Dissertations / Theses on the topic 'Tissu adipeux – Modèles mathématiques'
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Chassonnery, Pauline. "Modélisation mathématique en 3D de l'émergence de l'architecture des tissus conjonctifs." Electronic Thesis or Diss., Toulouse 3, 2023. http://www.theses.fr/2023TOU30354.
In this thesis, we investigate whether simple local mechanical interactions between a reduced set of components could govern the emergence of the 3D architecture of biological tissues. To explore this hypothesis, we develop two mathematical models. The first one, ECMmorpho-3D, aims at reproducing a non-specialised connective tissue and is reduced to the Extra-Cellular Matrix (ECM) component, that is a 3D dynamically connected fibre network. The second, ATmorpho-3D, is built by adding to this network spherical cells which spontaneously appear and grow in order to mimic the morphogenesis of Adipose Tissue (AT), a specialised connective tissue with major biomedical importance. We then construct a unified analysis framework to visualise, segment and quantitatively characterise the fibrous and cellular structures produced by our two models. It constitutes a generic tool for the 3D visualisation of systems composed of a mixture of spherical (cells) and rod-like (fibres) elements and for the automatic detection of in such systems of clusters of spherical objects separated by rod-like elements. This tool is also applicable to biological 3D microscopy images, enabling a comparison between in vivo and in silico structures. We study the structures produced by the model ECMmorpho-3D by performing numerical simula- tions. We show that this model is able to spontaneously generate different types of architectures, which we identify and characterise using our analysis framework. An in-depth parametric analysis lead us to identify an intermediate emerging variable, the number of crosslinks per fibre, which explains and partly predicts the fate of the modelled system. A temporal analysis reveals that the characteristic time-scale of the organisation process is a function of the network remodelling speed, and that all systems follow the same, unique evolutionary pathway. Finally, we use the model ATmorpho-3D to explore the influence of round cells over the organisation of a fibre network, taking as reference the model ECMmorpho-3D. We show that the number of cells can influence the local alignment of the fibres but not the global organisation of the network. On the other hand, the cells inside the network spontaneously organise into clusters with realistic morphological features very close to those of in vivo structures, surrounded by sheet-like fibre bundles. Moreover, the distribution of the different morphological types of clusters is similar in in silico and in vivo systems, suggesting that the model is able to produce realistic morphologies not only on the scale of one cluster but also on the scale of the whole system, reproducing the structural variability observed in biological samples. A parametric analysis reveals that the proportion in which each morphology is present in an in silico system is governed mainly by the remodelling characteristic of the fibres, pointing to the essential role of the ECM properties in AT architecture and function (in agreement with several biological results and previous 2D findings). The fact that these very simple mathematical models can produce realistic structures supports our hypothesis that biological tissues architecture could emerge spontaneously from local mechanical inter- actions between the tissue components, independently of the complex biological phenomena taking place around them. This opens many perspectives regarding our understanding of the fundamental principles governing how biological tissue architecture emerges during organogenesis, is maintained throughout life and can be affected by various pathological conditions. Potential applications range from tissue engineering to therapeutic treatment inducing regeneration in adult mammals
Dichamp, Jules. "De l'imagerie tissu entier à la modélisation in silico du réseau vasculaire du tissu adipeux." Phd thesis, Toulouse, INPT, 2018. http://oatao.univ-toulouse.fr/23606/1/Dichamp.pdf.
Boucher, Jérémie. "Modèles murins d'obésité : implication des catécholamines et des adipocytokines." Toulouse 3, 2004. http://www.theses.fr/2004TOU30120.
Dysregulation of energetic balance results in modification of adipose tissue mass. A decrease in caloric intake leads to lipid mobilization whereas an increase results in energy storage mainly in existing adipocytes (hypertrophy) or newly differenciated ones (hyperplasia). Catecholamines are potent modulators of adipocyte activity (metabolic as well as trophic) through activation of adrenergic receptors (AR). There's no suitable animal model to study the role of catecholamines in adipose tissue metabolism or development. Indeed, the b3-AR is highly expressed in adipocytes of most of rodents whereas there's a few or no expression of a2-AR. The contrary is true for humans. Thus we created transgenic mice with " human like " adrenergic receptivity in adipocytes. In b3-AR knock-out mice, expression of human a2-AR was performed with injection of a large human genomic DNA fragment (>30 kb). This fragment contains the regulatory sequences before (11 kb) and after (18 kb) the coding sequence of the a2C10 gene coding the a2-AR. In transgenic mice, expression profile of a2-AR in adipose tissue is similar to that usually described in humans. Moreover, whereas there's no apparent phenotype on a chow diet, these transgenic mice become obese when fed a high fat diet. Excessive adipose tissue development in obese mice is mainly due to hyperplasia of adipose tissue rather than hypertrophy of fat cells. However, depite obesity, these mice don't develop obesity associated disorders such as type II diabetes or hypertension. .
Laplante, Mathieu. "Mécanismes impliqués dans le remodelage du tissu adipeux et dans l'amélioration de la lipémie par les agonistes PPAR-[gamma]." Thesis, Université Laval, 2007. http://www.theses.ulaval.ca/2007/24442/24442.pdf.
Douania, Inès. "Multi-scales, multi-physics personalized HD-sEMG model for the evaluation of skeletal muscle aging." Electronic Thesis or Diss., Compiègne, 2022. http://www.theses.fr/2022COMP2679.
The muscle aging, as a disease entity, is known as Sarcopenia. It is defined as a reduction of muscle strength/force accompanied by a loss of muscle mass and a decline in physical functions. The current methodologies used in clinical practice to assess this aging disease, are rather limited to capture the features of this decline at the macroscopic scale. Factors such as the loss of Motor Units (motor unit (MU) is made up of a motoneuron and all the skeletal muscle fibers innervated by the neuron's axon terminals), the atrophy of fibers and the disorder of the neural recruitment pattern are shown to have a clear influence on muscular function. However, diagnosing sarcopenia by only measuring the muscle strength and/or muscle mass is not enough accurate and cannot alert an early loss of muscular function. The inner scales (MU and fiber scale age-related changes) reflecting that loss of muscle mass and strength during aging are more interesting to exploit. Thus, recent studies, based on the surface electromyography (sEMG) technique, have demonstrated the great potential of this technique to be used as a biomarker to detect early signs of sarcopenic muscles. In fact, the sEMG signal is the electrical response of the muscle activation managed by the Central Nervous System (CNS). It is measured with a noninvasive manner at the skin surface using surface electrodes and can be correlated efficiently to the mechanical response of muscle activation. Moreover, mathematical models of sEMG signal can form a useful alliance with sEMG experimental measures and processing to identify and/or quantify bio-indicators (i.e., anatomical, and neural muscle parameters) of a healthy, early, accelerated or sarcopenic muscle aging. In this thesis work, we have used a fast and optimized electrical model describing the electrical activity of the muscle at the skin surface using High Density sEMG technique (HD-sEMG), developed in our laboratory team. The reduced computational time of this model is the major key feature to perform the identification of aging indicators using inverse methods and HD-sEMG technique. However, this identification needs pre-aided-methods such as the sensitivity and the identifiability analysis. Moreover, when dealing with this model, we have observed important limitations such as lack of physiological realism (e.g., MUS territories and the number of fibers per muscle), personalization (e.g., same recruitment pattern for young and elder subject), and simplicity (e.g., adjustment of 50 model parameters according to age and gender). These limitations restrain the use of this model in muscle aging diagnosis. Therefore, we aimed in this thesis to address the limitations of this model and deliver more realistic and user-friendly model to evaluate muscle aging. Therefore, in this work, we first propose an Improved Morris Sensitivity Analysis (IMSA) applied on the developed model. This analysis was performed on young and elder simulated subjects (at low and high force level). Using this IMSA, we success to spotlight with accuracy the influential neuromuscular parameters/factors for each age category, at each force level, and for each statistic feature computed over the HD-sEMG signals. Furthermore, using IMSA, we have outlined the model inaccuracies and limitations mentioned above. To address these limitations, we have modified the model schema implementation to be easier to manipulate (user-friendly model), with less error and inconsistency risks. Only the age and the gender of subject became needed as model entries to initiate a simulation of HD-sEMG signals. All other parameters necessary in simulations are then estimated through "statistical" models. The statistical models employ regression analysis to estimate the relation Parameter versus Age. A bibliographic research reporting these morphological and structural changes according to age, gender, and Biceps Brachii muscle was done
Girousse, Amandine. "Régulation de la protéine découplante UCP3 et inhibition génique ou pharmacologique de la lipase hormono-sensible." Toulouse 3, 2010. http://thesesups.ups-tlse.fr/1029/.
