Sprague-Dawley rats were administered daily, subcutaneous injections of methylmercuric chloride at a dose of 5 mg/Hg/kg beginning on postnatal day 5. By their fourth postnatal week, animals exhibited a constellation of neurological signs of motor impairment which resembled the cerebral palsy syndrome of humans perinatally exposed to methylmercury. Routine histological examination of the brain revealed no gross differences between methylmercury-treated (MeHg), normal control (NC) or weight-matched littermates. The histochemical localization of the mitochondrial enzyme cytochrome oxidase (CO) was utilized in Experiment I to examine possible alterations in the metabolic activity of motor nuclei which might contribute to the observed movement and postural disorders. A population of intensely-staining cytochrome oxidase neurons (ICONs) in the magnocellular portion of the red nucleus (RMC) and interrubral mesencephalon (IRM) were conspicuously present in all MeHg animals at the onset of motor impairment. These morphologically, histochemically, and anatomically distinct neurons did not exhibit intense CO staining in control animals. Conversely, a significant decrease was demonstrated in the oxidative metabolic activity of many neurons in the substantia nigra, zona reticulata of MeHg animals. In Experiment II, the postnatal appearance of ICONs was morphometrically quantified in MeHg animals sacrificed at PND 14, 16, 18, 20, 22, or 25. The histochemically-defined onset of increased metabolic activity in ICONs was first observed on PND 16, at least one week before the onset of clinical signs of neurological impairment. This was the earliest manifestation of methylmercury neurotoxicity yet described in this animal model. A subsequent four-fold increase in the total number of ICONs at PND 18 was followed by a gradual decrease in number to PND 25. Significantly more of the ICONs were found in the IRM than in the RMC at PND 18 & 20. The possibility that the increased activity of ICONs may result from disinhibition of specific afferents to the red nucleus was addressed by introducing either hemidecortication or hemicerebellectomy on PND 10 and then morphometrically determining the deviation from symmetry in the bilateral distribution of the total number of ICONs in the RMC and IRM at PND 22. The distribution of ICONs was symmetrical and not different in either hemidecorticate or unoperated controls. A significant (36%) decrease in the total number of ICONs was observed in both the RMC and IRM contralateral to hemicerebellectomy. The identical ipsilateral regions did not differ from control or hemidecorticate MeHg animals. In Experiment III, the anatomical distribution of major histocompatability complex antigens (MHC) in the brain of MeHg animals was examined using immunohistochemical methods. MHC immunoreactivity was widely distributed throughout the brain of MeHg animals. Areas with low immunoreactivity, or lack of it, stand out and include all of the hippocampus, thalamus, pyriform and entorhinal cortex, and lateral cerebellar hemispheres. Moderate staining intensity was observed in neocortical areas, basal forebrain, caudate-putamen and cerebellar vermis. Strong immunoreactivity was found in red nucleus, substantia nigra, cingulate cortex, retrosplenial cortex, presubiculum, parasubiculum and vestibular nuclei. It was suggested that the increased activity of ICONs likely contributes to the movement and postural disorders resulting from methylmercury intoxication. The increased activity in ICONs was determined to be, at least partially, dependent upon cerebellar input. The results are discussed with reference to the toxic effects of methylmercury and specifically to the susceptibility of GABAergic interneurons in perinatal trauma. Possible analogies are drawn between the mechanisms of methylmercury-induced cerebral palsy syndrome and those of other developmental movement and postural disorders. / Medicine, Faculty of / Graduate

No description available.

