Effects of the polysaccharide beta-glucan on clastogenicity and teratogenicity caused by acute exposure to cyclophosphamide in mice

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The Use of Ultrasonography to Study Teratogenicity in Ruminants: Evaluation of Ipomoea carnea in Goats

Background: Ipomoea carnea (I. carnea) is a poisonous plant found in Brazil and other tropical countries that often poison livestock. The plant contains the alkaloids calystegines and mainly swainsonine, which inhibit cellular enzymes and cause systematic cell death. The objective of this study was to evaluate the perinatal effects of I. carnea in goats. Methods: Forty-seven pregnant goats were randomly allocated into 5 treatment groups and given the following doses (g/kg BW) of I. carnea: 0 (IC0), 1.0 (IC1), 3.0 (IC3), 5.0 (IC5) and 7.5 (IC7). The treatment animals were given fresh I. carnea from day 27 of gestation to parturition. Weight gains and serum biochemistry were evaluated. Fetuses were evaluated using ultrasonographic measurements. Results: Goats from the IC7 group showed clinical signs of poisoning. Ultrasound examination revealed that I. carnea feeding in all treatment groups reduced fetal movement compared to the controls. There was an increase in the total number of birth defects (retrognathia and arthrogyposis) in the IC7 and IC5 groups compared to the controls. Conclusion: The results show that I. carnea has teratogenic potential in goats. In addition, ultrasounds were useful in evaluating fetotoxicity and teratogenicity. Birth Defects Res (Part B) 00:17, 2012. (c) 2012 Wiley Periodicals, Inc.

Critical relationship between sodium valproate dose and human teratogenicity: results of the Australian register of anti-epileptic drugs in pregnancy

To compare the incidence of foetal malformations (FMs) in pregnant women with epilepsy treated with different anti-epileptic drugs (AED) and doses, and the influence of seizures, family and personal history, and environmental factors. A prospective, observational, community-based cohort study. Methods. A voluntary, Australia-wide, telephone-interview-based register prospectively enrolling three groups of pregnant women: taking AEDs for epilepsy; with epilepsy not taking AEDs; taking AEDs for a non-epileptic indication. Four hundred and fifty eligible women were enrolled over 40 months. Three hundred and ninety six pregnancies had been completed, with 7 sets of twins, for a total of 403 pregnancy outcomes. Results. 354 (87.8%) pregnancy outcomes resulted in a healthy live birth, 26 (6.5%) had a FM, 4 (1%) a death in utero, 1 (0.2%) a premature labour with stillbirth, 14 (3.5%) a spontaneous abortion and 4 lost to follow-up. The FM rate was greater in pregnancies exposed to sodium valproate (VPA) in the first trimester (116.0%) compared with those exposed to all other AEDs (16.0% vs. 2.4%, P < 0.01) or no AEDs (16.0% vs. 3.1 %, P < 0.01). The mean daily dose of VPA taken in pregnancy with FMs was significantly greater than in those without (11975 vs: 1128 mg, P < 0.01). The incidence of FM with VPA doses greater than or equal to 1100 mg was 30.2% vs. 3.2% with doses < 1100 mg (P < 0.01). Conclusions. There is a dose-effect relationship for FM and exposure to VPA during the first trimester of pregnancy, with higher doses of VPA associated with a significantly greater risk than with lower doses or with other AEDs. These results highlight the need to limit, where possible, the dose of VPA in pregnancy. (C) 2004 Elsevier Ltd. All rights reserved.

Shared mechanism of teratogenicity of anti-angiogenic drugs identified in the chicken embryo model

This study was supported by a Wellcome Trust-NIH PhD Studentship to SB, WDF and NV. Grant number 098252/Z/12/Z. SB, CHC and WDF are supported by the Intramural Research Program, NCI, NIH. NHG and WL are supported by the Intramural Research Program, NIA, NIH.

Psoríase na infância e na adolescência

A psoríase é doença inflamatória crônica, imunologicamente mediada, recorrente e de caráter universal. Aproximadamente um terço dos adultos acometidos refere início da doença antes dos 16 anos de idade. Quanto mais precoce, mais grave tende a ser a evolução do quadro. Em crianças, as lesões podem ser fisicamente desfigurantes, causando prejuízos psicológicos e evidente comprometimento da qualidade de vida. As medicações sistêmicas utilizadas na psoríase, bem como a fototerapia, têm indicação limitada na infância, devido aos efeitos cumulativos das drogas, à baixa aceitação e ao risco de teratogenicidade. Nesta seção, discutiremos as principais manifestações clínicas da psoríase na infância e na adolescência, bem como os diagnósticos diferenciais, opções terapêuticas e prognóstico.

Psoriasis in childhood and adolescence

Psoriasis is a chronic, immunologically mediated, recurrent and universal inflammatory disorder. Approximately one third of adults refer onset before 16 years of age. The sooner the onset, the worse is the prognosis. In children, lesions may be physically disfiguring, leading to psychological impairment and evident loss of quality of life. Systemic therapy used in psoriasis, as well as phototherapy, has limited use in children due to accumulative effects of drugs, low acceptance, and risk of teratogenicity. In this section, we discuss the main clinical aspects of psoriasis in childhood and adolescence. differential diagnosis, therapeutic options, and prognosis.

