Introdução: Intoxicação ambiental por chumbo é uma questão extensamente investigada em diversos países. No Brasil existem poucos estudos sobre o tema, em sua maioria realizada em locais com relato prévio de contaminação do meio ambiente. O objetivo deste estudo é a determinação da prevalência de intoxicação por chumbo em crianças de uma Vila na cidade de Porto Alegre sem relatos prévios de contaminação do meio ambiente por chumbo e com fatores de risco descritos na literatura. Além disso, foram avaliados fatores associados e possíveis fontes de contaminação. Metodologia: Estudo transversal de prevalência com amostra randomizada de crianças de 0 a 5 anos, em que foi medido o nível de chumbo no sangue e aplicado um questionário para avaliação de fatores associados. Posteriormente, foi realizada uma avaliação ambiental preliminar com análise direta do solo e indireta da poluição atmosférica, utilizando bioindicadores, na tentativa de averiguar possíveis fontes de contaminação. Resultados: 97 crianças participaram do estudo (83.6% da amostra selecionada), com prevalência de intoxicação por chumbo encontrada de 16.5% ([Pb] sanguíneo >= 10,0?g/dL). Reciclagem de lixo, nível educacional do pai e idade estiveram relacionados a um aumento na concentração de chumbo no sangue. Foram encontrados níveis elevados de chumbo no solo e pouca indicação de poluição atmosférica por este metal. Discussão: Encontrou-se uma prevalência significativa de intoxicação por chumbo e as possíveis fontes de contaminação nesta comunidade parecem ter relação com atividades de reciclagem de lixo. Outros estudos sobre a questão com a população infantil em geral devem ser conduzidos, bem como avaliações de possíveis fontes locais e gerais, para que se possa dimensionar corretamente essa questão no Brasil. / Introduction: Environmental lead intoxication is an extensively investigated issue in several countries. In Brazil, there are only a few studies on the theme, most of which were carried out in places with previous reports of environmental lead contamination. The objective of this study was to determine the prevalence of lead intoxication in children, from a neighborhood of the city of Porto Alegre without previous descriptions of environmental lead contamination, but with risk factors described in the literature and additionally to evaluate associated factors and possible local sources of contamination. Methodology: Cross-sectional study of prevalence with random sample of children aged 0 to 5, in which the level of lead in the blood was measured and a questionnaire was applied to evaluate associated factors. Afterwards, a preliminary environmental evaluation was carried out with direct analyses of soil and indirect analyses of air pollution, using bioindicators, in an attempt to verify possible local sources of contamination. Results: 97 children participated in the study (83.6% of the selected sample), with 16.5% of the sample showing intoxication (blood [Pb] >= 10.0 ?g/dL). Waste recycling at home, father\'s educational level and age were factors related to an increase in the concentration of lead in the blood. High levels of lead were found in the soil and there was little indication of lead deposition through atmospheric emissions. Discussion: A significant prevalence of lead intoxication was found and the possible sources of contamination in this community seem to be related to activities of waste recycling. Other studies on this matter in children in the general Brazilian population should be carried out, as well as assessments of possible sources and local risk factors.