Kwok, Ka Ming. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 124-146). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABSTRACT / In English --- p.ii / In Chinese --- p.v / LIST OF TABLES --- p.vii / LIST OF FIGURE --- p.ix / ABBREVIATIONS / For Units --- p.x / For Prefixes of the International System of Units --- p.x / For Terms Commonly Used --- p.xi / Role of research workers --- p.xv / Chapter CHAPTER 1 --- Overview of methylmercury / Chapter 1.1 --- Source of methylmercury --- p.1 / Chapter 1.2 --- Toxicokinetics --- p.3 / Chapter 1.2.1 --- Absorption and distribution --- p.3 / Chapter 1.2.2 --- Half-life --- p.5 / Chapter 1.2.3 --- Metabolism/Biotransformation --- p.5 / Chapter 1.2.4 --- Biochemical mechanism of toxicity --- p.7 / Chapter 1.3 --- Health effects of mercury exposure --- p.9 / Chapter 1.3.1 --- Adult central nervous system --- p.10 / Chapter 1.3.2 --- The developing central nervous system --- p.11 / Chapter 1.3.3 --- Cardiovascular effects --- p.13 / Chapter 1.3.4 --- Immunotoxicity --- p.14 / Chapter 1.4 --- Biomarkers for prenatal exposure --- p.15 / Chapter 1.5 --- MeHg exposure in high risk populations in Hong Kong --- p.17 / Chapter CHAPTER 2 --- Neurocognitive performance / Chapter 2.1 --- Introduction --- p.19 / Chapter 2.1.1 --- New Zealand --- p.20 / Chapter 2.1.2 --- Seychelles --- p.21 / Chapter 2.1.3 --- Faroe Islands --- p.22 / Chapter 2.1.4 --- The Hong Kong situation --- p.23 / Chapter 2.2 --- Method --- p.23 / Chapter 2.2.1 --- Subjects and study design --- p.23 / Chapter 2.2.2 --- Questionnaires --- p.24 / Chapter 2.2.3 --- Hg concentration measurement --- p.25 / Chapter 2.2.4 --- Neurocognitive measurements --- p.26 / Chapter 2.2.4.1 --- Hong Kong - Wechsler Intelligence Scale for Children --- p.27 / Chapter 2.2.4.2 --- Hong King List Learning Test --- p.28 / Chapter 2.2.4.3 --- Test of Everyday Attention for Children --- p.29 / Chapter 2.2.4.4 --- Boston Naming Test --- p.31 / Chapter 2.2.4.5 --- Grooved Pegboard Test --- p.31 / Chapter 2.2.5 --- Statistical analysis --- p.32 / Chapter 2.3 --- Results --- p.33 / Chapter 2.3.1 --- Subject characteristic --- p.33 / Chapter 2.3.2 --- Test results --- p.34 / Chapter 2.3.3 --- Statistical analysis results --- p.35 / Chapter 2.4 --- Discussion --- p.36 / Chapter CHAPTER 3 --- Cardiac autonomic function / Chapter 3.1 --- Introduction --- p.60 / Chapter 3.1.1 --- Mechanism --- p.60 / Chapter 3.1.2 --- The association between HRV and the ANS --- p.61 / Chapter 3.1.3 --- Clinical applications and related studies --- p.63 / Chapter 3.1.4 --- Associations between MeHg exposure & HRV --- p.64 / Chapter 3.2 --- Methods --- p.65 / Chapter 3.2.1 --- Subjects and study design --- p.65 / Chapter 3.2.2 --- Physical and HRV measurement --- p.66 / Chapter 3.2.3 --- Time domain analysis --- p.68 / Chapter 3.2.4 --- Frequency domain analysis --- p.68 / Chapter 3.2.5 --- Non-linear method --- p.69 / Chapter 3.2.6 --- Statistical analysis --- p.70 / Chapter 3.3 --- Results --- p.71 / Chapter 3.3.1 --- Subjects characteristics --- p.71 / Chapter 3.3.2 --- HRV and statistical analysis results --- p.71 / Chapter 3.4 --- Discussion --- p.73 / Chapter CHAPTER 4 --- Immuno-toxicity / Chapter 4.1 --- Introduction --- p.91 / Chapter 4.2 --- Methods --- p.96 / Chapter 4.2.1 --- Subjects and Study Design --- p.96 / Chapter 4.2.2 --- Cytokine measurement --- p.96 / Chapter 4.2.3 --- Reversibility --- p.98 / Chapter 4.2.4 --- Statistical Analysis --- p.99 / Chapter 4.3 --- Results --- p.101 / Chapter 4.3.1 --- Subject Characteristics --- p.101 / Chapter 4.3.2 --- Atopic and non-atopic diseases group --- p.101 / Chapter 4.3.3 --- Cytokine profiles --- p.102 / Chapter 4.3.4 --- Reversibility --- p.103 / Chapter 4.4 --- Discussion --- p.104 / Chapter CHAPTER 5 --- Conclusion --- p.119 / Reference List --- p.124

