En raison de leur accumulation possible dans la glande thyroïde, les radio-isotopes de l'iode, 131I (t1/2 = 8,07 jours) et 129I (t1/2 = 15,7 106 ans), sont préoccupants pour la santé humaine. En raison de sa longue demi-vie, 129I est également d’une importance radio-écologique majeure du fait de son intégration potentielle au cycle biogéochimique naturel de son isotope stable (127I). Les forêts dont la surface couvre près du tiers du territoire en France et en Europe, se caractérisent par leur longévité, un haut niveau de recyclage de la biomasse et une forte influence sur les cycles hydrologiques et des nutriments. La végétation forestière peut intercepter puis recycler et accumuler les polluants et radionucléides émis dans l’environnement. Dans ce contexte, des axes de recherche ont été développés dans cette thèse afin de décrire qualitativement et quantitativement le cycle de l’iode et améliorer les prédictions à long-terme du comportement de 129I dans les écosystèmes forestiers.Les pluies constituent une source majeure d’iode pour les sols et la végétation forestière, les quantités apportées dépendant de la distance côtière et de la pluviométrie. La végétation modifie les quantités et la spéciation de l’iode apporté par les pluies. L'humus représente un compartiment d'accumulation provisoire d'iode associé à la matière organique. Ce compartiment constitue également une zone de réémission possible de l’iode par lessivage lors d’évènements pluvieux et/ou par volatilisation. Cette thèse a montré que les teneurs d'iode dans les sols forestiers dépendaient à la fois des apports atmosphériques et des chutes de biomasse, mais également de la capacité du sol à fixer l'iode. Ainsi, les conditions environnementales conduisant à une accumulation de matière organique et la présence d’(hydr)oxydes métalliques dans les sols favorisent la rétention de l’iode. A l’échelle de la placette forestière, le sol constitue le principal réservoir en iode (~99,9%). Du fait de la proportion d'iode au sein des arbres (< 0,03% du stock total en iode), les quantités d’iode recyclées par la végétation sont faibles, l’iode n’étant pas un oligo-élément pour les végétaux. Ainsi ces travaux de thèse ont permis de combler le manque de données relatives d’une part à la répartition de l’iode au sein des écosystèmes forestiers et d’autre part, aux processus de réémissions (lessivage et volatilisation) liés à la dégradation de la matière organique. Les données générées par cette thèse permettent de mieux appréhender la modélisation du cycle de l’iode dans cet écosystème forestier. / As radioisotopes of iodine may concentrate in thyroid gland, 131I (t1/2 = 8.07 days) and 129I (t1/2 = 15.7 106 years) are of health concern. 129I is of major radioecological importance because it can potentially integrate natural biogeochemical cycle of its stable isotope (127I) due to its long half-life. Forests, characterized by their longevity, a high biomass turnover and a strong influence on hydrological and nutrients cycles, can intercept, recycle and accumulate a significant amount of pollutants and radionuclides released into environment. In this context, research developed in this thesis had the purpose of correct long-term prediction of iodine behaviour in forest ecosystems.Rainfall appears to be a significant input flux of iodine in forest soils and vegetation, depending on coastal distance and precipitation amount. Forest canopy modifies quantities and speciation of iodine initially present in rainfall. Humus would act as temporary iodine accumulation layer through its association with organic matter. However, humus layer also behaves as potential iodine mobilisation source by leaching and/or volatilization. This thesis has demonstrated that iodine levels in soils depend both on its atmospheric and litterfall inputs, but also on the soil's ability to fix iodine. Thus, environmental conditions characterized by organic matter accumulation and presence of metal (hydr)oxides in soils promote iodine retention. Thereafter, soil is the main iodine reservoir at the forest plot scale (~99.9%). Given small amounts of iodine in the trees (<0.03% of the total iodine stock), recycling of iodine by vegetation is low, iodine being not an essential element for vegetables.This thesis contributes to fill some gaps in the knowledge of iodine distribution within forests and on the processes of iodine reemission related to organic matter degradation. Data generated by this thesis help to better understand the modeling of iodine cycle in this forest ecosystem.

