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Acute traumatic coagulopathy
No full textUne coagulopathie aigüe traumatique est constatée chez environ un tiers des patients traumatisés sévères. Ce trouble précoce, endogène et spécifique nécessite l’association d’importantes lésions tissulaires et d’une hémorragie. La phase initiale est caractérisée par l’expression d’un phénotype hémorragique responsable d’une mortalité précoce, la phase tardive par l’expression d’un profil pro-thrombotique responsable d’une mortalité retardée. La physiopathologie de ce phénomène est encore mal comprise. Celle-ci pourrait impliquer une dysrégulation de la voie de la protéine C, une CIVD fibrinolytique, une diminution des stocks en fibrinogène, une altération de la fonction plaquettaire et une agression endothéliale. Plusieurs auteurs ont relevé l’absence de modèle animal pertinent pour vérifier ces hypothèses. Les objectifs de ce travail de thèse ont été la mise au point d’un modèle animal de coagulopathie aigüe traumatique et l’étude de sa physiopathologie. Une première étude a été réalisée, permettant la mise au point d’un modèle murin de coagulopathie traumatique. Celle-ci a mis en évidence un trouble de la coagulation précoce, endogène et spécifique associé à l’expression d’un phénotype hémorragique et répondant à tous les critères clinico-biologiques d’une coagulopathie aigue traumatique. Une deuxième étude basée sur ce modèle a été réalisée afin de mettre en évidence les mécanismes généraux intervenant dans la physiopathologie de la coagulopathie aigüe traumatique. Le rôle protecteur du fibrinogène a été confirmé dans cette étude. Le profil clinicobiologique observé associait une génération de thrombine normale, une discrète thrombopénie et un phénotype hémorragique. Celui-ci infirmait l’hypothèse d’une CIVD mais était compatible avec celle d’une fibrinolyse médiée par une production accrue de protéine C activée.An acute traumatic coagulopathy is observed in about one-third of severely traumatized patients. This early, endogenous and specific disorder occurs when tissue damages are combined with hemorrhage. The early phase of this condition is characterized by the expression of a bleeding phenotype and a lengthening in prothrombin time.The late phase is characterized by a pro-thrombotic profile leading to multiple organ failure. The physiopathology of this phenomenon is still poorly understood. This could involve a dysregulation of the protein C pathway, fibrinolytic DIC, a decrease in fibrinogen, impairment in platelet function and endothelial damages. Various authors have emphasized the lack of relevant animal model to study this phenomenon.The objective of this work was to develop an animal model of acute traumatic coagulopathy to study its pathophysiology. A first study was performed and led to the development of a murine model of traumatic coagulopathy. This study revealed a hemostasis disorder that meets all the criteria of acute traumatic coagulopathy. Then, a second study based on this model was performed to observe general hemostasis disorders occurring in the context of traumaassociated hemorrhage. This study confirmed the protective role of fibrinogen against ATC. The clinicalbiological profile observed in the case of ATC combining normal thrombin generation, subtle thrombocytopenia and hemorrhagic phenotype observed in the case of ATC invalidated the hypothesis of DIC but was compatible with fibrinolysis mediated by an increase in activated protein C
Long-term effect of atorvastatin at low-dose concentration on atherosclerosis : a multidisciplinary study on an animal model, the Watanabe rabbit
No full textLes maladies cardiovasculaires sont la première cause de mortalité dans le monde, en lien notamment avec la présence et la rupture de plaques d’athérome. Afin d’éviter la survenue d’évènements aigus, un traitement par statines peut être proposé. Cependant, leur utilisation engendre un risque d’effets délétères. Afin de réduire ce risque, une réduction des doses utilisées pourrait être envisagée. Ce travail de thèse étudie les effets potentiels d’un traitement à très faible dose d’atorvastatine et à long terme sur un modèle animal : le lapin Watanabe. Des mesures ont été menées sur des individus contrôles et traités de 3 à 12 mois. Le suivi de la lipidémie et des principaux facteurs biochimiques, de l’adhésion et de l’inflammation a été fait