Lead is a highly toxic metal that has been used by humans for over 2000 years. Over this time it has become increasingly apparent that despite its usefulness, lead is one of the most highly toxic substances known to man. Current research into lead exposure of humans focuses on low-level chronic exposure and its effects on learning and behaviour. However, investigations into lead exposure of wildlife are still focussed on mortalities, particularly of waterfowl and raptors, with little known about low-level exposures or the effects on other species. This study examines the exposure of free-ranging kea (Nestor notabilis) from the Aoraki/ Mt Cook village and national park, takahe (Porphyrio hochstetteri) from Tiritiri Matangi, Kapiti and Mana Islands, and the lead associated syndrome of clenched-claw paralysis and leg paresis in harriers (Circus approximans) in New Zealand. Thirty-eight kea had detectable blood lead with concentrations ranging from 0.028 mg/L to 3.43 mg/L (mean = 0.428 mg/L ± 0.581). Analysis of tissue samples found that seven of 15 birds died with elevated tissue lead. Lead exposure may be an important contributing factor in kea mortality. As a result of these findings, lead abatement in areas frequented by kea is being considered. Eighteen of 45 takahe had detectable blood lead concentrations ranging from 0.015 mg/L to 0.148 mg/L (mean = 0.028 mg/L ± 0.042). Analysis of tissue samples from offshore island and Murchison Mountains birds found that all had detectable lead. Despite levels of lead exposure in the population being low and unlikely to result in overt clinical signs, it is widespread and there may be significant exposure of birds living around old buildings. An investigation into the clinical signs, pathology and response to treatment of clenched-claw paralysis and leg paresis in wild harriers was carried out. Harriers with clenched feet had significantly higher blood lead concentrations than those without. In conclusion, lead is a major factor in the expression of this clinical syndrome but other factors not yet identified are playing a role. This study demonstrates that lead is widespread in the New Zealand environment exposing a diverse range of avifauna, and has made some progress towards exploring some of its effects on health and survival.

A falta de consenso na literatura acerca dos efeitos tóxicos do chumbo no sistema auditivo é notória, tanto em estudos clínicos quanto experimentais. Em adição, tem sido relatado que o ferro apresenta um efeito protetor na toxicidade cerebral causada pelo chumbo. Assim, estudos clínicos e bioquímicos têm sido realizados no intuito de compreender a relação entre o chumbo e o sistema auditivo, bem como identificar possíveis substâncias protetoras para a toxicidade deste metal. Neste sentido, no presente estudo verificou-se o processo maturacional do nervo auditivo e tronco encefálico, associado à análise proteômica da porção auditiva do tronco encefálico de ratos expostos a acetato de chumbo e suplementados com sulfato ferroso. O experimento foi realizado por seis semanas com 30 ratos (Rattus norvergicus, variedade Wistar) machos, recém-desmamados, divididos em seis grupos de cinco animais cada, sendo um controle, que recebeu água deionizada; dois grupos experimentais que receberam 100 mg/L de Pb(CH3COO)2 na água de beber, sendo administrado simultaneamente para um deles 20 mg/kg de FeSO4 a cada dois dias; dois grupos que receberam a dose de 400 mg/L de Pb (CH3COO)2 na água de beber, onde para um deles foi administrado simultaneamente 20 mg/kg de FeSO4 a cada dois dias e um grupo experimental que recebeu água deionizada e uma solução de 20 mg/kg de FeSO4 a cada dois dias. O processo maturacional do sistema auditivo foi verificado por meio da análise do Potencial Evocado Auditivo de Tronco Encefálico (PEATE) em dois momentos distintos, antes e depois da exposição ao chumbo. Os animais foram então sacrificados, coletado sangue e removido o tronco encefálico. A concentração de chumbo no sangue