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

Objetivo: Estudar as alterações morfométricas da retina de ratos expostos agudamente à fumaça de cigarro. Métodos: Em um estudo experimental, controlado, mascarado, foram utilizados 24 ratos Wistar machos (8 semanas de idade), sendo metade deles expostos por duas horas contínuas à fumaça de cigarro em uma câmara de inalação e a outra metade exposta a ar comprimido como grupo controle. A fumaça foi aspirada diretamente do cigarro utilizando um sistema venturi, e conduzida para a câmara. A concentração de monóxido de carbono no interior da câmara de inalação foi mantida em uma faixa constante de 45 a 55 partes por milhão, monitorada eletronicamente no interior do recipiente. Os ratos foram sacrificados imediatamente após a inalação e nos momentos 24 e 48 horas após exposição. Os olhos foram enucleados e analisados por meio da morfometria em microscópio óptico, por examinador mascarado. Resultados: Foram identificadas regiões da retina do grupo exposto que sofreram redução das estimativas morfométricas em comparação ao grupo controle, com significância estatística correspondendo às regiões dos fotorreceptores, camada nuclear interna e plexiforme interna 48 horas após a exposição. Comparando os grupos expostos entre si houve uma redução progressiva nas estimativas morfométricas das camadas retinianas com o aumento do intervalo entre o término da exposição e o sacrifício, de forma estatisticamente significante na camada nuclear interna. Conclusão: As retinas dos ratos expostos agudamente à fumaça de cigarro sofreram uma redução nas estimativas morfométricas, com uma tendência a redução progressiva nas estimativas no decorrer das primeiras 48 horas após exposição / Objective: To evaluate morphometric alterations of the retina, from rats acutely exposed do cigarette smoking. Methods: In an experimental, prospective, masked study with 24 male Wistar rats (8 weeks old), half of them were exposed during two hours continually to cigarette smoking inside an intoxicating chamber, while the other half exposed to compressed air. The smoke was aspirated directly from cigarette, using a venturi system, and conducted to the chamber. The carbon monoxide concentration was constantly kept in between 45 to 55 parts per million, electronically monitored inside de chamber. The rats were sacrificed immediately after the inhalation, 24 and 48 hours after exposition. The eyes were enucleated and analyzed trough morphometry, in an optical microscope, by a masked examiner. Results: It was identified regions of the retina in the experimental group that suffered a reduction in the morphometric estimates, comparing to control group, with statistical significance, corresponding to the photoreceptor layer, the inner nuclear and inner plexiform layers, 48 hours after exposure. Comparing the exposed groups between themselves, there was a progressive reduction in the morphometric estimates of retinal layers after an increase in time between finishing the exposure and sacrifice, with statistical significance in inner nuclear layer. Conclusion: The retina of rats acutely exposed to cigarette smoke suffered a reduction in the morphometric estimates, with a tendency to progressive reduction in the estimates during the initial 48 hours after exposure

Exposição a substâncias tóxicas e distúrbios metabólicos são fatores que afetam as funções neuropsicológicas. Foram realizados 2 estudos descritivos com os objetivos de verificar a possibilidade de disfunções neuropsicológicas em indivíduos com histórico de exposição ocupacional ao vapor de mercúrio e em pacientes diabéticos do tipo 2 sem diagnóstico de retinopatia, em ambos os casos, comparados com controles. A bateria neuropsicológica incluiu testes de atenção (Dígitos), controle inibitório (teste de stroop), memória verbal (teste de Buschke) e visual (Reprodução Visual), destreza manual (Grooved Pegboard), fluência verbal (FAS), habilidade viso-motora (Cubos), funções executivas (teste de Wisconsin), conhecimento semântico (Vocabulário) e sintomas de depressão (Inventário Beck de Depressão) e ansiedade (Inventário de Ansiedade Traço-Estado). Adotou-se p<0,05 como nível de significância. As avaliações neuropsicológicas de 26 ex-trabalhadores de fábricas de lâmpadas de mercúrio foram comparadas com 20 controles. Os ex-trabalhadores têm diagnóstico de mercurialismo crônico ocupacional, foram expostos ao vapor de mercúrio no trabalho durante 10,2 ± 3,8 anos e estão afastados da função há 6 ± 4,7 anos. A concentração de mercúrio urinário medida um ano após o afastamento da exposição teve média de 1,8 ± 0,9 mg/gCr. Comparados com os controles, os ex-trabalhadores demonstraram pior desempenho no teste de Stroop partes 1 (p=0,004) e 2 (0,010), no teste de Buschke para recuperação de longo prazo (p=0,028), armazenamento de longo prazo (p=0,045), recuperação consistente longo prazo (p=0,006), e recuperação tardia (p=0,008), fluência verbal (p=0,010) e no Grooved Pegboard tanto para a mão dominante (p=0,019) quanto a não dominante (p=0,008). Os escores de depressão, de estado e traço de ansiedade foram significantemente superiores aos do grupo controle (p<0,001). Os indivíduos com histórico de exposição ao vapor de mercúrio demonstraram redução da velocidade de processamento de informações e déficits de recuperação espontânea de informações verbais, fluência verbal, função motora, além de sintomas de depressão e ansiedade. Os escores altos de depressão e ansiedade são esperados em indivíduos com mercurialismo crônico, mas também podem se associar a problemas psicosociais relacionados ao desemprego. O outro estudo comparou o desempenho neuropsicológico de 19 pacientes diabéticos sem diagnóstico de retinopatia (avaliada através de exame de fundo de olho) e 20 sujeitos controles não diabéticos. Os pacientes têm diabetes há 8,2 ± 8,1 anos, média de hemoglobina glicada (HbA1C) de 7 ± 1,3%, não fazem uso de insulina como tratamento, não manifestam queixas de neuropatia e apresentam valores de microalbuminúria dentro dos limites de normalidade. Nove (47%) são hipertensos. Não foram encontradas diferenças significantes (p<0,05) entre pacientes diabéticos e sujeitos controles em quaisquer medidas realizadas. Os resultados sugerem que o diabetes tipo 2 não se associa diretamente aos déficits