Methylmercury (MeHg) is the most toxic form of Hg to wildlife, partly because of its ability to biomagnify through the food chain. Previous studies have shown that river otter (Lutra canadensis) is particularly susceptible to increased exposure and body burdens of MeHg due to the piscivorous nature of its diet. The objectives of this study were to attempt to establish a relationship between MeHg concentrations in otter tissues and DNA fragmentation using single cell electrophoresis (comet assay) as well as evaluate the effectiveness of the comet assay as a tool in genotoxicity assessment in field samples. Results of preliminary experiments indicate that both time and storage temperature markedly influence the rate of spontaneous DNA degradation. Increased numbers of freeze/thaw cycling also appear to have a negative effect on DNA integrity. In addition, a cell culture experiment was set up to measure the effects of differing levels of MeHg on a neuroblastoma cell line.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 6 uppsatser.

No description available.

Les effets de la contamination au méthylmercure chez le poisson zèbre Danio rerio ont été interrogés au sein de deux tissus, le muscle squelettique et le système nerveux central, dont le choix fut motivé par leur fort potentiel bioaccumulateur de cet organométallique. Après contamination par voie trophique, à un niveau d’exposition représentatif de ce qui peut advenir dans certains écosystèmes aquatiques, nos observations expérimentales indiquent que ce métal perturbe fortement le métabolisme mitochondrial dans les muscles, mais épargne celui du cerveau ; en outre, l’analyse de l’expression génique suggère une perturbation de l’homéostasie du calcium dans ces deux tissus. Dans le système nerveux central, parmi les synapses glutamatergique et GABAnergique, seule la voie métabolique du GABA semble montrer une adaptation face au MeHg. Concernant le muscle squelettique, l’analyse SAGE a permis d’appréhender les impacts du MeHg à l’échelle cellulaire, révélant également une perturbation de la synthèse protéique, l’induction d’un stress au niveau du reticulum endoplasmique ainsi que l’induction de plusieurs gènes impliqués dans les processus de détoxication et les voies de réponse générale au stress. Notre étude a également mis en évidence la surexpression du gène de la vitellogénine dans le muscle chez des poissons mâles désignant ainsi ce métal comme un perturbateur endocrinien. Enfin, nous avons également révélé une perturbation importante de l’éclosion des œufs associée à un transfert maternel de ce toxique. / The effects of methylmercury contamination on the zebrafish, Danio rerio, were assessed in two tissues, the skeletal muscle and the central nervous system, whose choice was motivated by their high potential to bioaccumulate this organometallic. After contamination by dietary, at a representative exposure level of which may arise in some aquatic ecosystems, our experimental observations indicate that metal strongly disrupts the mitochondrial metabolism in the muscles, but savings that the brain; in addition, the gene expression analysis suggests a disruption of the calcium homeostasis in these two tissues. In the central nervous system among glutamatergique and GABAnergique synapses, only the metabolic pathway of the GABA seems to show an adaptation to the MeHg. Concerning the skeletal muscle scanning SAGE analysis helped to understand the impacts of the MeHg at the cellular scale. It is also revealing a disruption of the protein synthesis, the induction of a stress at the endoplasmic reticulum level as well as the induction of several genes involved in detoxification process and general stress response. Our study has also highlighted the induction of the vitellogenin gene in the muscle of male fish designating this metal as an endocrine disruptor. Finally, we have also revealed a significant disruption of hatching eggs associated with maternal transfer of this toxic.

