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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
41

Les études de la dynamique du système micellaire P103/Eau et système de rhéoépaississement CTA-n-Fluorobenzoato. / Study of the rheology and dynamics in micellar triblock copolymers and the shear thickening of CTA-n-Fluorobenzoate systems

Landazuri Gomez, Gabriel 19 July 2013 (has links)
Cette thèse vise à comprendre l’effet des dynamiques des micelles de copolymères sur leurs propriétés rhéologiques. En effet les copolymères amphiphiles peuvent s'auto-assembler dans l’eau pour former diverses microstructures micellaires sphériques, cylindriques ou lamellaires. Leur dynamique est un paramètre crucial pour définir leur spectre d’applications, en particulier dans le transport de médicaments et dans la synthèse de matériaux méso-structurés. Les micelles se structurent en continu: elles peuvent se former et se dissocier en monomères, se fusionner ou se fragmenter. Nous avons développé une méthode basée sur la fluorescence pour sonder directement les dynamiques micellaires collectives de fusion et de fission dans un bon nombre de copolymères triblocs de la famille PEO-PPO-PEO. Cette thèse se concentre sur l'étude des systèmes micellaires formés par des copolymères triblocs (tensioactifs non ioniques) et les tensioactifs cationiques à des concentrations et des températures où micelles sphériques et micelles cylindriques sont formées. De telles structures peuvent être formées spontanément lorsque le système est soumis à des conditions appropriées de concentration et de température ou à l'induction entre elles en ajoutant des sels inorganiques ou organiques, ou en appliquant des contraintes de cisaillement au système tensioactif/eau.La technique de diffusion de la lumière dynamique (DLS) a été utilisée pour évaluer la transition de la structure dans des solutions micellaires en changeant la température du système et de la structure du système correspondant à des conditions de concentration - température.Des expériences de relaxation de contraintes ont été effectuées où l’assouplissement temporaire de contrainte est mesuré après une déformation instantanée dans des solutions aqueuses de P103. Les temps de relaxation (ou taux) sont comparés avec ceux obtenus par diffusion de la lumière et de leur rapport à la taille des micelles est montré. La relaxation des contraintes présente le comportement de Maxwell. Les temps de relaxation ont montré la dépendance de la température avec des comportements caractéristiques des régimes de micelles sphériques et allongées respectivement.Dans ce travail, nous étudions également le système micellaire CTAnFB avec n la substitution de fluor en positions ortho (F: 2), meta (F: 3) et para (F: 4), à savoir les systèmes CTAortoFB/, CTAmetaFB/eau et CTAparaFB/eau à des concentrations diluées. Nous présentons aussi une étude de la dynamique de la simulation moléculaire de l'hydratation de tensioactifs ortho-, méta- et para-fluorobenzoate et son effet sur la formation de micelles.Nous avons étudié l'effet des contre-ions organiques hydrotropes, 2-, 3- et 4-fluorobenzoïque (2FB-, 3FB- et 4FB-, respectivement) sur le comportement d'épaississement par cisaillement de solutions aqueuses micellaires de micelles en forme de tige de leurs sels avec des cations de cétyltriméthylammonium (CTA2FB, CTA3FB et CTA4FB).Ce travail a contribué à la compréhension de la synergie entre la structure, la dynamique micellaire et la rhéologie dans cette famille de copolymère. / This thesis aims to understand the effect of the dynamics of copolymer micelles on their rheological properties. Indeed amphiphilic copolymers can self-assemble in water to form various micellar microstructures spherical, cylindrical or lamellar. Their dynamic is a critical parameter to define their range of applications, particularly in the transport of drugs and in the synthesis of mesostructured materials. Micelles are structured continuous: they can form and dissociate into monomers, merge or fragment. We have developed a method based on fluorescence to probe directly collective micellar dynamics of fusion and fission in a number of triblock copolymers of PEO -PPO -PEO family.This thesis focuses on the study of micellar systems formed by triblock copolymers (nonionic surfactants) and cationic surfactants at concentrations and temperatures where spherical micelles and rod like micelles are formed. Such structures may be formed spontaneously when the system is subjected to appropriate conditions of concentration and temperature or to the induction of these by adding inorganic or organic salts, or by applying shear stresses to the surfactant/water system.The technique of dynamic light scattering (DLS) was used to evaluate the transition of the structure in micellar solutions by changing the temperature and the structure of the system itself at given concentration - temperature conditions.Stress relaxation experiments were performed where temporary relaxation of stress is measured after a momentary deflection in aqueous solutions of P103. The relaxation times (or rate) are compared with those obtained by light scattering and their relation to the size of the micelles is shown. The stress relaxation presented a Maxwelian behavior. The relaxation times showed temperature dependence with characteristic behavior schemes for elongated and spherical micelles respectively.In this work, we also study the micellar system CTAnFB where “n” is substitution of fluorine in the ortho position (F:2) meta ( F:3) and para (F:4), namely CTAortoFB/water CTAmetaFB/water and CTAparaFB/water systems in diluted concentrations. We presented a study of molecular dynamics simulation of the hydration of ortho-, meta-, para- Fluorobenzoate surfactants and its effect on the formation of micelles.The effect of hydrotropes organic counterions , 2- , 3- and 4- fluorobenzoic acid (2FB-, 3FB- and 4FB-, respectively), the shear thickening behavior of aqueous micellar solutions of rod like micelles thereof salts with cations of cetyltrimethylammonium (CTA2FB, CTA3FB and CTA4FB ) were studied.This work has contributed to the understanding of the synergy between the structure, dynamics and rheology of micellar in this family of copolymer.
42