In a first part, this study focuses on the regulation of the expression of the uncoupling protein-3 (UCP3). UCP3 is an inner mitochondrial protein almost exclusively expressed in skeletal muscle in human which could be implicated in fatty acid metabolism. A transgenesis approach has been used to create animal bearing all or part of the UCP3 gene in order to delineate the sequences responsible for the muscle specific expression. A 600 bp sequence of the human UCP3 intron 1 gene has been identified which confers the muscular expression in vivo. The second part of this study is dedicated to the functional consequences of the alteration of lipolytic capacities in mouse adipose tissue. Adipocyte lipolysis is partly achieved by the hormone sensitive-lipase (HSL). HSL expression and activity is altered in adipose tissue of obese and/or insulin resistant subjects. We developed mouse models of genetic and pharmacological inhibition of HSL. Reduction of lipolytic capacity was associated with an improvement of insulin sensitivity and fatty acid metabolism in both animal models. Adipose tissue inflammation, that is a well known modulator of insulin sensitivity, did not seem to be involved in this phenotype
Volat, Fanny. "Rôle des aldose réductases dans la physiologie du tissu adipeux blanc : modèles génétiques murins perte et gain de fonction." Phd thesis, Université Blaise Pascal - Clermont-Ferrand II, 2011. http://tel.archives-ouvertes.fr/tel-00686589.
Roy, Christian. "Les mécanismes de dépense énergétique associés avec l'ASP et son récepteur C5L2." Thesis, Université Laval, 2009. http://www.theses.ulaval.ca/2009/25928/25928.pdf.
Obesity is a well established problem in North America and studying the mechanisms of fat storage may be key in understanding and treating this problem. Acylation Stimulating Protein (ASP) is an adipose tissue derived hormone that acts through its receptor, C5L2, to stimulate triglyceride (TG) synthesis and glucose transport. C3 is the precursor for ASP; therefore, C3 knockout (KO) mice are ASP-deficient. These mice display hyperphagia yet normal body weight due to increased energy expenditure. Calorimetric chamber studies demonstrated that C3KO have increased oxygen consumption and lowered respiratory quotient, indicating that deficiency of ASP alters substrate preference for energy metabolism in C3KO mice. It still remains to be determined whether the alterations in skeletal muscle energy metabolism are a direct or indirect consequence of ASP deficiency, but in vivo data suggest targeting ASP may provide insights toward treatment of obesity.
Garcia, dos Santos Esther. "Interactions des hormones sexuelles avec des voies de signalisation impliquées dans le développement du tissu adipeux blanc chez le rat : particularités anatomiques." Paris 11, 2000. http://www.theses.fr/2000PA11T043.
Maillard, Florie. "Influence des modalités d'exercices sur le microbiote intestinal et la masse grasse abdominale : interrelation intestin / tissu adipeux sur des modèles de pathologies inflammatoires." Thesis, Université Clermont Auvergne (2017-2020), 2018. http://www.theses.fr/2018CLFAS007/document.
Obesity and Crohn's disease (CD) are two chronic inflammatory diseases characterized by development of visceral fat mass and dysbiosis. Physical activity (PA) has a positive impact on these two parameters. Consequently, PA appears as a promising therapeutic strategy for the management of these patients. In this context, the objective of this work was to study the effect of PA on the microbiota-adipose tissue cross-talk. Our clinical results confirmed the effectiveness of high intensity intermittent training (HIIT) to reduce visceral adipose tissue in overweight and/or obese volunteers. Then, using an animal model of genetic obesity (Zucker rats), we found that HIIT decreases total and visceral fat mass, independently of gut microbiota. Analysis of the lipolysis pathway showed an anti-lipolytic effect of HIIT in the subcutaneous adipose tissue, and this could explain the decrease in visceral adipose tissue. In addition, compared with continuous moderate intensity training, HIIT improved glucose tolerance and the inflammatory status despite the shorter exercise duration. Finally, in an animal model of CD, we found that spontaneous PA increased the expression of tight junction proteins, contributing to the reduction of metabolic endotoxemia. Concomitantly, spontaneous PA promoted healthy bacteria in the colon and increased fecal butyrate levels. These adaptations limited the expansion of mesenteric visceral adipose tissue, a typical CD feature. In conclusion, PA, through different exercise modalities, appears as an attractive and innovative « therapy » for these two chronic inflammatory diseases
Roy, Christian. "La voie ASP/C5L2 dans le métabolisme énergétique." Thesis, Université Laval, 2014. http://www.theses.ulaval.ca/2014/30270/30270.pdf.
Obesity is a major health problem that results in an imbalanced energy metabolism. Acylation Stimulating Protein (ASP, C3adesArg) is a protein produced by the adipose tissue, which stimulates triglycerides (TG) synthesis and glucose transport by binding to its receptor C5L2. Our previous studies have shown that mice with a disabled C3 gene (C3KO) are ASP deficient, hyperphagic but of normal weight and demonstrate greater energy expenditure than wild-type mice. From these results, our goal was to determine the role of the ASP-C5L2 pathway in energy metabolism. In our first study, we observed that a central injection of ASP in the third ventricle of Wistar rats brought a reduction in food intake and body weight gain and an increased mRNA expression of the anorexigenic neuropeptide POMC in the region of the arcuate nucleus. Our studies also showed that the levels of intramyocellular lipids (IMCL) were increased six-fold in C5L2-deficient mice (C5L2KO) compared to wild mice (WT) after a high-fat diet. Furthermore, in humans, the protein expression of C5L2 is reduced in patients with type 2 diabetes compared with obese controls. Physical training increased protein expression of C5L2 and ASP output in obese insulin-resistant men. Finally, our work with C5a receptor-deficient mice (C5aRKO) showed that after 12 weeks of a high-fat and high-sugar diet (DIO), the C5aRKO mice exhibited reduced body weight and smaller gonadal and inguinal fat mass than their WT counterparts. This was accompanied with lower plasma levels of non-esterified fatty acids and triglycerides and faster postprandial triglyceride clearance. Our studies have demonstrated that the ASP/C5L2 pathway represents an attractive target in the control of food intake and skeletal muscle fatty acid metabolism.
