Introduction: This study investigated the systemic response of serum bone alkaline phosphatase (SBAP) and urinary N-telopeptide (UNTX) to tobacco exposure and environmental tobacco smoke (ETS) and the possible effect modification (and variability) of this response by racial/ethnic origin. Methods: Data (n=5411) were obtained from the National Health and Nutrition Examination Survey, with data analysis done on adults aged ≥ 20years. Outcome variables were SBAP and UNTX. Independent variable was tobacco exposure measured using serum cotinine levels and adjusted for covariates. Generalized linear models were used to explore associations. Results: A percentage increase in log transformed serum cotinine was associated with a 0.005 percentage increase in log transformed SBAP (CI: 0.002, 0.008) and 0.02 percentage increase in log transformed UNTX (CI: −0.01, 0.04) with interaction between cotinine and race/ethnicity (p=0.01). Stratifying by race/ethnicity, tobacco exposure was associated with significant decreases in UNTX among non-Hispanic Whites–0.008(−0.014, −0.002) and Mexican Americans −0.014 (−0.025, −0.002) only. Categories of serum cotinine were associated with a monotonic increase in SBAP (p for trend <0.001) and monotonic non-linear decrease in UNTX (p for trend>0.05). Conclusions: Tobacco and environmental tobacco exposure are associated with SBAP and increased bone formation. The response of UNTX to these exposures is modified by race/ethnicity with non-Hispanic Whites and Mexican-Americans less sensitive to the resorptive effects of tobacco exposure on bone.

<p dir="ltr">Neurodegenerative disease (ND) is a debilitating neurological disorder characterized by progressive loss of neurons in central nervous system (CNS), resulting in the decline in memory, cognition and motor functions. Alzheimer's disease (AD) and Parkinson's disease (PD) are the two of the most prevalent NDs, affecting millions of individuals in the United States. While hundreds of genetic risk factors have been identified in association with ND, familial cases with genetic origin only account for 10% and 15% of diagnosed AD and PD incidences, respectively. The majority of ND cases occur sporadically. Mounting evidence from epidemiology studies suggests that environmental stressors are one of the key ND associated risk factors where exposure to environmental stressors leads to the on-set of ND years or decades later. Little is known about the molecular mechanism facilitating the establishment of the persistent and potentially permanent neurotoxic state after exposures, particularly at a developmental stage. Hence, there is a pressing need in understanding the cellular machineries involved in establishment of a persistent neurotoxic state resulting from early-life exposure to environmental toxins. Subcellular compartments are crucial for the maintenance of neuronal homeostasis. Alterations in various subcellular compartments, including the nucleus, mitochondria, and lysosomes, have been commonly noted in cases of AD and PD; and are believed to play a crucial role in the establishment of a persistent neurotoxic state. The primary goal of my thesis is thus to uncover the dysregulation in multiple subcellular compartments and their contributes to ND pathogenesis induced by early-in-life exposure to environmental stressors, including atrazine (ATZ), per-and polyfluoroalkyl substances (PFAS), and neurofibrillary tangles.</p><p dir="ltr">I started by developing live-cell compatible tools to track cellular and sub-cellular changes. Mitochondria DNA methylation is of particular interest, due to its potential regulatory role in the expression of electron transport chain (ETC) subunits and thus mitochondrial activity. Thus, I started expanding the mitochondria probe tool set by designing a novel probe targeting methylated CpGs of mitochondrial DNA (mtDNA). We demonstrated the capability of our probe to reveal spatial distribution of methylated mtDNA and capture mtDNA methylation change at single cell level. Combined with our previously developed probe for nuclear DNA methylation, we monitored mtDNA and nuclear DNA methylation simultaneously on the single-cell level where unsynchronized dynamics of DNA methylation from nucleus and mitochondria were discovered.</p><p dir="ltr">Our tool offers a unique opportunity to understand epigenetic regulation of mtDNA and its dynamic response to microenvironment and cellular changes. Later, I further extended these efforts to develop in situ probes for tracking the formation of tau aggregates based on fluorescence resonance energy transfer (FRET); and demonstrated the superior performance of our engineered probes compared to the current state-of-the-art.</p><p dir="ltr">I explored two neuronal culture systems, namely SH-SY5Y- and human induced pluripotent stem cell (hiPSC)-derived neurons; and their feasibility in studying neurotoxic effects of developmental exposure to environmental stressors. Specifically, I used SH-SY5Y derived neuron-like cells to study the impact of pre-differentiation exposure to PFOA, abundant chemical in environment due to its historical uses in consumer products and industrial applications. hiPSC-derived neurons were used to study the effects of developmental exposure to ATZ. Both studies identified cellular changes, for example neurite morphology and expression of enzyme catalyzing the production of neurotransmitters, that last after completion of differentiation. We also identified changes of pathogenic markers aligning with increased PD risks associated with developmental PFOA and ATZ exposure. Compared to SH-SY5Y, hiPSC-derived neurons were more advantageous due to their ability to recapitulate neuronal activity and pathogenic changes related to ND, and thus were used in my follow-up studies.