e tronco encefálico, apresentou um efeito dose-resposta, confirmado pela alta correlação entre a concentração nos dois compartimentos (r2=0,905, p<0,0001), tendo o sulfato ferroso reduzido a concentração de chumbo no sangue e no tecido, embora a diferença só tenha sido significativa para o sangue grupo que recebeu 100 mg/L de Pb(CH3COO)2). Com relação ao PEATE observou-se diferença estatisticamente significativa para o interpico I-II (p=0,049) nos grupos experimentais 100 mg/L Pb(CH3COO)2 e 400 mg/L Pb(CH3COO)2 e interpico I-IV, quando comparados os grupos 100 mg/L Pb(CH3COO)2 e 100 mg/L Pb(CH3COO)2 + FeSO4 (p=0,033). A análise proteômica apontou uma diminuição considerável no número de spots proteicos detectados em todos os grupos experimentais em relação ao controle, bem como uma redução na expressão do padrão proteico. Assim, o presente estudo reforça a hipótese do papel deletério do chumbo nas dosagens de 100 e 400 mg/L de Pb (CH3COO)2 na maturação do nervo auditivo e região do núcleo coclear, com possível efeito protetor do ferro. A análise proteômica do tronco encefálico de ratos demonstrou que o acetato de chumbo altera a expressão proteica desta estrutura, contudo o efeito protetor do sulfato ferroso não foi confirmado nas proteínas identificadas. / There is a lack of consensus in the literature about the toxic effects of lead in the auditory system, both in clinical and experimental studies. In addition to that, it has been reported that iron has a protective effect on brain toxicity caused by lead. Therefore, clinical and biochemical studies have been carried out to understand the relationship between Pb and the auditory function, as well as if the ferreous sulfate as an otoprotectant. In this study the maturational process of the auditory nerve and brainstem and the proteomic profile of the auditory portion of the brainstem of rats exposed to lead and supplemented with iron were evaluated. The experiment was carried out for six weeks with 30 wealing rats (Rattus norvegicus, Wistar), divided into six groups of five animals each: a control group that received deionized water; two experimental groups receiving 100 mg/L Pb(CH3COO)2 in drinking water, being given 20 mg/kg FeSO4 simultaneously to one of them every two days; two groups received 400 mg/LPb(CH3COO)2 in drinking water, where to one of them was given 20 mg/kg FeSO4 simultaneously every two days; and an experimental group that received deionized water and a solution of 20 mg/kg FeSO4 every two days. The maturational process of the auditory system was verified by analyzing the Brainstem Auditory-Evoked Potential (BAEP) at two different times, before and after lead exposure. The animals were sacrificed, their blood collected and brainstem removed. The concentration of lead in blood and brain stem showed a dose-response, confirmed by correlation between the concentration in the two compartments (rr2 = 0.905, p <0.0001). Ferreous sulfate reduced the levels of lead in blood and tissue, although the difference was only significant for blood (group receiving 100 mg/L Pb(CH3COO)2). Concerning to BEAP we observed a statistically significant difference for the interpeak I-II (p = 0.049) in the experimental groups 100 and 400 mg/L Pb(CH3COO)2 and for the interpeak I-IV, when groups 100 and 100 mg/L Pb(CH3COO)2 + FeSO4 were compared (p = 0.033). The proteomic analysis showed a considerable decrease in the number of protein spots detected in all experimental groups compared to control, as well as a reduction in the expression pattern of the proteins. Thus, the present study reinforces the hypothesis of deleterious role of Pb in dosages of 100 and 400 mg/L Pb(CH3COO)2 in the maturation of the auditory nerve and cochlear nucleus region, with a possible protective effect of ferreous sulfate. The proteomic analysis of the brainstem of rats showed that lead acetate alters protein expression of this structure. However, the protective effect of ferreous sulfate was not confirmed for the identified proteins.

