Prevalence of congenital anomalies at birth among live births in the state of Maranhão from 2001 to 2016: temporal and spatial analysis / Prevalências ao nascimento de anomalias congênitas entre nascidos vivos no estado do Maranhão de 2001 a 2016: análise temporal e espacial

ABSTRACT: Objectives: To analyze the prevalence at birth and the spatial and temporal distribution of congenital anomalies (CAs) among live births in the state of Maranhão in 2001 to 2016. To describe demographic, gestational and neonatal variables of interest. Methods: Ecological, population-based study, using secondary data from the Live Birth Information System (SINASC). Annual prevalence of total and per-group CAs was calculated. Spatial analyzes were based on the Local Indicators of Spatial Association (LISA) and the Moran I Index, and interactive maps were generated. Demographic, gestational and neonatal variables of interest available from SINASC were described in the group of newborns with CAs. Results: 1,831,830 live births, 6,110 with CAs (33.4/10,000) were included. Higher frequencies occurred in more recent years. Spatial clusters have been observed in specific years. The prevalence of newborns with CAs was different between categories of variables considered as risk factors for this outcome. Conclusion: The prevalence at birth of total CAs was lower than expected for major human defects (3%). The temporal peak of records in 2015/2016 is probably related to the increase in CAs caused by gestational infection by the Zika virus. The spatial clusters were probably due to variations at random due to the small number of births as they are not repeated in other years. Studies like this are the basis for the establishment of CA surveillance programs.

RESUMO: Objetivos: Analisar as prevalências ao nascimento e a distribuição espacial e temporal das anomalias congênitas (ACs) entre nascidos vivos no estado do Maranhão nos anos de 2001 a 2016; descrever variáves de interesse demográficas, gestacionais e neonatais. Métodos: Estudo ecológico, de base populacional, a partir de dados secundários do Sistema de Informações sobre Nascidos Vivos (SINASC). Foram calculadas prevalências ao nascimento anuais de ACs totais e por grupos. Análises espaciais utilizaram o cálculo de Indicadores Locais de Associação Espacial (LISA) e o Índice Global de Moran I, e mapas interativos foram gerados. Variáveis de interesse demográficos, gestacionais e neonatais disponíveis no SINASC foram descritas no grupo dos recém-nascidos com ACs. Resultados: Neste estudo, foram incluídos 1.831.830 nascidos vivos, 6.110 com ACs (33,4/10 mil). Maiores frequências ocorreram nos anos mais recentes. Aglomerados espaciais foram observados em anos específicos. As prevalências de nascidos vivos com anomalias foram diferentes entre categorias de variáveis consideradas como fatores de risco para esse desfecho. Conclusão: A prevalência ao nascimento de nascidos com ACs foi inferior ao esperado para defeitos maiores na espécie humana (3%). O pico temporal de registros em 2015/2016 está provavelmente relacionado ao aumento de microcefalia causada pela infecção gestacional por vírus Zika. Os aglomerados espaciais provavelmente se deveram a variações ao acaso pelo número pequeno de nascimentos, pois não se repetem em outros anos. Estudos como este são base para o estabelecimento de programas de vigilância de defeitos congênitos.

Embryonic loss, abortion, and malformations in ewes caused by the ingestion of hay leaves of Cenostigma pyramidale / Perda embrionária, aborto e malformações em ovinos por ingestão de Cenostigma pyramidale na forma fenada

Determining if reproductive failures in ewes at the semiarid region in the state of Bahia are related to the consumption of the species Cenostigma pyramidale (Tul.) Gagnon & G.P. Lewis, and this study was developed using pregnant ewes divided into six groups: G1, G2, G3, G4 with six animals each, G5 and G6 with ten animals. Each group received fence leaves in the proportion of 1%, 2%, 0.5%, and 0.25% of live weight (LW) respectively; G5 and G6, with ten animals each, receiving 0.25% and 0.5% of the LW, respectively, and the Control Group, comprising 16 ewes, were grass feeding (Cynodon dactylon). Ewes from G1 to G4 were the same, except for two, and started ingestion of the plant four days after ending of natural mating on the 80th day of gestation, while those regarding from G5 to G6 groups started ingestion on the 26th day of gestation ending on the 98 day. The ultrasonographic test was performed weekly. In G1 ewes (1%), there was an embryonic loss on the 32nd and 39th days of gestation and abortion on the 46th day. In G2 (2%), the embryo loss was earlier (on the 26th day of gestation), and abortion on the 46th day of gestation. In G3 group (0.5%), there was an embryonic loss around the 40th day of gestation. In G4 group (0.25%), it was observed the occurrence of one death lamb with bone malformations. In G6 (0.5%), abortion occurred later (108 days), followed by retained placenta. This was also verified in G5 group (0.25%). The presence of fetal malformation was found in death lambs born in G4 group, born alive from G5 and G6 groups, and one aborted from G6. In G5 and G6 groups, there were also genetic alterations on surviving lambs. In addition to these results, recurrent estrus was observed without gestation in G1, G2, G3, and G4 ewes. From the Control Group, 13 normal lambs were born without genetic alterations; furthermore, concerning a quadruple birth, three lambs were born dead. The results infer that species of C. pyramidale in low doses causes reproductive losses in pregnant ewes, therefore it is not recommended for sheep diet over the first 60 days of gestation.(AU)

Para determinar se falhas reprodutivas em ovelhas na região semiárida da Bahia estão relacionadas ao consumo de Cenostigma pyramidale (Tul.) Gagnon & G.P. Lewis, foi realizado um estudo utilizando-se ovelhas prenhes divididas em seis grupos e dois Grupos Controle. Os grupos G1, G2, G3 e G4 com seis animais cada. Cada grupo recebeu folhas fenadas na proporção de 1%, 2%, 0,5% e 0,25% do peso vivo (PV) respectivamente; G5 e G6, com 10 animais cada, que receberam 0,25% e 0,5% do PV respectivamente. Os Grupos Controle foram alimentados com ração e capim (Cynodon dactylon). Ovelhas dos grupos 1 a 4 iniciaram ingestão da planta quatro dias após monta natural com término aos 80 dias de gestação, enquanto as dos grupos 5 a 6 iniciaram ingestão no 26º dia de gestação com término aos 98 dias. Avaliação ultrassonográfica foi realizada semanalmente. Nos animais do G1 (1%), verificou-se perda embrionária aos 32 e 39 dias de gestação, e aborto aos 46 dias. Nos do G2 (2%) a perda embrionária foi mais precoce (26 dias), e aborto aos 46 dias. No G3 (0,5%), houve perda embrionária em torno dos 40 dias. No G4 (0,25%), verificou-se ocorrência de natimorto com malformações aos 150 dias de gestação. No G6 (0,5%) o aborto ocorreu mais tardiamente (108 dias), seguido de retenção de placenta. Essa ocorrência também foi verificada no G5 (0,25%). A presença de malformação fetal foi encontrada em fetos natimorto do G4, nascidos vivos do G5 e G6, e um abortado do G6. No G5 e G6 também foram observadas alterações de aprumos em cordeiros sobreviventes. Do Grupo Controle nasceram 13 borregos normais, porém uma ovelha apresentou gestação quádrupla com três natimortos. Os resultados inferem que C. pyramidale fenada em baixas doses causa perdas reprodutivas em ovelhas gestantes, não sendo por isso recomendada para a dieta de ovelhas durante os primeiros 60 dias de gestação.(AU)

