A exposição ambiental aos poluentes orgânicos persistentes tem recebido amplo destaque na literatura recentemente devido à extensa associação entre o desenvolvimento de doenças metabólicas, obesidade e/ou diabetes mellitus, e a presença destes poluentes, principalmente os organoclorados, como as bifenilas policloradas (PCBs), no organismo. Por outro lado, os mecanismos de ação destes poluentes é controverso devido à elevada quantidade de representantes destas classes, gerando diversidade de protocolos de exposição e escassez de estudos experimentais. Por isto, foi objetivo deste trabalho elucidar os mecanismos de ação tóxica do PCB126, nas doses de 0,1; 1 ou 10 µg/kg de massa corpórea, em ratos Wistar machos, durante quinze dias, expostos por instilação intranasal. O procotolo de exposição empregado foi caracterizado e considerado suficiente para causar toxicidade, uma vez que foram observadas alterações no sistema imune, metabolismo e em parâmetros relacionados à gênese do diabetes mellitus. A caracterização da exposição foi determinada pela quantificação da concentração de PCB126 no fígado e pulmão (CG/MS) e pelo aumento da expressão do receptor aril hidrocarboneto (AhR) no rim, fígado, pulmão e tecido adiposo (Western Blot). O efeito imunossupressor do PCB126 foi evidenciado pelo comprometimento da produção de células na medula óssea e, consequentemente, no número de células totais no sangue circulante. Adicionalmente, foi evidenciada a interferência do poluente na via de ativação mediada por receptores acoplados à proteína G (GPCRs), principalmente em neutrófilos, alterando importantes funções destas células, como a expressão de moléculas de adesão, geração de espécies reativas de oxigênio e migração. Entre as alterações metabólicas observadas, destacamos o aumento dos níveis de triglicerídeos e colesterol sérico, aumento da liberação de ácidos graxos livres; aumento da atividade da enzima hepática gama glutamil transferase; aumento da resistência à insulina e aumento da geração de óxido nítrico pelas ilhotas de Langerhans, dados estes, possivelmente relacionados ao comprometimento das células beta (β) pancreáticas, confirmados pelo aumento da expressão de GLUT4 no tecido adiposo, aumento da concentração de insulina sérica e aumento do estresse oxidativo nas ilhotas de Langerhans. Em conjunto, os dados obtidos destacam importantes alterações causadas pela exposição intranasal ao PCB126, evidenciando a participação do poluente na gênese do diabetes mellitus do tipo II. / The environmental exposure to persistent organic pollutants has been widely highlighted in recent literature due to the extensive association between the development of metabolic diseases, obesity and/or diabetes mellitus, and presence of these pollutants, especially organochlorines such as polychlorinated biphenyls (PCBs) in organism. Moreover, the mechanisms of action of these pollutants are controversial due to the high number of PCBs congeners, diversity of exposure protocols and lack of experimental studies. Therefore, the aim of this study was to elucidate the mechanisms of PCB126\'s toxic action at doses of 0.1; 1 or 10 µg/kg body weight in male Wistar rats exposed by intranasal instillation for 15 days. The established exposure procotol was characterized and considered sufficient to cause toxicity since changes were observed in the immune system, metabolism and in parameters related to the pathogenesis of diabetes mellitus. Characterization of exposure was determined by quantifying the concentration of PCB126 in liver and lung (GC-MS) and by the increased expression of aryl hydrocarbon receptor (AhR) in kidney, liver, lung, and adipose tissue (Western blot). The immunosuppressive effect of PCB126 was evidenced by impairment of cell production in the bone marrow and thus the total number of cells in the circulation. In addition, the interference of the pollutant in the activation pathway mediated by G-protein coupled receptors (GPCRs), in particular in neutrophils, was observed by changing important functions of these cells such as the expression of adhesion molecules, reactive oxygen species generation, and migration. Among the metabolic changes observed, we highlight the increased levels of triglycerides and serum cholesterol, increased release of free fatty acids; increased gamma glutamyl transferase hepatic enzyme activity; increased insulin resistance and increased generation of nitric oxide by the islets of Langerhans, these data possibly related to the impairment of beta cells (β) pancreatic function, suggested by the increased expression of GLUT4 in adipose tissue, increased serum insulin concentration and increased oxidative stress in the islets of Langerhans. Altogether, these results highlight important changes caused by intranasal exposure to PCB126, suggesting participation of the pollutant in the genesis of diabetes mellitus type II.