</p><p dir="ltr">I adopted hiPSC derived neuron model to study the molecular mechanism of ND using established ND etiology. Patients with neurodegenerative disorders (ND) exhibit varying levels and temporal patterns of aggregated β-amyloid (Aβ) and tau protein. We exposed neurons derived from hiPSC with preformed fibrils (PFFs) of Aβ, tau and Aβ+tau, respectively. These treatments result in significant alterations in neurite network morphology, nuclear morphology, chromatin compactness and synaptic density. Interestingly, Aβ and tau fibrils seem to have opposite effects on mitochondrial membrane potential on neurites. Increased quantity of lysosomes was found in neurons treated with Aβ, tau and Aβ+tau, while decrease of lysosomal acidity was only observed in neurons treated with Aβ and tau sequentially. Collectively, our data suggests the potential synergy between Aβ and tau in establishing a neurotoxic state.</p><p dir="ltr">In summary, my thesis work has developed enabling engineering tools to monitor cellular and subcellular changes in neurons; identified hiPSC-derived neurons as a promising platform for studying developmental neurotoxicity; and paved the way towards understanding multi-etiology and its molecular underpinning for ND.</p>

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When using evidence from non-randomized studies (NRS) to answer questions about the effects of environmental exposures on health, it is important to assess risk of bias (RoB) of individual studies as part of determining the certainty in the body of evidence. The recently released RoB in Non-randomized Studies of Interventions (ROBINS-I) instrument has undergone careful development and piloting on NRS of health interventions. A key feature of ROBINS-I is evaluating the RoB of studies against an ideal target trial, therefore establishing a structured comparison of RoB against a reference standard. While several instruments exist to evaluate the RoB of NRS of exposure, none of them use such a structured comparison of RoB. Using the fundamental design of ROBINS-I, we explored development of a version of the instrument to evaluate RoB in studies of environmental exposure. We identified important modifications necessitating a distinct instrument: The RoB instrument for NRS of exposures. This work highlights the importance of standardized methods for environmental health decision making, proposes a modified instrument to evaluate the RoB of NRS of exposures, provides guidance for the implementation of the instrument and integration into structured evidence-synthesis frameworks (such as GRADE [Grading of Recommendations Assessment, Development and Evaluation]), and presents evidence on the reliability and validity of the instrument. The RoB instrument for NRS of exposures delivers a standardized instrument that systematic review authors and guideline developers can use to evaluate RoB in NRS of exposures. The nature of these methodological changes allow better integration of RoB assessment in the environmental health field with GRADE. / Thesis / Doctor of Philosophy (PhD) / When making a decision about interventions to reduce or remove an environmental exposure, evidence is needed to weigh the desirable and undesirable consequences of the decision. No research study is perfect. Most of the studies documenting environmental exposures cannot control for the fact that people who might be highly exposed may have different characteristics compared to those who have low levels of exposure other than just the exposure itself. For example, people exposed to more environmental air pollution living in inner cities may also be more likely to smoke or have occupational exposures that could predispose them to lung cancer than those exposed to lower levels of air pollution. Understanding limitations in studies that address those questions informs our certainty that the data represents the truth. The greater the confidence we have in the data, the more likely we are to be certain that removing or reducing exposure will lead to a desirable outcome. A tool can be used to walk people through the evaluation of limitations within each study. However, it is important that the tool evaluates the correct limitations within the study. It is also important that people using the tool can apply it reliably. Without a reliable or valid tool to evaluate the limitations of the studies, it can be difficult to inform decisions on whether or not to implement specific policies. In our study, we tested the ability of a new and well-developed tool (ROBINS for interventions) to identify the limitations in studies linking environmental exposures to health outcomes. Based on the findings from our evaluation, we modified our protocol to see if we could improve our ability to evaluate these studies of environmental exposures. We asked people with an understanding of scientific methods to independently evaluate 35 studies with our modified tool (ROBINS for exposures). We compared those responses to see whether all the reviewers came up with similar decisions and if their decision was similar or different than the conclusion they made using more commonly used tools. Based on our results, we determined that our modified tool does provide a consistent evaluation of study limitations and accurately measures the limitations present in studies of exposure. This tool can be used to inform decisions about removing or reducing one’s exposure to environmental hazards.

