University, Diss., 2001--München.

Thèse (Ph. D.)--Université Laval, 2002. / Bibliogr. Publié aussi en version électronique.

München, Techn. University, Diss., 2001.

Made available in DSpace on 2015-07-22T20:49:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-07-28 / A resposta inflamatória é modulada durante a sepse e a regulação positiva ou negativa da atividade celular depende das células e funções avaliadas. IFN-γ e IL-17 são citocinas características das subpopulações de linfócitos Th1 e Th17, respectivamente, e desempenham papel importante na resposta imune, ligando a imunidade inata e adaptativa. Objetivo: Avaliar a presença das células Th1 e Th17 em pacientes sépticos na admissão do estudo (D0) comparado-a com sadios e após 7 dias (D7) de seguimento. Casuística e Métodos: Foram incluídos 59 pacientes sépticos no D0, dos quais 31 tiveram amostras colhidas no D7, e 30 indivíduos sadios. As células mononucleares do sangue periférico foram separadas e congeladas em nitrogênio líquido. Após descongelamento e ajuste da concentração para 1x106 células/mL, as células foram estimuladas ou não com PMA/ionomicina e mantidas por 30 minutos em estufa a 37ºC a 5% CO2. Foi acrescentado brefeldina A e incubadas por mais 15 horas. Em seguida, foi feita marcação de superfície para a identificação dos linfócitos TCD4 (CD3+CD8-). As células foram permeabilizadas e marcadas para detecção de IL-17A e IFN-γ intracelular. As amostras foram lidas em citômetro FACSCanto e analisadas no programa FlowJo. Resultados: A produção basal de IFN-γ e IL-17A foi maior nos pacientes comparado aos sadios (P=0,002 e P<0,001, respectivamente). Após estímulo, a produção de IL-17A foi maior nos pacientes (P=0,027) enquanto a de IFN-γ foi superior nos sadios (P=0,001). Ao comparar os diferentes estadios da sepse, foi observado aumento na produção de IFN-γ após estímulo com PMA/ionomicina nos pacientes em choque séptico em relação aos pacientes em sepse grave (P=0,039). A produção de IFN-γ basal e após estímulo mostrou-se aumentada no D7 em relação ao D0 (P=0,007 e P=0,018, respectivamente). Em contraste, a produção de IL-17 após estímulo foi maior no D0 comparado ao D7 (P=0,003), mas não foi encontrada diferença significativa na condição basal. Nos pacientes que evoluíram a óbito, as amostras do D0 apresentaram menor produção constitutiva de IFN-γ em relação ao D7 (P=0,023), mas após estímulo não foi encontrada diferença. Nos pacientes que sobreviveram, não houve diferença na condição basal e após estímulo com PMA/ionomicina. A produção de IL-17, após estímulo foi maior na amostra D0 em relação ao D7 (P=0,006) nos pacientes que sobreviveram, já na condição basal não houve diferença. Os pacientes que evoluíram a óbito não apresentaram diferença na condição basal e após estímulo com PMA/ionomicina. Conclusão: Os resultados basais com maior produção de citocinas nos sépticos refletem o grau de inflamação característico da sepse. Observamos uma dicotomia entre as respostas Th1 e Th17 após PMA/ionomicina nos pacientes sépticos, com aumento da população Th17 e diminuição da Th1 em relação aos sadios. Aumento da população Th1 no D7 foi relacionado com mortalidade, enquanto diminuição da população Th17 foi relacionada com sobrevida, indicando que a persistência ou exacerbação das respostas Th1 e Th17 podem ser deletérias. Estes achados sugerem regulação da resposta inflamatória na sepse das populações Th1 e Th17. / The inflammatory response is modulated during sepsis and up or down regulation of cell activity depends on cells and functions evaluated. IFN-g and IL-17 are cytokines characteristics of lymphocyte subsets Th1 and Th17, respectively, and play an important role in immune response, linking innate and adaptative immunity. Objective: To evaluate the presence of Th1 and Th17 cells in septic patients at admission of the study (D0) compared it with healthy volunteers and after 7 days (D7) follow-up. Material and Methods: We included 59 septic patients on D0, of which 31 had samples collected on D7, and 30 healthy individuals. The peripheral blood mononuclear cells were separated and frozen in liquid nitrogen. After thawing and adjust the concentration to 1x106 cells/mL, cells were stimulated or not with PMA/ionomycin for 30 minutes and maintained at 37oC 5% CO2. Brefeldin A was added and cells were incubated for another 15 hours. Then cells were surface stained for identification of TCD4 lymphocytes (CD3+CD8-). Cells were permeabilized and stained for detection of IL-17A and IFN-g intracellular. The samples were read in FACSCanto cytometer and analyzed with FlowJo program. Results: The basal production of IFN-g and IL-17A was higher in patients compared to healthy volunteers (P=0,002 e P<0,001, respectively). After stimulation, the production of IL-17A was higher in patients (P=0,027) while the IFN-g was higher in healthy (P=0,001). An increase IFN-g production after stimulation with PMA/ionomycin was found in patients with septic shock compared to severe sepsis (P=0,039). The baseline production of IFN-g and after PMA/Ionomycin stimulation was found to be increased in D7 in relation to D0 (P=0,007 e P=0,018, respectively). In contrast, the production of IL-17 after stimulation was higher in D0 compared to D7 (P=0,003). In patients who died, the D0 samples showed lower constitutive IFN-g production compared to D7 (P=0,023), but after a stimulus, no difference was found. In patients who survived, there was no difference at baseline and after stimulation with PMA/ionomycin. The IL-17 production, after stimulation, was higher in D0 sample compared to D7 (P=0,006) in patients who survived. No difference between D0 and D7 was found in patients who survived. Conclusion: The results with higher basal detection of IFN-g and IL-17 producing cells in septic patients reflect the degree of inflammation characteristic of sepsis. A dichotomy between Th1 and Th17 responses after PMA/ionomycin stimulation was found in septic patients, with increased Th17 population and decreased Th1 compared to healthy individuals. A higher proportion of Th1 in D7 was observed in patients who died; while a decrease of Th17 population was observed in patients who survived, indicating that the persistence or higher Th1 and Th17 responses may be deleterious. These findings suggest regulation of the inflammatory response in sepsis of Th1 and Th17 populations. / TEDE / BV UNIFESP: Teses e dissertações

