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Le diagnostic précoce de l'hypothyroïdie permet d'initier le traitement au plus tôt et ainsi de préserver la santé du patient. Le bénéfice du traitement de l'hypothyroïdie franche a été depuis longtemps établi, mais les critères de prise en charge des patients en hypothyroïdie fruste sont encore difficiles à définir. En effet, les symptômes ne sont pas toujours présents et leur appréciation est subjective. Afin d'établir le diagnostic et la prise en charge, le médecin s'appuie sur le dosage de la thyréostimuline (TSH) dans le sang, qui peut éventuellement être complété par le dosage des hormones thyroïdiennes. Le dosage de la TSH, très sensible, peut présenter sur un même échantillon sanguin d'importantes variations qui rendent d'autant plus difficiles la décision du médecin et le suivi du patient. Le polymorphisme naturel de la TSH peut expliquer en partie ces variations. La TSH appartient en effet à la famille des hormones glycoprotéiques et sa glycosylation peut constituer jusqu'à 30% de son poids. Dans le cas de l'hypothyroïdie en particulier, ces glycanes sont modifiés et présentent une plus grande quantité d'acides sialiques terminaux. Ainsi, certaines variations entre les dosages de la TSH, qui freinent actuellement leur harmonisation, peuvent être dues à des différences de reconnaissance de glycoformes par les anticorps utilisés dans les dosages. Dans ce contexte, l'objectif de de ces travaux était de contribuer à la construction de dosages plus performants que ceux actuellement utilisés dans le diagnostic de l'hypothyroïdie. Un nouveau calibrateur recombinant sialylé plus proche de la TSH circulante dans l'hypothyroïdie a alors été produit. De nouvelles associations d'anticorps monoclonaux ont été utilisées pour construire des dosages. Les nouveaux dosages sélectionnés ont ensuite été calibrés avec la TSH sialylée produite et le calibrateur de référence international. Ils ont alors servi à doser plusieurs séries de sérums de patients. Ces travaux ont donc validé l'utilisation d'un nouveau calibrateur d'origine recombinante pour les dosages de la TSH, ce qui devrait à l'harmonisation des dosages existants. / If iodine deficiency is the first cause of low thyroid hormone levels in the world, there are also other etiologies to thyroid disorders. Diagnosis of those allow an early treatment to preserve patient's health. Although there is a general agreement concerning treatment of overt hypothyroidism, treatment of subclinical hypothyroidism is still under debate. In these cases, symptoms are, by definition, not always present. In order to establish diagnosis, the clinicians rely on the measurement of circulating thyroid stimulating hormone (TSH, potentially completed with thyroid hormones measurement). TSH assays are now very sensitive, but can present important between assays variations. The diagnosis and follow up of the patient are consequently complicated. Natural polymorphism of TSH can explain a part of this variability. TSH belongs to the glycoprotein hormones family and its glycans can count for more than 30% of its weight. In hypothyroidism, these glycans are subject of modulation and present higher levels of terminal sialylation. Variation in immuno-assays can be explained by these modifications of sialylation if recognition by antibodies used in immuno-assays is glycosylation dependent. In this context, the aim of this work was to contribute to the construction of new immuno-assays, more reliable in the early diagnosis of subclinical hypothyroidism. During this thesis a new recombinant standard closer to circulating TSH was produced. The total level of sialylation was higher and better mimic the circulating forms in hypothyroidism. In order to select the best antibodies associations in immuno-assays, new antibodies were obtained and associated with commercially available antibodies. New immuno assays improvement is based on the following two approaches: the first one is the use of a new standard which presents glycoformes closer to the circulating TSH and the second one consists in an appropriate selection of antibodies involved in the assays. The new assays were used to measure TSH concentration in blood samples. These studies associated with validation steps allow us to select four assays and constitute a proof of concept for the use of a new sialylated recombinant standard for TSH assays. This can contribute to the needed harmonization of TSH assays.

