Submitted by Jean Medeiros (jeanletras@uepb.edu.br) on 2017-11-22T12:29:08Z No. of bitstreams: 1 PDF - Fernanda Ílary Costa Duarte.pdf: 24657537 bytes, checksum: 9b772bea9140014dc3032302a9add7fd (MD5) / Approved for entry into archive by Secta BC (secta.csu.bc@uepb.edu.br) on 2017-12-06T18:34:10Z (GMT) No. of bitstreams: 1 PDF - Fernanda Ílary Costa Duarte.pdf: 24657537 bytes, checksum: 9b772bea9140014dc3032302a9add7fd (MD5) / Made available in DSpace on 2017-12-06T18:34:10Z (GMT). No. of bitstreams: 1 PDF - Fernanda Ílary Costa Duarte.pdf: 24657537 bytes, checksum: 9b772bea9140014dc3032302a9add7fd (MD5) Previous issue date: 2016-03-17 / The lipoic acid acts as a cofactor for mitochondrial multienzyme complex, with intense ability to inhibit free radicals in aqueous and lipid being touted as a promising substance in antioxidant defense. In Brazil it is commonly marketed in capsule form for master pharmacies. Solid pharmaceutical forms tend to have problems related to bioavailability, making it necessary to perform the test of dissolution. The Brazilian Pharmacopeia does not show us in the percentage dissolution for the lipoic acid in the form of capsules, while the American Pharmacopoeia presents only the liquid chromatography (HPLC) method feeder on dissolution of this active pharmaceutical ingredient (IFA). In view of the absence of conditions in the Brazilian official code for these tests and the search for less costly techniques the goal is the development and validation of a methodology for quantification of lipoic acid on its dissolution in vitro study in capsules by UV/Vis spectrophotometry and high performance liquid chromatography ultraeficiência (CLUE). For that, physical and chemical characterization of the IFA, lipoic acid, through your recrystallization to assess purity and presence of polymorphism using TG/DTG, DSC, FTIR and DRX. To evaluate the ability of encapsulation of the wording proposed was conducted study of micromériticas properties, from analysis of the angle of repose, Hausner factor (FH), Carr index (CI) and flow rate. The method of dissolution employee followed the parameters recommended by the American Pharmacopoeia, and for the analysis of dissolution profiles was developed and validated methods of quantification of the drug by UV/Vis spectrophotometry and by CLUE, following the parameters of specificity, linearity, precision, accuracy, limits of detection and quantification, robustness. It was observed, from the results of TG/DTG-DSC, FTIR and XRD, the IFA used presented considerable purity and lacks polymorphism. The microméritico study has shown that the formulation presented a good flow. The methodologies for the quantification of samples of dissolution by UV/Vis spectrophotometry and CLUE fit in all validation parameters established, the developed formulation presented dissolved content percentage above 70%, in accordance with the official textbooks. There was a statistically significant difference between the methods studied, demonstrating the feasibility of using the Spectrophotometric method for evaluation of the in vitro dissolution, for their greater accessibility and lower cost. With this, it is concluded that the methods developed are safe and effective for the purpose intended and that the wording developed with lipoic acid led to the dissolution of the active ingredient. / O ácido lipóico funciona como um cofator para complexos multienzimáticos mitocondriais, com intensa capacidade de inibir radicais livres em meio aquoso e lipídico, sendo apontado como uma substância promissora na defesa antioxidante. No Brasil é comumente comercializado na forma de cápsulas por farmácias magistrais. Formas farmacêuticas sólidas tendem a apresentar problemas relacionados à biodisponibilidade, tornando-se necessário realizar o ensaio de dissolução. A Farmacopeia Brasileira não apresenta percentual de cedência no ensaio de dissolução para o ácido lipóico na forma de cápsulas, enquanto que a Farmacopeia Americana apresenta apenas a cromatografia liquida de alta eficiência (CLAE) como método dosador na dissolução deste ingrediente farmacêutico ativo (IFA). Tendo em vista a ausência de condições no código oficial brasileiro para estes ensaios e a busca por técnicas menos onerosas, objetiva-se o desenvolvimento e a validação de metodologia para quantificação do ácido lipóico no estudo de sua dissolução in vitro em cápsulas, por meio da espectrofotometria UV/Vis e da cromatografia líquida de ultraeficiência (CLUE). Para isso, realizou-se caracterização físico-química do IFA, ácido lipóico, através de sua recristalização, a fim de avaliar pureza e