conducted in the femoral bones of the foetal Wistar rat by the ...

  12. 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 ...

  13. 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. (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…

  14. Cleft deformities (lip and palate)

    African Journals Online (AJOL)


    The gestational period in which these drugs where taken was not stated so we could not ascertain their influence on the embryogenesis of the neonates born with clefts. 5/17 mothers reported to have suffered from syphilis in the past; although it is considered to be one of the teratogenic infections, the association was not ...

  15. Intermittent Preventive Therapy and Treatment of Malaria during ...

    African Journals Online (AJOL)

    INTRODUCTION. Treatment with artemisinin combination therapies (ACTs) in the first trimester is not recommended because of concerns raised by animal experiments which suggested that artemisinin and its derivatives might be teratogenic and cause foetal resorption if given to experimental animals during a narrow time ...

  16. Psychiatry Trainees' Training and Experience in Fetal Alcohol Spectrum Disorders (United States)

    Eyal, Roy; O'Connor, Mary J.


    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…

  17. 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 ...

  18. Phytoremediation of Groundwater at Air Force Plant 4, Carswell, Texas (United States)


    of man made and natural carcinogens , mutagens, and teratogens. Some vegetation even has the ability to make compounds such as chloromethane...various combinations. The weed control treatments were as follows: Glyphosate Linuron – Legume Linuron – Glyphosate Linuron – Cultivation... Glyphosate was found to be extremely difficult to apply after planting without damaging tree seedlings. Actively growing young hybrid poplars are easily

  19. Development Enamel Defects in Children Prenatally Exposed to Anti-Epileptic Drugs

    DEFF Research Database (Denmark)

    Jacobsen, Pernille Endrup; Henriksen, Tine Brink; Haubek, Dorte


    Objective Some anti-epileptic drugs (AED) have well-known teratogenic effects. The aim of the present study was to elucidate the effect of prenatal exposure to AED and the risk of enamel defects in the primary and permanent dentition. Methods A total of 38 exposed and 129 non-exposed children, 6...

  20. 75 FR 72727 - Addition of National Toxicology Program Carcinogens; Community Right-to-Know Toxic Chemical... (United States)


    ... Mg per year, represent approximately 44 to 51% of total global natural volatile organic compound... reasonably be anticipated to cause cancer in humans. DATES: This final rule is effective November 30, 2010...) cancer or teratogenic effects, or (ii) serious or irreversible-- (I) reproductive dysfunctions, (II...

  1. Aflatoxin in commercial poultry feeds and clinico-pathological ...

    African Journals Online (AJOL)

    Aflatoxin remains the most studied mycotoxin with aflatoxin B1 making up 66 to 82% of total aflatoxin found in feed. In poultry, it can cause high production losses and vaccine failure resulting from its hepatocarcinogenic, mutagenic, teratogenic and immunosuppressive effects. This study aimed to determine the level of ...

  2. CASE REPORT Mermaid baby

    African Journals Online (AJOL)

    A 40-year-old woman delivered a baby at 36 weeks with fused lower limbs. There was no maternal history of ingestion of teratogenic agents or diabetes mellitus. Initial X-rays (Figs 1 and 2) showed fused feet, lower limbs with 2 tibiae, 2 femurs and a single fibula. There was a single femoral head and incomplete ...

  3. 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: [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)


    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

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

    Directory of Open Access Journals (Sweden)

    Beata Starek-Świechowicz


    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

  5. [Ethylene glycol and propylene glycol ethers - Reproductive and developmental toxicity]. (United States)

    Starek-Świechowicz, Beata; Starek, Andrzej


    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. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  6. Toxic effect prediction of cefatirizine amidine sodium and its impurities by structure-toxicity relationship of cephalosporins. (United States)

    Qian, Jianqin; Han, Ying; Li, Jin; Zhang, Jingpu; Hu, Changqin


    The three-dimensional (3D) structure-toxicity relationship of cephalosporins was explored by computing the most stable conformations of 33 kinds of cephalosporins in aqueous solution and using the teratogenicity and lethality of these compounds obtained in zebrafish embryo toxicity testing to evaluate their toxic effects. The toxic effect of cefatirizine amidine sodium, a novel cephalosporin which has finished preclinical study, was investigated. It is thought that the teratogenic effect of the triazine ring at the C-3 position is the main toxic effect of cefatirizine amidine. In addition, cefatirizine amidine is no more toxic than cefathiamidine and ceftriaxone. The results of the zebrafish embryo toxicity test combined with gene expression microarray technology were consistent with the prediction. The toxic effects of some potential process-related impurities of cefatirizine amidine were also predicted. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Risk perception regarding drug use in pregnancy. (United States)

    Widnes, Sofia F; Schjøtt, Jan


    Pregnant women, but also physicians, have unrealistically high perceptions of teratogenic drug effects. This may result in suboptimal treatment of disease and even influence decisions of whether to continue pregnancy. To attain more realistic teratogenic risk perceptions, several factors that influence this issue should be considered, and these are further discussed in this Clinical Opinion. Importantly, drug use may have several benefits, both for the pregnant woman's health and to avoid negative fetal effects of untreated maternal disease. A greater focus on this aspect may act to balance risk perceptions. Furthermore, both pregnant women and physicians need access to drug information sources that provide realistic risk estimates to increase confidence in appropriate drug use and prescribing. We suggest that access to decision support and individually tailored information provided by drug information centers may contribute to this goal. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. 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


    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....

  9. [Immunosuppressants for auto-immune diseases and pregnancy]. (United States)

    Elefant, Elisabeth; Cournot, Marie-Pierre; Assari, Faïza; Vauzelle, Catherine


    Therapeutic stability of a systemic disease is a priority during pregnancy. To stop an effective treatment, to reduce dosages or to switch to less effective treatments might induce some loss of chance for pregnant women, and eventually harmful consequences for fetuses. Due to the teratogenic effects of some immunosuppressants, childbearing susceptible women should use effective contraception and be informed of risks in case of pregnancy. A pre-conceptional consultation is of interest, allowing an adaptation of treatment and advices before pregnancy is ongoing. Mycophenolate is highly suspected to be teratogenic in humans. Mycophenolate should not be prescribed in women of childbearing potential unless some criteria are met. Maternal (even fetal) infectious conditions can occur during immunosuppressive treatments. Therefore, obstetricians and pediatricians should be aware of the maternal treatment in order to allow adequate monitoring of the mother and the neonate.

  10. [Parasitic infections in pregnancy and congenital protozoan infections. Part I.: Protozoan infections]. (United States)

    Bialek, R; Knobloch, J


    Intestinal protozoan disease diagnosed in pregnancy is mostly controlled by symptomatic treatment. Specific therapy can be delayed until after delivery. Only severe cases, i.e. continued diarrhea leading to malnutrition of either mother or fetus, require an immediate specific drug therapy, which might be harmful to the fetus due to toxic and teratogenic potentials. Vertical transmission of intestinal protozoa has not been described. Invasive protozoan infections can be lethal to the mother making immediate drug therapy mandatory, even if the potentials of fetotoxicity or teratogenicity are known. Vertical transmission occurs independent of maternal symptoms, causing clinical disease in the child either directly after birth or during the first months of life. The knowledge of endemic regions and of the maternal travel history is essential for early diagnosis and treatment of protozoan disease in pregnancy and of congenital protozoan infections.

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

    Directory of Open Access Journals (Sweden)

    Sarah Dotters-Katz


    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.

  12. Carbimazole/methimazole embryopathy in siblings: a possible genetic susceptibility. (United States)

    Goel, Himanshu; Dudding, Tracy


    The teratogenic effects of antenatal exposure of antithyroid drugs, carbimazole and methimazole have been well reported in the literature. These comprise of typical facial features and a wide variety of malformations such as choanal atresia, tracheo-esophageal anomalies, congenital heart disease and ectodermal defects. However, the longitudinal studies have failed to establish the consistent teratogenicity of these drugs. we report here two siblings with physical features consistent with carbimazole/methimazole embryopathy. We also describe previously unreported minor dental anomalies in these siblings with antenatal exposure of carbimazole. Generally, only a small proportion of prenatally exposed children have the typical manifestations, and the presence in siblings supports a possible hereditary susceptibility to carbimazole/ methimazole embryopathy. This highlights the importance of recognizing this diagnosis before a subsequent pregnancy. Copyright © 2013 Wiley Periodicals, Inc.

  13. Screening, diagnosing and prevention of fetal alcohol syndrome: is this syndrome treatable? (United States)

    Ismail, Sahar; Buckley, Stephanie; Budacki, Ross; Jabbar, Ahmad; Gallicano, G Ian


    Prenatal alcohol exposure can lead to a wide range of adverse effects on a developing fetus. As a whole, these teratogenic outcomes are generally known as fetal alcohol spectrum disorders, the most severe of which is fetal alcohol syndrome (FAS). Clinically, children diagnosed with FAS vary greatly in their presentation of symptoms, likely due to the amount of alcohol and timing of exposure, as well as maternal and genetic influences. All these factors play a role in determining the mechanisms through which alcohol damages a developing brain, the details of which are still largely unknown. However, continuing research and recent developments have provided promising results that may lead to screening mechanisms and treatment therapies for children with FAS. Here we review the teratogenic effects of alcohol, strategies for detecting maternal alcohol consumption, identification of fetal biological markers, and prevention methods for FAS. Copyright 2010 S. Karger AG, Basel.

  14. Shedding light on an old mystery: thalidomide suppresses survival pathways to induce limb defects. (United States)

    Knobloch, Jürgen; Rüther, Ulrich


    Many hypotheses have been proposed to explain the molecular mechanism of thalidomide teratogenicity, in particular regarding to limb defects. Most experimental evidence in vivo has been provided for a model that suggests the generation of oxidative stress by thalidomide with subsequent downregulation of Wnt and Akt survival pathways. As a consequence apoptosis is induced during early embryonic limb development resulting in limb truncations. Here we summarize and discuss the relevant data supporting this hypothesis. We extend this model by presenting new data demonstrating an involvement of the transcription factors Tbx5 and Sall4 in thalidomide-induced molecular pathology. Finally, we discuss a possible participation of other stress-responsive and/or pro-apoptotic transcription factors in the mechanism of thalidomide teratogenicity.

  15. Women's experiences with isotretinoin risk reduction counseling. (United States)

    Werner, Carly A; Papic, Melissa J; Ferris, Laura K; Lee, Jessica K; Borrero, Sonya; Prevost, Noel; Schwarz, Eleanor Bimla


    Isotretinoin, an effective anti-acne therapy, is a known teratogen that is strictly regulated through the iPLEDGE program. However, since this program has not significantly reduced rates of pregnancies exposed to isotretinoin, new strategies for reducing rates of isotretinoin-exposed pregnancies are needed. To explore women's experiences with counseling about isotretinoin risk reduction. Structured interviews were conducted between January and September 2012. Two independent coders performed content analysis using a grounded theory approach. The study participants were 16 women who had used isotretinoin to treat severe skin disease and who were recruited from a single urban community via flyers displayed on college campuses, at dermatology clinics, and at student health facilities. Perceptions of isotretinoin-associated risks and understanding of ways teratogenic risks can be avoided. Participants clearly understood that isotretinoin is teratogenic but had less understanding of contraceptive methods that effectively prevent pregnancy. Most described the counseling they received as anxiety provoking. Few were counseled about highly effective reversible contraceptives such as the subdermal implant or intrauterine contraception; most counseling focused on oral contraceptives. Women cited multiple influences on their contraceptive choices, including friends, family, physicians, the internet, and other media; however, some expressed concerns about the accuracy of these sources of information. For many, iPLEDGE was their first introduction to contraception. When presented with evidence-based information on the relative effectiveness of available contraceptives, participants expressed surprise that this was not part of the iPLEDGE materials. Since few clinicians provide women information on highly effective (ie, intrauterine or subdermal) contraceptives, the iPLEDGE program increases anxiety about isotretinoin more than it helps women feel protected from the teratogenic

  16. The Effects of Quercetin and Retinoic acid on Skeletal System of Rat Embryos in Prenatal Period

    Directory of Open Access Journals (Sweden)

    Nahid Gohari-Behbahani


    Full Text Available Background: Prenatal rat embryo exposure to retinoid induces some malformations in various organs, the most active and teratogenic metablolite is all-trans-retinoic acid (atRA. The teratogenic effects of some drugs can be prevented by the application of antioxidant drugs and stimulation of the maternal immune system. Also, quercetin, a naturally occurring flavonoid has excellent antioxidant properties. Therefore, in this study, the prophylactic effect of quercetin on teratogenic effects of atRA was evaluated. Materials and Methods: In this experimental study, 40 pregnant rats were divided into 7 groups. Control group received normal saline and test groups received dimethylsulfoxide (DMSO, quercetin (75 mg/kg, quercetin (200 mg/kg, atRA (25 mg/kg, atRA (25 mg/kg plus quercetin (75 mg/kg and atRA (25 mg/kg plus quercetin (200 mg/kg, intraperitoneally at 8-10th days of gestation. Fetuses were collected at 20th day of gestation and after determination of weight and length; they were stained by Alizarin red-Alcian blue method. Results: Cleft palate, exencephaly and spina bifida incidence were 30.76%, 61.53% and 30.76% range in group which received only atRA. Cleft palate, exencephaly and spina bifida incidence were 11.11%, 16.66% and 5.55% in group which received atRA plus quercetin (75 mg/kg. However, cleft palate, exencephaly and spina bifida incidence were 10.52%, 10.52% and 0% in group which received atRA plus quercetin (200 mg/kg. The means of weight and length of fetuses from rat that received atRA plus quercetin (75 mg/kg were significantly greater than those received only atRA. Conclusion: It is concluded that quercetin decreased teratogenicity induced by atRA, but this subject needs more detailed evaluation.

  17. 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


    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.

  18. Prenatal Diagnosis and Perinatal Management of Maternal—Fetal Congenital Parvovirus B19 Infection

    Directory of Open Access Journals (Sweden)

    Shih-Tien Hsu


    Conclusion: Termination of pregnancy is rarely indicated, because B19 virus is not teratogenic. Although intravascular transfusion offers obvious theoretical advantages, in some cases in which access to the fetal circulation is difficult or impossible, IPT should be performed combined with appropriate medical treatment. Thus, there is still a place for IPT in modern management of the severely anemic fetus, and this technique should not be neglected.

  19. Further Development and Validation of the frog Embryo Teratogenesis Assay - Xenopus (FETAX) (United States)


    al. (42) reported teratogenic responses in rabbits, chickens , mice and rats when DMSO was administered at very high doses. However, at low doses few...species (120 hrs or 5 days) and for similar embryological events to occur during exposure. The fathead minnow (Pimephales promelas) has been established in... embryological stages. Differing exposure periods (time) can strongly influence bioassay results as the assumption that internal toxicant levels are equal to the

  20. Pregnancy outcome following gestational exposure to azithromycin

    Directory of Open Access Journals (Sweden)

    Woodland C Cindy


    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.

  1. Toxicity of food additives (excluding antioxidants). January 1978-November 1987 (citations from the Life Sciences Collection data base). Report for January 1978-November 1987

    Energy Technology Data Exchange (ETDEWEB)


    This bibliography contains citations concerning the toxicity of food additives (excluding antioxidants) and their effects on the liver, kidneys, bladder, and other organs. The carcinogenic and teratogenic properties of these substances are also considered. The synthetic sweeteners, particularly the saccharins and cyclamates, and other additives, including nitrates and nitrites are discussed. Methods to detect and quantitate these additives are also included. (This updated bibliography contains 340 citations, 132 of which are new entries to the previous edition.)

  2. Effect Of Permethrin, Pirimiphos Methyl And Bendiocarb On The Osmotic Resistance Of Rat Erythrocytes


    Salwa A.Metwally and Hala M. Fawzy


    Environmental pollution by insecticides is one of the most important problems in the world. Some of the pesticides were found to exert carcinogenic, teratogenic and/or mutagenic effects even following normal agricultural use (U.S.Geological Survey, 1997). On the other hand residues from insecticides, herbicides and insect growth hormones are known to represent the most common food contaminants particularly in developing countries. Thus the wide spread use of insecticides in agriculture stimul...

  3. Peyote use during pregnancy. (United States)

    Gilmore, H T


    Peyote is a substance with varied potential. Used properly it may be a spiritual aid but used in excess, it can be a hallucinogenic agent with teratogenic potential. There is a growing community of devout people who use it as part of their religious observance. The active ingredient, mescaline, has been linked to a specific group of fetal abnormalities when the substance is used inappropriately.

  4. Suppression of morphogenesis in embryonic mouse limbs exposed in vitro to excess gravity (United States)

    Duke, Jackie C.


    The effect of excess gravity on in vitro mammalian limb chondrogenesis is studied. Limb buds from mice of various gestational stages were exposed to excess gravity (2.6G) using a culture centrifuge. Both forelimbs and hind limbs were cultured, and the development of various limb elements was scored after four to six days. The 2.6G force significantly depressed the development of limb elements when applied during the teratogen-sensitive period of chondrogenesis.

  5. Foetal fibular hemimelia with focal femoral deficiency following prenatal misoprostol use: A case report. (United States)

    Pallavee, P; Samal, Rupal; Begum, Jasmina; Ghose, Seetesh


    Misoprostol is a well known abortifacient. It can cause teratogenicity like Mobius sequence and terminal transverse limb defects. We report a rare case of proximal focal femoral deficiency with fibular hemimelia in a woman who had attempted abortion with self-administered misoprostol and later continued the pregnancy. Though the absolute risk of congenital malformations with its use is low ∼1%, this should be clearly communicated to the women requesting abortion to help them make fully informed reproductive health decisions.

  6. Water Quality Criteria for Disperse Red 9 (United States)


    mixture were identified as azobenzene , azoxybenzene, aminobiphenyl, and phenyldiazo- benzene. The second fraction, 73.6 percent of the mixture...antagonistic effects; and genotoxicity, teratogenicity, and carcinogenicity. The data are derived primarily from animal studies, but clinical case histories ...on can be used for calculating a water quality criterion (using the uncertainty factor approach). Also the history of each TLV should be examined to

  7. Toxicity of Fastac 10 EC, a pyrethroid insecticide, to Paramecium primaurelia and Tubifex sp. (United States)

    Komala, Z


    The pyrethroide, Fastac 10 EC was tested on the paramecia and Tubifex sp. The results showed that both tests are valid for estimation of the toxicity of the pesticide. However, the Paramecium test is more sensitive when one is investigating the direct toxicity of the compound. The great validity of the Tubifex test lies in the possibility of tracing the teratogenic effects of the pesticides.

  8. Magnesium and Embryonic Development


    Komiya, Yuko; Su, Li-Ting; Chen, Hsiang-Chin; Habas, Raymond; Runnels, Loren W.


    Important for energy metabolism, neurotransmission, bone stability, and other cellular functions, Mg2+ has well-established and undisputedly critical roles in adult tissues. Its contributions to early embryonic development are less clearly understood. For decades it has been known that gestational Mg2+ deficiency in rodents produces teratogenic effects. More recent studies have linked deficiency in this vital cation to birth defects in humans, including spina bifida, a neural fold closure def...