Desde os anos 50 o mercúrio tem chamado a atenção de muitos pesquisadores. No Brasil, a preocupação inicial se restringia à exposição humana pelo seu uso na mineração do ouro. Entretanto, nos últimos anos a atenção de muitos pesquisadores se voltou para outras fontes de exposição, incluindo fontes naturais. Na região Amazônica, os solos são naturalmente ricos em mercúrio. Devido a constante degradação da floresta, o solo se torna mais exposto à ação das chuvas que facilitam a passagem do mercúrio aos rios. Na água o mercúrio sofre um processo de metilação, se transformando em metilmercúrio (MeHg) que se acumula principalmente nos peixes da região. As populações ribeirinhas, que têm sua alimentação baseada no consumo de peixes, são as principais vítimas da exposição a este metal. Muito tem se estudado a respeito dos efeitos tóxicos do metilmercúrio, reconhecido como a forma do mercúrio mais perigosa à saúde humana, devido à alta solubilidade para atravessar barreiras biológicas, capacidade de bioacumulação e elevada meia-vida de eliminação dos tecidos. Dentre os efeitos tóxicos mais documentados do MeHg, encontram-se aqueles relacionados ao sistema nervoso. Entretanto, o sistema cardiovascular tem tomado destaque como um outro alvo a toxicidade do metal. Apesar do número considerável de estudos nesta área, ainda não há um consenso quanto aos mecanismos cardiotóxicos do mercúrio e muitos resultados em estudos clínicos são muito conflitantes. Alguns estudos em ratos sugerem uma relação entre a diminuição de disponibilidade do óxido nítrico (NO), com aumento na exposição ao metilmercúrio. O NO é um componente de extrema importância na fisiologia cardiovascular, porque mantêm o tônus vascular e inibe a agregação plaquetária. Por outro lado, uma dieta rica em peixes e castanhas, comum na região Amazônica, fornece ao organismo quantidades consideráveis de selênio (Se), um nutriente conhecido por propriedades antioxidantes bem como antagonista de efeitos tóxicos de alguns metais, principalmente o mercúrio. Isso sugere que os efeitos danosos do MeHg podem ser minimizados pela presença de selênio na dieta. Neste sentido, o presente estudo avaliou em uma população ribeirinha (n=265), do Rio Tapajós, no Estado do Pará a relação entre as concentrações de mercúrio e selênio em sangue, plasma e cabelo e os níveis de óxido nítrico no plasma. / Since the 1950s, the mercury has attracted attention of many researchers. In Brazil, the initial concern was restricted to human exposure of its use in gold mining. However in the latest years, many researchers have concerned to others exposure sources, including natural sources. In Amazon region, the soils are naturally rich in mercury. Soils become more exposed to rain actions, which provide the passage of mercury to the rivers due to forest degradation. In the water, mercury suffers a methylation process changing to methyl mercury (MeHg), which stores up mainly in the fish of that area. The riverside population, who has a diet based on fish, is the main victims of the exhibition to this metal. The toxic effects of methyl mercury have been studied and this metal is recognized as the most dangerous type of mercury to human health due to the high solubility to cross biological barriers, the capacity of bioaccumulation and the high half-life of elimination from tissues. Among the most studied toxic effects of MeHg, there are those related to the nervous system. However the cardiovascular system has been a highlight as another metal toxicity target. In spite of the large number of studies, there is not an agreement about the cardio toxic mechanisms of mercury and many results in clinical studies are very controversial. Some studies in mice suggest a relationship between the reduction of nitric oxide (NO) and the increase of methyl mercury exposure. Nitric oxide is a very important component in cardiovascular physiology because it maintains the vascular tone and inhibits the platelets aggregation. On the other hand, a diet based on fish and nuts, which are common in Amazon region, provides a large quantity of selenium (Se) to the organism. This nutrient is known by its antioxidant qualities and it is also known as an antagonist of some metal, especially mercury, toxic effects. These facts suggest that the harmful effects of MeHg may be reduced due to the presence of selenium in diet. Therefore, the present study has estimated the relationship among mercury and selenium concentrations in blood, plasma and hair and the nitric oxide levels in plasma, in a riverside population (n=265) of Tapajós River in Pará

