La Bruton tyrosine kinase ou Btk est une protéine dont le rôle dans la maturation des lymphocytes B est connu depuis plusieurs années. Par contre, son rôle dans le contrôle de l’immunité innée est moins établi. Nous avons montré que, en réponse à la voie des Toll like Receptors ou TLRs, Btk régule la stabilité de l’ARN messager du TNF-α par l’intermédiairede la protéine TTP ou Tristétraproline. Par ailleurs, nous avons montré que l’expression d’un microARN, le miR-346, régulait négativement la protéine Btk et donc la synthèse de TNF-α. L’amplification de l’expression de ce miR-346 par transfection permet d’avoir un effet anti-TNF-α et anti-Btk interessant notamment dans le modèle cellulaire de la polyarthrite rhumatoïde. Enfin, nous avons montré que, en réponse au TLRs, la modulation de l’expression du TNF-α en fonction de l’état de méthylation de l’ADN et d’acétylation des histones dépendait directement de l’expression du couple miR-346 et Btk. Btk est donc une protéine charnière dans le contrôle de l’inflammation par les mécanismes épigénétiques que sont les miARNs, la méthylation de l’ADN et l’acétylation des histones. Sur le plan thérapeutique, l’inhibition de cette protéine par ces différents mécanismes de régulation semble donc être très interessante, à la fois dans les maladies inflammatoires et néoplasiques. / Bruton tyrosine kinase, or Btk, is a protein whose role in the maturation of B cells has been known for several years. However, its role in the control of innate immunity is less established. We have shown that, in response to Toll like Receptors pathway or TLRs, Btk regulates the stability of the mRNA of TNF-α via the TTP or Tristetraprolin protein. Furthermore, we showed that the expression of microRNA, the miR-346, negatively regulated the Btk protein and thus the synthesis of TNF-α. Upregulation of miR-346 by transfection act as an anti-TNF-α and anti-Btk drugs, especially in the cellular model of rheumatoid arthritis.Finally, we showed that, in response to TLRs, the modulation of the expression of TNF-α according to the state of DNA methylation and histone acetylation depended directly on crosstalk beetween miR-346 and Btk. Btk is a key protein in the control of inflammation by epigenetic mechanisms such as miRNAs, DNA methylation and histone acetylation. As therapeutic interest, inhibition of Btk by those different regulatory mechanisms seems to be very interesting, both in inflammatory and neoplastic diseases.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-12-15T17:25:29Z No. of bitstreams: 1 marianamonteirodecastro.pdf: 2120293 bytes, checksum: dcba0c3cda52c2a4e9b102a13ed8b6c9 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-12-16T11:25:17Z (GMT) No. of bitstreams: 1 marianamonteirodecastro.pdf: 2120293 bytes, checksum: dcba0c3cda52c2a4e9b102a13ed8b6c9 (MD5) / Made available in DSpace on 2016-12-16T11:25:17Z (GMT). No. of bitstreams: 1 marianamonteirodecastro.pdf: 2120293 bytes, checksum: dcba0c3cda52c2a4e9b102a13ed8b6c9 (MD5) Previous issue date: 2010-02-05 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A vespa social Mischocyttarus cassununga ocorre no sudeste do Brasil, Bahia e Santa Catarina e apresenta fundação do tipo independente por meio de uma fêmea inseminada ou por uma associação destas fêmeas, sendo o papel social dos indivíduos determinado por meio de interações de dominância. O objetivo deste trabalho foi caracterizar o desenvolvimento dos estágios imaturos e analisar a ocorrência de oofagia durante as fases de pré e pós-emergência e sua relação com os fatores climáticos, além de identificar e relacionar as interações de dominância com a atividade forrageadora e verificar a participação da fêmea α no controle das atividades das forrageadoras de M. cassununga nas fases de pré e pós-emergência em ambiente antropizado. O estudo foi realizado em Juiz de Fora de julho/2008 a junho/2009, através de mapeamentos semanais em 60 colônias e de 150h de filmagens em cinco colônias. A duração média dos estágios imaturos nas fases de pré e pós-emergência foram de 13,2 ±4,2 (6-24) e 14,4 ±5,2 (6-28) dias para ovos, 34,8 ±11,9 (15-69) e 32,2 ±7,7 (18-55) para larvas e 17,4 ±6 (7-29) e 18,5 ±5,3 (629) para pupas, respectivamente. Não houve diferença para a duração entre as fases de desenvolvimento e entre as estações do ano. A média registrada da fase de ovo até a emergência adulto foi de 65 dias. Houve maior incidência de oofagia em pré do que em pós (x2=11,852; p=0,007) e diferença para a razão entre oofagia/célula (U=58; p=0,023). Houve maior ocorrência de oofagia na estação chuvosa (x2=53,878; p<0,001). Foram descritos para o etograma cinco atos de dominância e quatro de subordinação. A fêmea α permaneceu na primeira posição do rank, com maior frequência de comportamentos de dominâcia na pré (U=3; p=0,047) e na pós (U=3; p=0,047). Houve correspondência entre o Índice de Dominância e a Matriz de Dominância em 4 das 5 colônias para a posição da fêmea α, que participaram menos das atividades forrageadoras do que as demais na pré (x2=63,131; p<0,001) e na pós (x2=51,882; p<0,001). As saídas foram influenciadas pela fêmea α na pré (x2=10,652; p=0,001) e na pós (x2=52,509; p<0,001). A quantidade de retornos das forrageadoras provenientes de saídas influenciadas em que houve coleta de carboidrato foi superior aos demais na pós (x2=38; p<0,001) e a fêmea α teve participação em todos os retornos com recursos. Foram identificadas diferentes rotas das forrageadoras ao retornarem à colônia com os recursos 7 coletados no forrageio. Portanto, foi verificado que a fêmea α induz as saídas das forrageadoras e controla os retornos das mesmas à colônia. / The social wasp Mischocyttarus cassununga occurs in the southeast of Brazil, Bahia and Santa Catarina and presents independent foundation, by means of an inseminated female