Valproate Induced Nephrotoxicity On Fetal Mice Kidney

Background: Valproate is an antiepileptic drug which is also known as 2-propylvaleric acid. Valproic acid ispresently the most widely used antiepileptic drug because of its antiepileptic effectiveness in a broad range ofseizure types: tonic-clonic, myoclonic, absence and partial seizures. Present work was done to evaluate the grossand histological effect of valproate on fetal mice kidney.Materials and Methods: This study was done in anatomy department of Institute of medical sciences, BanarasHindu University, Varanasi (U.P.). Single dose of valproate (200mg/kg) was administered intraperitoneally on 8thday of gestation and then fetuses were collected at the 18th day of gestation.Results: Kidney was reduced in size in valproate treated group fetuses as compared to kidney of control groupfetuses. On histological examination, distorted developing nephrons and clumping of bowman capsule indeveloped nephrons were seen.Conclusions: Various authors worked on valproate treated adult mice kidney. There are only few study conductedon kidney of mice fetus. In present study, valproate was found teratogenic at the dose of 200mg/kg so it shouldbe avoided in human pregnancy if possible

Enfrentamiento práctico a patologías otorrinolaringológicas frecuentes durante el embarazo, una revisión de la literatura / Treatment of frequent otorhinolaryngological pathologies during pregnancy, a review of the literature

RESUMEN Durante el embarazo ocurren una serie de cambios, como edema y disminución de la actividad ciliar en la mucosa respiratoria alta, que pueden favorecer la aparición de síntomas y patologías del área otorrinolaringológica. La eficacia de los tratamientos farmacológicos en la rinitis del embarazo es pobre. El tratamiento de primera línea de la rinitis alérgica son los corticoides intranasales. Existe evidencia sobre la seguridad en el embarazo para furoato de fluticasona, mometasona y budesonida intranasal. El tratamiento del resfrio común está enfocado en el manejo sintomático, los antinflamatorios no esteroidales están contraindicados. En rinosinusitis aguda bacteriana la amoxicilina es de primera línea. En rinosinusitis crónica el manejo quirúrgico está reservado sólo para las complicaciones. Tanto la otitis media aguda como la amigdalitis aguda deben ser tratadas con antibióticos sólo si se sospecha origen bacteriano, el esquema de primera linea es amoxicilina y en caso de alergias se debe usar cefpodoxime o azitromicina. En caso de otorrea no existe evidencia sobre la seguridad de las gotas de antibióticos ótico durante el embarazo. Múltiples medicamentos utilizados habitualmente en otorrinolaringologia no pueden ser usados durante el embarazo. Se debe privilegiar la seguridad materno fetal, utilizando aquellos medicamentos con seguridad demostrada.

ABSTRACT During pregnancy a series of changes occur, such as edema and decreased ciliary activity in the upper respiratory mucosa, which may favor the appearance of symptoms and pathologies of the otorhinolaryngological area. The efficacy of pharmacological treatments in rhinitis of pregnancy is poor. The first-line treatment of allergic rhinitis is intranasal corticosteroids. There is evidence on safety in pregnancy for fluticasone furoate, mometasone and intranasal budesonide. The treatment of the common cold is focused on symptomatic management, nonsteroidal anti-inflammatory drugs are contraindicated. In acute bacterial rhinosinusitis, amoxicillin is first-line. In chronic rhino-sinusitis in surgical management is reserved only for complications. Both acute otitis media and acute tonsillitis should be treated with antibiotics only if bacterial origin is suspected, the first-line treatment is amoxicillin, in the case of allergies, cefpodoxime or azithromycin should be used. In case of otorrhea there is no evidence on the safety of otic antibiotic drops during pregnancy. Conclusion: multiple medications commonly used in otorhinolaryngology cannot be used during pregnancy. Maternal and fetal safety should be privileged, using those medications with proven safety.

Os riscos do uso de plantas medicinais durante o período gestacional: uma revisão bibliográfica / The risks of the use of medicinal plants during the gestational period: A bibliographic review

Esta revisão de literatura teve como objetivo principal identificar as plantas medicinais utilizadas por gestantes capazes de provocar efeitos nocivos à gestação, assim como descrever os principais metabólitos secundários responsáveis por estes efeitos. Foram utilizados artigos escritos entre os anos de 2011 e 2018, disponíveis em bases de dados eletrônicas como Scielo, Periódicos Capes, Lilacs, Medline e Science Direct. Foram selecionadas 98 publicações, destas 52 foram excluídos por apresentarem problemas metodológicos ou não se adequarem ao tema, sendo 46 artigos aproveitados. Foram apresentadas as plantas medicinais frequentemente utilizadas por mulheres durante o período gestacional, as quais acredita-se não provocarem danos a gestação. Plantas como boldo, sene, camomila, carqueja, angélica, arruda e outras são comumente utilizadas pela população gestante a fim de aliviar os desconfortos desse período, como enjoo, flatulência, insônia, azia, depressão, insônia, dores articulares, emagrecimento, dentre outros. No entanto, as plantas medicinais possuem metabólitos secundários que são considerados tóxicos e capazes de provocar efeitos embriotóxico, teratogênico e abortivo, quando utilizados durante a gestação. Diante do que foi pesquisado, avaliando a relação risco/benefício, onde os estudos apontam muitos riscos oferecidos pelas plantas medicinais utilizadas na gestação, sugere-se o uso controlado destes tratamentos durante o período gestacional com o devido acompanhamento médico.

