Fármacos antiepilépticos usados en el embarazo y sus consecuencias sobre los resultados fetales: una revisión de la literatura / Antiepileptic drugs used in pregnancy and their consequences on fetal outcomes: a review of the literature

Los riesgos teratogénicos ocasionados por la exposición intrauterina a fármacos antiepilépticos (FAE) son conocidos, por lo que su prescripción se mantiene bajo estricto control. Describir los efectos adversos fetales de la exposición a FAE durante la gestación, reportados en la literatura durante el período 2016-2022. Revisión sistematizada de estudios que reportaron los efectos adversos fetales inducidos por la exposición a FAE en mujeres embarazadas en tratamiento por diagnósticos neurológicos, principalmente de epilepsia. La búsqueda se realizó en PubMed, Cochrane, Web of Science, SCOPUS, Biblioteca Virtual en Salud, Lilacs y SciELO. Se identificaron 37 artículos distribuidos en 13 países de Asia, Europa, América del Norte y Oceanía. Se observaron resultados perinatales adversos, tanto físicos como cognitivos, en la mayoría de los estudios. Los fármacos identificados como los más utilizados en los últimos años fueron valproato, topiramato, carbamazepina, lamotrigina y levetiracetam. Los FAE tienen potencial teratogénico en distintos grados de riesgo, provocando anomalías congénitas o efectos adversos en múltiples sistemas del cuerpo humano, siendo los sistemas nervioso, circulatorio y osteomuscular los más afectados.

The teratogenic risks caused by intrauterine exposure to antiepileptic drugs (AED) are known, so their prescription is kept under strict control. To describe the fetal adverse effects AED exposure during gestation, reported in the literature during the period 2016-2022. Systematized review of studies that reported fetal adverse effects induced for the exposure to AED in pregnant women in treatment for neurological diagnoses, mainly epilepsy. The search was carried out in PubMed, Cochrane, Web of Science, SCOPUS, Virtual Health Library, Lilacs and SciELO. 37 articles distributed in thirteen countries in Asia, Europe, North America and Oceania were identified. Adverse perinatal outcomes, both physical and cognitive, were observed in most studies. The most common drugs identified were valproate, topiramate, carbamazepine, lamotrigine and levetiracetam. AED have teratogenic potential in different degrees of risk, causing congenital anomalies or adverse effects in multiple systems of the human body, being the nervous, circulatory and musculoskeletal systems the most affected.

Reacción a fármacos con eosinofilia y síntomas sistémicos (DRESS) / Drug reaction with eosinophilia and systemic symptoms (DRESS)

La reacción a fármacos con eosinofilia y síntomas sistémicos (del acrónimo en inglés DRESS: drug reaction with eosinophilia and systemic symptoms) o síndrome de hipersensibilidad inducida por fármacos (del acrónimo en inglés DIHS: drug induced hypersensitivity syndrome), es una reacción adversa a fármacos (RAF) grave e infrecuente. Los mecanismos involucrados en su fisiopatogenia incluyen diversas alteraciones de las enzimas metabolizadoras de fármacos, con la consecuente acumulación de metabolitos reactivos, la reactivación secuencial de virus de la familia del herpes, la predisposición genética asociada a ciertos alelos de antígenos leucocitarios humanos (HLA) y una respuesta de hipersensibilidad retardada de tipo IV. En la actualidad, se han ido incorporando nuevos fármacos responsables de este cuadro como medicamentos biológicos, inmunosupresores y quimioterápicos. La presentación clínica del DRESS es variable. Tiene una morbimortalidad alta y supone costos elevados en la atención médica. Su tratamiento consiste, en primer lugar, en la suspensión de los fármacos causales o sospechosos de desencadenar el síndrome. Luego, según la gravedad del cuadro, se pueden indicar corticosteroides sistémicos o inmunoglobulina (IGIV) combinada con corticosteroides, plasmaféresis, ciclosporina, micofenolato de mofetilo y rituximab. El objetivo de este trabajo fue realizar una revisión sobre el DRESS y destacar los aspectos nuevos y relevantes de los últimos 5 años.

Drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS), is a serious and rare adverse drug reaction. Among the mechanisms involved in its pathophysiology, there are various alterations in drugmetabolizing enzymes with the consequent accumulation of reactive metabolites, sequential reactivation of viruses of the herpes family, genetic predis-position associated with certain HLA, and a type IV hypersensitivity response. Currently, new drugs responsible for this pathology have been incorporated, such as biologicals, immunosuppressants and chemotherapy. The clinical presentation of DRESS is variable. It has a high morbidity and mortality and involves high costs in medical care. Its treatment consists, in the first place, in the suspension of the causal or suspected drugs. Then, depending on severity, systemic corticosteroids or IVIG combined with corticosteroids, plasmapheresis, cyclosporine, mycophenolate mofetil, and rituximab may be indicated.The objective of this work was review DRESS and highlight the new and relevant aspects of the last 5 years.