  9. Seroprevalence Survey of Rubella Antibodies among Pregnant ...

    African Journals Online (AJOL)

    Key words: Rubella virus, teratogen, antibodies, Maiduguri. La rubéole est une infection virale évitable par la vaccination. Son agent étiologique, virus de la rubéole a été identifié comme un tératogène humain capable de provoquer le spectre de malformation congénitale décrite comme le syndrome de rubéole congénitale ...



    ESİN, yar.Doç.Dr. M.Nihal


    SUMMARY     Occupational Health Nursing on Prevention of Worker's Respiratory System:Workers are exposed to a variety of chemical in the production of materials in the work environment. Health effects from chemical expossure may be manifested as a mutagenic, carcinogenic or teratogenic. Chemicals are entire into the body via respiratory system and multiplicative effect on biological system. So worker's respiratory systemmust be prevented. Effective assessment and management of workp...

  11. Occupational hazards for pregnant nurses. (United States)

    Alex, Marion Rita


    Depending on her working environment, specific immunities, and stage of pregnancy, a pregnant nurse may find it difficult to avoid teratogenic and fetotoxic exposures, as well as working conditions that could jeopardize her pregnancy. A clinical review of the occupational hazards faced by pregnant nurses can be useful to the concerned nurse or health care system, as can suggestions on ways to reduce risk and a list of pertinent occupational safety resources.

  12. Field Manual of Wildlife Diseases. General Field Procedures and Diseases of Birds (United States)


    orange colored parasites that are firmly at- tached to the mucosa (Fig. 33.3). Some parasites can pen- etrate the gut wall and project into the...Himatione sanguinea ) Cassin’s finch (Carpodacus cassinii) : Eurasian bullfinch (Pyrrhula pyrrhula) . Evening grosbeak (Coccothraustes vespertinus...a chemical component of defoliants, such as agent orange , that are considered to be carcinogenic (cause can- cer), teratogenic (cause fetal

  13. Pregnancy, Proteinuria, Plant-Based Supplemented Diets and Focal Segmental Glomerulosclerosis: A Report on Three Cases and Critical Appraisal of the Literature


    Rossella Attini; Filomena Leone; Benedetta Montersino; Federica Fassio; Fosca Minelli; Loredana Colla; Maura Rossetti; Cristiana Rollino; Maria Grazia Alemanno; Antonella Barreca; Tullia Todros; Giorgina Barbara Piccoli


    Chronic kidney disease (CKD) is increasingly recognized in pregnant patients. Three characteristics are associated with a risk of preterm delivery or small for gestational age babies; kidney function reduction, hypertension, and proteinuria. In pregnancy, the anti-proteinuric agents (ACE–angiotensin converting enzyme-inhibitors or ARBS -angiotensin receptor blockers) have to be discontinued for their potential teratogenicity, and there is no validated approach to control proteinuria. Furtherm...

  14. A Reliable and Reproducible Model for Assessing the Effect of Different Concentrations of α-Solanine on Rat Bone Marrow Mesenchymal Stem Cells


    Adriana Ordóñez-Vásquez; Lorenza Jaramillo-Gómez; Camilo Duran-Correa; Erandi Escamilla-García; Myriam Angélica De la Garza-Ramos; Fernando Suárez-Obando


    Αlpha-solanine (α-solanine) is a glycoalkaloid present in potato (Solanum tuberosum). It has been of particular interest because of its toxicity and potential teratogenic effects that include abnormalities of the central nervous system, such as exencephaly, encephalocele, and anophthalmia. Various types of cell culture have been used as experimental models to determine the effect of α-solanine on cell physiology. The morphological changes in the mesenchymal stem cell upon exposure to α-solani...

  15. Transcriptomic responses of the basidiomycete yeast Sporobolomyces sp. to the mycotoxin patulin


    Ianiri, Giuseppe; Idnurm, Alexander; Castoria, Raffaello


    Background Patulin is a mycotoxin produced by Penicillium expansum, the causal agent of blue mold of stored pome fruits, and several other species of filamentous fungi. This mycotoxin has genotoxic, teratogenic and immunotoxic effects in mammals, and its presence in pome fruits and derived products represents a serious health hazard. Biocontrol agents in the Pucciniomycotina, such as the yeasts Sporobolomyces sp. strain IAM 13481 and Rhodosporidium kratochvilovae strain LS11, are able to resi...

  16. Toxicological aspects and occurrence of patulin in apple juice/
    Aspectos toxicológicos e ocorrência de patulina em suco de maçã


    Miguel Machinski Junior; Rubia Andreia Falleiros de Pádua


    Patulin is a secondary metabolite produced by different species of fungi, being Penicillium expansum the most important species. Patulin is a mycotoxin that has been found mainly in mature apples used in the production of concentrated apple juice, but it can also be in other fruits, vegetables and nutritious products. Experiments carried out with laboratory animals have demonstrated that this mycotoxin produces several harmful effects, including mutagenicity, teratogenicity, carcinogenicity, ...

  17. Congenital diplopodia

    Energy Technology Data Exchange (ETDEWEB)

    Brower, Jason S.; Wootton-Gorges, Sandra L.; Costouros, John G.; Boakes, Jennette; Greenspan, Adam [University of California, Davis, Department of Radiology, 4860 Y. Street, Suite 3100, CA 95817, Davis (United States)


    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.)

  18. The status of diabetic embryopathy. (United States)

    Eriksson, Ulf J; Wentzel, Parri


    Diabetic embryopathy is a theoretical enigma and a clinical challenge. Both type 1 and type 2 diabetic pregnancy carry a significant risk for fetal maldevelopment, and the precise reasons for the diabetes-induced teratogenicity are not clearly identified. The experimental work in this field has revealed a partial, however complex, answer to the teratological question, and we will review some of the latest suggestions.

  19. Potential terrestrial fate and effects on soil biota of a coal liquefaction product spill

    Energy Technology Data Exchange (ETDEWEB)

    Strayer, R.F.; Edwards, N.T.; Walton, B.T.; Charles-Shannon, V.


    Contaminated soil samples collected from the site of a coal liquefaction product spill were used to study potential fates and effects of this synthetic fuel. Simulated weathering in the laboratory caused significant changes in residual oil composition. Soil column leachates contained high phenol levels that decreased exponentially over time. Toxicity tests demonstrated that the oil-contaminated soil was phytotoxic and caused embryotoxic and teratogenic effects on eggs of the cricket Acheta domesticus.

  20. USAFSAM Review and Analysis of Radiofrequency Radiation Bioeffects Literature: Second Report. (United States)


    Rosenbaum, and W. F. Pickard THE RELATION OF TERATOGENESIS IN TENEBRIO MOLITOR TO THE INCIDENCE OF LOW-LEVEL MICROWAVES IEEE Trans. Microwave Theory...Teratogenic and developmental abnormalities; ’N VIVO; TENEBRIO MOLITOR (DARKLING BEETLE) Effect type: Abnormalities in emergent adult beetles due to RFR...early pupae of the mealworm beetle, Tenebrio molitor . Each pupa was inserted in a waveguide and irradiated therein at waveguide powers of 80 mW for

  1. USAFSAM (USAF School of Aerospace Medicine) Review and Analysis of Radiofrequency Radiation Bioeffects Literature: Third Report. (United States)



  2. Long-term functional consequences of early clonazepam exposure in immature rats


    Šubrt, Martin


    Benzodiazepines (BZs) are widely prescribed because of broad spectrum of therapeutic effects. Under specific conditions they can be used during the pregnancy and early postnatally in humans. However, clinical studies suggest their possible behavioral teratogenicity even though it is difficult to separate consequences of early BZs exposure from underlying pathologies in clinical practice. Therefore experimental studies can help us to determine risks of early BZs treatment for later development...

  3. Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides: Study Protocol (United States)


    placen- tal passage, and in mice, which show placental passage only in late gestation . Clearance from plasma and from the body varies greatly among...barrier and accel- erated fetal uptake with advancing gestation . P. 59-79. In Tissue Localization of Some Teratogens at Early and Late Gestation Reated to...Republics VA Veterans Administration VDRL/FTA Serological Tests for Syphilis WAIS Wechsler Adult Intelligence Scale WRAT Wide Range Achievement Test 172 U i .. ’ ’ " . . . .- - .. ’ - i . . . .’

  4. Isotretinoin embryopathy: report of one case


    Cláudia Patraquim; Albina Silva; Ângela Pereira; Miguel Gonçalves-Rocha; João Fernandes; Almerinda Pereira


    Retinoic acid is a derivative of vitamin A.Retinoic acid embryopathy is an association of malformations caused by the teratogenic effect of retinoic acid, a drug used for the treatment of cystic acne.Isotretinoin is also known as 13-cis-retinoic acid.The risk of malformations after exposure to oral isotretinoin has been evaluated to be around 20%.Affected infants may present craniofacial, central nervous system, cardiac, and thymus abnormalities. There is also an increased risk of spontaneous...


    Directory of Open Access Journals (Sweden)

    S.A. Sher


    Full Text Available The article focuses on the issue of evaluating potential risk posed by medications to the fetus during pregnancy. For this purpose various countries use classifications of medications broken down into risk categories during pregnancy. The most popular classification is US FDA classification, which identifies five categories of medications (А, В, С, D and Х depending on the degree of their embryotoxic and teratogenic side effect, which enables physicians to make informed choices in selecting pharmacotherapy during the entire gestational period. The article discusses possible specific fetal and neonatal disorders when administering medications in categories X and D. Medications in category D may be prescribed to pregnant women only in extreme situations. Administering medications in category X is absolutely inadvisable before and during pregnancy. Further research in this area makes it possible to improve the classification of medications by degree of their embryotoxic and teratogenic risk and address the issue of selecting safe medications during pregnancy. Key words: medications, gestational period, embryo, fetus, embryotoxic and teratogenic action, fetal and neonatal disorders. (Pediatric Pharmacology. – 2010; 7(3:78-81

  6. Successful treatment of palmoplantar pustulosis with isotretinoin. (United States)

    Wilken, Reason; Sharma, Ajay; Patel, Forum; Maverakis, Emanual


    Variably considered as a localized subtype of pustular psoriasis, palmoplantar pustulosis (PPP) is commonly treated with topical steroids, acitretin, and local phototherapy with oral or topical psoralen (PUVA). The utility of acitretin for PPP is limited by adverse effects such as myalgias and an extended risk of teratogenicity in female patients. Isotretinoin is a more tolerable retinoid with a shorter teratogenic window, but to date its effectiveness in PPP has not been reported. Herein we present two patients with PPP who responded well to isotretinoin treatment. Two patients with PPP refractory to topical therapies were started on acitretin. Both patients developed adverse effects (including headache, myalgias, and mood alterations) leading to acitretin discontinuation. Isotretinoin monotherapy was started in one patient resulting in significant clearing of palmar plaques and scale, and the addition of isotretinoin to UVA therapy resulted in near-complete clearing of recalcitrant plantar plaques in the second patient. Acitretin represents an important treatment for PPP, but is limited by adverse effects and extended teratogenicity. Our experience supports the utility of isotretinoin as a potential therapeutic alternative, which may be particularly beneficial in patients who are poor candidates for or unable to tolerate acitretin therapy.

  7. The Effects of Essential Oil of Galbanum on Caffeine Induced-Cleft palate in Rat Embryos

    Directory of Open Access Journals (Sweden)

    Mahmood Khaksary-Mahabady


    Full Text Available Background: Caffeine at high doses is a known rodent teratogen and induces limb malformations along with cleft palate in various strains of rats and mice. The teratogenic effects of some drugs can be prevented by the application of antioxidant drugs and stimulation of the maternal immune system. Also, there is some evidence that galbanum is antioxidant. Therefore, in this study, the prophylactic effect of galbanum on teratogenic effects of caffeine was evaluated. Materials and Methods: This experimental study was performed on 28 pregnant rats that were divided into four groups. Control group received normal saline and test groups received caffeine (80 mg/kg, caffeine (80 mg/kg plus galbanum (200 mg/kg and galbanum (200 mg/kg, intraperitonealy at 9-11thP Pdays of gestation, respectively. Fetuses were collected at 20thP Pday of gestation and after determination of weight and length; they were stained by Alizarin red - Alcian blue method. Results: Cleft palate incidence was 33.3%, in caffeine group and decreased to 8.3% by galbanum. The mean of weight and length of fetuses from rat that received galbanum were significantly greater than those received only caffeine. Conclusion: It is concluded that galbanum decreased cleft palate induced by caffeine; but its mechanism needs more details evaluation.

  8. Sublethal effects of atrazine on embryo-larval development of Rhinella arenarum (Anura: Bufonidae). (United States)

    Svartz, Gabriela V; Herkovits, Jorge; Pérez-Coll, Cristina S


    Atrazine (ATR), one of the most widely used herbicides in the world, affects not only target organisms but also the biota in general. Here, the teratogenic and neurotoxic effects of ATR on Rhinella arenarum (South American toad) embryos, and larvae were evaluated by means of standardized bioassays during acute and chronic exposures. The herbicide had a significant incidence of malformations, with a Teratogenic Index (TI) of 3.28. The main effects were delayed development, reduced body size, microcephaly, axial flexures, wavy tail and edema. In addition, delayed development, reduced development of forelimbs, and edema were recorded at metamorphosis stages. Scanning electron microscopy allowed observing different degrees of cellular dissociation and persistent cilliar cells in specific regions like the adhesive structure and tail fin. Results obtained by ATR 24 h pulse exposures at six developmental stages pointed out blastula as the most susceptible developmental stage both for immediate and delayed adverse effects. A noteworthy recovery capacity from acute toxic effects was recorded from the neural plate stage onwards. Regarding neurotoxic effects, abnormal, and erratic swimming and spasmodic contractions were recorded. Both the teratogenic and neurotoxic effects reported in this study demonstrate the importance of evaluating sublethal effects in non-target organisms as they could imply reduced fitness of individuals and eventually a population decline. The Hazard Quotients (HQ) for ATR ranged from 0.14 to 10.80, and the fact that some of these values are above USEPA's level of concern indicate that ATR is likely a risk to R. arenarum.

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


    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.

  10. Role of Helicobacter pylori in the pathogenesis of hyperemesis gravidarum. (United States)

    Mansour, Ghada M; Nashaat, Ehab H


    To evaluate the role of Helicobacter pylori (H. pylori) in the pathogenesis of hyperemesis gravidarum (HG) and the value of adding a non teratogenic regimen for its treatment in intractable cases. Eighty hyperemesis gravidarum cases were recruited from Ain Shams University out patient clinics. A complete history was taken including history of medical disorders and chronic medications intake as non steroidal anti-inflammatory drugs. After general and local examination, ultrasound was done for all cases to exclude obstetric causes of hyperemesis. Eighty normal pregnant women acted as control. Serum test for H. pylori IgG antibody titre was done for all patients and controls. Seventy-one cases among the 80 HG cases and twenty-four out of the 80 controls were H. pylori positive. Eight HG cases developed severe intractable vomiting. Three of them developed attacks of hematemesis. Gastroscopy done for the eight cases revealed antral gastritis and duodenitis. Gastric and duodenal erosions were found in two cases. The eight patients received a non teratogenic regimen for treatment. Attacks of vomiting decreased and pregnancy continued till delivery of healthy newborns. Screening for H. pylori should be added to the investigations of hyperemesis gravidarum cases. Non teratogenic treatment can be considered in intractable cases.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    John Russell Williams


    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.

  13. The effects of inhalation exposure to sulfuryl fluoride on fetal development in rats and rabbits. (United States)

    Hanley, T R; Calhoun, L L; Kociba, R J; Greene, J A


    Sulfuryl fluoride is a fumigant insecticide used for soils and permanent structures. Pregnant Fischer 344 rats and New Zealand White rabbits were exposed to 0, 25, 75, or 225 ppm of sulfuryl fluoride vapor via inhalation for 6 hr/day on Days 6-15 and 6-18 of gestation, respectively. Among rats, maternal water consumption was increased in the 225 ppm exposure group, but there were no indications of embryotoxicity, fetotoxicity, or teratogenicity in any of the exposed groups. Among rabbits, maternal weight loss during the exposure period (Days 6-18) was observed in the 225 ppm group. Decreased fetal body weights, considered secondary to maternal weight loss, were also observed at 225 ppm. However, no evidence of embryotoxicity or teratogenicity was observed among rabbits in any exposure group. Thus, inhalation exposure to sulfuryl fluoride was not teratogenic in either rats or rabbits exposed to levels of up to 225 ppm, and fetotoxic effects (reduced body weights) were observed among fetal rabbits only at an exposure level that produced maternal weight loss.

  14. Human Cytochrome P450 Oxidation of 5-Hydroxythalidomide and Pomalidomide, an Amino Analog of Thalidomide (United States)

    Chowdhury, Goutam; Shibata, Norio; Yamazaki, Hiroshi; Guengerich, F. Peter


    The sedative and antiemetic drug thalidomide [α-(N-phthalimido)glutarimide] was withdrawn in the early 1960s due to its potent teratogenic effects but was approved for the treatment of lesions associated with leprosy in 1998 and multiple myeloma in 2006. The mechanism of teratogenicity of thalidomide still remains unclear, but it is well established that metabolism of thalidomide is important for both teratogenicity and cancer treatment outcome. Thalidomide is oxidized by various cytochrome P450 (P450) enzymes, the major being P450 2C19, to 5-hydroxy-, 5’-hydroxy-, and dihydroxythalidomide. We previously reported that P450 3A4 oxidizes thalidomide to the 5-hydroxy and dihydroxy metabolites, with the second oxidation step involving a reactive intermediate, possible an arene oxide, that can be trapped by glutathione (GSH) to GSH adducts. We now show that the dihydroxythalidomide metabolite can be further oxidized to a quinone intermediate. Human P450s 2J2, 2C18, and 4A11 were also found to oxidize 5-hydroxythalidomide to dihydroxy products. Unlike P450s 2C19 and 3A4, neither P450 2J2, 2C18, nor 4A11 oxidized thalidomide itself. A recently approved amino analog of thalidomide, pomalidomide (CC-4047, Actimid™), was also oxidized by human liver microsomes and P450s 2C19, 3A4, and 2J2 to the corresponding phthalimide ring-hydroxylated product. PMID:24350712

  15. In vivo phenytoin-initiated oxidative damage to proteins and lipids in murine maternal hepatic and embryonic tissue organelles: potential molecular targets of chemical teratogenesis. (United States)

    Liu, L; Wells, P G


    The widely used anticonvulsant drug phenytoin may be bioactivated by peroxidases such as prostaglandin H synthase (PHS) to a reactive free radical intermediate that initiates teratogenesis. This in vivo study evaluated the potential molecular targets mediating phenytoin teratogenicity. In vivo phenytoin-induced oxidative tissue damage following bioactivation was quantified in both maternal hepatic and embryonic tissues from pregnant CD-1 mice using lipid peroxidation and protein oxidation and degradation as indices. Pregnant mice were injected with a teratogenic dose of phenytoin, 65 mg/kg ip, during organogenesis on Gestational Day 12. alpha-Phenyl-N-t-butylnitrone (PBN), a free radical spin trapping agent, 41.5 mg/kg, or acetylsalicylic acid (ASA), an inhibitor of the cyclooxygenase component of PHS, 10 mg/kg, were injected ip 2 hr before phenytoin treatment, and maternal hepatic and embryonic tissues were obtained at 0, 3, 6, 8, and 24 hr. Phenytoin enhanced lipid peroxidation in maternal plasma, hepatic microsomes, cytosol, mitochondria, and nuclei and in embryonic microsomes, cytosol, and mitochondria (p teratogenicity by PBN and ASA, suggest that peroxidase-catalyzed bioactivation of phenytoin may initiate oxidative damage to lipids and proteins in embryonic tissues, with teratological consequences.