neuropsicológicos. Há a possibilidade de que as alterações cognitivas e de humor observadas em pacientes diabéticos do tipo 2 em estudos prévios estejam relacionadas à presença de complicações como retinopatia, hipoglicemia ou neuropatia com sinais clínicos. / Neuropsychological function is known to be affected by exposure to toxic substances and metabolic disorders. Two descriptive studies were performed. The aim was to examine possible neuropsychological dysfunction in individuals with history of occupational exposure to mercury vapor, and in type 2 diabetic patients without retinopathy, in comparison with controls. The neuropsychological assessment included measures of attention (WMS Digit Span), inhibitory control (Stroop Interference Test), verbal memory (Buschke Selective Reminding Test), visual memory (WMS Visual Reproduction), manual dexterity (Grooved Pegboard), verbal fluency (FAS), visuomotor ability (WAIS Block Design), executive function (Wisconsin Card Sorting Test), verbal knowledge (WAIS Vocabulary), and depression (Beck Depression Inventory) and anxiety (State-Trait Anxiety Inventory) symptoms. P<0.05 was taken as significance level. Neuropsychological assessments of 26 fluorescent lamp ex-workers with chronic mercurialism diagnosis who had been exposed to mercury vapor for 10.2 ± 3.8 years were compared with 20 controls. The time since the cessation of exposure was 6 ± 4.7 years and the mean urinary mercury concentration was 1.8 ± 0.9 mg/gCr. Compared with the controls, the ex-workers performed worse on the Stroop Test part 1 (p=0.004) and 2 (0.010), SRT long term recall (p=0.028), long term storage (p=0.045), consistent long term recall (p=0.006), and delayed recall (p=0.008), FAS (p=0.010) and Grooved Pegboard dominant hand (p=0.019) and nondominant hand (p=0.008). Their depression, anxiety state and trait scores were higher than control’s (p<0.001). Individuals with history of exposure to mercury vapor presented slowed processing speed and verbal memory spontaneous recall, verbal fluency and motor function impairment along with symptoms of depression and anxiety. The high scores on depression and anxiety are expected in chronic mercurialism and may be also associated with psychosocial problems related to unemployment. The other study compared the neuropsychological performances of 19 diabetic patients without retinopathy diagnosis (assessed by eye fundus examination) with 20 nondiabetic control subjects. The patients had diabetes for 8.2 ± 8.1 years and their recent glycaemic control levels (HbA1C) mean was 7 ± 1.3%. Other diabetic group’s characteristics included non-insulin treatment, no neuropathy complaints, normal microalbumin urine tests, and 9 (47%) hypertensive patients. No significant (p<0.05) differences were found between the diabetic and control groups on any measure. The results suggest that type 2 diabetes is not directly related to significantly neuropsychological alterations. It is possible that cognitive decrements and mood alterations among type 2 diabetic patients described in previous studies are associated with the presence of complications such as retinopathy, hypoglicaemia, or even neuropathy with clinical signs.

Para avaliar o benefício da utilização parenteral das vitaminas C e/ou E associadas ao quelante de cobre, tetratiomolibdato de amônio (TTM), na recuperação de ovinos com intoxicação cumulativa por cobre (ICC), foram analisados os parâmetros vitais; o metabolismo oxidativo, através das concentrações séricas de ácido úrico e malondialdeído, atividade sanguínea da glutationa reduzida, habilidade de redução férrica plasmática, atividade urinária de N-acetil-&beta;-D-glucosamidase; peso vivo, hematócrito, concentração sérica de cobre, uréia, creatinina e as alterações anatomo-patológicas de 26 ovinos da raça Santa Inês, machos, com peso médio de 25 kg e distribuídos em quatro tratamentos: apenas com TTM, TTM + vitamina C (TTM+VC), TTM + vitamina E (TTM+VE) e TTM + vitaminas C e E (TTM+VCE). A associação das duas vitaminas aumentou o tempo de recuperação renal, porém reduziu a concentração sérica de cobre. A vitamina E mostrou efeito adverso ao esperado em relação à glutationa reduzida e ao malondialdeído séricos. Em algumas variáveis, como concentração sérica de creatinina e glutationa reduzida a utilização da vitamina C proporcionou tendência para melhores resultados em relação aos demais grupos, principalmente ao que possuíam vitamina E no tratamento, coincidentemente os animais deste grupo (TTM+VC) apresentaram a maior taxa de sobrevivência. Os estudos histopatológios e histoquímicos revelaram que a principal lesão hepática encontrada foi infiltrado inflamatório. Nos rins foram freqüentes o infiltrado inflamatório, glomérulonefrite e pigmentos. Constatou-se que, embora tenham ocorrido algumas variações pontuais entre os grupos, o tratamento com TTM associado às vitaminas C e/ou E não surtiu benefícios na recuperação física dos animais nem na redução do estresse oxidativo. / The efficiency of intra muscular vitamin C (VC) and/or E (VE) associated with the classical copper chelate tetrathiomolybdate (TTM) in cumulative copper poisoning treatment was evaluated. Twenty six Santa Inês male lambs weighting 25 kg were distributed in four treatment groups (TTM; TTM+VC; TTM+VE; TTM+VCE). The oxidative metabolism was analyzed through measurement of: serum concentrations of uric acid, malondialdehyde (MDA), blood reduced glutathione, ferric reducing ability of plasma and urinary activity of N-acetyl-&beta;-D-glucosamidase. Live weight, hematocrit; copper, urea and creatinine serum concentrations and histopathological changes were determinated. Vitamins C and E association increased the time of renal recuperation, but reduced copper serum concentration. Serum MDA raised and blood reduced glutathione concentrations diminished in animals of TTM+VE group. Serum creatinine and blood reduced glutathione concentrations had tendency of better results in TTM+VC than TTM+VE and TTM+VCE. Survival index was greater in TTM+VC. Histopathology and histochemistry showed inflammatory infiltrate in liver as well as Glomerulonephritis, inflammatory infiltrate and pigments in the kidneys, in almost all animals. The association of TTM with vitamins C and/or E didnt reduce oxidative stress and had no positive effect on treatment.