Avaliação da ozonioterapia no tratamento da osteonecrose induzida por zoledronato em ratas senis / Evaluation of ozone therapy in the treatment of zoledronate-induced osteonecrosis in senile rats

A ozonioterapia vem se demonstrando uma ferramenta promissora na prevenção de infecções e no auxílio da reparação tecidual, conciliando com os desafios no tratamento da osteonecrose dos maxilares induzida por medicamentos (ONM-M), este projeto objetiva analisar os efeitos da ozonioterapia, em 55 ratas senis (18 meses), entre 300-350g, induzidas a osteonecrose via medicamentosa (Zoledronato 100µg/kg), após exodontia do primeiro molar inferior. Os animais foram divididos em 4 grupos equitativos (10 ratas por grupo), o primeiro grupo SAL, recebeu aplicações de soro fisiológico por 7 semanas, grupo SAL + OZ recebeu aplicações de soro fisiológico por 7 semanas e o tratamento com a ozonioterapia (0,7mg/kg) a cada 2 dias por 28 dias, o grupo ZOL recebeu aplicações de zoledronato (100µg/kg) por 7 semanas e por último o grupo ZOL + OZ recebeu também aplicações de zoledronato no mesmo protocolo e foi tratado com a ozonioterapia (0,7mg/kg) a cada 2 dias por 28 dias. Todos as ratas receberam a antibioticoterapia (Cristacilina® 0,1ml/kg por dia) iniciando 3 dias antes do procedimento de extração, se estendendo até 4 dias de pós-operatório, passaram pela extração do molar na terceira semana de experimento e foram submetidas a eutanásia na sétima semana de experimento. Após a eutanásia as mandíbulas foram ressecadas, reduzidas e preparadas para as análises microtomográficas (caracterização óssea do osso senil (MCT0) e após terapia com zoledronato (MCT1ZOL) contra seu par controle (MCT1SAL), parâmetros volumétricos (Bv,Bv.Tv,Tb.Th,Tb.N,Tb.Sp,Po.Tot) dos grupos experimentais), histométricas (porcentagem de osso neoformado e porcentagem de osso não vital) e imunoistoquímicas (expressão de TNFa, IL-1b, VEGF, OCN e TRAP). Os resultados da caracterização óssea não apresentaram diferença quando comparado os grupos experimentais (p> 0,05), possivelmente devido ao pouco tempo decorrido na terapia com zoledronato. Os demais resultados comparando os grupos experimentais mostrou com diferenças estatisticamente significativas (p< 0,05) uma característica de osso vítreo, denso, sem vitalidade, pobre em vascularização, com elevados valores para marcadores de inflamação, traduzindo isso em osteonecrose dos maxilares relacionada com a medicação, destoando principalmente do grupo controle SAL, que apresentou melhora na reparação alveolar e características de osso vital e vascularizado. A ozonioterapia (ZOL+OZ, SAL+OZ) apresentou valores significantes estatisticamente quando comparado ao grupo sem tratamento, traduzindo em melhora na vascularização do tecido ósseo, em melhora reparacional do alvéolo, modulação da inflamação local e o aparecimento/manutenção de células osteoblásticas ativas (p< 0,05). Mostrando-se uma terapia viável no controle/tratamento da osteonecrose dos maxilares relacionado com medicamentos(AU)

Ozone therapy has been shown to be a promising tool in the prevention of infections and in the aid of tissue repair, reconciling with the challenges in the treatment of medication-induced jaw osteonecrosis (ONM-M), this project aims to analyze the effects of ozone therapy in 55 rats senile (18 months), between 300-350g, induced to osteonecrosis via medication (Zoledronate 100µg / kg), after extraction of the lower first molar. The animals were divided into 4 equitable groups (ten rats per group), the first SAL group, received saline applications for 7 weeks, SAL + OZ group received saline applications for 7 weeks and ozone therapy (0, 7mg / kg) every 2 days for 28 days, the ZOL group received applications of zoledronate (100µg / kg) for 7 weeks and lastly the ZOL + OZ group also received applications of zoledronate in the same protocol and was treated with ozone therapy (0.7mg / kg) every 2 days for 28 days. All rats received antibiotic therapy (Cristacilina® 0.1ml / kg per day) starting 3 days before the extraction procedure, extending up to 4 days after the operation, underwent molar extraction in the third week of the experiment and were submitted to euthanasia in the seventh week of experiment. After euthanasia, the mandibles were resected, reduced and prepared for microtomographic analysis (bone characterization of senile bone (MCT0) and after therapy with zoledronate (MCT1ZOL) against its control pair (MCT1SAL), volumetric parameters (Bv, Bv.Tv, Tb .Th, Tb.N, Tb.Sp, Po.Tot) of the experimental groups), histometric (percentage of newly formed bone and percentage of non-vital bone) and immunohistochemistry (expression of TNFa, IL-1b, VEGF, OCN and TRAP) . The results of bone characterization did not show any difference when comparing the experimental groups (P> 0.05), possibly due to the short time elapsed in zoledronate therapy. The other results comparing the experimental groups showed with statistically significant differences (P < 0.05) a characteristic of vitreous bone, dense, without vitality, poor in vascularization, with high values for inflammation markers, translating this into a related jaw osteonecrosis with medication, disagreeing mainly with the SAL control group, which showed improvement in alveolar repair and characteristics of a vital and vascularized bone. Ozone therapy (ZOL + OZ, SAL + OZ) showed statistically significant values when compared to the untreated group, translating into an improvement in bone tissue vascularization, a reparational improvement of the alveolus, modulation of local inflammation and the appearance/maintenance of cells active osteoblasts (P < 0.05). Showing to be a viable therapy in the control/treatment of osteonecrosis of the jaws related to drugs(AU)