This literature review had as main objective to identify the medicinal plants used by pregnant women capable of causing harmful effects to gestation, as well as to describe the main secondary metabolites responsible for these effects. Articles used in this review were written between the years 2011 and 2018 and are available in electronic databases such as Scielo, Periodical Capes, Lilacs, Medline and Science Direct. A total of 98 publications were selected, of which 52 were excluded because they presented methodological problems or did not fit the theme, with 46 articles being used. The medicinal plants frequently used by women during the gestational period were shown, which are believed not to cause pregnancy damage. Plants such as boldo, sene, camomile, carqueja, angelica, arruda and others are commonly used by the pregnant population to relieve the discomforts of this period, such as nausea, flatulence, insomnia, heartburn, depression, joint pain, weight loss, among others. However, medicinal plants have secondary metabolites that are considered to be toxic and capable of causing embryotoxic, teratogenic and abortive effects when used during pregnancy. In the light of the research, evaluating the risk / benefit relationship, where the studies point out many risks offered by the use of medicinal plants during pregnancy, it is suggested controlled use of these treatments during the gestational period with the appropriate medical follow-up.

Impact of educational intervention on the awareness of undergraduate medical students towards teratogenicity: an observational study

Background: The term teratogenicity is defined as any morphological, behavioral or biochemical effect induced during embryonic life or fetal life detected at birth or later. the factors that lead to teratogenicity include both non-genetic and genetic factors. The objective of the present study was to assess the impact of educational interventions on the awareness of undergraduate medical students towards teratogenicityMethods: The present study was a questionnaire-based comparative observational study carried out at Department of Pharmacology and Therapeutics, Government Medical College, Jammu (J&K) for a period of three months from 1st November 2017 to 31st January 2018. The questionnaire was designed and validated by conducting pilot study on a sample of ten students. The questionnaire comprised of two main parts. The first part comprised of questions pertaining to the demographic profile of the students and second part consisted of questions assessing the students’ knowledge and awareness towards teratogenicity. The scoring of the assessment of the performance of the students regarding knowledge of various aspects of teratogenicity was done before and after the educational intervention and was compared using paired t-test.Results: A total of 134 second year MBBS undergraduate students participated in the study. Mean age of students was 19.32±0.82 years. In the present study it was found that before the educational intervention about 98.5% of the students and after the intervention all the students were aware of the term teratogenicity. About 69.4% of students knew about all the causes that lead to teratogenicity but after the intervention about 76.1% of the students knew about it. Also, the percentage of students who knew about the name of two teratogenic drugs and two teratogenic defects associated with drugs were only 31.3% and 22.3% respectively. After the educational intervention it increased to 61.9% and 52.2% respectively.Conclusions: In the present study, it was found that after the educational intervention, there was a significant improvement in the mean knowledge score of the students. This reflects the need of early exposure of students to this important issue of teratogenicity.

Protección de la Spirulina maxima sobre la citotoxicidad de la hidroxiurea en células embrionarias de ratón / Protection of Spirulina maxima on cytotoxicity of hydroxyurea in mouse embryonic cells / Proteção de Spirulina maxima em citotoxicidade de hidroxiureia em células embrionárias de camundongo

La Spirulina maxima (SP) tiene efectos farmacológicos protectores por su contenido de ficobiliproteínas que están relacionados con su actividad antioxidante. La hidroxiurea (HU) es un fármaco antineoplásico, citotóxico y teratógeno que implica la inducción del estrés oxidativo. El objetivo de este trabajo fue determinar si la SP y su extracto acuoso de proteína (SPE) protegen contra el efecto citotóxico de HU en cultivos celulares primarios a partir de embriones de ratón de once días. Los efectos de SP, SPE e HU sobre la viabilidad celular se determinaron por el ensayo de fluorescencia de resazurina en cultivos celulares de embriones completos de ratones de once días, de encéfalo y de brotes de extremidades anteriores. Se demostró que ni SP ni su extracto provocaron efectos citotóxicos en ninguna concentración ensayada, por lo que se aumentaba la viabilidad celular. Se encontró que las células expuestas a HU de embriones completos y encéfalo mostraron mayor toxicidad que las células de los miembros anteriores. La SP y el SPE protegieron contra la citotoxicidad de HU de una manera dependiente de la concentración hasta 48 h después de la exposición al fármaco. Este efecto podría ser adecuado para prevenir la muerte celular que deriva en un proceso teratogénico, atribuido a sus propiedades antioxidantes.

Spirulina maxima (SP) has protective pharmacological effects that are related to the antioxidant activity due to its phycobiliprotein content. Hydroxyurea (HU) is an antineoplastic, cytotoxic and teratogenic drug, which involves the induction of oxidative stress. The aim of this study was to determine whether SP and its aqueous protein extract (SPE) protect against the cytotoxic effect of HU in primary cell cultures from mouse embryos. The effects of SP, SPE, and HU on cell viability were determined by resazurin fluorescence assay in whole embryo cell cultures, encephalon, and eleven-day-old forehead bud outbreaks. It was shown that neither SP nor its extract caused cytotoxic effects at any concentration tested, increasing cell viability. It was found that cells exposed to HU of whole embryos and encephalon showed higher toxicity than cells of the previous limbs. SP and SPE protected HU cytotoxicity in a concentration-dependent manner up to 48 hours after exposure to the drug. This effect could be adequate to prevent cell death resulting in a teratogenic process attributed to its antioxidant properties.

Spirulina maxima (SP) tem efeitos farmacológicos protetores devido a seu conteúdo de ficobiliproteínas, que estão relacionadas com sua atividade antioxidante. A hidroxiureia (HU) é uma droga antineoplásica, citotóxica e teratogênica, que envolve a indução do estresse oxidativo. O objetivo deste estudo foi determinar se a SP e seu extrato aquoso de proteína (SPE) protegem contra o efeito citotóxico da HU em culturas celulares primárias a partir de embriões de camundongo de onze dias. Os efeitos de SP, SPE e HU na viabilidade celular foram determinados pelo ensaio de fluorescência de resazurina em culturas celulares de embriões inteiros de camundongos de onze dias, de encéfalo e de surtos de extremidades anteriores. Demonstrou-se que nem a SP nem seu extrato causaram efeitos citotóxicos em qualquer concentração testada, aumentando a viabilidade celular. Verificou-se que as células expostas à HU de embriões completos e encéfalo mostraram maior toxicidade do que as células dos membros anteriores. SP e SPE protegem contra a citotoxicidade de HU de forma dependente da concentração até 48 h após a exposição ao medicamento. Esse efeito poderia ser adequado para prevenir a morte celular, que resulta em um processo teratogênico atribuído a suas propriedades antioxidantes.