Le diagnostic précoce de l'hypothyroïdie permet d'initier le traitement au plus tôt et ainsi de préserver la santé du patient. Le bénéfice du traitement de l'hypothyroïdie franche a été depuis longtemps établi, mais les critères de prise en charge des patients en hypothyroïdie fruste sont encore difficiles à définir. En effet, les symptômes ne sont pas toujours présents et leur appréciation est subjective. Afin d'établir le diagnostic et la prise en charge, le médecin s'appuie sur le dosage de la thyréostimuline (TSH) dans le sang, qui peut éventuellement être complété par le dosage des hormones thyroïdiennes. Le dosage de la TSH, très sensible, peut présenter sur un même échantillon sanguin d'importantes variations qui rendent d'autant plus difficiles la décision du médecin et le suivi du patient. Le polymorphisme naturel de la TSH peut expliquer en partie ces variations. La TSH appartient en effet à la famille des hormones glycoprotéiques et sa glycosylation peut constituer jusqu'à 30% de son poids. Dans le cas de l'hypothyroïdie en particulier, ces glycanes sont modifiés et présentent une plus grande quantité d'acides sialiques terminaux. Ainsi, certaines variations entre les dosages de la TSH, qui freinent actuellement leur harmonisation, peuvent être dues à des différences de reconnaissance de glycoformes par les anticorps utilisés dans les dosages. Dans ce contexte, l'objectif de de ces travaux était de contribuer à la construction de dosages plus performants que ceux actuellement utilisés dans le diagnostic de l'hypothyroïdie. Un nouveau calibrateur recombinant sialylé plus proche de la TSH circulante dans l'hypothyroïdie a alors été produit. De nouvelles associations d'anticorps monoclonaux ont été utilisées pour construire des dosages. Les nouveaux dosages sélectionnés ont ensuite été calibrés avec la TSH sialylée produite et le calibrateur de référence international. Ils ont alors servi à doser plusieurs séries de sérums de patients. Ces travaux ont donc validé l'utilisation d'un nouveau calibrateur d'origine recombinante pour les dosages de la TSH, ce qui devrait à l'harmonisation des dosages existants. / If iodine deficiency is the first cause of low thyroid hormone levels in the world, there are also other etiologies to thyroid disorders. Diagnosis of those allow an early treatment to preserve patient's health. Although there is a general agreement concerning treatment of overt hypothyroidism, treatment of subclinical hypothyroidism is still under debate. In these cases, symptoms are, by definition, not always present. In order to establish diagnosis, the clinicians rely on the measurement of circulating thyroid stimulating hormone (TSH, potentially completed with thyroid hormones measurement). TSH assays are now very sensitive, but can present important between assays variations. The diagnosis and follow up of the patient are consequently complicated. Natural polymorphism of TSH can explain a part of this variability. TSH belongs to the glycoprotein hormones family and its glycans can count for more than 30% of its weight. In hypothyroidism, these glycans are subject of modulation and present higher levels of terminal sialylation. Variation in immuno-assays can be explained by these modifications of sialylation if recognition by antibodies used in immuno-assays is glycosylation dependent. In this context, the aim of this work was to contribute to the construction of new immuno-assays, more reliable in the early diagnosis of subclinical hypothyroidism. During this thesis a new recombinant standard closer to circulating TSH was produced. The total level of sialylation was higher and better mimic the circulating forms in hypothyroidism. In order to select the best antibodies associations in immuno-assays, new antibodies were obtained and associated with commercially available antibodies. New immuno assays improvement is based on the following two approaches: the first one is the use of a new standard which presents glycoformes closer to the circulating TSH and the second one consists in an appropriate selection of antibodies involved in the assays. The new assays were used to measure TSH concentration in blood samples. These studies associated with validation steps allow us to select four assays and constitute a proof of concept for the use of a new sialylated recombinant standard for TSH assays. This can contribute to the needed harmonization of TSH assays.

