<p>Uvod: Poslednjih godina u fokusu istraživača je efekat sintetskih jednjenja na endokrini sistem. Estri ftalne kiseline se koriste u procesu plastifikacije, kao industrijski rastvarači, lubrikanti, aditivi u tekstilnoj industriji, u pesticidima, kozmetičkim proizvodima. Raste broj dokaza da je tiroidna žlezda podložna dejstvu endokrinih disruptora. Tiroidni hormoni imaju važnu ulogu u regulaciji rasta, tkivne diferencijacije, energetskog metabolizma, reprodukcije i formiranja centralnog nervnog sistema. Brojna istraživanja ukazala su da ftalati deluju kao EDs. Ciljevi istraživanja: 1. Procena izloženosti populacije mono-etilheksil-ftalatu (MEHP) i mono-etil-ftalatu (MEP). 2. Evaluacija razlika u nivou pokazatelja tirodine funkcije između ftalat pozitivnih i ftalat negativnih ispitanika i između gojaznih i normalno uhranjenih ftalat pozitivnih ispitanika. 3.Utvrđivanje razlika u serumskom nivou leptina gojaznih ispitanika sa i bez pozitivnih ftalatnih metabolita i procena povezanosti leptina sa MEP i MEHP i pokazateljima tiroidne funkcije. Izbor ispitanika i metod rada: Istraživanje je sprovedeno kao studija preseka, obuhvatilo je 201 ispitanika. Ispitanici su podeljeni u grupu MEP/MEHP pozitivnih i negativnih i na podgupe normalno uhranjenih i gojaznih. Od antropometrijskih mera određena je telesna visina, telesna masa, obim struka i indeks telesne mase. Laboratorijske analize: jutarnji uzorak urina za određivanje MEP i MEHP; na&scaron;te uzet uzorka venske krvi za FT4, FT3, TSH i leptin. Statististička analiza sprovedena je na softverskom paketu SPSS. Rezultati: Polovina stanovni&scaron;tva je izložena ftalatima. MEP dovodi do povi&scaron;enja FT4 samo u subpopulaciji gojaznih. Nije utvrđen statistički značajan uticaj MEP na FT3. Kod gojaznih MEP pozitivnih osoba ženskog pola povi&scaron;en je TSH. MEHP uzrokuje sniženje FT4 kod normalno uhranjenih ispitanika, a kod normalno uhranjenih mu&scaron;karaca snižava FT3. Nije utvrđen uticaj MEHP na tirotropin. U gojaznih nije ustanovljen uticaj DEHP i DEP na leptinsku sekreciju.Uočena je tendencija negativne korelacije leptina i FT4 kod gojaznih, dok uticaja na FT3 i TSH nema. Zaključak: Na&scaron;a populacija je u velikoj meri izložena ftalatima. Potvrđeno je da MEP i MEHP imaju uticaj na pojedine indikatore tiroidne funkcije. Ftalati u na&scaron;em istraživanju ne uzrokuju poremećaj leptinske skrecije, a leptin ima blag uticaj jedino na FT4.</p> / <p>Introduction: Effects of synthesized chemicals on endocrine system has been in the focus in the last years. Phthalates are used in plasticization, as industrial solvents, lubricants, textile industry additives, in pesticides and cosmetic products. Evidence for thyroid disruption is growing. Thyroid hormones (TH) have an important role in regulation of growth, tissue differentiation, energy metabolism, reproduction and central nervous system formation. Studies show phthalates can cause endocrine disruption. Aims: 1. Estimation of burden of mono-ethyl phthalate (MEP) and di-2-ethylheksyl phthalate(MEHP) in the population. 2. Evaluation of differences in TH and TSH in MEP/MEHP positive and negative participants, as in obese and lean MEP/MEHP positive participants. 3. Evaluation of differences in leptin in obese MEP/MEHP positive and negative subjects and evaluation of the connection between leptin, MEP, MEHP and thyroid indicators. Patients and methods: This was a cross-sectional study that comprised 201 subjects divided into MEP/MEHP positive and negative group, further subdivided in obese and lean. Anthropometric parameters done: body height, body weight, waist and body mass index. Laboratory tests done: morning urine sample analysis for MEP/MEHP and venous sample analysis for free thyroxine (FT4), free tri-iodothyronine (FT3), thyroid stimulating hormone (TSH) and leptin. Statistical analysis was done in SPSS. Results: Half of subjects were exposed to phthalates. MEP induced an increase in FT4 in obese participants and had no influence on FT3. TSH was increased in obese MEP positive female subjects. MEHP induced a decrease in FT4 in lean participants and a decrease of FT3 in lean males. There was no correlation between MEHP and TSH. Influence of MEP/MEHP on leptin secretion. A tendency for negative correlation between leptin and FT4 was seen. There was no influence of leptin on FT3 and TSH. Conclusion: Our population is greatly exposed to phthalates. MEP and MEHP influence certain thyroid indicators i.e. cause thyroid disruption. Phthalates do not influence leptin secretion in our study. There is a mild effect of leptin on FT4.</p>

