Browsing by Issue Date, starting with "2018-05-11"
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- Health Examination Surveys and Human Biomonitoring – the added value of combined studiesPublication . Namorado, SóniaHealth Examination Surveys (HES) are health surveys where information collected by questionnaire is complemented with information obtained through physical measurements, such as blood pressure and anthropometric measurements, and through clinical analysis of biological samples. Between 2000 and 2017, 15 European countries have conducted a national HES and in many countries smaller, regional or disease specific surveys have been carried out. Portugal is one of the countries that has recently conducted a first National Health Examination Survey (INSEF), which collected interview and anthropometric data and blood samples in a nationally representative sample of 4911 individuals aged between 25 and 74 years old. Human Biomonitoring (HBM) is a scientific approach used to assess individual human exposure to environmental chemicals by measuring substances, their metabolites or reaction products in biological specimens. Many countries have established HBM programs to monitor the chemical exposures of their populations. HES and HBM studies are very similar in terms of the infrastructure and procedures necessary for their implementation, as in either type of studies data is collected through fieldwork, which constitutes one of the largest expenditures for such studies. Combined studies could then result in more costeffective ways to conduct health and environmental monitoring. Some countries, like the USA, Canada, Germany, Belgium and France have already recognized the potential to combine these two types of studies and have successfully implemented surveys with both components. However, in practice, the opportunity for adding an HBM module to a health study and vice versa is rarely used. Reasons for this may be multifarious and may differ from country to country, and between different study settings. Within the HBM4EU project the advantages and obstacles of combined studies are being evaluated and feasibility studies will be conducted in order to identify practical/logistic, financial and scientific benefits and short comings.
- CYP21A2 gene duplication with a severe pathogenic variant is a benign allele that does not confirm clinical suspicions of 21-hydroxylase deficiencyPublication . Gomes, Susana; Silva, Júlia; Pereira-Caetano, Iris; Gonçalves, JoãoIntroduction: Congenital Adrenal Hyperplasia (CAH), one the most common autosomal recessive disorders, is regularly managed during genetic counselling (GC). The coding gene (CYP21A2) for 21-hydroxylase (21-OH), is located (in cis) with its pseudogene (CYP21A1P) in the RCCX cluster (6p21.3) and, the most common structure of this cluster comprises a single copy of each one. However, genotypes associated with CYP21A2 duplications can be detected in individuals during familial and/or pre-conceptional studies. In this duplicated alleles, the severe variant c.955C>T p.(Glu319*) is frequently detected, but is usually present in the proximal CYP21A2 copy. This means, that even in the presence of a severe variant, its allele is not pathogenic. Therefore, the aim of this work is to emphasize the importance of a better strategy of molecular analysis and an accurate interpretation of its results, in order to establish a correct genotyping of family members and partners, and provide a more reliable genetic counselling.
- Molecular diagnosis of CYP21A2 gene in affected cases with congenital adrenal hyperplasia and familial implications for prenatal diagnosisPublication . Gomes, Susana; Silva, Júlia; Pereira-Caetano, Iris; Gonçalves, João; Gomes, SusanaCongenital Adrenal Hyperplasia (CAH) can be due to one of seven different enzymes involved in the synthesis of cortisol. Deficiency in 21-hydroxylase (21-OHD) is responsible for 90 – 95% of the CAH cases. The clinical symptoms of CAH are directly related with 21-OH activity which is associated with the CYP21A2 genotype. CYP21A2 gene cluster is prone to genetic recombination events leading to a wide variety of complex rearrangements (duplications, deletions, conversions) and point mutations. CAH can be divided in two clinical conditions – the classic form [saltwasting(SW) and simple virilising(SV)] and the non-classic(NC) form of the disease. While SW is usually diagnosed in neonates, SV are mainly detected during the first years of life and, most cases of NC-CAH are usually diagnosed from the 4th year of life until puberty or until adulthood. We present here the molecular results obtained in 265 patients with CAH. The clinical diagnose was established in these patients between the 5th day of life until adulthood (<18 years old). When available, both parents of the affected patients were also analysed after informed consent has been obtained.