au niveau sanguin. Le développement de l’athérosclérose a été évalué en tomographie par cohérence optique (OCT). Des mesures en histologie ont permis de valider un classement proposé avec l’OCT et de quantifier les macrophages intra plaques. L’élasticité artérielle a été testée in vivo par la mesure de la vitesse de l’onde de pouls et in vitro par un test de traction statique. La fonction vasculaire a été appréhendée en vasoréactivité sur différents territoires (aorte, carotide, mésentérique). Le contenu en élastine et collagène de la paroi des vaisseaux a été effectué en microscopie à deux photons et génération de seconde harmonique. Enfin la respiration mitochondriale du myocarde et sa susceptibilité aux ROS a été évaluée sur fibres cardiaques perméabilisées, l’activité de systèmes antioxydants enzymatiques mesuré, ainsi que la peroxydation lipidique. Les résultats montrent des effets bénéfiques de ce traitement à très faible dose d’atorvastatine sur la fonction cardiovasculaire indépendamment d’un effet hypolipidémiant.Cardiovascular diseases are the first worldwide causes of death, associated to the presence and rupture of atherosclerotic plaques. To limit acute events, statins may be prescribed. However, its use leads to deleterious effects risk. To reduce this risk, a dose reduction could be considered. The work of this thesis is to study potential effects of a very low dose of atorvastatin, taken in the long term, in an animal model: the Watanabe rabbit. Measurements are made on control and treated animals from the age of 3 to 12 months. Circulating lipids, biochemical parameters and parameters of adhesion and inflammation were studied. Atherosclerosis evolution was evaluated by optical coherence tomography (OCT). Histological measurements allowed to validate a ranking proposed with OCT observations and to quantify intra-plaque macrophage content. Arterial stiffness was tested in vivo with pulse wave velocity and in vitro with a static tensile test. Vascular function was approached with vasoreactivity in different territories (aorta, carotid, mesenteric). Elastin and collagen contents of the artery wall were determined with two-photon and second harmonic generation microscopy. Finally, mitochondrial respiration and its susceptibility to ROS were evaluated in permeabilized cardiac fibers, any enzymatic antioxidant systems and lipid peroxidation were measured. Results show beneficial effects of this very low dose atorvastatin treatment in cardiovascular function, independently of a lipid-lowering effect.Keywords: atherosclerosis
Effects of variation oxygen partial pressure on fat tissue before fat grafting in reconstructive surgery
No full textLe transfert de tissu adipeux est une des révolutions de la chirurgie réparatrice des vingt dernières années. Cette technique s’est rapidement imposée au vu de sa facilité de réalisation, de son faible coût et de son innocuité. Cependant, le taux de résorption imprévisible entre 20 et 80% demeure le principal facteur limitant de cette technique. Après son prélèvement, le tissu adipeux greffé est oxygéné par diffusion, jusqu’à sa revascularisation. Une amélioration des conditions locales en oxygène pourrait améliorer les résultats de la greffe. Dans un premier temps, nous avons montré que le tissu adipeux était en hypoxie et présentait des signes de souffrance tissulaire au moment de la réinjection. Nous avons démontré que des pressions partielles élevées augmentaient les phénomènes inflammatoires observés. Inversement, si le tissu était en hypoxie, il utilisait plus rapidement la voie anaérobie avec des conséquences néfastes au niveau cellulaire. Nous avons alors utilisé l’hémoglobine issue du ver marin pour augmenter l’oxygène disponible au tissu sans s’exposer aux effets indésirables de l’hyperoxie. Ce transporteur d’oxygène ne parait pas diminuer les effets de l’hypoxie sur le tissu adipeux après son prélèvement, aux concentrations et dans les conditions testées.Autologous fat grafting has gained in popularity in the field of reconstructive surgery over the past 20 years. Fat is an optimal, simple, low-cost soft-tissue filler. However, unpredictable fat retention remains a major concern as the extent of fat resorption ranges from 20 to 80%. Until revascularization occurs, fat tissue is supplied by oxygen diffusion only. An improvement of oxygen partial pressure of the tissue could improve fat graft retention. First, we demonstrated that fat exhibited severe hypoxia, inflammation, and increased levels of reactive oxygen species at the time of injection. Fat tissue exposed to high oxygen partial pressure exhibited higher signs of inflammation. Conversely, hypoxia reduced the aerobic capacity of the tissue which leads to harmful effects and cell death. Haemoglobin based artificial oxygen carrier M101 from lungworm was used to increase available oxygen without exposing the tissue to high partial pressure of oxygen. Signs of inflammation were not decrease with use of haemoglobin M101 in the concentrations and conditions used