Abortos, malformações congênitas e falhas reprodutivas espontâneas em caprinos causados na intoxicação pelas folhas da catingueira, Poincianella pyramidalis (sin. Caesalpinia pyramidalis) / Spontaneous abortion, congenital malformation and reproductive losses in goats due to poisoning by the leaves of Poincianella pyramidalis (syn. Caesalpinia pyramidalis)

O objetivo deste estudo foi investigar os efeitos de folhas da espécie arbórea Poincianella pyramidalis (Tul.) L.P. Queiroz como causa espontânea de abortos, malformações e falhas reprodutivas em rebanhos caprinos no semiárido brasileiro. Foram realizadas investigações epidemiológicas, avaliações clínicas de caprinos acometidos por malformações e necropsias de fetos abortados em 12 propriedades localizadas nos municípios de Gurjão e Soledade, na Paraíba, e no município de Pau dos Ferros, Rio Grande do Norte. O estudo considerou apenas as propriedades que tinham basicamente a presença de P. pyramidalis entre as plantas teratogênicas. Na propriedade localizada no município de Pau dos Ferros foi verificada a ocorrência de grande número de abortos e o nascimento de cabritos malformados, acometendo 90% das cabras gestantes. Nas 12 propriedades pertencentes aos municípios de Gurjão e Soledade na Paraíba os casos espontâneos de mortalidade embrionária, abortos e malformações acometeram 257 cabras (41,1% das cabras dos rebanhos). A artrogripose foi a principal malformação congênita observada. Exames de necropsia e histopatológico de quatro fetos acompanhados das placentas não constataram a presença de agentes infecciosos. Os casos de perda embrionária, abortos e malformações foram concentrados predominantemente nas épocas do ano em que a pastagem estava escassa, mas havia disponibilidade de P. pyramidalis nas propriedades, devido à ocorrência das chuvas da pré-estação, que não permitiu a germinação de pasto, mas a rebrotação de P. pyramidalis. Os achados desse estudo comprovam que esta planta interfere consideravelmente na eficiência reprodutiva dos rebanhos caprinos do Semiárido.(AU)

The aim of this study was to investigate the effects of the leaves of the tree Poincianella pyramidalis (Tul.) L.P. Queiroz as a spontaneous cause of abortion, malformation and reproductive failure in goat herds in the Brazilian semiarid region. Epidemiological investigations, clinical evaluation of goats affected by malformation and necropsy of aborted fetuses was carried out on 12 farms located in the municipalities of Gurjão and Soledade, state of Paraíba, and on a farm located at the municipality of Pau dos Ferros, state of Rio Grande do Norte. The study considered only the farms where occurred predominantly P. pyramidalis among teratogenic plants. On the farm located in the municipality of Pau dos Ferros the occurrence of frequent abortion and birth of malformed goats, affecting 90% of pregnant goats, was observed. On the 12 farms belonging to the municipalities of Gurjão and Soledade, spontaneous cases of embryonic mortality, abortion and malformation occurred in 257 goats (41.1% of goats). Arthrogryposis was the main congenital malformation observed. Necropsy and histopathological exams of four fetuses and their placentas did not detect the presence of infectious agents. The cases of embryonic mortality, abortion and malformation were predominantly concentrated during the seasons of the year when pasture was scarce, but P. pyramidalis was available, due to the occurrence of pre-seasonal rains, which did not allow the pasture to germinate but P. pyramidalis to regrowth. The findings of this study confirm that this plant significantly interferes in the reproductive efficiency of semi-arid goat herds.(AU)

Efeitos tóxicos de compostos de vanádio sobre os parâmetros biológicos de embriões e adultos de zebrafish (Danio rerio) / Toxic effects of vanadium compounds on biological parameters of embryos and adults of zebrafish (Danio rerio)

Foram avaliados os efeitos tóxicos do metavanadato de sódio (MV), pentóxido de vanádio (PV) e sulfato de oxovanádio (SV), potenciais fármacos antidiabéticos, em embriões e adultos de zebrafish (Danio rerio). Os embriões foram expostos a concentrações de 10-1000µg/mL para avaliação da CL50 96h e seus efeitos teratogênicos. Os adultos foram expostos a 10 e 20µg/mL dos mesmos compostos para se avaliarem alterações comportamentais relacionadas à exposição química e à mortalidade. A CL50 96h foi de 22,48, 53,62 e 74,14µg/mL para MV, SV e PV, respectivamente. Houve 100% de mortalidade nas concentrações de 400-1000µg/mL dos três compostos. Os efeitos teratogênicos mais observados (P<0,05) nos embriões foram edemas de pericárdio e saco vitelínico. Foram constatados, nos animais adultos expostos aos compostos de vanádio, maior batimento opercular e congestão nos arcos branquiais. A exibição dos comportamentos Flutuar e Descansar nos adultos expostos foi significativa (P<0,05), como também a exibição do comportamento Respiração Aérea. Pode-se concluir que a exposição química aos compostos de vanádio causou efeitos tóxicos em embriões e adultos de zebrafish com alta mortalidade. Diante disso, o seu uso como potencial fármaco antidiabético deve ser mais bem estudado em razão do efeito tóxico dessas substâncias.(AU)

The toxic effects of sodium metavanadate (MV), vanadium pentoxide (PV) and oxovanadium sulfate (SV), potential antidiabetic drug, on embryos and adults of zebrafish (Danio rerio) were evaluated. Embryos were exposed to concentrations of 10-1000µg/mL for evaluation of 96-h LC50 and their teratogenic effects. Adults were exposed to 10 and 20µg/mL of the same compounds to evaluate behavioral changes related to chemical exposure and mortality. The 96-h LC50 were 22.48, 53.62, and 74.14µg/mL for MV, SV, and PV, respectively. Mortality of 100% was observed at the concentrations of 400-1000µg/mL of the three compounds. The teratogenic effects most observed (P<0.05) were pericardial and yolk sac edemas. Adult animals exposed to the vanadium compounds had higher opercular beats and congestion in the gill arches. The exhibition of behaviors Floating and Resting in the exposed adults was significant (P<0.05), as well as the Air breathing behavior. Chemical exposure to vanadium compounds caused toxic effects in embryos and adults of zebrafish with high mortality. In conclusion, its use as a potential antidiabetic drug should be better studied due to the toxic effect.(AU)