presença de polimorfismo, utilizando TG/DTG, DSC, FTIR e DRX. Para avaliar a capacidade de encapsulamento da formulação proposta foi realizado estudo das propriedades micromériticas, a partir de análise do ângulo de repouso, Fator de Hausner (FH), Índice de Carr (IC) e velocidade de escoamento. O método de dissolução empregado seguiu os parâmetros preconizados pela Farmacopeia Americana, e para a análise dos perfis de dissolução foi desenvolvido e validado métodos de quantificação do fármaco por espectrofotometria UV/Vis e por CLUE, seguindo os parâmetros de especificidade, linearidade, precisão, exatidão, limites de detecção e quantificação, robustez. Foi observado, a partir dos resultados de TG/DTG-DSC, FTIR e DRX, que o IFA utilizado apresentou pureza considerável e não possui polimorfismo. O estudo microméritico demonstrou que a formulação apresentou um bom fluxo. As metodologias para quantificação das amostras de dissolução por espectrofotometria UV/Vis e CLUE se enquadraram em todos os parâmetros de validação estabelecidos, a formulação desenvolvida apresentou percentual de teor dissolvido acima de 70% , estando de acordo com os compêndios oficiais. Não se verificou diferença estatística significativa entre os métodos estudados, demonstrando a viabilidade do uso do método espectrofotométrico para avaliação da dissolução in vitro, por sua maior acessibilidade e menor custo. Com isto, conclui-se que os métodos desenvolvidos são seguros e eficazes para o objetivo pretendido e que a formulação desenvolvida com ácido lipóico permitiu a dissolução considerável do princípio ativo.

Taludes escavados em filitos muitas vezes estão sujeitos à instabilidade, principalmente quando há outras famílias de descontinuidades presentes na estrutura. Este problema está presente na mina de Candiota, onde foi identificado, em um dos taludes, potencialidade para ruptura por tombamento. Este trabalho aborda uma discussão sobre métodos analíticos e numéricos aplicado a tombamento primário, com objetivo de avaliar o fator de segurança do talude em estudo por meio de método numérico por elementos finitos, utilizando o Phase2 da Rocscience, e métodos analíticos. Também são apresentadas doze simulações para avaliar se o movimento de tombamento em modelagens numéricas obedece a um efeito de escala. Com uso de métodos numéricos dois modelos foram construídos: um contínuo equivalente e outro contínuo (mas com as descontinuidades inseridas no modelo). No modelo com as descontinuidades a rocha foi tratada como elástica por meio do critério de Hoek-Brown e as descontinuidades foram tratadas como elasto-plásticas por meio do critério de Mohr-Coulomb. Os resultados das modelagens da mina de Candiota foram semelhantes e mostraram fatores de segurança em níveis de estabilidade, sendo que no modelo contínuo (mas com descontinuidades inseridas) se observou de forma mais clara as tensões cisalhantes induzidas nas descontinuidades quando ocorre o movimento de tombamento. O uso dos métodos analíticos mostrou-se ineficientes para o problema apresentado. Os resultados das doze modelagens sugerem que o aumento do espaçamento das descontinuidades influencia nos fatores de resistência dos taludes e na forma do movimento de tombamento. / Slopes in phyllites are often subject to instability, especially when there are other families of discontinuities in the structure. This problem is present in Candiota mine, which was identified in one of the slopes potential to toppling. This work show a discussion of analytical and numerical methods applied to toppling, to evaluate the slope safety factor being studied by numerical method finite element using the Phase2 of Rocscience, and analytical methods. Also shown are twelve simulations to evaluate if the toppling in numerical modeling follows a scaling effect. With use of numerical methods two models were built: an equivalent continuous and another solid (but with discontinuities inserted in the model). In the model with the discontinuities the rock was treated as elastic by the Hoek-Brown criterion and discontinuities were treated as elastic-plastic by the Mohr-Coulomb criterion. The results of Candiota mine were similar and showed safety factors in stability levels, and in the continuous model (with discontinuities) was observed more clearly the shear stress induced in discontinuities when the movement of overturning occurs. The use of analytical methods proved inefficient for the problem presented. The results of the twelve modeling suggests increasing the spacing of the discontinuities of slope influences the resistance factor and the form of the toppling movement.

