Neural tube defects (NTDs), which is a congenital malformation, in significant part on the statistics of perinatal morbidity and mortality due to their high incidence rates. The DA can be limited to the central nervous system and / or peripheral, and may also include the overlying tissues (bones, muscles and connective tissue). Folic acid (FA) is a nutrient that plays a fundamental role in the process of cell multiplication. And the remarkable importance of folic acid in preventing NTDs where published studies portray the relationship between the levels of PA and the birth of children with NTDs, whereby the higher the rate of serum folate, less frequent are the births of children with NTDs . Although he knows that the AF is directly linked to the prevention of NTDs, little has been epidemiologically demonstrated the use of it in our population (especially from the Northeast-SE Brazil). All study women received prenatal (PN), however from the second month of conception outside the period in which it is contemplated by the AF prevention, highlighting the lack of an effective family planning. Was not performed by folic acid supplementation in 56.6% of women studied and the other 43.3% who did, began after the second month of pregnancy, which had become ineffective in the prevention, the same vitamin, the DTN. Showed that only 3.3% of cases of NTD group had a gestational age was less than 37 weeks and 50% were primigravida, the same group. The women studied were aged 24.8 years on average to become pregnant. Epidemiological parameters when compared with the comparison group, were similar, since both groups used the same health service, with the characteristic of high risk. The levels of serum folate in a group of women studied, remained normal and the highest of scientific studies published so far with similar characteristics. Prevention with the use of folic acid should be intensified by the various sectors of society, the risk group studied, so to avoid the recurrence of neural tube defects, reducing the incidence and recurrence in women who are more likely to generate conceptuses with this malformation. / O defeito do tubo neural (DTN), que é uma malformação congênita, participa de modo considerável nas estatísticas de morbidade e mortalidade perinatais devido a suas elevadas taxas de incidência. Os DTN, podem se limitar ao sistema nervoso central e/ou periférico, e também podem incluir os tecidos sobrejacentes (ossos, músculos e tecido conjuntivo). O ácido fólico (AF) é um micronutriente que apresenta papel fundamental no processo de multiplicação celular. E notória a importância do ácido fólico na prevenção dos DTN onde, estudos publicados retratam a relação dos níveis de AF e o nascimento de crianças com DTN, segundo os quais, quanto maior a taxa de folato sérico, menos frequentes são os nascimentos de crianças com DTN. Embora que saiba-se que o AF está ligado diretamente à prevenção do DTN, pouco se tem evidenciado epidemiologicamente o uso do mesmo na população brasileira (em especial a da região Nordeste/SE/Brasil). Todas as mulheres estudadas realizaram pré-natal (PN), entretanto a partir do segundo mês de concepção, fora do período que contempla-se a prevenção pelo AF, evidenciando a falta de um planejamento familiar efetivo. Não foi realizada a suplementação por ácido fólico em 56,6% das mulheres estudadas e as outras 43,3% que a fizeram, iniciaram após o segundo mês de gestação, o que tornara ineficaz a prevenção, pela mesma vitamina, ao DTN. Evidenciou-se que apenas 3,3% dos casos do grupo DTN tiveram idade gestacional foi inferior a 37 semanas e 50% foram primigesta, do mesmo grupo. As mulheres estudadas tiveram idade média ao engravidar 24,8 anos. Os parâmetros epidemiológicos, quando comparados com o grupo de comparação, mostraram-se semelhantes, uma vez que ambos os grupos utilizaram o mesmo serviço de saúde, com a característica de alto risco. Os níveis de ácido fólico sérico, em um grupo, das mulheres estudadas, mantiveram-se normais e mais elevados dos que os estudos científicos publicados até o momento com semelhantes características. A prevenção com o uso do ácido fólico deve ser intensificada pelos vários setores da sociedade, ao grupo de risco estudado, para evitarmos assim a recorrência do defeito do tubo neural, reduzindo a incidência e recorrência em mulheres que tem maior chance de gerarem conceptos com essa malformação.

