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Efeito dual de FGF2 e PMA em células HEK 293 transformadas por H-rasV12 / Dual effects of FGF2 and PMA on H-rasV12 transformed HEK293 cell lineSilva, Juliana Galvão da 19 September 2014 (has links)
Sabe-se há décadas que mutações nos genes ras estão presentes em cerca de 20% dos cânceres humanos, mas o desenvolvimento de terapias eficazes para o tratamento de câncer dependente dos oncogenes ras permanece um desafio científico importante. Nesse contexto, o nosso grupo publicou recentemente resultados interessantes mostrando que FGF2 exógeno ou PMA, contrariamente à expectativa geral, inibem a proliferação de células de camundongo malignas dependentes dos oncogenes H- ou K-Ras. Para dar continuidade a estes estudos o projeto desta tese foi planejado para investigar os mecanismos subjacentes a possíveis efeitos citotóxicos de FGF2 e PMA em células humanas transformadas por ras. Para esse fim, a linhagem humana imortalizada HEK 293 foi condicionalmente transformada pela expressão ectópica da construção quimérica de DNA ER:H-rasV12, que codifica a oncoproteína de fusão ER:H-RasV12, cuja atividade é induzível por 4-hidroxi-tamoxifen (4OHT). Essa abordagem nos permitiu verificar os efeitos de FGF2 e PMA em sublinhagens HEK/ER:HrasV12 fenotipicamente \"normais\" ou transformadas por níveis crescentes da oncoproteína H-RasV12. Os principais resultados mostraram que tanto FGF2 como PMA tem efeito dual promovendo ou inibindo a proliferação das células transformadas em função da concentração intracelular crescente de H-RasV12. Ensaios de crescimento de colônias em suspensão de agarose mostraram que: a) as células parentais HEK293 não desenvolveram colônias mesmo quando tratadas com FGF2 ou PMA, resultados que estão de acordo com seu fenótipo não tumoral; b) mas, as sublinhagens HEK/ER:HrasV12 deram origem a colônias mesmo quando tratadas com concentrações pequenas de 4OHT, que condicionaram níveis intracelulares baixos de ER:HRasV12; nestas condições experimentais, FGF2 foi um forte promotor do crescimento de colônias, condizente com sua reconhecida atividade promotora do crescimento de células tumorais em suspensão; ainda nestas condições, PMA não teve efeito significante sobre o crescimento de colônias; c) coerentemente, concentrações elevadas de 4-OHT levaram aos níveis intracelulares mais altos de ER:HRasV12 e, por conseguinte, a desenvolvimento máximo de colônias de células HEK/ER:HrasV12, no entanto, nestas condições, ambos FGF2 e PMA inibiram completamente o crescimento de colônias. Por outro lado, transformação de HEK293 com um vetor de expressão constitutiva de HrasV12 levou à seleção e isolamento das sublinhagens tumorais HEK/HrasV12, cujo fenótipo se caracterizou por: a) nenhum efeito de FGF2 sobre a sua proliferação e b) forte inibição de sua proliferação por PMA. A ação citotóxica de PMA exclusivamente observada em células HEK 293 transformadas por H-rasV12 se caracterizou por: a) total dependência de PKC, provavelmente mediada pela ativação proteolítica específica de PKC δ; b) envolvimento de níveis elevados e sustentados de ROS com disparo tardio de apoptose. / It is known for nearly 20 years that mutated ras oncogenes are found in 20% of human malignancies, however efficacious therapies are not yet available for Ras-driven cancer. Along of these lines, our group recently published provocative results showing, against common belief, that FGF2 and PMA inhibited proliferation of Ras-dependent malignant mouse cells. Aiming to gain insight into this intriguing phenomenon, the present thesis project was planned to investigate the