O excesso de iodo inibe a proliferação celular e secreção hormonal, enquanto retarda os efeitos oncogênicos da ativação de RET/PTC3 na célula folicular tiroidiana. A mutação BRAF (T1799A) é a mais prevalente no câncer de tiroide, e modelo transgênico desenvolve câncer que progride para histotipo agressivo. Altos níveis de microRNAs (miRNAs) do cluster miR-17-92 estão associados a histotipos agressivos de câncer de tiroide e modulam a tradução de mRNAs alvo componentes de vias de sinalização oncogênicas. Neste estudo, avaliamos a influência da alta dose de iodo sobre miRNAs frente ativação do oncogene BRAF e seu efeito na biologia da célula folicular tiroidiana. A indução de BRAFT1799A ativa uma robusta expressão de miR-17-92 enquanto alta dose de iodo bloqueia este efeito na célula tiroidiana. miR-19 inibe a tradução de Smad4 e bloqueia a transdução do sinal de TGFb, efeito revertido pelo iodo. O iodo interfere na expressão de miR-17-92 por bloquear ativação da sinalização Notch induzida por BRAF. Estes resultados indicam que o iodo protege a célula folicular tiroidiana durante a indução de BRAFT1799A, revertendo a ativação dos miRNAs oncogênicos do cluster miR-17-92 e restaurando os níveis protéicos de Smad4 por interferir na via de sinalização Notch. / Iodine excess blocks cell proliferation and inhibits hormone synthesis, while delays oncogenic effects of RET/PTC3 activation in thyroid follicular cells. BRAF mutation (T1799A) is the most prevalent genetic alteration in thyroid cancer, and transgenic mice model for BRAF develops thyroid cancer that progress to aggressive histotypes. High levels of microRNAs (miRNAs) of miR-17-92 cluster are associated to aggressive thyroid cancer and modulate translation of target mRNAs in oncogenic signaling pathways. In this study, we evaluated the influence of high dose iodine in miRNAs under BRAF oncogene activation, and its effects in thyroid follicular cell biology. BRAF induction induces high expression of miR-17-92 while high dose iodine blocks this effect in thyroid follicular cells. miR-19 inhibits Smad4 translation and impairs TGFb signaling transduction, effect reverted by iodine. Iodine modulates miR-17-92 expression by interfering in BRAF-induced Notch signaling activation. These results indicate that iodine protects thyroid follicular cell during BRAF induction, reverting oncogenic miR-17-92 activation and restoring protein levels of Smad4 by Notch signaling modulation.

Esta tese de doutorado está dividida em três partes. Na primeira parte é tratada a expansão de anéis de 1-alquenil-cicloalcanóis promovida por hidróxi(tosilóxi)iodobenzeno (HTIB), com ênfase na síntese de anéis de sete membros. A metodologia se mostrou versátil, possibilitando que diferentes compostos de anéis expandidos pudessem ser obtidos a partir de alcoóis alílicos livres e protegidos. Além disso, foi possível sintetizar uma ceto-lactona de 11 membros a partir da clivagem oxidativa de um dos compostos de anel expandido obtido anteriormente, em bom rendimento num total de quatro etapas. Na segunda parte, está discutida a ciclização de alcoóis homoalílicos promovida por HTIB e iodobenzeno diacetato (DIB) e catalisadas por iodo para obtenção de derivados tetrahidrofurânicos desfavorecidos pelas regras de Baldwin. Foi proposto um mecanismo reacional baseado em intermediários isolados da reação e em precedentes da literatura. Finalmente, na última parte é descrito um estudo do mecanismo de desproporção de DIB e HTIB em acetonitrila por espectrometria de massas de alta resolução por electrospray. Foi mostrado que para o DIB a formação de compostos de I(I) e I(V) passa por intermediários diméricos como [PhI(OH)OIPh]+, [PhI(OAc)OIPh]+, [PhI(OAc)OI(O)Ph]+ e [PhI(O)OAc]+, enquanto que para o HTIB os dímeros [PhI(OH)OIPh]+, [PhIO(OTs)IPh]+ e [PhI(OTs)OI(O)Ph]+, são as principais espécies envolvidas na desproporção. / This thesis is presented in three parts. In the first part, the ring expansion of 1-vinylcycloalkenols promoted by hydroxy(tosyloxy)iodobenzene (HTIB) is discussed. This study focused on the synthesis of seven-membered ring compounds. This reaction is versatile, because different ring expanded molecules could be obtained by slightly changing the reaction conditions. Furthermore, it was possible to synthesize an eleven-membered ring keto-lactone by oxidative cleavage in good yield, achieving a relatively complex structure in four steps. In the second part, the iodine catalysed cyclization of homoallylic alcohols promoted by HTIB and iodobenzene diacetate (DIB) is investigated. This reaction allows to obtain tetrahydrofuran derivatives disfavored by Baldwin\'s rules. A mechanism was proposed based on intermediates isolated from the cyclization and in previous data from literature. Finally, the last part describes the application of high-resolution electrospray mass spectrometry for the elucidation of the disproportionation reaction of DIB and of HTIB in acetonitrile. It is supposed that mechanism of formation of iodine(I) and iodine(V) from DIB involves dimeric intermediates like [[PhI(OH)OIPh]+, [PhI(OAc)OIPh]+, [PhI(OAc)OI(O)Ph]+ and [PhI(O)OAc]+. By the other hand, the main species involved in the disproportionation of HTIB, are the dimers [PhI(OH)OIPh]+, [PhIO(OTs)IPh]+ and [PhI(OTs)OI(O)Ph]+.