or an association of them, where individuals' social function determined by dominance interactions. The aim of this work was to characterize the development of the immature stages and to analyze oophagy occurrence during the pre and post-emergency phases and its relation with the climatic factors, besides to identify and to relate dominance interactions with the foraging activity and to verify the α female participation in foraging activities control of M. cassununga in the pre and post-emergency phases in antropized environment. The study was accomplished in Juiz de Fora from july/2008 to june/2009, through weekly mappings in 60 colonies and of 150h of videotape in five colonies. The average duration of the immature stages in the pre and post-emergency phases went of 13,2 ±4,2 (6-24) and 14,4 ±5,2 (6-28) days for egg, 34,8 ±11,9 (15-69) and 32,2 ±7,7 (18-55) for larvae and 17,4 ±6 (7-29) and 18,5 ±5,3 (6-29) for pupae, respectively. There was no difference on the duration among development phases and seasons. The average registered of the egg phase until the adult emergency belonged to 65 days. There was more oophagy in pre than in post-emergence (x2=11,852; P=0,007) and difference for the reason between oophagy/cells (U=58; P=0,023). There was more oophagy at the rainy season (x2=53,878; P<0,001). For etogram, there were described five dominance acts and four of subordination. The α female remained in the first rank position, with dominance behaviors larger frequency in the pre (U=3; P=0,047) and in the post (U=3; P=0,047). There was correspondence between Dominance's Index and Matrix in 4 of the 5 colonies for the α female position that joined less of the foraging activities than the others in the pre (x2=63,131; P<0,001) and in the post (x2=51,882; P<0,001). The exits were influenced by the α female in the pre (x2=10,652; P=0,001) and in the post (x2=52,509; P<0,001). The numbers of returns originating of foragers exits with carbohydrate collection was superior to the others resources in the post (x2=38; P<0,001) and the α female had participation in all returns with resources. They were identified foragers different routes to the return to the colony with resources collected in the forage. Therefore, It was verified that the α female induces the foragers exits and controls them returns to the colony.

Submitted by Geandra Rodrigues (geandrar@gmail.com) on 2018-01-19T16:53:31Z No. of bitstreams: 1 humbertovargasduque.pdf: 4514345 bytes, checksum: 706c4aafb25bb9c14ffc14039c8c53d0 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-01-24T11:47:55Z (GMT) No. of bitstreams: 1 humbertovargasduque.pdf: 4514345 bytes, checksum: 706c4aafb25bb9c14ffc14039c8c53d0 (MD5) / Made available in DSpace on 2018-01-24T11:47:55Z (GMT). No. of bitstreams: 1 humbertovargasduque.pdf: 4514345 bytes, checksum: 706c4aafb25bb9c14ffc14039c8c53d0 (MD5) Previous issue date: 2016-07-29 / O avanço dos estudos teóricos e experimentais dos processos de interação de radiações ionizantes com o DNA [1]–[7] demonstrou que estas radiações, ao interagirem com sistemas biológicos, podem levar à produção de um número significativo de elétrons secundários. Tais elétrons, por sua vez, ao realizarem colisões inelásticas com biomoléculas, as levam a estados excitados (estados vibracionais e eletrônicos) e à produção de estados ressonantes. Estudos recentes [1], [3], [6] reportam que estes processos têm a real capacidade de causar mutação celular ou necrose, devido à simples e dupla quebra da cadeia de DNA, possuindo, portanto, grande potencialidade danosa a qualquer tecido vivo. Com o intuito de entender melhor estas interações de elétrons de baixa energia com as espécies encontradas em sistemas biológicos, no presente trabalho utilizou-se a Espectroscopia de Perda de Energia de Elétrons para estudar as seções de choque diferenciais (SCD) e integrais (SCI). A região de energias de impacto utilizada foi capaz de promover excitação de níveis vibracionais do tetrahidrofurano (THF) e do álcool α-tetrahidrofurfuril (THFA - α-tetrahydrofurfuryl álcool) e bandas de Rydberg de estados eletrônicos do THFA. Estas espécies moleculares foram escolhidas por serem quimicamente análogas aos anéis de açúcar presentes na estrutura do fosfato-desoxirribose, constituintes do DNA, sendo THFA identificado recentemente, como uma melhor opção análoga à estrutura desoxirribose, quando comparado a sua espécie química semelhante, a molécula de THF. As energias de impacto de elétrons utilizadas para o THFA, foram de 20, 30, 40 e 50eV, enquanto o intervalo angular dos elétrons espalhados foi de 10°- 90°. Já para a molécula de THF, tais energias foram de 15, 20, 30 e 50eV, enquanto que os processos de espalhamento foram estudados na faixa angular de 15º - 90º. Nesse sentido, as SCD’s e SCI’s de THFA, apresentaram sutil diferença das obtidas por Khakoo et al. [8] para THF, em razão de suas propriedades físico-químicas diversas. A importância do momento de dipolo e polarizabilidade das moléculas nos espalhamentos de elétrons foi verificada, principalmente seus reflexos nas SCD’s para os baixos ângulos de espalhamento (≤30°). Foram utilizados, ainda, cálculos teóricos, realizados pela parte teórica deste grupo de pesquisa, para a comparação com os dados experimentais aqui apresentados, obtendo-se excelente concordância, o que levou a comprovação dos modelos utilizados. Ademais, realizou-se a revisão do trabalho de Garland et al. [9], o que demonstrou que a faixa de energia e os poucos modos vibracionais considerados em seu trabalho, derivados de Allan [10], deixam a desejar no que tange a completude dos estudos das propriedades de transporte. A apresentação do trabalho inclui primeiramente os embasamentos teóricos importantes para a análise dos dados obtidos e dos cálculos teóricos realizados. Posteriormente, é