possible cytotoxicity of FGF2 and PMA in human Ras-driven malignant cells. To this end an immortalized non-tumorigenic human cell line (HEK293) was stably transformed with the DNA construction ER:H-rasV12, which encodes the fusion protein ER:H-RasV12, whose activity requires activation by 4-hidroxitamoxifen (4-OHT). This approach allowed us to evaluate FGF2 and PMA effects on HEK/ER:HrasV12 sublines under switching from \"normal\" to transformed phenotypes upon 4-OHT induction. Our main results have shown that both FGF2 and PMA displayed dual effects promoting or inhibiting proliferation of HEK/ER:HrasV12 cells in function of ER:HRasV12 intracellular levels. Clonogenic assays in agarose suspension have shown: a) parental HEK293 line did not develop colonies under FGF2 and PMA treatment or not, in agreement with its non-tumorigenic nature; b) however, HEK/ER:HrasV12 sublines developed colonies even under low 4-OHT concentrations, which led to low ER:HRasV12 intracellular levels; under these conditions FGF2 strongly promoted colony growth and PMA had no effect; c) furthermore, in HEK/ER:HrasV12 sublines, elevated 4-OHT concentrations led to high ER:HRasV12 intracellular levels and maximal colony growth; but, under these experimental conditions both FGF2 and PMA abolished colony growth. On the other hand, HEK293 transformation with a vector that constitutively express HrasV12 yielded HEK/ER:HrasV12 sublines displaying the following phenotypic traits: a) non FGF2 effects on proliferation and b) severe proliferation inhibition by PMA. PMA toxicity, exclusively observed in HrasV12 -transformed HEK293 cells, was characterized by: a) total dependency on PKC, likely mediated by specific proteolytic activation of PKCδ; b) involvement of high and sustained ROS levels correlated with late apoptosis triggering.
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Efeito dual de FGF2 e PMA em células HEK 293 transformadas por H-rasV12 / Dual effects of FGF2 and PMA on H-rasV12 transformed HEK293 cell lineJuliana Galvão da Silva 19 September 2014 (has links)
Sabe-se há décadas que mutações nos genes ras estão presentes em cerca de 20% dos cânceres humanos, mas o desenvolvimento de terapias eficazes para o tratamento de câncer dependente dos oncogenes ras permanece um desafio científico importante. Nesse contexto, o nosso grupo publicou recentemente resultados interessantes mostrando que FGF2 exógeno ou PMA, contrariamente à expectativa geral, inibem a proliferação de células de camundongo malignas dependentes dos oncogenes H- ou K-Ras. Para dar continuidade a estes estudos o projeto desta tese foi planejado para investigar os mecanismos subjacentes a possíveis efeitos citotóxicos de FGF2 e PMA em células humanas transformadas por ras. Para esse fim, a linhagem humana imortalizada HEK 293 foi condicionalmente transformada pela expressão ectópica da construção quimérica de DNA ER:H-rasV12, que codifica a oncoproteína de fusão ER:H-RasV12, cuja atividade é induzível por 4-hidroxi-tamoxifen (4OHT). Essa abordagem nos permitiu verificar os efeitos de FGF2 e PMA em sublinhagens HEK/ER:HrasV12 fenotipicamente \"normais\" ou transformadas por níveis crescentes da oncoproteína H-RasV12. Os principais resultados mostraram que tanto FGF2 como PMA tem efeito dual promovendo ou inibindo a proliferação das células transformadas em função da concentração intracelular crescente de H-RasV12. Ensaios de crescimento de colônias em suspensão de agarose mostraram que: a) as células parentais HEK293 não desenvolveram colônias mesmo quando tratadas com FGF2 ou PMA, resultados que estão de acordo com seu fenótipo não