Ferro bisglicinado (Fe-bis-gli) é um aminoácido quelado, formado pela ligação de duas moléculas de glicina a uma molécula de ferro (II), utilizado para prevenção e tratamento da anemia ferropriva. Não há descrição de métodos analíticos em códigos oficiais para o controle de qualidade do ferro bisglicinado em formas farmacêuticas. É comercializado na forma de cápsulas, produzidas por farmácias magistrais e em forma oral líquida. Deste modo, o objetivo deste trabalho foi a validação de métodos analíticos para o controle qualitativo e quantitativo do Febis- gli em cápsulas e forma oral líquida. A identificação e caracterização do fármaco foram realizadas através da determinação dos caracteres físicos, solubilidade, aquametria, espectrofotometria na região do infravermelho (IV), reações específicas e espectroscopia de Mössbauer. Para a determinação quantitativa foram validados métodos de espectrofotometria na região do visível (VIS), ordem-zero e primeira derivada (VIS-D¹), e cromatografia líquida de alta eficiência (CLAE). A análise estatística demonstrou equivalência entre os métodos CLAE / VIS para a determinação do teor das cápsulas e entre os métodos CLAE / VIS-D¹ para a determinação do Fe-bis-gli na forma oral líquida. / Ferrous bisglicycinate (Fe-bis-gli) is an amino acid chelate which is formed by the binding of two molecules of glycine to one molecule of Fe(II), used for prevention and treatment of iron deficiency. There are no analytical methods in official codes for the quality control of Fe-bis-gli in pharmaceutical forms; however it is marketed in the form of capsules , produced by compounding pharmacies and as oral liquid form. The aim of this work was the validation of analytical methods for the qualitative and quantitative analysis of Fe-bis-gli capsules and oral liquid form. The identification and characterization of the drug were performed through the determination of physical characteristics, solubility, water, infrared (IR), specific reactions and Mössbauer spectroscopy. For the quantitative determination VIS spectrophotometry methods have been validated, zero-order and first derivative (VIS-D¹) and high performance liquid chromatography (HPLC). Statistical analysis showed that HPLC / VIS methods were equivalent to assay capsules and HPLC / VIS-D¹ methods were equivalent to assay Fe-bis-gli in oral liquid form.

Esta tesis analiza los métodos estáticos, los cuales comprenden los métodos analíticos y semi empíricos que son utilizados para determinar la capacidad de carga teórica en pilotes, y los compara con las pruebas de carga dinámica, las cuales brindan el resultado real de la capacidad de carga de un pilote. El análisis realizado recopila las teorías de Therzaghi, Hansen, Meyerhof y Bowles, en cuanto a los modelos analíticos, y las teorías de Aoki Velloso, Decourt Quaresma, Pedro Paulo Velloso y Texeira, por parte de las teorías semi empíricas. / This thesis analyzes the static methods, which include the analytical and semi-empirical methods that are used to determine the theoretical load capacity in piles, and compares them with the dynamic load tests, which provide the real result of the load capacity of a pile. The analysis compiles the theories of Therzaghi, Hansen, Meyerhof and Bowles, regarding the analytical models, and the theories of Aoki Velloso, Decourt Quaresma, Pedro Paulo Velloso and Texeira, by the semi-empirical theories. / Tesis

No description available.