Magister Scientiae (Physiotherapy) - MSc(Physio) / Neural tube defects (NTDs) are the world‘s second most common birth defects after cardiovascular defects. In developing countries, poor access to health care services among children with NTDs contributes to early infant deaths, while those who survive live with severe disabilities. In Zambia, all children with NTDs in need of surgery are referred to Lusaka and physiotherapy services are not available in health facilities below the first level hospitals. The aim of the current study was to determine the profile of children with NTDs and to explore the experiences of mothers with accessing health care services for these children. The study which was conducted at the University Teaching Hospital (UTH) in Lusaka consisted of both quantitative and qualitative methods. The quantitative phase consisted of a retrospective record review of children with NTDs, who were admitted to UTH from January to December, 2010. A sample of 50 medical records was used based on available records, and data collection was done using a data extraction sheet which was specifically designed for the study. Analysis of quantitative data was done using Statistical Package for Social Science (SPSS) version 20.0. The qualitative phase had two parts, with the first part involving in-depth interviews with a purposefully selected sample of 20 mothers of children who were admitted to UTH. The second part used a sample of convenience of four mothers who had brought their children for follow up visits. All interviews were audiotaped, transcribed verbatim and translated, and recurring ideas were coded and collapsed into categories and themes. Permission to conduct the study was obtained from the UWC Research Grant and Study Leave Committee, University of Zambia Research Ethics Committee, and University Teaching Hospital management. Informed written consent was obtained from the mothers who accepted to take part in the study. Results from the record review revealed that the majority of children were from Lusaka province, with ages ranging from one day to 48 months and a male predominance of 58%. Myelomeningocele was the most common type of NTD (44%) with the lumbar region being the common site (52%). Hydrocephalus was present in 74% of children, 30% of children had both paraplegia and incontinence and 22% (n=11) of the files had no information on the neurological impairments. Wound infection was present in 40% (n=20) of the children. The majority (66%) of children were lost to follow up. Mothers of children who were admitted in UTH cited transport to UTH and back home as the main challenge. Other challenges included the lack of a prenatal diagnosis, the need for information, uncertainty about future of their children, and concerns about their family. Interviews with mothers on experiences with accessing physiotherapy services found that the lack of knowledge among mothers was the main reason children were not accessing physiotherapy services. Findings on access to health care were related to the ―Four A‘s‖ access theory which consists of four dimensions of access namely geographical accessibility, availability, affordability and acceptability. It is recommended that health care providers and policy makers ensure that all children with NTDs are provided with free transport to and from referral hospitals. Policy makers need to consider involving physiotherapists in out-reach programmes and mobile clinics to ensure access to physiotherapy services for all children in need of the service. Health care providers must also ensure that they give adequate information to mothers of children born with birth defects as this enhances their access to appropriate health care services.

This project was the first study of the genetics and embryo-pathology of exencephaly in a partially inbred mouse stock, SELH/Bc. Exencephaly was found in 17% of SELH fetuses. Analysis of day 8-9 gestation embryos indicated that SELH embryos were collectively normal in general development, but delayed in neural tube closure relative to overall or general development compared to two normal strains of mice, ICR/Be and SWV/Bc. Exencephaly was observed to be caused by a failure of fusion of the cranial neural folds in the mesencephalon region in SELH. All SELH embryos appeared to be abnormal in their pattern of cranial neural tube closure. They fail to make initial contact at the prosencephalon/mesencephalon junction region of the cranial neural folds (the first