Nanoparticules en réseau pour la protection cutanée / Nanoparticular network for the skin protection

Bignon, Cécile 10 November 2015 (has links)
Les agents chimiques de guerre et leurs dérivés pesticides sont des molécules toxiques qui provoquent une incapacité temporaire ou des dommages permanents allant jusqu’à la mort de l’individu. Une des voies majeures de la contamination est la pénétration cutanée. La protection de la peau semble donc importante pour prévenir de ces dangers. Cette thèse concerne l’élaboration de nouveaux topiques protecteurs cutanés contenant des polymères HASE fluorés greffés avec des nanoparticules de silice, cérine ou titane. Dans un premier temps les actifs ont été synthétisés en grosse quantité et leurs propriétés de mouillabilité améliorées. Les tests toxicologiques ont montré que les actifs n’étaient pas irritants pour la peau et non toxiques pour l’environnement. La formulation de ces polymères a permis le développement de deux nouvelles crèmes barrières contre la pénétration du paraoxon dont l’efficacité est dépendante de la présence des nanoparticules. Le greffage des nanoparticules à un polymère HASE fluoré et leur formulation a donc permis le développement de nouveaux topiques efficaces. L’évaluation de l’efficacité a été réalisée sur membranes artificielles et confirmée sur explants de peaux humaines. Enfin, le peu de disponibilité des explants de peaux humaines a motivé le développement d’un modèle d’efficacité utilisant des épidermes humains reconstruits. / Chemical warfare agents and pesticides are toxic molecules causing temporary incapacitation or permanent harms leading to the death of people. One of the major routes of contamination is the percutaneous penetration. Skin protection is important to prevent these dangers. The aim of this thesis is to develop new active topical skin protectants based on nanoparticular networks containing fluorinated HASE polymers grafting with silica, cerium or titanium nanoparticles. First, polymers were synthesized in larger quantity and their wettability properties improved. Toxicological studies have showed that these compounds are non-irritant and non-toxic for the environment. The formulation of these polymers has led to the elaboration of two new barrier creams against paraoxon penetration whose efficiency is dependent on the presence of nanoparticles. Therefore, the grafting of nanoparticles to fluorinated HASE polymer and their formulation have enabled the development of new active topical skin protectant. Efficiency evaluation was done using artificial membranes and was confirmed on ex vivo human skin. The limited availability of human skin explants has motivated the development of a new efficiency model using reconstructed human epidermis.
43

Propriétés d'écoulement de suspensions concentrées de particules de PVC et leur lien avec la physico-chimie du système / Flow properties of PVC-particles concentrated suspensions and their relation to physico-chemistry of the system