Biochemical markers (i.e., biomarkers) are of key importance to guide clinical decisions and public health policies by enabling early detection, accurate diagnosis and/or prevention of human diseases. However, major challenges remain due to the limited clinical utility of many biomarkers and the lack of robust analytical methods for their reliable measurements in a routine clinical setting that is also suitable to large-scale epidemiological studies. This thesis includes two major research themes involving the analysis of known biomarkers that lack appropriate methods, and the discovery of new biomarkers for complex disease conditions. In particular, this thesis describes the (1) development and validation of robust analytical methods based on capillary electrophoresis (CE) with photometric detection for the measurement of inorganic anions in volume-restricted biofluids; and (2) characterization of the sweat metabolome in infants and identification of sweat biomarkers in asymptomatic cystic fibrosis (CF) infants using multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS). Chapter II introduces a simple CE assay that is remarkably selective for the analysis of sulfate, sulfite and chloride, which was applied in a pilot study to investigate the role of urinary sulfate as a biomarker for kidney stone risk assessment in children. Chapter III introduces a novel CE method for assessing iodine nutrition, which is followed by an inter-method comparison with inductively coupled plasma-mass spectrometry as described in Chapter IV. This led to the development of a fully validated CE method for monitoring the prevalence of iodine deficiency on a population level as required for global health initiatives. Chapter V demonstrates that more than 64 endogenous and exogenous compounds are present in the sweat of screen-positive CF infants, including a panel of differentiating metabolites that are associated with CF status, as well as treatment responsivity to nutritional and/or drug intervention. In summary, this thesis has contributed novel analytical methods suitable for routine biomarker analysis, in addition to the first non-targeted characterization of the sweat metabolome from infants, which require further studies to evaluate their clinical utility as biomarkers that allow for improved diagnosis, prognosis and treatment monitoring of the highly variable CF disease spectrum. / Thesis / Doctor of Philosophy (PhD)

[pt] A metodologia estatística escolhida para validação de métodos analíticos aplicável à metrologia em química é fundamental para assegurar a qualidade, comprovar a eficiência e demonstrar a exatidão dos resultados das medições nas análises químicas. Essa metodologia, desenvolvida em conformidade com o rigor metrológico, resulta num sistema de medições validado, confiável e com incertezas quantificadas. Este trabalho propõe uma metodologia geral para validação de métodos analíticos. A metodologia desenvolvida resultou de uma síntese de métodos parciais descritos na literatura, e inclui uma escolha crítica de técnicas mais adequadas dentro das alternativas existentes. A abordagem proposta combina quatro diferentes aspectos da validação: a modelagem da curva de calibração; o controle da especificidade do método; a comparação da tendência e precisão (repetitividade e precisão intermediária) do método com um método de referência; e a estimação das componentes de incerteza inerentes a todos esses aspectos. Como resultado, além de uma proposta para validação de métodos para uso em análises químicas, obtêm- se a função de calibração inversa e as incertezas expandidas, que permitem obter os resultados analíticos associados aos valores da resposta, com suas respectivas incertezas associadas. Na modelagem geral para obtenção da curva de calibração, empregam-se técnicas estatísticas para avaliação da linearidade e para o cálculo do mínimo valor detectável e do mínimo valor quantificável. A especificidade do método analítico é avaliada pela adição de padrões a um conjunto de amostras representativas e posterior recuperação dos mesmos, com ajuste por mínimos quadrados e testes de hipóteses. Para estudar a tendência e a precisão do método quando comparado a um método de referência, utiliza-se um modelo hierárquico de quatro níveis e a aproximação de Satterthwaite para determinação do número de graus de liberdade associados aos componentes de variância. As técnicas estatísticas utilizadas são ilustradas passo a passo por exemplos numéricos. / [en] The use of statistical methodology for analytical methods validation is vital to assure that measurements have the quality level required by the goal to be attained. This thesis describes a statistical modelling approach for combining four different aspects of validation: checking the linearity of the calibration curve and compute the detection and the quantification limits; controlling the specificity of the analytical method; estimating the accuracy (trueness and precision) of the alternative method, for comparison with a reference method. The general approach is a synthesis of several partial techniques found in the literature, according to a choice of the most appropriate techniques in each case. For determination of the response function, statistical techniques are used for assessing the fitness of the regression model and for determination of the detection limit and the quantification limit. Method specificity is evaluated by adjusting a straight line between added and recovered concentrations via least squares regression and hypotheses tests on the slope and intercept. To compare a method B with a reference method A, the precision and accuracy of method B are estimated. A 4-factor nested design is employed for this purpose. The calculation of different variance estimates from the experimental data is carried out by ANOVA. The Satterthwaite approximation is used to determine the number of degrees of freedom associated with the variance components. The application of the methodology is thoroughly illustrated with step-by-step examples.