"Descansar e dormir sem riscos": o Jornal do Médico (Portugal) e o desastre da talidomida, 1960-1962 / "Risk-free rest and sleep: " Jornal do Médico (Portugal) and the thalidomide disaster, 1960-1962

Resumo O artigo analisa como o periódico Jornal do Médico, editado na cidade do Porto, em Portugal, divulgou o desastre da talidomida. A pesquisa percorreu as páginas da fonte desde o início de 1960 até o final de 1962. Aqui, objetivam-se apontar e discutir duas questões interligadas: a morosidade em publicar matérias sobre os efeitos deletérios do medicamento, vendido no país sob a denominação Softenon®, e a construção discursiva da isenção da responsabilidade do médico no fenômeno da iatrogenia medicamentosa.

Abstract This article analyzes the way the Porto-based journal Jornal do Médico reported on the thalidomide disaster. The pages of the publication are researched from the beginning of 1960 to the end of 1962 with the aim of identifying and discussing two interconnected questions: the delay in publishing news on the harmful effects of the drug, which was sold in the country under the brand name Softenon®, and the discursive construction of a lack of accountability on the part of physicians for the phenomenon of medication iatrogenesis.

Perfil de pacientes em idade reprodutiva tratadas por epilepsia / Profile of patients in reproductive age treated by epilepsy

Objetivo: Descrever o perfil de pacientes em idade reprodutiva internadas por epilepsia nas regiões brasileiras em 5 anos, elucidando os riscos promovidos por ela durante a gravidez e abordando o gerenciamento do quadro. Métodos: Pesquisa e análise de dados disponibilizados pelo Departamento de Informática do Sistema Único de Saúde (DATASUS), acerca das internações em mulheres em idade reprodutiva (10 a 49 anos) por epilepsia, avaliando a ocorrência, de acordo com faixa etária, etnia e região do Brasil, no período de janeiro de 2012 a dezembro de 2016. Resultados: No total, foram notificadas 42.204 internações de mulheres em idade reprodutiva associadas à epilepsia, estando a maior parte delas (22,66%) na faixa de 20 a 29 anos e na de 40 a 49 anos (22,59%). O Sudeste correspondeu a 43,01% do total de casos (18.152), seguido pela Região Sul, com 9.456 registros (22,4%), e pelo Nordeste (8.245; 19,53%). A etnia mais atingida foi a de brancas (15.804; 37,44% dos atendimentos) e pardas (12.200; 28,9%). Conclusão: O planejamento da gravidez em mulheres epilépticas contribui para redução dos riscos tanto maternos quanto fetais, pois permite ao prescritor e à gestante pesar quais os benefícios e os malefícios de cada terapia anticonvulsivante disponível. Vale lembrar que uma abordagem individualizada da paciente epiléptica grávida por equipe multidisciplinar se faz necessária para melhorar os desfechos e prevenir internações por crises convulsivas. (AU)

Objective: To describe the profile of female patients in childbearing age hospitalized due to epilepsy in the Brazilian regions in 5 years, elucidating the risks it causes during pregnancy, and addressing the management of the condition. Methods: Research and analysis of data provided by the Informatics Department of the Unified Health System (DATASUS), concerning hospitalizations of women of childbearing age (10-49 years) due to epilepsy, evaluating the occurrence according to age, ethnicity and the region in Brazil, from January 2012 to December 2016. Results: A total of 42,204 admissions of women of childbearing age due to epilepsy were reported, with most of them in the age group from 20 to 29 years old (22,66%), and in the 40-49 age group (22.59%). The Southeast Region accounted for 43.01% of the total number of cases (18,152), followed by the South Region, with 9,456 records (22.4%), and the Northeast (8,245 - 19.53%). The most affected ethnic group was the white one (15,804; 37,44% of the admissions) and brown one (12,200; 28,9%). Conclusion: Pregnancy planning in epileptic women contributes to both maternal and fetal risk reduction, since it allows the prescriber and the pregnant woman to weigh the benefits and harms of each available anticonvulsant therapy. It is worth remembering that an individualized, multidisciplinary approach of the epileptic pregnant patient is necessary to improve the outcomes, and to prevent hospitalizations due to seizures. (AU)

Embriopatía por isotretinoína: Una entidad que puede evitarse / Isotretinoin embryopathy: An entity that can be avoided

La isotretinoína es el medicamento más efectivo en el tratamiento del acné noduloquístico recalcitrante grave. Sin embargo, el tratamiento con este fármaco se encuentra asociado con efectos adversos, y el más grave es la teratogénesis. Se ha estimado que 40% de los embarazos expuestos a isotretinoína presenta un aborto espontáneo y 35% desarrolla embriopatía. Se presenta el caso de un recién nacido con antecedente de exposición prenatal a isotretinoína, una entidad clínica que puede evitarse, con graves defectos congénitos en el sistema nervioso central e importantes dismorfias faciales, con evolución clínica desfavorable.