apresentado uma descrição do Espectrômetro de Perda de Energia de Elétrons utilizado e a estrutura de análise de dados. Por fim, são apresentados os dados experimentais e teóricos obtidos no trabalho e as discussões. Adicionalmente, é feita uma revisão do conjunto de dados de excitações de estados vibracionais do THF utilizados em outros estudos publicados na literatura, para a obtenção de propriedades de transporte de elétrons neste gás. / The progress of theoretical and experimental studies of ionizing radiation interaction processes with DNA [1]–[7] demonstrated that such radiation when interacting with biological systems can lead to the production of a significant number of secondary electrons. These electrons, in turn, carry the inelastic collisions with biomolecules, leading to the excited states (vibrational and electronic states) and the production of resonant states. Recent studies [1], [3], [6] report that those processes have the actual ability to cause cell mutation or necrosis, due to single and double break of the DNA chain, having therefore, great potential harmful to any living tissue. In order to better understand these interactions of low-energy electrons with the species found in biological systems, we used in this thesis the Electron Energy Loss Spectroscopy to study the differential (DCS) and integral cross sections (ICS). The region of impact energies used was able to promote excitation of vibrational levels of the tetrahydrofuran (THF) and α-tetrahydrofurfuryl alcohol (THFA), and bands of electronic Rydberg states of TFA. These molecular species were chosen because they are chemically similar to sugar rings present in phosphate-deoxyribose structure, DNA constituents, and the THFA recently identified as a best analogous option for deoxyribose structure, when compared to their similar chemical species, the THF molecule. The electron impact energies used for THFA, were 20, 30, 40 and 50eV, while the angular interval of the scattered electrons was 10 ° - 90 °. The THF molecule was studied for energies of 15, 20, 30 and 50eV, while scattering processes were studied in the angular range of 15º - 90º. In this sense, the DCS's and ICS's of THFA showed subtle difference from those obtained by Khakoo et al. [8] for THF, because of their different physical and chemical properties. The role of the dipole moment and polarizability of the molecules in the electron scattering process was observed, especially its effects on DCS's for low scattering angles (≤30 °). Theoretical calculations, carried out by the theoretical part of this research group, were used also in order to compare with the experimental data presented here, resulting in an excellent agreement, which led to confirmation of the models used. In addition, there was a review of work of Garland et al. [9], which has shown that the energy range and the few vibrational modes considered in their work, derived from Allan [10], were underestimating the role of vibrational excitation with respect to completion of studies of the transport properties. The presentation of this work firstly includes the important theoretical background for data analysis and theoretical calculations performed. Posteriorly, is presented a description of the Electron Energy Loss Spectrometer used and the data analysis framework applied. Finally, the experimental and theoretical data at work and discussions are presented. Additionally, is made a review of the set of vibrational states excitations data of THF used in other studies published in the literature for obtaining electron transport properties of this gas.

Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2015-02-03T09:34:31Z No. of bitstreams: 2 Dissertacao - Sandro de Melo Braga - 2014.pdf: 4351893 bytes, checksum: abf7d37b6f843e30fee499929c15eb91 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2015-02-05T13:09:32Z (GMT) No. of bitstreams: 2 Dissertacao - Sandro de Melo Braga - 2014.pdf: 4351893 bytes, checksum: abf7d37b6f843e30fee499929c15eb91 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-02-05T13:09:32Z (GMT). No. of bitstreams: 2 Dissertacao - Sandro de Melo Braga - 2014.pdf: 4351893 bytes, checksum: abf7d37b6f843e30fee499929c15eb91 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-07-15 / Agonist drugs α-2 adrenergic receptors are used in veterinary medicine to promote sedation, analgesia and muscle relaxation. In horses with xylazine and detomidine are used in preanesthetic medication such as sedatives for procedures or surgeries in the standing position with the aid of locoregional anesthesia in analgesic infusions associated with general anesthesia for invasive procedures, or associated with dissociative drugs to anesthesia Overall the equine field. In the first study aimed to evaluate the sedative, gastrointestinal, cardiovascular and blood gas of xylazine and detomidine administered at different doses in horses effects. Eight horses, four males and four females, aged between five and 15 years, weighing 276.58±9.23 kg were used. The experimental design was randomized crossover using animals of six different occasions to receive: xylazine 0.5 mg/kg (X05), 1.0 mg/kg (X1), 1.5 mg/kg (X15); 20μg/kg detomidine (D20), 40 mg/kg (D40) and 60μg/kg (D60). The parameters evaluated were heart rate (HR); the electrocardiogram (ECG); respiratory frequency (f); systolic blood pressure (SBP), diastolic (DBP) and mean (MAP) by invasive method; Sedation (RAC); rectal temperature (T); intestinal motility (MI); blood gases and electrolytes. Some showed similar results to those previously reported with xylazine and detomidine as good sedation, significant reduction of HR and f, however, there was an increase in BP lasting with increasing dose of detomidine, as well as a reduction in intestinal motility for periods there are 180 minutes