  16. Excess caffeine exposure impairs eye development during chick embryogenesis (United States)

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


    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

  17. The Effect of Saffron Decoction Consumption on Pregnant Mice and Their Offspring

    Directory of Open Access Journals (Sweden)



    Full Text Available Introduction: In traditional medicine, saffron is used as a drug for treating many diseases. However there are many documents and evidences concerning its abortive and teratogenic effect especially in high doses. Aim: This study was conducted to evaluate the effect of saffron decoction consumption on pregnant mice and their offspring. Methods: In this study, 20 female mice after breeding and observation of vaginal plaque, randomly and equally divided into two groups. During pregnancy, animals were housed under the same environmental and nutritional condition while the test group received 0.5% saffron decoction as their drinks instead of tape water for control group. The pregnant mice were weighted during pregnancy and after delivery. Following the parturition, the number of live kids, their weight and sex and any pretended obvious abnormality were assigned. Results: The duration of pregnancy period and the number of live kids in test group were significantly less than control group while the mean infant’s weight in test group was more than control group. There was obvious one-eye blindness in 4 kids from saffron consumed group. In the case of mother's weight and sex ratio of live kids there was no significant difference between the two groups. Conclusion: This study indicated that saffron has a specific teratogenic effect on visual system and causes preterm labor and reduces the number of live infants which may be due to its abortive effect. Keywords: Saffron, Pregnancy, Infant, Teratogen, Mice

  18. Is there an embryopathy associated with first-trimester exposure to angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists? A critical review of the evidence. (United States)

    Polifka, Janine E


    Drugs that interfere with the renin-angiotensin system, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are widely used to manage hypertension and heart failure. Adequate functioning of the RAS is essential for normal fetal kidney development. The potential for ACEIs and ARBs to impair fetal and neonatal renal function if taken after the first trimester of pregnancy has been well documented. Although these drugs were not found to be teratogenic in animals, until recently little was known about the teratogenic effects of ACEIs and ARBs in humans when exposure was limited to the first trimester of pregnancy. New evidence from epidemiologic studies indicates that there may be an elevated teratogenic risk when these drugs are taken during the first trimester of pregnancy. However, this elevated risk does not appear to be specific to ACEIs and ARBs, but is instead related to maternal factors and diseases that typically coexist with hypertension in pregnancy, such as diabetes, advanced maternal age, and obesity. Women who become pregnant while being treated with an ACEI or ARB should be advised to avoid exposure to these drugs during the second and third trimesters of pregnancy by switching to a different class of antihypertensive drugs between weeks 8 and 10 after conception. Copyright © 2012 Wiley Periodicals, Inc.

  19. Activation and Desensitization of Peripheral Muscle and Neuronal Nicotinic Acetylcholine Receptors by Selected, Naturally-Occurring Pyridine Alkaloids

    Directory of Open Access Journals (Sweden)

    Benedict T. Green


    Full Text Available Teratogenic alkaloids can cause developmental defects due to the inhibition of fetal movement that results from desensitization of fetal muscle-type nicotinic acetylcholine receptors (nAChRs. We investigated the ability of two known teratogens, the piperidinyl-pyridine anabasine and its 1,2-dehydropiperidinyl analog anabaseine, to activate and desensitize peripheral nAChRs expressed in TE-671 and SH-SY5Y cells. Activation-concentration response curves for each alkaloid were obtained in the same multi-well plate. To measure rapid desensitization, cells were first exposed to five potentially-desensitizing concentrations of each alkaloid in log10 molar increments from 10 nM to 100 µM and then to a fixed concentration of acetylcholine (ACh, which alone produces near-maximal activation. The fifty percent desensitization concentration (DC50 was calculated from the alkaloid concentration-ACh response curve. Agonist fast desensitization potency was predicted by the agonist potency measured in the initial response. Anabaseine was a more potent desensitizer than anabasine. Relative to anabaseine, nicotine was more potent to autonomic nAChRs, but less potent to the fetal neuromuscular nAChRs. Our experiments have demonstrated that anabaseine is more effective at desensitizing fetal muscle-type nAChRs than anabasine or nicotine and, thus, it is predicted to be more teratogenic.

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

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Gustavo Glotz de, E-mail:; 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)


    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.

  1. Thalidomide Analogs in Brazil: Concern About Teratogenesis / Análogos da Talidomida no Brasil: Preocupação com a Teratogênese

    Directory of Open Access Journals (Sweden)

    Fernanda Sales Luiz Vianna


    Full Text Available It has been more than 50 years since thalidomide was withdrawn from the world market due to its teratogenic potential. However, its widespread use around the world resumed due to its immunomodulatory and anti-angiogenic properties. The drug established itself in new therapies, and interest continued with the emergence of more potent analogs, the most notable being lenalidomide and pomalidomide, which are not approved in Brazil. The question that arises after analog synthesis is: Do these drugs also have the same teratogenic potential? The answer to this question is based only on experimental studies because exposure to humans is not authorized and has not yet been descri-bed. Although thalidomide has been recognized as a powerful human teratogen for many years, its molecular mechanisms of teratogenesis remain to be fully explained. Efforts with animal models and human genetic studies have clarified some important pathways that are most likely involved in the teratogenic action of thalidomide. However, it has not yet been possible to identify the teratogenic domain of the molecule from the therapeutic ones. Moreover, there are species-specific differences that must be taken into consideration when teratogenicity is evaluated. -------------------------------------------------------------- Faz mais de 50 anos que a talidomida foi retirada do mercado mundial devido ao seu potencial teratogênico. Entretanto, seu uso disseminado em todo o mundo foi retomado devido às suas propriedades imunomodulatórias e antiangiogênicas. A droga foi utilizada em novas terapias e o interesse continuou com a emergência de análogos mais potentes, os mais notáveis deles sendo a lenalidomida e a pomalidomida, que não estão aprovados no Brasil. A questão que surge após a síntese dos análogos é: Estas drogas também têm o mesmo potencial teratogênico? A resposta a esta pergunta baseia-se apenas em estudos experimentais, pois a exposição a humanos não est

  2. L-Carnitine Protect against Cyclophosphamide Induced Skeletal and Neural Tube Malformations in Rat Fetuses. (United States)

    Khaksary Mahabady, Mahmood; Najafzadeh Varzi, Hossein; Zareyan Jahromi, Saeedeh


    Cyclophosphamide (CP) is a mustard alkylating agent used in the treatment of a number of neoplastic diseases and as an immunosuppressant for the prevention of xenograft rejection. There are many reports that the teratogenic effects of cyclophosphamide can be prevented by application of antioxidant drugs and stimulation of the maternal immune system. Also, there is some evidence that L-carnitine is antioxidant. Therefore, in this study, the prophylactic effect of L-carnitine on teratogenic effects of CP was evaluated. This study was performed on 31 pregnant rats divided into 5 groups. Control group received normal saline and test groups received L-carnitine (500 mg/kg), CP (15 mg/kg), CP (15 mg/kg) plus L-carnitine (250 mg/kg) and CP (15 mg/kg) plus L-carnitine (500 mg/kg) intraperitoneally at 9th day of gestation. Fetuses were collected at 20th day of gestation and after determination of weight and length; they were stained by Alizarin red-Alcian blue method. Cleft palate, spina bifida, and exencephaly incidence were 55.55%, 33.34% and 27.77% in fetuses of mice that received only CP. Cleft palate, spina bifida, exencephaly incidence were 21.42%, 4.76% and 9.52% in the group which received CP plus L-carnitine (250 mg/kg), respectively. However, cleft palate, spina bifida, and exencephaly incidence were 8%, 0% and 8% range in the group received CP plus L-carnitine (500 mg/kg), respectively. In addition, skeletal anomalies incidence including limbs, vertebrae, and sternum defects were decreased by L-carnitine. The mean of weight and length of animals' fetuses received L-carnitine were significantly greater than those received only CP. In conclusion, L-carnitine significantly decreased teratogenicity induced by CP; but this subject needs more detailed evaluation.

  3. Maternal Stress Combined with Terbutaline Leads to Comorbid Autistic-Like Behavior and Epilepsy in a Rat Model. (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


    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.

  4. An Update on Fetal Alcohol Syndrome-Pathogenesis, Risks, and Treatment. (United States)

    Gupta, Keshav K; Gupta, Vinay K; Shirasaka, Tomohiro


    Alcohol is a well-established teratogen that can cause variable physical and behavioral effects on the fetus. The most severe condition in this spectrum of diseases is known as fetal alcohol syndrome (FAS). The differences in maternal and fetal enzymes, in terms of abundance and efficiency, in addition to reduced elimination, allow for alcohol to have a prolonged effect on the fetus. This can act as a teratogen through numerous methods including reactive oxygen species (generated as by products of CYP2E1), decreased endogenous antioxidant levels, mitochondrial damage, lipid peroxidation, disrupted neuronal cell-cell adhesion, placental vasoconstriction, and inhibition of cofactors required for fetal growth and development. More recently, alcohol has also been shown to have epigenetic effects. Increased fetal exposure to alcohol and sustained alcohol intake during any trimester of pregnancy is associated with an increased risk of FAS. Other risk factors include genetic influences, maternal characteristics, for example, lower socioeconomic statuses and smoking, and paternal chronic alcohol use. The treatment options for FAS have recently started to be explored although none are currently approved clinically. These include prenatal antioxidant administration food supplements, folic acid, choline, neuroactive peptides, and neurotrophic growth factors. Tackling the wider impacts of FAS, such as comorbidities, and the family system have been shown to improve the quality of life of FAS patients. This review aimed to focus on the pathogenesis, especially mechanisms of alcohol teratogenicity, and risks of developing FAS. Recent developments in potential management strategies, including prenatal interventions, are discussed. Copyright © 2016 by the Research Society on Alcoholism.

  5. A comparison of electronic and traditional cigarette butt leachate on the development of Xenopus laevis embryos

    Directory of Open Access Journals (Sweden)

    Tatiana Tatum Parker

    Full Text Available Potential developmental toxicities of three different cigarette butt leachates were evaluated using the frog embryo teratogenesis assay–Xenopus (FETAX. Xenopus laevis embryos were exposed to regular cigarette butt (RCB, menthol (MCB and electronic (ECB in concentrations ranging from 0 to 4 butts/l for RCB and MCB and 0–10 butts/l for ECB. The embryos were from stage 8 to 11 and were exposed for a 96-h period in static renewal test conditions. Median lethal concentration (LC50, malformation (EC50, non-observed adverse effect concentration (NOAEC, and lowest observed adverse effect concentration (LOAEC were calculated. Results from these studies suggest that each tested leachate is teratogenic for X. laevis embryos. The lowest LC50 was determined for ECB exposure at 17.9 cigarette butts/L. The LC50 value was the highest with RCB and MCB having LC50 s of approximately 1 cigarette butt/L. There were notable EC50 differences with RCB having the highest and ECB the lowest. The NOAEC and LOAEC levels for RCB and MCB were below 1 cigarette butt/L for both mortality and malformations; over 8 butts/L for ECB mortality and over 4 butts/L for malformations. From these results, we conclude that RCB leachate is the most toxic compound, while MCB leachate has the higher teratogenicity. ECB leachate has the lowest toxic and teratogenic effects on embryos but there were still noticeable effects. The results confirmed that the FETAX assay can be useful in an integrated biological hazard assessment for the preliminary screening for ecological risks of cigarette butts, and electronic cigarettes, in aquatic environment. Keywords: Cigarette butt leachate, Xenopus laevis, Development

  6. Perceptions and Attitudes Towards Medication Adherence during Pregnancy in Inflammatory Bowel Disease. (United States)

    Gallinger, Zane R; Rumman, Amir; Nguyen, Geoffrey C


    Women with inflammatory bowel disease [IBD] report concerns about medication safety during pregnancy. Adherence to IBD medications may be lower in pregnant patients as a result. The aim of this study was to assess medication adherence during pregnancy in women with inflammatory bowel disease. Female patients of childbearing age completed a self-administered, structured survey. We collected demographic data, medication history, and self-reported adherence to IBD medications during pregnancy. We also assessed knowledge and perceptions of IBD medication safety in pregnancy. A time trade-off [TTO] analysis was done to assess health utilities for continuing or discontinuing IBD medications during pregnancy. A total of 204 women completed the survey [mean age was 32.8 years]. Current or previous pregnancy was reported by 101 patients [median parity 2, median gravity 1]. While pregnant or attempting to conceive, 47 [46.5%] participants reported stopping a prescribed IBD medication. Of those, 20 participants reported stopping medications without the advice of a physician. TTO analysis was completed by 31 patients. When presented with the option of continuing a potentially teratogenic medication, switching to less effective medication that is non-teratogenic, or stopping medication all together, participants consistently preferred to not remain on the most effective IBD therapy. Women with IBD report preference to not remain on IBD medications during pregnancy. This is driven by concerns about safety and uncertainty about teratogenic effects. Women with IBD may benefit from increased education about medication safety in pregnancy. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email:

  7. Potential uses of sea urchin embryos for identifying toxic chemicals: description of a bioassay incorporating cytologic, cytogenetic and embryologic endpoints. (United States)

    Hose, J E


    A method for evaluating pollutant genotoxicity, embryotoxicity and teratogenicity using sea urchin embryos has been developed and was tested using benzo(a)pyrene (BP). Initial results suggested that the bioassay may be a sensitive indicator of pollutant toxicity and mutagenicity since several endpoints can be simultaneously assessed. The bioassay is rapid, inexpensive and appears applicable to a variety of toxicants and delivery methods. The test is based upon the standard 48 h sea urchin development assay and incorporates cytologic-cytogenetic analysis of embryos. Following toxic exposure of gametes, fertilization success is assessed. Embryos then develop for 48 h at which time survival and teratogenesis are evaluated. A subsample of embryos is stained and dissociated into monolayers and mitotic configurations are examined using light microscopy. Embryo mitotic rates are used as an indicator of overall embryonic health. Cytotoxic effects are concomitantly evaluated. Genotoxicity is measured using two methods: (1) anaphase aberration analysis, a technique which assesses abnormalities in the chromosome configurations (such as bridges and fragments) as the groups of chromosomes move to opposite poles and (2) micronucleus formation, a procedure examining the incidence of smaller, secondary nuclei composed of whole chromosomes or chromatid fragments. These two measurements preclude the need to examine individual chromosomes for deletions and exchanges, a laborious process in most aquatic organisms which possess numerous relatively small chromosomes. This genotoxicity-teratogenicity test appears promising for laboratory evaluations of individual substances or of complex chemical mixtures as well as for environmental monitoring of nearshore areas. The standard development assay has been used to screen pharmaceuticals and environmental contaminants and some recent investigations have included mitotic aberration analysis. Experiments in our laboratory suggest that the

  8. A comparison of electronic and traditional cigarette butt leachate on the development of Xenopus laevis embryos. (United States)

    Parker, Tatiana Tatum; Rayburn, James


    Potential developmental toxicities of three different cigarette butt leachates were evaluated using the frog embryo teratogenesis assay-Xenopus (FETAX). Xenopus laevis embryos were exposed to regular cigarette butt (RCB), menthol (MCB) and electronic (ECB) in concentrations ranging from 0 to 4 butts/l for RCB and MCB and 0-10 butts/l for ECB. The embryos were from stage 8 to 11 and were exposed for a 96-h period in static renewal test conditions. Median lethal concentration (LC50), malformation (EC50), non-observed adverse effect concentration (NOAEC), and lowest observed adverse effect concentration (LOAEC) were calculated. Results from these studies suggest that each tested leachate is teratogenic for X. laevis embryos. The lowest LC50 was determined for ECB exposure at 17.9 cigarette butts/L. The LC50 value was the highest with RCB and MCB having LC50 s of approximately 1 cigarette butt/L. There were notable EC50 differences with RCB having the highest and ECB the lowest. The NOAEC and LOAEC levels for RCB and MCB were below 1 cigarette butt/L for both mortality and malformations; over 8 butts/L for ECB mortality and over 4 butts/L for malformations. From these results, we conclude that RCB leachate is the most toxic compound, while MCB leachate has the higher teratogenicity. ECB leachate has the lowest toxic and teratogenic effects on embryos but there were still noticeable effects. The results confirmed that the FETAX assay can be useful in an integrated biological hazard assessment for the preliminary screening for ecological risks of cigarette butts, and electronic cigarettes, in aquatic environment.

  9. The safety of methimazole and propylthiouracil in pregnancy: a systematic review. (United States)

    Hackmon, Rinat; Blichowski, Monica; Koren, Gideon


    Hyperthyroidism is one of the most common endocrine disorders in pregnant women, and it can severely complicate the course and outcome of pregnancy. Methimazole (MMI) and propylthiouracil (PTU) are the standard anti-thyroid drugs used in the treatment of hyperthyroidism in pregnancy. Traditionally, MMI has been considered to have clearer evidence of teratogenicity than PTU. Recent studies suggest that PTU can be hepatotoxic, leading to a United States Food and Drug Administration "black box alert." We wished to systematically review the effects of PTU and MMI during pregnancy, and to compare maternal and fetal safety. We conducted a systematic search of PubMed, EMBASE, TOXNET, TOXLINK, DART, Medscape, EBSCO, and Google. Both English and non-English publications were included. We excluded studies using anti-thyroid therapies other than PTU and MMI, studies not allowing interpretation of results, and abstracts of meetings. Overall, insufficient statistical power precluded determination of accurate rates of either MMI teratogenicity or PTU hepatotoxicity in cohort studies. However, a case-control study helped identify the relative risk of MMI-induced choanal atresia. A second case-control study failed to show that aplasia cutis congenita is associated with MMI. PTU has been associated with a rare but serious form of hepatic failure. MMI causes a specific pattern of rare teratogenic effects after first trimester exposure, while PTU therapy may be followed by rare but severe hepatotoxic sequelae. It is therefore appropriate to use PTU to treat maternal hyperthyroidism during the first trimester of pregnancy, and to switch to MMI for the remainder of the pregnancy.