Thesis (MScEng (Civil Engineering)--University of Stellenbosch, 2009. / ENGLISH ABSTRACT: A study of the state of reservoir sedimentation in South Africa based on reservoir sediment deposit data, has shown that a considerable number of reservoirs have serious sedimentation problems. The analysis of the reservoir sediment deposit data showed that almost 25% of the total number of reservoirs have lost between 10 to 30% of their original storage capacity. The average storage loss due to sedimentation in South African reservoirs is approximately 0.3% per year while the average annual storage loss for all the reservoirs in the world is 0.8%. The aim of this research was to develop sediment yield prediction methods based on analytical approaches and mathematical modelling. The sediment yield prediction methods can be used in planning and management of water resources particularly in reservoir sedimentation control. The catchment erosion and sediment yield modelling methods can be applied in temporal and spatial analysis of sediment yields which results are essential for detailed design of water resources, particularly in the identification of critical erosion areas, sediment sources and formulation of catchment management strategies. Current analytical methods for the prediction of sediment yield have been reviewed. Nine sediment yield regions have been demarcated based on the observed sediment yields and catchment characteristics. Empirical and probabilistic approaches were investigated. The probabilistic approach is based on analysis of the observed sediment yields that were calculated from reservoir sediment deposit, river suspended sediment sampling data and soil erodibility data. The empirical equations have been derived from regression analysis of the variables that were envisaged to have a significant effect on erosion and sediment yields in South Africa. Empirical equations have been developed and shown to have accurate and reliable predictive capability in six of the nine regions. The probabilistic approach has been recommended for the prediction of sediment yields in the remaining three regions where reliable regression equations could not be derived. The predictive accuracy of both the probabilistic and empirical approaches was checked and verified using the discrepancy ratio and graphs of the observed and calculated data. While the analytical methods are needed to predict the sediment yield for the whole catchment, mathematical modelling to predict sediment yields is applied for more detailed analysis of sediment yield within the catchment. An evaluation of available catchment sediment yield mathematical modelling systems was carried out. The main criteria for the choice of a numerical model to be adopted for detailed evaluation was based on the following considerations: the model’s capabilities, user requirements and its application. The SHETRAN model (Ewen et al., 2000) was therefore specifically chosen because of its ability to simulate relatively larger catchment areas (it can handle catchment scales from less than 1km2 to 2500km2), its ability to simulate erosion in channels, gullies and landslides, its applicability to a wide range of land-use types and ability to simulate land use changes. Another model, ACRU (Smithers et al., 2002) was also reviewed. The aim of the model evaluation was to provide a conceptual understanding of catchment sediment yield modelling processes comprising model set up, calibration, validation and simulation. The detailed evaluation of the SHETRAN model was done through a case study of Glenmaggie Dam in