Lee Nga Lan. / Thesis submitted in: June 1997. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references. / Abstract also in Chinese. / Abstract --- p.i / Acknowledgment --- p.iii / Table of contents --- p.iv / List of tables --- p.viii / List of figures --- p.x / Glossary of abbreviations --- p.xi / Chapter CHAPTER 1. --- INTRODUCTION --- p.1 / Chapter CHAPTER 2. --- BACKGROUND --- p.3 / Chapter 2.1 --- OUTBREAKS OF SOLVENT INDUCED NEUROPATHY IN MAN --- p.3 / Chapter 2.2 --- WORLD-WIDE INVESTIGATIONS ON ORGANIC SOLVENTS HAZARDS --- p.5 / Chapter 2.3 --- HEALTH EEFECTS OF ORGANIC SOLVENTS --- p.8 / Chapter 2.3.1 --- Effects on the Nervous System --- p.9 / Chapter (a) --- Peripheral Nervous System / Chapter (b) --- Central Nervous System / Chapter 2.3.2 --- Other Effects --- p.13 / Chapter 2.4 --- METHODOLOGICAL ISSUES IN THE INVESTIGATION OF SOLVENT NEUROTOXICITY --- p.14 / Chapter 2.4.1 --- Study Design --- p.15 / Chapter 2.4.2 --- Exposure Measurements --- p.17 / Chapter 2.4.3 --- Outcome Effects Measurements --- p.18 / Chapter 2.5 --- UNSOLVED PROBLEMS IN THE STUDY OF SOLVENT NEUROTOXICITY --- p.20 / Chapter 2.6 --- ORGANIC SOLVENTS IN THE PRINTING INDUSTRY --- p.21 / Chapter 2.7 --- PRINTING METHODS --- p.25 / Chapter 2.8 --- OFFSET LITHOGRAPHY --- p.27 / Chapter 2.8.1 --- Principles of Offset Lithography --- p.28 / Chapter 2.8.2 --- Image Carriers for Offset Lithography --- p.29 / Chapter 2.8.3 --- Lithographic Presses --- p.32 / Chapter 2.8.4 --- Printing Process --- p.34 / Chapter CHAPTER 3. --- STUDY OBJECTIVES AND METHODS --- p.37 / Chapter 3.1 --- OBJECTIVES --- p.37 / Chapter 3.2 --- METHODS --- p.38 / Chapter 3.2.1 --- Study Population --- p.38 / Chapter 3.2.2 --- Visits --- p.41 / Chapter 3.2.3 --- Workers' Health Assessment --- p.42 / Chapter 3.2.4 --- Air Sampling --- p.44 / Chapter 3.2.5 --- Definition of Exposures --- p.48 / Chapter 3.3 --- DATA ANALYSIS --- p.49 / Chapter CHAPTER 4. --- RESULTS --- p.51 / Chapter 4.1 --- RESPONSE RATE --- p.51 / Chapter 4.2 --- CHARACTERISTICS OF THE STUDY POPULATION --- p.53 / Chapter 4.2.1 --- Printing Companies --- p.53 / Chapter 4.2.2 --- Study Subjects --- p.56 / Chapter 4.3 --- HEALTH PROBLEMS OF STUDY SUBJECTS --- p.60 / Chapter 4.3.1 --- Sick Leave --- p.60 / Chapter 4.3.2 --- Prevalence of Subjective Symptoms --- p.61 / Chapter 4.3.3 --- Mean Number of Symptoms --- p.64 / Chapter 4.4 --- AIR SAMPLING RESULTS --- p.66 / Chapter 4.4.1 --- Mean Concentration Levels of Solvents --- p.71 / Chapter 4.4.2 --- Mean Concentration Levels of Solvents by Printing Plants --- p.73 / Chapter 4.4.3 --- Mean Concentration Levels of Solvents by Locations --- p.75 / Chapter 4.5 --- EXPOSURE-RESPONSE RELATIONSHIPS BETWEEN ORGANIC SOLVENTS AND SYMPTOMS --- p.77 / Chapter 4.6 --- RISK FACTORS FOR SUBJECTIVE SYMPTOMS --- p.85 / Chapter CHAPTER 5. --- DISCUSSIONS --- p.90 / Chapter 5.1 --- RESPONSE RATE --- p.90 / Chapter 5.2 --- SOURCES OF BIAS --- p.91 / Chapter 5.3 --- STUDY SUBJECTS --- p.92 / Chapter 5.4 --- SOLVENT EXPOSURES --- p.93 / Chapter 5.4.1 --- Occupational Hygiene --- p.93 / Chapter 5.4.2 --- Exposure Classification --- p.95 / Chapter 5.4.3 --- Chemical Interaction --- p.98 / Chapter 5.5 --- HEALTH PROBLEMS --- p.99 / Chapter CHAPTER 6. --- CONCLUSION --- p.103 / REFERENCES --- p.105 / APPENDICES --- p.120 / Appendices A1 to A9: Newspaper reports on polyneuropathy induced by organic solvents in a Hong Kong printing factory --- p.120 / Appendix B: Telephone follow up form --- p.129 / Appendix C: Letter to the printing factory employer --- p.130 / Appendix D: Subjective symptom questionnaire for solvent workers --- p.131 / Appendix E: Questionnaire for exposed group workers --- p.132 / Appendix F: Questionnaire for non-exposed group workers --- p.140 / Appendix G: NIOSH Sampling and Analytical Method 1400 --- p.145 / Appendix H: NIOSH Sampling and Analytical Method 1500 --- p.150 / "Appendix I: Chemical Analytical Method from Department of Hygiene, School of Public Health, Sun Yat Sen University of Medical Sciences" --- p.157 / Appendix J: Air Sampling Worksheet --- p.159 / BIBLIOGRAPHY --- p.162