fusion in the cranial neural folds in normal embryos). SELH embryos, fused their anterior neural folds via an alternate (possibly passive) mechanism compared to normal strains of mice (SWV/Bc, and ICR/Be), by fusing the folds in a "zipper-like" fashion from the rostral base of the prosencephalon. This closure of the neural tube in genetically liable embryos by an abnormal sequence of events suggests a new model for anterior neural tube closure failure. Liability to exencephaly appeared to be fixed in the SELH stock. Of the 53 SELH males tested, all produced exencephaly. SELH animals were found to be heterogeneous in the frequency of exencephaly they produced, indicating that there are still genes segregating in the stock which affect the ability of embryos to complete anterior neural tube closure. Exencephaly in SELH does not appear to be caused by an autosomal dominant, sex-linked dominant or recessive, or simple autosomal recessive single gene, although F2, BCl, and BC2 exencephaly frequencies (after an outcross to ICR/Be) suggest that only a small number of genes are involved. A marked excess of female exencephalics was observed in SELH, F2, BCl, and BC2 fetuses. / Medicine, Faculty of / Medical Genetics, Department of / Graduate

Orientadores: Sergio Tadeu Matins Marba, Helder José Lessa Zambelli / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-22T03:05:39Z (GMT). No. of bitstreams: 1 Zomignani_AndreaPeterson_M.pdf: 1128762 bytes, checksum: 59ae9805910c4b220c7bfa8d2e7bcbab (MD5) Previous issue date: 2012 / Resumo: Objetivo: Descrever uma população de recém-nascidos com encefalocele. Método: Estudo restrospectivo, descritivo e analítico por análise dos prontuários de recém-nascidos com diagnóstico de encefalocele, no Hospital da Mulher Prof. Dr. José Aristodemo Pinotti - Centro de Atenção Integral à Saúde da Mulher (CAISM), da Universidade Estadual de Campinas (UNICAMP). Foram incluídos todos os pacientes nascidos com diagnóstico de encefalocele no período de janeiro/1997 a julho/2008. Foram estudados: idade materna, paridade, pré-natal, apresentação fetal, tipo de parto, sexo, idade gestacional, índice de Apgar, peso, tipo de encefalocele, tratamento cirúrgico, ocorrência de óbitos, período de internação e retardo do desenvolvimento neuropsicomotor (RDNPM). Foram calculadas as frequências para cada variável analisada e a associação entre algumas variáveis foi verificada estatisticamente pelos testes qui-quadrado e exato de Fisher, considerando alfa de 5%. Resultados: Foram analisados 43 casos com prevalência de 1,24/1000 nascimentos. A faixa de idade materna de maior ocorrência foi 18 a 32 anos (83%), em mães não primigestas (65%), que fizeram os exames pré-natais (95%). A apresentação fetal mais recorrente foi cefálica (45%) com parto cesáreo (65%). Foram encontrados mais casos em meninas, com idade gestacional _37 semanas, tendo a maioria das crianças com a malformação nascido a termo (79%). No primeiro minuto houve Apgar menor ou igual a 7 em 58% dos casos. Em 67% dos casos o peso foi adequado, 27% foram baixo peso e 4,6% muito baixo peso. O tipo de encefalocele mais prevalente foi occipital e em 67% dos casos houve cirurgia. O óbito ocorreu em 31% dos recém nascidos e 55% tiveram período de internação de 1 a 15 dias. Em 62% dos casos foi descrito retardo do desenvolvimento neuropsicomotor. Conclusões: A prevalência de encefalocele foi de 1,24/1000 nascimentos e esteve associada às mães jovens e não primigestas. A apresentação cefálica foi à apresentação mais comum e o tipo de parto mais frequente foi parto cesáreo. Foi mais comum a presença de encefalocele em meninas, com idade gestacional _37 semanas, em nascidos a termo, com índice de Apgar baixo e com peso adequado. A maioria teve encefalocele occipital e precisou de cirurgia, sendo a taxa de mortalidade alta. Na maioria dos casos houve RDNPM / Abstract: Objective: To describe a serie of newborns with encephalocele. Method: Retrospective, descriptive and analytical study, with medical records analysis of newborns with encephalocele, born at the Hospital da Mulher Prof. Dr. José Aristodemo Pinotti - Center for Integral Assistance to Women's Health at the University of Campinas (UNICAMP). All the patients born with these conditions were selected from January/1997 until July/2008. It was studied: maternal age, parity, prenatal care, fetal presentation, mode of delivery, gender, gestational age, Apgar score, birth weight, type of encephalocele, surgical treatment, occurrence