  10. Rat embryos express transcripts for cyclooxygenase-1 and carbonic anhydrase-4, but not for cyclooxygenase-2, during organogenesis. (United States)

    Streck, Randal D; Kumpf, Steven W; Ozolins, Terence R S; Stedman, Donald B


    Acetylsalicylic acid (ASA) is a rat teratogen, and exposures on gestational days (GDs) 9 and 10 induce diaphragm, cardiac, and midline defects. ASA inhibits members of the cyclooxygenase (COX) family and potentially members of the carbonic anhydrase (CA) family. The objective of this study was to determine whether the mRNA developmental expression pattern for any COX or CA isoform was consistent with a model in which ASA teratogenicity is mediated through direct interaction with one of these enzymes within embryos or within the adjacent ectoplacental cone (EPC) or yolk sac. Staged embryos, over a range (GD 9.5-12) that included ASA-sensitive and ASA-insensitive stages of organogenesis, were assayed for COX and CA mRNA levels by three techniques: microarrays; in situ hybridization quantitated by a micro-imager; and quantitative reverse transcription polymerase chain reaction. ASA- and vehicle-treated embryos also were compared to determine whether inhibition led to upregulated COX or CA mRNA expression. COX-2 mRNA was undetectable in embryos throughout organogenesis by any assay (although it was abundant in EPC). In contrast, COX-1 mRNA was moderately abundant in embryos throughout organogenesis. One CA isoform, CA-4, demonstrated developmentally regulated embryonic mRNA expression that coincided with ASA sensitivity ASA exposure failed to induce upregulation of any of these mRNAs. Although ASA may affect the embryo indirectly through interaction with COX-2 within EPC, failure to detect embryonic COX-2 mRNA argues against COX-2 functioning as a direct mediator of ASA teratogenic activity in induction of cardiac, diaphragm, and midline defects. Correlation of COX-1 and CA-4 expression with ASA sensitivity suggested that embryonic COX-1 and possibly CA4 are much more likely candidates for mediators of ASA developmental toxicity.

  11. 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: [Aquatic Ecology and Toxicology Section, Center for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg (Germany); Weigt, Stefan, E-mail: [Institute of Toxicology, Merck KGaA, 64293 Darmstadt (Germany); Braunbeck, Thomas, E-mail: [Aquatic Ecology and Toxicology Section, Center for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg (Germany)


    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.

  12. Hydroxycarbamine: from an Old Drug Used in Malignant Hemopathies to a Current Standard in Sickle Cell Disease (United States)

    Cannas, Giovanna; Poutrel, Solène; Thomas, Xavier


    While hydroxycarbamide (hydroxyurea, HU) has less and fewer indications in malignant hemopathies, it represents the only widely used drug which modifies sickle cell disease pathogenesis. Clinical experience with HU for patients with sickle cell disease has been accumulated over the past 25 years in Western countries. The review of the literature provides increasing support for safety and efficacy in both children and adults for reducing acute vaso-occlusive events including pain episodes and acute chest syndrome. No increased incidence of leukemia and teratogenicity was demonstrated. HU has become the standard-of-care for sickle cell anemia but remains underused. Barriers to its use should be identified and overcome. PMID:28293403

  13. [Moebius syndrome due to the use of misoprostol. Case report]. (United States)

    Sánchez, Otto; Guerra, Dania


    We report a patient affected with Moebius Syndrome (OMIM 157900) due to the use of misoprostol during the first trimester of the pregnancy, when abortion was intended twice using this drug, vias vaginal (600 mg) and oral (900 mg), with failure to induce abortion on both occasions. Since the use of misoprostol for abortion, without any medical indication or supervision, appears to be rather frequent in our population and since there are reports of severe malformations in children born after failed intents of abortion with this medication, it is necessary to alert the medical community and the population in general about the teratogenic risks of this drug.

  14. Mucocutaneous and systemic toxicity of retinoids: monitoring and management. (United States)

    Shalita, A R


    Oral retinoid therapy is associated with significant mucocutaneous and systemic toxicity similar to that found in hypervitaminosis A. Beside the well-known mucocutaneous adverse effects like cheilitis, xerosis, desquamation, dryness of mucous membranes, more troublesome findings are ocular effects, hair loss or hypergranulation tissue. The most unwanted systemic side effects under both retinoids (isotretinoin and etretinate) are teratogenicity, bone toxicity and serum lipid increments. Careful patient counselling and monitoring will enable the physician to modulate these effects and reduce their impact on patient compliance.

  15. Drug therapy during pregnancy: implications for dental practice. (United States)

    Ouanounou, A; Haas, D A


    Pregnancy is accompanied by various physiological and physical changes, including those found in the cardiovascular, respiratory, gastrointestinal, renal and haematological systems. These alterations in the pregnant patient may potentially affect drug pharmacokinetics. Also, pharmacotherapy presents a unique matter due to the potential teratogenic effects of certain drugs. Although medications prescribed by dentists are generally safe during pregnancy, some modifications may be needed. In this article we will discuss the changes in the physiology during pregnancy and its impact on drug therapy. Specific emphasis will be given to the drugs commonly given by dentists, namely, local anaesthetics, analgesics, antibiotics and sedatives.


    Directory of Open Access Journals (Sweden)

    A.V. Ostrovskaya


    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. Environmental occurrence and toxicity of bentazone on embryos of the amphibian Xenopus laevis; Ritrovamento ambientale e tossicita` del bentazone sull`embrione dell`anfibio Xenopus laevis

    Energy Technology Data Exchange (ETDEWEB)

    Bacchetta, Renato; Compagnoni, Enrico; Giarei, Cristina; Vailati, Giovanni [Milan, Univ. (Italy). Dipt. di Biologia


    In this work concentrations of bentazone at the closing section of the River Po (Pontelagoscuro, FE) are reported together with the results of toxicity test performed on embryos of the amphibian Xenopus laevis. The environmental analyses show value higher than the U E limit of 100 ng l{sup -1} for drinking water with a peak in June of 311 ng l{sup -1}. The toxicity and teratogenicity test show no significant mortality up to 10 mg l{sup -1} and developmental malformations concerning corporal axis, eyes, neural tube and coelom starting from 5 mg l{sup -1}.

  18. Fetal surveillance in late pregnancy and during labor. (United States)

    Izquierdo, Luis A; Yonke, Nicole


    During early gestation, drugs have teratogenic effects and can be associated with structural anomalies in the fetus. Substance abuse can also have physiologic effects on the mother and fetus, including decreased uterine blood flow, increased vascular resistance, and an increase in fetal blood pressure. Women at increased risk for stillbirth should undergo antepartum fetal surveillance initiated at 32 weeks of gestation. Because of the high incidence of low birth weight, fetal anomalies, preterm delivery, and growth restriction in these patients, ultrasonography for appropriate pregnancy dating, a detailed anatomic survey, and cervical length should be performed at 20 weeks' gestation. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Aplasia Cutis Congenita Associated With Aplasia of the Superficial Temporal Artery. (United States)

    Choi, Matthew Seung Suk; Choi, Jong Hwan; Ki, Sae Hwi; Jun, Yong Hoon


    Aplasia cutis congenita with or without congenital anomalies is a rare congenital disorder most commonly involving the skin of the scalp, as well as the skull and dura.The etiology is uncertain, and several theories, including vascular accident intrauterine period, vascular anomaly, intrauterine infection, teratogen, and aminiotic adhesion, have been proposed. One theory is that lesions of the scalp are usually caused by vascular anomalies.The authors report on a patient with aplasia cutis congenita presenting with a huge skin and skull defect combined with aplasia of the superficial temporal artery, which was thought to be the etiology.

  20. The Danish (Q)SAR Database Update Project

    DEFF Research Database (Denmark)

    Nikolov, Nikolai Georgiev; Dybdahl, Marianne; Abildgaard Rosenberg, Sine


    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 ( 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...

  1. 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))


    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.

  2. Proteins in growth regulation during early development. Progress report, 1976--1977

    Energy Technology Data Exchange (ETDEWEB)

    Klein, N.W.


    Studies were conducted to determine mechanisms regulating the synthesis of serum proteins by the yolk-sac and to determine if serum proteins are developmental signals. Synthesis of serum proteins in the yolk-sac and liver was determined at various stages of development and effects of teratogenic agents and genetic mutations on protein synthesis were studied. The regulation of serum protein synthesis was studied in cell cultures and in cell-free protein synthesizing systems derived from the yolk-sac. Studies were also conducted on effects of serum proteins on rat embryos, chick embryos without yolk-sacs, and isolated brains. (HLW)

  3. Helping women choose appropriate hormonal contraception: update on risks, benefits, and indications. (United States)

    Spencer, Abby L; Bonnema, Rachel; McNamara, Megan C


    Primary care physicians frequently provide contraceptive counseling to women who are interested in family planning, have medical conditions that may be worsened by pregnancy, or have medical conditions that necessitate the use of potentially teratogenic medications. Effective counseling requires up-to-date knowledge about hormonal contraceptive methods that differ in hormone dosage, cycle length, and hormone-free intervals and are delivered by oral, transdermal, transvaginal, injectable, or implantable routes. Effective counseling also requires an understanding of a woman's preferences and medical history as well as the risks, benefits, side effects, and contraindications of each contraceptive method. This article is designed to update physicians on this information.

  4. Cutis Marmorata Telangiectatica Congenita in a Preterm Female Newborn: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    C. De Maio


    Full Text Available Cutis Marmorata Telangiectatica Congenita (CMTC is a rare, sporadic condition usually present at birth characterized by localized or generalized persistent cutis marmorata, telangiectasia and phlebectasia. We report a preterm female newborn, the third child of non-related caucasian parents, with CMTC at birth who showed typical cutaneous features and monolateral congenital glaucoma. The pathogenesis of this disorder is unknown and the cause is probably multifactorial. Teratogens and autosomal dominant mode of inheritance with incomplete penetrance have been considered as etiological factors. Prognosis, in uncomplicated cases, is good.

  5. [Genetic and epigenetic factors of polycystic ovary syndrome]. (United States)

    Herczeg, Zita; Vanya, Melinda; Szili, Károly; Dézsi, Csilla; Nagy, Zsolt; Szabó, János


    The development of polycystic ovary syndrome and its exact pathophysiological mechanism is still unclear, but environmental and genetic factors likely play a role. Exposition to teratogenic effects during the prenatal development can lead to chronic diseases in the postnatal period. This finding confirms the common familial aggregation as well. A literature search was conducted up to January 1, 2016 for articles dealing with the genetic or epigenetic factors of polycystic ovary syndrome. This review will discuss the current understanding of the genetic basis and clinical presentation of this disease. Orv. Hetil., 2016, 157(32), 1275-1281.

  6. 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


    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.

  7. Fetal Valproate Syndrome with Limb Defects: An Indian Case Report

    Directory of Open Access Journals (Sweden)

    Manisha Goyal


    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.

  8. Thalidomide–A Notorious Sedative to a Wonder Anticancer Drug (United States)

    Zhou, Shuang; Wang, Fengfei; Hsieh, Tze-Chen; Wu, Joseph M.; Wu, Erxi


    In the past 50 years, thalidomide has undergone a remarkable metamorphosis from a notorious drug inducing birth defects into a highly effective therapy for treating leprosy and multiple myeloma. Today, most notably, thalidomide and its analogs have shown efficacy against a wide variety of diseases, including inflammation and cancer. The mechanism underlying its teratogenicity as well as its anticancer activities has been intensively studied. This review summarizes the biological effects and therapeutic uses of thalidomide and its analogs, and the underlying mechanisms of thalidomide’s action with a focus on its suppression of tumor growth. PMID:23931282

  9. Anthelmintic induced congenital malformations in sheep embryos using netobimin. (United States)

    Navarro, M; Cristofol, C; Carretero, A; Arboix, M; Ruberte, J


    Benzimidazole compounds have teratogenic effects in domestic and experimental animals. In this study, 14 Manchega ewes were treated orally, under controlled conditions, with 20 mg netobimin (a prodrug of a benzimidazole compound) per/kg bodyweight on the 17th day of pregnancy. Congenital malformations and abortions affected 60 per cent of the lambs. The main malformations were skeletal and renal, but vascular malformations were observed for the first time. The abnormalities were investigated using radiological, dissection and vascular injection techniques, and associations among them were recorded. The anomalies are discussed in terms of embryological considerations.

  10. Hazard of Sulfonamides and Detection Technology Research Progress (United States)

    Jiang, Jiahui; Wang, Guangyu


    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.

  11. Determination of metal ion contents of two antiemetic clays use in Geophagy

    Directory of Open Access Journals (Sweden)

    Solomon E. Owumi


    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.

  12. Contraceptive use and pregnancy intentions among transgender men presenting to a clinic for sex workers and their families in San Francisco. (United States)

    Cipres, Danielle; Seidman, Dominika; Cloniger, Charles; Nova, Cyd; O'Shea, Anita; Obedin-Maliver, Juno


    Although many transgender men may be able to conceive, their reproductive health needs are understudied. We retrospectively reviewed charts of transgender men presenting to a clinic for sex workers to describe the proportion at risk for pregnancy, pregnancy intentions, and contraceptive use. Of 26 transgender men identified, half were at risk for pregnancy. Most desired to avoid pregnancy but used only condoms or no contraception. Two individuals desired pregnancy, were taking testosterone (a teratogen), and not using contraception. Further research is needed to explore how to best provide family planning services including preconception and contraception care to transgender men. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Clinical trial considerations on male contraception and collection of pregnancy information from female partner: update. (United States)

    Banholzer, Maria Longauer; Wandel, Christoph; Barrow, Paul; Mannino, Marie; Schmitt, Georg; Guérard, Melanie; Müller, Lutz; Greig, Gerard; Amemiya, Kenjie; Peck, Richard; Singer, Thomas; Doessegger, Lucette


    This is an update to our 2012 publication on clinical trial considerations on male contraception and collection of pregnancy information from female partner, after critical review of recent (draft) guidances released by the International Council for Harmonisation [ICH] the Clinical Trial Facilitation Group [CTFG] and the US Food & Drug Administration [FDA]. Relevant aspects of the new guidance documents are discussed in the context of male contraception and pregnancy reporting from female partner in clinical trials and the approach is updated accordingly. Genotoxicity The concept of a threshold is introduced using acceptable daily intake/permissible daily exposure to define genotoxicity requirements, hence highly effective contraception in order to avoid conception. The duration for highly effective contraception has been extended from 74 to 90 days from the end of relevant systemic exposure. Teratogenicity Pharmacokinetic considerations to estimate safety margins have been contextualized with regard to over- and underestimation of the risk of teratogenicity transmitted by a vaginal dose. The duration of male contraception after the last dose takes into account the end of relevant systemic exposure if measured, or a default period of five half-lives after last dose for small molecules and two half-lives for immunoglobulins (mAbs). Measures to prevent exposure of the conceptus via a vaginal dose apply to reproductively competent or vasectomized men, unless measurements fail to detect the compound in seminal fluid. Critical review of new guidance documents provides a comparison across approaches and resulted in an update of our previous publication. Separate algorithms for small molecules and monoclonal antibodies are proposed to guide the recommendations for contraception for male trial participants and pregnancy reporting from female partners. No male contraception is required if the dose is below a defined threshold for genotoxic concern applicable to small

  14. Review of PAH contamination in food products and their health hazards. (United States)

    Bansal, Vasudha; Kim, Ki-Hyun


    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.

  15. European recommendations for primary prevention of congenital anomalies: A joined effort of EUROCAT and EUROPLAN projects to facilitate inclusion of this topic in the National Rare Disease Plans

    DEFF Research Database (Denmark)

    Taruscio, Domenica; Arriola, Larraitz; Baldi, Francesca


    . The resulting EUROCAT-EUROPLAN 'Recommendations on Policies to Be Considered for the Primary Prevention of Congenital Anomalies in National Plans and Strategies on Rare Diseases' were issued in 2012 and endorsed by EUCERD (European Union Committee of Experts on Rare Diseases) in 2013. The recommendations......, consideration is given to topics specifically related to CA (e.g. folate status, teratogens) as well as of broad public health impact (e.g. obesity, smoking) which call for specific attention to their relevance in the pre- and periconceptional period. The recommendations, reported entirely in this paper......, are a comprehensive tool to implement primary prevention into national policies on rare diseases in Europe....

  16. Polydactyly: A Review. (United States)

    Farrugia, Marie Claire; Calleja-Agius, Jean


    Polydactyly, also known as hyperdactyly, is a common congenital limb defect, which can present with various morphologic phenotypes. Apart from cosmetic and functional impairments, it can be the first indication of an underlying syndrome in the newborn. Usually, it follows an autosomal dominant pattern of inheritance with defects occurring in the anteroposterior patterning of limb development. Although many mutations have been discovered, teratogens have also been implicated in leading to this anomaly, thus making it of multifactorial origin. There are three polydactyly subtypes (radial, ulnar, and central), and treatment options depend on the underlying feature.

  17. Population-based case control study of the safety of sulfasalazine use during pregnancy

    DEFF Research Database (Denmark)

    Nørgård, Bente; Czeizel, A.E.; Rockenbauer, M.


    Background: We studied the human teratogenic risk of sulfasalazine because this drug interferes with folate metabolism. Methods: Case control study within the Hungarian Case Control Surveillance of Congenital Abnormalities, 1980–1996; based on 22 865 new-born infants or foetuses with congenital...... abnormalities, and 38 151 babies without any detected congenital abnormalities (control group). Results: Seventeen pregnant women (0.07%) were treated with sulfasalazine in the case group, and 26 (0.07%) in the control group. The overall adjusted adds ratio of congenital abnormalities after sulfasalazine...

  18. 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.


    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......; the corresponding figures for cases were 22,865 and 11 (0.05%). The prevalence odds ratio was 0.6 (95%CI 0.3-1.3). Analysis of isoniazid and other oral antituberculosis drug use during the second and third months of gestation, i.e., in the critical period for most major congenital abnormalities, in case...

  19. Toluene embryopathy

    Energy Technology Data Exchange (ETDEWEB)

    Hersh, J.H.; Podruch, P.E.; Rogers, G.; Weisskopf, B.


    Three children with microcephaly, central nervous system dysfunction, minor craniofacial and limb anomalies, and variable growth deficiency were born to women who inhaled large quantities of pure toluene throughout pregnancy. The features in there patients were reminiscent of the patterns of malformation previously described following in utero exposure to alcohol, certain anticonvulsants, and hyperphenylalaninemia. It is possible that there is a variable and nonspecific teratogenic phenotype characterized by alterations in growth, development, and morphogenesis. Careful evaluation and monitoring of infants exposed to toluene in utero are needed to determine the significance of these findings.

  20. Transcriptomic changes in mouse embryonic stem cells exposed to thalidomide during spontaneous differentiation

    Directory of Open Access Journals (Sweden)

    Xiugong Gao


    Full Text Available Thalidomide is a potent developmental toxicant that induces a range of birth defects, notably severe limb malformations. To unravel the molecular mechanisms underpinning the teratogenic effects of thalidomide, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on the differentiation of mouse embryonic stem cells (mESCs, and published the major findings in a research article entitled “Thalidomide induced early gene expression perturbations indicative of human embryopathy in mouse embryonic stem cells” [1]. The data presented herein contains complementary information related to the aforementioned research article.