INTRODUÇÃO: Os efeitos deletérios do mercúrio (Hg) no sistema nervoso central, em diferentes formas químicas, têm sido descritos em diversos estudos, entretanto, a ação tóxica sobre a tireoide ainda é pouco compreendida. Experimentos em animais, expostos ao Hg, em diversas formas, mostraram evidências de alterações do parênquima e dos hormônios tireoidianos. A elevada deposição do metal na tireoide e a alta afinidade pelo selênio das desiodases podem ser fatores relevantes para a explicação dos seus efeitos tóxicos. OBJETIVOS: avaliar se a exposição crônica ocupacional ao Hg metálico pode estar associada a alterações da função hormonal tireoidiana, bem como do parênquima da glândula, mesmo depois de cessar a exposição. MÉTODOS: Realizado estudo seccional em 55 expostos ao Hg e 55 controles, do sexo masculino, pareados por idade. Analisadas as concentrações dos hormônios: T3 total e livre (T3T e T3L), T4 livre (T4L) e TSH por eletroquimioluminescência, T3 Reverso (T3R) por cromatografia líquida acoplada à espectrometria de massas em tandem, selênio (no sangue) e Hg na urina (HgU) por espectrofotometria de absorção atômica, iodo urinário por detecção indireta pela Reação de Sandell - Kolthoff, anticorpos anti-tireoperoxidase por ensaio imunoquimioluminométrico. A Ultrassonografia (US) Modo B e Dúplex-doppler da tireoide avaliou as dimensões, ecogenicidade, ecotextura, vascularização e nódulos. Os nódulos com aspecto suspeito de malignidade foram submetidos à punção aspirativa por agulha fina (PAAF) e a análise citológica seguiu a classificação de Bethesda. A análise das variáveis contínuas utilizou os testes t ou U de Mann-Whitney e o Qui-quadrado para associação das variáveis categóricas. A correlação de Spearman utilizada para avaliar a relação entre as variáveis de exposição e as concentrações hormonais. O modelo de regressão logística univariada e múltipla foram empregados para análise do risco. O nível de significância dos testes foi Alfa = 0,05. RESULTADOS: a média de idade dos expostos ao Hg foi 55,2 anos (±6,6 anos) e dos controles 53,4 anos (±6,8 anos). Não houve diferença estatisticamente significativa entre as médias de idade dos grupos (p=0,158). A média das concentrações de Hg urinário, durante o período laboral, foi significativamente mais elevada em expostos (51,9 Microg/L versus 1,79 Micrpg/L; p < 0,01). A média de duração do período laboral foi de 14,5 anos (dp=±7,26). A média das concentrações de TSH foi mais elevada em expostos (3,31 MicroIU/ml versus 2,31MicroIU/ml), com diferença estatisticamente significante entre os grupos (p=0,030). As concentrações de TSH excederam o limite de normalidade (4,20 MicroIU/ml) em 13 indivíduos expostos (27,3%) e em quatro controles (7,3%), com associação estatisticamente significativa entre a elevação de TSH e a exposição ao mercúrio (p =0,018). No modelo de regressão logística, a exposição ao mercúrio mostrou uma razão de chances estatisticamente significativa para elevação das concentrações de TSH (OR=4,86; p=0,038). Não houve diferença estatisticamente significativa da relação T4L:T3L entre os indivíduos expostos e o grupo controle (p=0,791). As médias das concentrações dos hormônios T3, T3L e T4L não apresentaram diferença estatisticamente significativa entre os grupos (p > 0,05). A comparação de médias das concentrações de T3 Reverso mostrou um valor de p próximo do nível de significância do teste (p = 0,06). As proporções de alterações da ecogenicidade foram maiores em expostos (27,3% versus 9,1 %; p=0,026), com associação estatisticamente significativa à exposição ao Hg. Não foi observada associação, estatisticamente significativa, entre a exposição ao Hg e o padrão heterogêneo de ecotextura, ou o aumento de vascularização do parênquima (p > 0,05). A presença de nódulos foi similar entre os grupos. O exame citológico identificou a presença de carcinoma papilífero de tireoide em três indivíduos expostos e um controle. O anatomopatológico confirmou a presença de carcinoma papilífero em quatro indivíduos e identificou o carcinoma folicular em um dos controles. CONCLUSÕES: Os resultados deste estudo mostraram a presença de elevação das concentrações de TSH, e alterações do parênquima tireoidiano, mais frequentes entre os trabalhadores expostos ao Hg, mesmo depois de cessar a atividade laboral, indicando a importância do monitoramento da tireoide / INTRODUCTION: The deleterious effects of mercury (Hg) on the central nervous system, in different chemical forms, have been described in several studies, however, the toxic action on the thyroid is still little understood. Experiments in animals exposed to mercury (Hg), in different states, showed parenchymal and thyroid hormones alterations. The accumulation of metal on thyroid and high affinity for selenium of deiodinases can be a relevant factor for the explanation of his toxic effects. OBJECTIVE: Evaluate the occupational exposure of metallic Hg and its association with the hormones and thyroid parenchyma alterations, even after the labor exposure was discontinued. METHODS: A sectional study in 55 exposed and 55 control males, paired by age was conducted. Serum dosages of total triiodothyronine (T3), free T3 (TT3 and FT3), free T4 (FT4) and TSH were obtained by electrochemical luminescence, the reverse T3 (RT3) by chromatography, selenium (blood), urinary Hg (U-Hg) by atomic absorption spectrophotometry, anti-thyroid peroxidase antibody by immunochemiluminometric assay, urinary iodine by Sandell-Kolthoff reaction. The thyroid parenchyma was evaluated by B-mode ultrasonography with Doppler. The nodules with suspicious aspect of malignancy were submitted to aspiration puncture with a thin needle. The t-test, or Mann-Whitney, chi-square and Spearman correlation were performed. For the risk analysis a univariate and multivariate logistic regression model was used (Alfa = 0.05). RESULTS: The mean age of the exposed to Hg was 55.2 years (SD± 6.6 years) and controls was 53.4 years (SD± 6.8 years). The U-Hg average was significantly higher in exposed (51.9 Microg/L versus 1.79 Microg/L; p=0.000). The longer work duration was 14.5 years (SD ±7.26 years). TSH concentrations exceeded the normality limit (4.20 MicroIU/ml) in 13 exposed individuals (27.3%) and four controls (7.3%), with a statistical significant association between the increase in serum TSH and exposure to mercury (p = 0.018). In the logistic regression model, the exposure to mercury (yes or no) showed a predictive value to the increase of TSH concentrations (OR=4.86; p=0.038). There was no statistical significant difference in the T4L:T3L ratio between the exposed individuals and the control group (p=0.791). The mean concentrations of the hormones T3, T3L and T4L showed no statistically significant difference between the groups (p > 0.05). The comparison of means of the Reverse T3 concentrations showed a p value borderline (p = 0.06). The proportions of the echogenicity alterations were higher at the exposed group (27.3% versus 9.1 %; p=0.026). There was no statistical significant association between the exposure to Hg and the thyroid echotexture pattern or parenchyma increased vascularization (p > 0.05). It was observed a papillary carcinoma in three exposed and one control individual and a follicular in one control. CONCLUSIONS: The results of this study showed the higher serum TSH concentration and prevalence of parenchyma alteration in the Hg exposed group, after cessation of exposure, and indicate the importance of the thyroid monitoring

A poluição atmosférica é uma das maiores preocupações para a saúde pública, pois tem sido associada ao aumento nas taxas de morbimortalidade. Entretanto, para muitos desfechos, o conhecimento científico acerca do tema ainda é limitado para se inferir uma associação robusta com a exposição a essa poluição. A avaliação da exposição por meio de métodos individuais possui um custo elevado e de difícil execução; por isso, diversos estudos de epidemiologia ambiental têm sido conduzidos utilizando medidas indiretas, que se baseiam em dados viários e de tráfego veicular como avaliação da exposição. Diante da importância do tema, este trabalho pretendeu