A tartaruga verde (Chelonia mydas) é uma tartaruga marinha que se alimenta e nidifica em locais da costa brasileira, ilhas e atóis. Esta espécie tem sido acometida pela fibropapilomatose (FP), doença considerada como uma das mais importantes ameaças à sua sobrevivência e caracterizada por tumores cutâneos benignos. A etiologia é multifatorial e complexa, possivelmente havendo relação entre Chelonid Fibropapilloma-associated Herpesvirus, fatores ambientais e genéticos. Foram estudadas 133 tartarugas verdes com e sem tumores provenientes de cinco áreas brasileiras: Florianópolis/SC, Ubatuba/SP, Vitória/ES, Almofala/CE e Fernando de Noronha/PE. Foram obtidos dados de biometria (comprimento curvilíneo da carapaça-CCC, massa corporal-MC e índice de condição corporal-ICC), tamanho (classificado por categorias A, B, C e D), quantidade e localização anatômica dos tumores, além da colheita de amostra sanguínea. Os objetivos foram (1) avaliar a atividade dos leucócitos por citometria de fluxo (fagocitose e burst oxidativo); (2) investigar a presença de sete congêneres de bifenilas policloradas (PCBs) e (3) estabelecer correlações entre PCBs e a atividade dos leucócitos. Houve diferenças no CCC entre tartarugas sem tumores de acordo com a área de estudo, na MC e no ICC entre animais acometidos ou não capturados em Ubatuba. Foram quantificados e classificados 1033 tumores de 50 tartarugas verdes, sendo que a quantidade por tartaruga variou de 1 a 61 e a maior parte foi classificada nas categorias de tamanho A (446 tumores) e B (520 tumores) e na região anterior (669 tumores). Foi observada diferença significativa nas concentrações do congênere PCB 138 entre tartarugas com e sem FP capturadas em Vitória. Animais acometidos tiveram maiores concentrações de todas as PCBs quantificadas, exceto as tartarugas verdes capturadas em Vitória no caso dos congêneres PCBs 118, 138, 153 e 180. PCB 138 foi quantificado em maior concentração nas amostras e PCB 180 em níveis menores. Não foram observadas correlações significativas entre concentrações de PCBs e atividade celular. A FP tem sido amplamente pesquisada e os estudos que visam estabelecer correlações entre poluentes químicos e saúde animal são extremamente importantes, pois podem contribuir para novas direções nos planos de ação para conservação. / The green sea turtle (Chelonia mydas) feeds and nests in Brazilian coast, islands and atolls. This species has been affected by fibropapillomatosis (FP), disease considered one of the most important threats to its survival and characterized by benign skin tumors. The etiology is multifactorial and complex, possibly having relation between Chelonid Fibropapilloma-associated Herpesvirus, environmental and genetic factors. Were studied 133 green sea turtles with and without FP from five Brazilian areas: Florianópolis/SC, Ubatuba/SP, Vitória/ES, Almofala/CE and Fernando de Noronha/PE. Were taken biometric data (curved carapace length-CCL, body mass-BM and body condition index-BCI), as well as size (classified by categories A, B, C and D), numbers and anatomical distribution of tumors, besides blood sample collection. The aims were (1) to assess leukocytes activity by flow cytometry (phagocytosis and oxidative burst); (2) to investigate the presence of seven congeners of polychlorinated biphenyls (PCBs) and (3) to establish correlations between PCBs and leukocytes activity. There were differences in CCL between turtles without FP according to the study area, in BM and BCI between affected and non-affected animals caught in Ubatuba. Were quantified and classified 1033 tumors of 50 green sea turtles, the number of tumors ranged from 1 to 61 and the most part of them was classified in categories of size A (446 tumors) and B (520 tumors) and in anterior region (669 tumors). Was observed difference in PCB 138 concentrations between green sea turtle with and without FP caught in Vitória. Affected animals had higher concentrations of all PCBs quantified, except green sea turtles caught in Vitória in the event of PCBs 118, 138, 153 and 180. Were quantified highest concentrations of PCB 138 and lowest of PCB 180. There were not significant correlations between PCBs concentration and leukocyte activity. The FP has been widely investigate and the studies that aimed to establish correlations between pollutants and animal health are very important, because can contribute for new directions in sea turtle conservation issues.