Introdução: Intoxicação ambiental por chumbo é uma questão extensamente investigada em diversos países. No Brasil existem poucos estudos sobre o tema, em sua maioria realizada em locais com relato prévio de contaminação do meio ambiente. O objetivo deste estudo é a determinação da prevalência de intoxicação por chumbo em crianças de uma Vila na cidade de Porto Alegre sem relatos prévios de contaminação do meio ambiente por chumbo e com fatores de risco descritos na literatura. Além disso, foram avaliados fatores associados e possíveis fontes de contaminação. Metodologia: Estudo transversal de prevalência com amostra randomizada de crianças de 0 a 5 anos, em que foi medido o nível de chumbo no sangue e aplicado um questionário para avaliação de fatores associados. Posteriormente, foi realizada uma avaliação ambiental preliminar com análise direta do solo e indireta da poluição atmosférica, utilizando bioindicadores, na tentativa de averiguar possíveis fontes de contaminação. Resultados: 97 crianças participaram do estudo (83.6% da amostra selecionada), com prevalência de intoxicação por chumbo encontrada de 16.5% ([Pb] sanguíneo >= 10,0?g/dL). Reciclagem de lixo, nível educacional do pai e idade estiveram relacionados a um aumento na concentração de chumbo no sangue. Foram encontrados níveis elevados de chumbo no solo e pouca indicação de poluição atmosférica por este metal. Discussão: Encontrou-se uma prevalência significativa de intoxicação por chumbo e as possíveis fontes de contaminação nesta comunidade parecem ter relação com atividades de reciclagem de lixo. Outros estudos sobre a questão com a população infantil em geral devem ser conduzidos, bem como avaliações de possíveis fontes locais e gerais, para que se possa dimensionar corretamente essa questão no Brasil. / Introduction: Environmental lead intoxication is an extensively investigated issue in several countries. In Brazil, there are only a few studies on the theme, most of which were carried out in places with previous reports of environmental lead contamination. The objective of this study was to determine the prevalence of lead intoxication in children, from a neighborhood of the city of Porto Alegre without previous descriptions of environmental lead contamination, but with risk factors described in the literature and additionally to evaluate associated factors and possible local sources of contamination. Methodology: Cross-sectional study of prevalence with random sample of children aged 0 to 5, in which the level of lead in the blood was measured and a questionnaire was applied to evaluate associated factors. Afterwards, a preliminary environmental evaluation was carried out with direct analyses of soil and indirect analyses of air pollution, using bioindicators, in an attempt to verify possible local sources of contamination. Results: 97 children participated in the study (83.6% of the selected sample), with 16.5% of the sample showing intoxication (blood [Pb] >= 10.0 ?g/dL). Waste recycling at home, father\'s educational level and age were factors related to an increase in the concentration of lead in the blood. High levels of lead were found in the soil and there was little indication of lead deposition through atmospheric emissions. Discussion: A significant prevalence of lead intoxication was found and the possible sources of contamination in this community seem to be related to activities of waste recycling. Other studies on this matter in children in the general Brazilian population should be carried out, as well as assessments of possible sources and local risk factors.

No description available.

Includes bibliographical references. / xvi, 201, [35] leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / An introduction to the general topic of lead as an environmental contaminant and a critical review of epidemiloogical evidence of lead exposure and neuropsychological (particularly cognitive) development, a description of the research design and methods, and an evaluation of the validity of the precision of the study. / Thesis (Ph.D.)--University of Adelaide, Dept. of Community Medicine,1995