Orientador: Dalton José Carneiro / Banca: Maria Cristina Thomaz / Banca: Elizabeth Romagosa / Resumo: Avaliou-se os efeitos de três doses de 17-a- metiltestosterona (30, 45 e 60 mg) em dietas microencapsuladas em "spray dryer", de três tempos de sua administração (20, 30 e 40 dias) e da dieta testemunha (sem hormônio) administrada por 40 dias, sobre o crescimento, a sobrevivência e a reversão sexual da tilápia do Nilo. Foi utilizado o D.I.C. em esquema fatorial com testemunha (3 x 3 + 1), com três repetições. As 3.000 larvas de tilápia foram distribuídas em 30 caixas de fibrocimento e alimentadas com as dietas microencapsuladas com 37,6 % de PB e 4.480 Kcal de energia bruta kg-1 da dieta. Após cada período de administração, as larvas receberam dietas comerciais sem hormônio, até o final do experimento (90 dias). O baixo crescimento na fase de reversão sexual possibilitou a disponibilidade do hormônio para agir nas gônadas e reverter o sexo dos peixes. Quanto maior foi o tempo de administração das dietas microencapsuladas menor foi o crescimento das larvas na fase de reversão. Aos 90 dias houve um incremento de peso dos peixes para todos os tratamentos. As maiores doses do hormônio e os menores tempos de administração das dietas microencapsuladas contribuíram para obter maior peso corporal dos peixes no final do experimento. A sobrevivência não foi influenciada pelos fatores e apresentou-se baixa. As taxas de reversão sexual foram altas (em torno de 95%) não havendo efeito significativo entre os tratamentos que diferiram somente da testemunha (68,21%). Sugere-se utilizar dietas microencapsuladas contendo a menor dose de hormônio (30 mg) e o menor tempo de administração (20 dias) que garantem valores satisfatórios de reversão sexual. / Abstract: It has been evaluated the effect of three 17-a-metilthestostherone doses (30,45 and 60) on diets microencapsulated on "spray dryer", three administration times (20, 30 and 40 days) and a testimony diet (no hormone) administrated for 40 days, on growth, survival and sexual reversion of the Nile tilapia. It was used a CRD on a factorial scheme with testimony (3 x 3 + 1), with three replicates. The 3.000 tilapia larvae were distributed in 30 fibercement boxes and fed the microencapsulated diets with 37.6% CP and 4,480 Kcal of gross energy kg-1 of the diet. After each administration time, the larvae received commercial diets with no hormone, until the end of the experiment (90 days). The low growth on the sexual reversion phase has made possible the availability of the hormone to actuate on the gonads and revert the fish sex. The longer the administration time of the microencapsulated diets, lower the larvae growth on the reversion phase. At 90 days there was increase on fish weight for all treatments. The highest doses of hormone have contributed to obtain the higher fish body weight at the end of the experiment. Survival has not been influenced by the factors and was low. The sexual reversion rates were high (around 95%) with no significant effect among the treatment, which differed only from the testimony (68.21%). It is suggested to use microencapsulated diets containing the lowest hormone dose (30 mg) and the shortest administration time (20 days) that guarantee satisfactory sexual reversion values. / Mestre

Made available in DSpace on 2014-06-11T19:28:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-12-08Bitstream added on 2014-06-13T19:36:53Z : No. of bitstreams: 1 antonio_c_me_jabo.pdf: 431145 bytes, checksum: 3ca687417b503beacc5530cc37c73eb8 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Avaliou-se os efeitos de três doses de 17-a- metiltestosterona (30, 45 e 60 mg) em dietas microencapsuladas em spray dryer, de três tempos de sua administração (20, 30 e 40 dias) e da dieta testemunha (sem hormônio) administrada por 40 dias, sobre o crescimento, a sobrevivência e a reversão sexual da tilápia do Nilo. Foi utilizado o D.I.C. em esquema fatorial com testemunha (3 x 3 + 1), com três repetições. As 3.000 larvas de tilápia foram distribuídas em 30 caixas de fibrocimento e alimentadas com as dietas microencapsuladas com 37,6 % de PB e 4.480 Kcal de energia bruta kg-1 da dieta. Após cada período de administração, as larvas receberam dietas comerciais sem hormônio, até o final do experimento (90 dias). O baixo crescimento na fase de reversão sexual possibilitou a disponibilidade do hormônio para agir nas gônadas e reverter o sexo dos peixes. Quanto maior foi o tempo de administração das dietas microencapsuladas menor foi o crescimento das larvas na fase de reversão. Aos 90 dias houve um incremento de peso dos peixes para todos os tratamentos. As maiores doses do hormônio e os menores tempos de administração das dietas microencapsuladas contribuíram para obter maior peso corporal dos peixes no final do experimento. A sobrevivência não foi influenciada pelos fatores e apresentou-se baixa. As taxas de reversão sexual foram altas (em torno de 95%) não havendo efeito significativo entre os tratamentos que diferiram somente da testemunha (68,21%). Sugere-se utilizar dietas microencapsuladas contendo a menor dose de hormônio (30 mg) e o menor tempo de administração (20 dias) que garantem valores satisfatórios de reversão sexual. / It has been evaluated the effect of three 17-a-metilthestostherone doses (30,45 and 60) on diets microencapsulated on spray dryer, three administration times (20, 30 and 40 days) and a testimony diet (no hormone) administrated for 40 days, on growth, survival and sexual reversion of the Nile tilapia. It was used a CRD on a factorial scheme with testimony (3 x 3 + 1), with three replicates. The 3.000 tilapia larvae were distributed in 30 fibercement boxes and fed the microencapsulated diets with 37.6% CP and 4,480 Kcal of gross energy kg-1 of the diet. After each administration time, the larvae received commercial diets with no hormone, until the end of the experiment (90 days). The low growth on the sexual reversion phase has made possible the availability of the hormone to actuate on the gonads and revert the fish sex. The longer the administration time of the microencapsulated diets, lower the larvae growth on the reversion phase. At 90 days there was increase on fish weight for all treatments. The highest doses of hormone have contributed to obtain the higher fish body weight at the end of the experiment. Survival has not been influenced by the factors and was low. The sexual reversion rates were high (around 95%) with no significant effect among the treatment, which differed only from the testimony (68.21%). It is suggested to use microencapsulated diets containing the lowest hormone dose (30 mg) and the shortest administration time (20 days) that guarantee satisfactory sexual reversion values.

Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2016-12-15T11:54:43Z No. of bitstreams: 2 Dissertação - Débora Nascimento Sousa - 2016.pdf: 4367047 bytes, checksum: 35c38302a78c568610631ef86cddb6c3 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Jaqueline Silva (jtas29@gmail.com) on 2016-12-15T17:17:55Z (GMT) No. of bitstreams: 2 Dissertação - Débora Nascimento Sousa - 2016.pdf: 4367047 bytes, checksum: 35c38302a78c568610631ef86cddb6c3 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-12-15T17:17:55Z (GMT). No. of bitstreams: 2 Dissertação - Débora Nascimento Sousa - 2016.pdf: 4367047 bytes, checksum: 35c38302a78c568610631ef86cddb6c3 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-10-10 / The depressant used in the iron ore flotation are starches, basically made up of amylose and amylopectin, and the most widely used corn because of its availability and economic viability. The objective was to study the performance of seven starches from different botanical sources in reverse flotation cation of iron ore through Microflotation and flotation test bench cell. We evaluated the influence of different dosage depressants in the buoyancy of the minerals quartz and hematite, the tests used to passing particle size of 180 m and held 75 micrometre (-80 + # 200 #). Any material used in the present study was completely released, ie without the presence of mixed particles. The samples were analyzed chemically and physically by Scanning Electron Microscopy, Energy Dispersive X-ray (EDS) and chemical analysis. In the modified Hallimond tube, we used the following depressants: Conventional corn starch, cassava starch, potato flour, cassava flour HIPIX®100, HIPIX®101 and HIPIX®102, the dosages 400, 800, 1600, 3200 , 4800 and 6400 (g / t) maintaining fixed collector dosage Flotigam EDA Clariant at a dosage of 70 g / t was observed to influence the dosing of depressant tested in floatability of minerals. There was better efficiency in depressant HIPIX®100, HIPIX®101 and cassava starch. In the flotation cell counter, model engendering power was used with 60% hematite and 40% quartz with high purity. is homogenized and the following pre-depressant was tested: Cassava flour, cassava starch, HIPIX®100, HIPIX®101 and normal corn starch (using it as a comparison), the measurements 400, 800 and 1600 (g / t). This single step in flotation cell bench worked as a rougher stage compared to mining companies. The results of Microflotation and flotation bench were statistically analyzed by analysis of variance (ANOVA), checking variation of doses of depressants are factors that influence the recovery of the mineral compared to conventional corn starch. At this stage, the results prove to be technically possible to replace the corn starch in the flotation cation reverse iron ore, apart from replacing the conventional corn starch was noticed that the performance of some starches leads to a lower specific consumption reagent, which can result in economic and environmental gains. / Os depressores utilizados na flotação de minério de ferro são os amidos, constituídos basicamente de amilose e amilopectina, sendo o de milho mais utilizado devido à sua disponibilidade e viabilidade econômica. O objetivo do trabalho foi estudar o desempenho de sete amidos provenientes de diferentes fontes botânicas na flotação catiônica reversa de minério de ferro, através de ensaios de microflotação e flotação em célula de bancada. Foram avaliados a influência da dosagem de diferentes depressores na flotabilidade dos minerais de quartzo e hematita, nos testes utilizou-se granulometria passante em 180 µm e retido 75 µm (-80# + 200#). Todo material utilizado no presente trabalho estava totalmente liberado, ou seja, sem presença de partículas mistas. As amostras foram analisados química e fisicamente por meio de Microscopia Eletrônica de Varredura, Energia Dispersiva de Raios-X (EDS) e análises químicas. No tubo de Hallimond modificado, utilizou-se os seguintes depressores: amidos milho convencional, amido de mandioca, féculas de batata, fécula de mandioca, HIPIX®100, HIPIX®101 e HIPIX®102, nas dosagens 400, 800, 1600, 3200, 4800 e 6400 (g/t) mantendo fixa dosagem de coletor Flotigam EDA da Clariant, na dosagem de 70 g/t, observou-se a influência da dosagem dos depressores testados na flotabilidade dos minerais. Observou-se melhor eficiência nos depressores HIPIX®100, HIPIX®101 e fécula de mandioca. Já na célula de flotação de