Chatté, Guillaume 18 September 2017 (has links)
Nous étudions des suspensions concentrées de particules non-colloïdales de PVC. Ces suspensions, appelées plastisols, sont utilisées principalement pour la fabrication de revêtements de sols.Elles présentent notamment un phénomène de rhéoépaississement (hausse de la viscosité en cisaillant). Nous montrons que cela provient des forces de frottement entre particules. En effet, à l’aide d’un microscope à force atomique, nous sommes pour la 1ère fois capable de relier directement la contrainte macroscopique d’apparition du rhéo-épaississement à la contrainte microscopique d’apparition de la friction solide entre particules.Nous caractérisons la viscosité de la suspension jusqu’à 100 000 s-1 et nous observons qu’une plus grande polydispersité limite le rhéoépaississement. Les différences de contraintes normales N1 et N2 sont aussi mesurées. Par ailleurs, des mesures à l’aide de rayons X ou d’ultrasons ne montrent aucune migration de particules sous cisaillement.Nous montrons également que la géométrie a un fort impact sur l’écoulement de la suspension concentrée. Un entrefer plus petit provoque une baisse de la viscosité et retarde le rhéoépaississement. Une approche non-locale permet de rationaliser les résultats.La substitution de particules de PVC par des particules de CaCO3 modifie profondément la viscosité et la densité d’empilement maximum. Nous développons alors des modèles simples pour modéliser ces effets. En outre, nous mesurons l’impact sur la rhéologie d’un éventuel surfactant à la surface des particules.Nous avons pu finalement étudier des instabilités observées en étalant ces suspensions à haute vitesse. Une instabilité de surface est d’abord observée. A plus haute vitesse, un dépôt se forme en aval sur le couteau. Nous corrélons ces instabilités avec l’apparition de différences de contraintes normales. / Highly concentrated and non-colloidal suspensions consisting of micrometric PVC particles dispersed in a liquid phase, were studied. These suspensions, called plastisol, are mostly used in vinyl flooring manufacture.A key feature of these suspensions is shear-thickening, since viscosity greatly increases as a function of the applied shear rate. This phenomenon is explained as being related to frictional forces between particles. Indeed, using an Atomic Force Microscope, we were able, for the first time, to link the macroscopic stress, at which shear-thickening appears, with the microscopic stress needed to enter a frictional regime.We then characterize the suspension viscosity up to 100 000 s-1. We observed that shear thickening is lowered with a more polydisperse powder. Large normal stress differences N1 and N2 were also measured, along with shear thickening. In addition, using both X-ray radiography and ultrasound, no particle migration in the sheared suspension could be detected.We also found that geometry plays a major role in the features of the flow of concentrated suspensions. For a smaller gap, the viscosity is lower and shear-thickening is pushed to higher shear rates. A non-local approach accounts for our experimental results.Replacing a number of PVC particles with CaCO3 particles changes both the viscosity and the maximum packing fraction quite dramatically. For both of these, we developed simple models that matched quite well with the experimental data. Moreover, we elucidate the rheological changes resulting from adding surfactant at the surface of each particle type.Finally, we investigated some instabilities observed while coating at high speed. At a moderate speed, a ribbing phenomenon appears. At a higher speed, a deposit is formed on the knife (downstream). The appearance of these instabilities correlates with normal stress differences
44

Poruchovost městských čistíren odpadních vod / Failure rate wastewater treatment plants

Boryśová, Michaela January 2012 (has links)
This thesis deals with the sludge management in wastewater treatment plants. It provides a basic overview of methods for modifying risk material in sludge ending. The main goal of this work is to create a fault trees based on faults which occurred in the sludge management facilities. Furthermore, it was created frequency of failures assessment of the objects on wastewater treatment plant in Hodonín. Provided information were obtained during excursions of WWTP Hodonín and Zbýšov.
45

An Investigation of the ca. 2.7 Ga Late Archean Magmatic Event (LAME) in the Superior Province using 1-D Thermal Modelling