Model validation and evaluation of developmental toxicity of five drugs using zebrafish embryos / 中国药理学通报

Aim To explore the toxicity and safety of five kinds of known positive drugs, cyclophosphamide, acetyl salicylic acid, tetracycline hydrochloride, dexa-methasone acetate and azacitidine, using zebrafish em-bryos. Methods We selected normally developed 4 hpf zygote, and used water bath infecting method to add the drug to the artificial seawater. Each drug had five concentrating groups, a separate control group and solvent control group. We observed the dead zebrafish embryos after 120 hpf drugs, counted the number of deaths and deformities of zebrafish embryos, and cal-culated mortality abnormal rate, the median lethal con-centration (LC50 ), concentration for 50% of maximal effect (EC50 ), therapeutic index (TI) under 120 hpf condition. We also used the formula TI = LC50 / EC50 to calculate positive drug therapeutic index. Based on measured LC50 we calculated most nonlethal concentra-tion (MNLC) of each drug setting, namely 1 / 10 MN-LC, 1 / 3 MNLC, MNLC,LC10 four concentration, tha-lidomide as a positive control, vitamin C as a negative control, artificial seawater as control, 0. 5% DMSO as solvent control. Put in 28. 5 ℃ environment for 120 hours,embryo development was observed daily for de-velopmental state,mortality,deforming rate and abnor-mal condition. Results The result of five drugs LC50 in descending order: cyclophosphamide > azacitidine> tetracycline hydrochloride > acetylsalicylic acid >dexamethasone acetate. EC50 in descending order: cy-clophosphamide > tetracycline hydrochloride > azaciti-dine > acetylsalicylic acid > dexamethasone acetate. The TI values of cyclophosphamide, acetyl salicylic acid, tetracycline hydrochloride, dexamethasone ace-tate, azacitidine were 1. 92, 1. 11, 1. 05, 1. 44, 2. 99, respectively. Conclusion Zebrafish embryo model can be used in the preliminary evaluation of drugs, and the study of early developmental toxicity and safety.

Micro hardness of dental tissues influenced by administration of aspirin during pregnancy / Microdureza de los tejidos dentales influenciada por la administración de aspirina durante el embarazo

The study is associated with the effect of aspirin (Acetyl Salicylic Acid) on the microhardness of mineralized tissues of the offspring's teeth, in response to the ingestion of the drug during pregnancy. Aspirin is a widely used analgesic and antipyretic medicine, for symptomatic treatment. Misuse of this drug during pregnancy may instigate developmental defects in offspring. An experimental control study was designed, in which female rabbits were taken as representative mammalian models and treated with aspirin during pregnancy. Their offspring's teeth were used to assess the microhardness of dental tissues. The rabbits were alienated into two groups, treated and control, consisting of seven rabbits in each set (n= 7). Microhardness was evaluated in three types of the sample teeth. The total number of teeth examined were, 2x7x12= 168 samples. Vicker's Hardness degree values were measured and recorded vis-à-vis (50 g for 15 s with 3 indentations per specimen on enamel and dentine separately). The range of hardness obtained was statistically analyzed and the Student's t-tests was applied, with the aid of SPSS version 20. The P-values for both enamel and dentine from maxillary incisors and molars were less than 0.05. The same trend was observed in the mandibular teeth. However, a teratogenicity of Acetyl Salicylic Acid was pragmatic in the recent in vivo studies. Based on the analysis, it was evident that the aspirin administration could produce negative effects leading to reduction in the microhardness of dental tissues of the offsprings.

El estudio asocia el efecto de la aspirina (ácido acetil salicílico) sobre la microdureza de los tejidos mineralizados de los dientes de crías, en respuesta a la ingesta del fármaco durante la preñez. La aspirina es un analgésico y antipirético ampliamente utilizado para el tratamiento sintomático. El mal uso de esta droga durante la preñez puede inducir defectos en el desarrollo de las crías. Se diseñó un estudio experimental de control, en el que se tomaron conejas como modelos de mamíferos representativos y fueron tratados con aspirina durante la preñez. Los dientes de sus crías fueron utilizados para evaluar la microdureza de los tejidos dentales. Los animales fueron distribuidos en dos grupos, tratados y control, con siete animales en cada grupo (n= 7). La microdureza se evaluó en tres tipos de dientes de la muestra. El número total de dientes examinados fueron 168 (2x7x12). Se midieron y registraron valores del grado de dureza Vickers vis-à-vis (50 g por 15 s con 3 indentaciones por especimen sobre el esmalte y la dentina por separado). Se analizó estadísticamente la gama de dureza obtenida y se aplicaron pruebas t de Student con la ayuda del programa SPSS versión 20. Los valores de p para el esmalte y la dentina de los incisivos maxilares y molares fueron menores a 0,05. Se observó la misma tendencia en los dientes mandibulares. Sin embargo, teratogenicidad producto del ácido acetil salicílico se encontró en recientes estudios in vivo. De acuerdo al análisis de los resultados, se evidenció que la administración de aspirina provocó efectos negativos que determinaron la reducción de la microdureza de los tejidos dentales de las crías.

Facts about Magnesium Sulfate: Time to Revise the Safety Concern in Obstetric Use.