with the same drug. In the review of blood gas analysis showed a decrease in PaO 2 and increase in PaCO 2 in arterial blood, indicative of respiratory depression, increased bicarbonate ion (HCO 3 -) and base excess, however they remained within normal limits for the species. It follows that promotes more efficient detomidine sedation, however promotes a greater depression in cardiac system and intestinal motility compared with xylazine in horses. In the second study aimed to evaluate the sedative, cardiovascular and echodopplercardiographic effects of xylazine and detomidine in horses. Six horses, two males and four females, aged between five and 15 years, weighing 276.58 ± 9.23 kg were used . The animals used in randomized crossover design twice for receiving xylazine 1.0 mg/kg (GX) detomidine or 40 µg/kg (GD), administered intravenously. In addition to the parameters evaluated in the first phase of the study, also cardiac output (CO), cardiac index (CI), aortic diameter (AD), ejection fraction (FE) and fractional shortening (FS) by echocardiography were recorded. The results showed intense cardiorespiratory depression in animals that received detomidine, however with greater sedative effects compared to xylazine group. BP values showed an initial increase only in the detomidine group, lasting approximately 30 minutes and subsequent reduction of the values, without characterizing hypertension and hypotension. In echodopplercardiographic evaluation, the GD had major depression in ventricular function parameters, for the group GX and this review was efficient compared with values obtained in other studies by methods already established. It is concluded that detomidine sedation promotes more efficient compared to xylazine in horses, however the depressive effects on cardiovascular variables are evaluated by echocardiogram greatest method. / Em equinos a xilazina e a detomidina são utilizadas na medicação pré-anestésica, como sedativos para procedimentos ou cirurgias em posição quadrupedal com o auxílio de anestesia locorregional, em infusões analgésicas associadas à anestesia geral para procedimentos invasivos, ou associadas a fármacos dissociativos na manutenção da anestesia geral a campo. No primeiro estudo objetivou-se avaliar os efeitos sedativos, gastrointestinais, cardiovasculares e hemogasométricos da xilazina e da detomidina administradas em diferentes doses em equinos. Foram utilizados oito equinos, quatro machos e quatro fêmeas, com idade entre cinco e 15 anos, pesando 276,58 ± 9,23 kg. O delineamento foi cruzado aleatório, utilizando os animais em seis ocasiões diferentes para receberem: xilazina 0,5 mg/kg (X05), 1,0 mg/kg (X1), 1,5 mg/kg (X15), detomidina 20 µg/kg (D20), 40 µg/kg (D40) e 60 µg/kg (D60). Os parâmetros avaliados foram frequência cardíaca (FC); traçado eletrocardiográfico (ECG); frequência respiratória (f); pressões arteriais sistólica (PAS), diastólica (PAD) e média (PAM) pelo método invasivo; grau de sedação (SD); temperatura retal (T); motilidade intestinal (MI); gases sanguíneos e eletrólitos. Foram obtidos resultados similares aos descritos na literatura com xilazina e detomidina, como boa sedação, redução significativa da FC e f, no entanto, observou-se aumento duradouro da PA com o incremento da dose de detomidina, assim como redução na motilidade intestinal por períodos superiores a 180 minutos, com o mesmo fármaco. Houve redução da PaO 2 e aumento da PaCO 2 e do bicarbonato(HCO3) -com déficit de base. No entanto os valores permaneceram dentro dos limites de normalidade para a espécie. Concluiu-se que a detomidina promove sedação mais eficiente, no entanto induz maior depressão cardiorrespiratória e da motilidade intestinal, quando comparada à xilazina em equinos. No segundo ensaio objetivou-se avaliar os efeitos sedativos, cardiovasculares e ecodopplercardiográficos da xilazina e da detomidina em equinos. Foram utilizados seis equinos, dois machos e quatro fêmeas, com idade entre cinco e 15 anos, pesando 276,58 ± 9,23 kg. Os animais foram usados em delineamento cruzado aleatório, para receberem xilazina, 1,0 mg/kg (GX) ou detomidina 40 µg/kg (GD), pela via endovenosa. Além dos parâmetros avaliados na primeira fase do estudo, também foram registrados débito cardíaco (DC), índice cardíaco (IC), diâmetro da aorta (DA), fração de ejeção (FE) e fração de encurtamento (FS), por ecodopplercardiografia. Houve depressão cardiorrespiratória e efeito sedativo mais intensos nos animais que receberam detomidina. Os valores de PA apresentaram aumento inicial apenas no grupo detomidina, com duração de aproximadamente 30 minutos e posterior redução dos valores, sem caracterizar hipertensão ou hipotensão. Na avaliação ecodopplercardiográfica o GD apresentou maior depressão nos parâmetros de função ventricular, em relação ao GX. Com base nos valores obtidos em outros estudos utilizando métodos já consagrados, observou-se que a ecodopplercardiografia foi eficiente na avaliação hemodinâmica de equinos. Conclui-se que a detomidina promove sedação mais eficiente comparada à xilazina em equinos, no entanto os efeitos depressivos sobre as variáveis cardiovasculares são maiores, conforme avaliação ecodopplercardiográfica