Isotretinoin is the most effective drug in the treatment of severe recalcitrant nodulocystic acne. However, treatment with this drug is associated with adverse effects, the most severe being teratogenesis. It has been estimated that 40% of pregnancies exposed to isotretinoin present spontaneous abortion and 35% develop embryopathy. We present the case of a newborn with a history of prenatal exposure to isotretinoin, a clinical entity that can be avoided, with severe congenital defects in the central nervous system and important facial dysmorphisms, with unfavorable clinical course.

Neurological responses of embryo-larval zebrafish to short-term sediment exposure to decabromodiphenylethane / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Decabromodiphenylethane (DBDPE) has been widely used as an alternative flame retardant due to the restriction or phase-out of traditional polybrominated diphenyl ethers (PBDEs), and is of increasing concern regarding its ubiquity, persistence, and potential adverse effects. In the present study, the toxicological effects of DBDPE were evaluated using zebrafish as an in vivo model. Upon being exposed to DBDPE-polluted sediments for a short term, it was found that the mortality and malformation of zebrafish (including edema, bent notochord, and bent tail) were not affected even at the highest concentration tested (1000.0 µg/kg dry sediment). Regarding behavioral responses, it was found that zebrafish larvae of 48 hours post fertilization (hpf) in all groups escaped successfully with a touch to the dorsal fin. However, when exposed to the highest DBDPE concentration, the larvae of 120 hpf exhibited significantly smaller distances as compared to the control. Moreover, the results of the acetylcholinesterase (AChE) activity, the expression levels of two important nerve-related genes, and the cell apoptosis all indicated that DBDPE posed low neurotoxicity in embryo-larval zebrafish. The results in this study shed some light on the potential risks of DBDPE in the real environment and highlight the application of the sediment exposure route in the future.

Hepatic toxicity caused by PLGA-microspheres containing usnic acid from the lichen C ladonia substellata (AHTI) during pregnancy in Wistar rats

ABSTRACT This study aimed to evaluate the teratogenic and hepatotoxic potential of the usnic acid encapsulated into PLGA-microspheres. In total, 12 female Wistar rats in pregnancy were randomly distributed in the control group (n= 6) that received 1.0 mL of physiological solution and treatment group (n= 6) that received 25 mg/kg of encapsulated usnic acid by oral administration. All females were euthanized at day 20 of pregnancy and their fetuses were removed and analyzed. During the pregnancy was observed a reduction in weight gain. There was no difference in serum transaminases levels analyzed as well as any difference in liver weight in both groups. The histomorphometric analysis of the liver from the treatment group revealed an increase in number of hepatocytes and a decrease in nuclear area of these cells. Moreover, no alteration was observed in cell area of hepatocytes or number of Kupffer cells. The fetuses had an increase in total number of hepatocytes and a reduction in the amount of megakaryocytes. These results show the hepatotoxic potential of usnic acid during pregnancy. However, its toxicity can be minimized by encapsulation in microspheres.

Investigación epidemiológica y medicamentos: farmacoepidemiología / Epidemiological research and medicines: pharmacoepidemiology

La Farmacoepidemiología, como disciplina que estudia los efectos y consecuencias del uso de medicamentos en poblaciones humanas, tiene como objetivo fundamental promover su uso adecuado. Para ello se sustenta en el método epidemiológico y sus diversos diseños de investigación, cada uno de los cuales presenta objetivos y características particulares, pero todos con el propósito global de mejorar el uso de medicamentos, prevenir eventos adversos y sus factores asociados; así como, descubrir nuevas indicaciones, determinar posibles efectos nocivos por uso crónico, describir las posibles interacciones con otros medicamentos, identificar el desarrollo de nuevas patologías, además del uso en poblaciones especiales, entre otros. Entre las acciones de la Farmacoepidemiología destacan la aplicación de la investigación para la producción de evidencia científica sólida para la toma de decisiones en salud; así como para la ejecución de acciones de capacitación destinadas a mejorar las prácticas en torno al medicamento de pacientes, proveedores, personal de salud, industria, gobierno y público en general. La presente revisión pretende hacer una breve descripción de los principales diseños de investigación epidemiológica y su vinculación con el uso de medicamentos, destacando como principales ventajas, además de la diversa disponibilidad de métodos, la sencillez, rapidez y facilidad de ejecución de la mayoría de ellos, aunado al hecho de destacar los esfuerzos que se vienen realizando mediante la publicación de guías dirigidas a mejorar la divulgación de resultados, esperando que estas actividades se traduzcan en una mejora en el uso adecuado de medicamentos en la población, su salud y calidad de vida

Pharmacoepidemiology, as a discipline that studies the effects and consequences of the use of drugs in human populations, has as its fundamental objective to promote its adequate use. This is based on the epidemiological method and its various research designs, each of which presents particular objectives and characteristics, but all with the overall purpose of improving drug use, preventing adverse events and their associated factors; as well as to discover new indications, to determine possible harmful effects by chronic use, to describe the possible interactions with other drugs, to identify the development of new pathologies, besides the use in special populations, among others. Among the actions of Farmacoepidemiología, the application of research for the production of solid scientific evidence for health decision making emphasizes; as well as for the execution of training actions aimed at improving practices around the medicine of patients, providers, health personnel, industry, government and the public in general. The present review aims to give a brief description of the main designs of epidemiological research and their linkage with the use of medicines, highlighting as main advantages, besides the diverse availability of methods, the simplicity, speed and ease of execution of most of them , coupled with the fact that efforts are being made by publishing guidelines aimed at improving the dissemination of results, hoping that these activities will result in an improvement in the adequate use of medicines in the population, their health and quality of life