No description available.

<p>The polychlorinated biphenyls (PCBs) comprise a group of 209 congeners varying in the number of chlorine atoms and substitution patterns. These compounds tend to be biomagnified in foodwebs and have been shown to induce an array of effects in exposed organisms. The structural characteristics of the PCBs influence their potency as well as mechanism of action. In order to assess the biological potency of these compounds a multi-step quantitative structure-activity relationship (QSAR) procedure was used in the project described in this thesis.</p><p>The ultraviolet absorption (UV) spectra were measured for all 209 PCBs, and digitised for use as physico-chemical descriptors. Interpretations of the spectra using principal component analysis (PCA) showed the number of ortho chlorine atoms and para-para substitution patterns to be significant. Additional physico-chemical descriptors were derived from semi-empirical calculations. These included various molecular energies, the ionisation potential, electron affinity, dipole moments, and the internal barrier of rotation. The internal barrier of rotation was especially useful for describing the conformation of the PCBs on a continuous scale.</p><p>In total 52 physico-chemical descriptors were compiled and analysed by PCA for the tetra- to hepta-chlorinated congeners. The structural variation within these compounds was condensed into four principal properties derived from a PCA for use as design variables in a statistical design to select congeners representative for these homologue-groups. The 20 selected PCBs have been applied to study structure-specific biochemical responses in a number of bioassays, and to study the biomagnification of the PCBs in various fish species.</p><p>QSARs were established using partial least squares projections to latent structures (PLS) for the PCBs potency to inhibit intercellular communication, activate respiratory burst, inhibit dopamine uptake in synaptic vesicles, compete with estradiol for binding to estrogen receptors, and induce cytochrome P4501A (CYP1A) related activities. By the systematic use of the designed set of PCBs the biological potency was screened over the chemical domain of the class of compounds. Further, sub-regions of highly potent PCBs were identified for each response measured. For risk assessment of the PCBs potency to induce dioxin-like activities the predicted induction potencies (PIPs) were calculated. In addition, two sets of PCBs were presented that specifically represent congeners of environmental relevance in combination with predicted potency to induce estrogenic and CYP1A related activities.</p>

Thesis (M. Environmental Science (Water Science))--North-West University, Potchefstroom Campus, 2007.