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2016-09-16T15:27:12Z No. of bitstreams: 2 Dissertação - Marcia Felipe Mendes - 2016.pdf: 3733938 bytes, checksum: a83e0262d1671e990c617cd0061f8d2f (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-09-16T15:27:41Z (GMT) No. of bitstreams: 2 Dissertação - Marcia Felipe Mendes - 2016.pdf: 3733938 bytes, checksum: a83e0262d1671e990c617cd0061f8d2f (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-09-16T15:27:41Z (GMT). No. of bitstreams: 2 Dissertação - Marcia Felipe Mendes - 2016.pdf: 3733938 bytes, checksum: a83e0262d1671e990c617cd0061f8d2f (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-02-26 / Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG / Because of the toxicological relevance of pesticides introduced into the environment through agricultural practices, it is necessary to develop simple methodologies with low cost, enabling remove these pollutants from the environment, in particular of water intended for human consumption. The adsorption process is an efficient and low cost technique that have wide application. The adsorbent capacity of the leaves of Typha angustifolia L. herbaceous perennial plant belonging to the family Typhaceae, in Brazil it is also popularly known as taboa, was investigated for the removal of pesticides trifluralin, chlorpyrifos and α-endosulfan from aqueous medium. The the analytical method using solid phase extraction (SPE) and chromatography with electron capture detector (GC/ECD) was optimizates and validate. The validation criterions were reached and the analytical methos was considered efficient for trifluralin, chlorpyrifos and α-endosulfan quantification in an aqueous medium, providing credibility to the results obtained in the adsorption experiments. The adsorption capacity of T. angustifolia was evaluated under different parameters: treatment of the material, amount of material, contact time between the plant material and the pesticides solution and concentration of the pesticides solution. The results showed that treatment of the material with distilled water and was satisfactory and, for all doses evaluated the pesticide removal was efficient, with best results obtained at a dose of 3.0 g L-1 , equivalent to 60 mg of adsorbent in 20.0 mL of solution, in which the pesticide removal were between 73 and 80%. The adsorption kinetics of the pesticide by T. angustifolia showed that the adsorption equilibrium was reached in 40 minutes for all pesticides, removing up to 90% and using a very small amount of plant material (3 g L-1 ). The experimental data were evaluated using the kinetic models of pseudo-first order, pseudo-second order and Avrami. One of the limitations encountered in the concentration influence study is the limited solubility of the agrochemical in aqueous medium (between 0.33 and 1.00 mg L-1 ), resulting in the study of a small concentration range in the adsorption experiments. To study the pesticides adsorption mechanism by T. angustifolia material, the experimental data were applied to Langmuir, Freundlich and Sips non-linear isotherms models. Additional tests showed that the adsorption capacity is unaffected when using natural water in the adsorption experiments. The results indicate that the material obtained from of T. angustifolia leaves, has a great potential to be used as an alternative adsorbent material in pesticide contaminated aqueous solution treatment. / Devido à relevância toxicológica dos agrotóxicos introduzidos no ambiente através de práticas agrícolas, torna-se necessário o desenvolvimento de metodologias simples e de baixo custo, que permitam remover esses poluentes do meio ambiente, em especial, das águas destinadas a consumo humano. O processo de adsorção é uma técnica que possui grande aplicação, por ser eficiente e de baixo custo. A capacidade adsorvente das folhas de Typha angustifolia L., planta herbácea perene pertencente à família Typhaceae, no Brasil também conhecida popularmente como taboa, foi investigada para a remoção dos agrotóxicos trifluralina, clorpirifós e α-endossulfam de meio aquoso. Foi realizada a otimização e validação da metodologia analítica de extração em fase sólida (SPE) e determinação por cromatografia gasosa utilizando-se o detector por captura de elétrons (GC/ECD). A metodologia (SPEGC/ECD) atendeu aos critérios de validação estabelecidos e foi eficiente para a quantificação dos agrotóxicos em meio aquoso, fornecendo credibilidade aos resultados obtidos nos ensaios de adsorção. A capacidade de adsorção da T. angustifolia foi avaliada sob diferentes parâmetros: tratamento do material, dose de material, tempo de contato entre o material vegetal e a solução dos agrotóxicos e concentração dos agrotóxicos na solução. Os resultados obtidos mostraram que o tratamento do material com água destilada foi satisfatório e que para todas as doses de adsorvente avaliadas a remoção dos agrotóxicos foi eficiente, sendo obtido um melhor resultado para a dose de 3,0 g L-1 , equivalente a 60 mg de adsorvente para 20,00 mL de solução, onde se obteve remoção entre 73 e 80% dos agrotóxicos. O estudo cinético do processo de adsorção dos agrotóxicos pela T. angustifolia mostrou que o equilíbrio de adsorção foi alcançado em 40 minutos, para todos os agrotóxicos, com remoção de até 90%, utilizando uma dose muito pequena de material vegetal (3 g L-1 ). Os dados experimentais foram avaliados utilizando-se os modelos cinéticos de pseudo-primeira ordem, pseudo-segunda ordem e Avrami. Uma das limitações encontradas no estudo da influência da concentração foi a solubilidade limitada dos agrotóxicos em meio aquoso (entre 0,33 e 1,00 mg L-1 ), que fez com que os ensaios de adsorção fossem avaliados para uma pequena faixa de concentração. Para estudar o mecanismo de adsorção dos agrotóxicos pelo material T. angustifolia, os dados experimentais foram aplicados aos modelos não lineares de Langmuir, Freundlich e Sips. Ensaios adicionais mostraram que a capacidade de adsorção é pouco afetada quando se utiliza água natural obtida em represas nos ensaios de adsorção. Os resultados obtidos indicam que o material vegetal, obtido a partir das folhas de T. angustifolia, possui um grande potencial para ser utilizado como material adsorvente alternativo no tratamento de meio aquoso contaminado com os agrotóxicos trifluralina, clorpirifós e α-endossulfam.