Taibi, El Hassane. "Caractérisation, modélisation et simulation du comportement d'un tissu textile." Bordeaux 1, 2001. http://www.theses.fr/2001BOR12441.
Fisette, Alexandre. "La voie ASP-C5L2 : un pont entre l'homéostasie métabolique et l'inflammation." Thesis, Université Laval, 2013. http://www.theses.ulaval.ca/2013/30372/30372.pdf.
Recent research findings have characterized adipose tissue as en endocrine organ and have shown that obesity triggers the development of low-grade inflammation, termed metaflammation. This thesis focuses on one adipokine and its receptor, acylation stimulating protein (ASP) and C5L2 receptor, and their relationship with energy metabolism and metaflammation. ASP derives from the complement system and acts on adipocytes by upregulating fatty acid and glucose absorption, resulting in a net increase in lipid storage. Mice genetically deficient in components of the ASP–C5L2 pathway are obesity-resistant but hyperphagic, suggesting that the disruption of this pathway could hold a therapeutical value. This thesis sequentially evaluates in mouse models (i) the consequences of an acute ASP stimulation, (ii) metabolism in C5L2-deficient animals treated with a diabetogenic diet, (iii) and the dynamics of the ASP–C5L2 pathway in diet-induced obesity. ASP acts acutely as an anabolic hormone, stimulating glucose absorption in tissues with active glucose transport. Paradoxically, ASP also generates an acute proinflammatory response with increased cytokine release, macrophage migration and classical activation. The disruption of C5L2 receptor in a murine model treated with a diabetogenic diet induced the opposite effects on energy metabolism, aggravating the development of insulin resistance and rerouting glucose to the liver. A more pronounced phenotype of metaflammation is also measurable in C5L2 knockout mice, probably linked to the second function of the C5L2 receptor, the sequestration of the anaphylatoxin C5a. In a model of diet-induced obesity, the proof-of-concept of ASP resistance is demonstrated and possibly linked with a reduction in C5L2 expression. The final study in this thesis (iv) evaluates the clinical contribution of ASP and the complement system in the outcome of an intervention designed to modulate the interaction between metabolism and immunity in a surgical context of hepatic resection. The results shown in the present work clarify the role and the therapeutical potential of the ASP–C5L2 pathway and describe it as a bridge between inflammation and metabolic homeostasis.
Makki, Kassem. "Rôle de modulateurs immunologiques et métaboliques dans le développement de l’obésité et de la résistance à l’insuline : administration de la rapamycine ou de probiotiques chez la souris obèse." Thesis, Lille 2, 2014. http://www.theses.fr/2014LIL2S006/document.
Obesity is characterized by a low-grade chronic inflammation reflected by increased blood levels of inflammatory factors, which are known to contribute to the development of metabolic complications such as insulin resistance and type 2 diabetes.Obesity-related inflammation is initiated by the accumulation of inflammatory immune cells within the adipose tissue as observed in obese subjects, contributing to alteration of the physiology and the metabolic homeostasis of the tissue. A better understanding of the mechanisms controlling the balance between adipose tissue immune cells and the interaction of these cells with the metabolic tissues (e.g. white adipose tissue) could lead to the development of immune-based new therapeutic strategies to treat metabolic complications associated with obesity.During my PhD thesis, we worked on two projects that both aimed at studying the link between immunity and metabolism. We studied the consequences of the treatment of obese mice with the immunomodulatory drug rapamycin (Part 1) and with probiotics having anti-inflammatory properties (Part 2).Part 1: Beneficial Metabolic Effects of Rapamycin are Associated with Enhanced Regulatory Cells in Diet-Induced Obese MiceThis part corresponded to my main project. We aimed to analyze the effect of rapamycin (or Sirolimus), on the inflammatory response and the metabolic status of high-fat diet fed mice. Rapamycin is an immunosuppressive drug commonly used in transplanted patients to prevent graft rejection. However, the effects of rapamycin on metabolism remain elusive and it has been reported that rapamycin may have pro-inflammatory and prodiabetic properties since some transplanted patients can develop diabetes and inflammatory diseases. Rapamycin is a specific inhibitor of mTOR (mechanistic Target Of Rapamycin), a highly conserved kinase which play a key role in both metabolism and immunity. Our aims were: 1) to define the metabolic consequences of long-term rapamycin administration and 2) to analyze the immune profile of treated animals.Part 2: A Probiotic Mixture Alleviates Diet-Induced Obesity and Insulin Resistance in Mice through Adipose Tissue Cell-RemodelingThe effects of probiotics on the development of obesity and its associated-metabolic complications are contradictory and thus remain to be clarified. In our study, we evaluated the consequences of the consumption of different strains of probiotics (or a combination of strains) selected for their anti-inflammatory properties, on the development of obesity and inflammation. We thus defined the metabolic and immune profile of probiotic-treated obese mice, mostly focusing on the adipose tissue. Finally, we attempted to identify the cellular and molecular mechanisms by which our selected probiotics exerted their metabolic and immune protective effects
Fisette, Alexandre, and Alexandre Fisette. "Implications de la résistine et de la protéine stimulant l'acylation dans le développement de co-morbidités de l'obésité." Master's thesis, Université Laval, 2010. http://hdl.handle.net/20.500.11794/21370.
Tableau d’honneur de la Faculté des études supérieures et postdoctorales, 2009-2010
Le tissu adipeux, autrefois perçu comme un organe inerte voué au stockage de gras est maintenant reconnu comme un organe sécrétant de nombreux facteurs, nommés adipokines. Certains de ces facteurs – on en compte plusieurs dizaines – influencent le métabolisme de la même façon que des hormones plus connues comme l’insuline ou le glucagon peuvent le faire. Ce mémoire porte sur l’étude de deux adipokines en particulier, la protéine stimulant l’acylation (ASP) et la résistine, en relation avec l’obésité et ses co-morbidités. Le premier projet visait à étudier les adaptions du métabolisme hépatique dans des modèles murins ne possédant pas de voie de signalisation fonctionnelle de l’ASP, des modèles résistants à l’obésité. Cette étude a permis de démontrer l’absence de stéatose hépatique et de surproduction de lipoprotéines chez ces souris en plus de mettre en évidence une utilisation altérée des substrats énergétiques par le foie. Le second projet visait à étudier les corrélations entre la résistine plasmatique et de nombreux paramètres liés au syndrome métabolique dans une population d’enfants et d’adolescents chinois. Cette étude a démontré que la résistine n’y est pas corrélée avec la résistance à l’insuline, mais qu’elle y est retrouvée en plus grande concentration s’il y a présence d’obésité centrale. Globalement, ce mémoire met en lumière tant de façon fondamentale que clinique les implications physiologiques des deux adipokines étudiées – l’ASP et la résistine – et clarifie leur potentiel thérapeutique.