Prevalencia y factores asociados a la presencia de reacciones adversas a medicamentos en los pacientes tratados por medicina interna en el Hospital Universitario Hernando Moncaleano Perdomo / Prevalence and risk factors related with adverse reactions to drugs in patients from Hospital Universitario Hernando Moncaleano Perdomo

Objetivo: Estimar la prevalencia y factores asociados para presentar reacciones adversas a medicamentos en los pacientes tratados por medicina interna del Hospital Universitario Hernando Moncaleano Perdomo (HUHMP) durante un período de 2 meses. Materiales y métodos: Estudio prospectivo de corte transversal. El análisis estadístico se realizó con Epi info v7.0 Resultados: De los 284 pacientes, se obtuvieron 89 reacciones adversas a medicamentos (RAM) que corresponde al 31.34 porciento de la muestra, el 52.4 porciento eran del género masculino con una edad media de 58.5 años. Las RAM se clasificaron segúnsu mecanismo de producción en tipo A en 79 porciento, tipo B 14 porciento y tipo C 5 porciento; la mayoría fueron leves en el 88 porciento de los casos. El principal sistema farmacológico afectado fue el gastrointestinal seguido por el hematológico en un 22 porciento y 19 porciento respectivamente; la enoxaparina fue el principal fármaco relacionado con la producción de RAM en el 17 porciento; al igual es el fármaco con más interaccionesmedicamentosas junto con el ácido acetilsalicílico en el 26 porciento de los casos. Entre los factores asociados para la producción de RAM son la polifarmacia IC: 1.96-5.57, p 0.000027 y las interacciones medicamentosas IC: 1.32 – 3.81, p 0.0011.Conclusiones: Las interacciones medicamentosas y la polifarmacia son los factores asociados a la presencia de reacciones adversas a medicamentos enpacientes de medicina interna.

Pharmacotherapy of obsessive-compulsive disorder during pregnancy: a clinical approach

Obsessive-compulsive disorder (OCD) is a relatively common psychiatric disorder in the perinatal period. However, specific pharmacological treatment approaches for patients with OCD during pregnancy have not been satisfactorily discussed in the literature. In addition, there are no randomized controlled studies on the treatment of this disorder during pregnancy. The present paper discusses the pharmacological treatment of OCD in the light of data on the safety of antipsychotics and serotonergic antidepressants during pregnancy and their efficacy in the non-perinatal period. Treatment decisions should be individualized because the risk-benefit profile of pharmacotherapy is an important issue in the treatment of pregnant women with any psychiatric diagnosis.

História da talidomida no Brasil a partir da mídia impressa (1959-1962) / History of thalidomide in Brazil based on the print media (1959-1962)

O artigo discute algumas questões relacionadas à droga talidomida, a partir de notícias da mídia impressa. As fontes utilizadas na pesquisa foram jornais editados na cidade do Rio de Janeiro entre 1959 e 1962. O estudo destaca o contexto histórico brasileiro que antecede a chegada da talidomida no Brasil, com ênfase em alguns aspectos relativos à indústria farmacêutica no cenário da década de 1950; traz algumas informações sobre o Instituto Pinheiros Produtos Terapêuticos S/A, o principal laboratório que produziu e comercializou a droga no país; demonstra como os jornais veicularam as primeiras propagandas incentivando a prescrição do medicamento e acompanha as notícias sobre os malefícios da talidomida; aponta quais ações foram tomadas para a retirada da droga do mercado brasileiro, uma vez que ela era amplamente comercializada no país naquele momento; conclui que a mídia impressa deu destaque moderado para a tragédia, que a talidomida circulou largamente pelo território nacional e sugere que a primeira geração de bebês vítimas da talidomida deve ser maior do que normalmente se supõe.

The article reviews and discusses the events surrounding the thalidomide tragedy based on news from the print media. Newspapers published in the city of Rio de Janeiro, RJ, Brazil, from 1959 to 1962 were investigated. The analysis highlights the historical context that predates the arrival of the drug in Brazil, with emphasis on some aspects of the pharmaceutical industry in the country. It provides information on the Instituto Pinheiros Produtos Terapêuticos, the main laboratory that produced and marketed the drug in the country, and demonstrates how newspapers presented the first news about the dangers of thalidomide. Furthermore, it indicates what actions were taken to withdraw the drug from the Brazilian market, as the drug was widely marketed in the country at that time. It concludes that the print media reported the event without urgency and without featuring it on the front pages of the newspapers. The article concludes that thalidomide ended up circulating widely throughout Brazil and suggests that the first generation of thalidomide babies must be greater than is commonly supposed.