Ahmad, Seema 03 March 2010 (has links)
The Late Archean Magmatic Event (LAME), ca. 2.7 Ga, was the greatest crustal addition event in Earth history. My focus is the Superior Province of Canada, where LAME occurred ca. 2.75 – 2.65 Ga. Mantle plumes impinged on the Abitibi subprovince, where ~ 16 km regional thickness of tonalite-trondhjemite-granodiorite (TTG) melt was produced. Granites (sensu stricto) were the last magmatic phase of LAME, with a Superior-wide regional thickness of ~ 1 – 3 km. Assuming a crustal source for both TTG and granites, I use 1-D thermal models to investigate the origin of TTG in the Abitibi subprovince and that of late granites in the Superior Province. Melting curves appropriate to the source of TTG and granites are used to determine the thickness of melt produced in the models. I show that the incorporation of upward melt transfer into a standard model of lower crustal melting may increase the amount of predicted melt by ~ 1/(1-f), where f denotes the fraction of melt that is on average being extracted from the source rocks. Partitioning of heat producing elements between melt and restite reduces the amount of melt produced, but the effect is secondary compared to the increase in melt production through upward melt transfer. For the Abitibi subprovince, I show that the emplacement of a single plume coupled with the emplacement of a 12-km-thick greenstone cover can generate a maximum of ~ 9-km-thickness of TTG melt. However, the emplacement of a series of plumes, each coupled with the emplacement of a 3-km-thick greenstone cover and a 10-km-thick sill results in ~ 20-km-thickness of TTG melt. My model incorporates delamination of restitic eclogite. Finally, I show that late granites in the Superior Province may have resulted from thickening of a crust that had been “pre-heated” during earlier arc activity and that prolonged granitic magmatism observed in some areas of the Superior Province may be explained by late underthrusting of fertile source rocks into deeper and hotter regions of the crust.
46

An Investigation of the ca. 2.7 Ga Late Archean Magmatic Event (LAME) in the Superior Province using 1-D Thermal Modelling

Ahmad, Seema 03 March 2010 (has links)
The Late Archean Magmatic Event (LAME), ca. 2.7 Ga, was the greatest crustal addition event in Earth history. My focus is the Superior Province of Canada, where LAME occurred ca. 2.75 – 2.65 Ga. Mantle plumes impinged on the Abitibi subprovince, where ~ 16 km regional thickness of tonalite-trondhjemite-granodiorite (TTG) melt was produced. Granites (sensu stricto) were the last magmatic phase of LAME, with a Superior-wide regional thickness of ~ 1 – 3 km. Assuming a crustal source for both TTG and granites, I use 1-D thermal models to investigate the origin of TTG in the Abitibi subprovince and that of late granites in the Superior Province. Melting curves appropriate to the source of TTG and granites are used to determine the thickness of melt produced in the models. I show that the incorporation of upward melt transfer into a standard model of lower crustal melting may increase the amount of predicted melt by ~ 1/(1-f), where f denotes the fraction of melt that is on average being extracted from the source rocks. Partitioning of heat producing elements between melt and restite reduces the amount of melt produced, but the effect is secondary compared to the increase in melt production through upward melt transfer. For the Abitibi subprovince, I show that the emplacement of a single plume coupled with the emplacement of a 12-km-thick greenstone cover can generate a maximum of ~ 9-km-thickness of TTG melt. However, the emplacement of a series of plumes, each coupled with the emplacement of a 3-km-thick greenstone cover and a 10-km-thick sill results in ~ 20-km-thickness of TTG melt. My model incorporates delamination of restitic eclogite. Finally, I show that late granites in the Superior Province may have resulted from thickening of a crust that had been “pre-heated” during earlier arc activity and that prolonged granitic magmatism observed in some areas of the Superior Province may be explained by late underthrusting of fertile source rocks into deeper and hotter regions of the crust.
47

Proudění nestlačitelných tekutin s viskozitou závislou na tlaku (a jejich aplikace při modelování proudění v ložisku) / Flows of incompressible fluids with pressure-dependent viscosity (and their application to modelling the flow in journal bearing)

Lanzendörfer, Martin January 2011 (has links)
Title: Flows of incompressible fluids with pressure-dependent viscosity (and their application to modelling the flow in journal bearing) Author: Martin Lanzendörfer Department: Mathematical Institute of Charles University Supervisor: prof. RNDr. Josef Málek, DSc. Abstract: The viscosity of the fluids involved in hydrodynamic lubrication typically depends on pressure and shear rate. The thesis is concerned with steady isothermal flows of such fluds. Generalizing the recent results achieved in the case of homogeneous Dirichlet boundary conditions, the existence and uniqueness of weak solutions subject to the boundary conditions employed in practical applications will be established. The second part is concerned with numerical simulations of the lubrication flow. The experiments indicate that the presented finite element method is successful as long as certain restrictions on the constitutive model are met. Both the restrictions involved in the theoretical results and those indicated by the numerical experiments allow to accurately model real-world lubricants in certain ranges of pressures and shear rates. The last part quantifies those ranges for three representative lubricants. Keywords: existence and uniqueness of weak solutions, finite element method, pressure- thickening, shear-thinning, incompressible fluids,...
48