  1. Embryonic oxidative stress as a mechanism of teratogenesis with special emphasis on diabetic embryopathy. (United States)

    Ornoy, Asher


    Reactive oxygen species (ROS) are involved in the etiology of numerous diseases including cardio-vascular diseases and diabetes mellitus. There is evidence that several teratogens affect the developing embryo by increasing its oxidative stress and, because of its relatively weak antioxidant defense, especially at the early stages of organogenesis, result in severe embryonic damage. This mechanism seems to operate in diabetes-induced embryonic damage as well as in the mechanism of teratogenicity caused by ionizing radiation, hypoxia, alcohol and cocaine use and cigarette smoking. We studied the role of oxidative stress in diabetic induced embryopathy, both in vivo and in vitro. Under diabetic condition there was a significant decrease in the activity of endogenous antioxidant enzymes and of vitamins C and E in the embryos and their yolk sacs. The lowest activity was observed in the malformed experimental embryos when compared to experimental embryos without anomalies. Similar results were obtained in the Cohen diabetic rats, where the diabetic prone (CDs) rats were unable to increase their antioxidant enzyme activity in spite of the diabetes. Studies performed by other investigators show similar results. Human and animal studies show that the main mechanism of fetal damage induced by high levels of ionizing irradiation, cocaine and alcohol abuse, hypoxia and cigarette smoking is also by increased embryonic oxidative stress. Similarly, several drugs exert their teratogenic activity via embryonic oxidative stress. Abnormal placentation may also cause enhanced placental oxidative stress, resulting in embryonic death, preeclampsia or congenital anomalies. Inability of the developing embryo to cope with that stress may result in embryonic death and/or congenital anomalies. Animal studies also show that a variety of antioxidants are effective in decreasing the damaging effects of heightened oxidative stress induced by teratogens. Effective antioxidants, which might also

  2. 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)


    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.

  3. Prenatal diagnosis by isoenzymic differentiation of Treacher Collins' syndrome induced by retinoids in rats

    DEFF Research Database (Denmark)

    Granström, G; Kirkeby, S


    ear ossicles, short cochleas, defectively differentiated Meckel's cartilages, micrognathia, rudimentary malar bones, lateral facial clefts, fistulas and skin tags, all of which were similar to Treacher Collins' syndrome in man. The defects were accompanied by a pathological differentiation pattern...... of various isoenzymes in maxillary and mandibular processes. These isoenzymes could be detected in amniotic fluid from the 9th to the 20th days of pregnancy and showed a pathological differentiation pattern here as well. We conclude that a teratogenically induced syndrome affecting the first and second...

  4. Propuesta de una metodología de asesoramiento genético prenatal para la prevención de defectos congénitos inducidos por medicamentos Proposal of a prenatal genetic counselling methodology to prevent congenital defects induced by drugs

    Directory of Open Access Journals (Sweden)

    Noel Taboada Lugo


    Full Text Available Se conoce que los medicamentos constituyen la tecnología médica más utilizada en el mundo contemporáneo. Se han identificado muchos con efectos teratogénicos. Son 2 las situaciones a las que se enfrenta el médico de la familia u otro personal facultativo que asiste a embarazadas: la de aquellas con una enfermedad crónica a quienes debe prescribirse un medicamento con potencialidades teratogénicas conocidas o no y la de otras que los consumieron o los requieren para aliviar síntomas o trastornos agudos asociados o provocados por el embarazo. Dada la relativa frecuencia con que pueden presentarse estas situaciones se relacionaron las categorías de riesgo teratogénico de algunos medicamentos y se propuso además una estrategia de asesoramiento genético prenatal para atender gestantes que requieran o hayan ingerido fármacos con determinado riesgo teratogénico o no, lo que resulta una útil herramienta en manos de los médicos de familia para prevenir defectos congénitos inducidos por medicamentos.It is known that drugs are the most advanced medical technology in the present world. Many of them have been identified with teratogenic effects. The family physician or other medical personnel giving attention to pregnant women have to face two situations: that of pregnant women with chronic diseases who should be prescribed a drug with teratogenic potentialities known or not, and that of other pregnant women that received or require them to alleviate symptoms or acute disorders associated with or caused by pregnancy. Due to the relative frequency with which these situations may occur, the categories of teratogenic risk of some drugs were related and a strategy of prenatal genetic counselling was proposed to attend gravid women who require or have taken drugs with certain teratogenic risk or not, which is a useful tool in the hands of family physicians to prevent congenital defects induced by drugs.

  5. 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


    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.........

  6. Immunotoxicity of mercury: Pathological and toxicological effects. (United States)

    Maqbool, Faheem; Niaz, Kamal; Hassan, Fatima Ismail; Khan, Fazlullah; Abdollahi, Mohammad


    Mercury (Hg) is toxic and hazardous metal that causes natural disasters in the earth's crust. Exposure to Hg occurs via various routes; like oral (fish), inhalation, dental amalgams, and skin from cosmetics. In this review, we have discussed the sources of Hg and its potential for causing toxicity in humans. In addition, we also review its bio-chemical cycling in the environment; its systemic, immunotoxic, genotoxic/carcinogenic, and teratogenic health effects; and the dietary influences; as well as the important considerations in risk assessment and management of Hg poisoning have been discussed in detail. Many harmful outcomes have been reported, which will provide more awareness.

  7. Use of TNF-inhibitors and ustekinumab for psoriasis during pregnancy

    DEFF Research Database (Denmark)

    Lund, Tamara; Thomsen, Simon Francis


    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......, but so far appears to be safe due to the lack of absorption across the gastrointestinal lining. Currently biological therapy with either TNF-inhibitors or ustekinumab is not recommended during pregnancy, however in selected women with severe psoriasis these treatment modalities may be considered....

  8. Placental examination in intrauterine coinfection with herpes simplex virus and cytomegalovirus. (United States)

    Mühlemann, K; Menegus, M A


    Intrauterine coinfections have rarely been reported. However, pregnancies exposed to multiple sexually transmitted infectious agents and drugs are likely to occur with increasing frequency and lead to complex pathology in the newborn. Often it will be difficult to establish a diagnosis, above all when this has to be done retrospectively. A premature (34 weeks) newborn presented with a complex clinical picture after exposure to multiple infectious and noninfectious teratogens during gestation. Immunocytochemical staining of the placental membranes and parenchyma suggested intrauterine coinfection by herpes simplex virus (HSV) type 2 and cytomegalovirus. This case illustrates the importance of careful placental investigation with modern techniques for the diagnosis of intrauterine HSV infection and coinfections.

  9. Can exposure to electromagnetic radiation in diathermy operators be estimated from interview data? A pilot study. (United States)

    Larsen, A I; Skotte, J


    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.

  10. The Impact of Proposed Radio Frequency Radiation Standards on Military Operations. (United States)


    Teratogenesis in Tenebrio Molitor to the Incidence of Low-Level Microwaves," IEEE Trans. Microwave The- ory and Tech., 23(11):929-931, 1975. 47. Green, D.R...F.J. Rosenbaum, and W.F. Pickard, "Intensity of Microwave Irradia- tion and the Teratogenic Response of Tenebrio molitor ," Radio Sol., Vol. 14, No. 6S...pp. 181-185 (1979). 48. Pickard, W.F., and R.G. Olsen, "Developmental Effects of MIcrowaves on Tenebrio ; Influences of Culturing Protocol and of

  11. Ethanol and Cognition: Indirect Effects, Neurotoxicity and Neuroprotection: A Review

    Directory of Open Access Journals (Sweden)

    John C.M. Brust


    Full Text Available Ethanol affects cognition in a number of ways. Indirect effects include intoxication, withdrawal, brain trauma, central nervous system infection, hypoglycemia, hepatic failure, and Marchiafava-Bignami disease. Nutritional deficiency can cause pellagra and Wernicke-Korsakoff disorder. Additionally, ethanol is a direct neurotoxin and in sufficient dosage can cause lasting dementia. However, ethanol also has neuroprotectant properties and in low-to-moderate dosage reduces the risk of dementia, including Alzheimer type. In fetuses ethanol is teratogenic, and whether there exists a safe dose during pregnancy is uncertain and controversial.

  12. Ochratoxin A exposure biomarkers in the Czech Republic and comparison with foreign countries. (United States)

    Malir, Frantisek; Ostry, Vladimir; Pfohl-Leszkowicz, Annie; Roubal, Tomas


    Among ochratoxins, ochratoxin A (OTA) occupies a dominant place and represents significant risk for human and animal health which also implies economic losses around the world. OTA is nephrotoxic, hepatotoxic, teratogenic and immunotoxic mycotoxin. OTA exposure may lead to formation of DNA adducts resulting to genotoxicity and carcinogenicity (human carcinogen of 2B group). Now it seems that OTA could be "a complete carcinogen" which obliges to monitor its presence in biological materials, especially using the suitable biomarkers. In this article, OTA findings in urine, blood, serum, plasma and human kidneys (target dose) in the Czech Republic and comparison with foreign countries are presented.

  13. 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


    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.

  14. The effect of perinatal hormonal imprinting with 13-cis-retinoic acid (isotretinoin) on the thymic glucocorticoid receptors of female and testosterone level of male adult rats. (United States)

    Csaba, G; Gaál, A; Inczefi-Gonda, A


    In earlier experiments, the long-term effect of perinatal treatment (hormonal imprinting) with all-trans-retinol and all-trans-retinoic acid on the thymic glucocorticoid and uterine estrogen receptors was studied and was found effective. In the present experiments, the imprinting effect of four retinoids (13-cis-retinaldehyde, 13-cis-retinoic acid, 9-cis-retinaldehyde and 9-cis-retinoic acid) was investigated, using receptor kinetic analysis and sexual hormone (testosterone and progesterone) level determinations. Exclusively 13-cis-retinoic acid (isotretinoin) had an effect, significantly decreasing glucocorticoid receptor affinity and increasing serum testosterone level. Relationships with RAR-RXR receptor binding and teratogenicity is discussed.

  15. 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...

  16. 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


    Objective: Our purpose was to study the human teratogenic potential of cephalosporin treatment during pregnancy. Study Design: Pair analysis of cases with congenital abnormalities and matched controls without congenital abnormalities was performed. The population-based data set of the Hungarian...... delivered of babies affected with Down syndrome (patient controls). Results: In the case group, 308 (1.35%) pregnant women were treated with cephalosporin. In the population and patient control groups, 440 (1.15%) and 16 (1.97%) pregnant women had similar treatments. The somewhat higher use...

  17. Amended safety assessment of Sesamum indicum (sesame) seed oil, hydrogenated sesame seed oil, Sesamum indicum (sesame) oil unsaponifiables, and sodium sesameseedate. (United States)

    Johnson, Wilbur; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan


    Sesamum indicum (sesame) seed oil and related cosmetic ingredients are derived from Sesamum indicum. Sesamum indicum (sesame) seed oil, sesamum indicum (sesame) oil unsaponifiables, and hydrogenated sesame seed oil function as conditioning agents. Sodium sesameseedate functions as a cleansing agent, emulsifying agent, and a nonaqueous viscosity increasing agent. These ingredients are neither skin irritants, sensitizers, teratogens, nor carcinogens at exposures that would result from cosmetic use. Both animal and human data relevant to the cosmetic use of these ingredients were reviewed. The CIR Expert Panel concluded that these ingredients are safe in the present practices of use and concentration as described in this safety assessment.

  18. 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


    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...... increased plasticity in the neocortex. Enhanced plasticity introduces a surprising perspective to the potential molecular and synaptic mechanisms involved in children prenatally exposed to VPA.......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...

  19. [Isotretinoin (RoAccutane) embryopathy. A case report]. (United States)

    Pilorget, H; Alessandri, J L; Montbrun, A; Ah-Hot, M; Orvain, E; Tilmont, P


    Retinoids are synthetic vitamin A derivatives, particularly used in dermatology. Their prescription in women of childbearing age can cause, if pregnancy occurs, a serious malformative embryopathy, mainly involving external ear, brain and heart. A neonatal case caused by isotretinoin (RoAccutane) emphasizes the clinical and epidemiological data concerning this embryopathy. The aetiopathological hypothesis of an interaction between isotretinoin and Hox genes is advanced. Prophylactic measures are difficult since neonatal reported cases are uncommon, but antenatal exposition to this strong teratogenic agent results in multiple spontaneous abortions or pregnancy interruptions.

  20. VACTERL association and Moebius syndrome in a newborn girl prenatally exposed to misoprostol = Asociación VACTERL y síndrome de Moebius en un recién nacido expuesto prenatalmente a misoprostol

    Directory of Open Access Journals (Sweden)

    Ramírez Cheyne, Julián


    Full Text Available Misoprostol, a synthetic analogue of prostaglandin E1, has been associated with an increased risk of occurrence of the Moebius syndrome (congenital paralysis of the seventh cranial nerve that may be associated with involvement of other cranial nerves or of other systems and cross-terminal limb defects in pregnancies in which mothers used this drug during the first trimester of pregnancy. Vascular disruption has been proposed as a teratogenic mechanism of misoprostol. The VACTERL association is the statistically non-random co-occurrence of vertebral defects, vascular anomalies, anal atresia, cardiac abnormalities, tracheo-esophageal fistula with esophageal atresia, radial and renal dysplasia, and other limb anomalies. There is no evidence for a unifying cause for the co-occurrence of VACTERL malformations, so this condition is still called an association and not a syndrome. We report the case of a newborn girl with VACTERL association and Moebius syndrome associated with prenatal exposure to misoprostol in the first trimester of pregnancy. Given the teratogenic mechanism of misoprostol, we propose a vascular origin for VACTERL association.

  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. The impact of thalidomide use in birth defects in Brazil. (United States)

    Sales Luiz Vianna, Fernanda; Kowalski, Thayne Woycinck; Fraga, Lucas Rosa; Sanseverino, Maria Teresa Vieira; Schuler-Faccini, Lavinia


    Although the thalidomide tragedy occurred more than 50 years ago, the medication is still being used worldwide for different reasons, and several aspects regarding its teratogenicity remain unsolved. Despite the strict regulation implemented, new cases of thalidomide embryopathy (TE) are still being registered in Brazil. Furthermore, the molecular processes that lead to malformations when the embryo is exposed to thalidomide have not yet been fully identified. In this article, we perform a critical analysis of thalidomide's history in Brazil, highlighting aspects of the occurrence of TE over the decades. Finally, we present the main perspectives and challenges for ongoing surveillance and prevention of TE in Brazil. The effective control of dispensing thalidomide, especially in areas where leprosy is endemic, is one of the most important and challenging points. Furthermore, the emergence of thalidomide analogues is fast approaching, and their availability would pose additional concerns. The understanding of the molecular mechanisms and targets of thalidomide in both experimental and human models is essential for generating new insights into teratogenic mechanisms, so that safer thalidomide analogues can be developed. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Biological evaluation of both enantiomers of fluoro-thalidomide using human myeloma cell line H929 and others. (United States)

    Tokunaga, Etsuko; Akiyama, Hidehiko; Soloshonok, Vadim A; Inoue, Yuki; Hara, Hideaki; Shibata, Norio


    Over the last few years, thalidomide has become one of the most important anti-tumour drugs for the treatment of relapsed-refractory multiple myeloma. However, besides its undesirable teratogenic side effect, its configurational instability critically limits any further therapeutic improvements of this drug. In 1999, we developed fluoro-thalidomide which is a bioisostere of thalidomide, but, in sharp contrast to the latter, it is configurationally stable and readily available in both enantiomeric forms. The biological activity of fluoro-thalidomide however, still remains virtually unstudied, with the exception that fluoro-thalidomide is not teratogenic. Herein, we report the first biological evaluation of fluoro-thalidomide in racemic and in both (R)- and (S)-enantiomerically pure forms against (in vitro) H929 cells of multiple myeloma (MM) using an annexin V assay. We demonstrate that all fluoro-thalidomides inhibited the growth of H929 MM cells without any in-vivo activation. Furthermore, we report that the enantiomeric forms of fluoro-thalidomide display different anti-tumour activities, with the (S)-enantiomer being noticeably more potent. The angiogenesis of fluoro-thalidomides is also investigated and compared to thalidomide. The data obtained in this study paves the way towards novel pharmaceutical research on fluoro-thalidomides.

  4. The role of diclofenack on inducing of aplasia cutis congenita: a case report (United States)


    Background 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. Case report 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. Conclusion 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. PMID:19946521

  5. Pregnancy in Systemic Lupus Erythematosus Patients with Nephritis

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    Panagiotis Pateinakis


    Full Text Available Pregnancy in patients with lupus nephritis is a challenging clinical situation. Although not absolutely contraindicated, it is associated with increased risk for foetal and maternal complications, including foetal loss, preterm delivery, intrauterine growth retardation, hypertension, pre-eclampsia, nephritis flare, and, rarely, maternal death. The complication rate is further increased in the presence of antiphospholipid antibodies or the antiphospholipid syndrome. Proliferative classes of nephritis (III and IV also appear to confer excess risk for complications. Immunosuppressives such as cyclophosphamide and mycophenolate, and antihypertensives such as angiotensin-converting-enzyme (ACE inhibitors and angiotensin receptor blockers need to be stopped due to teratogenic effects. Agents like corticosteroids, azathioprine, and probably calcineurin inhibitors are considered compatible with gestation. Lupus activity needs to be assessed and carefully monitored. Thrombotic risk due to antiphospholipid antibodies, thrombotic events, or nephrosis needs to be evaluated and managed accordingly, with the use of aspirin and/or unfractioned or low molecular weight heparin. Differentiating between severe pre-eclampsia and lupus nephritis flare might require a renal biopsy, which might not always be feasible, for example after the 32nd gestational week or in a setting of uncontrolled hypertension or thrombocytopaenia. A 6-month history of quiescent disease on non-teratogenic agents seems to be associated with best chance for favourable outcomes. Pregnancy is optimally managed by a multidisciplinary team of experienced specialists, and close monitoring for disease activity during gestation; additionally, follow-up for maternal flare postpartum is also advised.

  6. Ultrastructural changes in the developing chicken cornea following caffeine administration.

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    Bartel Hieronim


    Full Text Available Caffeine is one of the most frequently consumed psychoactive substances. It has been known for many years that caffeine at high concentrations exerts harmful effects on both women's and laboratory animals' fertility, moreover it may impair normal development of many organs in the prenatal period. So far there have been few studies performed that demonstrate teratogenic effects of caffeine on structures of the developing eye, particularly the cornea. The aim of the study was to show ultrastructural changes in the developing cornea, as the effect of caffeine administration to chicken embryos. The experimental materials were 26 chicken embryos from incubated breeding eggs. Eggs were divided into two groups: control (n=30 in which Ringer liquid was administrated, and experimental (n=30 in which teratogenic dose of caffeine 3.5mg/egg was given. In 36th hour of incubation solutions were given with cannula through hole in an egg shell directly onto amniotic membrane. After closing the hole with a glass plate and paraffine, eggs were put back to incubator. In 10th and 19th day of incubation corneas were taken for morphological analysis with a use of electron microscopy. Administration of caffeine during chicken development causes changes of collagen fibers of Bowman's membrane patterns and of the corneal stroma but it also changes proportion of amount of collagen fibers and of the stromal cells.