<p>This thesis summarizes three novel and general reaction protocols for the synthesis of diaryliodonium salts. All protocols utilize mCPBA as oxidant and the acids used are either TfOH, to obtain triflate salts, or BF3•Et2O that gives the corresponding tetrafluoroborate salts in situ.</p><p>Chapter two describes the reaction of various arenes and aryl iodides, delivering electron-rich and electron-deficient triflates in moderate to excellent yields.</p><p>In chapter three, it is shown that the need of aryl iodides can be circumvented, as molecular iodine can be used together with arenes in a direct one-pot, three-step synthesis of symmetric diaryliodonium triflates.</p><p>The final and fourth chapter describes the development of a sequential one-pot reaction from aryl iodides and boronic acids, delivering symmetric and unsymmetric, electron-rich and electron-deficient iodonium tetrafluoroborates in moderate to excellent yields. This protocol was developed to overcome mechanistic limitations existing in the protocols described in chapter two and three.</p><p>The methodology described in this thesis is the most general, efficient and high-yielding existing up to date, making diaryliodonium salts easily available for various applications in synthesis.</p>

Since the beginning of the nuclear era, starting during the 1940s, large amount of radioactivity has been released into the environment. This thesis deals with the temporal and spatial distribution of the anthropogenic radioisotope 129I (T1/2= 15.7 Myr) in northern Europe. A routine sample preparation procedure for extraction of iodine from milligram amounts of solid materials has been developed and aimed for measuring the 129I concentration by the ultra-sensitive accelerator mass spectrometry method. The technique was further used for the analysis of 129I in sediments collected from two lakes in Sweden and one lake in Finland as well as sediments from two sites in the Baltic Sea. In addition, 129I concentrations in aerosol samples from northern and southern Sweden covering the period 1983 to 2000 have been measured. The results reveal a gradual increase in the anthropogenic 129I fluxes since the 1950s that are linked to emissions from the nuclear fuel reprocessing facilities in Sellafield (UK) and La Hague (France). A sharp increase coinciding with the Chernobyl accident is identified from the Swedish lakes located in areas characterised by relatively high Chernobyl fallout. Numerical modeling of the 129I deposition predicts that &gt;50% of the flux to the lake sediments is related to the liquid emissions from the reprocessing facilities. The modeling also reasonably simulates the contribution of the Chernobyl event to the total 129I flux. The novel time series from northern Europe on 129I in aerosols show about one order of magnitude higher concentration in northern compared to southern Sweden. Estimate of 129I dry fallout based on the aerosol data suggests &lt;25% contribution to the total fallout. The distribution of 129I in the sediment archives demonstrates the potential of the isotope as a new time marker for chronological and environmental investigations.

129I is a radioactive isotope (T1/2= 15.7 million years) produced through natural and anthropogenic pathways, but the anthropogenic production is presently dominating the Earth’s surface environments. Sparse data from previous investigations in the Baltic Sea clearly indicated the occurrence of 129I at levels 3-4 orders higher than natural pre-atomic era (before 1940) without comprehensive evaluation of distribution and inventory. In this thesis extensive data on the distribution and inventory of iodine isotopes, 129I and 127I, and their species in waters of the Baltic Sea, Kattegat and Skagerrak are presented and used for estimation of water masses exchange and impact on the environment.  To fulfill these objectives seawater samples were collected in August 2006 and April 2007 in the Baltic Proper, Kattegat and Skagerrak as well as in December 2009 in the Bothnian Sea. After elaborative chemical separation of total iodine and iodine species, the analysis was performed using ICP-MS for 127I and AMS for 129I. The results reveal considerable differences in 129I concentration in terms of spatial and temporal variability and expose relatively high concentrations in the deep waters. Inventory estimates show higher amounts of 129I in August 2006 (24.2 ±15.4 kg) than in April 2007 (14.4± 8.3 kg) within the southern and central Baltic Proper, whereas almost a constant inventory is found in the Kattegat Basin. Relatively high 127I-/127IO3- and 129I-/129IO3- values in water of the Baltic Proper suggest effective reduction of iodate at a maximum rate of  8×10-7 (127IO3-) and 6×10-14 (129IO3-) (g/m3.day). The combination of 129I and 127I as tracers of water circulation in the Baltic Sea suggest that upwelling deep basinal water occurs into the surface along the Gotland deep and intrusion of North Atlantic water into southern Baltic. Furthermore, 129I-based model inventory reveals inflow of 330 km3/y (230-450 km3/y) water from the Kattegat into the Baltic Proper. Water exchange between the Baltic Proper and the Bothnian Sea and vice versa is estimated at 980 km3/y (600-1400 km3/y) and 1180 km3/y (780-1600 km3/y) respectively. Finally, an environmental assessment of radioactivity associated with 129I burden in the Baltic Sea region is discussed.