tumoral; b) mas, as sublinhagens HEK/ER:HrasV12 deram origem a colônias mesmo quando tratadas com concentrações pequenas de 4OHT, que condicionaram níveis intracelulares baixos de ER:HRasV12; nestas condições experimentais, FGF2 foi um forte promotor do crescimento de colônias, condizente com sua reconhecida atividade promotora do crescimento de células tumorais em suspensão; ainda nestas condições, PMA não teve efeito significante sobre o crescimento de colônias; c) coerentemente, concentrações elevadas de 4-OHT levaram aos níveis intracelulares mais altos de ER:HRasV12 e, por conseguinte, a desenvolvimento máximo de colônias de células HEK/ER:HrasV12, no entanto, nestas condições, ambos FGF2 e PMA inibiram completamente o crescimento de colônias. Por outro lado, transformação de HEK293 com um vetor de expressão constitutiva de HrasV12 levou à seleção e isolamento das sublinhagens tumorais HEK/HrasV12, cujo fenótipo se caracterizou por: a) nenhum efeito de FGF2 sobre a sua proliferação e b) forte inibição de sua proliferação por PMA. A ação citotóxica de PMA exclusivamente observada em células HEK 293 transformadas por H-rasV12 se caracterizou por: a) total dependência de PKC, provavelmente mediada pela ativação proteolítica específica de PKC δ; b) envolvimento de níveis elevados e sustentados de ROS com disparo tardio de apoptose. / It is known for nearly 20 years that mutated ras oncogenes are found in 20% of human malignancies, however efficacious therapies are not yet available for Ras-driven cancer. Along of these lines, our group recently published provocative results showing, against common belief, that FGF2 and PMA inhibited proliferation of Ras-dependent malignant mouse cells. Aiming to gain insight into this intriguing phenomenon, the present thesis project was planned to investigate the possible cytotoxicity of FGF2 and PMA in human Ras-driven malignant cells. To this end an immortalized non-tumorigenic human cell line (HEK293) was stably transformed with the DNA construction ER:H-rasV12, which encodes the fusion protein ER:H-RasV12, whose activity requires activation by 4-hidroxitamoxifen (4-OHT). This approach allowed us to evaluate FGF2 and PMA effects on HEK/ER:HrasV12 sublines under switching from \"normal\" to transformed phenotypes upon 4-OHT induction. Our main results have shown that both FGF2 and PMA displayed dual effects promoting or inhibiting proliferation of HEK/ER:HrasV12 cells in function of ER:HRasV12 intracellular levels. Clonogenic assays in agarose suspension have shown: a) parental HEK293 line did not develop colonies under FGF2 and PMA treatment or not, in agreement with its non-tumorigenic nature; b) however, HEK/ER:HrasV12 sublines developed colonies even under low 4-OHT concentrations, which led to low ER:HRasV12 intracellular levels; under these conditions FGF2 strongly promoted colony growth and PMA had no effect; c) furthermore, in HEK/ER:HrasV12 sublines, elevated 4-OHT concentrations led to high ER:HRasV12 intracellular levels and maximal colony growth; but, under these experimental conditions both FGF2 and PMA abolished colony growth. On the other hand, HEK293 transformation with a vector that constitutively express HrasV12 yielded HEK/ER:HrasV12 sublines displaying the following phenotypic traits: a) non FGF2 effects on proliferation and b) severe proliferation inhibition by PMA. PMA toxicity, exclusively observed in HrasV12 -transformed HEK293 cells, was characterized by: a) total dependency on PKC, likely mediated by specific proteolytic activation of PKCδ; b) involvement of high and sustained ROS levels correlated with late apoptosis triggering.