Introdução: Os dados epidemiológicos e experimentais têm mostrado efeitos adversos da exposição pré e pós natal ao material particulado (MP2,5) sobre a saúde fetal e adulto. Entretanto, poucos estudos abordaram a toxicidade fetal da exposição gestacional à poluição do ar ambiental, bem como efeitos a longo prazo de adversos da exposição pré-natal sobre o desenvolvimento pós-natal e maturação de vários sistemas de órgãos. Objetivos: O objetivo deste estudo foi determinar se a exposição pré-natal e / ou pós-natal ao material particulado, influencia o desenvolvimento pulmonar e resposta vascular pulmonar em um modelo de camundongo suscetível a aterosclerose (LDLr-/- camundongos knockout). Métodos: Camundongos LDLr-/- foram expostos durante a gestação ao ar filtrado (AF) ou ar poluído (AC). Após o período de desmame, os filhotes foram subdivididos e novos quatro grupos foram formados de acordo com a exposição gestacional ou a exposição pós natal contínua no ar poluído. Atingindo a idade de 3 meses, esses grupos foram novamente subdivididos, formando um total de 8 grupos e uma dieta hipercolesterolêmica foi introduzida. Os seguintes parâmetros foram analisados: desfechos gestacionais, dosagem de colesterol total (CT) e triglicerídeos (TG) do fígado, avaliação de citocinas no LBA, e avaliação imunohistoquímica da resposta vascular pulmonar . Resultados: Nos grupos que receberam dieta hipercolesterolêmica (DH) os níveis de colesterol apresentaram-se aumentados (p=0,002); A expressão da IL6 no LBA mostrou-se elevada (p=0,01) somente no grupo que não foi exposto a poluição em nunhum período da vida e recebeu dieta postnatalmente. Diferenças significativas também foram observadas na expressão pulmonar vascular dos seguintes imunomarcadores: endotelina (p=0,05); ENOS (p=0,04); IL1? (p=0,005); INOS (p=0,002); ISOP (p=0,001); NOX2 (0,01) e ICAM (0,04) quando comparados ao grupo controle. O volume pulmonar total também se mostra alterado em decorrência do tratamento. Assim, conclui-se que a resposta do desenvolvimento pulmonar à exposição gestacional à poluição particulada do ar pode ser evidenciada mais tarde durante a vida adulta e agir como um fator modulador de insultos pós-natal devido à exposição a poluição do ar e a uma dieta hipercolesterolemica em individuos predispostos aterosclerose / Epidemiological and experimental data have shown adverse effects of gestational and post natal exposure to ambient particulate matter (PM) on the fetal and adult health. However, few studies addressed the fetal toxicity of gestational exposure to environmental air pollution as well as long-term adverse consequences of prenatal exposure on postnatal development and maturation of several organ systems. The aim of this study was to determine if prenatal and/or postnatal exposure to concentrated ambient particles influences lung development and pulmonary vascular response in an atherosclerosis susceptible mouse model (LDLr-/- knockout mice). LDLr-/- mice were exposed during the pregnancy to either filter (AF) or polluted air (CAP). After weaning period, pups were subdivided and new 4 groups formed according to gestational and continuous or not post natal exposure to air pollution. Reaching the age of 3 months these groups were again subdivided and a hypercholesterolemic (HC) diet introduced and a total of 8 groups were formed. Then the following parameters were analyzed: evaluation of the offspring outcomes, assessment of airway responsiveness, evaluation of cytokines in BALF, dosage of total cholesterol (TC) and triglycerides (TG) in the liver and pulmonary vascular response by immunohistochemistry. Results: Animals that received HC diet presented higher levels of cholesterol (p=0.002) when compared to those animals that received normal diet. Expression of IL-6 was only increased in the groups of mice exposed not exposed to particulate air pollution and that received the HC diet (p=0.01). Significant differences were also observed in vascular expression of immunomarkers in the lung endothelin (p=0.05); ENOS (p=0.04); IL1? (p=0.005); INOS (p=0.002); ISOP (p=0.001); NOX2 (0.01) e ICAM (0.04). Total lung volume was also different, there was an increase in those animals receiving a HC diet. In conclusion, the response of the lung development to gestational exposure to particulate air pollution can be evidenced later in life and act as a modulator factor for postnatal insults due to exposures to particulate air pollution and hypercholesterolemic diet in individual predisposed to atherosclerosis