The polychlorinated biphenyls (PCBs) comprise a group of 209 congeners varying in the number of chlorine atoms and substitution patterns. These compounds tend to be biomagnified in foodwebs and have been shown to induce an array of effects in exposed organisms. The structural characteristics of the PCBs influence their potency as well as mechanism of action. In order to assess the biological potency of these compounds a multi-step quantitative structure-activity relationship (QSAR) procedure was used in the project described in this thesis. The ultraviolet absorption (UV) spectra were measured for all 209 PCBs, and digitised for use as physico-chemical descriptors. Interpretations of the spectra using principal component analysis (PCA) showed the number of ortho chlorine atoms and para-para substitution patterns to be significant. Additional physico-chemical descriptors were derived from semi-empirical calculations. These included various molecular energies, the ionisation potential, electron affinity, dipole moments, and the internal barrier of rotation. The internal barrier of rotation was especially useful for describing the conformation of the PCBs on a continuous scale. In total 52 physico-chemical descriptors were compiled and analysed by PCA for the tetra- to hepta-chlorinated congeners. The structural variation within these compounds was condensed into four principal properties derived from a PCA for use as design variables in a statistical design to select congeners representative for these homologue-groups. The 20 selected PCBs have been applied to study structure-specific biochemical responses in a number of bioassays, and to study the biomagnification of the PCBs in various fish species. QSARs were established using partial least squares projections to latent structures (PLS) for the PCBs potency to inhibit intercellular communication, activate respiratory burst, inhibit dopamine uptake in synaptic vesicles, compete with estradiol for binding to estrogen receptors, and induce cytochrome P4501A (CYP1A) related activities. By the systematic use of the designed set of PCBs the biological potency was screened over the chemical domain of the class of compounds. Further, sub-regions of highly potent PCBs were identified for each response measured. For risk assessment of the PCBs potency to induce dioxin-like activities the predicted induction potencies (PIPs) were calculated. In addition, two sets of PCBs were presented that specifically represent congeners of environmental relevance in combination with predicted potency to induce estrogenic and CYP1A related activities.

Water resources in South Africa are scarce, and should therefore be protected against pollutants, also from persistent organic pollutants (POPs). This is emphasised by the Stockholm Convention on POPs, which aims at reducing and ultimately eliminating POPs. South Africa signed and ratified the treaty, and it became international law on 17 May 2004. POPS are highly stable, toxic, hydrophobic and lipophilic compounds, with the ability to accumulate in biological tissues. Previous research had shown that dioxin-like POPS are present in the aquatic environments of South Africa, with the highest concentrations of these substances measured in industrialised areas of South Africa. The present study aimed at investigating the extent of polychlorinated dibenzo-para-dioxin (PCDD), polychlorinated dibenzo-furan (PCDF) and polychlorinated biphenyl (PCB) pollution in the Vaal Triangle, by targeting aquatic sediments and biota. Sediment samples were collected from the Blesbok Spruit, Taaibos Spruit, Leeu Spruit and Suikerbosrand River, and fish tissue samples were collected from Blesbok Spruit and Suikerbosrand River, to determine bio-accumulation. The samples were extracted with organic solvents, cleaned-up and fractionated. Raw extracts and fractions were analysed with the H4IIE-luc reporter gene bio-assay. This bio-assay is a rapid, sensitive and relatively cost-effective method, which measures the effects of dioxin-like compounds on rat hepatoma cells, transfected with firefly luciferase gene. Selected samples were analysed with gas chromatographylmass spectrometry (GCIMS) to confirm results. Only one site had quantifiable amounts of dioxin-like substances in the sediment, measured to be 52.35 ng/kg [Effective Concentration 50 (EC 50)]. This value exceeds many of the European and USA quality guidelines, proposed for sediments. No dioxin-like substances were found in fish tissues. The absence of PCDD/Fs and PCBs in aquatic sediments and fish tissues from the Vaal Triangle area might be due to the climatic conditions of the area, dilution effects in streams, and degradation of these compounds by UV-radiation and microbial organisms. / Thesis (M. Environmental Science (Water Science))--North-West University, Potchefstroom Campus, 2007.