Song Hong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves ). / Abstracts in English and Chinese; questionnaire in Chinese. / Abstract (English) --- p.i / Abstract (Chinese) --- p.iv / Acknowledgments --- p.vi / Table of Contents --- p.vii / List of tables --- p.x / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Printing industry and organic solvents exposure --- p.1 / Chapter 1.2 --- Risk of low level exposures to organic solvents --- p.2 / Chapter 1.3 --- Using neurobehavioral methods to study the subclinical effects --- p.3 / Chapter Chapter 2 --- Literature review --- p.4 / Chapter 2.1 --- Organic solvents and neurobehavioral impairment --- p.4 / Chapter 2.2 --- Methodology of Neurobehavioral Test --- p.6 / Chapter 2.2.1 --- Criteria for selecting test battery --- p.7 / Chapter 2.2.2 --- Standardization of neurobehavioral test battery --- p.8 / Chapter 2.2.3 --- Reliability and validity --- p.9 / Chapter 2.2.4 --- Confounding factors of neurobehavioral test --- p.10 / Chapter 2.3 --- Neurobehavioral effects of different levels of solvent exposures --- p.12 / Chapter 2.3.1 --- Positive results in field studies --- p.12 / Chapter 2.3.2 --- Negative results in field studies --- p.17 / Chapter 2.3.3 --- Dose-response relationship in the field studies --- p.18 / Chapter 2.3.4 --- To separate acute and chronic effects --- p.20 / Chapter 2.3.5 --- The long-term effects of solvent exposure --- p.21 / Chapter 2.4 --- Limitations of these studies --- p.23 / Chapter 2.5 --- Summary --- p.26 / Chapter Chapter 3 --- Aims and Objectives --- p.31 / Chapter 3.1 --- Aims of the present research --- p.31 / Chapter 3.2 --- Position of this study cm this research domain --- p.32 / Chapter Chapter 4 --- Subjects and Method --- p.33 / Chapter 4.1 --- Study design --- p.33 / Chapter 4.2 --- Study population and sampling --- p.33 / Chapter 4.2.1 --- Participation --- p.33 / Chapter 4.2.2 --- Exposed group --- p.34 / Chapter 4.2.3 --- Reference group --- p.34 / Chapter 4.2.4 --- Sample size estimation --- p.34 / Chapter 4.3 --- Data collection --- p.36 / Chapter 4.3.1 --- Exposure assessment --- p.36 / Chapter 4.3.1.1 --- Air sample measurements --- p.36 / Chapter 4.3.1.2 --- Biological monitoring --- p.38 / Chapter 4.3.2. --- Medical assessment --- p.38 / Chapter 4.3.2.1 --- Pre-test questionnaire --- p.39 / Chapter 4.3.2.2 --- Neurobehavioral assessment --- p.39 / Chapter 4.4 --- Data Analysis --- p.43 / Chapter 4.4.1 --- Data Processing --- p.43 / Chapter 4.4.2 --- Statistical analysis --- p.44 / Chapter 4.4.2.1 --- Descriptive analysis --- p.44 / Chapter 4.4.2.2 --- Identifying the main confounding factories --- p.44 / Chapter 4.4.2.3 --- Comparing the tests score adjusted for confounding --- p.45 / Chapter 4.4.2.4 --- Dose-response analysis --- p.45 / Chapter Chapter 5 --- Results --- p.47 / Chapter 5.1 --- Demographic characteristics of the subjects --- p.47 / Chapter 5.2 --- Comparison of the basic characteristics between the exposed group and the reference group --- p.48 / Chapter 5.3 --- Comparison of the symptoms between the exposed group and the reference group --- p.49 / Chapter 5.4 --- Comparison of the scores of neurobehavioral tests between the exposed group and the reference group --- p.51 / Chapter 5.5 --- Identifying potential confounding of neurobehavioral test --- p.51 / Chapter 5.5.1 --- Main confounding factors of NCTB test on performance tests --- p.51 / Chapter 5.5.2 --- Main confounding factors of Profile of Mood States --- p.54 / Chapter 5.6 --- Groups comparison of the neurobehavioral effects --- p.57 / Chapter 5.6.1 --- Comparison of the adjusted mean scores between the exposed group and the reference group --- p.57 / Chapter 5.6.2 --- Groups comparison of the adjusted tests score in Factories C and G respectively --- p.58 / Chapter 5.7 --- Exposure assessment --- p.61 / Chapter 5.7.1 --- Air sampling results of the printing factories --- p.62 / Chapter 5.7.2 --- Relationship between results of active and passive sampling systems --- p.63 / Chapter 5.7.3 --- Biological monitoring --- p.63 / Chapter 5.8 --- Dose-response relationship --- p.65 / Chapter Chapter 6 --- Discussion --- p.69 / Chapter 6.1 --- Findings of this study --- p.69 / Chapter 6.1.1 --- Subjective symptoms --- p.69 / Chapter 6.1.2 --- Neurobehavioral effects --- p.70 / Chapter 6.1.3 --- Exposure intensity --- p.72 / Chapter 6.1.4. --- Dose-response relationship --- p.75 / Chapter 6.2 --- Applications of the study results --- p.76 / Chapter 6.2.1 --- The need for prevention measures --- p.77 / Chapter 6.2.2 --- Contributing to re-setting of OELs --- p.77 / Chapter 6.2.3. --- The evidence on neurotoxicology --- p.78 / Chapter 6.3 --- Limitations of the study --- p.79 / Chapter 6.3.1. --- Possibility of bias --- p.79 / Chapter 6.3.2. --- Lack