bancada, modelo ENGENDRAR utilizou-se alimentação com 60% de hematita e 40% de quartzo com alta pureza. Homogeneizou-se previamente e testou-se os seguintes depressores: Fécula de mandioca, amido de mandioca, HIPIX®100, HIPIX®101 e amido de milho convencional (utilizando-o como comparação), nas dosagens 400, 800 e 1600 (g/t). Esta única etapa em célula de flotação em bancada funcionou como uma etapa rougher comparado à empresas de mineração. Os resultados da microflotação e da flotação por bancada foram analisados estatisticamente através da análise de variância (ANOVA), verificando se variação das dosagens dos depressores são fatores que influenciaram na recuperação do mineral comparado ao amido de milho convencional. Nesta etapa os resultados mostram-se possibilidades técnicas para a substituição do amido de milho na flotação catiônica reversa de minérios de ferro, além da substituição do amido de milho convencional, percebeu-se que o desempenho de alguns amidos leva a um menor consumo específico de reagente, o que pode acarretar em ganhos econômicos e ambientais.

Made available in DSpace on 2016-01-26T18:56:29Z (GMT). No. of bitstreams: 1 Wellington Eduardo Xavier Guerra.pdf: 517213 bytes, checksum: e4312a4c04b742d7d293d503e16d7494 (MD5) Previous issue date: 2013-12-13 / In the western region of São Paulo state the cultivation of brassica plants it is commonly indicated B application at planting, because of the lack of information about this element in its type of soil. The objective of this study was to observe the reaction of B dosages in the culture of canola (Brassica napus L. var. oleifera) in Red Sandy Latosol in the Western São Paulo state. The experimental design was a completely randomized type, under a factorial 2 x 4 with 4 replications (two cultivars and four dosages of B). It was evaluated two different cultivars: Hyola 401 and Hyola 76. The concentration of Boron (0,0, 0,5, 1,0 and 2,0 kg B ha-1), was calculated by using boric acid - PA reagent, applied directly to the soil. The biometric parameters analyzed involved: plant height, stem diameter, shoot dry mass, root dry mass, number of branches, production of seeds per plant, seeds moisture content, 1000 grain weight, germination, seed oil content and accumulation of nutrients. All of them were subjected to the analysis of variance by F test, and comparison of means by Tukey test at 5% significance, and polynomial regression analysis through statistical programs. The results indicated that the culture of canola responded doses of B in the parameters of grain weight plant-1, root dry mass and oil percentage to grow Hyola 76. The Hyola 401 had the highest percentage of germination with 0,5 kg B ha-1. But Hyola 76 showed higher germination percentage than Hyola 401. Ratings among the cultivars Hyola 76 had a better performance in all biometric parameters regarding Hyola 401. / Na região oeste do estado de São Paulo para plantas do grupo das brássicas é indicada aplicação de B no plantio, em virtude da carência de informações sobre aplicação de B no solo. O objetivo do trabalho foi avaliar a resposta da cultura da canola (Brassica napus L. var. oleifera) à doses de B em Latossolo Vermelho Arenoso na região oeste paulista. O delineamento experimental adotado foi o delineamento inteiramente casualizados, em esquema fatorial 2 x 4 com 4 repetições (dois cultivares e quatro doses de B), avaliando dois cultivares, Hyola 401 e a Hyola 76. As doses de Boro em forma de ácido bórico P.A foram de (0,0, 0,5, 1,0 e 2,0 kg B ha-1) aplicados no solo. Os parâmetros biométricos analisados foi a altura da planta, diâmetro do caule, massa seca da parte aérea, massa seca da raiz, número de ramificações, massa de sementes por plantas, massa de mil grãos, germinação, teor de óleo e acúmulo de nutrientes. Os dados foram submetidos à análise de variância pelo teste F, comparação das médias pelo de Tukey a 5% de probabilidade e também á análise de regressão polimonial por meio de programa estatístico. Os resultados indicaram que a cultura da canola respondeu as doses de B nos parâmetros de massa de grão planta-1, massa seca da raíz e na porcentagem de óleo para o cultivar Hyola 76. A Hyola 401 apresentou a maior porcentagem de germinação com 0,5 kg B ha-1. Mas a Hyola 76 apresentou maior porcentagem de germinação que a Hyola 401. Nas avaliações entre os cultivares a Hyola 76 teve um melhor desempenho em todos os parâmetros biométricos em relação à Hyola 401.