Made available in DSpace on 2014-10-09T12:43:21Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:58:04Z (GMT). No. of bitstreams: 1 06428.pdf: 6304808 bytes, checksum: 564076d766d1209b8ce5d2f96ff4876b (MD5) / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Resumo: Na região Amazônica Sul - Ocidental encontram-se espécies cujos frutos encerram quantidade apreciável de óleo com valor econômico para diferentes aplicações industriais, como a produção de biodiesel. O presente trabalho teve como objetivo avaliar o potencial do óleo de tucumã (Astrocaryum aculeatum) para produção de biodiesel. Os frutos de tucumã foram colhidos em áreas ao longo das BR- 364 e BR-317 a aproximadamente 150 km de Rio Branco - AC. Dos frutos, avaliou-se a massa, e posteriormente foram despolpados com a finalidade de separá-los em: polpa (epicarpo + mesocarpo), castanha ou caroço (endocarpo) e amêndoas (semente retirado do interior do endocarpo), cujas massas também foram determinadas. A extração do óleo de cada fração foi feita por prensagem. Foram avaliados os teores de lipídios totais na amêndoa e na polpa, o rendimento aparente da prensa e as características físico-químicas e cromatográficas do óleo extraído. O valor médio de lipídios totais na amêndoa foi de 21,9%, enquanto que o valor médio de lipídios totais na polpa foi de 31,9%. Observou-se um rendimento aparente de 70-73%. Os valores médios de densidade, viscosidade, índice de acidez, índice de iodo, índice de peróxido e índice de saponificação foram, respectivamente, 0,903 ± 0,003 g cm-3; 76,3 ± 1,6 mm2 s-1; 7,11 ± 1,47 mg KOH g-1; 113,84 ± 3,28 g I2 10-2 g-1; 30,79 ± 0,39 meq kg-1; 211,38 ± 1,68 mg KOH g-1. Atrávez da cromatografia gasosa pode se determinar que 56,5% da fração dos ácidos graxo do óleo de tucumã foi constituída por ácidos graxos saturados. O tucumanzeiro é uma espécie que possui boa produtividade em óleo, mesmo em solos ácidos e com baixa fertilidade, apresentando potencial para ser utilizado como uma fonte adicional de renda pelas comunidades da Amazônia / Abstract: In southwestern Amazonia, various plant species produce oil-rich fruits that have economic potential for the production of biodiesel. To evaluate the potential of oils extracted from tucumã palm fruits (Astrocaryum aculeatum), we collected fruits from pasture areas along the BR-364 and BR-317 highways, approximately 150-km from Rio Branco, Acre, Brazil, Fruits were weighed, depulped, and separated into three components: pulp (epicarp + mesocarp), nut or seed (endocarp), and kernel (extracted from the endocarp). Each component was weighed and subjected to oil extraction using a mechanical press. The oil obtained was analyzed for density and viscosity, as well as acidity, iodine, peroxide, and saponification values. The total lipids average content in the kernel was 21.9%, while the mean total lipids content in the pulp was 31.9%. An apparent yield of 70-73% was observed. Physicochemical data analyses revealed significant differences in viscosity and acidity index values among fruit samples. Average density, iodine, peroxide, and saponification values were 0.903 ± 0.003 g cm-3; 76.3 ± 1.6 mm2 s-1; 7,11 ± 1.47 mg KOH g-1; 113.84 ± 3.28 g I2 10-2 g-1; 30.79 ± 0.39 meq kg-1; 211.38 ± 1.68 mg KOH g-1, respectively. Through gas chromatography could determine that 56.5% of fat acids portion in the tucumã oil was saturated fat acids. The tucumã palm is a good oil producer specie, even in acid and low fertility soils, showing a potential to be used as an additional income to be used by the Amazonic communities / Orientador: Wanderley José de Melo / Coorientador: Gabriel Maurício Peruca de Melo / Banca: Afonso Lopes / Banca: Nelson Ramos Stradiotto / Mestre

The aim of this work was to assess the long-term effect of excessive iodine intake on thyroid activity and selected immunological, haematological and biochemical parameters in blood of ewes and their lambs. The experiment was conducted from August 2009 to February 2010 in an experimental barn of Faculty of Agriculture, University of South Bohemia in České Budějovice. Into the experiment were used Šumava sheep breed ewes and their born lambs. Group A (control) consisted of 6 ewes after lambing was extended to 7 born lambs, group B (experimental) 6 of 6 ewes and lambs. Lambs were put into the experiment from the 1st to the 60th day after birth and received iodine in the milk of their mothers. Iodine supplementation to the diet of ewes was launched during the first to second months of pregnancy