levantar as várias abordagens relatadas na literatura e desenvolvê-las no município de São Paulo, em desfechos como doenças do aparelho circulatório e baixo peso ao nascer. Foram elaborados quatro artigos científicos: 1) revisão de literatura sobre as diversas abordagens que se basearam em informações de tráfego para avaliar exposição à poluição atmosférica; 2) análise da densidade de vias e volume de tráfego, para avaliar sua relação com a mortalidade por doenças do aparelho circulatório, nos distritos administrativos; 3) desenvolvimento de um modelo de regressão do uso do solo, para estimar a dispersão de MP10; e 4) avaliação da ocorrência de baixo peso ao nascer e poluição atmosférica, por meio de três indicadores: Densidade de Tráfego Ponderada pela Distância (DTPD), menor distância do domicílio materno em relação às vias movimentadas e regressão do uso do solo. Os artigos destacam a importância da fonte veicular como contribuinte dos níveis de poluentes e também na mortalidade por doenças do aparelho circulatório no município de São Paulo / Air pollution is a major concern for public human health and it has been associated with increasing rates of morbidity and mortality. However, many outcomes scientific knowledge about this topic is limited to infer a robust association with exposure to this pollution. The exposure assessment through individual methods is expensive and difficult to perform. Therefore many environmental epidemiology studies have been conducted using indirect measurements, which are based in vehicular traffic and road data. Evaluating the importance of the topic, this study aimed to review several approaches reported in the literature and to apply them in São Paulo city in cardiovascular diseases and low birth weight. Four papers were prepared: 1) review the literature about several approaches relied on traffic data; 2) density of roads and traffic volume to evaluate their relation with mortality from diseases of circulatory system at administrative districts; 3) development of a model of land use regression to estimate the dispersion of PM10; and 4) shortest distance from major traffic, DWTD and land use regression to assess the occurrence of low birth weight. The articles emphasize the importance of vehicular traffic as contributor of levels of pollutants and also in the mortality from diseases of circulatory system in the city of São Paulo

Submitted by Rosina Valeria Lanzellotti Mattiussi Teixeira (rosina.teixeira@unisantos.br) on 2015-04-28T17:23:21Z No. of bitstreams: 1 Zuleika Maria Vieira de Andrade.pdf: 3405435 bytes, checksum: 13c04fd8d37e619abe54b3f588abbdd8 (MD5) / Made available in DSpace on 2015-04-28T17:23:21Z (GMT). No. of bitstreams: 1 Zuleika Maria Vieira de Andrade.pdf: 3405435 bytes, checksum: 13c04fd8d37e619abe54b3f588abbdd8 (MD5) Previous issue date: 2013-09-24 / Basal Cell Carcinoma (BCC) is the most common malignancy in humans corresponds to 75% of epithelial malignant tumors. Its incidence is increasing around the world, generating significant burden to the health care system and configuring it as a public health problem. It lies mainly on the face and fair-skinned individuals, involves those over 40 years of age, with a history of exposure to sunlight. We analyzed medical records of all patients diagnosed with BCC in the pathology laboratory of a cancer referral hospital in the state of Paraiba, during the period of 2009 to 2011, with the purpose of analyzing its distribution according to gender, age, location of the tumor, histological subtype, situation of surgical margins, size of the lesions and the origin of the patients. We carried out descriptive analysis of the main variables included in the study, qui-square test, and logistic regression models to identify possible risk factors. The cases were distributed geographically according to the municipality of residence. Along the study period, 3,088 patients were identified with BCC, 48.8% female and 51.52% male. Most of the tumors were located in the head/neck (85.1%), followed by the trunk (10.2%), upper (3.01%) and lower limbs (1.04%); 87.6% were located in the photoexposed areas and only 12.4% in not photoexposed areas. In relation to the location on the head, 33.6% were located in the nose, followed by malar region (23.7%). The nodular subtype was the most frequent (69%), followed by surface type (16%), sclerodermiform (6%), Pigmented (4%) and metatypic (2%). The age group most affected was between 70 to 80 years (26%). Most of the injuries were classified as small, with free surgical margins. A total of 56% of the patients was coming from Zona da Mata region. In bivariate logistic regression models, women had 2.4 times higher risk of developing BCC. The higher age group (OR=5.21) and the origin of Borborema mesoregion (OR=3.88) had significantly higher chance. In the multiple regression mode by including variables that showed statistical significance in bivariate model, showed that the variables Borborema mesoregion (OR=4.88), age ¿ 60 years (OR=5.16) and females (OR=1) remained significant. In this study, we found that the BCC was more frequent in males, above 60 years of age, located in the head, nodular histological type, small size, with free surgical margins and coming from Zona da Mata region. More studies are needed to assess risk factors such as skin color, the profession, sun-exposed activities and family history. / O Carcinoma Basocelular (CBC) é a neoplasia maligna mais comum em humanos, corresponde a 75% dos tumores epiteliais malignos, e sua incidência vem aumentando em todo o mundo, gerando significativo ônus ao sistema de saúde e configurando-o como problema de saúde pública. Localiza-se principalmente na face e acomete indivíduos de pele clara, acima de 40 anos, com história de exposição à luz solar. Foi feita uma análise dos prontuários de todos os pacientes com diagnóstico de CBC no Laboratório de Patologia de Hospital de Referência em Câncer na Paraíba, durante o período de 2009 a 2011, com o objetivo de analisar a sua distribuição segundo sexo, idade, localização do tumor, tipo histológico, situação das margens cirúrgicas, tamanho das lesões e a procedência dos pacientes. Realizou-se uma análise descritiva das principais variáveis incluídas no estudo, além de teste de associação e modelos de regressão logística, para identificar possíveis fatores de risco. Os casos foram distribuídos geograficamente, tendo como unidade o município de residência. Foram identificados 3088 pacientes com CBC, sendo 48,8% do sexo feminino e 51,52% do sexo masculino. A maioria dos tumores estava localizada na cabeça/pescoço (85,1%), seguidos pelo tronco (10,2%), membros superiores (3,01%) e membros inferiores (1,04%), 87,6% estavam localizados nas áreas fotoexpostas e apenas 12,4% nas áreas não fotoexpostas. Em relação à localização na cabeça, 33,6% estavam localizados na região nasal, seguida pela região malar (23,7%). O tipo nodular foi o mais frequente (69%), seguido pelo tipo superficial (16%), esclerodermiforme (6%), pigmentado (4%) e metatípico (2%). A faixa etária mais acometida foi entre 70 a 80 anos (26%). A maioria das lesões foi classificada como pequena, com margens cirúrgicas livres. Um total de 56% dos pacientes foi proveniente da Zona da Mata Paraibana. Nos modelos de regressão logística bivariada, o sexo feminino apresentou 2,4 vezes maior chance de desenvolver CBC. As faixas etárias mais altas (OR=5,21) e a procedência da mesorregião Borborema (OR=3,88) tiveram chance significante maior. No modelo de regressão múltipla, ao incluir as variáveis que mostraram significância estatística nos modelos bivariados, evidenciou-se que as variáveis mesorregião Borborema (OR=4,88), faixa etária ¿ 60 anos (OR=5,16) e sexo feminino (OR=1) mantiveram-se significantes. Neste estudo, concluímos que o CBC foi mais frequente no sexo masculino, acima de 60 anos de idade, localizados na cabeça, do tipo histológico nodular, de tamanho pequeno, com margens cirúrgicas livres e provenientes da Zona da Mata paraibana. São necessários mais estudos para avaliar fatores de risco como a cor da pele, a profissão, atividades expostas ao sol e história familiar.