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-02-03T13:11:46Z No. of bitstreams: 1 caiocesardesouzaalves.pdf: 1872262 bytes, checksum: f03fadd9407262d508f6744a7f73820f (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-02-03T13:14:01Z (GMT) No. of bitstreams: 1 caiocesardesouzaalves.pdf: 1872262 bytes, checksum: f03fadd9407262d508f6744a7f73820f (MD5) / Made available in DSpace on 2017-02-03T13:14:01Z (GMT). No. of bitstreams: 1 caiocesardesouzaalves.pdf: 1872262 bytes, checksum: f03fadd9407262d508f6744a7f73820f (MD5) Previous issue date: 2007-08-30 / A Paracoccidioidomicose é uma micose sistêmica humana causada pelo fungo dimórfico, Paracoccidioides brasiliensis, que acomete, principalmente, indivíduos adultos do sexo masculino. O presente estudo propôs a padronização do modelo de infecção com P. brasiliensis pela via intratorácica em camundongos BALB/c. Este estudo foi monitorado pela detecção do P. brasiliensis através da contagem de unidades formadoras de colônia e pela presença de DNA do fungo nos pulmões dos animais infectados em diferentes pontos pósinfecção (2o, 7o, 15o, 30o, 45o, 60o e 90o dias) e a taxa de sobrevida dos camundongos. Além disto, foram avaliados alguns parâmetros imunológicos como a produção de óxido nítrico, TNF-alpha, IFN-gama, e IL-10 por células presentes no lavado intratorácico, contagem total e diferencial do número de células do lavado intratorácico, o estudo histopatológico dos pulmões e a detecção de anticorpos específicos anti-P. brasiliensis nos pulmões e no soro. Os resultados mostram um aumento gradual do número de colônias e de DNA de P. brasiliensis nos pulmões. Até o 15o dia após a infecção pode ser observado um aumento na produção de óxido nítrico e IFN-gama pelas células do lavado intratorácico, bem como um aumento do número total de células e da porcentagem de leucócitos mononucleares. A partir do 30o dia após a infecção observa-se um aumento de anticorpos específicos (IgG1) no soro e no pulmão, um aumento da produção de IL-10 e TNF-alpha pelas células do lavado intratorácico e conseqüente diminuição da produção de IFN-gama e óxido nítrico. Além disso, observa-se um aumento da porcentagem de células polimorfonucleares no lavado. No estudo histopatológico pode ser constatado um aumento gradual no tamanho e complexidade dos granulomas presentes nos cortes histológicos. Os camundongos utilizados no estudo de sobrevida começaram a morrer no 60o dia após a infecção. Os resultados mostram uma resposta inicial do hospedeiro com um perfil Th1 mudando durante a infecção para uma resposta Th2 que leva ao óbito dos camundongos BALB/c. / Paracoccidioidomycosis or South American blastomycosis, is a chronic granulomatous human male infection caused by the Paracoccidioides brasiliensis. The present study it considered the standardization of the model of infection with P. brasiliensis for the intrathoracic route in BALB/c mice. This study was monitored by the detection of the P. brasiliensis through the counting of colony forming units and by the presence of DNA of fungi in the lungs of the infected animals in different points (2, 7, 15, 30, 45, 60 and 90 days) and the survival rate of the mice. Moreover, some immune parameters had been evaluated as the nitric oxide production, TNF-alpha, IFN-gamma, and IL-10 for cells in the intrathoracic washed, total and distinguishing counting of cells of the intrathoracic washed, the lung histopathology and the detection of specific antibodies anti-P. brasiliensis in the lungs and serum. The results show a gradual increase of the number of colonies and P. brasiliensis DNA in the lungs. Until 15 day after the infection can be observed an increase in the nitric oxide production and IFN-gamma for the cells of the washed, as well as an increase of the total number of cells and the percentage of mononuclear. From 30 day after the infection observes an increase of specific antibodies (IgG1) in the serum and the lung, an increase of the production of IL-10 and TNF-alpha for the cells of the washed and consequent reduction of the IFN-gamma production and nitric oxide. Moreover, observed an increase of the percentage of cells polimorphonuclear in the washed. In the histopathology it can be evidenced a gradual increase in the size and complexity of granulomas in the cuts. The mice used in the survival study had started to die in 60 day after the infection. The results show an initial reply of the host with a Th1 profile moving during the infection for a Th2 reply that leads to the death of the BALB/c mice.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-06-21T11:43:47Z No. of bitstreams: 1 alexandresilvachaves.pdf: 1552343 bytes, checksum: e93b7672976058e0adc057d62686adba (MD5) / Rejected by Adriana Oliveira (adriana.oliveira@ufjf.edu.br), reason: on 2017-06-21T12:22:29Z (GMT) / Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-06-21T12:24:25Z No. of bitstreams: 1 alexandresilvachaves.pdf: 1552343 bytes, checksum: e93b7672976058e0adc057d62686adba (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-08-07T19:04:35Z (GMT) No. of bitstreams: 1 alexandresilvachaves.pdf: 1552343 bytes, checksum: e93b7672976058e0adc057d62686adba (MD5) / Made available in DSpace on 2017-08-07T19:04:35Z (GMT). No. of bitstreams: 1 alexandresilvachaves.pdf: 1552343 bytes, checksum: e93b7672976058e0adc057d62686adba (MD5) Previous issue date: 2014-08-29 / A tuberculose é uma doença infecciosa cujo principal agente etiológico é o Mycobacterium tuberculosis (Mtb). Macrófagos constituem a primeira linha de defesa contra a tuberculose, bem como o habitat preferencial para o Mtb. Antígenos específicos do Mtb tais como ESAT-6, CFP-10 e Rv1733 podem modular a produção de citocinas, influenciando o curso da infecção. Macrófagos infectados liberam uma grande quantidade de citocinas incluindo fator de necrose tumoral-alfa (TNF-a). As ações do TNF-a são iniciadas por seus dois