Caracterização de Estafilococos Coagulase-Negativa de origem hospitalar e comunitária quanto à diversidade clonal e a determinantes de resistência antimicrobiana

Pinheiro, Luiza. January 2018 (has links)
Orientador: Maria de Lourdes Ribeiro de Souza da Cunha / Resumo: A alta frequência de Estafilococos Coagulase-Negativa (CoNS) na pele de indivíduos saudáveis e em doenças associadas ao sangue, associados à seleção de cepas resistentes devido a uso indiscriminado de antimicrobianos, tornou mais estreitos os limites entre o ambiente hospitalar e o comunitário quanto à distribuição de cepas. Objetivou-se, com este estudo, caracterizar isolados de CoNS de origem hospitalar e comunitária da cidade de Botucatu-SP quanto ao perfil clonal, analisar os aspectos de resistência à oxacilina pela aferição de metodologia de detecção, e investigar os determinantes de heterorresistência à vancomicina nessas cepas. As espécies estudadas incluíram S. epidermidis, S. haemolyticus, S. warneri, S. hominis, S. lugdunensis, S. capitis, S. saprophyticus, S. pasteuri, S. simulans e S. xylosus. O teste de disco-difusão (TDD) com discos de oxacilina e cefoxitina, fitas de Etest impregnadas com oxacilina e pesquisa do gene mecA por PCR em tempo real foram realizadas. A triagem em ágar com 6 e 8 µg/ml de vancomicina, microdiluição em caldo para aferição da Concentração Inibirtória Mínima (MIC), microscopia eletrônica de transmissão para verificar espessamento da parede celular e alterações fenotípicas por testes bioquímicos foram realizadas. O perfil clonal foi determinado por PFGE (Pulsed-Field Gel Eletrophoresis) e para clones de S. epidermidis, o MLST (Multilocus Sequence Typing). S. epidermidis apresentou alta diversidade clonal, mas presença de clusters no ambien... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The high frequency of Coagulase-Negative Staphylococci (CoNS) on the skin of healthy individuals and in bloodstream infections, together with the selection of resistant strains, has narrowed the boundaries between the hospital and the community environment for the distribution of strains. This study aimed to characterize CoNS isolated from clinical and colonization specimens of patients and individuals from Botucatu-SP, to compare their clonal profile, to analyze the determination of oxacillin resistance by the evaluation of the methodology of detection, and to investigate the determinants of reduced susceptibility to vancomycin in those strains. CoNS species included S. epidermidis, S. haemolyticus, S. warneri, S. hominis, S. lugdunensis, S. capitis, S. saprophyticus, S. pasteuri, S. simulans and S. xylosus. The disc diffusion test (DDT) using oxacillin and cefoxitin discs was employed, Etest strips impregnated with oxacillin and mecA gene detection by real-time PCR were used. An agar screening with 6 and 8 µg/ml of vancomycin, the broth microdiluition method for the Minimal Inhibitory Concentration (MIC), the transmission eletronic microscopy for evaluation of cellwall thickening and phenotypic modifications by biochemical tests were performed. Clonal profile was determined by PFGE (Pulsed-Field Gel Eletrophoresis) and, for S. epidermidis clones, MLST (Multilocus Sequence Typing). S. epidermidis presented high clonal diversity, despite some clusters circulating within hospi... (Complete abstract click electronic access below) / Doutor
49

Avaliação da expressão dos fatores angiogênicos VEGF a e seus receptores e FGFB em tecido hepático de pacientes com atresia biliar