of historical hygiene measurement data --- p.80 / Chapter 6.3.3. --- Influence of workshift --- p.81 / Chapter 6.3.4. --- Combined exposures to noise and organic solvents --- p.82 / Chapter 6.4 --- Conclusion --- p.83 / Appendices --- p.84 / Appendix 1 --- p.84 / Appendix 2 --- p.97 / Appendix 3 --- p.102 / Appendix 4 --- p.103 / Appendix 5 The Administration of The WHO-NCTB Tests --- p.114 / Test 1 Profile of Mood States Test --- p.115 / Test 2. Simple Reaction Time Test --- p.116 / Test 3. Digit Span Test Test --- p.119 / Test 4. Santa Ana Test --- p.120 / Test 5. Digit Symbol Test --- p.122 / Test 6. Benton Visual Retention Test --- p.123 / Test 7. Pursuit Aiming Test --- p.125 / Appendix 6 --- p.126 / Reference List --- p.127

Lead (Pb²⁺) is an environmental toxin that is known to cause lasting cognitive deficits following early life exposure. Previously, our laboratory demonstrated increased sensitivity to the psychostimulant effects of cocaine in animals with elevated blood Pb²⁺ levels (BLL). This effect was abolished following introduction of dopamine (DA) receptor antagonists, indicating that the dopaminergic (DAergic) system may be a target of Pb²⁺’s toxic effects. However, the biological mechanisms through which Pb²⁺ increased sensitization to cocaine’s psychostimulant effects have not been fully elucidated. There is some disagreement regarding the magnitude and direction of Pb²⁺’s effects on the DAergic system. Furthermore, many studies to date have measured the effects of Pb²⁺ in only one sex (usually male), one exposure, and one or two time-points, making it difficult to determine any potential sex-, age-, and exposure-dependent effects. In the present study, we used a well-validated animal model and Pb²⁺ exposure paradigm that uses chronic dietary exposure to 180ppm and 1500ppm Pb²⁺ acetate (PbAC) in the diet. These levels of Pb²+ in the diet resulted in low and moderate levels of BLLs that on average approximated 4.5 and 22.0µg/dl in young adult rats. These levels of Pb²⁺ exposure are relevant to contemporary levels of BLL in intoxicated children in many cities in the United States and in many parts of the world where Pb²⁺ exposure continues to be a major public health concern. It should be noted that at the low level of Pb²⁺ exposure, the resulting BLL of 4.5µg/dl is just below the current CDC level of action. Using this well-defined rat model of chronic Pb²⁺ exposure, in Aim 1, we measured DA concentration and turnover in the dorsal striatum (STR) of juvenile (PN14), adolescent (PN28), and young adult (PN50) male and female rats. Tyrosine hydroxylase (TH) protein, the rate-limiting step in the synthesis of DA, and phosphorylation of TH at serine 40 (pser40TH) were assessed as an indirect measure of TH activity. Thus, we measured the ratio of pser40TH to total TH protein. We also measured vesicular monoamine transporter-type 2 (VMAT2) levels in the STR, nucleus accumbens (NAC), and olfactory tubercle (OT) since this protein is critical for the sequestration of DA in presynaptic vesicles and has been used as a biomarker for DA terminal integrity. In Aim 2, we examine the effect of chronic Pb²⁺ exposure on D1 and D2 dopamine receptor (D1R and D2R) in the OT, NAC, and STR. Analysis of D1R and D2R is important since the downstream effects of DA are dependent on the DA receptor subtype it activates. In Aim 1, we observed significant increases in DA and its metabolites homovanillic acid (HVA) and 3,4-Dihydroxyphenylacetic acid (DOPAC) in the STR of adolescent and young adult male rats with BLL as low as 4.5µg/dl in the absence of phosphorylation at the serine 40 residue of TH or altered VMAT2 levels. In Aim 2, a significant increase in D2R was detected in the juvenile male rat STR. We also observed increases in D1R expression in adolescent male rats in the NAC, OT, STR, and in the OT of adolescent female rats. Together, these results demonstrate that chronic Pb²⁺ exposure alters DA receptor levels in a manner characteristic of a hyperactive DAergic state. The observations presented in this work suggest that a hyperactive DAergic system underlies the heightened sensitization to cocaine we previously observed in Pb²⁺-exposed animals. This work builds upon the current understanding of how Pb²⁺ modulates the DAergic system and provides some elucidation of the mechanisms underlying increased drug sensitization our laboratory has previously observed in rats exposed to Pb²⁺.