receptores de membrana, mTNF-R1 e mTNF-R2, os quais podem sofrer clivagem proteolítica, resultando nas formas solúveis sTNF-R1 e sTNF-R2, respectivamente. No presente estudo, macrófagos RAW264.7 (2x105/mL) foram estimulados com a proteína de fusão ESAT6:CFP10 ou com o antígeno recombinante DosR, Rv1733, na concentração de 5pg/mL por 24 e 48 horas e a produção de TNF-a, bem como a expressão dos mTNF-Rs e concentração dos sTNF-Rs foram investigadas. Os sobrenadantes de cultura foram coletados e os níveis de TNF-a, IL-10, sTNF-R1 e sTNF-R2 foram avaliados por ELISA, enquanto que os níveis de óxido nítrico (NO) foram analisados pela reação de Griess. A determinação da viabilidade celular foi realizada pelo ensaio de MTT. Níveis de mTNF-R1 e mTNF-R2 foram analisados por citometria de fluxo e a expressão de iNOS e Arg-1 determinada por imunocitoquímica. Os resultados mostraram que ambos os antígenos induziram um aumento na expressão de TNF-a (p<0,05) sem afetar os níveis de NO, IL-10, iNOS e Arg-1. A expressão elevada de mTNF-R1 (p<0,05) em células RAW264.7 foi observada para ambos os antígenos após 24 horas de cultura, mas apenas o Rv1733 foi capaz de diminuir os níveis de sTNF-R1 (p<0,05) nos sobrenadantes de cultura. A expressão de mTNF-R2 e a detecção de sTNF-R2 (p<0,05) foi maior após estimulação com Rv1733, em 24 e 48 horas de cultura. Esses resultados sugerem que a proteína de fusão ESAT6:CFP10 e o antígeno DosR, Rv1733, modulam diferentemente a produção de TNF-a e a expressão de seus receptores em macrófagos, o que influenciar na suscetibilidade à infecção. / Tuberculosis is a severe infectious disease caused by Mycobacterium tuberculosis (Mtb). Macrophages provide a first line of defense against tuberculosis and major habitat for Mtb. Specific Mtb antigens, such as ESAT-6, CFP-10 and Rv1733, may modulate the production of cytokines, influencing the course of infection. Infected macrophages release a range of cytokines including tumor necrosis factor-alpha (TNF-a). TNF-a actions are triggered by its two membrane receptors, mTNF-R1 and mTNF-R2, which may undergo a shedding process, resulting in the soluble form sTNF-R1 and sTNF-R2, respectively. In the present study, RAW264.7 macrophages (2 x 105/mL) were stimulated with the fusion protein ESAT6:CFP10 or the recombinant DosR antigen Rv1733 at 5[1,g/mL for 24 and 48 hours and the production of TNF-a and expression membrane and soluble TNFRs were investigated. Culture supernatants were collected and levels of TNF-a, IL-10, sTNF-R1 and sTNF-R2 evaluated by ELISA, while levels of nitric oxide (NO) were assessed by the Griess reaction. To determine cell viability the MTT assay was used. Levels of mTNF-R1 and mTNF-R2 were analysed by flow cytometry and the expression of iNOS and Arg-1 were determined by immunocytochemistry. The results show that both antigens induced an increase in TNF-a production (p<0.05) without affecting levels of NO, IL-10, iNOS and Arg-1. Elevated expression of mTNFR1 (p<0,05) in RAW264.7 cells was observed for both antigens after 24h of culture, but only Rv1733 decreased sTNF-R1(p<0,05) in culture supernatants. Expression of mTNF-R2 and detection of sTNF-R2 (p <0.05) was enhanced by Rv1733 after 24h and 48h of culture. These results suggest that the fusion protein ESAT6:CFP10 and the DosR antigen Rv1733 differentially modulate the production of TNF-a and the expression of its receptors on macrophages, which may affect the susceptibility to infection.

Made available in DSpace on 2014-08-20T13:32:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-10-02 / Avian Necrotic Enteritis (NE) is an acute enterotoxaemia caused by Clostridium perfringens A and C. The control of the disease is based on antibiotics added to animal feed. The ban of this practice by consumer markets, considered the biggest challenge to industrial aviculture, demanded the adoption of other alternatives for its control, among others, immunization with recombinant vaccines. The aim of this work was to produce and evaluate C. perfringens recombinant α toxin (rAT) vaccines adjuvanted with either Al(OH)3 (rAT+Al(OH)3 or recombinant B subunit of the heat-labile enterotoxin of Escherichia coli (rLTB) (rAT+rLTB), and a chimeric protein containing the α toxin fused to rLTB (rLTB-AT). The rAT+Al(OH)3 was innocuous and protected mice against a challenge with native α toxin (sT), and it was immunogenic and did not affect productivity parameters in broilers. The rAT+rLTB showed a dose-protection relationship in mice, while rLTB-AT did not protect mice against sT challenge. The rAT could be an alternative for controlling NE. / A Enterite Necrótica Aviar (ENA) é uma enterotoxemia aguda, causada pelos Clostridium perfringens A e C, cujo controle baseia-se na adição de antibióticos na ração. A restrição dessa prática pelo mercado consumidor, que tornou seu controle o maior desafio para o setor avícola, exigiu a adoção de novas estratégias para o controle, entre elas a imunização. Vacinas recombinantes vêm despertando grande interesse entre pesquisadores e empresas do setor. O objetivo deste trabalho foi elaborar vacinas de toxina α recombinante de C. perfringens (rAT) utilizando como adjuvantes Al(OH)3 (rAT+Al(OH)3) e subunidade B recombinante da enterotoxina termolábil de Escherichia coli (rLTB) (rAT+rLTB), e construir e avaliar uma proteína quimérica contendo rAT fusionada a rLTB (rLTB-AT). A rAT+Al(OH)3 foi inócua e protetora contra agressão de toxina α nativa (sT) em camundongos, e imunogênica em frangos de corte, sem afetar a produtividade. A rAT+rLTB demonstrou relação dose-proteção em camundongos, entanto a rLTB-AT não protegeu camundongos contra agressão de sT. A rAT demonstrou ser uma alternativa para controlar a ENA. Palavras-chave: Enterite Necrótica Aviar, Clostridium perfringens A, toxina α recombinante, vacinas.