  7. Approach to Investigating Congenital Skeletal Abnormalities in Livestock. (United States)

    Dittmer, K E; Thompson, K G


    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.

  8. Toxico-pathological effects of in ovo inoculation of ochratoxin A (OTA) in chick embryos and subsequently in hatched chicks. (United States)

    Zahoor-ul-Hassan; Khan, Muhammad Zargham; Saleemi, Muhammad Kashif; Khan, Ahrar; Javed, Ijaz; Bhatti, Sheraz Ahmed


    This study was designed to investigate the toxico-pathological effects of in ovo inoculation of ochratoxin A (OTA) in chicken embryos and subsequently in the hatching chicks. Nine hundred fertile white leghorn (WL) layer breeder eggs were divided into eight groups (A-H). Group A was maintained as untreated control, whereas group B was kept as sham control (10 µL of 0.1 M NaHCO(3) solution). Before incubation, groups C, D, E, F, G, and H were injected with 0.01, 0.03, 0.05, 0.10, 0.50, and 1.00 µg OTA/egg, respectively. At 53 hrs of incubation, crown to rump length, optic cups, and eye lens diameters were significantly (p ≤ .05) lower, whereas neural tube closure defects were higher in the OTA-treated embryos. Teratogenic defects (studied at day 9 of incubation) and embryonic mortalities were higher in the groups administered high doses of OTA. A significant increase was noted in the serum concentration of ALT, urea, and creatinine, along with higher weights of liver and kidney, in chicks hatched from OTA-contaminated eggs. These findings suggested that there are teratogenic and substantive toxicological risks in the developing chicken embryos and hatched chicks that could be exposed to OTA in ovo.

  9. Prenatal choline supplementation mitigates behavioral alterations associated with prenatal alcohol exposure in rats. (United States)

    Thomas, Jennifer D; Idrus, Nirelia M; Monk, Bradley R; Dominguez, Hector D


    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.

  10. First-trimester anesthesia exposure and the risk of central nervous system defects: a population-based case-control study. (United States)

    Sylvester, G C; Khoury, M J; Lu, X; Erickson, J D


    Although up to 2% of women undergo surgery during pregnancy, teratogenic effects of general anesthesia have not been adequately studied. Recently, an association between first-trimester operations and central nervous system defects has been described. This issue was explored in a population-based case-control study. Case patients included live-born and stillborn infants with central nervous system defects born to residents of metropolitan Atlanta, Ga, between 1968 and 1980. Control patients included normal babies frequency matched to case patients by race, birth hospital, and period of birth. Conditional logistic regression analysis was used to adjust for potential confounding factors. Of 694 mothers of infants with central nervous system defects, 12 reported first-trimester anesthesia exposure; 34 of 2984 control mothers reported such exposure (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 0.8, 3.3). A striking association was observed between reported anesthesia exposure and hydrocephalus with another major defect (OR = 9.6, 95% CI = 3.8, 24.6). The strongest association was that of anesthesia exposure with hydrocephalus and eye defects (OR = 39.6, 95% CI = 7.5, 209.2). An increased risk of hydrocephalus with other defects was found among offspring of mothers with reported first-trimester anesthesia. Further studies are needed to explore the possible teratogenic effects of general anesthesia.

  11. [Wilson's disease and its pharmacological treatment]. (United States)

    Hayashi, Hisao; Suzuki, Rie; Wakusawa, Shinya


    Wilson's disease is an inherited copper toxicosis caused by defective putative copper transporting ATPase in the liver. Because of impaired biliary secretion, copper remains in the liver, resulting in chronic hepatic lesions including fatty metamorphosis, chronic hepatitis and cirrhosis. In the latter stage, extrapyramidal syndromes may develop with and without symptomatic hepatic lesions. Acute liver damage associated with hemolysis and deep jaundice may be the first manifestation. The majority of patients show hypoceruloplasminemia, which has been used as a screening test for the disease. A large number of mutations in the ATP7B gene have been reported. Thus, genetic diagnosis might be limitedly used to presymptomatic diagnosis of siblings when mutations are identified in an index patient. Introduction of penicillamine caused a revolution in the treatment of patients. Another chelater, trientine, is now available for those intolerant of penicillamine. Tetrathiomolibdate and zinc acetate are additional alternatives currently being tested. Hypoceruloplasminemia and further reduction after chelation therapy may be associated with iron overload. This complication is closely related with impaired transport of ferrous ion due to ferroxidase deficiency. Noncompliance and teratogenicity are other major concerns because any treatment with the agents listed above is a life long regimen. Despite various side effects of penicillamine, its teratogenicity is negligible. These data indicate that penicillamine is the first choice of drug for this disease.

  12. A Comparison Study of the Effects of Echinacea purpurea Ethanolic Extract and Mesna on Cyclophosphamide-Induced Macroscopic Fetal Defects in Rats

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    Hossein Najafzadeh Varzi


    Full Text Available Objective(s There are some reports that the teratogenic effects of cyclophosphamide (CPA can be prevented by application of antioxidant drugs and stimulation of the maternal immune system. Echinacea purpurea extract is antioxidative and immunomodulator drug. Mesna (Sodium 2-mercaptoethane sulfonate is used for decreasing side effects of CPA, especially hemorrhagic cystitis. In this study, we compared the prophylactic effects of mesna and Echinacea extract on teratogenic effects of CPA. Materials and Methods This study was performed on 32 pregnant rats that were divided into 4 groups. The first group (control group received normal saline and the other groups received CPA (15 mg/kg intraperitoneally on 13th day of gestation. Mesna and E. purpurea extracts were administrated at doses of 100 and 400 mg/kg by IP injection, respectively, along with it and 12 hr later, after CPA injection. Rats were dissected on day 20 of gestation, embryos harvested and after determination of gross malformations they were stained by Alizarin red-Alcian blue method. ResultsCleft palate incidence was 38.46, 30.77 and 14.28% in fetuses of rats that received only CPA, CPA with mesna and CPA with Echinacea extract, respectively. In addition, skeletal anomalies incidence including limbs, vertebra, sternum, and scapula defects were decreased by Echinacea extract.ConclusionE. purpurea has significant effect on preventing CPA-induced malformations and better prophylactic effect than mesna on cases like CPA-induced cleft palate.

  13. Hydra, a model system for environmental studies. (United States)

    Quinn, Brian; Gagné, François; Blaise, Christian


    Hydra have been extensively used for studying the teratogenic and toxic potential of numerous toxins throughout the years and are more recently growing in popularity to assess the impacts of environmental pollutants. Hydra are an appropriate bioindicator species for use in environmental assessment owing to their easily measurable physical (morphology), biochemical (xenobiotic biotransformation; oxidative stress), behavioural (feeding) and reproductive (sexual and asexual) endpoints. Hydra also possess an unparalleled ability to regenerate, allowing the assessment of teratogenic compounds and the impact of contaminants on stem cells. Importantly, Hydra are ubiquitous throughout freshwater environments and relatively easy to culture making them appropriate for use in small scale bioassay systems. Hydra have been used to assess the environmental impacts of numerous environmental pollutants including metals, organic toxicants (including pharmaceuticals and endocrine disrupting compounds), nanomaterials and industrial and municipal effluents. They have been found to be among the most sensitive animals tested for metals and certain effluents, comparing favourably with more standardised toxicity tests. Despite their lack of use in formalised monitoring programmes, Hydra have been extensively used and are regarded as a model organism in aquatic toxicology.

  14. Organizer formation in Hydra is disrupted by thalidomide treatment. (United States)

    Brooun, Maria; Manoukian, Armen; Shimizu, Hiroshi; Bode, Hans R; McNeill, Helen


    Thalidomide is a drug that is well known for its teratogenic properties in humans. Surprisingly, thalidomide does not have teratogenic effects on mouse development. We investigated the effect of thalidomide on patterning in hydra, an early metazoan with a very simple axial symmetry. Hydra develops asexually via Wnt-dependent organizer formation, leading to the budding of a new organism. We observe both induction and inhibition of organizer formation depending on cellular context. Interestingly, thalidomide treatment altered budding and the developing organizer, but had little effect on the adult. Expression of Hybra1, a marker of the organizer increased upon thalidomide treatment. However when the organizer is induced by ectopic activation of Wnt signaling via GSK3 inhibition, thalidomide suppresses induction. We show that inhibition of Wnt signaling is not mediated by induction of the BMP pathway. We show that thalidomide activity on organizer formation in hydra depends on the activity of casein kinase1 and the abundance of β-catenin. Finally, we find that interstitial cells, multipotent cells which give rise to nemoatocytes, neural, digestive and germline cells, are partially responsible for the inhibitory effect of thalidomide. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Therapeutic Potential of Thalidomide and Its Analogues in the Treatment of Cancer. (United States)

    Sherbet, Gajanan V


    Thalidomide was synthesised and launched several decades ago as a drug against respiratory infections and was administered to pregnant women for relief of morning sickness. The drug was withdrawn when its teratogenic effects came to light. Thalidomide and its analogues suppressed cell proliferation and angiogenesis and controlled invasion and metastasis of tumours in pre-clinical studies. With the recognition of its immunomodulatory and anti-inflammatory, properties, thalidomide may have found a place in the treatment of many forms of cancer and autoimmune conditions. Herein the signalling pathways modulated by thalidomides via the mediation of vascular endothelial growth factor, phosphoinositide-kinase/protein kinase B and nuclear factor kappa B, and mammalian target of rapamycin, which integrates these signalling systems, are discussed. The mode of action of thalidomides and their strategic utility in therapy are evaluated in the context of potential clinical benefits. Notwithstanding the perceived benefits, the side-effects of thalidomides need to be taken into account; they do exert teratogenic effects in animal models, although being effective at lower doses, the drugs seem to show comparatively manageable and reduced toxicity. Combination therapy of thalidomides and modulators of signaling that they influence may further reduce the severity of the side-effects by delivering inhibitory effects at reduced drug dosages. Pre-clinical evaluations of this kind seem warranted. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Transcriptomic Analysis of Thalidomide Challenged Chick Embryo Suggests Possible Link between Impaired Vasculogenesis and Defective Organogenesis. (United States)

    Veeriah, Vimal; Kumar, Pavitra; Sundaresan, Lakshmikirupa; Mafitha, Zeenath; Gupta, Ravi; Saran, Uttara; Manivannan, Jeganathan; Chatterjee, Suvro


    Since the conception of thalidomide as a teratogen, approximately 30 hypotheses have been put forward to explain the developmental toxicity of the molecule. However, no systems biology approach has been taken to understand the phenomena yet. The proposed work was aimed to explore the mechanism of thalidomide toxicity in developing chick embryo in the context of transcriptomics by using genome wide RNA sequencing data. In this study, we challenged the developing embryo at the stage of blood island formations (HH8), which is the most vulnerable stage for thalidomide-induced deformities. We observed that thalidomide affected the early vasculogenesis through interfering with the blood island formation extending the effect to organogenesis. The transcriptome analyses of the embryos collected on sixth day of incubation showed that liver, eye, and blood tissue associated genes were down regulated due to thalidomide treatment. The conserved gene coexpression module also indicated that the genes involved in lens development were heavily affected. Further, the Gene Ontology analysis explored that the pathways of eye development, retinol metabolism, and cartilage development were dampened, consistent with the observed deformities of various organs. The study concludes that thalidomide exerts its toxic teratogenic effects through interfering with early extra-embryonic vasculogenesis and ultimately gives an erroneous transcriptomic pattern to organogenesis.

  17. Effective treatment of gastrointestinal bleeding with thalidomide - Chances and limitations (United States)

    Bauditz, Juergen


    For more than 50 years bleeding from gastrointestinal angiodysplasias has been treated by hormonal therapy with estrogens and progesterons. After a randomized study finally demonstrated that hormones have no effect on bleeding events and transfusion requirements, therapy has switched to endoscopic coagulation. However, angiodysplasias tend to recur over months to years and endoscopy often has to be repeated for long time periods. Thalidomide, which caused severe deformities in newborn children in the 1960s, is now increasingly used after it was shown to suppress tumor necrosis factor alpha, inhibit angiogenesis and to be also effective for treatment of multiple myeloma. In 2011 thalidomide was proven to be highly effective for treatment of bleeding from gastrointestinal angiodysplasias in a randomized study. Further evidence by uncontrolled studies exists that thalidomide is also useful for treatment of bleeding in hereditary hemorrhagic telangiectasia. In spite of this data, endoscopic therapy remains the treatment of choice in many hospitals, as thalidomide is still notorious for its teratogenicity. However, patients with gastrointestinal bleeding related to angiodysplasias are generally at an age in which women have no child-bearing potential. Teratogenicity is therefore no issue for these elderly patients. Other side-effects of thalidomide like neurotoxicity may limit treatment options but can be monitored safely. PMID:27003992

  18. A preliminary assessment of the toxic and mutagenic potential of steroidal alkaloids in transgenic mice. (United States)

    Crawford, L; Myhr, B


    Impregnated CD2 transgenic mice, which contain multiple copies of a lambda gt10lacZ construct integrated into the genome of each cell, were given a predetermined estimated maximum tolerated dose of several steroidal alkaloids: Solanum glycoalkaloids from potato, alpha-chaconine and alpha-solanine; aglycones, solanidine and solasodine, and a Veratrum alkaloid, jervine. Observations were made of dams and foetuses for indications of toxicity and/or terata; some dam livers and foetuses were assayed for mutagenicity using the lacZ gene. Other dams were gavaged with a single dose of 75 mg all-trans-retinol/kg to serve as a reference teratogen. Unexpectedly, this level of retinol was not clearly teratogenic. The results of both positive and non-positive selection systems showed that the mutation frequencies in the livers of the dams dosed with alpha-chaconine, alpha-solanine and solanidine were three to four times higher than historically normal in the livers of this transgenic mouse strain.

  19. Selective serotonin reuptake inhibitor exposure during early pregnancy and the risk of birth defects. (United States)

    Gentile, S


    To assess the methodological value of studies that signaled one or more selective serotonin reuptake inhibitors (SSRIs) as teratogenic agents. Medical literature, published in English (1980-November 2010), was searched using MEDLINE/PubMed, TOXNET, EMBASE, and The Cochrane Library to identify all articles, reporting primary data that suggested any increased rate of congenital malformations following prenatal exposure to SSRIs as a group or single SSRI agents. Reviewed studies showed some severe methodological limitations, such as data coming from retrospective studies and incomplete information available with reference to timing of exposure and dosages. Further, data continue to be extrapolated from automated databases that do not declare whether the women reported actually used the prescribed medication. Further, it should be noted the distinct lack of research analysis available with reference to the potential impact of non-iatrogenic confounders on pregnancy. In light of such considerations, the hypothesized teratogenicity of SSRIs remains undemonstrated. Hence, further, well-designed research is needed to differentiate definitively the detrimental impact of depression on pregnancy outcomes from potential iatrogenic events. © 2011 John Wiley & Sons A/S.

  20. Effects of Cadmium and Zinc on the Gamete Viability, Fertilization, and Embryonic Development of Tripneustes gratilla (Linnaeus

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    Ivan Patrick B. Tualla


    Full Text Available Heavy metals are frequently reported for their mutagenic and teratogenic effects on benthic organisms. Thus, this study aimed to determine the toxicity of cadmium (Cd and zinc (Zn in the gametes of T. gratilla and to compare its fertilization and embryonic development under the highest nongametotoxic concentrations of these heavy metals. Gamete viability of T. gratilla under CdCl2 and ZnSO4 treatments was assayed through resazurin reduction test (RRT and was confirmed through gamete morphology assay. ZnSO4 was more toxic to T. gratilla gametes than CdCl2 and egg cells were more sensitive to both than the sperm cells. Higher concentrations of CdCl2 and ZnSO4 induced gamete apoptosis and necrosis while highest nongametotoxic concentrations were determined at 1 × 10−3 M and 1 × 10−4 M, respectively, and were used in an in vitro fertilization and embryonic development experiment. ZnSO4 treatment inhibited fertilization more than CdCl2 and yielded more deformed embryos, while both induced abnormalities and hindered further embryonic development. This study gives the first report on the specific concentrations of Cd and Zn that are toxic to T. gratilla gametes and has confirmed the teratogenic effects of these heavy metals.

  1. Detection and investigation of temporal clusters of congenital anomaly in Europe: seven years of experience of the EUROCAT surveillance system. (United States)

    Dolk, Helen; Loane, Maria; Teljeur, Conor; Densem, James; Greenlees, Ruth; McCullough, Nichola; Morris, Joan; Nelen, Vera; Bianchi, Fabrizio; Kelly, Alan


    Detection and investigation of congenital anomaly clusters is one part of surveillance to detect new or changing teratogenic exposures in the population. The EUROCAT (European Surveillance of Congenital Anomalies) cluster monitoring system and results are described here. Monitoring was conducted annually from 2007 to 2013 for 18 registries covering an annual birth population up to 0.5 million births. For each registry and 72 anomaly subgroups, the scan "moving window" technique was used to detect clusters in time occurring within the last 2 years based on estimated date of conception. Registries conducted preliminary investigations using a standardised protocol to determine whether there was cause for concern, and expert review was used at key points. 165 clusters were detected, a rate of 3.4% of all 4823 cluster tests performed over 7 years, more than expected by chance. Preliminary investigations of 126 new clusters confirmed that 35% were an unusual aggregation of cases, while 56% were explained by data quality or diagnostic issues, and 9% were not investigated. For confirmed clusters, the registries' course of action was continuing monitoring. Three confirmed clusters continued to grow in size for a limited period in subsequent monitoring. This system is best suited to early detection of exposures which are sudden, widespread and/or highly teratogenic, and was reassuring in demonstrating an absence of a sustained exposure of this type. Such proactive monitoring can be run efficiently without overwhelming the surveillance system with false positives, and serves an additional purpose of data quality control.

  2. [Particularities of epileptic women's care]. (United States)

    Ben Hamouda, Ibtissem; Mrabet, Amel


    Development on the epileptic women's care. A research in the medical literature on PubMed and an exhaustive review of the published summaries and reports of Epileptology International Meetings, in the last five years. We included cohort studies, reviews and randomized double blinded therapeutic trials. Case reports and fundamental research studies have been excluded. sensitizing of the epileptic women starts with adolescence with an education and a preparation to sexual life and available contraceptive methods, in order to avoid undesired pregnancies and the serious consequences which they are likely to generate. Approximately 1/3 of the epileptic women have variations of their disease related to the menstrual cycle, probably because of a neurotoxic effect of estrogens (not counterbalanced by progestational hormones). Antiepileptic teratogenicity issue is not, yet, solved, in spite of new molecules commercialisation. The upkeep of a register concerning the use of AED during pregnancy makes it possible to better identify the problems and to establish an optimal therapeutic control for the mother and the child. Epilepsy impact on women's life is very different compared to men, because it interferes with the fields of sexuality, reproduction, menstrual cycle and contraception, in addition of AED teratogenicity. A close cooperation between obstetricians and neurologist and a sensitizing of health professionals are essential for the global care of the epileptic pregnant women or in age of procreation.

  3. Experimental methods in behavioral teratology

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    Zbinden, G.