Comparison of Sodium Selenite and Selenium-Enriched Spirulina Supplementation Effects After Selenium Deficiency on Growth, Tissue Selenium Concentrations, Antioxidant Activities, and Selenoprotein Expression in Rats
No full textSelenium contributes to physiological functions through its incorporation into selenoproteins. It is involved in oxidative stress defense. A selenium deficiency results in the onset or aggravation of pathologies. Following a deficiency, the repletion of selenium leads to a selenoprotein expression hierarchy misunderstood. Moreover, spirulina, a microalga, exhibits antioxidant properties and can be enriched in selenium.. Our objective was to determine the effects of a sodium selenite or selenium-enriched spirulina supplementation. Thirty-two female Wistar rats were fed for 12 weeks with a selenium-deficient diet. After 8 weeks, rats were divided into 4 groups and were fed with water, sodium selenite (20 μg Se/kg body weight), spirulina (3 g/kg bw), or selenium-enriched spirulina (20 μg Se/kg bw + 3 g spirulina/kg bw). Another group of 8 rats was fed with normal diet during 12 weeks. Selenium concentration and antioxidant enzyme activities were measured in plasma, urine, liver, brain, kidney, heart, and soleus. Expression of GPx (1, 3), Sel (P, S, T, W), SEPHS2, TrxR1, ApoER2, and megalin were quantified in liver, kidney, brain, and heart. We showed that a selenium deficiency leads to a growth delay, reversed by selenium supplementation despite a minor loss of weight in week 12 for SS rats. All tissues displayed a decrease in selenium concentration following deficiency. The brain seemed protected. We demonstrated a hierarchy in selenium distribution and selenoprotein expression. A supplementation of sodium selenite improved GPx activities and selenoprotein expression while a selenium-enriched spirulina was more effective to restore selenium concentration especially in the liver, kidney, and soleus
Effect of Induced Mild Hypothermia on Acid-Base Balance During Experimental Acute Sepsis in Rats
No full textInternational audienceThe aim of this study was to determine the effect of induced mild hypothermia (34°C) on acid-base balance in septic rats. Twenty-eight male Sprague-Dawley rats median weight 306 g, range 251–333 g were used. After anesthesia and when the target temperature was reached (normothermia: 38°C or induced mild hypothermia: 34°C), sepsis was induced by cecal ligation and perforation. Measurements of cardiopulmonary parameters and blood samples were performed at T0h (occurring immediately after chirurgical procedures), T2h, T4h (at each temperature), and T6h (at 34°C only). Blood oxygen saturation, heart and respiratory rates, arterial blood pH, carbon dioxide partial pressure, sodium, potassium, chloride and calcium concentrations, hematocrit, blood lactate, tumor necrosis factor-α and interleukin-6 concentrations were measured on anesthetized rats. Other parameters such as bicarbonate concentration, hemoglobin concentration, base excess, and anion gap were estimated from measured parameters. Main results showed that an increase in both cytokines concentrations was observed in septic rats compared with sham rats. This increase was less marked at 34°C compared with 38°C. Moreover, sepsis induction led to a marked metabolic acidosis and hypothermia delayed this acidosis. Induced mild hypothermia delays the evolution of cytokines and metabolic acidosis during experimental sepsis
Quand le Corps des Femmes et des Hommes ne Réagit pas Pareil
No full textNational audienceInduction de l'inflammation 1 Récupération des Auricules L'auricule : Un tissu cardiaque récupéré lors des opérations du coeur.</div
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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