Le tissu adipeux, autrefois perçu comme un organe inerte voué au stockage de gras est maintenant reconnu comme un organe sécrétant de nombreux facteurs, nommés adipokines. Certains de ces facteurs – on en compte plusieurs dizaines – influencent le métabolisme de la même façon que des hormones plus connues comme l’insuline ou le glucagon peuvent le faire. Ce mémoire porte sur l’étude de deux adipokines en particulier, la protéine stimulant l’acylation (ASP) et la résistine, en relation avec l’obésité et ses co-morbidités. Le premier projet visait à étudier les adaptions du métabolisme hépatique dans des modèles murins ne possédant pas de voie de signalisation fonctionnelle de l’ASP, des modèles résistants à l’obésité. Cette étude a permis de démontrer l’absence de stéatose hépatique et de surproduction de lipoprotéines chez ces souris en plus de mettre en évidence une utilisation altérée des substrats énergétiques par le foie. Le second projet visait à étudier les corrélations entre la résistine plasmatique et de nombreux paramètres liés au syndrome métabolique dans une population d’enfants et d’adolescents chinois. Cette étude a démontré que la résistine n’y est pas corrélée avec la résistance à l’insuline, mais qu’elle y est retrouvée en plus grande concentration s’il y a présence d’obésité centrale. Globalement, ce mémoire met en lumière tant de façon fondamentale que clinique les implications physiologiques des deux adipokines étudiées – l’ASP et la résistine – et clarifie leur potentiel thérapeutique.
Adipose tissue has been recently recognized to function as an endocrine organ in addition to its fat storage capacities. Adipose tissue secretes a number of factors named adipokines. Some of these hormones influence metabolism similarly to other well-known factors such as insulin and glucagon. This thesis is the result of studies done on two particular adipokines, acylation stimulating protein (ASP) and resistin, as well as their relationship with obesity and its co-morbidities. The aim of the first project was to understand the adaptations of hepatic metabolism in murine models with ASP-C5L2 pathway deficiencies, models that are also obesity resistant. This study demonstrated the absence of hepatic steatosis or lipoprotein overproduction in these mice in addition to showing signs of altered substrate use by the liver. The second study evaluated correlations between plasma resistin and several parameters related to the metabolic syndrome in a population of Chinese children and adolescents. This study demonstrated that resistin does not correlate with insulin resistance, but that circulating levels of resistin are increased in the presence of central obesity. Globally, this thesis shows, from both a clinical and basic science perspective, the physiological implications of the two adipokines studied – ASP and resistin – and clarifies their therapeutical potential.
Adipose tissue has been recently recognized to function as an endocrine organ in addition to its fat storage capacities. Adipose tissue secretes a number of factors named adipokines. Some of these hormones influence metabolism similarly to other well-known factors such as insulin and glucagon. This thesis is the result of studies done on two particular adipokines, acylation stimulating protein (ASP) and resistin, as well as their relationship with obesity and its co-morbidities. The aim of the first project was to understand the adaptations of hepatic metabolism in murine models with ASP-C5L2 pathway deficiencies, models that are also obesity resistant. This study demonstrated the absence of hepatic steatosis or lipoprotein overproduction in these mice in addition to showing signs of altered substrate use by the liver. The second study evaluated correlations between plasma resistin and several parameters related to the metabolic syndrome in a population of Chinese children and adolescents. This study demonstrated that resistin does not correlate with insulin resistance, but that circulating levels of resistin are increased in the presence of central obesity. Globally, this thesis shows, from both a clinical and basic science perspective, the physiological implications of the two adipokines studied – ASP and resistin – and clarifies their therapeutical potential.
Lucas, Stéphanie. "Etude de la lipase hormono-sensible à l'aide de modèles transgéniques : effet d'une surexpression dans le tissu adipeux, analyse du promoteur adipocytaire et caractérisation dans l'intestin." Toulouse 3, 2002. http://www.theses.fr/2002TOU30221.
Barthelemy, Johanna. "Infections virales respiratoires et tissus adipeux blancs : Exemple de la grippe et de la COVID-19." Thesis, Université de Lille (2022-....), 2022. http://www.theses.fr/2022ULILS009.
Respiratory viral infections remain a major public health issue, worldwide. This is particularly the case with flu, caused by influenza viruses, and COVID-19, an emerging infectious disease caused by the SARS-CoV-2 virus. Importantly, the populations most at risk of developing severe forms of flu or COVID-19 are obese individuals and the elderly. Although obesity and aging are both associated with major functional alterations of the white adipose tissue, the latter's involvement in the pathophysiology of influenza or COVID-19 remains poorly studied. The thesis project falls within this general theme.Recent work by our team has shown, in mice, that infection with the influenza virus causes metabolic reprogramming of the subcutaneous fat depots, mainly characterized by the browning of the tissue: a phenomenon which corresponds to the emergence of beige adipocytes with increased thermogenic activity. During my PhD, using complementary experimental in vivo, in vitro, ex vivo and in silico approaches, we showed that the response to influenza-infection-induced endoplasmic reticulum stress, and more specifically the PERK signaling pathway, is involved in white adipose tissue browning. Besides identifying a novel molecular mechanism that regulates thermogenesis, our work further specifies the role of the white adipose tissue in influenza infection.In parallel, we studied the impact of infection with the SARS-CoV-2 virus on the white adipose tissues of young adult and old hamsters - a preclinical model of COVID-19 recently implemented in our team. Our results showed that the infection is more severe - in terms of morbidity and mortality - in older animals than in young adults. Histomorphometric analysis of subcutaneous and visceral white adipose tissues showed that infection with SARS-CoV-2 is associated with a decrease in the size of adipocytes in these two depots; an effect that persists only in the older animals. Remarkably, the histological analysis of the tissues reveals the presence of numerous and large areas of adipocyte necrosis (resembling the “crown-like structures” that can be observed in white adipose tissues in the context of obesity) only in the subcutaneous fat depots of the older animals, even at distance from infection. As such, our study confirms and strengthens the most recent data in the literature, which describes a major role of the white adipose tissue in the pathophysiology of COVID-19
Ni, Annaidh Aisling. "Mécanique du coup de couteau : étude numérique et expérimentale de l'attaque à l'arme blanche." Paris 6, 2012. http://www.theses.fr/2012PA066261.
Pileyre, Baptiste. "Etude préclinique évaluant l'utilisation de la fraction vasculaire stromale et les cellules souches dérivées de tissu adipeux dans le traitement des myosites." Electronic Thesis or Diss., Normandie, 2023. http://www.theses.fr/2023NORMR054.