Edom, Patrícia Turnes January 2009 (has links)
A atresia biliar (AB) é uma colangiopatia de etiologia indeterminada que leva à necessidade de transplante hepático, mesmo com a realização da Portoenterostomia em tempo hábil. O espessamento da camada média da artéria hepática sugere o envolvimento de um distúrbio angiogênico. Este estudo objetivou avaliar a expressão imunoistoquímica do VEGF A e seus receptores nas estruturas hepatobiliares de pacientes com AB. Nós avaliamos, por método semiquantitativo, a positividade do VEGF A, VEGFR1 e VEGFR2 em biópsia de fígados obtidas por ocasião da Portoenterostomia de crianças com AB (n=52),com (n=14) e sem (n=38) malformação extra-hepáticas. Seviram como controles, pacientes com colestase intra-hepática (CI)\ (n=7). A positividade do VEGFA foi também avaliada em explantes (n=33) e porta hepatis (n=16) de pacientes com AB. Avaliamos morfometricamente as variáveis positividade de CK7 (PCK7) em biópsia de pacientes com AB e a relação espessura da camada média arterial/ diâmetro luminal (REMD) em ramos da artéria hepática de pacientes com AB e de pacientes com CI. Nós encontramos que a positividade do VEGF A foi maior em pacientes com AB por ocasião da Portoenterostomia (p=0, 006) que nos outros grupos, enquanto que nos explantes, a positividade de VEGF A foi maior no parênquima (P<0.001). A positividade do VEGFR2 em ducto biliares e hepatócitos foi menor em pacientes com AB que nos casos de CI (P=0.023 e P=0.011, respectivamente). Maior positividade de CK7 ocorreu em pacientes com artérias e estruturas biliares positivas para VEGF A (P<0.001 e P=0.040, respectivamente). Nos pacientes com AB por ocasião da Portoenterostomia a positividade do VEGF A em estruturas biliares, artérias e hepatócitos correlacionou-se com PCK7 (P=0.031, P=0.031 e P=0.032, respectivamente). O VEGF A foi expresso no porta hepatis de pacientes com AB em artérias e em ductos biliares, principalmente nos pacientes sem malformações extra-hepáticas (P=0.013). A positividade do VEGF A associou-se com a maior REMD (P=0.016 e P=0.044, respectivamente). Nossos achados sugerem que a colangiopatia isquêmica, agravada pela proliferação biliar, ocorre na AB por ocasião da Portoenterostomia, começando no porta hepatis. O espessamento da camada média arterial está associada à expressão do VEGF A. / In Biliary atresia (BA) a cholangiopathy of elusive etiology leads to the need of liver transplantation regardless of timely performance of Portoenterostomy; hepatic arterial medial thickening suggests involvement of a disturbed angiogenesis. This study aimed to evaluate the immunohistochemical expression of VEGF A and its receptors in hepatobiliary structures in BA. We semiquantitatively analyzed the positivity rate of VEGF A, VEGF-R1 and -R2 in liver biopsies obtained at Portoenterostomy from infants with BA (n=52), with (n=14) and without (n=38) extrahepatic malformations. Controls were infants with intrahepatic cholestasis (IC, n=7). VEGF A positivity was also evaluated in explants (n=33) and at porta hepatis (n=16) from patients with BA. We morphometrically assessed the variables percentage of CK-7 positivity (PCK7) in biopsies from patients with BA, and the ratio medial layer thickness/luminal diameter (RMED) in hepatic arterial branches from infants with BA and IC. We found that arterial VEGF A positivity was higher in patients with BA at the time of Portoenterostomy (P=0.006) than in other groups, while explants’parenchyma presented the highest VEGF A positivity (P<0.001). Biliary and hepatocytic VEGFR2 positivity was lower in BA than IC (P=0.023 and P=0.011, respectively). Higher PCK7 occurred in arterial and biliary VEGF A-positive patients (P<0.001 and P=0.040, respectively). Biliary, arterial and hepatocytic VEGF A positivity in BA at Portoenterostomy was correlated with PCK7 (P=0.031, P=0.031 and P=0.032, respectively). VEGF A was expressed at porta hepatis from BA patients in arteries, and, in bile ducts mainly in patients without extrahepatic malformations (P=0.013). Biliary and arterial VEGF A positivity was associated with higher RMED (P=0.016 and P=0.044, respectively). Our findings suggest that an ischemic cholangiopathy, aggravated by biliary proliferation, exists in BA at the time of Portoenterostomy, beginning at porta hepatis. Medial layer thickening is associated with VEGF A expression.
50

Avaliação da expressão dos fatores angiogênicos VEGF a e seus receptores e FGFB em tecido hepático de pacientes com atresia biliar