Os materiais de referência certificados (MRCs) desempenham importante papel na obtenção de resultados de medições rastreáveis ao Sistema Internacional de Unidades (SI), por meio de uma cadeia contínua de comparações. Dessa forma, a demanda por novos materiais de referência certificados (MRC) aumenta a cada dia em todas as áreas do conhecimento. A disponibilidade de materiais de referência, principalmente no Brasil, ainda é incipiente, face a demanda que excede em muito a variedade disponível desses materiais. Entre as diversas áreas carentes de materiais de referência, destaca-se a área de alimentos pela importância desses produtos na balança comercial do país. A certificação de produtos alimentícios, destinados tanto para exportação como para o consumo interno, requer metodologias de análise que ofereçam resultados precisos e exatos a fim de assegurar a qualidade do produto. Este trabalho descreve a produção e certificação de um material de referência na matriz peixe em mercúrio e metilmercúrio. O estudo reúne desde a etapa de seleção do material, preparação, desenvolvimento dos estudos de homogeneidade e estabilidade e a caracterização. A certificação foi realizada por meio de medições utilizando duas técnicas analíticas, a Espectrofotometria de Absorção Atômica (AAS) com sistema de injeção em fluxo e geração de vapor frio (FIA-CV-AAS) e a Diluição Isotópica aplicada a Espectrometria de Massas (IDMS), sendo este um método primário. Neste trabalho as normas da série ISO 30 (ABNT 3034) e ISO Guide 35 foram utilizadas como base para a preparação e caracterização do material. Para o cálculo de incertezas foi utilizado o GUM e o guia Eurachem. Como resultado, foi produzido e certificado um lote do material em relação ao teor de mercúrio (Hg = 0,271±0,057 μg g-1) e metilmercúrio (MeHg = 0,245±0,038 μg g-1), além de valores informativos de chumbo e arsênio. / The certified reference materials (CRMs) play an important role in obtaining measurement results traceable to the International System of Units, through an unbroken chain of comparisons. Thus, the demand for new certified reference materials (CRMs) increases every day in all areas of knowledge. The availability of reference materials, mainly in Brazil is still incipient, given that the demand far exceeds the available variety of these materials. The amount of certified reference materials available in the country is insufficient to meet the need of the scientific community and demands for development of new methodologies. Among the many areas in need of reference materials, we highlight the importance for the food trade balance for these products within the country. The certification of food products, intended both for export and for domestic consumption, requires analysis methods that provide precise and accurate results to ensure product quality. This paper describes the preparation and certification of a reference material in the fish matrix in mercury and methylmercury. The study brings together since the stage of material selection, preparation, development of homogeneity and stability studies and characterization. The certification was performed by means of measurements using two analytical techniques, flow injection analysis - cold vapor atomic absorption spectrometry (FIA-CV-AAS) and isotope dilution applied to mass spectrometry (IDMS), which is a primary method. In this work the standards of the ISO 30 (ABNT 30-34) and ISO Guide 35 was used as the basis for the preparation and characterization of the material. For the calculation of uncertainties was used the GUM and Eurachem guide. As a result, was produced and certified a lot of material in relation to the concentration of mercury (Hg = 0.271 ± 0.057 mg g-1) and methylmercury (MeHg = 0.245 ± 0.038 mg g-1), and informational values of lead and arsenic .