Cardiovascular disease remains the leading causing of death worldwide. American Indians experience an elevated prevelance of cardiovascular disease (CVD) and chronic metal exposures. Determining the impact of metal exposures on CVD can inform prevention and exposure reduction strategies. This dissertation will advance environmental monitoring and biological monitoring of lead, uranium, and selenium exposures using both established biomarkers and novel epigenetic biomarkers to determine the associations of metals with CVD, leveraging the Strong Heart Study (SHS), a prospective cohort of CVD and its risk factors among American Indian adults from tribes and communities in Arizona, Oklahoma, North Dakota, and South Dakota. In Chapter 1, we discuss lead, uranium, and selenium, sources of exposure, and relevance to cardiovascular disease. This includes an overview of metal toxicokinetics and how we can assess these contaminants in both established biomarkers, including blood and urine, as well as in epigenetic biomarkers. In Chapter 2, we estimated urinary uranium concentrations from data on uranium in water among Strong Heart Family Study participants. These estimates were derived from relationships between urinary uranium and water uranium assessed in Strong Heart Family Study (SHFS) participants (n=1,356). Predictions were made using generalized linear models and included demographic and clinical participant characteristics in addition to other metal contaminants measured in water and urine. The root mean square error (RMSE) of the prediction model was 1.01, and predicted urine uranium levels were comparable (median: 0.04 μg/g creatinine, 25th-75th: 0.02-0.08 μg/g creatinine) to urine uranium measured in the SHFS (0.04 μg/g creatinine, 0.02-0.07 μg/g creatinine). These findings emphasize the contribution of uranium in water to urine uranium (reflecting internal dose), and demonstrate the relevance of estimating metal contaminants in urine for the SHS to inform relationships with health effects. In Chapter 3, we evaluated whether urinary uranium concentrations were associated with measures of cardiac geometry and functioning among 1,332 American Indian youth and young adults from the SHFS. Transthoracic echocardiography and blood pressure was assessed at baseline (2001-2003) and a follow-up visit (2006-2009). We estimated mean differences in measures of cardiac geometry and functioning at baseline and follow-up using linear mixed effect models with random intercept and slope over time. In fully adjusted models, a log-doubling of urinary uranium was positively associated with left ventricular (LV) mass index (mean difference: 0.49 g/m2, 95% CI: 0.07-0.92 g/m2), left atrial systolic diameter (0.02 cm, 0.01-0.03 cm), and stroke volume (0.66 mL, 0.25-1.08 mL) at baseline. At follow-up, uranium was associated with increases in left atrial diameter (0.02 cm, 0.01-0.03 cm), pulse pressure (0.28 mmHg, 0.05-0.52 mmHg), and incident LV hypertrophy (OR: 1.25, 95% CI: 1.06, 1.48). These findings support the need to determine the potential long-term clinical and subclinical cardiovascular effects of chronic uranium exposure in the general population, and the need for future strategies to reduce exposure. In Chapter 4, we evaluated if blood lead was associated with CVD incidence and mortality in 1,818 adult American Indian participants. This study estimated the risk of incident CVD and CVD deaths in models adjusted for demographic, lifestyle, and cardiovascular risk factors. Blood lead levels in American Indian adults were associated with increased risk of CVD and coronary heart disease (CHD) incidence and mortality. The hazard ratio (HR) (95% CI) of mortality per change across the 80th-20th quantiles in blood lead was 1.15 (1.02-1.30) for CVD overall and 1.22 (1.08-1.37) for CHD. The corresponding HR was 1.11 (1.01-1.22) for incident CVD and 1.12 (1.00-1.25) for incident CHD. These findings contribute to the evidence of lead as a CVD risk factor at low levels and highlight the importance of further reducing lead exposure in communities across the United States, including American Indian communities. In Chapter 5, we leveraged novel epigenetic biomarkers of lead exposure to investigate their association with cardiovascular disease (CVD) incidence and mortality among 2,231 participants of the Strong Heart Study. Blood DNA methylation was measured using the Illumina MethylationEPIC BeadChip at baseline (1989-1991) and epigenetic biomarkers of lead levels in blood, patella, and tibia were estimated using previously developed biomarkers of DNA methylation at specific CpG sites. In adjusted models, the hazard ratio (HR) (95% CI) of CVD mortality per doubling increase in lead epigenetic biomarkers were 1.42 (1.07-1.87) for tibia lead, 1.22 (0.93-1.60) for patella lead, and 1.57 (1.16-2.11) for blood lead. The corresponding HRs for incident CVD were 0.99 (0.83-1.19), 1.07 (0.89-1.29), and 1.06 (0.87-1.30). The association between the tibia lead epigenetic biomarker and CVD mortality was modified by sex (interaction p-value: 0.014), with men at increased risk (HR: 1.42, 95% CI:1.17-1.72) compared to women (HR: 1.04, 