Myositis is a group of autoimmune muscular diseases affecting skeletal muscles, leading to severe damage. While most patients respond to conventional treatments, some remain refractory. The stromal vascular fraction (SVF), freshly extracted from adipose tissue, or stem cells derived from it (ADSC) by expansive culture have shown promising results in various autoimmune pathologies and could enable the management of these patients. To assess their potential and study the mechanisms of action of these therapies, we carried out preclinical studies in vitro and in vivo. To this end, we characterized and used a mouse model of myositis, the Icos-/- NOD mouse, showing spontaneous muscle damage associated with extensive leukocyte infiltrates. To be closer of the autologous use of these therapies, we performed syngeneic transplants of FVS and ADSC in this model. We observed a slowdown in the progression of symptoms, a reduction in the loss of muscle strength and a decrease in muscle atrophy in vivo. We have demonstrated a greater efficacy of ADSCs, particularly in in vitro assays. These tests, carried out with donor cells and assessing regenerative efficacy (fibroblast colony forming unit assay) and immunomodulatory effect (lymphocyte proliferation inhibition assay), demonstrated the dose-dependent effect of these therapies, as well as the superiority of ADSCs in terms of both maximum efficacy and 50% inhibitory dose of the immunomodulatory effect. They also enabled us to identify markers predictive of the proliferative (CD90, CD105 or high hematopoietic stem cell count) and immunomodulatory (CD73 or macrophage count) effects of these therapies. All these elements demonstrate the potential of these therapies in the treatment of myositis, and the interest of investigating their effect through clinical trials
Delahaye, Fabien. "Conséquences d’une dénutrition maternelle périnatale sur la mise en place de l’axe hypothalamo-adipocytaire chez le rat mâle : focus sur la leptine." Thesis, Lille 1, 2010. http://www.theses.fr/2010LIL10182/document.
Perinatal malnutrition sensitizes to the development of chronic adult diseases such as the metabolic syndrome. These metabolic disorders frequently result from an imbalance between food intake and energy expenditure.The brain-adipose axis (BAA) that is constituted from central nervous system and adipose tissues plays a crucial role in the regulation of metabolism. These two tissues indeed control both food intake and energy expenditure, via different factors such as leptin. Little is known concerning the consequences of perinatal stress on the development of BAA in newborns,.The major goal of my Ph D was to analyze the consequences of a 50% maternal perinatal undernutrition (FR50 model) on the development of BAA in male rat from birth to weaningControl animals exhibited a plasma surge of leptin around the second week of life while this peak was drasticallyreduced in FR50 pups. This reduction is associated with an alteration of the hypothalamic projections of POMC nerve fibers. The decreased leptin plasma levels in FR50 pups is accompanied by a reduction of leptin concentration both in plasma from mothers as in the milk from undernourished mothers, reinforcing the idea that lactation and nutritional status of the mother during this period are key “programming” factors. Interestingly, in postnatal day (PND) 21 FR50 animals, perigonadal adipose tissue exhibited a transient modification with the acquisition of a brown-like Altogether, our results indicate that maternal perinatal undernutrition modifies the development of the BAA and that lactation is a critical timewindow for the programming of mechanisms involved in the regulation of energy metabolism
Gaudreault, Mathieu. "Modèles d’identification de tissu basés sur des images acquises avec un tomodensitomètre à double énergie pour des photons à faible énergie en curiethérapie." Master's thesis, Université Laval, 2014. http://hdl.handle.net/20.500.11794/25366.
Clinical Dual-Energy Computed Tomography (DECT) images provide the determination of the effective atomic number and the electronic density. The purpose of this study is to develop a new assessment model of tissues, named the reduced three elements tissue model, for dose calculations from DECT images in brachytherapy and compare it to a known identification method, assignment through the Mahalanobis distance. Both models are applied to DECT scans of the Gammex RMI 467 phantom and for a subset of 10 human tissues. Dose distributions are calculated from Monte Carlo simulations with a point source having the energy spectrum of 125I. The reduced three elements tissue model provides dose equivalence to reference tissues and is equivalent to the calculation of the Mahalanobis distance. The model constructed can be used as a scheme to assess tissues from DECT images for dose calculation.
Teyssier, Jacques. "Analyse des différents types de variabilité, individu, âge, tissu, dans une étude de la lipogenèse et une étude longitudinale de la taille des adipocytes chez le lapin en croissance." Montpellier 2, 1988. http://www.theses.fr/1988MON20161.
Seigneuric, Renaud. "Étude d'hétérogénéités simulées et in vitro du tissu cardiaque et de leurs rôles dans les tachycardies ventriculaires par réentrée." Grenoble 1, 2000. http://www.theses.fr/2000GRE19003.
Adam, Sylvie. "La trame urbaine : Hexagone et analyse théorique des semis urbains." Rouen, 1992. http://www.theses.fr/1992ROUEL153.
The main aim of this research is to look into the heuristic value of the regular hexagonal patterns as these appear in central place theories. The link between regular hexagonal patterns, principles of organization, and concepts of central place theories is first examined. Particular attention is given to the theory of centrality and other works by Walter Christaller, and to the theory of economic regions proposed by August Losch. An overview of more recent theories of central places and applications of hexagonal patterns on urban webs in regional settings is provided. The regular hexagonal pattern can be conceived either as a mesh (only nodes and edges are significant), or as a grid which actually contains people and functions. The second part deals with the regular hexagonal tesselation. Using the example of France, the regular geometric pattern is shown not to fit the structure and organization of the urban web. The third part, based upon Georges Nicolas research on Western Switzerland, confirms the same lack of fit for the regular hexagonal grid. For this reason, an adaptable polygonal grid is proposed as a substitute for the traditional and regular hexagonal tesselations. (abstract by Peter R. Gould and Sylvie Adam)
Oudry, Jennifer. "L' élasticité: nouveau biomarqueur du foie : analyse biomécanique et validation par élastographie impulsionnelle." Université Louis Pasteur (Strasbourg) (1971-2008), 2008. http://www.theses.fr/2008STR13236.
Elastography is to quantitatively measure the elasticity of tissue to replace the tactile control often exercised by physicians. This tactile control known as palpation, aims at qualitatively estimate the elasticity of tissues. Elastography is motivated by the large difference of elasticity observed between normal tissues and tumors in which elasticity can be up to 30 times greater. Elasticity becomes an important parameter in the characterization of soft tissues. In soft tissues, elasticity is driven by the shear elasticity, which is involved in the propagation of shear waves. Their study can thus help quantify the tactile information. We propose to develop computational tools for the theoretical study of shear wave propagation in elastic medium. An evolution of the transient elastography technique, based on the use of a new type of ultrasonic transducer combined with an ultrasonic multichannel acquisition system, is also proposed. The validation of this system and corresponding algorithms are then performed on phantoms. We develop a new kind of material models, a mixture of copolymer-in-oil, mimicking the mechanical and acoustic properties of soft tissues for elastography. Finally, we conduct a comparison of the measurement of elasticity obtained by transient elastography with that obtained by magnetic resonance elastography to study possible differences between these techniques increasingly used for the diagnosis of liver fibrosis
Chan, Yone Claudia. "Modèle numérique de vieillissement de l'os trabéculaire considérant l'hyperminéralisation du tissu et le chargement mécanique." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM4731/document.