- Prematuridade e Rastreio NeonatalPublication . Lopes, Lurdes; Sousa, Carmen; Fonseca, Helena; Carvalho, Ivone; Marcão, Ana; Rocha, Hugo; Vilarinho, LauraIntrodução: Os programas de rastreio neonatal são programas de saúde pública, com o objetivo de uma deteção precoce de recém-nascidos afetados por determinada patologia, com vista a um início atempado do tratamento, que conduza a uma diminuição da morbilidade e mortalidade. Em todo o mundo, a taxa média dos prematuros ao nascimento é estimada em cerca de 10%, tendo a evolução científica e tecnológica no campo da neonatologia contribuído para o recente aumento significativo da sua taxa de sobrevivência. Também em Portugal, e de acordo com dados da Sociedade Portuguesa de Neonatologia (SPN), apesar da natalidade ter vindo a descer nos últimos anos, o número de recém-nascidos de extremo baixo peso (RNEBP), isto é, que nascem com menos de 1500 gramas e/ou menos de 30 semanas de gestação, tem vindo a aumentar. A imaturidade e complicações clinicas associadas à prematuridade originam frequentemente alterações no rastreio neonatal destes bebés, contribuindo para o aumento da percentagem de resultados falsos positivos e negativos no rastreio neonatal deste grupo de recém-nascidos. O objetivo deste trabalho consiste na avaliação da estratégia utilizada na URN para efetuar o rastreio neonatal dos RNBP, e que consiste na análise de três amostras colhidas entre o 3º e o 6º dia, às duas semanas e às quatro semanas de vida.
- Mixtures health effects: mycotoxins in foodPublication . Pinhão, Mariana; Loureiro, Susana; Louro, Henriqueta; Alvito, Paula; Silva, Maria JoãoIn recent years, the risk assessment paradigm has shifted from the single-exposure and single-chemical adverse effect scenario to the one of multiple exposures and combined adverse effects. The present work describes the in vitro combined toxicity of mycotoxins at the renal level, as a case study. Mycotoxins are often present in food and feed, as secondary metabolites of contaminating fungi and human co-exposure mainly occurs though diet. Even though predictions about the toxic effects of mycotoxins mixtures can be based on their individual toxicities, experimental data is still limited to allow a reliable hazard assessment. This study aimed at characterizing the combined cytotoxic and genotoxic effects of ochratoxin A (OTA) and fumonisin B1 (FB1), in a kidney human cell line. The toxicity of several combinations of OTA and FB1 was compared with their individual toxicities (MTT assay) and interactions were ascertained using the reference models of concentration addition and independent action. A synergistic pattern for combinations of FB1 with the lower doses of OTA was detected, shifting to antagonism at higher dose levels, irrespectively of the reference model applied. Neither OTA nor FB1, individually or in combination, were genotoxic. In conclusion, this study revealed that, OTA and FB1 exert a synergistic toxic effect at the lowest dose levels, which are the most realistic ones in terms of human co-exposure. This finding emphasizes the relevance of assessing the combined toxicity of mycotoxins to allow the development of qualitative/semi-quantitative or probabilistic models for the hazard assessment of combined human exposure to these food contaminants.
- Prevalence of general and abdominal obesity in Portugal: comprehensive results from the National Food, nutrition and physical activity survey 2015-2016Publication . Oliveira, Andreia; Araújo, Joana; Severo, Milton; Correia, Daniela; Ramos, Elisabete; Torres, Duarte; Lopes, Carla; by the IAN-AF ConsortiumBACKGROUND: This study includes, for the first time, estimates of general and abdominal obesity prevalence for all ages of the Portuguese population, using common standardized methodologies. Results are compared by sex, age groups, educational level and geographical regions. METHODS: Participants were a representative sample of the Portuguese population aged between 3 months and 84 years of age (n = 6553), enrolled in the National Food, Nutrition and Physical Activity Survey, 2015-2016. Objective anthropometric measurements included length/height, weight and body circumferences, performed according to standard procedures. Body mass index (BMI) was classified according to the World Health Organization (WHO) growth charts for children and adolescents, and WHO criteria for adults. Abdominal obesity was defined in adults as waist-hip ratio ≥ 0.85 in women or ≥ 0.90 in men. Prevalence estimates and 95% confidence intervals (95%CI) were weighted according to a complex sampling design, considering stratification by seven geographical regions and cluster effect for the selected Primary Health Care Unit. RESULTS: The national prevalence of obesity is 22.3% (95%CI: 20.5-24.0), significantly higher in women. Obesity prevalence is much higher in the elderly (39.2%, 95%CI. 34.2-44.2), while children and adolescents have the lowest prevalence around 8-9%. In a regression model, three knot points denoting an inflection of obesity prevalence across the life span were observed around 5, 15 and 75 years. The prevalence of pre-obesity at national level is 34.8% (95%CI: 32.9-36.7), higher in men, and almost 18% of children and 24% of adolescents have pre-obesity. The sex- and age-standardized prevalence of obesity ranged from 38.3% (95%CI: 34.6-42.1) to 13.1% (95%CI: 10.3-15.9) for the less and the most educated individuals, respectively. Although some geographical region disparities, obesity prevalence did not significantly differed across regions (p = 0.094). The national prevalence of abdominal obesity in adults is 50.5% (95%CI: 47.9-53.1), particularly high in the elderly (80.2%). CONCLUSION: Almost 60% of the general Portuguese population is obese or pre-obese. Women, elderly and less educated individuals present the highest obesity prevalence. Abdominal obesity, in particular, seems to be a relevant public health problem among the elderly men.