95% CI:0.89-1.22). These findings support that epigenetic biomarkers of lead exposure may capture some of the disease risk associated with lead exposure. In Chapter 6, we investigated the association between urinary selenium levels and DNA methylation (DNAm) among 1,357 participants free of CVD and diabetes in the SHS. Selenium concentrations were measured in urine (collected in 1989-1991) using inductively coupled plasma mass spectrometry. DNAm in whole blood was measured cross-sectionally using the Illumina Methylation EPIC BeadChip (850K) Array. We used epigenome-wide robust linear regressions and elastic net to identify differentially methylated CpG sites associated with urinary selenium levels. Across 788,368 CpG sites, five differentially methylated positions (DMP) (cg00163554, cg18212762, cg25194720, cg11270656, cg00886293) were significantly associated with Se in linear regressions after accounting for multiple comparisons (false discovery rate p-value: 0.10). The top associated DMP (cg00163554) was annotated to the Disco Interacting Protein 2 Homolog C (DIP2C) gene, which relates to transcription factor binding. Future analyses should explore these relationships prospectively and investigate the potential role of differentially methylated sites with disease endpoints. In Chapter 7, we evaluated if declines in blood lead were associated with changes in systolic and diastolic blood pressure in adult American Indian participants from the SHFS (n=285). Using generalized estimating equations, a significant non-linear association between declines in blood lead and declines in systolic blood pressure was detected, with significant linear associations where blood lead decline was 1 µg/L or higher. These findings suggest the need to further study the cardiovascular impacts of reducing lead exposures and the importance of lead exposure prevention. In conclusion, we find that established biomarkers of metal exposure reflecting internal dose such as blood and urine, as well as epigenetic biomarkers of metals exposures, were associated with subclinical CVD and CVD incidence and mortality. Findings concerning blood lead emphasize that low levels of lead remain relevant for CVD, and declines in blood lead even when small (1.0-10.0 µg/L), were associated with reductions in systolic blood pressure. Novelly, we present that urinary uranium levels were adversely associated with measures of cardiac geometry and left ventricular functioning among American Indian adults, and that future attention must be paid to investigating associations with subclinical disease. We also find utility in using epigenetic biomarkers to capture CVD risk, as tibia and blood epigenetic biomarkers of lead, were associated with increased risk of CVD mortality, and urinary selenium was associated with distinct changes in DNAm. Although further work must further validate these epigenetic biomarkers in different populations, future work must continue to investigate these epigenetic biomarkers given their potential to capture CVD risk.

Introdução - A intoxicação por chumbo é um conhecido problema de saúde pública e o envenenamento por este metal pode causar danos a vários órgãos, especialmente ao Sistema Nervoso Central de crianças em desenvolvimento. Objetivo geral- estudar a associação entre exposição a chumbo e comportamento anti-social (CAS) em adolescentes brasileiros. Objetivos específicos: a) analisar a associação entre exposição a chumbo e CAS / cometimento de atos infracionais (CAI); b) estudar potenciais fontes de exposição domiciliar a chumbo que mais estão associadas a altas concentrações de chumbo no esmalte dentário (CCED) e; c) avaliar o impacto de alterações metodológicas na técnica de microbiópsia ácida de esmalte dentário superficial (MAEDS) sobre CCED e profundidade da bíópsia. Métodos- Um estudo transversal foi conduzido com 173 jovens (Bauru, SP). MAEDS foram realizadas nestes jovens por dois diferentes protocolos metodológicos. Além disso, questionários sobre comportamento dos adolescentes e exposição a possíveis fontes de contaminação por chumbo foram aplicados a pais e adolescentes. Análises de regressão logística, testes de Wilcoxon e testes t pareados foram aplicados aos dados. Resultados- Odd ratios ajustados para covariáveis indicaram que alta CCED está associada a risco aumentado de exceder o escore clínico para queixas somáticas, problemas sociais, comportamento de quebrar regras e problemas externalizantes (IC 95%). Alta CCED não foi associado com escores elevados de CAI. Os fatores de risco mais associados com alta CCED foram residir em área contaminada ou até 2 km da área contaminada