Osteoporosis is characterized by a low bone mass density but also an alteration of mechanical properties. The clinical diagnostic is made from the measure of the bone mineral density (BMD) but this examen seems insufficient to quantify bone resistance. In this work, a numerical model of cancellous bone degradation, aging and mechanical adaptation is proposed. Based on hypermineralization, this model simulates the cancellous bone remodeling process over many years. This model allows to predict the behavior of cancellous adaptation in a mechanical low loading case for instance. Results are similar to clinicial tendancy
Thurieau, Nicolas. "Sur la modélisation du tissu cardiaque comme un milieu à microdilatation : une investigation numérique." Thesis, Université de Lorraine, 2014. http://www.theses.fr/2014LORR0018/document.
Background: A soft biological tissue is subjected to numerous exchange phenomena and has an extremely complex structural organization. The knowledge of its mechanical behavior is required in many applications ranging from clinical diagnostic to tissue engineering. To achieve this goal, more or less satisfactory approaches are developed. They all seek to take into account in a more or less systematic manner the microstructure of the medium. Assuming that the biological tissue is a particular micromorphic medium (micropolar medium) leads to good results in the case bone tissue. It is therefore likely that the results of this kind will be obtained for other tissues. Our interest is on the heart tissue and the problem of ischemic heart attack. In this context, it seemed that the most appropriate behavior particularization is that of a microdilatation medium. Work done: The work presented in this thesis is essentially numerical. It aims to highlight the features of the response of microdilatation medium to an external mechanical load. This step is essential for the analysis of the experimental results to be conducted in the future. The work also aims to investigate the potentialities of the model with respect to the heart tissue regarding heart attack and the associated loss of the ability to eject sufficient blood volume. The numerical tools for the analysis of such media are in increasing development. We had to develop our own tool based on the LPI-BEM (Local Point Interpolation - Boundary Element Method). Because of the similarity of the associated field equations, the validity of the numerical strategy is assessed in the case of a piezoelectric material. This choice is not innocent because the piezoelectric medium with microdilatation will allow analyzing the case of an electrical solicitation of the tissue. The details of this original numerical approach are given in Chapter 2 of the thesis. Chapter 3 is devoted to the analysis of the robustness of the method and to the peculiarities of the response of a microdilatation medium. The fourth chapter is devoted to the application to the cardiac tissue. By limiting the study to the case of small strains, it is shown that the model is well suited to the representation of the behavior of cardiac tissue. Indeed, considering the left ventricle as a tubular structure, the left ventricle ejection fraction (clinical criterion of the heart failure) is greatly reduced in the presence of an infarcted area. The latter is modeled as a zone with diffuse boundary where the material points have lost their ability to "breath". These results are promising and encourage further investigations in this direction by taking into account the anisotropic nature of the tissue in a geometrically nonlinear context
Assar, Cuevas Rodrigo. "Modeling and simulation of hybrid systems and cell factory applications." Thesis, Bordeaux 1, 2011. http://www.theses.fr/2011BOR14335/document.
The main aim of this thesis is to develop an approach that allows us to describe biological systems with theoretical sustenance and good results in practice. Biological functions are the result of the interaction of many processes, that connect different hierarchy levels going from macroscopic to microscopic level. Each process works in different way, with its own goal, complexity and hierarchy level. In addition, it is common to observe that changes in the conditions, such as nutrients or environment, modify the behavior of the systems. So, to describe the behavior of a biological system over time, it is convenient to combine different types of models: continuous models for gradual changes, discrete models for instantaneous changes, deterministic models for completely predictable behaviors, and stochastic or non- deterministic models to describe behaviors with imprecise or incomplete information. In this thesis we use the theory of Composition and Hybrid Systems as basis, and the BioRica framework as tool to model biological systems and analyze their emergent properties in silico.With respect to Hybrid Systems, we considered continuous models given by sets of differential equations or more general dynamics. We used Stochastic Transition Systems to describe the dynamics of model changes, allowing cofficient switches that control the parameters of the continuous model, and strong switches that choose different models. Composition, reconciliation and reusing of models allow us to build complete and consistent descriptions of complex biological systems by combining them. Compositions of hybrid systems are hybrid systems, and the refinement of a model forming part of a composed system results in a refinement of the composed system. To implement our approach ideas we complemented the theory of our approach with the improving of the BioRica framework. We contributed to do that giving a BioRica specification of Hybrid Systems that assures integrity of models, allowing composition, reconciliation, and reuse of models with SBML specification.We applied our approach to describe two systems: wine fermentation kinetics, and cell fate decisions leading to bone and fat formation. In the case of wine fermentation, we reused known models that describe the responses of yeasts cells to different temperatures, quantities of resources and toxins, and we reconciled these models choosing the model with best adjustment to experimental data depending on the initial conditions and fermentation variable. The resulting model can be applied to avoid process problems as stuck and sluggish fermentations. With respect to cell fate decisions the idea is very ambitious. By using accurate models to predict the bone and fat formation in response to activation of pathways such as the Wnt pathway, and changes of conditions affecting these functions such as increments in Homocysteine, one can analyze the responses to treatments for osteoporosis and other bone mass disorders. We think that here we are giving a first step to obtain in silico evaluations of medical treatments before testing them in vitro or in vivo
Adam, Jérémy. "Développement, modélisation et caractérisation d'une maille innovante réalisée en fabrication additive pour les grands défauts osseux." Thesis, Paris, ENSAM, 2017. http://www.theses.fr/2017ENAM0068/document.
The work detailed in this thesis is about a titanium 3D printed mesh for large bone defects. Large bone defects are often due to surgical resections, performed after a cancer or an infection. When the defect reach a critical size, bone regeneration is impossible and it often leads to the loss of function. When it happened, the wound need to be cured using reconstructive surgery. The mandibular reconstruction is one of the most performed reconstructive surgery. Nowadays, we reconstruct the mandible with the fibula free flap technique, which require huge amount of time and resources for mixed results (around 10% failure rate). Based on the international literature, we developed a titanium 3D printed mesh to replace the fibula autograft and limit its side effect while offering to mesenchymal cells optimal growing environment. On the mechanical point of view, this environment requires to decrease the titanium initial rigidity from 110GPa to a range between 0.1 and 1GPa. In order to achieve that goal, we have developed a design methodology that lead us to innovation. We developed a load restauration system that allow us to combine low rigidity and high resistance. In order to find the final design, we used finite element modeling. Then, the final design have been tested mechanically in compression, traction and flexion. Because most of the requirements were reached, we designed an animal study which should take place in the next years. Eventually, we discovered some limitation for metallic 3D printing, essentially due to unsupported areas required for the load restauration. This innovative mesh is today optimized in order to be rapidly given to patients in the need
Kandil, Karim. "Modélisation multi-physique et multi-échelle des tissus mous stratifiés : application à la réponse multi-axiale du disque intervertébral humain." Thesis, Lille 1, 2020. http://www.theses.fr/2020LIL1I040.