of death, hospitalization period, delayed neuropsychomotor development. Frequencies were calculated for each variable and the association among then were assessed statistically using the chi-square and Fisher exact test, considering a 5% alpha. Results: There were 43 cases with prevalence of 1,24/100 births. Maternal age range most frequent was 18 to 32 years (83%), in not primigravidae (65%), who made the prenatal care (95%). The most recurrent fetal presentation was cephalic (45%) with cesarean sections (65%). More cases were found in girls, with gestational age _37 weeks, with the majority of infants with malformations born at term (79%). First minute Apgar score was less than or equal to 7 in 58% of the cases. In 67% of the cases the weight was appropriate, 27% were low birth weight, and 4,6% were very low birth weight infants. The most prevalent type of encephalocele was occipital; 67% of the cases were underwent the surgery. Death occurred in 31% of the newborns and hospitalization period, in most cases, was 1 to 15 days. Neuropsychomotor development delay was observed in 62% of the cases. Conclusions: The prevalence of encephalocele was 1,24/1000 births and there was associated with young mothers and not primiparous. The cephalic presentation was common and there were more cesarean sections. It was more common the presence of encephalocele in girls, with gestational age _37 weeks in term newborns with low Apgar score and appropriate weight. Most had occipital encephalocele and needed surgery, and there was a high mortality rate. In most cases there were neurological deficit / Mestrado / Saude da Criança e do Adolescente / Mestra em Ciências

Valproic Acid Promotes Acetylation of Superoxide Dismutase-2 During Neurogenesis. Valproic acid (VPA) is a known developmental toxicant associated with a high prevalence of neural tube defects (NTD). The mechanism of VPA-induced NTD is unclear, but oxidative stress may be implicated. To understand how embryotoxic oxidative stress may occur, we measured superoxide dismutase (SOD) activity following VPA treatment in the embryonic pluripotent P19 mouse carcinoma cell line. In undifferentiated P19 cultures treated with VPA (5 mM), dichlorofluorescein fluorescence increased 15% compared to untreated controls over 20 min, indicating a modest, yet statistically significant increase in ROS generation. Undifferentiated P19 cells were treated with VPA for 6 h, after which total SOD and mitochondrial SOD (SOD2) activities were measured. VPA treatment decreased total SOD activity by approximately 20% but SOD2 activity was undetectable; but this was not a consequence of changes to SOD (SOD1 or SOD2) protein concentrations. Interestingly, glutathione redox state increased from -262 mV to -245 mV after a 6 h treatment with VPA, indicating significant oxidation of the cellular redox environment. Measurement of mitochondrial superoxide levels showed an increase following VPA treatments. While it is unlikely that VPA works directly as an oxidant, these data suggest that VPA may promote oxidative stress through an alternative means, such as via the inhibition of SOD activity and thus, allow for an increase in ROS. Importantly, VPA is a known deacetylase inhibitor, and SOD2 function is regulated by acetylation. As such, we evaluated the acetylation state of SOD2 to determine potential disruption via acetylation. Treated undifferentiated P19 cells showed a significant increase in SOD2 acetylation. However, in fully differentiated P19-derived neurons, cells showed no such SOD2 acetylation. Additionally, pretreatment with dithiole-3-thione (D3T), a Nrf2 activator of the antioxidant response, attenuated VPA-induced mitochondrial ROS production and SOD2 acetylation and improved SOD2 activity, suggesting Nrf2 as a potential means to reduce VPA-mediated oxidative stress. To evaluate the effects in the embryo proper, gestational day 8 mouse embryos were treated with VPA in culture for 6 h. Similar to P19 cells, VPA-treated neurulating embryos showed significant SOD2 acetylation and a concomitant decrease in total SOD activity. These data support a similar consequence of VPA-induced oxidative stress in embryos as is demonstrated in our cellular model. Since no SOD2 acetylation is observed in differentiated neurons and VPAinduced SOD2 acetylation occurs more prevalently in undifferentiated/differentiating cells, these data purport means by which VPA preferentially induces oxidative stress in developing systems.