- The relevance of effect biomarkers in human biomonitoringPublication . Gomes, Bruno; Louro, Henriqueta; Silva, Maria JoãoA fundamental goal of environmental/occupational health policy is to reduce and, whenever possible, prevent human exposure to chemical substances that may lead to mobility or mortality. Human biomonitoring (HBM) allows the assessment of the levels of certain substances in the body, through the analysis of biomarkers of exposure (chemical substances, metabolites) and it has been considered as an extremely important tool in public health. A great strength of HBM is that it provides unambiguous indication that both exposure and absorption have occurred. On the other hand, measuring uniquely exposure biomarkers does not provide information on preclinical effects that may allow establishing a link between exposure and health effects. This work aims summarizing the most used biomarkers of effect and give evidence of the importance of these biomarkers in HBM and public health protection, based on recently published data. Briefly, these biomarkers consist of biochemical alterations in urine or blood, endocrine changes, cytogenetic alterations [micronuclei, chromosomal aberrations, translocations, sister chromatid exchanges and DNA repair] or interactions with macromolecules such as DNA, RNA and proteins through the recent –omics technologies. The inclusion of biomarkers of effect in HBM studies contributes to bridge the gap between exposure and health effects, because they give information on early biological alterations before the onset of disease. Given that these biomarkers reflect reversible alterations in the organism, the effects detected are likely to be prevented, if exposure to the critical substance (or mixture of substances) is reduced or ceased. Thus, the joint information gathered from biomarkers of exposure and effect in HBM can be used to improve health risk assessment and reinforce the scientific basis to implement preventive policies in occupational and environmental settings.
- Impact of DINCH® in human cells: evaluation of its potential cytotoxic and genotoxic effectsPublication . Vasconcelos, Ana Luisa; Silva, Maria João; Louro, HenriquetaThe chemical Di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH) has been applied as a non-aromatic plasticizer and substitute for other phthalate plasticizers such as di-(2-ethylhexyl) phthalate (DEHP) and di-(iso-nonyl) phthalate (DINP), that have shown to have adverse effects. Since DINCH detected in indoor dust has increased after the market introduction of this plasticizer in 2002, the human exposure is a concern. Health-related guidance values have been derived for children and adults, namely 3 mg/L and 4.5 mg/L of DINCH metabolites in the urine, respectively. Recently, the exposure of Portuguese children to DINCH was reported, in spite the low levels detected in children’s urine, which were below the established health guidance levels. Conversely, few studies have addressed the potential toxicity of DINCH but in vivo studies suggest its bioavailability, leading to concerns in respect to systemic exposure or longer term consequences of its use, namely to liver or kidney cells. To contribute to the hazard characterization of DINCH, its potential cytotoxicity and genotoxicity was investigated in human liver cells, following the exposure of HepG2 cells to a range of concentrations of this chemical agent. The methodology included the MTT assay for cytoxicity determination, the comet assay for the detection of DNA damage and the micronucleus assay for determination of chromosomal damage, based on the OECD TG 487 guideline (2016). The results showed that concentrations ranging from 1 to 500 µg/mL were neither cytotoxic following 24h exposure of HepG2 cells, nor had impact on DNA or chromosome damage. Underway studies focus on the effects under the presence of exogenous liver metabolic enzymes (S9 fraction) and on the detection of oxidative DNA damage. Further ongoing investigation is addressing the potential nephrotoxic effects of DINCH using kidney cells.