INTRODUÇÃO: Vários estudos tem mostrado associação entre a poluição atmosférica e efeitos adversos na gravidez, como baixo peso ao nascer, prematuridade e crescimento intra-uterino retardado. OBJETIVO: O objetivo deste estudo foi investigar a associação existente entre prematuridade e baixo peso ao nascer e exposição materna aos contaminantes atmosféricos (partículas inaláveis, dióxido de enxofre e ozônio), no município de Volta Redonda, no estado do Rio de Janeiro, Brasil. MÉTODOS: Esta coorte histórica, de base populacional, foi composta por todos os nascidos vivos, de mães residentes em Volta Redonda, no período de 2003 a 2006. Os dados sobre nascimento foram obtidos do Sistema de Informações sobre Nascidos Vivos (SINASC), do Ministério da Saúde. Os dados referentes à exposição foram fornecidos pelas estações automáticas de monitoramento da qualidade do ar, instaladas no município e controladas pela Fundação Estadual de Engenharia do Meio Ambiente (FEEMA). Modelos de regressão logística e linear, ajustados para potenciais fatores de confusão, foram empregados para avaliar a contribuição da poluição do ar sobre o peso ao nascer e a idade gestacional. RESULTADOS: O total de nascidos vivos no período estudo foi igual a 13.660 nascimentos. O peso médio (desvio padrão) dos recém-nascidos no período foi de 3162,2 g (561,8). O baixo peso ao nascer representou 9,1% dos nascimentos no período e os casos de prematuros foi equivalente a 7,4%. Após análises de regressão logística, seguindo modelos propostos e ajustes para os fatores de confusão identificados, foi observado aumento do risco de baixo ao nascer relacionado à exposição materna às partículas inaláveis durante os segundo e terceiro trimestres de gestação. Também foi verificado aumento do risco de baixo peso ao nascer associado à exposição materna ao ozônio nos segundo e terceiro trimestres de gestação. Com relação à prematuridade foi encontrado aumento no risco associado à exposição materna ao dióxido de enxofre durante os três trimestres de gestação. CONCLUSÕES: Este estudo sugere que exposições a O3, SO2 e PM10, mesmo em concentrações ambientais abaixo dos padrões de qualidade do ar, contribuem para a ocorrência de prematuridade e baixo peso ao nascer no município de Volta Redonda. A pesquisa reforçou a necessidade de revisão dos padrões de qualidade do ar em vigência no Brasil, para a garantia da qualidade da saúde da população. / BACKGROUND: Several studies have shown the association between outdoor air pollution and adverse pregnancy outcomes, related to low birth weight (LBW), preterm birth and intrauterine grow restriction (IUGR). OBJECTIVES: To investigate the association between low birth weight and preterm delivery and maternal exposure to specific outdoor air contaminants, particulate matter (PM10), sulfur dioxide (SO2) and ozone (O3) in Volta Redonda, an industrialized city in the state of Rio de Janeiro, Brazil. METHODS: This population-based cohort study comprised all infants born to women resident in Volta Redonda, Rio de Janeiro, Brazil, in the period of 2003-2006. Birth data used in this retrospective study were obtained from the Information System on Live Births (SINASC) of Brazilian Ministry of Health. Exposure information was provided by air quality monitoring system operated by Environmental Agency for the State of Rio de Janeiro (FEEMA). Logistic and linear models were employed to assess the contribution of air pollution to low birth weight (LBW) and prematurity. RESULTS: The study covered 13660 births occurred from 1 January 2003 to 31 December 2006. The mean (SD) birth weight was 3162.2 g (561.8), and low birth weight represented 9.1% of all newborns. Prematurity was observed in 7.4% of all newborns. Adjusted relative risk for LBW showed that second and third trimesters maternal exposure to PM10 increased the risk for low birth weight, as well as exposure to O3 increased the risk for LBW in second and third trimesters. We observed a reduction in birth weight due to interquartile increase of O3 in third trimester of pregnancy. We also found dose response relationship between low birth weight and PM10 and O3 during the second and third trimester. In relation to preterm delivery we found an increased risk associated to maternal exposure to SO2 during all three trimesters, as well as we found dose relationships between prematurity and exposure to SO2 in each trimester. CONCLUSIONS: This study suggests that exposures to O3, SO2 and PM10, even below brazilian air quality standards, contribute to risks of low birth weight and preterm delivery, in the city of Volta Redonda/Brazil. The results highlight the need of revising air quality parameters to guarantee people health.