Edom, Patrícia Turnes January 2009 (has links)
A atresia biliar (AB) é uma colangiopatia de etiologia indeterminada que leva à necessidade de transplante hepático, mesmo com a realização da Portoenterostomia em tempo hábil. O espessamento da camada média da artéria hepática sugere o envolvimento de um distúrbio angiogênico. Este estudo objetivou avaliar a expressão imunoistoquímica do VEGF A e seus receptores nas estruturas hepatobiliares de pacientes com AB. Nós avaliamos, por método semiquantitativo, a positividade do VEGF A, VEGFR1 e VEGFR2 em biópsia de fígados obtidas por ocasião da Portoenterostomia de crianças com AB (n=52),com (n=14) e sem (n=38) malformação extra-hepáticas. Seviram como controles, pacientes com colestase intra-hepática (CI)\ (n=7). A positividade do VEGFA foi também avaliada em explantes (n=33) e porta hepatis (n=16) de pacientes com AB. Avaliamos morfometricamente as variáveis positividade de CK7 (PCK7) em biópsia de pacientes com AB e a relação espessura da camada média arterial/ diâmetro luminal (REMD) em ramos da artéria hepática de pacientes com AB e de pacientes com CI. Nós encontramos que a positividade do VEGF A foi maior em pacientes com AB por ocasião da Portoenterostomia (p=0, 006) que nos outros grupos, enquanto que nos explantes, a positividade de VEGF A foi maior no parênquima (P<0.001). A positividade do VEGFR2 em ducto biliares e hepatócitos foi menor em pacientes com AB que nos casos de CI (P=0.023 e P=0.011, respectivamente). Maior positividade de CK7 ocorreu em pacientes com artérias e estruturas biliares positivas para VEGF A (P<0.001 e P=0.040, respectivamente). Nos pacientes com AB por ocasião da Portoenterostomia a positividade do VEGF A em estruturas biliares, artérias e hepatócitos correlacionou-se com PCK7 (P=0.031, P=0.031 e P=0.032, respectivamente). O VEGF A foi expresso no porta hepatis de pacientes com AB em artérias e em ductos biliares, principalmente nos pacientes sem malformações extra-hepáticas (P=0.013). A positividade do VEGF A associou-se com a maior REMD (P=0.016 e P=0.044, respectivamente). Nossos achados sugerem que a colangiopatia isquêmica, agravada pela proliferação biliar, ocorre na AB por ocasião da Portoenterostomia, começando no porta hepatis. O espessamento da camada média arterial está associada à expressão do VEGF A. / In Biliary atresia (BA) a cholangiopathy of elusive etiology leads to the need of liver transplantation regardless of timely performance of Portoenterostomy; hepatic arterial medial thickening suggests involvement of a disturbed angiogenesis. This study aimed to evaluate the immunohistochemical expression of VEGF A and its receptors in hepatobiliary structures in BA. We semiquantitatively analyzed the positivity rate of VEGF A, VEGF-R1 and -R2 in liver biopsies obtained at Portoenterostomy from infants with BA (n=52), with (n=14) and without (n=38) extrahepatic malformations. Controls were infants with intrahepatic cholestasis (IC, n=7). VEGF A positivity was also evaluated in explants (n=33) and at porta hepatis (n=16) from patients with BA. We morphometrically assessed the variables percentage of CK-7 positivity (PCK7) in biopsies from patients with BA, and the ratio medial layer thickness/luminal diameter (RMED) in hepatic arterial branches from infants with BA and IC. We found that arterial VEGF A positivity was higher in patients with BA at the time of Portoenterostomy (P=0.006) than in other groups, while explants’parenchyma presented the highest VEGF A positivity (P<0.001). Biliary and hepatocytic VEGFR2 positivity was lower in BA than IC (P=0.023 and P=0.011, respectively). Higher PCK7 occurred in arterial and biliary VEGF A-positive patients (P<0.001 and P=0.040, respectively). Biliary, arterial and hepatocytic VEGF A positivity in BA at Portoenterostomy was correlated with PCK7 (P=0.031, P=0.031 and P=0.032, respectively). VEGF A was expressed at porta hepatis from BA patients in arteries, and, in bile ducts mainly in patients without extrahepatic malformations (P=0.013). Biliary and arterial VEGF A positivity was associated with higher RMED (P=0.016 and P=0.044, respectively). Our findings suggest that an ischemic cholangiopathy, aggravated by biliary proliferation, exists in BA at the time of Portoenterostomy, beginning at porta hepatis. Medial layer thickening is associated with VEGF A expression.

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