Submitted by Erika Demachki (erikademachki@gmail.com) on 2014-09-04T19:33:18Z No. of bitstreams: 2 Batista, Mariana Pedrosa - Avaliação citogenética e molecular de indivíduos ocupacionalmente expostos aos agrotóxicos - 2014.pdf: 1556018 bytes, checksum: 89fbad76ace350a8cf9c7db5c92f015d (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-09-04T19:33:18Z (GMT). No. of bitstreams: 2 Batista, Mariana Pedrosa - Avaliação citogenética e molecular de indivíduos ocupacionalmente expostos aos agrotóxicos - 2014.pdf: 1556018 bytes, checksum: 89fbad76ace350a8cf9c7db5c92f015d (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-02-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Rural workers are constantly exposed to pesticides they use on crops, and this exposure may be responsible for genetic damage causing a health risk. A problem with the use of pesticides is the genotoxicity, which can lead to the onset of disease. Little is known about the relationship between genotoxicity and the variation of genetic polymorphisms of xenobiotic metabolism that may modify individual susceptibility to the possible genotoxic effects of pesticides. Therefore, there is a need to study genes as glutathione-S-transferase mu (GSTM1) and theta glutathione S-transferase (GSTT1) encoding detoxification enzymes of genotoxic compounds. Another important assessment in individuals exposed to pesticides is the presence of chromosomal translocation t(14;18) (q31,q21), which can be investigated at the molecular level. Thus, this study evaluated the polymorphisms of GSTM1 and GSTT1 genes in 120 individuals occupationally exposed to pesticides and 115 controls (without exposure to pesticides), by real-time PCR. The frequencies of GSTM1 and GSTT1 genotypes were found in 49 % and 18 %, respectively in the exposed group and 37 % and 18 %, respectively, for the control group. It has been found that there is a greater possibility of poisoning in workers who have null genotypes. There was no statistically significant correlation between the increased risk of intoxication and alcohol consumption, smoking and use of PPE. In addition, 29 workers exposed to pesticides for more than 15 years and with null genotypes in GSTT1 and / or GSTM1, were evaluated for the presence of the t (14;18)(q31, q21), in 100 nuclei, by fluorescent in situ hybridization (FISH) . The translocation was observed in only one individual, which may have been caused by prolonged exposure to pesticides, increasing age or alcohol consumption. Thus, the study of genetic polymorphisms and translocations as biomarkers of susceptibility is of fundamental importance in understanding the processes involved in genotype distribution mutagenesis and carcinogenesis and could help minimize the risks for susceptible individuals who are exposed to pesticides. / Os trabalhadores rurais estão constantemente expostos aos agrotóxicos que utilizam nas lavouras, e esta exposição pode ser responsável por danos genéticos causando um risco para a saúde. Um dos problemas da utilização de agrotóxicos é a genotoxicidade, que pode levar ao aparecimento de doenças. Pouco se sabe sobre a relação entre a genotoxicidade e a variação de polimorfismos genéticos de metabolização de xenobióticos que podem modificar a suscetibilidade individual aos possíveis efeitos genotóxicos dos agrotóxicos. Por isso, há a necessidade do estudo de genes como a glutationa-S-tranferase mu (GSTM1) e glutationa-S–transferase teta (GSTT1) que codificam enzimas de detoxificação de compostos genotóxicos. Outra avaliação importante em indivíduos expostos a agrotóxicos é a pesquisa da translocação cromossômica t(14;18)(q31;q21), a qual pode ser investigada em nível molecular. Nesse sentido, esse estudo avaliou os polimorfismos dos genes GSTT1 e GSTM1, em 120 indivíduos ocupacionalmente expostos aos agrotóxicos e de 115 controles (sem exposição aos agrotóxicos), pela metodologia de PCR em tempo real. As frequências de genótipos GSTM1 e GSTT1 encontradas foram de 49% e 18%, respectivamente, para o grupo exposto e 37% e 18%, respectivamente, para o grupo controle. Verificou-se que não há maior possibilidade de intoxicação em trabalhadores que apresentam genótipos nulos. Não houve correlação estatisticamente significativa entre o aumento do risco de intoxicação e o consumo de álcool, tabaco e uso de EPI. Além disso, 29 trabalhadores, expostos a agrotóxicos por mais de 15 anos e com genótipos nulos, GSTT1 e/ou GSTM1, foram avaliados quanto à presença da translocação t(14;18)(q31; q21), pela análise de 100 células, por Hibridação Fluorescente in situ (FISH). Com essa análise, a translocação foi observada em apenas um indivíduo, a qual pode ter sido causada pela exposição prolongada a agrotóxicos, aumento da idade ou consumo de álcool. Dessa forma, o estudo de polimorfismos genéticos e translocações, como biomarcadores de suscetibilidade é de importância fundamental na compreensão dos processos de distribuição genotípica envolvidos na mutagênese e carcinogênese e poderia ajudar a minimizar os riscos para indivíduos suscetíveis que são expostos a agrotóxicos.