Magnesium sulfate (MgSO4) is the agent most commonly used for treatment of eclampsia and prevention of eclampsia in patients with severe pre-eclampsia. Another commonly practiced offlabel use of this drug is in preventing preterm labor in pregnant women where the duration of the treatment might be more than one week. It is usually given either by intramuscular or intravenous route. After administration, about 40% of plasma magnesium is bound with protein. The unbound magnesium ion diffuses into the extravascular extracellular space and then diffuses into bone. It also crosses the placenta and fetal membranes and then diffuses into the fetus and amniotic fluid. Magnesium is almost exclusively excreted in the urine; 90% of the dose is excreted during the first 24 hours after an intravenous infusion of MgSO4. The clinical effect and toxicity of MgSO4 can be linked to its concentration in plasma. A concentration of 1.8–3.0 mmol/L has been suggested for treatment of eclampsia. The actual magnesium dose and concentration needed for prophylaxis have never been estimated. Maternal toxicity is rare when MgSO4 is carefully administered and monitored. Deep tendon reflexes, respiratory rate, urine output and serum concentrations are the most common variables for monitoring the toxic effect. Currently the United States (US) Food and Drug Administration (FDA) is advising health care professionals against using MgSO4 injection for more than 5–7 days to stop preterm labor in pregnant women (off-label use). Administration of MgSO4 injection to pregnant women for more than 5–7 days may lead to low calcium levels and bone problems in the fetus, including osteopenia and fractures. The harmful effect in the fetus with the shortest duration is not established. In light of this new safety information, the drug label for MgSO4 injection, USP 50% has also been changed, including changing the pregnancy category to D from A and denoting the effect as “New teratogenic effects”. Similarly, the manufacturers of other MgSO4 injection products have made similar changes to their drug labels. In this review, the currently available knowledge of the pharmacokinetics of MgSO4 and its clinical usage for women with pre-eclampsia and eclampsia, its off-label use and safety concern regarding the warning announced by the FDA will be outlined.

Perceptions by pregnant and childbearing-age women in southern Brazil towards teratogenic risk from medicines and radiotherapy / Percepções de risco teratogênico de medicamentos e radioterapia por gestantes e mulheres em idade fértil no Sul do Brasil / Percepciones de riesgo teratogénico de medicamentos y radioterapia en mujeres embarazadas y en edad fértil en el sur de Brasil

Mistaken perception of teratogenic risk can keep pregnant women from using safe medicines. The current study analyzed women’s concepts and perceptions towards teratogenic risk from medicines and exposure to radiotherapy during pregnancy. The quantitative data resulted from interviews with 287 pregnant and non-pregnant women. Two qualitative focus groups were conducted. No significant differences were observed between the two groups in terms of perceptions of teratogenic risk. Median perceptions of non-teratogenic exposures (paracetamol and metoclopramide) were close to the expected values, while higher values were found for teratogenic exposures (misoprostol and radiotherapy). The logic women used to estimate risk was classification of medicines as “strong” or “weak”. Medicines perceived as “weak” by the women do not pose any teratogenic risk, as shown by the median perceptions close to the true values. Meanwhile, “strong” medicines were viewed as dangerous, thus explaining the high median perceptions of teratogenic exposures.

Percepção de risco teratogênico equivocada pode privar a gestante do uso de medicamentos seguros. O estudo analisou concepções e percepções de risco teratogênico de mulheres sobre o uso de medicamentos e exposição à radioterapia durante a gestação. Dados quantitativos resultaram da realização de entrevistas com 287 gestantes e não gestantes. Qualitativamente, dois grupos focais foram realizados. Não se observaram diferenças significativas nas percepções de risco teratogênico entre grupos. As medianas das percepções para as exposições não teratogênicas – paracetamol e metoclopramida – foram próximas do valor esperado, e para as exposições teratogênicas – misoprostol e radioterapia – valores maiores foram encontrados. A lógica acionada pelas mulheres na estimação do risco é a da classificação dos medicamentos em fortes e fracos. Medicamentos percebidos pelas mulheres como fracos não apresentam risco, evidenciado pela aproximação das medianas ao valor esperado. Já medicamentos fortes são vistos como perigosos, justificando as altas medianas das exposições teratogênicas.

Percepción equivocada del riesgo teratogénico puede privar a las embarazadas de la utilización de medicamentos seguros. En este estudio se analizan las concepciones y la percepción de riesgo teratogénico de mujeres con respecto al uso de medicamentos y exposición a la radioterapia durante el embarazo. Los datos cuantitativos resultan de la administración de entrevistas a 287 mujeres embarazadas y no embarazadas; los cualitativos, de dos grupos focales. No se encontraron diferencias significativas en la percepción de riesgo entre los grupos. Las medianas para la percepción de riesgo a las exposiciones no teratogénicas resultaron cerca del valor esperado, mientras que para las exposiciones teratogénicas se encontraron valores más altos. La lógica usada por las mujeres para estimar el riesgo clasifica los medicamentos en fuertes y débiles. Aquellos percibidos como débiles no suponen riesgo (lo que se evidencia por la aproximación de las medianas al valor real). Por otra parte, los fuertes son vistos como peligrosos, lo que justifica las medianas altas para los riesgos teratogénicos.

Brazilian blood donation eligibility criteria for dermatologic patients / Critérios brasileiros de elegibilidade à doação de sangue para pacientes dermatológicos

A focused and commented review on the impact of dermatologic diseases and interventions in the solidary act of donating blood is presented to dermatologists to better advise their patients. This is a review of current Brazilian technical regulations on hemotherapeutic procedures as determined by Ministerial Directive #1353/2011 by the Ministry of Health and current internal regulations of the Hemotherapy Center of Ribeirão Preto, a regional reference center in hemotherapeutic procedures. Criteria for permanent inaptitude: autoimmune diseases (>1 organ involved), personal history of cancer other than basal cell carcinoma, severe atopic dermatitis or psoriasis, pemphigus foliaceus, porphyrias, filariasis, leprosy, extra pulmonary tuberculosis or paracoccidioidomycosis, and previous use of etretinate. Drugs that impose temporary ineligibility: other systemic retinoids, systemic corticosteroids, 5-alpha-reductase inhibitors, vaccines, methotrexate, beta-blockers, minoxidil, anti-epileptic, and anti-psychotic drugs. Other conditions that impose temporary ineligibility: occupational accident with biologic material, piercing, tattoo, sexually transmitted diseases, herpes, and bacterial infections, among others. Discussion: Thalidomide is currently missing in the teratogenic drugs list. Although finasteride was previously considered a drug that imposed permanent inaptitude, according to its short halflife current restriction of 1 month is still too long. Dermatologists should be able to advise their patients about proper timing to donate blood, and discuss the impact of drug withdrawal on treatment outcomes and to respect the designated washout periods.