Australia. The flow was calibrated and validated using data from 1975 to 1984, and 1996 to 2006 respectively. The results for both the calibration and validation were reasonable and reliable. The sediment load was validated against turbidity derived sediment load data from 1996 to 2006. The model was used to identify sources of sediment and areas of higher sediment yield. The land use of a selected sub-catchment was altered to analyse the impact of land use and vegetative cover on the sediment yield. Based on the results, the SHETRAN model was confirmed to be a reliable model for catchment sediment yield modelling including simulation of different land uses. / AFRIKAANSE OPSOMMING: ‘n Studie van die stand van damtoeslikking in Suid-Afrika toon dat daar ernstige toeslikkingsprobleme by baie reservoirs bestaan. ’n Ontleding van die toeslikkingsyfers gegrond op damkomopmetings toon dat omtrent 25% van die totale getal reservoirs tussen 10 en 30% van hulle oorspronklike opgaarvermoë verloor het. Die gemiddelde tempo van damtoeslikking in Suid-Afrika is 0.3%/jaar, wat laer is as die wêreld gemiddeld van 0.8%/jaar. Die oogmerk met hierdie navorsing was om sedimentlewering voorspellingsmetodes te ontwikkel deur gebruik te maak van analitiese metodes en wiskundige modellering. Die sedimentlewering voorspellingsmetodes kan gebruik word vir die beplanning en bestuur van waterbronne en veral vir damtoeslikking beheer. Die opvangsgebied erosie en die sedimentlewering modelleringsmetodes kan toegepas word in tydveranderlike en ruimtelike ontleding van sedimentlewering. Hierdie inligting word benodig vir die detail ontwerp van waterhulpbronne en veral vir die identifisering van kritiese erosiegebiede, bronne van sediment en die formulering van opvangsgebied-bestuur strategië. ‘n Literatuuroorsig oor die huidige metodes vir die voorspelling van erosie en sedimentlewering is gedoen. Nege sedimentasie streke is afgebaken in Suid-Afrika, gegrond op waargenome damtoeslikkingsdata en opvangsgebied-eienskappe. Proefondervindelike en waarskynlikheidsbenaderinge is ondersoek. Die waarskynlikheidsbenadering is gegrond op die ontleding van waargenome damtoeslikking wat bereken is uit reservoir opmeting data en rivier gesuspendeerde sediment data, asook data oor gronderosie. Die proefondervindelike metode se vergelykings is afgelei vanuit regressie ontleding van die veranderlikes wat ‘n belangrike invloed het op die erosie en sedimentlewering in Suid-Afrika. Daar is bevestig dat die ontwikkelde proefondervindelike (empiriese) vergelykings ‘n akkurate en betroubare voorspellingsvermoë in ses van die nege streke het. Die waarskynlikheidsbenadering is aanbeveel vir die voorspelling van sedimentlewering in die ander drie streke, waar betroubare regressie vergelykings nie afgelei kon word nie. Die voorspellingsakkuraatheid van albei metodes is nagegaan en bevestig deur gebruik te maak van die teenstrydigheidsverhouding en grafieke van die waargenome en berekende data. Analitiese metodes van sedimentleweringsvoorspelling is nodig vir ‘n volle opvangsgebied, terwyl wiskundige modellering om sedimentlewerings te voorspel gebruik kan word om ‘n meer in diepte ontleding van die sedimentlewering binne ‘n opvanggebied te doen. ‘n Evaluasie van beskikbare wiskundige modelle wat opvangsgebied sedimentlewering kan voorspel, is gedoen. Die hoofkriteria vir die keuse van ‘n model vir gebruik by gedetailleerde ontleding is gegrond op die volgende: die vermoëns van die model, wat verbruikers benodig en die aanwending van die model. Die SHETRAN model (Ewen et al., 2000) is spesifiek gekies