Made available in DSpace on 2016-04-28T20:18:26Z (GMT). No. of bitstreams: 1 Bruno Jose Martini Santos1.pdf: 1883262 bytes, checksum: 395f219cf3935956cd50161c96cd1a19 (MD5) Previous issue date: 2010-02-10 / The administration of the aerial parts of Pteridium arachnoideum during 15 to 57 days in proportions that varied from 50 to 75% of the supplied grass (Pennicetum purpureum) mixed with hay of bracken fern, caused in 3 of the 4 experimental horses, a clinical and pathological picture that can be attributed to the thiaminases, one of the poisonous principles of the plant. The clinical picture consisted, in a progressive way, apathy, lethargy, sleepiness, hyporrexia with evolution to anorexia, reluctance in moving, increase of heart frequency, arrhythmia and sternal decubitus passing to lateral decubitus. The decubitus lasted at the most 48 hours. In this phase, the clinical signs previously observed got more intense; additionaly the animals refused water, made attempts of getting up without success, made intense intermittent peddling movements, followed by dyspnoea, had muscular tremors, tonic muscle spasms of limbs, opistotonus, intense sweating and finally death. The electrocardiographic analysis showed hydropericardium and myocardial failure in the last 48 hours before death. Post-mortem and histopathological examinations did not show significant lesions, unless congestion in various organs, indicating congestive heart failure. Clinical pathology revealed, in relation to the blood count, in one of the three horses, anemia in the final part of the experiment, and trombocitopenia in only two. No changes were seen in the leucograma. Parallel to a fall of serous thiamine, an increase the pyruvic acid was seen in the three animals. One of the experimental horses developed a taste for the fern, and the other two only consumed the P. arachnoideum-grass mixture with addition of sugar. / A administra??o das partes a?reas de Pteridium arachnoideum durante per?odos de 15 a 57 dias na propor??o que variou de 50 a 75% da mistura com capim (Pennicetum purpureum) fornecida, causou em 3 dos 4 equinos do experimento um quadro cl?nico-patol?gico que pode ser atribu?do a tiaminase, um dos princ?pios t?xicos da planta. No quadro cl?nico foram verificados de forma progressiva apatia, letargia, sonol?ncia, hiporrexia com evolu??o para anorexia, relut?ncia em se movimentar, aumento da frequ?ncia card?aca, arritmia e finalmente dec?bito esternal passando para o lateral. O dec?bito era de no m?ximo 48 horas. Nesta fase os sinais cl?nicos anteriormente observados se intensificaram, os animais, recusavam ?gua, faziam tentativas de se levantar sem sucesso, movimentos de pedalagem intensos intermitentes, seguidos de dispn?ia, tremores musculares, espasmos musculares t?nicos dos membros, opist?tono, sudorese intensa e finalmente morte. As an?lises eletrocardiogr?ficas indicaram hidroperic?rdio e insufici?ncia mioc?rdica nas ultimas 48 horas antes da morte. Os achados de necropsia e os exames histopatol?gicos n?o revelaram altera??es significativas, a n?o ser congest?o em diversos ?rg?os e efus?es cavit?rias de colora??o amarelo ocre, o que est? relacionado com insufici?ncia card?aca congestiva. A patologia cl?nica revelou, em rela??o ao hemograma, em um dos tr?s animais, anemia na parte final do experimento, e em dois equinos trombocitopenia. O leucograma n?o apresentou altera??es. Paralelamente a queda da tiamina s?rica, foi verificado um aumento do ?cido pir?vico nos tr?s animais. Um dos animais experimentais desenvolveu um gosto pela samambaia, os outros dois consumiram a mistura de capim com feno de samambaia mediante o acr?scimo de a??car.

Varios fatores contribuem para o desenvolvimento da anemia, que constitui um dos mais graves problemas de saude publica. A anemia hipocromica microcitica e a forma mais comum em criancas e adolescentes. Dentre as causas desta anemia estao: a) deficiencia de ferro, que resulta de um longo periodo do balanco negativo do micronutriente e causa retardo no crescimento e comprometimento do desempenho cognitivo de criancas; b) contaminacao por chumbo (plumbismo) que tambem afeta o desenvolvimento das criancas, podendo ser agravada nos portadores de polimorfismo da enzima ALAD; c) hemoglobinopatias (hemoglobinas variantes e talassemias), anemias herdadas que afetam 7% da populacao mundial. Devido a alta prevalencia destas patologias, o presente trabalho teve como objetivo estudar um grupo de criancas de escolas publicas, identificando os fatores que contribuem para o desenvolvimento de anemias hipocromicas microciticas e estabelecer relacoes entre as caracteristicas laboratoriais das doencas. Participaram do estudo 427 criancas, com idade entre 6 a 9 anos, sendo 235 do sexo feminino e 192 do sexo masculino, alunos de Escolas Municipais e Estaduais, da zona norte da cidade de Ribeirao Preto-SP. Foram analisados: a) numero global de eritrocitos e leucocitos, concentracao de hemoglobina, hematocrito, indices hematimetricos e distribuicao da amplitude das celulas vermelhas (contador automatico Micros 45 . Horiba ABXR) e calculo do indice matematico RDWI; b) niveis plasmaticos de chumbo (espectrometro de massa com plasma indutivamente acoplado VG Plasmaquad PQIIR) e estudo das delecoes dos polimorfismos da enzima ALAD, por PCR; c) status ferrico pelos niveis de ferritina serica (imunoquimioluminescencia utilizando kit Ferritin Immulite . DPCR e equipamento Immulite 1 - DPCR), receptor de transferrina soluvel (ensaio imunoenzimatico, utilizando o kit Quantikine soluble transferrin receptor da R&D SystemsR e o leitor de microplacas de ELISA READER 210, modelo Microwell System Organon TeknikaR) e calculo do indice sTfR/log ferritina; d) analise das hemoglobinas por eletroforese em acetato de celulose, pH alcalino, por HPLC (sistema automatizado Variant II Bio-RadR e kit gÀ-talassemia Short Program) e PCR para a principal delecao de ¿- talassemias. Com base no criterio recomendado pela OMS para definir anemia (Hb menor que 11,5 g/dL), verificou-se que 75 (17,6%) criancas eram anemicas, sendo 33 (44%) portadoras de algum tipo de hemoglobinopatia, 29 (38,6%) com anemias de causa desconhecida