Made available in DSpace on 2015-06-17T19:33:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-15. Added 1 bitstream(s) on 2015-06-18T12:47:57Z : No. of bitstreams: 1 000830096.pdf: 323394 bytes, checksum: d31a089f3bf47b648bbfdf120de818b3 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / O objetivo deste trabalho foi avaliar a influência da periodontite apical e/ou doença periodontal associadas à diabetes na quantificação sérica da citocina pró-inflamatória IL-17 e na glicemia. Foram utilizados 80 ratos da linhagem Wistar divididos em 8 grupos de 10 ratos: G1 - ratos normoglicêmicos ; G2 - ratos com infecção endodôntica; G3 - ratos com infecção periodontal; G4 - ratos com infecção endodôntica e periodontal; G5 - ratos diabéticos; G6 - ratos diabéticos com infecção endodôntica; G7 - ratos diabéticos com infecção periodontal; G8 - ratos diabéticos com infecção endodôntica e periodontal. A diabetes foi induzida pela aplicação de estreptozotocina via veia peniana, cujo desenvolvimento da doença foi confirmado no sexto e último dia do experimento pela avaliação glicêmica no sangue por meio de uma punção na extremidade da cauda do animal, seguida de pequena compressão para a obtenção de uma gota de sangue. A infecção endodôntica foi induzida pela exposição pulpar do primeiro molar superior direito. A infecção periodontal foi induzida por meio da confecção de uma amarria junto ao colo dentário do segundo molar superior esquerdo. Com 30 dias pós-operatórios foi realizada a glicemia novamente e a coleta de sangue pela punção cardíaca para a quantificação da citocina IL-17 empregando a técnica de ELISA de captura. Os resultados foram analisados do pelo teste de análise de variância e teste de Tukey (p<0,05). O nível glicêmico foi maior em ratos diabéticos quando comparados com ratos controle aos 6 e 30 dias (p<0,05). Entretanto, aos 30 dias nos grupos de ratos diabéticos, observou-se que a presença da infecção periodontal isolada (G7) ou associada à endodôntica (G8) aumentou de forma significante a glicemia quando... / The aim of the study was to evaluate the influence of periapical lesions and/or periodontal disease on the IL-17 serum and dosage glycemic a rat model of diabetes mellitus. Eighty male Wistar rats were divided into eight groups of ten animals each: normal rats (G1), rats with pulpal infection (G2), rats with periodontal disease (G3), rats with pulpal infection and periodontal disease (G4), diabetic rats (G5), diabetic rats with pulpal infection (G6), diabetic rats with periodontal disease (G7), diabetic rats with pulpal infection and periodontal disease (G8). Diabetes was induced using streptozotocin, pulpal infection were induced by dental pulp exposure to the oral environment and the periodontal disease by periodontal ligature. Blood glucose was measured by means of a perforation in the tail of the animal after 0, 6 and 30 days post-operative. The animals were sacrificed after 30 days and the IL-17 levels were measured by ELISA. The total assessed values was tabulated according to each experimental group and statistically analyzed by analysis of variance (ANOVA) followed by Tukey test (p<0.05). Glucose levels were higher in diabetic rats compared to control rats at 6, and 30 days (p <0.05). However, at 30 days, and among the groups of diabetic rats, it was observed that the presence of periodontal infection alone (G7) or associated with endodontic (G8) increased significantly the blood glucose compared to diabetic rats without oral infections (G5 ) (p <0.05). The presence of systemic disease diabetes was not able to increase the level of serum IL-17 (p <0.05). However, the presence of the associated oral infections (G4, G8) significantly elevated the serum level of IL-17, regardless of the presence of diabetes (p <0.05). It can be concluded that the endodontic infection when associated with periodontal disease may increase blood glucose levels in diabetic rats and the serum level of IL-17 in normoglycemic or diabetic rats