This study was designed to document the prevalence of neural tube defects in Cape Town and to determine the outcome of children born with a myelomeningocele and operated on within the Neurosurgical service of the University of Cape Town. The aim of the prevalence study was to document the frequency of neural tube defects (NTD) over a twenty year period in Cape Town (1973 - 1992) and to determine the effects of race, gender, maternal age, parity, and season of conception on the prevalence. Multiple sources of ascertainment were used, including all maternity hospital records, neurosurgical and spinal defects clinic data, as well as those from the Human Genetics Department and Fetal Abnormality Group. The prevalence rates for NTD fluctuated between 1,74 and 0,63 per 1 000 births, but showed no significant trends over the twenty year period. Prevalence rates were highest for the white population group at 2,56 per 1 000 births compared to 0,95 per 1 000 for blacks and 1,05 per 1 000 for those of mixed ancestry. The higher rates in the whites, who are of British and European extraction and belong to the more affiuent section of the community, would suggest that the possible effects of nutrition and infection are overshadowed by genetic factors. There was a female preponderance for both spina bifida (M:F ratio 0,89) and anencephaly (M:F ratio 0,67). The highest NTD rates were found at both ends of the maternal age range (<20 years and >35 years of age). The prevalence was highest at the extremes of birth order (1,65 and 1,58 for birth order 1 and >7, respectively, and 0,56 and 0,45 for birth order 5 and 6, respectively). A seasonal variation occurred which differed from that reported for the Northern Hemisphere and may reflect local climatic conditions. The aim of the outcome study was to follow a group of infants who were operated on for myelomeningocele (01 January 1979 - 31 December 1985) and evaluate their outcome at five years of age, in an attempt to identify factors that may influence the quality of survival and their outcome, and to utilise these findings to recommend altering and improving ( where possible) the management of children born with myelomeningocele.

The teratogenic effects of valproic acid (VPA) are well known, though its teratogenic mechanism remains unknown. VPA induces oxidative stress, which may lead to double strand breaks (DSBs) in DNA. Though the cell may repair this damage via homologous recombination (HR) and non-homologous end joining (NHEJ), repair is not always error-free; genomic instability may arise from gene deletions, amplifications, rearrangements, and loss of heterozygosity. Such alterations may underpin VPAʼs teratogenicity. The present study evaluated VPAʼs ability to induce NHEJ and HR and characterized the changes in expression of two proteins key to HR (RAD51) and NHEJ (XRCC4). Using pKZ1 transgenic mice (C57BL/6 genetic background), we sought to measure NHEJ events via X-gal staining. Although consistent staining was observed in adult male brain (positive control), no staining was observed in embryos 12 or 24 hours after in utero exposure to a teratogenic dose of VPA (500 mg/kg, maternal subcutaneous dose) on gestational day 9 (GD9). To determine whether the lack of staining observed in embryos was due to low/absent expression of key DSB-repair proteins, we measured mRNA/protein expression of RAD51 and XRCC4 in C57BL/6, GD9-exposed embryos and maternal brain. One hour after treatment, XRCC4 was increased at the protein level in brain and embryo. RAD51 was not increased in embryos and not detected in adult brain. These data suggest that embryos do possess the protein mediators of NHEJ and HR and that VPA-induced changes in expression of XRCC4 may influence the type of repair pursued, potentially affecting DSB repair fidelity (accuracy). Determination of fidelity of VPA-induced HR was attempted with the Chinese hamster ovary cell line (CHO33) using DNA sequencing; low template concentration and purity precluded successful sequencing of DNA from recombinant colonies and the assessment of fidelity. Overall, these data demonstrate that the lack of X-gal staining observed in pKZ1 embryos is not due to an underexpression of at least one key protein in the NHEJ pathway. Furthermore, a VPA-induced change in the the type of repair pathway pursued by the embryo may have teratological implications. / Thesis (Master, Pharmacology & Toxicology) -- Queen's University, 2012-10-15 11:06:30.613