Risk of congenital anomalies associated with antithyroid treatment during pregnancy: a meta-analysis

To evaluate the association of either propylthiouracil or methimazole treatment for hyperthyroidism during pregnancy with congenital malformations, relevant studies were identified by searching Medline, PubMed, the Cochrane Library and EMBASE. We intended to include randomized controlled trials, but no such trials were identified. Thus, we included cohort studies and case-control studies in this meta-analysis. A total of 7 studies were included in the meta-analyses. The results revealed an increased risk of birth defects among the group of pregnant women with hyperthyroidism treated with methimazole compared with the control group (odds ratio 1.76, 95% confidence interval 1.47-2.10) or the non-exposed group (odds ratio 1.71, 95% confidence interval 1.39-2.10). A maternal shift between methimazole and propylthiouracil was associated with an increased odds ratio of birth defects (odds ratio 1.88, 95% confidence interval 1.27-2.77). An equal risk of birth defects was observed between the group of pregnant women with hyperthyroidism treated with propylthiouracil and the non-exposed group (odds ratio 1.18, 95% confidence interval 0.97-1.42). There was only a slight trend towards an increased risk of congenital malformations in infants whose mothers were treated with propylthiouracil compared with in infants whose mothers were healthy controls (odds ratio 1.29, 95% confidence interval 1.07-1.55). The children of women receiving methimazole treatment showed an increased risk of adverse fetal outcomes relative to those of mothers receiving propylthiouracil treatment. We found that propylthiouracil was a safer choice for treating pregnant women with hyperthyroidism according to the risk of birth defects but that a shift between methimazole and propylthiouracil failed to provide protection against birth defects. .

Clinical and cytogenetic features of a Brazilian sample of patients with phenotype of oculo-auriculo-vertebral spectrum: a cross-sectional study / Características clínicas e citogenéticas de uma amostra brasileira de pacientes com fenótipo de espectro óculo-aurículo-vertebral: um estudo transversal

CONTEXT AND OBJECTIVE: Oculo-auriculo-vertebral spectrum (OAVS) is considered to be a defect of embryogenesis involving structures originating from the first branchial arches. Our objective was to describe the clinical and cytogenetic findings from a sample of patients with the phenotype of OAVS. DESIGN AND SETTING: Cross-sectional study in a referral hospital in southern Brazil. METHODS: The sample consisted of 23 patients who presented clinical findings in at least two of these four areas: orocraniofacial, ocular, auricular and vertebral. The patients underwent a clinical protocol and cytogenetic evaluation through high-resolution karyotyping, fluorescence in situ hybridization for 5p and 22q11 microdeletions and investigation of chromosomal instability for Fanconi anemia. RESULTS: Cytogenetic abnormalities were observed in three cases (13%) and consisted of: 47,XX,+mar; mos 47,XX,+mar/46,XX; and 46,XX,t(6;10)(q13; q24). We observed cases of OAVS with histories of gestational exposition to fluoxetine, retinoic acid and crack. One of our patients was a discordant monozygotic twin who had shown asymmetrical growth restriction during pregnancy. Our patients with OAVS were characterized by a broad clinical spectrum and some presented atypical findings such as lower-limb reduction defect and a tumor in the right arm, suggestive of hemangioma/lymphangioma. CONCLUSIONS: We found a wide range of clinical characteristics among the patients with OAVS. Different chromosomal abnormalities and gestational expositions were also observed. Thus, our findings highlight the heterogeneity of the etiology of OAVS and the importance of these factors in the clinical and cytogenetic evaluation of these patients. .

CONTEXTO E OBJETIVO: O espectro oculoauriculovertebral (EOAV) é considerado um defeito de embriogênese envolvendo estruturas originadas a partir dos primeiros arcos branquiais. Nosso objetivo foi descrever os achados clínicos e citogenéticos de uma amostra de pacientes com fenótipo de EOAV. TIPO DE ESTUDO E LOCAL: Estudo transversal em um hospital de referência no sul do Brasil. MÉTODOS: A amostra foi composta de 23 pacientes que apresentaram achados clínicos em pelo menos duas das quatro áreas: orocraniofacial, oculares, auriculares e vertebrais. Os pacientes foram submetidos a um protocolo clínico e avaliação citogenética através do cariótipo de alta resolução, hibridização in situ fluorescente para as microdeleções 5p e 22q11 e pesquisa de instabilidade cromossômica para anemia de Fanconi. RESULTADOS: Alterações citogenéticas foram observadas em três casos (13%) e consistiam de: 47,XX,+mar; mos 47,XX,+mar/46,XX e 46,XX,t(6;10)(q13;q24). Observamos casos de EOAV com história de exposição gestacional à fluoxetina, ácido retinoico e crack. Um dos nossos pacientes foi um gêmeo monozigótico discordante que teve restrição de crescimento assimétrica durante a gravidez. Nossos pacientes com EOAV foram caracterizados por um amplo espectro clínico e alguns apresentaram achados clínicos atípicos como um defeito de redução de membro inferior e um tumor do braço direito, sugestivo de hemangioma/linfangioma. CONCLUSÕES: Verificamos grande variedade de características clínicas entre os pacientes com EOAV. Também foram observadas diferentes anomalias cromossômicas e exposições gestacionais. Assim, nossos achados salientam a heterogeneidade da etiologia do EOAV e a importância desses fatores na avaliação clínica e citogenética desses pacientes. .