La periodontitis es una enfermedad infecciosa de naturaleza inflamatoria, que involucra una respuesta inmune del hospedero y que se caracteriza por la destrucción de los tejidos de inserción del diente. Numerosos estudios han determinado que el infiltrado inflamatorio de la enfermedad se caracteriza por un predominio de células de la línea linfocitaria, principalmente linfocitos T. En otras enfermedades de naturaleza inflamatorio-destructivas, como la artritis reumatoide, se ha evidenciado un rol central de los linfocitos T en el perfil de citoquinas relacionado con la destrucción de los tejidos articulares y se ha propuesto que IL-17 regularía la diferenciación y activación de las células clásticas responsables de la destrucción del cartílago y hueso articular. Con el objeto de estudiar si existe asociación entre IL-17 y periodontitis, se determinaron los niveles de IL-17 en 16 individuos con periodontitis crónica y en 8 individuos periodontalmente sanos tanto en muestras biológicas de fluido gingival crevicular (FGC) como en los sobrenadantes de células mononucleares extraídas de biopsias de tejido gingival (CMG). Las muestras de FGC y los sobrenadantes de cultivos celulares de CMG fueron analizadas para determinar la presencia y síntesis de IL-17 mediante ELISA. En el FGC y los sobrenadantes de cultivo de CMG de individuos con periodontitis crónica se observó una presencia y síntesis significativamente mayor de IL-17 en comparación a individuos periodontalmente sanos. De estos resultados se puede concluir que IL-17 se encuentra sobreexpresada en individuos con peridontitis crónica y contribuiría a explicar, por lo menos en parte, los fenómenos etiopatogénicos involucrados en la destrucción del tejido óseo alveolar ocurrido en la periodontitis.

Real-time testing with dynamic substructuring provides an efficient way to simulate the nonlinear dynamic behaviour of civil structures or mechanical facilities. In this technique, the test structure is divided onto two substructures: the relatively crucial substructure is tested physically and the other is modelled numerically in the computer. The key challenge is to ensure that both substructures interact in real-time, in order to simulate the behaviour of the emulated structure. This has special demands on the utilized integration methods and their implementations. Researchers have devoted significant effort to implement second-order integrators, such as Newmark integration methods, in a monolithic way where both substructures are integrated altogether. However, in view of large and complex structures, time integration methods are required to advance large-scale systems hence endowed with high-frequency components of the response or mixed first- and second- order systems like in the case of controlled systems. In this case, the monolithic implementation of a second-order time integration method becomes inefficient or inaccurate. With these promises, the thesis adopts the Rosenbrock-based time integration methods for both dynamic simulations of complex systems and substructure tests, and in particular, focuses on the development of monolithic schemes with subcycling strategies for nonlinear cases and partitioned methods with staggered and parallel solution procedures for linear and nonlinear cases. Initially, the Rosenbrock integration methods endowed with one stage to three stages are introduced and their applicabilities to second-order systems are investigated in terms of accuracy, stability and high-frequency dissipation, such as stability analysis of the Rosenbrock methods with one stage and two stages via the energy approach and numerical experiments on an uncoupled spring-pendulum system. Then, these methods are implemented in a monolithic way for real time substructure tests also considering subcycling strategies. Meanwhile, real-time substructure tests considering nonlinearities both in the numerical and physical substructures were carried out to illustrate the performances of the monolithic methods. Moreover, three types of partitioned algorithms based on the element-to-element partitioning are successively proposed. Two of them are based on acceleration continuity with a staggered solution procedure and a parallel solution procedure, respectively, and one of them is based on velocity continuity and a projection method. Both stability and accuracy properties of the proposed algorithms are examined by means of analytical techniques and numerical studies on single-, two-, three- and four-degree-of-freedom model problems and a coupled spring-pendulum system. Finally, a novel test rig conceived to perform both linear and nonlinear substructure tests with different combinations of numerical and physical substructures are presented and commented.