INTRODUÇÃO: Vários estudos tem mostrado associação entre a poluição atmosférica e efeitos adversos na gravidez, como baixo peso ao nascer, prematuridade e crescimento intra-uterino retardado. OBJETIVO: O objetivo deste estudo foi investigar a associação existente entre prematuridade e baixo peso ao nascer e exposição materna aos contaminantes atmosféricos (partículas inaláveis, dióxido de enxofre e ozônio), no município de Volta Redonda, no estado do Rio de Janeiro, Brasil. MÉTODOS: Esta coorte histórica, de base populacional, foi composta por todos os nascidos vivos, de mães residentes em Volta Redonda, no período de 2003 a 2006. Os dados sobre nascimento foram obtidos do Sistema de Informações sobre Nascidos Vivos (SINASC), do Ministério da Saúde. Os dados referentes à exposição foram fornecidos pelas estações automáticas de monitoramento da qualidade do ar, instaladas no município e controladas pela Fundação Estadual de Engenharia do Meio Ambiente (FEEMA). Modelos de regressão logística e linear, ajustados para potenciais fatores de confusão, foram empregados para avaliar a contribuição da poluição do ar sobre o peso ao nascer e a idade gestacional. RESULTADOS: O total de nascidos vivos no período estudo foi igual a 13.660 nascimentos. O peso médio (desvio padrão) dos recém-nascidos no período foi de 3162,2 g (561,8). O baixo peso ao nascer representou 9,1% dos nascimentos no período e os casos de prematuros foi equivalente a 7,4%. Após análises de regressão logística, seguindo modelos propostos e ajustes para os fatores de confusão identificados, foi observado aumento do risco de baixo ao nascer relacionado à exposição materna às partículas inaláveis durante os segundo e terceiro trimestres de gestação. Também foi verificado aumento do risco de baixo peso ao nascer associado à exposição materna ao ozônio nos segundo e terceiro trimestres de gestação. Com relação à prematuridade foi encontrado aumento no risco associado à exposição materna ao dióxido de enxofre durante os três trimestres de gestação. CONCLUSÕES: Este estudo sugere que exposições a O3, SO2 e PM10, mesmo em concentrações ambientais abaixo dos padrões de qualidade do ar, contribuem para a ocorrência de prematuridade e baixo peso ao nascer no município de Volta Redonda. A pesquisa reforçou a necessidade de revisão dos padrões de qualidade do ar em vigência no Brasil, para a garantia da qualidade da saúde da população. / BACKGROUND: Several studies have shown the association between outdoor air pollution and adverse pregnancy outcomes, related to low birth weight (LBW), preterm birth and intrauterine grow restriction (IUGR). OBJECTIVES: To investigate the association between low birth weight and preterm delivery and maternal exposure to specific outdoor air contaminants, particulate matter (PM10), sulfur dioxide (SO2) and ozone (O3) in Volta Redonda, an industrialized city in the state of Rio de Janeiro, Brazil. METHODS: This population-based cohort study comprised all infants born to women resident in Volta Redonda, Rio de Janeiro, Brazil, in the period of 2003-2006. Birth data used in this retrospective study were obtained from the Information System on Live Births (SINASC) of Brazilian Ministry of Health. Exposure information was provided by air quality monitoring system operated by Environmental Agency for the State of Rio de Janeiro (FEEMA). Logistic and linear models were employed to assess the contribution of air pollution to low birth weight (LBW) and prematurity. RESULTS: The study covered 13660 births occurred from 1 January 2003 to 31 December 2006. The mean (SD) birth weight was 3162.2 g (561.8), and low birth weight represented 9.1% of all newborns. Prematurity was observed in 7.4% of all newborns. Adjusted relative risk for LBW showed that second and third trimesters maternal exposure to PM10 increased the risk for low birth weight, as well as exposure to O3 increased the risk for LBW in second and third trimesters. We observed a reduction in birth weight due to interquartile increase of O3 in third trimester of pregnancy. We also found dose response relationship between low birth weight and PM10 and O3 during the second and third trimester. In relation to preterm delivery we found an increased risk associated to maternal exposure to SO2 during all three trimesters, as well as we found dose relationships between prematurity and exposure to SO2 in each trimester. CONCLUSIONS: This study suggests that exposures to O3, SO2 and PM10, even below brazilian air quality standards, contribute to risks of low birth weight and preterm delivery, in the city of Volta Redonda/Brazil. The results highlight the need of revising air quality parameters to guarantee people health.