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Identification of the tumour-associated gene S100A14 and analysis of its regulationPietas, Agnieszka 04 March 2005 (has links)
Durch Analyse der Subtraktion-cDNA Bibliothek einer humanen Lungentumor Zelllinie haben wir ein neues Mitglied der S100 Genfamilie identifiziert und charakterisiert, welches S100A14 benannt wurde. Die vollständige cDNA hat eine Länge von 1067 bp und kodiert für ein Protein von 104 Aminosäuren, welches die S100-spezifische Kalzium-bindende Domäne enthält. Das Gen wird in normalen humanen Epithelien ubiquitär exprimiert, zeigt jedoch Expressionsverluste in vielen Tumorzelllinien. Im Gegensatz zu Tumorzelllinien ist S100A14 auf mRNA- und Proteinebene in vielen humanen Primärtumoren stärker exprimiert, unter anderem in Lungen- und Brustkarzinomen. Um den Mechanismus der erhöhten S100A14 Expression in Lungen- und Brustkarzinomen zu verstehen, haben wir die Effekte des EGF (epidermal growth factor) und des TGF-alpha (transforming growth factor-alpha) untersucht. Beide Faktoren sind Liganden des ERBB Rezeptors und induzieren in der immortalisierten bronchialen Epithelzelllinie S100A14 Expression. Unter Verwendung spezifischer Inhibitoren konnte gezeigt werden, dass für die EGF-vermittelte transkriptionelle Induktion der ERK1/2 Signalweg (extracellular signal-regulated kinase) verantwortlich ist und eine de novo Proteinsynthese erfordert. Diese Ergebnisse unterstützend konnte immunhistologisch eine signifikante Korrelation zwischen der Überexpression von ERBB2 und S100A14 in primären Brustkarzinomen nachgewiesen werden. Phorbolester-12-Myristat-13-Acetat (PMA) verstärkte gleichfalls die S100A14 mRNA Expression in 9442 Zellen, was eine Regulation durch die Protein Kinase C (PKC) vermuten lässt. Die PMA-induzierte Expression von S100A14 wird ebenso wie die TGF-alpha/EGF-Induktion durch die Aktivierung des ERK1/2 Signalweges vermittelt. In Anbetracht der großen Bedeutung der ERK1/2 und PKC Signalwege in der Tumorentstehung und Tumorprogression ist zu vermuten, dass S100A14 über die aberrante Regulation dieser Signalwege an die maligne Transformation gekoppelt ist. / By analysing a human lung tumour cell line subtraction cDNA library, we have identified and characterized a novel member of the human S100 gene family that we designated S100A14. The full-length cDNA is 1067 bp and encodes a putative protein of 104 amino acids. The predicted protein contains the S100-specific EF-hand calcium-binding domain. The gene is ubiquitously expressed in normal human tissues of epithelial origin. S100A14 transcript was found to be down-regulated in many immortalized and tumour cell lines from diverse tissues. In contrast to the tumour cell lines, S100A14 shows up-regulation at the mRNA and protein level in many human primary tumours, including lung and breast carcinomas. To elucidate mechanisms whereby S100A14 expression is enhanced in lung and breast tumours, we studied the effects of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) on its expression. Both are ligands of ERBB receptor and induced S100A14 expression in the immortalized bronchial epithelial cells. By use of specific inhibitors, we found that EGF-mediated transcriptional induction of S100A14 involves extracellular signal-regulated kinase (ERK1/2) signalling and requires de novo protein synthesis. In support of these findings, we demonstrated by immunohistochemistry a significant correlation between ERBB2 and S100A14 protein overexpression in primary breast carcinomas. Our studies showed that the phorbol ester 12-myristate 13-acetate (PMA) increases S100A14 mRNA expression in immortalized bronchial epithelial cells suggesting regulation by protein kinase C (PKC). Similar to TGF-alpha/EGF induction, the PMA-induced S100A14 expression was also mediated by activation of the ERK1/2 signalling cascade. Considering the importance of the ERK1/2 and PKC signalling pathways in tumour development and progression we suggest that it is the aberrant regulation of these signalling cascades that couples S100A14 to malignant transformation.