General toxicity evaluation and risk assessment for human exposure is essential when developing new pharmaceuticals and chemicals. Developmental toxicology is an important part of this risk assessment which consumes large resources and many laboratory animals. The prediction of developmental toxicity could potentially be assessed in vitro using embryo-derived pluripotent stem cells for lead characterization and optimization. This thesis explored the potential of short-time assays with pluripotent stem cells of embryonic origin using toxicogenomics. Three established pluripotent stem cell lines; P19 mouse embryonal carcinoma (EC) cells, R1 mouse embryonic stem (mES) cells, and SA002 human embryonic stem (hES) cells were used in the studies. Valproic acid (VPA), an antiepileptic drug which can cause the neural tube defects spina bifida in human and exencephaly in mouse, was used together with microarrays to investigate the global transcriptional response in pluripotent stem cells using short-time exposures (1.5 - 24 h). In addition to VPA, three closely related VPA analogs were tested, one of which was not teratogenic in mice. These analogs also differed in their ability to inhibit histone deacetylase (HDAC) allowing this potential mechanism of VPA teratogenicity to be investigated. The results in EC cells indicated a large number of genes to be putative VPA targets, many of which are known to be involved in neural tube morphogenesis. When compared with data generated in mouse embryos, a number of genes emerged as candidate in vitro markers of VPA-induced teratogenicity. VPA and its teratogenic HDAC inhibiting analog induced major and often overlapping deregulation of genes in mES cells and hES cells. On the other hand, the two non-HDAC inhibiting analogs (one teratogenic and one not) had only minor effects on gene expression. This indicated that HDAC inhibition is likely to be the major mechanism of gene deregulation induced by VPA. In addition, a comparison between human and mouse ES cells revealed an overlap of deregulated genes as well as species specific deregulated genes.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-03-29T18:19:17Z No. of bitstreams: 1 ricardocampelodaconceicao.pdf: 3005415 bytes, checksum: 93485f733d9f5ab38c981b4eca76fc2b (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-03-30T11:24:14Z (GMT) No. of bitstreams: 1 ricardocampelodaconceicao.pdf: 3005415 bytes, checksum: 93485f733d9f5ab38c981b4eca76fc2b (MD5) / Made available in DSpace on 2017-03-30T11:24:14Z (GMT). No. of bitstreams: 1 ricardocampelodaconceicao.pdf: 3005415 bytes, checksum: 93485f733d9f5ab38c981b4eca76fc2b (MD5) Previous issue date: 2009-12-17 / Os defeitos do fechamento do tubo neural (DFTN) figuram como a segunda maior causa de anomalias congênitas, e a sua incidência situa-se em torno de 1/1.000 nascidos vivos. Possui etiologia multifatorial, tendo na deficiência do ácido fólico seu principal fator de risco ambiental identificado. A suplementação de ácido fólico pré e pós-concepcional pode reduzir em até 70% o número de ocorrência e recorrência nos DFTN. O presente estudo tem o objetivo de avaliar o grau de conhecimento de médicos e enfermeiros obstetras sobre a prevenção dos DFTN. Foi realizado um estudo de natureza descritiva, do tipo transversal, em instituições públicas e privadas de saúde, maternidades e consultórios médicos da cidade de Juiz de Fora, MG, no período de dezembro de 2008 a junho de 2009. Participaram do estudo 118 voluntários (95 médicos obstetras e 23 enfermeiros obstetras), que responderam um questionário sem identificação, composto por 21 questões mistas, sobre a temática da prevenção dos DFTN. Foram analisadas as respostas em função das recomendações preconizadas pelo Ministério da Saúde em nosso país e das evidências científicas disponíveis. Verificou-se diferença entre as recomendações do Ministério da Saúde e o conhecimento baseado em evidências (p<0,001). Não foi encontrado nesse estudo, diferença entre o grau de conhecimento dos entrevistados quando comparado o nível de formação dos mesmos, o tempo que realizam atendimento pré-natal e entre as duas classes de profissionais avaliados. Houve diferença entre o grau de conhecimento relatado pelos profissionais e o grau de conhecimento avaliado pela pesquisa, baseado nas recomendações do Ministério da Saúde, e o que preconizam as evidências científicas (<0,001; p<0,001). Dos profissionais avaliados 94,1% relataram conhecer o papel do ácido fólico, embora apenas 11,9% afirmaram terem recebido capacitação sobre o assunto, e 64,2% relataram não saber ou erraram o período de início da suplementação do ácido fólico. Além disso, 68,6% responderam que a dose ideal deve ser de 5 mg/dia, e 68,6% também afirmaram que o período de suplementação deve ser o primeiro trimestre da gestação, conforme orientação do