e 13 (17,4%) com anemia por deficiencia de ferro. Das anemias, apenas 14 eram anemias hipocromicas microciticas, sendo que 10 (71,4%) eram algum tipo de hemoglobinopatia, 2 (14,2%) ADF e 2 (14,2%) de causa desconhecida. Na populacao estudada, a prevalencia de hemoglobinopatias foi de 16,6% , a saber: 11,6% com ¿-talassemia; 4% com aumento de Hb F; 3,5% com Hb AS; 2,8% com À-talassemia; 0,96% com ¿/À-talassemia e 0,24% com Hb AC. Os niveis de chumbo plasmatico, em todos os participantes do estudo, estavam dentro do recomendado pelo Center for Disease Control and Prevention (< 10 Êg/dL), nao havendo interferencia do metal na patogenese das anemias. Nao houve associacao entre os polimorfismos da ALAD-1 (ALAD1-1 e ALAD1-2) e os niveis de chumbo plasmatico. Anemia por deficiencia de ferro foi diagnosticada em 3% das criancas e DF em 6,1%, utilizando um cut off de 30 ng/mL para ferritina serica. Houve concordancia na identificacao de hemoglobinopatias utilizando as metodologias eletroforese de hemoglobina em acetato de celulose e HPLC, sendo que estas metodologias nao sao uteis para diagnosticar ¿-talassemia. Para identificar os portadores da delecao de ¿-talassemia (.¿3,7) e necessaria a utilizacao da análise molecular (PCR). A suspeita de Hb S/-talassemia identificada por HPLC deve ser confirmada por análise dos pais e/ou irmãos. A ferritina foi um bom parâmetro para identificar DF precocemente e útil para diferenciar os portadores de hemoglobinopatias dos portadores de DF e ADF. O índice sTfR/log da ferritina foi mais sensível do que o sTfR, na diferenciação de DF e talassemia. No diagnóstico das anemias hipocrômicas microcíticas é necessário analisar um conjunto de determinações, incluindo exame hematológico, status férrico, perfil eletroforético, em alguns casos incluindo avaliação dos familiares, e análise molecular das hemoglobinopatias. / Several factors contribute to the development of anemia, which constitutes one of the most serious problems in public health. The hypochromic microcytic anemia is the most common type in children and adolescents. Among the causes for this type of anemia are: a) iron deficiency, which results from a long period of negative balance of the micronutrient, causing delay in growth and compromising the cognitive performance of the children; b) contamination by lead (lead poisoning), which also affects the development of children, and may be aggravated in carriers of polymorphism of the enzyme ALAD; c) hemoglobinopathies (variants hemoglobin and thalassemia), inherited anemia that affects 7% of the world population. Due to the high prevalence of these pathologies, the present study aimed at studying a group of children from public schools, identifying the factors that contribute to the development of hypochromic microcytic anemia and establishing relations between the laboratorial characteristics of the diseases. The study had the participation of 427 children, aged between 6 and 9 years old, being 235 female and 192 male students from Municipal and State Schools in the north area of Ribeirao Preto-SP. It analyzed: a) number of erythrocytes and leucocytes, hemoglobin concentration, hematocrit, red cell indices and red cell distribution width (automatic counter Micros 45 . Horiba ABXR) and calculation of the mathematical index RDWI; b) plasma lead levels (inductively coupled plasma mass spectrometer VG PlasmaQuad PQIIR) and study of the deletions of the polymorphisms of the enzyme ALAD, by PCR; c) iron status by serum ferritin levels (immunochemiluminescence using the kit Ferritin Immulite . DPCR and the equipment Immulite 1 - DPCR), soluble transferrin receptor (enzyme immune assay, using the kit Quantikine soluble transferrin receptor of R&D SystemsR and the microplate reader ELISA READER 210, model Microwell System Organon TeknikaR) and calculation of the sTfR/log ferritin index; d) hemoglobin analysis by electrophoresis on cellulose acetate at alkaline pH, HPLC (automated system Variant II Bio-RadR and the kit gÀ-thalassemia Short Program) and PCR for the main deletion of ¿-thalassemias. Based on the WHO criteria by to define anemia (Hb under 11.5 g/dL), it was verified that 75 (17.6%) children were anemic, being 33 (44%) with hemoglobinopathy, 29 (38.6%) with anemia of unknown causes and 13 (17.4%) with iron deficiency anemia. Among the anemias, only 14 were hypochromic microcytic, 10 (71.4%) being some sort of hemoglobinopathy, 2 (14.2%) due to iron deficiency and 2 (14.2%) due to unknown causes. In the studied population, the prevalence of hemoglobinopathies was 16.6%, namely: 11.6% with ¿-thalassemia; 4% with Hb F elevated; 3.5% with Hb AS; 2.8% with À- thalassemia; 0.96% with ¿/À-thalassemia and 0.24% with Hb AC. The plasma lead levels, in all participants of the study, were within the levels recommended by the Center for Disease Control and Prevention (< 10 Êg/dL), without the interference of the metal in the pathogenesis of the anemias. There was no significant association between the polymorphisms of the ALAD-1 (ALAD1-1 and ALAD1-2) and the plasma lead levels. Iron deficiency anemia was diagnosed in 3% of the children and ID in 6.1%, using a cutoff of 30 ng/mL for serum ferritin. There was agreement in the identification of hemoglobinopathies using the methodologies electrophoresis of hemoglobin in cellulose acetate and the HPLC, as these methodologies are not useful to diagnose ¿-thalassemia. In order to identify the carriers of ¿-thalassemia gene deletion (.¿3,7) it is necessary to use the molecular analysis (PCR). The suspicion of Hb S/À-thalassemia identified by HPLC must be confirmed through the analysis iv of the parents and/or siblings. The ferritin was a good parameter to identify ID early and useful to differ the carriers of hemoglobinopathies of the carriers of ID and IDA. The sTfR/log ferritin level was more sensitive than the sTfR, in the differentiation of ID and thalassemia. In the diagnosis of the hypochromic microcytic anemias, it is necessary to analyze a set of determinations, including hematological exam, iron status, electrophoretic profile, in some cases including relatives, and molecular analysis of the hemoglobinopathies.