L’obésité est une maladie associée à des altérations métaboliques et inflammatoires et constitue un facteur de risque important de développer des comorbidités telles qu’un diabète de type 2. De plus, la prévalence de troubles de l’humeur et de la cognition est élevée chez les sujets obèses. Ces troubles neuropsychiatriques compliquent la prise en charge de l’obésité, contribuent à son aggravation et peuvent à terme favoriser le développement des comorbidités associées. Diminuer le développement de ces troubles pourrait donc permettre d’améliorer la santé et la qualité de vie des individus obèses. Dans ce contexte, l’objectif de cette thèse a été de comprendre les mécanismes neurobiologiques sous-tendant l’apparition de ces troubles neuropsychiatriques, dans le but d’identifier de nouvelles cibles potentielles pour le développement de stratégies préventives et/ou thérapeutiques visant à les réduire. Dans ce but, des modèles animaux d’obésité tels que la souris db/db, qui présentent une obésité sévère associée à des altérations caractéristiques du syndrome métabolique, peuvent être particulièrement utiles.[ ]Dans un premier temps, nous avons montré qu’une restriction calorique ou un traitement anti-inflammatoire diminuait les comportements de type anxieux chez la souris db/db. Cette amélioration était associée à une diminution sélective de l’expression génique du TNF-α dans l’hippocampe, ce qui suggère une contribution de cette cytokine pro-inflammatoire dans les comportements de type anxieux associés à l’obésité. Nous avons ensuite confirmé cette hypothèse en montrant que le blocage sélectif du TNF-α cérébral par administration i.c.v. d’étanercept (un récepteur leurre du TNF-α) diminuait les comportements de type anxieux chez les souris db/db. De façon intéressante, des mesures électrophysiologiques ont permis de montrer que cette amélioration des comportements émotionnels par l’étanercept impliquait la modulation de l’activité spontanée des neurones dans l’hippocampe ventral, région connue pour son rôle dans la régulation des émotions. Dans un second temps, nous avons essayé d’identifier de nouvelles stratégies préventives et/ou thérapeutiques pour améliorer l’humeur et la cognition chez les sujets obèses. Nous avons donc évalué l’effet d’un régime enrichi en acides gras polyinsaturés de type n-3 et antioxydants sur les altérations comportementales des souris db/db. En effet, ces nutriments sont connus pour moduler différents paramètres neurobiologiques impliqués dans la régulation du comportement. Nous avons montré que la consommation chronique de ce régime supprimait les déficits de mémoire spatiale dépendante de l’hippocampe chez les souris db/db dans le test de la piscine de Morris et que cette amélioration cognitive était probablement sous-tendue par des changements de plasticité neuronale. Enfin, nous avons évalué si des manipulations du microbiote intestinal pouvaient représenter une stratégie préventive et/ou thérapeutique pour améliorer les altérations neuropsychiatriques associées à l’obésité. Nous avons donc mesuré l’impact d’une manipulation du microbiote intestinal par des prébiotiques sur les altérations métaboliques et comportementales des souris db/db, mais également sur les systèmes biologiques et neurobiologiques auxquels elles sont associées. Nous avons montré que les améliorations métaboliques induites par l’administration de prébiotiques chez la souris db/db étaient accompagnées d’une diminution de l’inflammation périphérique et centrale. [ ] Pour conclure, ces expériences contribuent à montrer que l’inflammation, en particulier le TNF-α, pourrait être une cible importante pour le développement de traitements visant à améliorer les troubles de l’humeur chez les sujets obèses ; alors que des interventions nutritionnelles avec des nutriments d’intérêt pourrait plutôt aider à protéger des altérations métaboliques et/ou cognitives chez ces patients. / Obesity is a metabolic and inflammatory disorder that represents a major risk factor for the development of comorbidities such as type 2 diabetes. Obese patients also often experience mood and cognitive dysfunctions that represent important risk factors for aggravation of obesity and related outcomes. Reducing the development of such alterations may therefore allow improving health and quality of life of obese subjects. In this context, this thesis aimed to decipher the neurobiological mechanisms underlying such neuropsychiatric alterations, in order to identify new targets for the development of potential preventive and/or therapeutic strategies aiming to reduce these alterations. To do so, rodent models of obesity such as the db/db mice, which display severe obesity associated with classical features of metabolic syndrome, can be particularly useful.[ ] Second, we have investigated whether a nutritional intervention with n-3 polyunsaturated fatty acids (n-3 PUFAs) and antioxidants, which are well-known to display anti-inflammatory and neuroprotective properties, improved obesity-associated neuropsychiatric alterations. In addition, we have measured the consequences of chronic administration of the prebiotic oligofructose on the behavioral alterations displayed by db/db mice since previous studies pointed to the gut microbiota as an important player in the regulation of behavior. Finally, we have investigated the potential underlying mechanisms by measuring the impact of this treatment on the metabolism and systemic inflammation, but also on neurobiological systems known to be involved in the control of food intake and behavior. We first showed that an anti-inflammatory treatment or caloric restriction reduced anxiety-like behaviors, and this was associated with a selective decrease of hippocampal TNF-α mRNA expression, suggesting that this pro-inflammatory cytokine likely contributes to induce anxiety-like behavior associated with obesity. We then nicely confirmed this assumption by showing that selectively blocking brain TNF-α by chronically administrating etanercept i.c.v. (TNF-α decoy receptor) indeed decreased anxiety-like behaviors in obese db/db mice.[ ] Secondly, we tried identifying new preventive and/or therapeutic strategies aiming to improve mood and cognitive alterations associated with obesity. Hence, we measured if an n-3 polyunsaturated fatty acids/antioxidants enriched diet, well-known to modulate different neurobiological mechanisms potentially involved in behavioral alterations displayed by db/db mice, improved their behavioral alterations. We showed that chronic consumption of this diet reversed hippocampus-dependent spatial memory deficits displayed by db/db mice in a water-maze task and that this effect likely involved modulation of neuronal plasticity. Thirdly, we tested whether manipulating the gut microbiota composition may constitute a preventive and/or therapeutic strategy to improve the neuropsychiatric alterations associated with obesity. Hence, we assessed for the first time the effect of microbiota manipulation with a prebiotic on the metabolic and behavioral alterations displayed by db/db mice, but also on their systemic and neurobiological correlates. We showed that improvement of metabolic alterations following prebiotic administration in db/db mice was associated with selective reduction of peripheral and central inflammation, which is however not accompanied by detectable improvement of anxiety-like behavior or spatial memory deficits. To conclude, these experiments contribute to show that inflammation, and especially TNF-α, could be an important target to develop therapeutic treatments for mood alterations associated with obesity, whereas nutritional interventions with selective nutrients of interest may rather help preventing associated metabolic and/or cognitive alterations.

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