Made available in DSpace on 2016-07-18T17:51:12Z (GMT). No. of bitstreams: 1 Wellington Eduardo Xavier Guerra.pdf: 517213 bytes, checksum: e4312a4c04b742d7d293d503e16d7494 (MD5) Previous issue date: 2013-12-13 / In the western region of São Paulo state the cultivation of brassica plants it is commonly indicated B application at planting, because of the lack of information about this element in its type of soil. The objective of this study was to observe the reaction of B dosages in the culture of canola (Brassica napus L. var. oleifera) in Red Sandy Latosol in the Western São Paulo state. The experimental design was a completely randomized type, under a factorial 2 x 4 with 4 replications (two cultivars and four dosages of B). It was evaluated two different cultivars: Hyola 401 and Hyola 76. The concentration of Boron (0,0, 0,5, 1,0 and 2,0 kg B ha-1), was calculated by using boric acid - PA reagent, applied directly to the soil. The biometric parameters analyzed involved: plant height, stem diameter, shoot dry mass, root dry mass, number of branches, production of seeds per plant, seeds moisture content, 1000 grain weight, germination, seed oil content and accumulation of nutrients. All of them were subjected to the analysis of variance by F test, and comparison of means by Tukey test at 5% significance, and polynomial regression analysis through statistical programs. The results indicated that the culture of canola responded doses of B in the parameters of grain weight plant-1, root dry mass and oil percentage to grow Hyola 76. The Hyola 401 had the highest percentage of germination with 0,5 kg B ha-1. But Hyola 76 showed higher germination percentage than Hyola 401. Ratings among the cultivars Hyola 76 had a better performance in all biometric parameters regarding Hyola 401. / Na região oeste do estado de São Paulo para plantas do grupo das brássicas é indicada aplicação de B no plantio, em virtude da carência de informações sobre aplicação de B no solo. O objetivo do trabalho foi avaliar a resposta da cultura da canola (Brassica napus L. var. oleifera) à doses de B em Latossolo Vermelho Arenoso na região oeste paulista. O delineamento experimental adotado foi o delineamento inteiramente casualizados, em esquema fatorial 2 x 4 com 4 repetições (dois cultivares e quatro doses de B), avaliando dois cultivares, Hyola 401 e a Hyola 76. As doses de Boro em forma de ácido bórico P.A foram de (0,0, 0,5, 1,0 e 2,0 kg B ha-1) aplicados no solo. Os parâmetros biométricos analisados foi a altura da planta, diâmetro do caule, massa seca da parte aérea, massa seca da raiz, número de ramificações, massa de sementes por plantas, massa de mil grãos, germinação, teor de óleo e acúmulo de nutrientes. Os dados foram submetidos à análise de variância pelo teste F, comparação das médias pelo de Tukey a 5% de probabilidade e também á análise de regressão polimonial por meio de programa estatístico. Os resultados indicaram que a cultura da canola respondeu as doses de B nos parâmetros de massa de grão planta-1, massa seca da raíz e na porcentagem de óleo para o cultivar Hyola 76. A Hyola 401 apresentou a maior porcentagem de germinação com 0,5 kg B ha-1. Mas a Hyola 76 apresentou maior porcentagem de germinação que a Hyola 401. Nas avaliações entre os cultivares a Hyola 76 teve um melhor desempenho em todos os parâmetros biométricos em relação à Hyola 401.