e trabalhar na fabricação de tintas, pigmentos, cerâmicas ou baterias. A profundidade da biópsia, calculada pela fórmula da altura do cilindro, para um dos protocolos, levou a resultados errôneos de profundidade da biópsia, confirmados por testes de perfilometria. Conclusões- A exposição a altos níveis de chumbo parece disparar o estabelecimento de CAS, o que alerta para a necessidade de desenvolvimento e implantação de políticas públicas de saúde que previnam o envenenamento da população por chumbo. Adolescentes foram expostos ao chumbo por algumas fontes estudadas, no Brasil. O esmalte dentário é um marcador fidedigno e a MAEDS é bastante útil e confiável. No entanto, CCEDs não podem ser comparadas entre resultados de pesquisas diferentes quando houver qualquer variação metodológica entre os estudos, havendo a necessidade da padronização do procedimento. / Introduction - Lead poisoning is a long known public health problem. Thus, lead exposure may cause damage to diverse organs, especially in the Central Nervous System of children in developing process. Objectives- a) to analyze the association between lead exposure and antisocial / delinquent behavior; b) to study the potential sources of lead home exposure more associated to high dental enamel lead levels (DELL) and c) to evaluate two distinct enamel biopsy protocols in relation to biopsy depth and DELL. Methods- A cross-sectional study was conducted with 173 adolescents (Bauru, SP, Brazil). Surface dental enamel (SDE) etch-acid microbiopsies were performed in upper central incisors of these youths by two different methodological protocols. In addition, questionnaires about adolescents behavior and about possible sources of lead contamination were responded by youths and their parents. Logistic regression, Wilcoxon and paired t tests were applied to data. Results- Odd ratios adjusted for familial and social covariates indicated that high DELL is associated with increased risk of exceeding the clinical score for somatic complaints, social problems, rulebreaking behavior (T70) and externalizing problems (T63) (CI 95%). High DELL was not found to be associated with elevated SRD scores. The risk factors associated to high DELL were residing in contaminated area or close proximity and working in paints, pigments, ceramic or batteries manufacturing. The biopsy depth, calculated by the cylinder formula, for Protocol II induced misleading results, as confirmed by profilometry tests. Conclusions- It seems that exposure to high lead levels can indeed trigger antisocial behavior, which claims for public policies to prevent lead poisoning. Adolescents were exposed to lead, by some studied sources, in Brazil. SDE, measured by etch-acid microbiopsy, is a reliable biomarker, but DELL could not be compared when there is some methodological variation among the studies. A standardization of the procedure is necessary.

Introdução - A intoxicação por chumbo é um conhecido problema de saúde pública e o envenenamento por este metal pode causar danos a vários órgãos, especialmente ao Sistema Nervoso Central de crianças em desenvolvimento. Objetivo geral- estudar a associação entre exposição a chumbo e comportamento anti-social (CAS) em adolescentes brasileiros. Objetivos específicos: a) analisar a associação entre exposição a chumbo e CAS / cometimento de atos infracionais (CAI); b) estudar potenciais fontes de exposição domiciliar a chumbo que mais estão associadas a altas concentrações de chumbo no esmalte dentário (CCED) e; c) avaliar o impacto de alterações metodológicas na técnica de microbiópsia ácida de esmalte dentário superficial (MAEDS) sobre CCED e profundidade da bíópsia. Métodos- Um estudo transversal foi conduzido com 173 jovens (Bauru, SP). MAEDS foram realizadas nestes jovens por dois diferentes protocolos metodológicos. Além disso, questionários sobre comportamento dos adolescentes e exposição a possíveis fontes de contaminação por chumbo foram aplicados a pais e adolescentes. Análises de regressão logística, testes de Wilcoxon e testes t pareados foram aplicados aos dados. Resultados- Odd ratios ajustados para covariáveis indicaram que alta CCED está associada a risco aumentado de exceder o escore clínico para queixas somáticas, problemas sociais, comportamento de quebrar regras e problemas externalizantes (IC 95%). Alta CCED não foi associado com escores elevados de CAI. Os fatores de risco mais associados com alta CCED foram residir em área contaminada ou até 2 km da área contaminada e trabalhar na fabricação de tintas, pigmentos, cerâmicas ou baterias. A profundidade da biópsia, calculada pela fórmula da altura do cilindro, para