Water resources in South Africa are scarce, and should therefore be protected against pollutants, also from persistent organic pollutants (POPs). This is emphasised by the Stockholm Convention on POPs, which aims at reducing and ultimately eliminating POPs. South Africa signed and ratified the treaty, and it became international law on 17 May 2004. POPS are highly stable, toxic, hydrophobic and lipophilic compounds, with the ability to accumulate in biological tissues. Previous research had shown that dioxin-like POPS are present in the aquatic environments of South Africa, with the highest concentrations of these substances measured in industrialised areas of South Africa. The present study aimed at investigating the extent of polychlorinated dibenzo-para-dioxin (PCDD), polychlorinated dibenzo-furan (PCDF) and polychlorinated biphenyl (PCB) pollution in the Vaal Triangle, by targeting aquatic sediments and biota. Sediment samples were collected from the Blesbok Spruit, Taaibos Spruit, Leeu Spruit and Suikerbosrand River, and fish tissue samples were collected from Blesbok Spruit and Suikerbosrand River, to determine bio-accumulation. The samples were extracted with organic solvents, cleaned-up and fractionated. Raw extracts and fractions were analysed with the H4IIE-luc reporter gene bio-assay. This bio-assay is a rapid, sensitive and relatively cost-effective method, which measures the effects of dioxin-like compounds on rat hepatoma cells, transfected with firefly luciferase gene. Selected samples were analysed with gas chromatographylmass spectrometry (GCIMS) to confirm results. Only one site had quantifiable amounts of dioxin-like substances in the sediment, measured to be 52.35 ng/kg [Effective Concentration 50 (EC 50)]. This value exceeds many of the European and USA quality guidelines, proposed for sediments. No dioxin-like substances were found in fish tissues. The absence of PCDD/Fs and PCBs in aquatic sediments and fish tissues from the Vaal Triangle area might be due to the climatic conditions of the area, dilution effects in streams, and degradation of these compounds by UV-radiation and microbial organisms. / Thesis (M. Environmental Science (Water Science))--North-West University, Potchefstroom Campus, 2007.

Introduction Neuropsychological development is a genetically guided process which is continuously modified by socio-environmental factors. This thesis aimed to study the main socio-environmental determinants of neuropsychological development in different time-periods, such in the first two years of life, during preschool, and during preadolescence. This thesis also aimed to summarize the work done in environmental epidemiology on neuropsychological development in a novel conceptual framework. Methods This thesis is based on the data of the INMA (Infancia y Medio Ambiente) Project. The main objective of this project is to evaluate the impact of environmental exposures in children’s health in 7 population-based birth cohorts in different regions of Spain. The neuropsychological development of approximate total of 2,650 children was assessed at different time-periods following the same protocols. Results (1) Maternal cognitive capacities were positively related with child cognitive development early in life in more disadvantaged occupational social classes. (2) The levels of child cortisol were not related to child neuropsychological development during the second year of life. (3) Higher levels of long-chain polyunsaturated fatty acids in colostrum due to prolonged periods of breastfeeding improved early neuropsychological development of children, in particular in those children exposed to maternal smoking during pregnancy. (4) Prenatal exposure to PCBs (specially for PCB congener 153) impacted negatively on psychomotor development during the second year in life and on general neuropsychological development at the age of 4 years. (5) Postnatal exposure to organochlorine compounds was associated with a delay in reaction time (speed processing) during the preadolescent period. (6) The conceptual framework proposed will improve the quality of research in this area. Conclusions Social and cultural determinants such as maternal intelligence, educational level or occupational social class, are configuring the proximal environment in which a child develops and determine their neuropsychological development. Current levels of some organochlorine compounds, particularly polychlorinated byphenils, measured in blood samples (from umbilical cord, mothers, or children) are impairing on neuropsychological development in the general population. / Introducció El desenvolupament neuropsicològic infantil és un procés guiat genèticament, el qual és contínuament influenciat per factors socials i ambientals. L’objectiu d’aquesta