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Les règles d’origine préférentielles de l'UE et l’analyse de leur application en matière de marchandises d'importationLi, Fheng-Ying 29 June 2013 (has links)
Les règles d'origine sont employées pour définir l'endroit où un produit était manufacturé. Pour comprendre l'évolution du commerce, particulièrement lorsqu'il s'agit des accords unilatéraux et bilatéraux, la connaissance des règles d'origine préférentielles et le cumul est nécessaire. Les règles d'origine préférentielles jouent un rôle légitime dans la prévention des déviations commerciales. L'UE a le plus grand nombre d'accords commerciaux préférentiels avec un niveau élevé d'harmonisation des lois d'origine, par exemple l'accord économique d'association (EPA) pour 78 pays ACP et le système du cumul pour l'Euromed. Comme nous savons, la subvention pour le produit d'agriculture tel que le sucre de l'UE et le coton des Etats-Unis sont la raison principale qui cause la pauvreté des PMA. Ainsi, les objets principaux de cette dissertation est veulent trouver : Est-ce que l'UE emploie vraiment sincèrement les règles d'origine préférentielles pour aider les PMA ou veut juste garder leurs avantages coloniaux historiques? Pourquoi les pays membre de l'UE contre la nouvelle politique de la commission à la CJUE après les plaignantes a pris la consultation à l'OMC par le même produit ? Comment les règles d'origine préférentielles de l'UE garde-t-elle l'harmonie avec leurs pays membres et les Etats membres de l'OMC? Pourrions-nous trouver une solution de s'améliorer ou remplacer les règles d'origine préférentielles de l'UE pour empêcher un autre cas se produire dans l'OMC et le CJCE pour le même produit? Nous trouverons la réponse à la conclusion. / Rules of origin are used to define the place where a product was manufactured. To understand the evolution of trade, especially in the cases of unilateral and bilateral trade agreements, the knowledge of the preferential rules of origin and cumulation is necessary.The preferential rules of origin play a legitimate part in the prevention of the commercial deviations. The EU has the largest number of preferential trade agreements with a high degree of harmonization of origin laws, for example the Economic Partnership Agreement (EPA) for 78 ACP countries and the system of cumulation for EURO-MED.As we know, the subsidiary for agriculture product such as sugar and cotton of EU and USA are the main reason which causes the poverty of LCDs. So, the mains purpose of this dissertation is want to find: Does EU really sincerely uses the preferential rules of origin (PROO) to help the LCDs or just want to keep their historical colonial benefits? Why the EU member against the EU commission's newly policy after the WTO member by the same product? How the EU PROO does keep harmony with their member countries and the WTO's member countries? Could we find a way to improve or replace the PROO of EU for the same product to prevent another case happen both in WTO and CJCE? We have found the answer at the Conclusion.
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Hole transport layers in organic solar cells : A study of work functions in nanofilmsNilsson, Frida January 2019 (has links)
Organic solar cells have been showing promise as a way of producing renewableenergy with the help of light, flexible, and production effective materials.The efficiencies and lifetimes reached in organic solar cells have steadily beenincreasing over the years as more research in the field is being conducted.One way of increasing the efficiency in organic solar cell devices is introducingan interlayer between the photoactive material and the anode, referred toas the ’hole transport layer’. Most commonly used as a hole transport layer isthe material PEDOT:PSS, which offers desired properties such as transparency,simple processing and good ohmic contact between anode and photoactive material.PEDOT:PSS is also known to be a degradation site in organic solar cells,as it will corrode the electrode in the presence of water.This project has consisted of investigating PEDOT:PSS along with two othercandidates that may one day come to replace PEDOT:PSS as the most commonlyused material, molybdenum trioxide (MoO3) and phosphomolybdic acid(PMA). The aim was to investigate how the different materials energy bandstructure would be affected upon exposure to sunlight, air and annealing, byobserving the work function under different conditions.
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Feasibility Analysis of a Powered Lower-Limb Orthotic for the Mobility Impaired UserEby, Wesley R. January 2005 (has links)
Powered orthotic devices can be used to restore mobility to the impaired user, and may thereby assist them in daily living tasks. An investigation is performed herein to examine the feasibility of a powered lower-limb orthotic in assisting the sit-to-stand task by 50% of the required torque. Feasibility is considered via simulation.
A three-link sit-to-stand model, which is driven by kinematic data, is developed. Models of a Pneumatic Muscle Actuator and a DC motor are used to determine which of the two technologies can make a more appropriate contribution to the sit-to-stand task. Simulation revealed that both the Pneumatic Muscle Actuator and the DC motor are reasonable actuator choices, and neither limited the ability to achieve 50% torque assistance. The ability to assist the task was, however, limited by the ability to derive a control signal for the actuator from the user-orthotic interface.