Submitted by Eunice Novais (enovais@uepg.br) on 2018-07-03T17:15:26Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Lauryellen Aparecida Padilha.pdf: 1283785 bytes, checksum: 0ad4f7e4aed44908eaa1ad1b940f74c7 (MD5) / Made available in DSpace on 2018-07-03T17:15:26Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Lauryellen Aparecida Padilha.pdf: 1283785 bytes, checksum: 0ad4f7e4aed44908eaa1ad1b940f74c7 (MD5) Previous issue date: 2018-02-02 / A Doença Periodontal (DP) é uma inflamação crônica que atinge os tecidos de revestimento e suporte dos dentes, induzida pela presença de um biofilme dental. A resposta imune do hospedeiro é um fator determinante para a progressão desta doença e a produção de Espécies Reativas do Oxigênio (ROS) é um importante mecanismo causador dos danos teciduais observados. Atualmente a DP representa a maior causa da perda dos dentes nos indivíduos maiores que 40 anos e acomete cerca de 538 milhões de pessoas no mundo. Esta patogenia é influenciada por vários fatores endógenos e exógenos da vida do hospedeiro, sendo que residir em zona rural pode ser considerado um fator de risco para esta doença. Os moradores de áreas rurais possuem uma importante exposição à pesticidas utilizados na agricultura. Atualmente muito tem se estudado sobre os efeitos da exposição a pesticidas na saúde humana, e sabe-se que a exposição à determinados agrotóxicos pode representar um fator de risco, inclusive para a DP. O Paraquat, um herbicida amplamente utilizado na agricultura, tem seu principal mecanismo de ação baseado na liberação de ROS, que levam à peroxidação lipídica e o estresse oxidativo, causando danos teciduais. Deste modo, sugere-se que o Paraquat pode ter influência na maior prevalência da DP dos indivíduos moradores da zona rural. Deste modo, o presente estudo teve como objetivo principal avaliar os efeitos da exposição crônica ao Paraquat, sobre a perda óssea alveolar (POA) induzida pelo método de ligadura em ratos. Para isso, um total de 40 ratos foram divididos em quatro grupos: Grupo Sem Ligadura / Sem Paraquat (SL/SP); Grupo Com Ligadura / Sem Paraquat (CL/SP); Grupo Sem Ligadura / Com Paraquat (SL/CP); e Grupo Com Ligadura / Com Paraquat (CL/CP). A indução da POA foi realizada através do método de ligadura durante 30 dias e a exposição ao Paraquat por gavagem intragástrica durante 60 dias na dose de 0,1mg/Kg. Os dados obtidos foram analisados através do software GraphPad Prism 6.0, utilizando-se o teste estatístico two-way ANOVA e adotando um nível de significância de 5%. Foram avaliadas a POA através da análise macroscópica, a quantidade de leucócitos totais no sangue, a quantidade de glutationa reduzida sérica e alguns parâmetros clínicos, os quais foram mobilidade dentária, edema e sangramento gengival nestes animais. Nos resultados obtidos pode-se observar que o Paraquat teve uma influência significativa sobre o aumento da quantidade de leucócitos e dos sinais clínicos avaliados, porém apresentou apenas uma tendência em diminuir os níveis de glutationa reduzida e aumentar a POA nos ratos que tiveram a indução com ligadura. Deste modo, este estudo concluiu que o Paraquat na dose de 0,1 mg/Kg não foi capaz de aumentar a POA e nem diminuir a quantidade de glutationa reduzida sérica nestes animais significativamente, mas sim de aumentar a quantidade de leucócitos no sangue e os sinais clínicos da DP avaliados. / Periodontal disease (PD) is a chronic inflammation that affects the tissues of coating and support of the teeth, induced by the presence of a dental biofilm. The host’s immune response a determinant factor for the progression of this disease and the production of reactive oxygen species (ROS) is an important mechanism causing tissue damages. Currently, this is the main cause of tooth loss in individuals over 40 years of age and affects approximately 538 million of people worldwide. This pathogenesis is influenced by several endogenous and exogenous factors in the host’s life, and living in rural area can be considered a risk factor for this disease. Residents of the rural areas have significant exposure to pesticides used in agriculture. Currently, much has been studied about the exposure effects of pesticides on human health, and is known that exposure to determined pesticides may represent a risk factor, including for PD. Paraquat, herbicide widely used in agriculture, also has its main mechanism of action based on liberation of ROS, which lead to lipid peroxidation and oxidative stress, causing tissue damage. Therefore, is suggested that the Paraquat may have influence about the high prevalence of PD in individuals residents in rural areas. Thus, the present study had as main objective evaluate the effects of Paraquat chronic exposure on alveolar bone loss (POA) induced by ligature method in rats. For this, a total of 40 rats were divided into four groups: Without Ligature / Without Paraquat Group (SL / SP); Group With Ligature / Without Paraquat (CL / SP); Without Ligature / With Paraquat Group (SL / CP); and Group With Ligature / With Paraquat (CL / CP). POA induction was realized by ligature method during 30 days and Paraquat exposure via intragastric gavage with dose of 0,1 mg/Kg during 60 days. The data obtained were analyzed using GraphPad Prism 6.0 software, using the two-way ANOVA statistical test