Objective: To determine if paternal preconception exposure to ionizing radiation through uranium mining increases the risk of congenital anomaly (CA) in offspring. Methods: A population-based matched case-control study was conducted. Cases were infants with CAs recorded in the Canadian Congenital Anomalies Surveillance System and born alive in Ontario 1979-86 (ICD-9 codes 740-759); controls were liveborn infants without CAs identified from Ontario birth certificates and individually matched to cases (case-control file {CCF}). Exposed fathers were identified through the linkage of the CCF to the Mining Master File or the National Dose Registry file, which include those who worked in Ontario uranium mines 1952-1986. For men who linked with a case or control child, radon, gamma and total gonadal doses were estimated for three preconception periods: entire, 3-months and 6-months. Odds ratios were estimated using conditional logistic regression. Results: Linkage of 28,991 uranium miners and 40,482 case-control pairs of fathers and offspring in the CCF identified 431 discordant pairs. There was no evidence of increased risk of a child having a CA if the father was ever a uranium miner before conception of the child (OR=0.89, 95% CI=0.74–1.08). Since gamma radiation (especially during the 6-month preconception period) is more biologically relevant to gonads than radon, further analyses were performed on 117 discordant pairs where data on gamma exposures were available. When ever/never miner, exposed to gamma (yes/no), and gamma dose-response variables were all in the model, there was no ever/never miner effect (OR=1.20, 95% CI=0.85–1.69, p-value=0.30), an inverse association for exposure to gamma (OR=0.42, 95% CI=0.25–0.71, p-value=0.001), but most importantly, there was no statistically significant dose-response relationship between gamma dose during the 6-month preconception period and all CAs (OR=1.15 per loge {mSv+0.01}, 95% CI=0.83–1.59, p-value=0.40). Similarly, no dose-response relationship was observed for exposure to gamma radiation in the 3-month preconception period, or for radon or total gonadal radiation in the 3- or 6-month preconception periods. Conclusion: There was no increased risk of a CA among liveborn children of Ontario uranium miners who were exposed to radon, gamma or total radiation during the 3- or 6-month periods before conception.

Objective: To determine if paternal preconception exposure to ionizing radiation through uranium mining increases the risk of congenital anomaly (CA) in offspring. Methods: A population-based matched case-control study was conducted. Cases were infants with CAs recorded in the Canadian Congenital Anomalies Surveillance System and born alive in Ontario 1979-86 (ICD-9 codes 740-759); controls were liveborn infants without CAs identified from Ontario birth certificates and individually matched to cases (case-control file {CCF}). Exposed fathers were identified through the linkage of the CCF to the Mining Master File or the National Dose Registry file, which include those who worked in Ontario uranium mines 1952-1986. For men who linked with a case or control child, radon, gamma and total gonadal doses were estimated for three preconception periods: entire, 3-months and 6-months. Odds ratios were estimated using conditional logistic regression. Results: Linkage of 28,991 uranium miners and 40,482 case-control pairs of fathers and offspring in the CCF identified 431 discordant pairs. There was no evidence of increased risk of a child having a CA if the father was ever a uranium miner before conception of the child (OR=0.89, 95% CI=0.74–1.08). Since gamma radiation (especially during the 6-month preconception period) is more biologically relevant to gonads than radon, further analyses were performed on 117 discordant pairs where data on gamma exposures were available. When ever/never miner, exposed to gamma (yes/no), and gamma dose-response variables were all in the model, there was no ever/never miner effect (OR=1.20, 95% CI=0.85–1.69, p-value=0.30), an inverse association for exposure to gamma (OR=0.42, 95% CI=0.25–0.71, p-value=0.001), but most importantly, there was no statistically significant dose-response relationship between gamma dose during the 6-month preconception period and all CAs (OR=1.15 per loge {mSv+0.01}, 95% CI=0.83–1.59, p-value=0.40). Similarly, no dose-response relationship was observed for exposure to gamma radiation in the 3-month preconception period, or for radon or total gonadal radiation in the 3- or 6-month preconception periods. Conclusion: There was no increased risk of a CA among liveborn children of Ontario uranium miners who were exposed to radon, gamma or total radiation during the 3- or 6-month periods before conception.

Thesis (Ph. D.)--Uniformed Services University of the Health Sciences, 2005. / Typescript (photocopy).

Thesis (M.S.)--Uniformed Services University of the Health Sciences, 2005. / Typescript (photocopy).

Thesis (Ph. D.)--Uniformed Services University of the Health Sciences, 2005. / Typescript (photocopy).

Thesis (M.S.)--Uniformed Services University of the Health Sciences, 2005. / Typescript (photocopy).