The intervertebral disc is probably the most extraordinary tissue that the nature produces, mainly for its unusual time-dependent properties strongly influenced by the biochemical environment and the applied mechanical loading. Establishing accurate structure-property relationships for intervertebral disc annulus fibrosus tissue is a fundamental task for a reliable computer simulation of the human spine. The difficulty emanates from the multi-axiality and the anisotropy of the tissue response along with regional dependency of a complex hierarchic structure interacting with the biochemical environment. In addition, the annulus fibrosus exhibits an unusual time-dependent transversal behavior for which a complete constitutive representation is not yet developed. A physically-based chemo-viscoelastic constitutive model that takes into account an accurate disc annulus structure in relation with the biochemical environment is proposed. Numerical models of annulus specimens and lumbar functional spinal units (one disc and the adjacent vertebrae) are designed while taking into consideration the interlamellar matrix connecting the fibers-reinforced lamellae. At the specimen scale, the model capabilities are verified by experimental comparisons under various conditions in terms of osmolarity, strain-rate and multi-axiality while considering the regional dependency. Our results highlight the determinant role of the interlamellar matrix in the disc multi-axial response. The different scenarios applied to lumbar units show encouraging multi-axial predictive capabilities of our approach making it a promising tool for human spine behavior long-term prediction including age-dependency
Jguirim, Ines. "Modélisation et génération d'itinéraires contextuels d'activités urbaines dans la ville." Thesis, Brest, 2016. http://www.theses.fr/2016BRES0074/document.
The city is an urban aggregation allowing to offer diverse services to his city-dwellers. She establishes a complex system which depends on several social and economic factors. The configuration of the space influences in a important way the accessibility to the various features of the city. The spatial analysis of the urban structure is realized on cities to study the characteristics of the space and be able to estimate its functional potential. The aim of the thesis is to propose an approach to spatial analysis which takes into account the various structural and semantic aspects of the city. A model based on the graphs was proposed to represent the multimodal transport network of the city which guarantees the accessibility to the various points of interest. Super-networks were used to integrate the possibility of an intermodal transfer into the model of transport by links of interdependence between the sub-graphs associated to the various means of transportation. The temporal aspect was represented in the model by attributes specifying the temporal constraints characterizing the itinerary of every node and every edge such as the time of exploration, the waiting time and the time required for the road penalties. The functional aspect is introduced by the concept of activity. We proposed a conceptual model which aims to model the various contextual elements which can affect the planning and the execution of the urban activities such as the spatiotemporal frame and the profile of the user. This model was enriched by knowledge management which aims to represent information about individual behaviors. The extracted knowledge are represented by a management system of rules allowing the contextual planning of the activity
Abdesselam, Inès. "Dépôts de graisse ectopique : étude de leur développement et de leur modulation." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM5005.
The project of this thesis mainly focuses on ectopic lipid deposition development and their flexibility following therapeutic intervention. In our first study, we set out chronological order of ectopic fat onset and cardiac abnormalities in a high fat high sucrose mice model. Short duration exendin-4 treatment reverses every altered parameter. In the second study, we assessed treatment of obesity effect on cardiac ectopic fat deposition (EAT and steatosis), as well as hepatic and pancreatic fat at two different time points (6 months and 32 months) after bariatric surgery. We show significant reduction of every ectopic fat deposition, however in different kinetic. Finally, in a third study, we investigate birth weight effect on epicardial adipose tissue development. This study demonstrate important EAT accumulation in adulthood when birth weight is increased. Furthermore, birth weight and catch up growth in childhood between 2 and 12 years parameters impact significantly the development of epicardial fat.In summary, these results provide better understanding of ectopic fat deposition development and modulation
Ballit, Abbass. "Design and manufacturing process optimization for prosthesis of the lower limb." Thesis, Compiègne, 2020. http://www.theses.fr/2020COMP2589.
The prosthetic socket, an essential interface element between the patient's stump and prosthetic device, is most often the place where the degree of prosthetic success is defined. It is the most critical part of the prosthesis, customized to fit with the unique residual limb of the amputee. Without a proper socket shape and fit, the prosthesis becomes uncomfortable, or even unusable, and causes pain and skin issues. The state-of-the-art prosthetic production is still missing universal numerical standards to design a socket. The current practice is expensive and relies on the manual refinements of the orthopedic technician, and the fit quality strictly correlates with his skills as well as the subjective feedback of the patient. The thesis aims to conduct a deep analysis of an optimal design of the prosthetic socket by studying and developing an alternative computer-aided design process. This process is fully based on the virtual model of the patient’s residual limb and relies on the calculation of the socket-stump interaction. A fast calculation is favorable in this case, that’s why we propose to use the Mass-Spring System (MSS) instead of the widely used FE method to model the soft tissues of the residual limb. A new configuration of the MSS model is proposed to respect the non-compressibility property of the soft tissues by adding non-linear “Corrective Springs”. The numeric model is to be generated from the scanned model of the stump. For this purpose, we propose a fusion scheme of four RGB-Depth sensors for a rapid and low-cost scan with error reduction techniques. Finally, the virtual residual limb is used in the socket designing phase. A parametric design method is proposed and investigated. The design problem is transformed into a constraint-satisfaction-problem whose constraints are derived from the inverse calculation of the stump-socket interaction. The inverse approach has been chosen to eliminate the need for expensive contact formulation. This fact leads to rapid calculations, and consequently, allows to provide real-time numerical feedback during the designing process. The validation was done by comparing the results of our system with the output of FE simulations. The system has been implemented with a user-friendly graphical interface and virtually tested and numerically validated. This system reduces the limitations of the current practices. However, a lot of works is still ahead to refine and develop the system and validate it with clinical experiments
Fan, Ang-Xiao. "Geometric and numerical modeling of facial mimics derived from Magnetic Resonance Imaging (MRI) using Finite Element Method (FEM)." Thesis, Compiègne, 2016. http://www.theses.fr/2016COMP2307.
Human face plays an important role interpersonal communication. Facial dysfunction or disfigurement due to trauma or pathologies may impede normal social activities. Surgical treatment is often necessary. Nowadays, treatment outcome and rehabilitation condition are estimated only by qualitative methods, such as visual observation and palpation. In expectation of providing quantitative criteria, this thesis proposes to model facial mimics using FEM (Finite Element Method) on the basis of MRI (Magnetic Resonance Imaging) data. A subject-specific face model was reconstructed based on segmentation of MRI data; it contains bony parts, mimic muscles (e.g. zygomaticus major muscle), subcutaneous soft tissues and skin. Identification of biological soft tissues was conducted through bi-axial tension tests and numerical modeling. Then the geometric model was meshed to conduct FE calculations simulating three facial mimic movements (smile, pronunciation of sound “Pou” and “O”). Muscle was modeled as quasi-incompressible, transversely-isotropic, hyperelastic material, with activation ability. Relevant information (e.g. contraction amplitude of muscle) used in simulation was extracted from measurement of MRI data. It is to be noted that the same experimental MRI data as used in modeling was taken as validation reference for simulation results. This study can be applied clinically in evaluation of facial treatment andpostoperative recovery
Spingarn, Camille. "Contribution à la biomécanique de la régénération osseuse : modélisation, simulation et applications." Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAD010/document.