Errores relacionados con los medicamentos ocurridos en unidades de cuidados críticos y propuesta de mejora mediante la aplicación móvil de juegos educativos / Medication-related errors occurred in critical care units and improvement proposal by the mobile application of educational games", "_e": "n

Introducción: En unidades de Cuidados Críticos (UCC) Existe alcalde probability De que ocurran Errores DEBIDO un Múltiples factors. Los Relacionados a Medicamentos y los asociados al Cuidado de enfermería hijo Los Mas Frecuentes. Las Comunicaciones Móviles y el Internet de han Permitido Nuevas Alternativas de Educación, Asi los juegos Tienen el potencial de facilitar y Mejorar el Aprendizaje. Objetivo: Describir los Errores Relacionados Con Los MEDICAMENTOS ocurridos ES UNA UCC Y proponer Intervención de Enfermería Como Propuesta de Mejora Dirigida col personales Para La Seguridad de los Pacientes. Métodos y materiales: cuantitativo Y Descriptivo, Realizado en julio-diciembre 2014 En Una Institución de alta especialidad, Que ABORDA Los Errores de medicación (EM) ocurridos Estudio en UCC. Se analizaron con estadística descriptiva Datos. Con la base en los Resultados SE PROPONE Como intervention al personal Una Aplicación para Teléfono móvil de Juego Interactivo Sobre Medicamentos. Resultados: Del total de eventos de (n = 107) los EM ocuparon el 61,2% (n = 30). Se presentaron los más Es Varones (66%), 50% en estado de alerta, los medios de comunicación Edad de 37 años, Estancia Hospitalaria 9,5 Dias. La majority Ocurrió en turno matutino (Fo = 14), Durante la Administración (33,3%), Principalmente electrolitos Concentrados y broncodilatadores inhalados. No se Causo Daño es 70%, el 100% de los Casos se consideraron evitables. Entre los Factores Contribuyentes sobresalieron «sin adherirse una Protocolos¼ (63,3%) Y "Factores cognitivos" (53,3%). Conclusiones: Los EM ocurren Principalmente Durante la Administración por no Seguir Protocolos y por Cuestiones de cognición. Es practicable Que Los Juegos Educativos apoyen la gestión de Conocimientos y prevengan la Aparición de Nuevos EM.

Introduction: Critical Care Units (CCU) There mayor probability of occurrence Errors Causing a Multiple factors. The Drug-Related and associated nursing care child most frequent. Mobile Communications and the Internet have allowed New Alternatives education, games have the potential to facilitate and improve learning. Objective: To describe the related medication errors occurred IS A UCC and propose Nursing Intervention As Directed Personal Improvement Proposal cabbage for Patient Safety. Methods and Materials: quantitative and descriptive Realized in July-December 2014 in an institution highly specialized, addressing medication errors (EM) Study occurred in UCC. They were analyzed with descriptive statistics data. Based on the results is proposed as intervention personnel An Application for Mobile Interactive Gaming About Drugs. Results: Of the total number of events (n = 107) MS occupied 61.2% (n = 30). Is the Boys (66%), 50% on alert, the media age 37, hospital stay 9.5 days were presented. The majority occurred in the morning shift (Fo = 14), during the administration (33.3%), mainly electrolytes Concentrates and inhaled bronchodilators. Damage Caused is not 70%, 100% of the cases were considered preventable. Contributing factors excelled "not become a member of Protocols" (63.3%) and "Cognitive factors" (53.3%). Conclusions: EM occur mainly during the Administration for not following Protocols and cognition issues. It is practicable educational games Knowledge management support and prevent the emergence of new MS.

Protective effect of olive oil against Teratogenecity induced by Mancozeb in albino rats

Aim: this study aimed to investigate the protective effect of extra-virgin olive oil [EVOO] against teratogenicity of the fungicide mancozeb

Methods: after pregnancy confirmation, 32 pregnant rats were divided into 4-groups [n=8]. The 1[st] group orally administered tap water [-ve control], the 2[nd] group [+ve control] was administered EVOO [0.5ml/dam] from the1[st] to 20[th] day of pregnancy. The 3rd and the 4[th] groups were administered 200 mg/kg mancozeb during the period of organogenesis, from the 6[th] to 15[th] day of pregnancy. The 4[th] group received the mentioned dose of EVOO prior to the pesticide administration. Cesarean section was performed on day 20 of pregnancy and the maternal and fetal parameters were recorded

Results: mancozeb induced maternal toxicity manifested as lower body weight gain of dams, increased number of late resorption sites/litter in comparison with the control group and mancozeb group pretreated with EVOO. Mancozeb evoked a decrease in fetal body weight, altered sex ratio [M/F] as well as increased incidence of fetal external, visceral and skeletal abnormalities. Treatment with virgin oil reduced the congenital malformations

Conclusively, the present study elucidates the protective role of EVOO as a result of antioxidant activity which scavenges the reactive oxygen species which induced cytotoxicity and increased prenatal mortalities.