It was concluded that the user-orthotic interface requires further investigation. It was also found that while both actuator technologies are suitable for contributing 50% of the required torque, the Pneumatic Muscle Actuator is preferable due to its ability to scale to greater torques.
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Feasibility Analysis of a Powered Lower-Limb Orthotic for the Mobility Impaired UserEby, Wesley R. January 2005 (has links)
Powered orthotic devices can be used to restore mobility to the impaired user, and may thereby assist them in daily living tasks. An investigation is performed herein to examine the feasibility of a powered lower-limb orthotic in assisting the sit-to-stand task by 50% of the required torque. Feasibility is considered via simulation.
A three-link sit-to-stand model, which is driven by kinematic data, is developed. Models of a Pneumatic Muscle Actuator and a DC motor are used to determine which of the two technologies can make a more appropriate contribution to the sit-to-stand task. Simulation revealed that both the Pneumatic Muscle Actuator and the DC motor are reasonable actuator choices, and neither limited the ability to achieve 50% torque assistance. The ability to assist the task was, however, limited by the ability to derive a control signal for the actuator from the user-orthotic interface.
It was concluded that the user-orthotic interface requires further investigation. It was also found that while both actuator technologies are suitable for contributing 50% of the required torque, the Pneumatic Muscle Actuator is preferable due to its ability to scale to greater torques.
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Robust Generator System Using PM Assisted Synchronous Reluctance Generator with Current-fed DriveBaek, Jeihoon 2009 December 1900 (has links)
The growth of embedded generation and portable electrical installations has led
to an increased demand for low cost, flexible and reliable generator systems for military
and commercial applications. An interior permanent magnet (IPM) machine has high
power density due to its reluctance torque and magnetic torque components so it can
produce a large constant power-speed range. However, an IPM machine needs
demagnetizing current at high-speed during the flux-weakening region and thus develops
an inverter shutdown problem in an uncontrolled generator mode operation. In order to
overcome the disadvantages of the IPM machine, the permanent magnet assisted
synchronous reluctance generator (PMa-SynRG) can be a good solution for low cost,
high efficiency reliable generator systems. A PMa-SynRG can produce a high efficiency
drive by utilizing the proper amount of magnet and reluctance torque. This work
proposes a PMa-SynRG with two flux barriers and permanent magnets embedded in the
second layer of the rotor. A neodymium magnet (NdFeB) was used as permanent magnets in the rotor to prevent demagnetization. Finding the minimum amount of
magnet is one of the goals of the optimization process.
The objectives of this work are to build an optimal design for the 3kW generator
and an advanced power electronics converter for the PMa-SynRG drive system. In order
to find the optimized 3kW machine, a Lumped Parameter Model (LPM) was used to
achieve fast computation, and Differential Evolution Strategy (DES) was used to embed
the LPM in an efficient numerical optimization routine to identify optimum designs.
Finite Element Analysis (FEA) was used for test performance of optimum designs. On
the basis of differences between LPM and FEA, model predictions were used to fine
tune the LPM model. For new optimum design converges, numerical optimizations and
iterations were performed to produce LPM and FEA predictions.
For the drive system, the thyristor based, current-fed drive is much simpler and
has lower power losses compared to the pulse width modulation (PWM) drive.
Eliminating the requirement for self-controlled switches is a distinct advantage for lower
cost. Another feature of the developed current-fed drive is its inherent capability to
provide generating action by making the PMa-SynRG operates as a generator, rectifying
the phase voltages by means of the three-phase rectifier and feeding the power into the
load. These features make the current-fed drive a good candidate for driving any type of
synchronous generators including the proposed PMa-SynRG.