This work deals with modelization of bane remodeling. We present first a madel thal accounts for the cellular res panse to a mechanical stimulus in a general case at a continuous scale. This madel is applied to 2D and 3D geometries at macroscopic scale to mimic real cases, as weil as 2D trabecular-type geometries at mesoscopic scale. However, the complexity of bane remodeling does not allow a unique approach. Th us, the thesis work is focused on the particular case of orthodontie bane re mode ling. A new specifie madel is developed accounting for the influence of the periodontal ligament on orthodontie bane remodeling by integrating the oxygen concentration effect controling the evolutions of cellular densities. The cellular experimental data in vitro are extracted from the literature, and serve as input data of the developed madel in arder to ablain the evolution of bane density around the root of a 3D cylindrical tooth
Goda, Ibrahim. "Micromechanical models of network materials presenting internal length scales : applications to trabecular bone under stable and evolutive conditions." Thesis, Université de Lorraine, 2015. http://www.theses.fr/2015LORR0055/document.
A methodology based on micromechanics has been developed to determine the effective behavior of network materials endowed with a discrete architecture at the microscopic level. It relies on the discrete homogenization method, which has been applied to textile monolayers and trabecular bones. The initially discrete topology of the considered network materials results after homogenization at the mesoscopic level in anisotropic micropolar effective continuum, which proves able to capture the observed internal scale effects. Such micromechanical methods are useful to remedy the difficulty to measure the effective mechanical properties at the intermediate mesoscopic level scale. The bending and torsion responses of vertebral trabecular bone beam specimens are formulated in both static and dynamic situations, based on the Cosserat theory. 3D models have been developed for describing the multiaxial yield and brittle fracture behavior of trabecular bone, including the analysis of size-dependent non-classical plastic yield. We have constructed by FE analyses a homogeneous, orthotropic couple-stress continuum model as a substitute of the 3D periodic heterogeneous cellular solid model of vertebral trabecular bone, based on the equivalent strain energy approach. Bone tissues are able to adapt their local density and load bearing capacities as well as their size and shape to mechanical stimuli. We have developed models for combined internal and external bone remodeling in the framework of the thermodynamics of irreversible processes, at both the cellular and macroscopic levels. We lastly combined anisotropic internal remodeling with fatigue continuum damage
Lamantia, Valérie. "Effet des acides gras oméga-3 sur l’inflammasome NLRP3 et les facteurs de risque de diabète de type 2 chez l’humain : modèles in vivo et ex vivo." Thesis, 2019. http://hdl.handle.net/1866/24589.
Background: White adipose tissue (WAT) dysfunction promotes risk factors for type 2 diabetes (T2D), namely insulin resistance (IR), high glucose-stimulated insulin secretion (GIIS), delayed fat clearance and high concentrations of apoB-lipoproteins (measured as plasma apoB) including low density lipoproteins (LDL). Recent studies from our lab and others suggest that high plasma apoB (hyperapoB) is a cause and not only a consequence of WAT dysfunction. Moreover, upregulated receptor-mediated uptake of apoB-lipoproteins via LDL receptor (LDLR) and cluster of differentiation 36 (CD36), promotes the risk for T2D. However, underlying mechanisms as well as nutritional interventions to target them remain unclear. Activation of the NLRP3 inflammasome/interleukin (IL)-1β pathway promotes WAT dysfunction and risk factors for T2D and is activated by oxidized LDLs in immune cells. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce hyperapoB, NLRP3 inflammasome activity in immune cells and risk factors for T2D in humans. They are synthesized endogenously through δ-5 (D5D) and δ-6 (D6D) fatty desaturases. In humans, low levels of circulating EPA and DHA and D5D activity and high D6D activity predict the incidence of T2D and IR by unknown mechanisms. Objectives: The hypothesis of my thesis is that EPA and DHA improve T2D risk factors, namely WAT dysfunction, delayed fat clearance, IR and high GIIS, this via a reduction of plasma apoB and WAT NLRP3 inflammasome activity. The objectives are to examine whether: 1) the associations between the levels of D5D and D6D activities and the risk factors for T2D are dependent on plasma apoB; 2) supplementation with EPA+DHA reduces plasma apoB, WAT LDLR and CD36 expression, WAT NLRP3 inflammasome activity and T2D risk factors; 3) EPA+DHA directly inhibits IL-1β secretion from human WAT stimulated by canonical signals or native LDLs. Methods: Normoglycemic men and postmenopausal women were tested at baseline and after supplementation with EPA (1.8 g/day) and DHA (0.9 g/day) for 12 weeks. The activities of D5D and D6D were estimated from the product/precursor fatty acids in plasma phospholipids. We measured GIIS, IR and disposition index by a Botnia clamp. Following a 66% fat meal, delayed fat clearance was measured as the area under the curve (over 6 h) of plasma triglycerides (TG) or apoB48 (chylomicrons). Ex vivo in a WAT biopsy, we measured LDLR and CD36 surface expression by immunohistochemistry, NLRP3 and IL1B mRNA by RT-qPCR, and IL-1β secretion by alpha-LISA either unstimulated or stimulated by lipopolysaccharide (LPS), adenosine triphosphate (ATP), and/or native human LDLs, and during co-incubation with EPA+DHA. Results: At baseline (N=98), D5D activity correlated negatively with plasma apoB, 2nd phase GIIS, IR and delayed chylomicron clearance and these associations were dependent on plasma apoB. Conversely, D6D activity correlated positively with GIIS, IR, and delayed chylomicron clearance independently of plasma apoB. In subjects who completed the EPA+DHA supplementation (N=30), there was an amelioration in 1st phase GIIS, disposition index and TG clearance. Higher baseline levels of plasma apoB, plasma postprandial TGs, IR, WAT LDLR and CD36 surface expression, WAT IL-1β secretion and WAT NLRP3 mRNA predicted a greater reduction of these parameters. In comparison with palmitic acid, EPA+DHA inhibited IL-1β secretion from WAT, either unstimulated or stimulated by LPS, ATP and/or subjects’ native LDLs. Conclusion: The negative associations of D5D activity with risk factors for T2D are dependent on plasma apoB. Best responders to EPA and DHA supplementation to reduce plasma apoB, WAT LDLR and CD36 expression, WAT NLRP3 inflammasome activity, delayed TG clearance, and IR are subjects with elevated baseline levels of these parameters. EPA and DHA directly inhibit IL-1β secretion from human WAT induced by native LDLs or other signals. We propose that EPA and DHA supplementation may target upregulated WAT NLRP3 inflammasome activity induced by high plasma concentrations, or receptor-mediated uptake, of apoB-lipoproteins, and thus help prevent T2D.