tesis fou l’estudi dels principals determinants socio-ambientals del desenvolupament neuropsicològic infantil en diferents períodes de temps. Aquesta tesis també té l’objectiu de resumir en un marc conceptual els diferents components del desenvolupament neuropsicològic pel seu ús en estudis d’epidemiologia ambiental. Mètodes Aquesta tesis està basada en dades del projecte INMA (Infancia y Medio Ambiente). El principal objectiu d’aquest projecte és avaluar l’impacte de les exposicions ambientals en la salud infantil en 7 cohorts de població establides en diferents regions d’Espanya. Dintre del marc d’aquest projecte, s’ha avaluat el desenvolupament neuropsicològic d’aproximadament 2.650 nens en diferents moments, seguint els mateixos protocols. Resultats (1) Les capacitats cognitives maternes estan positivament relacionades amb el desenvolupament cognitiu infantil en les primeres etapes, en les classes socials ocupacionals menys afavorides. (2) Els nivells de cortisol infantil no mostren associació amb el desenvolupament neuropsicològic durant el segon any de vida. (3) Nivells elevats d’àcids grassos poliinsaturats de cadena llarga en conjunció amb períodes prolongats de lactancia materna afavoreixen el desenvolupament neuropsicològic a les primeres etapes, especialment en aquells nens de mares fumadores durant l’embaràs. (4) L’exposició prenatal a PCBs (espcialment, al congener 153) impacta negativament en el desenvolupament psicomotor infantil durant el segon any de vida i en el desenvolupament neuropsicològic general als 4 anys d’edat. (5) L’exposició postnatal a compostos organocloroats està associada a una capacitat de reacció (velocitat de processament) més alentida en etapes preadolescents. (6) L’ús del marc conceptual propossat tesis afavorirà la qualitat de l’investigació en aquesta àrea. Conclussions Els determinants socials, com l’intel•ligència materna, el nivell educatiu o la classe social basada en l’ocupació, configuren l’entorn més proper del nen i determinen el seu desenvolupament neuropsicològic. Els nivells actuals de certs compostos organoclorats, especialment els bifenils policlorinats, mesurats en mostres de sang (de cordó umbilical, mares o nens) mostren efectes negatius sobre el desenvolupament neuropsicològic en la població general. / Introducción El desarrollo neuropsicológico infantil es un proceso guiado genéticamente, el cual está contínuamente influenciado por factores sociales y ambientales. El objetivo de esta tesis fue estudiar los principales determinantes socio-ambientales del desarrollo neuropsicológico infantil en diferentes periodos de tiempo. Esta tesis también tenía como objetivo resumir en un marco conceptual el trabajo hecho en epidemiología ambiental en el estudio del desarrollo neuropsicológico infantil. Métodos Esta tesis está basada en datos del proyecto INMA (Infancia y Medio Ambiente). El principal objetivo de esto proyecto es evaluar el impacto de las exposiciones ambientales en la salud infantil en 7 cohortes de población establecidas en diferentes regiones de España. El desarrollo neuropsicológico de aproximadamente 2.650 niños ha sido evaluado en diferentes momentos siguiendo los mismos protocolos. Resultados (1) Las capacidades cognitivas maternas están positivamente relacionadas con el desarrollo cognitivo infantil en edades tempranas en las clases sociales ocupacionales menos aventajadas. (2) Los niveles de cortisol en el niño no se asocian con el desarrollo neuropsicológico durante el segundo año de vida. (3) Niveles altos de ácidos grasos poliinsaturados de cadena larga debido a periodos largos de lactancia materna mejoraron el desarrollo neuropsicológico a edades tempranas, especialmente en esos niños cuyas madres fumaron durante el embarazo. (4) La exposición prenatal a PCBs (espcialmente para el congener 153) impacta negativamente en el desarrollo psicomotor durante el segundo año de vida y en desarrollo neuropsicológico general a la edad de 4 años. (5) La exposición postnatal a compuestos organoclorados está asociado con una peor capacidad de tiempo de reacción (velocidad de procesamiento) durante la preadolescencia. (6) El marco conceptual propuesto mejorará la calidad de la investigación en esta área. Conclusiones Los determinantes sociales tales como inteligencia maternal, nivel educativo o clase social basada en la ocupación, configuran el entorno más cercano en el cual el niño se desarrolla y determinan su desarrollo neuropsicológico. Los niveles actuales de ciertos compuestos organoclorados, especialmente los bifeniles policlorinados, medidos en sangre (de cordón umbilical, madre, o niño) tienen efectos negativos sobre el desarrollo neuropsicológico de la población general.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2007. / Härtill 5 uppsatser.