weens sy vermoë om relatief groter opvangsgebiede te simuleer (dit kan opvangsgebiede van 1km2 tot 2500km2 wees) asook om erosie in kanale, dongas en grondverskuiwing simuleer. Dit kan toegepas word op ‘n wye reeks grondtipes en kan ook die gevolge simuleer as die gebruik van die grond verander. ‘n Ander model, ACRU (Smithers et al., 2002) is ook ondersoek. Die doel van die modelevaluering was om ‘n konseptuele begrip te kry van sedimentlewering modelleringsprosesse wat die opstelling, kalibrasie, toetsing en simulasies insluit. Die volledige evaluasie van SHETRAN is gedoen deur middel van ‘n gevalle-studie van die Glenmaggiedam in Australia. Die riviervloei is gekalibreer en getoets deur gebruik te maak van data wat strek van 1975 tot 1984, en van 1996 tot 2006 onderskeidelik. Die resultate van beide die kalibrasie en die toetswas redelik en betroubaar. Die sedimentlading is gekalibreer teen velddata van 1996 tot 2006. Die model is gebruik om bronne van sediment te identifiseer, asook gebiede met ‘n hoër sedimentlewering. Die gebruik van die grond op ‘n gekose sub-opvangsgebied is verander om die impak van grondgebruik en plantbedekking op sedimentlewering te ontleed. Die resultate bewys dat die SHETRAN model ‘n betroubare model is vir groot opvangsgebied sedimentlewering modellering, asook vir die simulasie van verskillende grondgebruike.

O uso hormônios como promotores de crescimento em animais de criação foi proibido em vários países, inclusive no Brasil, desde os anos setenta. Para o controle destes anabolizantes, foi desenvolvida uma enorme variedade de métodos, tanto com propósitos de triagem como de confirmação. Os métodos mais usados são os físico-quimicos, entre eles os cromatográficos, tais como cromatografia em camada delgada, cromatografia a gás acoplada a espectrômetro de massa, cromatografia líquida de alta eficiência com detector UV, e os ensaios imunoquímicos tais como radioimunoensaio ou enzimaimunoensaio. Este trabalho revisa os métodos analíticos mais usados internacionalmente no controle de substâncias anabolizantes em tecidos e urina de animais de criação para consumo humano. Atenção especial é dada ao anabolizante potencialmente cancinogênico, Dietilstilbeltrol (DES) em relação ao seu uso no Brasil e às dificuldades envolvidas em sua determinação. São propostos neste trabalho métodos para detecção do DES em sítios de aplicação, na urina, no tecido muscular e nas vísceras, bem como são apresentados os resultados da aplicação desta metodologia em amostras de animais implantado e de controle e amostras autênticas. / Since the seventies, the use of hormonal anabolics as growth promotors in lifestock fattening has been banned in many countries, including Brazil. For control purposes a wide range of methods have been developed for both large-scale screnning and confirmation. The most used methods are the physical-chemical ones, such as thin-layer chromatography (TLC), gas chromatography-mas spectrometry (CG-MS), high performance liquid cromatography (HF\'LC) with UV detector and immunochemical assay (RIA) or enzime imuno assay (ELISA). This thesis reviews the most used methods for the control of anabolics in tissue as well as in the urine of cattle raised for human consumption. Special attention is given to the potencially calcinogen Diethylstilbestrol, its possible use in Brazil and the difficulties envolved in its determination. Suitable methods for the detection of DES in samples from injection sites, urine, tissue and organs of implanted and control animals, are presented, as well as results obtained from authentic samples.