Maternal and Developmental Toxicity of Ayahuasca in Wistar Rats

INTRODUCTION: Ayahuasca is a psychotropic plant beverage initially used by shamans throughout the Amazon region during traditional religious cult. In recent years, ayahuasca has also been used in ceremonies of a number of modern syncretic religious groups, including pregnant women. However, no documented study has been performed to evaluate the risk of developmental toxicity of ayahuasca. METHODS: In the present work, maternal and developmental toxicity was evaluated in Wistar rats. Ayahuasca was administered to pregnant rats in three different doses [the equivalent typical dose (TD) administered to humans, five-fold TD and 10-fold TD] during the gestational period (6-20 days). RESULTS: Dams treated with the highest ayahuasca dose showed maternal toxicity with decrease of weight gain and food intake. Visceral fetal findings were observed in all treatment groups. Skeletal findings were observed in the intermediate- and high-dose groups. The fetuses deriving from the highest dose group also presented a decrease in body weight. CONCLUSIONS: From these results, it is possible to conclude that there is a risk of maternal and developmental toxicity following ayahuasca exposure and that the level of toxicity appears to be dose-dependent. Birth Defects Res (Part B) 89:207-212, 2010. (C) 2010 Wiley-Liss, Inc.

Are air-borne mycotoxins a public health concern in Portugal?

Introduction - Microscopic filamentous fungi, under suitable environmental conditions, can lead to the production of highly toxic chemical substances, commonly known as mycotoxins. The most widespread and studied mycotoxins are metabolites of some genera of moulds such as Aspergillus, Penicillium and Fusarium. Quite peculiar conditions may influence mycotoxin biosynthesis, such as climate, geographical location, cultivation practices, storage and type of substrate. Toxicity has been extensively investigated for the most important mycotoxins, such as aflatoxins, ochratoxin A and Fusarium toxins, and much information derived from toxicokinetics in animal models has also been obtained. The adverse effects are mainly related to genotoxicity, carcinogenicity, mutagenicity, teratogenicity and immunotoxicity. Aim of the study - To identify fungal species able to produce important mycotoxins in different Portuguese settings.

Segurança no circuito do medicamento citotóxico: contributos para a avaliação da realidade hospitalar em Portugal

Introdução: O medicamento citotóxico é definido pelas suas características de genotoxicidade, mutagenicidade, carcinogenicidade, teratogenicidade, toxicidade reprodutiva e toxicidade orgânica em baixas doses. Deste modo, existe uma grande preocupação no que concerne ao manuseamento deste tipo de medicamentos, devido aos riscos ocupacionais que podem surtir da exposição a que os profissionais de farmácia envolvidos estão sujeitos. Objectivos: Analisar a realidade da farmácia hospitalar face ao cumprimento das normas e procedimentos preconizados pelas actuais guidelines para o manuseamento seguro de medicamentos citotóxicos, e identificar as lacunas existentes, conduzindo à promoção de práticas centradas na minimização do risco de exposição/contaminação dos profissionais e do ambiente. Material e Métodos: Foi realizada uma pesquisa bibliográfica sistemática sobre o tema, utilizando-se como instrumento de recolha de dados um inquérito por questionário, em que os TDT de Farmácia foram abordados sobre os procedimentos verificados no hospital onde exercem actividade profissional. Resultados: Face ao cumprimento das normas na recepção, armazenamento e transporte de medicamentos citotóxicos, verifica-se que todos os hospitais se encontram acima da média. Apesar desta evidência, é na fase de transporte que se verifica um menor cumprimento. As principais lacunas detectadas foram ao nível da não utilização de EPI nas fases de recepção e armazenamento; a recepção de medicamentos citotóxicos em conjunto com outros medicamentos; a falta de um sistema de ventilação no local de armazenamento e, ainda, ausência de portas de correr e/ou gavetas fechadas nos carros de transporte de medicamentos citotóxicos. Conclusões: Os resultados deste estudo revelam alguma heterogeneidade de procedimentos nos hospitais Portugueses, sugerindo a necessidade de intervenção e reformulação do programa de segurança e gestão de risco desenvolvidos para o manuseamento de citotóxicos.

Occupational exposure to aflatoxin B1: new (old) occupational risk!

Contrary to fungi, exposure to mycotoxins is not usually identified as a risk factor present in occupational settings. This is probably due to the inexistence of limits regarding concentration of airborne mycotoxins, and also due to the fact that these compounds are rarely monitored in occupational environments. Aflatoxin B1 (AFB1) is the most prevalent aflatoxin and is associated with carcinogenicity, teratogenicity, genotoxicity and immunotoxicity but only a few studies examined exposure in occupational settings. Workers can be exposed to high airborne levels during certain operations in specific occupational settings. Aim of study: The study aimed to assess exposure to AFB1 in three settings: poultry, swine production and waste management.