um dos protocolos, levou a resultados errôneos de profundidade da biópsia, confirmados por testes de perfilometria. Conclusões- A exposição a altos níveis de chumbo parece disparar o estabelecimento de CAS, o que alerta para a necessidade de desenvolvimento e implantação de políticas públicas de saúde que previnam o envenenamento da população por chumbo. Adolescentes foram expostos ao chumbo por algumas fontes estudadas, no Brasil. O esmalte dentário é um marcador fidedigno e a MAEDS é bastante útil e confiável. No entanto, CCEDs não podem ser comparadas entre resultados de pesquisas diferentes quando houver qualquer variação metodológica entre os estudos, havendo a necessidade da padronização do procedimento. / Introduction - Lead poisoning is a long known public health problem. Thus, lead exposure may cause damage to diverse organs, especially in the Central Nervous System of children in developing process. Objectives- a) to analyze the association between lead exposure and antisocial / delinquent behavior; b) to study the potential sources of lead home exposure more associated to high dental enamel lead levels (DELL) and c) to evaluate two distinct enamel biopsy protocols in relation to biopsy depth and DELL. Methods- A cross-sectional study was conducted with 173 adolescents (Bauru, SP, Brazil). Surface dental enamel (SDE) etch-acid microbiopsies were performed in upper central incisors of these youths by two different methodological protocols. In addition, questionnaires about adolescents behavior and about possible sources of lead contamination were responded by youths and their parents. Logistic regression, Wilcoxon and paired t tests were applied to data. Results- Odd ratios adjusted for familial and social covariates indicated that high DELL is associated with increased risk of exceeding the clinical score for somatic complaints, social problems, rulebreaking behavior (T70) and externalizing problems (T63) (CI 95%). High DELL was not found to be associated with elevated SRD scores. The risk factors associated to high DELL were residing in contaminated area or close proximity and working in paints, pigments, ceramic or batteries manufacturing. The biopsy depth, calculated by the cylinder formula, for Protocol II induced misleading results, as confirmed by profilometry tests. Conclusions- It seems that exposure to high lead levels can indeed trigger antisocial behavior, which claims for public policies to prevent lead poisoning. Adolescents were exposed to lead, by some studied sources, in Brazil. SDE, measured by etch-acid microbiopsy, is a reliable biomarker, but DELL could not be compared when there is some methodological variation among the studies. A standardization of the procedure is necessary.

ABSTRACT The porphyrias are a diverse group of metabolic disorders arising from diminished activity of enzymes in the heme biosynthetic pathway. They can present with acute neurovisceral symptoms, cutaneous symptoms, or both. The complexity of these disorders is demonstrated by the fact that some acute porphyria patients with the underlying genetic defect(s) are latent and asymptomatic while others present with severe symptoms. This indicates that there is at least one other risk factor required in addition to the genetic defect for symptom manifestation. A systematic review of the heme biosynthetic pathway highlighted the involvement of a number of micronutrient cofactors. An exhaustive review of the medical literature uncovered numerous reports of micronutrient deficiencies in the porphyrias as well as successful case reports of treatments with micronutrients. Many micronutrient deficiencies present with symptoms similar to those in porphyria, in particular vitamin B6. It is hypothesized that a vitamin B6 deficiency and related micronutrient deficiencies may play a major role in the pathogenesis of the acute porphyrias. In order to further investigate the porphyrias, a computational model of the heme biosynthetic pathway was developed based on kinetic parameters derived from a careful analysis of the literature. This model demonstrated aspects of normal heme biosynthesis and illustrated some of the disordered biochemistry of acute intermittent porphyria (AIP). The testing of this model highlighted the modifications necessary to develop a more comprehensive model with the potential to investigated hypotheses of the disordered biochemistry of the porphyrias as well as the discovery of new methods of treatment and symptom control. It is concluded that vitamin B6 deficiency might be the risk factor necessary in conjunction with the genetic defect to trigger porphyria symptoms.