Le sous-sol français est traversé par un nombre considérable de cavités souterraines naturelles ou anthropiques : après mine, carrières, karsts, tunnels et ouvrages civils abandonnés, etc. Ces cavités sont à l’origine de différents risques de mouvements de terrains tels que les effondrements localisés (fontis) et les affaissements qui peuvent être graves de conséquence pour les biens et les personnes. Pour réduire ce risque, un renforcement par géosynthétique des remblais sur cavités potentielles peut être mis en œuvre. C’est dans ce cadre que s’inscrit cette thèse menée au sein de l’INERIS (projet de recherche EREVAN - Evaluation et Réduction de la Vulnérabilité des biens exposés aux Aléas Naturels et miniers), en partenariat avec le laboratoire 3SR. L’un des objectifs de ces travaux est notamment de mieux appréhender, suite à l’ouverture d’une cavité sous-jacente, le comportement et les mécanismes d’effondrement des remblais renforcés par géosynthétique, en particulier cohésifs, afin d’en optimiser le dimensionnement.Dans le cadre de cette thèse, différentes expérimentations sur des modèles physiques de laboratoire et en vraie grandeur ont été réalisées. Les résultats obtenus en laboratoire ont permis de préciser le rôle mécanique des renforcements géosynthétiques dans le cas d’effondrement localisé sous un remblai granulaire ou/et cohésif, une importante base de données expérimentales a ainsi été constituée. Une expérimentation en vraie grandeur a permis de valider l’intérêt au plan technique, économique et environnemental de la technique de renforcement par géosynthétique des zones sujettes à des risques fontis.La contribution particulière de ce travail réside dans l’utilisation de modèles physiques et de techniques de mesures originales développés pour simuler l’apparition d’une cavité et suivre de manière quantitative les mécanismes induits notamment dans le cas des remblais cohésifs. En particulier, une évaluation précise des mécanismes de transferts de charge et de l’interaction sol – renforcement géosynthétique due à un effondrement localisé a été rendue possible par le développement et la validation d’une technique de traitements des résultats par photogrammétrie. L’intensité de la charge transmise par le sol sur le renforcement géosynthétique, la géométrie de sa répartition, ainsi que son évolution sous l’effet d’une surcharge éventuelle en surface ont ainsi été plus spécifiquement étudiées.Les résultats expérimentaux ont été comparés avec des formulations analytiques issues de méthodes de dimensionnement existant dans la littérature. Cette comparaison nous a permis de mieux cerner les domaines de validité des méthodes de dimensionnement analytiques actuelles du renforcement géosynthétique que ce soit pour le cas d’un remblai granulaire ou cohésif et dans certains cas de formuler certaines recommandations. / The French underground is occupied by a considerable number of natural or anthropogenic underground cavities: former mining areas, quarries, karsts, tunnels and abandoned civil structures, etc. These cavities are the source of various risks of ground movements such as sinkholes and subsidence which can have a large impact on the safety people and structures or infrastructures. In order to reduce this risk, a reinforcement of the embankments by geosynthetic in the zones of potential cavities can be implemented. In this context, the thesis has been funded and managed by INERIS (research project EREVAN - Evaluation and Reduction of the Vulnerability of the properties exposed to the natural and mining Hazards), in partnership with 3SR laboratory. One of the objectives of this research is in particular to better understand, further to the opening of an underlying cavity, the behavior and the mechanisms of collapse of reinforced embankment, especially in the case of cohesive soil, in order to optimize its design.As a part of this work, various experiments on physical models in laboratory and on site have been realized. The results obtained in laboratory allowed to determine the behavior of the geosynthetic reinforcement following the collapse of a granular or/and cohesive embankment over a cavity, an important experimental database has thus been established. Full scale experiment allowed to validate the technical, economic and environmental benefits of geosynthetic reinforcement of zones subject to sinkhole.The particular contribution of this work is in the use of original physical models and measurement techniques used to simulate the occurrence of a sinkhole and follow in an accurate quantitative way the involved mechanisms, notably in the case of a cohesive backfill. In particular, a specific evaluation of load transfer mechanisms and soil - geosynthetic reinforcement interaction due to sinkhole has been enabled by the development and the validation of an image processing technique. The intensity of the load transmitted by the ground onto the geosynthetic reinforcement, the geometry of its distribution, as well as its evolution due to possible overburden load have been specifically investigated.Experimental results have been compared with analytical formulations resulting from existing design methods in the literature. This comparison allowed us to better define the domains of validity of the current analytical methods for design of geosynthetic reinforcement whether for granular or cohesive backfill, and in certain cases to formulate some recommendations.