    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.

  4. Epilepsy during pregnancy: focus on management strategies

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    Borgelt LM


    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

  5. 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


    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.

  6. Risk from exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans emitted from municipal incinerators

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    Maukerjee, D.; Cleverly, D.H.


    Incineration of wastes seems to be one of the major sources of PCDDs and PCDFs (dioxins). Their prevalence and extreme stability in the environment, bioavailability and bioaccumulation in the biota and human adipose tissues and breast milk are of much concern. 2,3,7,8-TCDD is one of the most toxic chemicals known and has been found to have teratogenic and carcinogenic activities in animals. Exposure to TCDD can result in chloracne, general weakness, drastic weight loss, hyperpigmentation of skin, hirsutism, porphyria cutanea tarda, liver damage, changes in activities of various liver enzymatic levels, abnormal lipid metabolism, abnormalities of the endocrine and immune systems, and possible teratogenic effects in humans. Moreover, chronic bioassay data indicate that TCDD is one of the most potent carcinogens known. It promotes liver and skin carcinogeneses, and is an initiator for various target organs in rodent test systems. According to the classification system of IARC, the qualitative evidence for carcinogenicity of TCDD is considered to be sufficient in animals and inadequate in humans. Consequently, TCDD has been placed in IARC's 2B category. In the absence of chronic bioassay data on other PCDDs and PCDFs, several TCDD equivalent approaches have been proposed for risk assessment on other congeners or mixtures. The paper compares the various approaches.

  7. Incidence of cleft pathology in Greater New Orleans before and after Hurricane Katrina. (United States)

    Goenjian, Haig A; Chiu, Ernest S; Alexander, Mary Ellen; St Hilaire, Hugo; Moses, Michael


    Reports after the 2005 Hurricane Katrina have documented an increase in stress reactions and environmental teratogens (arsenic, mold, alcohol). To assess the incidence of cleft pathology before and after the hurricane, and the distribution of cleft cases by gender and race. Retrospective chart review of cleft lip with or without cleft palate (CL/P) and cleft palate (CP) cases registered with the Cleft and Craniofacial Team at Children's Hospital of New Orleans, the surgical center that treated cleft cases in Greater New Orleans between 2004 and 2007. Live birth data were obtained from the Louisiana State Center for Health Statistics. The incidence of cleft cases, beginning 9 months after the hurricane (i.e., June 1, 2006) was significantly higher compared with the period before the hurricane (0.80 versus 1.42; p = .008). Within racial group comparisons showed a higher incidence among African Americans versus whites (0.42 versus 1.22; p = .01). The distribution of CL/P and CP cases by gender was significant (p = .05). The increase in the incidence of cleft cases after the hurricane may be attributable to increased stress and teratogenic factors associated with the hurricane. The increase among African Americans may have been due to comparatively higher exposure to environmental risk factors. These findings warrant further investigation to replicate the results elsewhere in the Gulf to determine whether there is a causal relationship between environmental risk factors and increased cleft pathology.

  8. The Fetal Safety of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

    Directory of Open Access Journals (Sweden)

    Myla E. Moretti


    Full Text Available Angiotensin converting enzyme (ACE inhibitors and angiotensin II receptor blockers (ARBs are known to cause fetal renal damage in pregnancy. Due to conflicting reports in the literature, their safety after first trimester exposure has been debated. Our aim was to determine whether the use of ACE inhibitors or ARBs in the first trimester of pregnancy is associated with an increased risk for major malformations or other adverse outcomes. All subjects were prospectively enrolled from among women contacting a teratogen information service. At initial contact, details of maternal medical history and exposures were collected and follow-up interviews were conducted to ascertain pregnancy outcomes. Two comparator groups, women with hypertension treated with other antihypertensives, and healthy controls were also recruited. Baseline maternal characteristics were not different among the three groups. There were no differences in rates of major malformations. Both the ACE-ARBs and disease-matched groups exhibited significantly lower birth weight and gestational ages than the healthy controls (P<0.001 for both variables. There was a significantly higher rate of miscarriage noted in the ACE/ARB group (P<0.001. These results suggest that ACE inhibitors/ARBs are not major human teratogens; however, they may be associated with an increased risk for miscarriage.

  9. Diabetic embryopathy. (United States)

    Eriksson, Ulf J; Wentzel, Parri


    Diabetic embryopathy reflects a scientific enigma--how does a seemingly rich intrauterine environment manage to disturb the development of the embryo? Which compounds in that environment may be teratogenic--and how shall we find them? How can we investigate a putative dose-response nature of the teratogen, i.e., how can we monitor the effects of varied severity of the diabetic state (which can be varied in a number of metabolic ways) on the embryonic development? Here, the whole embryo culture (WEC) technique provides an excellent tool for such studies. WEC is thus currently used to investigate the effect of graded levels of diabetes (e.g., hyperglycemia, hyperketonemia, increased branched chain amino acid (BCAA) levels), and putative antiteratogenic agents (antioxidants, folic acid, arachidonic acid, inositol), as well as the effect of different embryonic genotypes on diabetes-induced (mal)development. WEC is the only method, which is able to couple specific embryonic maldevelopment to precise changes in substrate levels or the (epi)genotype of the embryo. Using this method, we have been able to demonstrate that a diabetic environment--culture of embryos in serum from diabetic animals or in serum with increased levels of glucose, β-hydroxybutyrate or α-ketoisocaproic acid (KIC)--causes increased embryonic maldevelopment, and that this dysmorphogenesis is blocked by the addition of ROS scavenging agents to the culture medium. Genetically, others and we have demonstrated that Pax-3 downregulation predisposes for diabetes-induced dysmorphogenesis.

  10. The safety of proton pump inhibitors in pregnancy: a multicentre prospective controlled study. (United States)

    Diav-Citrin, O; Arnon, J; Shechtman, S; Schaefer, C; van Tonningen, M R; Clementi, M; De Santis, M; Robert-Gnansia, E; Valti, E; Malm, H; Ornoy, A


    Proton pump inhibitors are used to treat gastro-oesophageal reflux and peptic ulcers. Gastro-oesophageal reflux is a common condition in pregnancy. Human pregnancy experience with lansoprazole or pantoprazole is very limited. More data exist on the safety of omeprazole in pregnancy. To assess the safety of proton pump inhibitors in pregnancy. The rate of major anomalies was compared between pregnant women exposed to omeprazole, lanzoprazole, or pantoprazole and a control group counselled for non-teratogens. The study design is a multicentre (n = 8), prospective, controlled study of the European Network of Teratology Information Services. We followed up 295 pregnancies exposed to omeprazole [233 in the first trimester (T1)], 62 to lansoprazole (55 in T1) and 53 to pantoprazole (47 in T1), and compared pregnancy outcome to that of 868 European Network of Teratology Information Services controls. The rate of major congenital anomalies did not differ between the exposed and control groups [omeprazole nine of 249 (3.6%), lansoprazole two of 51 (3.9%) and pantoprazole one of 48 (2.1%) vs. controls 30 of 792 = 3.8%]. No differences were found when exposure was limited to the first trimester after exclusion of genetic, cytogenetic or infectious anomalies. This study suggests that proton pump inhibitors do not represent a major teratogenic risk in humans.

  11. Sodium Channel Blockers in the Treatment of Epilepsy. (United States)

    Brodie, Martin J


    Sodium channel blockers have been the mainstay of the pharmacological management of focal and generalised tonic-clonic seizures for more than 70 years. The focus of this paper will be on phenytoin, carbamazepine, lamotrigine, oxcarbazepine, rufinamide, lacosamide and eslicarbazepine acetate. All these antiepileptic drugs have similar efficacy and share similar dose-dependent, adverse effect profiles, although phenytoin, carbamazepine and oxcarbazepine are more likely to cause idiosyncratic reactions than the others. With the exception of lamotrigine, rufinamide and lacosamide, all are enzyme inducers and most are minor teratogens; although data on teratogenicity are sparse with lacosamide and eslicarbazepine acetate. There is increasing evidence that these drugs differ mechanistically, with the newer agents, lacosamide and eslicarbazepine acetate, having their major pharmacological effect on the slow inactivation state of the sodium channel, which may be associated with better tolerability at higher dosage, although hard evidence in support of this observation is currently not available. Rufinamide is licensed only for Lennox-Gastaut syndrome in children aged 4 years and above. There is a move away from using enzyme inducers, particularly phenytoin and carbamazepine, in everyday clinical practice. There seems little doubt, however, that some sodium channel blockers will have an enduring place in the management of epilepsy well into the 21st century.


    Directory of Open Access Journals (Sweden)

    Lucie Widowati


    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.

  13. Species Differences in Renal Development and Associated Developmental Nephrotoxicity. (United States)

    Frazier, Kendall S


    The developing kidney is sensitive to both morphological and functional disturbances during the gestational and postnatal phases of growth and differentiation. Exposure to drugs or chemicals during these critical windows of renal development can result in aplasia, dysplasia, polycystic kidney disease, hydronephrosis, or other features characteristic of nephrotoxicity, including tubule dilation, necrosis, or mineralization. Functional effects can occur without associated morphological abnormalities. Differences in the timing of nephrogenesis and morphologic renal development among species help to explain specific phenotypes of various gestational and postnatal teratogens and nephrotoxins. Functional maturation follows anatomical maturation, but important differences in maximally achieved glomerular filtration rate, concentrating ability and acid-base equilibrium between species makes comparison of these timings critical for accurate and consistent translation of laboratory animal toxicity data to the human clinical experience. Species and age dependent differences in the maturation of kidney transporters, renal xenobiotic metabolism and renal blood flow can have a profound effect on the toxicity profiles of agents and marked differences in the tolerability based on age. Advances in the understanding of the genetics of inherited renal diseases and the underlying cellular and molecular pathogenesis of renal developmental anomalies has helped provide mechanistic understanding of many teratogenic and perinatal nephrotoxic agents. Investigative studies have provided important translational and mechanistic information for assessing human pediatric nephrotoxic potential. Birth Defects Research 109:1243-1256, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Indole Alkaloids from Fischerella Inhibit Vertebrate Development in the Zebrafish (Danio rerio Embryo Model

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    Katherine Walton


    Full Text Available Cyanobacteria are recognized producers of toxic or otherwise bioactive metabolite associated, in particular, with so-called “harmful algal blooms” (HABs and eutrophication of freshwater systems. In the present study, two apparently teratogenic indole alkaloids from a freshwater strain of the widespread cyanobacterial genus, Fischerella (Stigonemataceae, were isolated by bioassay-guided fractionation, specifically using the zebrafish (Danio rerio embryo, as a model of vertebrate development. The two alkaloids include the previously known 12-epi-hapalindole H isonitrile (1, and a new nitrile-containing variant, 12-epi-ambiguine B nitrile (2. Although both compounds were toxic to developing embryos, the former compound was shown to be relatively more potent, and to correlate best with the observed embryo toxicity. Related indole alkaloids from Fischerella, and other genera in the Stigonemataceae, have been widely reported as antimicrobial compounds, specifically in association with apparent allelopathy. However, this is the first report of their vertebrate toxicity, and the observed teratogenicity of these alkaloids supports a possible contribution to the toxicity of this widespread cyanobacterial family, particularly in relation to freshwater HABs and eutrophication.

  15. Isotretinoin-induced craniofacial malformations in humans and hamsters. (United States)

    Willhite, C C; Hill, R M; Irving, D W


    Oral administration of 40-80 mg/d of isotretinoin (13-cis-retinoic acid, Ro 4-3780, Accutane) during the first month of human pregnancy can induce severe congenital malformation. The human Accutane dysmorphic syndrome includes rudimentary external ears, absent or imperforate auditory canals, a triangular microcephalic skull, cleft palate, depressed midface, and anomalies of the brain, jaw, and heart. Children who suffer from this syndrome have large occiputs with narrowing of the frontal bone. Microphthalmia is reported in two cases; notations are made about the orbits in three cases; and the fact that infants could not follow with their eyes is noted in three cases. A decrease in muscle tone is noted in six, cleft palate is present in four, and limb reduction defects are described in two. The cardiac malformations usually include overriding aorta, interrupted or hypoplastic aortic arch, and septation defects of atria and ventricles. There are at least two cases of abnormal origin of the subclavian arteries. Oral isotretinoin in the pregnant hamster also induces similar congenital malformations. A human case of isotretinoin-induced dysmorphia is presented and compared with other affected infants and affected hamsters. The metabolic fate and pharmacokinetic parameters of isotretinoin in humans and rodents are discussed in relation to the teratogenic response. The results suggest that humans are approximately 16 times more sensitive to the teratogenic effects of oral isotretinoin than are hamsters.

  16. Final results from the 16-year sumatriptan, naratriptan, and treximet pregnancy registry. (United States)

    Ephross, Sara A; Sinclair, Susan M


    To monitor for a signal of major teratogenicity by determining the risk of all birth major defects following in utero exposure to sumatriptan, naratriptan, and the sumatriptan/naproxen sodium combination product (tablets marketed in the United States as Treximet [GlaxoSmithKline, Research Triangle Park, NC, USA]), and to monitor for unusual patterns of defects that might suggest teratogenicity. The prevalence of migraine is highest in women of childbearing age. Coupled with the recurrent nature of migraine attacks and the high proportion of unplanned pregnancies, intentional and inadvertent exposure to anti-migraine drugs in pregnancy is likely. The Sumatriptan, Naratriptan, and Treximet Pregnancy Registry captured data on women exposed to those drugs during pregnancy to monitor for evidence of major teratogenicity. In this primarily prospective, observational study, health care professionals from anywhere in the world enrolled, on a voluntary basis, women exposed to sumatriptan, naratriptan, or the sumatriptan/naproxen sodium combination product during their pregnancies. Only pregnancies with unknown outcomes at the time of enrollment were included in the analysis. The proportion of infants or fetuses with major birth defects was calculated as the total number of infants/fetuses with major birth defects divided by the sum of the number of infants/fetuses with major birth defects + the number of live births without defects. The risk of major birth defects was further stratified by earliest trimester of pregnancy exposure. The registry enrolled 680 evaluable exposed pregnant women, which resulted in 689 infants and fetuses (outcomes). Of these outcomes, 626 were exposed to sumatriptan, 57 were exposed to naratriptan (seven were exposed to both sumatriptan and naratriptan), and six were exposed to the sumatriptan/naproxen sodium combination product. Twenty outcomes with major birth defects were reported among 528 outcomes exposed in the first trimester to

  17. Prenatal Exposure to Paint Thinner Alters Postnatal Development and Behavior in Mice. (United States)

    Malloul, Hanaa; Mahdani, Ferdaousse M; Bennis, Mohammed; Ba-M'hamed, Saadia


    Occupational exposure and sniffing of volatile organic solvents continue to be a worldwide health problem, raising the risk for teratogenic sequelae of maternal inhalant abuse. Real life exposures usually involve simultaneous exposures to multiple solvents, and almost all the abused solvents contain a mixture of two or more different volatile compounds. However, several studies examined the teratogenicity due to industrial exposure to a single volatile solvent but investigating the teratogenic potential of complex chemical mixture such as thinner remains unexplored. This study was undertaken to evaluate developmental neurotoxicity of paint thinner using a mouse model. Mated female mice (N = 21) were, therefore, exposed to repeated and brief inhalation episodes of 0, 300 or 600 ppm of thinner during the entire period of pregnancy. Females weigh was recorded and their standard fertility and reproductive parameters were assessed. After birth postnatal day 1 (PND1), offspring (N = 88) length and body weight were measured in a daily basis. At PND5, the pups were assessed for their postnatal growth, physical maturation, reflex development, neuromotor abilities, sensory function, activity level, anxiety, depression, learning and memory functions. At adulthood, structural changes of the hippocampus were examined by estimating the total volume of the dentate gyrus. Except one case of thinner induced abortion at the higher dose, our results showed that the prenatal exposure to the solvent did not cause any maternal toxicity or decrease in the viability of the offspring. Therefore, a lower birth weight, decrease in the litter size and delayed reflexes ontogeny were registered in prenatally exposed offspring to both 300 ppm and 600 ppm of thinner. In addition, prenatally exposure to thinner resulted in increased anxiolytic- and depression-like behaviors. In contrast, impaired learning and memory functions and decreased hippocampal dentate gyrus volume were revealed only in the

  18. Safety aspects of Chinese herbal medicine in pregnancy-re-evaluation of experimental data of two animal studies and the clinical experience. (United States)

    Wiebrecht, Axel; Gaus, Wilhelm; Becker, Simon; Hummelsberger, Josef; Kuhlmann, Kirsten


    Chinese herbal medicine is an increasingly popular worldwide medical therapy which also has an impact in pregnancy. However, the question of its drug safety during pregnancy remains unresolved. Potential problems include teratogenicity, abortion, perinatal toxicity, pre- and postnatal developmental abnormalities, and eventually an increased risk for carcinomas in the offspring. Standard Materia Medica textbooks contain unreliable information when it comes to risks during pregnancy. Wang and co-workers conducted an experimental study (WS) on mice in which they investigated the effects of 17 Chinese medicinals regarding embryotoxicity and fetotoxicity. All these drugs seemed to exhibit multiple significant toxic effects. Another study by Li and co-workers (LS) investigated the reproductive toxicity of Atractylodis macrocephalae Rhizoma in mice, rats and rabbits. They described an increased pre- and postnatal mortality and, at high doses, congenital malformations. In an attempt to identify the risks of the tested medicinals during pregnancy, we analysed these two experimental studies and compared their results with possible safety data for humans from two reviews of clinical studies on threatened miscarriage (AR and CR). We re-evaluated WS and LS in relation to accordance with internationally accepted rules, equivalence to human dose, biometric accuracy, plausibility, and coherence. Eligible studies of the two reviews on threatened miscarriage were evaluated for specific pregnancy risks concerning the 17 medicinals tested in WS and LS. We found that WS does not conform to international ICH guidelines and includes many inconsistencies, implausibilities and several severe biometrical flaws. It reported a total of 364 significant events out of which 145 false significant results are expected. The data-handling pointed to irregularities. Analysis of LS exhibited also many inconsistencies. The results regarding congenital malformations were statistically insignificant and

  19. Assessing the Risk of Birth Defects Associated with Exposure to Fixed-Dose Combined Antituberculous Agents during Pregnancy in Rats

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    O. Awodele


    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

  20. Prenatal Exposure to Paint Thinner Alters Postnatal Development and Behavior in Mice

    Directory of Open Access Journals (Sweden)