Uma revisão centrada no impacto de doenças e intervenções dermatológicas no ato solidário de doar sangue é apresentada aos dermatologistas para melhor aconselhamento dos seus pacientes. Esta é uma revisão das atuais normas técnicas brasileiras sobre procedimentos hemoterápicos conforme determinado pela Portaria Ministerial no 1353/2011 do Ministério da Saúde e atuais normas internas do Hemocentro de Ribeirão Preto, um centro de referência regional em procedimentos hemoterápicos. Critérios para inaptidão definitiva: doenças autoimunes (>1 órgão comprometido), antecedente pessoal de câncer diferente de carcinoma basocelular, dermatite atópica ou psoríase graves, pênfigo foliáceo, porfirias, filariose, hanseníase, tuberculose ou paracoccidioidomicose extrapulmonares e uso prévio de etretinato. São condições de inelegibilidade temporária: uso de outros retinóides sistêmicos, corticoides sistêmicos, inibidores da 5-alfa-redutase, vacinas, metotrexato, betabloqueadores, minoxidil, anticonvulsivantes e antipsicóticos. Outras condições responsáveis por inaptidão temporária: acidente ocupacional com material biológico, "piercing", tatuagem, doenças sexualmente transmissíveis, herpes, infecções bacterianas, entre outras. Discussão: Talidomida atualmente não consta na lista de medicações teratogênicas. Apesar do uso da finasterida já ter sido considerada como critério para inaptidão definitiva, de acordo com sua meia-vida curta a restrição atual de 1 mês ainda é demasiadamente longa. Dermatologistas devem ser capazes de aconselhar seus pacientes sobre o momento adequado para doar sangue e discutir o impacto da suspensão de medicações nos resultados do tratamento de forma a respeitar os períodos de restrição designados.

Effect of aspirin on the developing teeth of neonates / Efecto de la aspirina en el desarrollo de los dientes de neonatos

The objective of the present study was to evaluate the effect of aspirin (Acetyl Salicylic Acid) on the developing teeth of the fetus while the mothers were treated through out the pregnancy. Aspirin is a widely used analgesic and antipyretic drug used for symptomatic treatment. However, recent animal studies have indicated a potent teratogenicity of Acetyl Salicylic Acid. Its easy availability without prescription has been associated with high possibility of misuse, especially in the developing world. An experimental control study was carried out where female rabbits being treated with aspirin were taken as mammalian model, and their offspring were used to evaluate the developmental defects in teeth. Quantitative analysis of minerals in three types of the sample teeth, was done using scanning electron microscope and energy dispersive X-ray spectroscopy (SEM-EDX). Calcium was the most affected mineral and incisors and mandibular molars were found to be the most affected teeth. Voluminous variations were observed in the mineral contents of samples from the treated and control group, however, significant results could not be achieved. A larger sample size could possibly be needed to produce more conclusive results.

El objetivo del estudio fue evaluar el efecto de la aspirina (ácido acetilsalicílico) sobre el desarrollo de los dientes en fetos de conejos, cuyas madres fueron tratadas durante toda la gestación. La aspirina es un fármaco ampliamente utilizado como analgésico y antipirético para el tratamiento sintomático. Sin embargo, estudios recientes en animales han indicado una teratogenicidad potente por parte del ácido acetilsalicílico. Su fácil disponibilidad, sin la necesidad de receta médica, se ha asociado con una alta posibilidad de su mal uso, especialmente en el mundo desarrollado. Se diseñó un estudio de control experimental, donde conejos hembras fueron tratadas con aspirina, tomándose como modelo de mamíferos, y sus crías fueron utilizadoa para evaluar los defectos en el desarrollo de los dientes. Se realizó el análisis cuantitativo de tres tipos de minerales en los dientes de la muestra mediante microscopio electrónico de barrido y espectroscopía de rayos X por dispersión de energía (SEM-EDX). El calcio fue el mineral más afectado y los incisivos y molares inferiores fueron como los dientes más afectados. Grandes variaciones se observaron en el contenido mineral de las muestras de los grupos tratado y control, sin embargo, no se lograron resultados significativos. Un tamaño de muestra más sería necesario para producir resultados más concluyentes.

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

O uso milenar de plantas medicinais mostrou ao longo dos anos, que determinadas plantas apresentam substâncias potencialmente perigosas. Do ponto de vista científico, algumas pesquisas mostraram que muitas dessas plantas possuem substâncias agressivas e por essa razão devem ser utilizadas com cuidado, respeitando seus riscos toxicológicos. Os efeitos mais preocupantes do uso indiscriminado de plantas medicinais são embriotóxico, teratogênico e abortivo, uma vez, que os constituintes da planta podem atravessar a placenta, chegar ao feto e gerar um desses efeitos. Este estudo objetiva fornecer uma listagem das principais plantas medicinais que tenham efeitos embriotóxicos, teratogênicos e abortivos comprovados, conhecendo as partes da planta utilizadas e seus respectivos nomes científicos, com a finalidade de alertar gestantes quanto aos riscos de seu uso. Realizou-se buscas nas bases eletrônicas de dados SciELO, PubMed, MEDLINE, LILACS, CAPES e Google acadêmico. Nos resultados encontrados, plantas como Arnica (Arnica montana), Artemísia (Artemisia vulgaris), Arruda (Ruta chalepensis/ Ruta graveolens), Barbatimão (Stryphnodendron polyphyllum), Boldo (Vernonia condensata) dentre outras, podem vir a gerar um desses efeitos. A partir deste estudo comprova-se que para a maioria das plantas medicinais não há dados a respeito da segurança de seu uso durante a gravidez.

The ancient use of medicinal plants has shown over the years that certain plants have potentially dangerous substances. From a scientific point of view, some studies have shown that many of these plants contain aggressive substances and therefore should be used with caution, respecting their toxicological risks. The most important effects of the indiscriminate use of medicinal plants are embryotoxic, teratogenic and abortifacient since the plant constituents can cross the placenta, reaching the fetus and leading to one of these effects. This study aimed to provide a list of the major medicinal plants that have proven embryotoxic, teratogenic and abortifacient effects, including the used plant parts and their respective scientific names, in order to warn pregnant women about the risks of its use. Searches were carried out in the electronic databases SciELO, PubMed, MEDLINE, LILACS, CAPES and Google Scholar. Results indicated that plants such as mountain arnica (Arnica montana), mugwort (Artemisia vulgaris), fringed rue (Ruta chalepensis / Ruta graveolens), "Barbatimão" (Stryphnodendron polyphyllum) and "Boldo" (Vernonia condensata) are likely to generate such an effect. This study shows that for most medicinal plants there are not data regarding the safety of their use during pregnancy.