Teratogenic effect of Carbamazepine administration in pregnant rats

Background: Carbamazepine "CBZ" [Tegretol] is an anticonvulsant and mood stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia. It has been assigned to pregnancy category D by the U.S Food and Drug Administration [FDA]. CBZ can cause fetal harm when administered to pregnant women. Epidemiological data suggested that there may be an association between the use of CBZ during pregnancy and congenital malformations,specifically spina bifida and developmental disorders. The possible malformation-specific risks with CBZ use during pregnancy need to be considered, so the present work was conducted to evaluate the genotoxicity of two doses of CBZ [3.6 mg and 10.8 mg/ 100g body weight/ day] in pregnant female rats and their fetuses. Chromosomal aberration in bone marrow cells and histopathological examination of liver and kidney of pregnant rats were also determined

Materials and Methods: Fourty five pregnant Sprague Dawley rats were randomly divided into the groups. The first was administered oral doses of distilled water and served as control. The other two groups were administered oral doses of CBZ suspended in distilled water equivalent to 3.6 mg and 10.8 mg/100g body weight/day respectively for 15 day from the 6[th] day to the 20[th] day of gestation. Females were sacrificed on the 20[th] day of gestation

Results: Administration of CBZ 3.6 mg and 10.8 mg /100g body weight to pregnant rats from the 6[th] till the 20[th] day of gestation. Decreased fetal body weight, crown-rump length, increased resorbed and dead fetuses were observed compared to the control ones. Moreover, CBZ-high dose group[10.8mg/100g]causedmalformations that could be described as severe growth retardation. At the same time, bone marrow metaphases of CBZ-treated pregnant rats revealed structural chromosomal aberrations. Whereas, histopathological examination of liver and kidney of pregnant rats treated with both doses of CBZshowed cellular alterations

Conclusion: It has been found that usage of antiepileptic CBZ during gestational period may create risk, associated with maternal toxicity, hepato- and nephrotoxicity and chromosomal aberrations in pregnant rats, with intrauterine growth retardation which was manifested by low body weight, length reduction and malformations. These alterations were dose dependent. The benefits of taking CBZ must be weighed against the potential risks to boththe developing fetus and the mother

FTIR microspectroscopy reveals chemical changes in mice fetus following phenobarbital administration

Phenobarbital is a phenobarbiturate used as a sedative, anticonvulsant or hypnotic with the doses prescribed and can cause teratogenic effects. The goal of this study was to examine an alternative method for the recognition of the mechanism or the bimolecular potential changes in mice fetus caused by Phenobarbital using FTIR micro spectroscopy. The mice were injected with Phenobarbital [120 mg/Kg] on gestation day 9. Fetuses were dissected on day 15 of gestation and morphological and histological studies on the fetus were carried out. Sections [10 microm] of normal and Phenobarbital treated fetus brains and livers were used for FTIR measurement in the wave number region of 400- 4000 cm. The results were shown by 2 derivatization of spectra and also subtracting from control spectra. In liver, the intensity at 1054 cm, 1155 cm, 1353 cm, 1453cm,1645 cm, 1622 cm, 2944 cm, 2913 cm and 2845 cm were shifted and increased. In the brain, the intensity at 879 cm, 911 cm, 955 cm, 1223 cm, 1256 cm, 1304 cm, 1360 cm, 1453 cm, 1529 cm, 1636 cm, 2845 cm, 2915 cm and 2950 cm were increased and shifted. The most important changes of the fetus brain tissue are on the beta structure of proteins due to the amide I bands at 1636 cm, while extensive effects on the DNA structure were obvious for the Phenobarbital treated liver tissues. As a conclusion, FTIR spectroscopy might well be assumed as a potentially powerful teratogenic measurement instrument with a unique ability to identify the modified bimolecular structures

Teratogenic effect of carbamazepine use during pregnancy in the mice

Carbamazepine use is the first choice of antiepileptic drugs among epileptic pregnant females. There are many inconclusive studies regard the safety of carbamazepine use during pregnancy. This study aims to investigate the morphological and histopathological teratogenic effects of carbamazepine use during pregnancy. The healthy pregnant females mice divided into equal five groups [each n=20]. The first [control] group received distilled water/day. Second, third, fourth and fifth group received 8.75, 22.75, 52.5, 65 mg of carbamazepine/day respectively. Carbamazepine and water were given by gastric gavage throughout gestational period. Fetuses were delivered on the 18th day of gestation by hysterectomy. Fetal measurements and appearance were assessed with investigation the histopathological changes of brain and spinal cord. There was a significant decrease of weight, different organs weight, length, upper and lower limb length of mice in the first day of delivery in fifth group. There was a significant increase of weight, different organs weight, length, upper and lower limb length in the third group. Many congenital anomalies such as spina bifida, meromelia, microphalmia, oligodactyly, anencephaly, neurodegeneration of brain and spinal cord were noticedin fifth group. Teratogenic effect of carbamazepine represented as growth retardation and neurodevelopmental toxicity depending on its overdose degree

newborn with teratogenic effect of imatinib mesylate: a very rare case report

To report a case of teratogenic effect of imatinib mesylate [IM] in a newborn, whose mother was suffering from chronic myelogenous leukemia and was treated with IM for 4 years, including during her pregnancy. Case Presentation and Intervention: The newborn was diagnosed with microtia of the right ear, preauricular tag on the left side, absence of right depressor angular oris muscle, and imperforate anus. Infantogram showed dextrocardia, hemivertebrae in the thoracic region and cervical spina bifida occulta. The newborn was operated on for the imperforate anus and was discharged in good condition. This case revealed that IM is not safe for the fetus and leads to teratogenicity. Hence, we recommend that pregnant women should not be treated with IM