and finished 60 days after birth. During the experiment, a group of ewes A received 3,1 and group B 5,1 mg iodine per kg of dietary dry matter in the form of calcium iodate. During the experiment was regularly collected blood of ewes (before lambing and 1st, 10th, 30th and 60th day after birth) and lambs (1st, 3rd, 10th, 30th and 60th day after birth) to determine the concentration of thyroid stimulating hormone and immunoglobulin G (ELISA) in blood serum, thyroid hormones (RIA), total protein, urea and alkaline phosphatase activity in the blood plasma (biochemical analyser), the content of haemoglobin, white blood cell´s and red blood cell´s counts and haematocrit values in blood (haematological analyser), percentage of albumin, -1-globulins, -2-globulins, -globulins, and -globulins in blood serum (electrophoresis) and the content of iodine in the blood plasma, urine and milk of ewes (colorimetric method Sandell-Kolthoff). During the experiment were not observed in ewes and lambs clinical symptoms associated with an excessive intake of iodine. In experimental group of ewes with iodine intake 5,1 mg/kg of dietary dry matter were found higher values of thyroid stimulating hormone, lower values of free triiodothyronine, free thyroxine, IgG, white blood cells, -1-globulins, -2-globulin and -globulin, significantly lower values of -globulins after parturition, significantly higher values of urea and alkaline phosphatase activity. The iodine content in blood plasma, milk and urine of ewes is increased in direct proportion to its concentration in diet. Lambs of mothers with iodine intake of 5,1 mg/kg of dietary dry matter were significantly higher values of thyroid stimulating hormone from the 10th day after birth, significantly lower values of free triiodothyronine and free thyroxine first day after birth, immunoglobulin G and -globulins in 30th day after birth, lower (statistically significant in middle samples) values of total protein and white blood cells, higher values of urea and alkaline phosphatase activity. The weight gains of lambs were not significantly affected by iodine supplementation. These results in ewes with iodine intake of 5,1 mg/kg dietary dry matter and especially their lambs drawn to risk of reduce the activity of the thyroid gland and the negative impact of parameters of humoral immunity, mainly IgG and -globulins.

Durante a vida fetal e a infância, os processos fisiológicos da tireoide são peculiares, sendo os hormônios tireoidianos (T3 e T4) essenciais para o crescimento e o desenvolvimento da criança. Os níveis séricos de tireotrofina (TSH) são determinantes no diagnóstico de disfunção tireoidiana. Os dados de normalidade e os fatores que influenciam os níveis de TSH em crianças são pouco conhecidos, sendo que os estudos que disponibilizam esses dados nem sempre são bem conduzidos. A síntese de hormônios tireoidianos é dependente de iodo, e a deficiência desse elemento associa-se a alterações morfológicas e volumétricas da glândula. Os valores de normalidade para volume tireoidiano na infância são influenciados pelas medidas antropométricas e variam entre populações. Atualmente, a deficiência grave de iodo tem dado lugar a patologias relacionadas à ingestão excessiva desse elemento. É importante conhecer as particularidades e os valores de referência para função tireoidiana na infância a fim de evitar prejuízos antropométricos e cognitivos. / Distinct physiological processes occur in the thyroid gland during intrauterine life and childhood, with thyroid hormones (T3 and T4) playing an essential role in growth and development. Serum levels of thyroid-stimulating hormone (TSH) are determining factors of the diagnosis of thyroid dysfunction. Little is known about the normal range of TSH in children and the factors that influence TSH levels in this population, and the few studies that have addressed this issue have not all been well designed and conducted. Thyroid hormone synthesis is iodine-dependent, and iodine deficiency is associated with pathological changes in the morphology and volume of the thyroid gland. The normal range of thyroid volume in children is influenced by anthropomorphic parameters, and varies among populations. Severe iodine deficiency has now been surpassed by conditions associated with excessive iodine intake. Knowledge of the peculiarities of thyroid function in childhood and of the reference ranges of thyroid function tests in this period is important for the prevention of anthropometric and cognitive impairments.