and accepting significance level of 5%. Was evaluated the POA through the macroscopic analysis, the levels total of the leukocytes in the blood, the levels of the serum reduced glutathione and clinical parameters, what were dental mobility, gingival edema and gingival bleeding in these animals. On results obtained can be indicate that the Paraquat had a significant influence on the increase of the leucocytes and of the clinical signs evaluated, but only showed a tendency to decrease the levels of reduced glutathione and to increase the POA in the rats that had induction with ligature. Wherefore, this study concluded that Paraquat at dose of 0.1 mg / kg was not able to increase POA and neither decrease the levels of serum reduced glutathione in these animals significantly, but increase the levels of the leukocytes in the blood and the clinical signs of PD.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / As doenças infecto-parasitárias, ainda hoje, em pleno século XXI são responsáveis por uma quantidade generosa de morbidade e mortalidade no Brasil e no mundo. Muitas delas são amplamente influenciadas pelas mudanças climáticas que estão ocorrendo em todo o planeta fazendo com que sua incidência e distribuição geográfica aumentem. A dengue é considerada a principal doença reemergente nos países tropicais e subtropicais. A malária tem forte incidência nos países ao sul do deserto do Saara na África, ocorrendo também em vários países da América do Sul que possuem parte da região Amazônica em seu território. Várias doenças voltam a assolar a população de vários locais como as leishmanioses, a Doença de Lyme, erlichioses entre outras. Em março de 2009 começam a ocorrer os primeiros casos de uma nova doença inicialmente denominada Influenza suína, a qual, levou alguns indivíduos a óbito em Oaxaca, uma cidade mexicana localizada a 400 quilômetros da capital. Rapidamente, a doença se espalhou pelo país e posteriormente, no começo do mês de abril de 2009 já, existiam relatos de casos em vários países. O objetivo geral desta pesquisa é verificar em que medida o cuidado de enfermagem realizado expressou um maior ou menor grau de controle do enfermeiro sobre seu trabalho, apontando para os potenciais riscos (biológicos) de adoecimento e impactos negativos na saúde deste trabalhador. O presente estudo foi desenvolvido por meio de uma abordagem quantitativa com desenho longitudinal e observacional, delineamento de pesquisa não experimental e caráter descritivo. Foi feita a análise observacional nas tendas quanto a sua infraestrutura e posteriormente foi passado um questionário aos enfermeiros pautado em questões sobre o risco biológico que estes estavam sendo submetidos. Faz-se necessário que a cultura do improviso acabe e comece a se pensar em uma nova realidade: as doenças transmissíveis são uma realidade, elas existem e há de ser feito um adequamento de tudo que esteja ligado à área de saúde pensando em um novo contexto. É imperioso que tanto as autoridades como os profissionais revejam e reflitam sobre o que aconteceu, para que os erros do passado possam ficar para trás e não se repitam. / Infectious-parasitic diseases, up to the present, in XXI century are responsible for a high morbidity and mortality rate in Brazil as well as overseas. Many of them are widely influenced by climatic modifications that have been occuring all over the planet leading to an increase in their incidence and geographical distribution. Dengue is considered the main reemerging disease in tropical and subtropical countries. Malaria has strong incidence in countries that are in the south of Sahara desert in Africa, also occuring in many countries of South America that have part of their territory in Amazon region. A great deal of diseases have been frightening the population once again in many places, as leishmanioses, Lyme Disease, erlichioses, for instance. In March, 2009 the first cases of a new disease initially termed Influenza swine started to appear, leading some subjects to death in Oaxaca, a mexican city localized 400 kilometers far from the capital. Rapidly ,the disease had spread all over the country and later, in the beginning of April , 2009 there were some related cases in several countries. The overall aim of this study is to verify to what extent the nursing care that is carried out has expressed a higher or lower degree of control from the part of the nurse about his/her job, pointing at potential risks (biological) of illnesses and negative impacts into the worker health status. This study was developed by means of quantitative approach with longitudinal and observational design, a non experimental research and descriptive features. An observational analysis was carried out at the tents for their infra-structure and after this, a questionnaire was applied to the nurses based on matters as the biological risk they were being exposed. It is necessary that the improvisation culture comes to an end and a new reality come true : transmissible diseases are a reality, they exist and adjustments in relation to everything that is linked to health have to be achieved in order to envision a new context. It is essential that both authorities and professionals reflect and reconsider on the events from the past so as to old mistakes can be left behind and do not repeat again.