Progress on the apoptosis and the neural tube defects / 国际儿科学杂志

Apoptosis may play an important role in organ development and balance maintenance, which is beneficial to clear away the abnormal cells. Some teratogens may affect the key apoptotic genes expression, including the genetic defects, the nutritional, and the environmental factors, etc. Apoptotic dysfunction would interfere with the bodys normal development and result in deformity.

Malformações congênitas em ruminantes no semiárido do nordeste Brasileiro / Congenital malformations in ruminants in the semiarid of the Brazilian northeast

Congenital malformations caused by the ingestion of Mimosa tenuiflora have been reported in ruminants in the semiarid of the Brazilian Northeast. This paper reports malformations diagnosed in ruminants, from 2000 to 2008, by the Veterinary Pathology Laboratory of the Federal University of Campina Grande, Patos, PB, in municipalities of the states of Paraíba, Pernambuco and Rio Grande do Norte. During the period, 47 (3.48 percent) out of 1.347 ascensions were reported as malformations. Based in the type of malformation and in the origin of the animals, malformations were divided in: 1) caused by the ingestion of M. tenuiflora, and 2) sporadic malformations of unknown causes. In sheep, 21 out of 418 ascensions were malformations, being 18 (4.3 percent) of malformations caused by M. tenuiflora and 3 (0.71 percent) of sporadic malformations. In cattle, 14 out of 434 ascensions were malformations, from these 8 (1.84 percent) were caused by M. tenuiflora and 6 (1.38 percent) were sporadic malformations. In goats, 12 out of 495 ascensions were malformations, being 9 (1.81 percent) malformations related with the ingestion of M. tenuiflora and 3 (0.6 percent) sporadic malformations. More frequent malformations caused by M. tenuiflora were arthrogryposis, micrognatia, palatoschisis, microphtalmia and unilateral or bilateral hypoplasia or aplasia of the incisive bones. Sporadic malformations were acephaly and hermaphrodite, dicephaly and malformations of mesenteric vessel in sheep; atresia ani in three goats; and hydranencephaly, atresia ani, ribs malformation with eventracion, cerebellar hypoplasia with hydrocephalus, pulmonary choristoma and meningocele, and siamese twins in cattle. A case of cerebellar hypoplasia with hydrocephalus was negative on immunohistochemistry to bovine viral diarrhea virus. Malformations caused by M. tenuiflora occurred during the whole year...

Malformações congênitas causadas pela ingestão de Mimosa tenuiflora têm sido observadas em ruminantes no semiárido do Nordeste Brasileiro. Neste trabalho foram estudadas as malformações congênitas em ruminantes diagnosticadas entre 2000 e 2008, em municípios da Paraíba, Pernambuco e Rio Grande do Norte. Durante o período foram recebidos 1.347 materiais de ruminantes para diagnóstico, desses 47 (3,48 por cento) foram dignosticados como malformações congênitas. Com base no tipo de malformação e na procedência do animal as malformações foram divididas em: 1) causadas pelo consumo de M. tenuiflora; e 2) malformações esporádicas, sem causa conhecida. De 418 materiais de ovinos, 21 corresponderam a malformações, sendo 18 (4,3 por cento do total de materiais) de malformações causadas por M. tenuiflora e 3 (0,71 por cento) de malformações esporádicas. De 434 materiais de bovinos, 14 foram diagnosticados como malformações, sendo 8 (1,84 por cento) causadas por M. tenuiflora e 6 (1,38 por cento) malformações esporádicas. De 495 materiais de caprinos, 12 apresentaram malformações, sendo 9 (1,81 por cento) causadas pela ingestão de M. tenuiflora e 3 (0,6 por cento) malformações esporádicas. As principais malformações causadas por M. tenuiflora foram artrogripose, micrognatia, palatosquise, microftalmia e hipoplasia ou aplasia unilateral ou bilateral dos ossos incisivos. As malformações esporádicas incluiram: acefalia e hermafroditismo, dicefalia e malformações de vasos intestinais em ovinos; atresia anal em três caprinos; e hidranencefalia, atresia anal, malformações de costelas com eventração, hipoplasia cerebelar e hidrocefalia, coristoma pulmonar e meningocele, e gêmeos siameses em bovinos. O caso de hipoplasia cerebelar com hidrocefalia foi negativo pela imuno-histoquímica para o vírus da diarreia viral bovina. Malformações congênitas causadas por M. tenuiflora ocorreram durante todo o ano...

Embryo Toxicity and Teratogenic Effects of Microula Seed Oil on Rat / 中国康复理论与实践

@#Objective To investigate toxicity and teratogenic effect of Microula seed oil on embryo of rat.Methods 150 mature Wistar rats (100 females, 50 males) were selected with female∶ male = 2∶1 cage match. During the daily morning examination the sperm was discovered in the vagina as the zero day for conception.100 pregnant rats were randomly divided into 5 groups (n=20 in each group): treatment group (included 3 groups: to give Microula seed oil 2.5 g /kg, 5.0 g /kg, 10.0 g /kg body weight, ig, respectively), cyclophosphamide group(7 mg/ kg body weight, sc) and the edible oil group (to give dose, such as volume as Microula seed oil, ig). From the 7th day of pregnancy, the treatment group, the edible oil group were given intervention once a day for 10 days. From the 11th day of pregnancy cyclophosphamide group was given cyclophosphamide as intervention once a day, for 3 days. On the 20th day the pregnant rats were killed.Results The body weight of pregnant rats and the rate of live births were significantly higher in the Microula seed oil dose group than in the cyclophosphamide group (P<0.01), stillbirth rate and birth rate of absorption was significantly lower in the Microula seed oil dose group than in the cyclophosphamide group (P<0.01), and no significant difference from the edible oil group (P> 0.05); the fetal rat, body weight, body length, tail length in all groups of Microula seed oil was no significant difference from the edible oil group (P> 0.05). There was no malformation in appearance, viscera, bones in the treatment group and the edible oil group while there were 112 fetal rats with deformity in 140 in the cyclophosphamide group.Conclusion Microula seed oil at doses of 2.5 g /kg, 5.0 g /kg, 10.0 g /kg body weight had no significant role in the toxicity and teratogenicity on embryos of pregnant rats.

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

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 compared to the control group. Cd2+ administration was responsible for the most severe teratogenic signs compared to Cu2+ and Pb2+ treatments. It can be concluded that heavy metals are embryotoxic and teratogenics. We suggest that cutaneous and liver hemorrhages are the best signs to evaluate teratogenicity induced by Cd2+, Cu2+ and Pb2+.