Ministério da Saúde. Os resultados demonstraram claramente a necessidade de melhor capacitação dos profissionais na formação acadêmica e na pós-graduação, além da manutenção permanente de programas de atualização para os envolvidos no atendimento à mulher. / Neural tube defects (NTD) ranks as the second leading cause of congenital anomalies and its incidence is situated around 1/1000 live births. It has a multifactorial etiology and the lack of folic acid is the main identified environmental risk factor. Supplementation of folic acid pre-and post-conception can reduces by up to 70% the number of occurrence and recurrence of NTD. Our study aimed to evaluate the knowledge level of physicians and obstetric nurses on the use of folic acid in the prevention of neural tube defects. We conducted a cross-sectional descriptive study, in public and private health facilities, in the city of Juiz de Fora, MG, from December 2008 to June 2009. The study included 118 volunteers (95 obstetricians and 23 obstetric nurses) who answered an anonymous questionnaire composed of 21 questions about the folic acid use in the prevention of NTD. We analyzed the responses according to the recommendations issued by the Ministry of Health and available scientific evidence. We found no difference between the knowledge levels of respondents when comparing the level of their training, experience in prenatal care and between the two classes of professionals evaluated. There was a difference between the reported knowledge level and the knowledge assessed level, based on the recommendations of the Ministry of Health (MOH), and the scientific evidence (p <0.001, p <0.001), respectively. It was also noticed the difference between the level of knowledge based on the recommendations of the MOH and the level of knowledge based on scientific evidences (p <0.001). The great majority of the study population (94.1%) has reported know the role of folic acid, while only 11.9% said they received training on the subject, and 64.2% has reported not know or had a incorrect answered about the period of early supplementation of folic acid. In addition, 68.6% answered that the optimal dose should be 5 mg / day and 68.6% also said that the period of supplementation should be the first trimester of pregnancy, as directed by MOH. The results clearly demonstrated the need for better training for professionals in academic and during graduate school, as well as ongoing maintenance of training programs for those involved in the women treatment.

One of the first embryonic structures generated during early human development is the neural tube. The embryonic process of neurulation, including neural tube closure, is necessary for proper brain and spinal cord development, whereas improper closure leads to neural tube defects including anencephaly, spina bifida, and craniorachischisis. The mechanism by which these defects occur is unknown, but some evidence suggest that redox disruption may play a role. Cellular redox state is important in regulating key processes during neural tube closure, including differentiation, proliferation, gene expression, and apoptosis. This study aims to determine whether redox potential shifts and these key processes are affected similarly or differentially after treatment with three neural tube defect-inducing developmental toxicants: ceramide (C2), valproic acid (VPA), and fumonisin (FB1). Using the P19 cell model of neurogenesis, in both undifferentiated and terminally differentiated cells, we analyzed glutathione (GSH) redox (Eh) potential to evaluate the effect of each toxicant over time. We show that in C2 and VPA treated cultures an oxidizing shift occurs, but interestingly, FB1 treatment results in a reducing shift in embryonic GSH Eh as compared to untreated cultures. Using the chick embryo model, comparable redox shifts were observed as were seen in P19 cells, supporting similarity between the models. To better understand how differential shifts in the redox state can result in similar defects, we then examined potential variances in neuronal differentiation and cellular proliferation, survival, metabolism, adhesion, and gene expression under each treatment. We report changes to cellular and embryonic endpoints that support dysmorphogenesis, likely the result of oxidizing or reducing stress that altered redox state. These results support the need for broad comparative analyses such as this to determine whether toxicants that cause the same types of defects, whether NTDs or others, act through similar or different mechanisms. This can better inform preventative measures used to reduce the risk and occurrence of birth defects.