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Analýza datových zdrojů ve státní správě / Data Source Analysis in State AdministrationRezek, Martin January 2016 (has links)
This diploma thesis tackles the issue of data sources used in state administration. Its
aim is to carry out a process analysis of data sources used in internal processes within the
Czech Social Security Administration authority (Česká správa sociálního zabezpečení) and
propose changes to optimise processes within the institution. The theoretical part of the
thesis defines communication between a citizen and public administration and describes its
basic elements. It also looks at the Process Management In Public Administration project
and the evaluation of applications for new ICT projects.
The practical part deals with the application of the theoretical findings to processes
within a particular body of the state administration, the CSSA. The resulting proposal to
optimise selected processes within the entire CSSA institution is based on a process analysis
of data sources from a branch of the District Social Security Administration office (Okresní
správa sociálního zabezpečení) as well as two case studies.
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Apport de nouvelles fonctions à des treillis de soutènement en polypropylène : résistance à l’infection et visualisation en IRM / Addition of new functions to polypropylene meshes for soft tissue reinforcement : resistance to infection and MRI visualizationGuillaume, Olivier 02 December 2011 (has links)
Les opérations chirurgicales pour le traitement des défauts de soutènement d'organes dans les pays industrialisés sont des actes de plus en plus fréquents, et requièrent l'implantation de plus d'un million de prothèses par an. Même si l'usage des prothèses de soutènement a permis de diminuer les complications postopératoires, les taux de réinterventions restent très élevés. Ces travaux présentent différentes stratégies permettant d'apporter de nouvelles propriétés à des treillis en polypropylène, afin d'améliorer leur résistance à l'infection et de permettre leur suivi postopératoire en IRM. Des treillis anti-infectieux sont développés en enrobant les filaments de treillis d'un réservoir de polymère dégradable et biocompatible contenant des agents anti-infectieux, par une technique de pulvérisation à l'aide d'un aérographe. L'association ofloxacine – rifampicine incorporée présente une excellente activité antibactérienne in vitro, et la cinétique de libération prolongée des agents actifs permet d'inhiber la contamination des treillis pendant au moins 72 heures. Les techniques de stérilisation par rayonnement Gamma n'impactent ni la stabilité des agents actifs, ni l'efficacité antibactérienne des treillis anti-infectieux.Afin de permettre une visualisation en IRM des treillis implantés, des polymères ont été synthétisés par greffage d'agent de contraste (DTPA-Gd) sur de la poly(ε-caprolactone) (dégradable) et du poly(acrylate de méthyle) (biostable). Après enrobage des prothèses par ces polymères, le rehaussement du signal induit par la présence du gadolinium permet de visualiser les prothèses à la fois in vitro et in vivo sur différents types d'appareils d'IRM. La stabilité de l'agent de contraste est suffisante pour pouvoir visualiser les treillis pendant plusieurs mois, quelle que soit la technique de stérilisation utilisée. / Soft tissue reinforcement surgical operations in industrial countries are common and require annually at least one million of prostheses for treating this problem. Even if meshes used for organ prolapse surgical procedures allow decreasing postoperatory complications, reinterventions ratio is still relevant. This work present several strategies to bring new properties to polypropylene meshes in order to improve their resistance to infection and enable their postoperative MRI follow-up. Anti-infective meshes are developed by coating the filaments of the meshes with an antibiotics drug reservoir based on degradable and biocompatible polymers, using an airbrush system. Dual ofloxacin-rifampicin antibiotics incorporation on these coated meshes shows an excellent antibacterial activity in vitro and sustained release of the drugs can inhibit meshes contamination for at least 72 hours. Sterilization procedures using Gamma-ray irradiation impact neither the drugs stability nor the anti-infective meshes activity. In order to visualize by Magnetic Resonance Imaging (MRI) meshes after implantation, a contrast agent (DTPA-Gd) is covalently grafted onto the polymeric backbone of poly(ε-caprolactone) (degradable) or poly(methyl acrylate) (biostable). Meshes were coated with these new polymers and MR signal enhancement induced by the presence of gadolinium allows the visualization of the meshes in vitro and in vivo with several MR equipments. Coated meshes are visible during several months, whatever the sterilization procedures, showing the stability of the contrast agent.
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