Low Dose Thalidomide for Treatment of Resistant Discoid Lupus Erythematosus. A Case Report

Discoid lupus erythematosus (DLE) is a chronic, indolent, disfiguring disease that is characterized by scaly, erythematous, disk-shaped patches and plaques followed by atrophy, scarring and depigmentation. In a small number of patients, it is refractory to standard therapies. In several studies, thalidomide has been reported to be an effective treatment in those cases. The most fearful side effects are teratogenicity and neuropathy. Adequate counseling and vigilance must be given to the patients. We report a 45-year-old Portuguese woman who presented with a 20-year history of severe facial and scalp DLE confirmed by histopathology. For several years, it failed to respond to several therapies, including topical, intralesional and oral corticosteroids, hydroxychloroquine, methotrexate, azathioprine and topical tacrolimus. Thalidomide was initiated at a dosage of 50mg/day and the skin lesions had improved dramatically after three weeks with complete clinical remission. Two months later, the dose was reduced to 50mg, five days per week without disease rebound. The patient´s concomitant medications during the treatment included sunscreen, hydroxycholoroquine, enoxaparin and aspirin to prevent thromboembolic events. Pregnancy testing, routine laboratory and electrocardiography were performed at regular intervals for safety monitoring and the results were within normal limits. Only minor side effects as nausea, constipation and somnolence were noted, however, they improved with dose reduction. Our data confirm that thalidomide therapy is an alternative or adjunctive treatment for patients with severe, chronic DLE that is refractory to standard therapies. In this patient, low-dose thalidomide was an effective treatment with minimal side effects.

Options for clinical trials of pre and post-natal treatments for congenital toxoplasmosis

Clinical trials comparing different drug regimens and strategies for the treatment of congenital toxoplasmosis and its clinical manifestations in the liveborn child in different clinical settings should aim at formally evaluating the net benefit of existing treatments and at developing new therapeutic options. Currently, there is no ideal drug for congenital toxoplasmosis; future research should focus on the screening of new active drugs and on their pre-clinical and early clinical development, with a focus on pharmacokinetic/dynamic studies and teratogenicity. For the prenatal treatment of congenital toxoplasmosis, a trial comparing spiramycine to pyrimethamine-sulphadiazine and placebo would allow a formal estimation of the effect of both drugs in infected pregnant women. In newborn children, the net benefit of pyrimethamine-sulphadiazine should also be formally assessed. These trials will be implemented in settings where prenatal screening for Toxoplasma gondii is currently implemented. Trials should be carefully designed to allow for translation to other settings and modelling tools like cost-effectiveness analysis should be used to provide clinicians and founders with the best available evidence to establish recommendations.

Intrauterine exposure to carbamazepine and specific congenital malformations: systematic review and case-control study.

OBJECTIVE: To identify specific major congenital malformations associated with use of carbamazepine in the first trimester of pregnancy. DESIGN: A review of all published cohort studies to identify key indications and a population based case-control study to test these indications. SETTING: Review of PubMed, Web of Science, and Embase for papers about carbamazepine exposure in the first trimester of pregnancy and specific malformations, and the EUROCAT Antiepileptic Study Database, including data from 19 European population based congenital anomaly registries, 1995-2005. PARTICIPANTS: The literature review covered eight cohort studies of 2680 pregnancies with carbamazepine monotherapy exposure, and the EUROCAT dataset included 98 075 registrations of malformations covering over 3.8 million births. MAIN OUTCOME MEASURES: Overall prevalence for a major congenital malformation after exposure to carbamazepine monotherapy in the first trimester. Odds ratios for malformations with exposure to carbamazepine among cases (five types of malformation identified in the literature review) compared with two groups of controls: other non-chromosomal registrations of malformations and chromosomal syndromes. RESULTS: The literature review yielded an overall prevalence for a major congenital malformation of 3.3% (95% confidence interval 2.7 to 4.2) after exposure to carbamazepine monotherapy in the first trimester. In 131 registrations of malformations, the fetus had been exposed to carbamazepine monotherapy. Spina bifida was the only specific major congenital malformation significantly associated with exposure to carbamazepine monotherapy (odds ratio 2.6 (95% confidence interval 1.2 to 5.3) compared with no antiepileptic drug), but the risk was smaller for carbamazepine than for valproic acid (0.2, 0.1 to 0.6). There was no evidence for an association with total anomalous pulmonary venous return (no cases with carbamazepine exposure), cleft lip (with or without palate) (0.2, 0.0 to 1.3), diaphragmatic hernia (0.9, 0.1 to 6.6), or hypospadias (0.7, 0.3 to 1.6) compared with no exposure to antiepileptic drugs. Further exploratory analysis suggested a higher risk of single ventricle and atrioventricular septal defect. CONCLUSION: Carbamazepine teratogenicity is relatively specific to spina bifida, though the risk is less than with valproic acid. Despite the large dataset, there was not enough power to detect moderate risks for some rare major congenital malformations.