Made available in DSpace on 2016-08-10T10:55:56Z (GMT). No. of bitstreams: 1 EDER CARDOSO GUIMARAES.pdf: 3304401 bytes, checksum: db6088dee8f8263e53f3cdc4de171fbc (MD5) Previous issue date: 2009-12-02 / The hydrobiogeochemical cycle of mercury contemplates the natural and artificial sources of the metal, as well as the biotic and abiotic processes that occur in the distinct reservoirs and that they determine the transport and setting of the metallic forms in some final receiver. The process of methylation of mercury has deserved special attention in natural and artificial reservoirs in the Amazon region which had the raised toxic of the methylmercury for the human beings and animal, had the bioaccumulates in the aquatic alimentary chain. The present study it deals with the evaluation of total mercury and methylmercury natural levels in biotic and abiotic compartments of the basin of the river Mutum Paraná in the area of influence of the UHE - Jirau in the hidrography basin of the Madeira river. The values of total mercury in the water samples had been slow the 6,5 ng L-1, being approximately 150 lesser times that the values praised for the Ministry the Health for the human consumption, and the levels of the 0,3 methylmercury had been inferior ng L-1. The total mercury texts in the sediment of deep had presented values in the bands of 170+47 - 294+88 μg kg-1 whereas the texts of methylmercury the band of 0,84+0,25 - 1,40+0,35 μg kg-1, being the organic mercury fraction in the sediment in approximately 0.45% of the total mercury supply. The texts of total mercury in plankton and invertebrates had respectively presented values in the bands of 143+24 - 277+25 μg kg-1 and 191+25 - 323+45 μg kg-1, whereas the texts of methylmercury in the band of 4,41+1,22 - 9,76+0,67 μg kg-1 and 16,74+2,57 - 23,99+2,34 μg kg-1 respectively, evidencing the trend of the process of accumulation in the inferior levels of the eutrophic chain. The samples of ichthyofauna of consumption relevant in the traditional population of the study region had presented values of total mercury in the band of 0,06+0,19 - 0,12+0,04 mg kg-1 for the herbivores and omnivorous specimens and 0,28+0,5 0,40+0,1 mg kg-1 for the carnivorous specimens having evidenced the process of bioaccumulation and biomagnification in ichthyofauna. The values of the levels of the species of total methylmercury and methylmercury in the abiotics samples and bioptics had not evidenced points of diffuse contamination. / O ciclo hidrobiogeoquímico do mercúrio contempla as fontes naturais e antrópicas do metal, bem como os processos bióticos e abióticos que ocorrem nos distintos reservatórios e que determinam o transporte e fixação das formas metálicas em algum receptor final. O processo de metilação do mercúrio tem merecido especial atenção em reservatórios naturais e artificiais na região Amazônica devido a elevada toxicidade do metilmercúrio para os seres humanos e animais, devido a bioacumulação e biomagnificação na cadeia alimentar aquática. O presente estudo trata da avaliação dos níveis basais de mercúrio total e metilmercúrio em compartimentos bióticos e abiótico da bacia do rio Mutum Paraná na área de influência da UHE Jirau na bacia hidrográfica do rio Madeira. Os valores de mercúrio total nas amostras de água foram inferiores a 6,5 ng L-1, sendo aproximadamente 150 vezes menores que os valores preconizados pelo Ministério a Saúde para o consumo humano, e os níveis de metilmercúrio foram inferiores a 0,3 ng L-1. Os teores de mercúrio total no sedimento de fundo apresentaram valores nas faixas de 170+47 a 294+88 μg Kg-1 enquanto que os teores de metilmercúrio na faixa de 0,84+0,25 a 1,40+0,35 μg Kg-1, estando a fração de mercúrio orgânico no sedimento em aproximadamente 0,45% do estoque de mercúrio total. Os teores de mercúrio total no plâncton e invertebrados apresentaram valores nas faixas de 143+24 a 277+25 μg Kg-1 e 191+25 a 323+45 μg Kg-1 respectivamente, enquanto que os teores de metilmercúrio na faixa de 4,41+1,22 a 9,76+0,67 μg Kg-1 e 16,74+2,57 a 23,99+2,34 μg Kg-1 respectivamente, evidenciando a tendência do processo de acumulação nos níveis inferiores da cadeia eutrófica. As amostras de ictiofauna de relevante consumo na população tradicional da região de estudo apresentaram valores de mercúrio total na faixa de 0,06+0,19 a 0,12+0,04 mg Kg-1 para os espécimes herbívoras e onívoras e 0,28+0,5 a 0,42+0,1 mg Kg-1 para as espécimes carnívoras evidenciando o processo de bioacumulação e biomagnificação na ictiofauna. Os valores dos níveis das espécies de mercúrio total e metilmercúrio nas amostras abióticas e bióticas não evidenciaram pontos de contaminação difusa.