    Hanaa Malloul


    Full Text Available Occupational exposure and sniffing of volatile organic solvents continue to be a worldwide health problem, raising the risk for teratogenic sequelae of maternal inhalant abuse. Real life exposures usually involve simultaneous exposures to multiple solvents, and almost all the abused solvents contain a mixture of two or more different volatile compounds. However, several studies examined the teratogenicity due to industrial exposure to a single volatile solvent but investigating the teratogenic potential of complex chemical mixture such as thinner remains unexplored. This study was undertaken to evaluate developmental neurotoxicity of paint thinner using a mouse model. Mated female mice (N = 21 were, therefore, exposed to repeated and brief inhalation episodes of 0, 300 or 600 ppm of thinner during the entire period of pregnancy. Females weigh was recorded and their standard fertility and reproductive parameters were assessed. After birth postnatal day 1 (PND1, offspring (N = 88 length and body weight were measured in a daily basis. At PND5, the pups were assessed for their postnatal growth, physical maturation, reflex development, neuromotor abilities, sensory function, activity level, anxiety, depression, learning and memory functions. At adulthood, structural changes of the hippocampus were examined by estimating the total volume of the dentate gyrus. Except one case of thinner induced abortion at the higher dose, our results showed that the prenatal exposure to the solvent did not cause any maternal toxicity or decrease in the viability of the offspring. Therefore, a lower birth weight, decrease in the litter size and delayed reflexes ontogeny were registered in prenatally exposed offspring to both 300 ppm and 600 ppm of thinner. In addition, prenatally exposure to thinner resulted in increased anxiolytic- and depression-like behaviors. In contrast, impaired learning and memory functions and decreased hippocampal dentate gyrus volume were

  1. Talidomida: indicações em Dermatologia Thalidomide: indications in Dermatology

    Directory of Open Access Journals (Sweden)

    Rubem David Azulay


    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

  2. Prenatal Exposure to Paint Thinner Alters Postnatal Development and Behavior in Mice (United States)

    Malloul, Hanaa; Mahdani, Ferdaousse M.; Bennis, Mohammed; Ba-M’hamed, Saadia


    Occupational exposure and sniffing of volatile organic solvents continue to be a worldwide health problem, raising the risk for teratogenic sequelae of maternal inhalant abuse. Real life exposures usually involve simultaneous exposures to multiple solvents, and almost all the abused solvents contain a mixture of two or more different volatile compounds. However, several studies examined the teratogenicity due to industrial exposure to a single volatile solvent but investigating the teratogenic potential of complex chemical mixture such as thinner remains unexplored. This study was undertaken to evaluate developmental neurotoxicity of paint thinner using a mouse model. Mated female mice (N = 21) were, therefore, exposed to repeated and brief inhalation episodes of 0, 300 or 600 ppm of thinner during the entire period of pregnancy. Females weigh was recorded and their standard fertility and reproductive parameters were assessed. After birth postnatal day 1 (PND1), offspring (N = 88) length and body weight were measured in a daily basis. At PND5, the pups were assessed for their postnatal growth, physical maturation, reflex development, neuromotor abilities, sensory function, activity level, anxiety, depression, learning and memory functions. At adulthood, structural changes of the hippocampus were examined by estimating the total volume of the dentate gyrus. Except one case of thinner induced abortion at the higher dose, our results showed that the prenatal exposure to the solvent did not cause any maternal toxicity or decrease in the viability of the offspring. Therefore, a lower birth weight, decrease in the litter size and delayed reflexes ontogeny were registered in prenatally exposed offspring to both 300 ppm and 600 ppm of thinner. In addition, prenatally exposure to thinner resulted in increased anxiolytic- and depression-like behaviors. In contrast, impaired learning and memory functions and decreased hippocampal dentate gyrus volume were revealed only in the

  3. Neurocognitive development of children following in-utero exposure to labetalol for maternal hypertension: a cohort study using a prospectively collected database. (United States)

    Chan, Wee Shian; Koren, Gideon; Barrera, Maru; Rezvani, Massoud; Knittel-Keren, Dafna; Nulman, Irena


    To identify the effect of prenatal labetalol exposure on children's long-term neurodevelopment. A cohort study with matched controls using a prospectively collected database. Participants were women counseled for hypertension in pregnancy at the Motherisk Program at The Hospital for Sick Children, and The Sunnybrook Health Sciences Centre, Toronto, Canada and their children. Mother-child pairs were divided into groups based on in-utero exposure to labetalol (n = 32), non-teratogenic substances (n = 42), and methyldopa (n = 25). The main outcome measures were children's Full-Scale IQ, Performance IQ and Verbal IQ assessed with the Wechsler Preschool and Primary Scale of Intelligence. There were no statistically significant differences in scores on Full-Scale IQ, Performance IQ, or Verbal IQ between children exposed in utero to labetalol and to non-teratogenic substances (Full-Scale IQ: 109.60 +/- 8.20 vs. 111.90 +/- 11.39, p = 0.647; Performance IQ: 104.80 +/- 8.69 vs. 110.19 +/- 12.91, p = 0.186; Verbal IQ: 112.27 +/- 11.05 vs. 11.21 +/- 11.98, p = 0.922, respectively). Children in the methyldopa group achieved lower scores on measures of Full-Scale IQ and Performance IQ when compared to children exposed to non-teratogenic substances (Full-Scale IQ: 105.24 +/- 12.46 vs. 111.90 +/- 11.39, p = 0.043; Performance IQ: 98.80 +/- 16.16 vs. 110.19 +/- 12.91, p = 0.002, respectively). Linear regression analysis revealed that maternal Full Scale IQ was a significant predictor of children's Full-Scale IQ (p = 0.020, beta = 0.229). Maternal Performance IQ and duration of treatment with methyldopa were significant predictors of children's Performance IQ (p = 0.028, beta = 0.232; p = 0.16, beta = -0.255, respectively). In-utero exposure to labetalol does not appear to adversely affect the neurocognitive development of young children. These reassuring results may aid disease management for pregnant women with hypertension.

  4. Contraception in Patients with Rheumatic Disease. (United States)

    Sammaritano, Lisa R


    Contraception represents an important area of reproductive health for patients with rheumatic diseases given the potential pregnancy risks associated with active disease, teratogenic medications, and severe disease-related damage. A high proportion of patients with rheumatic disease do not use effective contraception. Long-acting contraceptives are most effective. Antiphospholipid-negative patients with stable systemic lupus erythematosus may use oral combined contraceptives. Antiphospholipid-positive patients, or patients with rheumatic disease with other risk factors for thrombosis, should avoid estrogen-containing contraceptives. Contraceptive methods should be addressed by both the rheumatologist and gynecologist to determine the safest, most effective, and most convenient form for each patient. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. [Moebius syndrome. Clinical case report]. (United States)

    Palmer-Morales, Yusvisaret; Zárate-Márquez, Rosario Elena; Prince-Vélez, Roberto; González-Méndez, Roberto; Zamarripa-Sandoval, Thania Ayerim; Verdugo-Salazar, Nahim; Torres-Félix, Victor Gabriel; Salcido-Daniel, Remigio; Valdez-Hernández, Pedro; Morfín-Vela, Andrés


    Moebius syndrome (MBS) is an infrequent disease, having an incidence of 1 in 10,000 births, mainly characterized by a congenital bilateral facial paralysis due to an agenesia of the sixth and seventh cranial nerves. In addition, orofacial and limb anomalies are frequently found in these patients. The diagnosis is fundamentally based on different clinical manifestations of the disorder. a female newborn with the clinical picture of Moebius syndrome is presented, and genetic or environmental aspects are discussed. Since the use of misoprostol for abortion and inducing uterine activity in combination with NSAIDs, the number of newborns with MBS associated with this drug has increased. Nowadays, either genetic or environmental factors are associated with MBS. it is necessary that the general and medical community be aware of the risk of teratogenic effects of misoprostol, and the usefulness of genetic counseling whenever there is a newborn with Moebius syndrome.

  6. Evidence of Some Natural Products with Antigenotoxic Effects. Part 1: Fruits and Polysaccharides (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


    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

  7. [Bipolar disorder, pregnancy and the postpartum--risks and possibilities of pharmacotherapy]. (United States)

    Krüger, Stephanie


    Pregnancy and the postpartum are times of increased risk for women with bipolar disorder to develop mood episodes, especially depressions that may require pharmacotherapy. If mood stabilizing agents are discontinued prior or due to pregnancy, the risk for relapse increases dramatically. On the other hand, there is no psychotropic drug that is completely risk-free for the unborn. Some mood stabilizing medications are teratogenic, others can cause severe perinatal complications. Thus, the decision whether to treat the pregnant women with psychotropic drugs is difficult to make. In this paper, the reproductive risks of mood stabilizing agents, antidepressants, neuroleptics and benzodiazepines for the fetus are reviewed. During the postpartum period severe mood disorders can occur. The signs and symptoms of these disorders are reviewed and therapeutic strategies are discussed.

  8. Ventricular arrhythmias in a pregnant female – clinical implications

    Directory of Open Access Journals (Sweden)

    Ewelina Nowak


    Full Text Available Physiological changes occurring during pregnancy, at the time of childbirth, and in the postpartum period may influence the occurrence, and increase in intensity of, heart rhythm abnormalities. There is insufficient data on the safety and effectiveness of pharmacological treatment in the group of pregnant women. Cardiac arrhythmia induced by pregnancy rarely requires introduction of pharmaceuticals. It should be noted that most antiarrhythmic agents are not recommended for use during pregnancy and the breastfeeding period. In cases where a drug use is necessary, the most popular choice is -blockers or a calcium channel blocker – verapamil, which does not have teratogenic effects, but does get transferred to the mothers’ milk. The presented case study concerns a woman with no structural heart defects in her third pregnancy, with very ill-tolerated ventricular arrhythmia.

  9. Isotretinoin: controversies, facts, and recommendations. (United States)

    Bauer, Lindsey B; Ornelas, Jennifer N; Elston, Dirk M; Alikhan, Ali


    Since it was introduced to the market by Hoffman-La Roche (Roche) in 1982, isotretinoin has remained the most effective treatment for severe and recalcitrant acne. However, it has also been surrounded by controversy due to its teratogenicity and inconsistent associations with depression, suicidality, inflammatory bowel disease, increases in lipid levels, and elevated transaminases. Areas covered: In this article, we reviewed data regarding safety of isotretinoin and its association with these conditions. A thorough and comprehensive search on the topics was performed using pubmed and google scholar. Expert commentary: Despite common misperceptions, there is weak evidence for increased incidence of depression, suicidality, or inflammatory bowel disease with isotretinoin use. Furthermore, data indicates that transient increases in transaminases and lipid levels do not typically necessitate discontinuation of therapy. We hope to provide clinicians with information necessary to have meaningful discussions with patients regarding the safety and efficacy of isotretinoin.

  10. Cervical and Vulvar Intraepithelial Neoplasia after Treatment with Oral Isotretinoin for Severe Acne Vulgaris

    Directory of Open Access Journals (Sweden)

    M.N. Al Hallak


    Full Text Available Oral isotretinoin is the drug of choice for severe acne vulgaris, but its use is still controversial in preventing, treating or stopping the progression of the cervical intraepithelial neoplasia [6–8]. It induces cell differentiation, inhibits cell proliferation, stimulates host immune reaction, inhibits the oncogene expression, augments cell-mediated cytotoxicity, and induces apoptosis [5]. The isotretinoin has many side effects including teratogenicity. There is no previous report of developing cervical intraepithelial neoplasia (CIN or vulvar intraepithelial neoplasia (VIN after introducing oral isotretinoin to a patient. We are reporting a 37-year-old female with no risk factors for cervical cancer who had developed CIN-I and VIN-I during a 6-month treatment period of oral isotretinoin for her severe acne vulgaris. Interestingly, the patient had complete spontaneous pathologic-proven remission after stopping the isotretinoin. Further case reports are warranted to support this incidence.

  11. Molecular detection and genetic analysis of Akabane virus genogroup Ib in small ruminants in Turkey. (United States)

    Şevik, Murat


    Akabane disease is a viral disease transmitted by biting midges and can cause teratogenic malformations in cattle, sheep and goats. Abortion outbreaks associated with arthrogryposis and cerebellar hypoplasia in two epidemiologically independent flocks were reported in the Mediterranean region of Turkey in 2015. Phylogenetic analysis based on nucleocapsid (N) gene sequences showed that the field isolates presented here belong to the genogroup Ib. The akabane virus (AKAV) field isolates analysed in this study displayed 6 new amino acid substitutions in N and non-structural protein chains compared with those of AKAV strains belonging to genogroup Ib. To the best of our knowledge, this is the first report on the presence of the AKAV genogroup Ib in Turkey.

  12. A Brighter Side to Thalidomide: Its Potential Use in Immunological Disorders. (United States)

    Millrine, David; Kishimoto, Tadamitsu


    Thalidomide and its derivatives are immunomodulatory drugs (IMiDs) known for their sedative, teratogenic, anti-angiogenic, and anti-inflammatory properties. Commonly used in the treatment of cancers such as multiple myeloma and myelodysplastic syndrome (MDS), IMiDs have also been used in the treatment of an inflammatory skin pathology associated with Hansen's disease/leprosy. They have also shown promise in the treatment of autoimmune disorders including systemic lupus erythmatosus (SLE) and inflammatory bowel disease (IBD). Recent structural and experimental observations have revolutionized our understanding of these properties by revealing the fundamental molecular events underpinning IMiD activity. We review these findings, their relevance to IMiD therapy in immunological disorders, and discuss how further research might unlock the vast clinical potential of these compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. [Treatment of depressed pregnant women by selective serotonin reuptake inhibitors: risk for the foetus and the newborn]. (United States)

    Favrelière, S; Nourrisson, A; Jaafari, N; Pérault Pochat, M-C


    This article is a review of literature data concerning the use of selective serotonin reuptake inhibitors (SSRIs) by depressed pregnant women. The adverse effects for the foetus, the newborn and the child were evaluated. The prevalence of depression during pregnancy is of around 10 to 20% of the population of childbearing women. Depression is often misdiagnosed and underestimated in pregnant women. Starting a pharmacological treatment for depression in these women is not easy because data concerning the safety of antidepressants during pregnancy are still unclear. The non-treated pathology is associated with higher risk of maternal morbidity, including arterial hypertension, which could lead to preeclampsia or eclampsia, ideation and suicide attempts, and postpartum depression. Foetal development is also affected and adverse outcomes such as prematurity, low birth weight, irritability, and sleep disorders are frequent. Pharmacological therapy is necessary when non-pharmacological treatment is insufficient. Suicide attempts and relapse of depression have been described when depressive women stopped their pharmacological treatment during pregnancy. Pregnant women diagnosed with depression must be treated. Selective SSRIs are now largely used in this pathology and have replaced tricyclic antidepressants because of fewer side effects. In general, drugs have a low teratogenic potential, only 4 to 5% of malformations are iatrogenic. Teratogenic risk is high between conception until the end of the second month of gestation. Safety of SSRIs treatment during pregnancy and potential risk for the foetus and newborn were unquestioned before publication, in the late 2005, of some alarming data concerning a possible teratogenic effect. Studies showed an increased risk for all congenital malformations with SSRIs and particularly with paroxetin. A few studies after 2005 have also found an association between prenatal exposure to SSRIs (especially paroxetin) and congenital


    Directory of Open Access Journals (Sweden)



    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.

  15. Aplasia Cutis Congenita in a Newborn Child Associated with Two Fetus Papyraceous. (United States)

    Šimić, Dubravka; Prohić, Asja; Puizina Ivić, Neira; Zeljko Penavić, Jasna; Tomić, Teo


    Aplasia cutis congenita (ACC) is a rare inborn lesion, presenting with absence of skin. The etiology is unknown and is probably not attributable to a single cause but to a combination of genetic factors. Multiple causes have been suggested for ACC: syndromes and teratogens, intrauterine infection--varicella zoster virus, herpes simplex virus--fetal exposure to cocaine, heroin, alcohol, or antithyroid drugs. The most common site is the scalp. We report a case with multiple lesions on the trunk, resembling an instance with ACC group 5. This form of ACC occurs in association with the in utero death of a twin or more (in this case triple) fetus. Histological findings are available in very few reports. Therapy options depend on the characteristics of the lesion, but conservative treatment is usually chosen.

  16. Influence of Selected Organic Micropollutants on Organisms (United States)

    Włodarczyk-Makuła, Maria


    This article describes the toxicity of organic micropollutants on tested microorganisms. Itis a current issue because organic micropollutants are identified in all elements of environmental (surface water, ground water, soils) and in food products. The organic micropollutants include: polychlorinated dibenzodioxyns PCDD, polychlorinated dibenzofurans PCDF, polychlorinated biphenyls PCB, polycyclic aromatic hydrocarbons PAH, halogenated compounds and by-products of water treatment. Some organic compounds cause hazard for health and human life due to their estrogenic biological activity, carcinogenic, mutagenic or teratogenic activity. The influence on organisms indicators of these compounds based on literature data were presented. The level of TEQ (toxic equivalency) in response to organic chlorine derivatives (PCDDs, PCDF, PCBs) is usually determined by toxic equivalency factor (TEF). The International Agency for Research on Cancer classifies organic micropollutants as carcinogenic to humans (Group 1), possibly carcinogenic (Group 2A) or probably carcinogenic to humans (Group 2B).

  17. The transformation suppressor gene Reck is required for postaxial patterning in mouse forelimbs

    Directory of Open Access Journals (Sweden)

    Mako Yamamoto


    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.

  18. Reproductive performance in East Greenland polar bears (Ursus maritimus) may be affected by organohalogen contaminants as shown by physiologically-based pharmacokinetic (PBPK) modelling

    DEFF Research Database (Denmark)

    Sonne, Christian; Gustavson, Kim; Rigét, Frank F.


    quotient (RQ) evaluation to more quantitatively evaluate the effect risk on reproduction (embryotoxicity and teratogenicity) based on the critical body residue (CBR) concept and using a physiologically-based pharmacokinetic (PBPK) model. We applied modelling approaches to PCBs, p,p′-DDE, dieldrin...... effects, including reproductive, were conducted during 1990–2006. However, it has been difficult to determine the nature of the effects induced by OHC exposures on wild caught polar bears using body burden data and associated changes in reproductive organs and systems. We therefore conducted a risk...... in bears in the year 1990 were in the range to elicit possible adverse health effects on reproduction in polar bears in East Greenland (all RQs greater-or-equal, slanted 1). Similar results were found for PCBs (range: 1928–17 376 ng g−1 lw) and PFOS (range: 104–2840 ng g−1 ww) in the year 2000...

  19. 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:


    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.

  20. [Azo dyes, their environmental effects, and defining a strategy for their biodegradation and detoxification]. (United States)

    Gudelj, Ivana; Hrenović, Jasna; Dragičević, Tibela Landeka; Delaš, Frane; Soljan, Vice; Gudelj, Hrvoje


    Intense industrial development has been accompanied by the production of wastewaters of very complex content, which pose a serious hazard to the environment, put at risk sustainable development, and call for new treatment technologies that would more effectively address the issue. One particular challenge in terms of science and technology is how to biodegrade xenobiotics such as azo dyes, which practically do not degrade under natural environmental conditions. These compounds tend to bioaccumulate in the environment, and have allergenic, carcinogenic, mutagenic, and teratogenic properties for humans. Removal of azo dyes from effluents is mostly based on physical-chemical methods. These methods are often very costly and limited, as they accumulate concentrated sludge, which also poses a significant secondary disposal problem, or produce toxic end-products. Biotechnological approach may offer alternative, lowcost biological treatment systems that can completely biodegrade and detoxify even the hard-to-biodegrade azo dyes.