Base isolation system, as one of the most popular means to mitigate the seismic risks, often exhibits strong nonlinearity. To simplify the procedure of structural design, bilinear force-deformation behavior is recommended for isolation systems in most modern structural codes. Although base isolation system can be analyzed through nonlinear time history method, solving of a system with a large number of degrees of freedom may require an exorbitant amount of time. As a substitute, the equivalent linearization method is frequently used. Apparently, under given earthquake ground motions, the accuracy of equivalent linearization analysis method is significantly related to the estimation of equivalent linear properties. How to improve the estimation accuracy of this approximate method constitutes a subject of wide and deep interest among researchers around the world. In this research, the equivalent linearization analysis method for base-isolated buildings was investigated. The literature survey on related aspects of base-isolated buildings was carried out firstly. Then, the estimation accuracy of fifteen equivalent linearization methods selected from the literatures was evaluated when subjected to twelve earthquake ground motions. After that, from simplicity to complexity, the base-isolated buildings were modeled using single-degree-of-freedom (SDOF) systems and multi-degree-of-freedom (MDOF) systems, respectively. For both considered systems, more comprehensive parametric analyses were performed with varying the parameters selected from the isolation system and the superstructure. Accordingly, improved equivalent linearization methods were derived for SDOF and MDOF systems to improve the prediction accuracy of the maximum displacement of isolation systems. Based on the proposed equivalent linearization methods, different analysis methods for base-isolated buildings were assessed, including equivalent static linear analysis, response spectral analysis, linear and nonlinear time history analyses. It was found that with the proposed equivalent linearization methods equivalent linear analyses could yield more accurate results when compared with the equivalent linearization method recommended by structural codes. As a result, the proposed equivalent linearization method could be potentially useful for the design and analysis of baseisolated buildings, as least in the preliminary stage of structural design.

Cette thèse étudie la naissance du consulat français de Barcelone comme institution royale (1679-1716). La longue adaptation aux réformes de Colbert et Pontchartrain caractérise la vie et le développement de l'institution comme le montrent l'étude de la correspondance, la naissance de la chancellerie ou des vice-consulats et l'obtention des postes consulaires. L'étude locale du consulat est envisagée dans les conséquences globales de sa gestion, notamment dans la perspective de la politique économique menée par Seignelay, Louis et Jérôme de Pontchartrain en Espagne et, au-delà, via le commerce interlope direct comme indirect, en Amérique latine. À cette fin, la figure du consul marchand et son attitude vis-à-vis des consignes royales sont étudiées à travers les trois consuls successifs : Laurent Soleil (1679-1705), Jean-Philippe Monclus (1705-1709) et Simon Dupin (1709-1716). Le consulat de Laurent Soleil et son activité marchande à Barcelone sont détaillées. L'implication de ce dernier dans des expériences originales avec les théoriciens catalans de l'économie tels que Marti Piles et Josep Aparici est démontrée. L'intérêt commun d'acteurs divers, dans un contexte de rivalités, pour des projets économiques communs est étudié à travers l'exemple du commerce avec Tunis. La question de l'utilisation du consulat comme moyen de consolider les affaires marchandes de son détenteur et comme assurance face aux aléas de la guerre est posée. Plus généralement, l'attitude et l'adaptation des acteurs marchands dans une province touchée par les guerres régulièrement sont étudiées. / This thesis studies the birth of the French consulate of Barcelona as a royal institution (1679-1716). The long adaptation to the reforms of Colbert and Pontchartrain characterizes the life and the development of the institution as shown through the study of the correspondence, the birth of the chancellery or the vice-consulates and the obtaining of the consular position. The local study of the consulate is envisaged in the global consequences of its management, in particular with the prospect of the economic policy led by Seignelay, Louis and Jérôme de Pontchartrain in Spain and, beyond, via the illicit business, in Latin America. To this end, the figure of the trade consul and his attitude towards the royal instructions are studied through three successive consuls: Laurent Soleil (1679-1705), Jean-Philippe Monclus (1705-1709) and Simon Dupin (1709-1716). Laurent Soleil's consulate and its trade activity in Barcelona are detailed. The implication of the latter in original experiences with the Catalan theorists of the economy such as Marti Piles and Josep Aparici is demonstrated. The common interest of diverse actors, in a context of rivalries, for common economic projects is studied through the example of the trade with Tw1Îs. The question of the use of the consulate as the way to strengthen the trade business of his holder and as insurance in front of hazards of the war is put. More generally, the attitude and the adaptation of the trade actors in a province regularly affected by the wars are studied.

Literatura Comparada Francesa/Inglesa. Saint-Évremond: estudo comparatista da comédia "Sir Politick Would-be" com a comédia "Volpone" de Ben Jonson (séc. XVII)