Les glioblastomes sont les tumeurs cérébrales les plus fréquentes avec une incidence en France de l'ordre de 4 nouveaux cas par an et pour 100 000 habitants (2400/ an). Le traitement standard pharmacologique des glioblastomes nouvellement diagnostiqués consiste en première ligne en une administration de témozolomide (75 mg/m2/j) pendant la radiothérapie, suivie d’une consolidation de 6 cycles. Cependant, malgré ce traitement, la médiane de survie n’est que de 15 mois et de 3 à 9 mois pour les rechutes. De nouvelles approches thérapeutiques sont donc indispensables. Parmi elles, ont été évalués le recours à d’autres chimiothérapies (irinotecan) et à l’inhibition de l’angiogénèse. L'angiogenèse est en effet un processus critique dans la progression GBM. L'inhibition de l'angiogenèse, induisant une réduction des vaisseaux sanguins, permet une diminution de l’apport des nutriments et d'oxygène à la tumeur. De manière générale, l’efficacité des traitements du glioblastome est soumise, dans un premier temps, à leur passage intra-cérébral au travers de la barrière hémato-encéphalique (BHE). L’objectif de notre travail était d’une part d’étudier l’impact de l’expression du transporteur d’efflux ABCB1 sur la distribution cérébrale du témozolomide (TMZ) et de l’irinotecan (CPT-11), et d’autre part, d’évaluer le rôle du bevacizumab (BVZ)(inhibiteur de l’angiogénèse) dans la modulation du passage intra-cérébral et intra-tumoral du TMZ et du CPT-11. A l'aide d'une étude pharmacocinétique comparative chez les souris CF1 mdr1a (+/+) et les souris CF1 mdr1a (-/-), nous avons mis en évidence un efflux actif du TMZ, du CPT-11 et de son métabolite actif le SN-38 du cerveau vers le plasma, impliquant ABCB1 au niveau de la BHE. Nous avons également démontré in vivo que le TMZ s'accumule dans la tumeur cérébrale et que le prétraitement par BVZ augmente la distribution tumorale de TMZ. En revanche, le BVZ n’a montré aucun effet sur la distribution cérébrale ou tumorale du CPT-11. Le BVZ apparaitrait donc comme un moyen intéressant d’augmenter la distribution intratumorale du TMZ. Dans ce même objectif, une collaboration initiée dans le cadre de cette thèse a permis de mettre en évidence l’intérêt de l’utilisation d’ultrasons dans l’ouverture de la BHE et l’amélioration de la distribution cérébrale des médicaments. / Glioblastomas are the most common brain tumors occurring in France with an incidence of 4 new cases per year per 100 000 population (2400/year). The gold standard pharmacological treatment of newly diagnosed glioblastoma relies on temozolomide administration (75 mg/m2/d) concomitant to radiotherapy, followed by six cycles consolidation. However, despite this treatment, the median survival is only 15 months and relapse occurs within 3 to 9 months. New therapeutic approaches are needed. Among them, other chemotherapies (irinotecan) and inhibition of angiogenesis were explored. Angiogenesis is a critical process in GBM progression. Inhibition of angiogenesis, inducing a reduction of the blood vessels, reduces supply of nutrients and oxygen to the tumor. The effectiveness of GBM treatment is subjected to intra-brain diffusion through the blood-brain barrier. The objective of this study was firstly to study the impact of efflux transporter ABCB1 brain expression on temozolomide (TMZ) and irinotecan (CPT-11) brain distribution, and secondly, to assess the role of bevacizumab (BVZ)(angiogenesis inhibitor) in the modulation of TMZ and CPT-11 brain and tumor distribution. Using a comparative pharmacokinetic study in CF1 mdr1a (+/+) and CF1 mdr1a (-/-) mice, we demonstrated an active efflux of TMZ, CPT-11 and its active metabolite SN-38 from the brain to the plasma involving ABCB1. We also demonstrated in vivo that TMZ accumulates in brain tumor and BVZ pretreatment increased TMZ tumor distribution. However no effect of BVZ on CPT-11 brain or tumor distribution was evidenced. Therefore BVZ would appear to be an interesting way to increase TMZ tumor distribution. The same objective was pursued through a different approach using ultrasound unfocused to open the BBB (Carthera collaboration).