INTRODUÇÃO: O tratamento para o câncer de cabeça e pescoço (CCP) envolve várias estruturas e tecido linfático que estão sob risco de prejuízo pelo tratamento cirúrgico e/ou radio-quimioterápico. O linfedema secundário externo e interno de cabeça e pescoço é sequela importante, ainda que subdiagnosticada, subtratada e subvalorizada e, em muitos casos, com impacto nas funções de respiração, deglutição e voz. OBJETIVO: Avaliar a presença, estadiamento e características do edema facial, cervical e laríngeo, a deglutição, após o tratamento para o câncer de cabeça e pescoço. MÉTODOS: O estudo utilizou as Escalas do MD Anderson Cancer Center (MDACC) para avaliar e estadiar o linfedema externo de face e pescoço e a Escala do Edema da Radioterapia de Patterson et al. para o edema interno faringolaríngeo após um mínimo de três meses de tratamento para o CCP, no Serviço de Cirurgia de Cabeça e Pescoço do Hospital das Clínicas da FMUSP e do ICESP. A deglutição foi avaliada por meio de videoendoscopia da deglutição (VED) nas consistências de líquido, néctar, pastoso e sólido. RESULTADOS: O linfedema foi detectado em 97,8% das avaliações com predomínio do tipo composto (73,9%). Foram detectados percentual alto de linfedema externo de pescoço (71,7%) e submandibular (63%), com predomínio para os níveis mais avançados (2 e 3) indicando tendência à fibrose. Encontrou-se edema interno em quase todas as estruturas e espaços avaliados. À VED, observou-se resíduo, penetração em todas as cosnistências analisadas. O tratamento combinado com Rt teve relação com o linfedema externo submandibular e pescoço, interno, bem como com a alteração de sensibilidade faringolaríngea, presença de resíduo e penetração para pastoso. CONCLUSÃO: O linfedema cervicofacial e faringolaríngeo é um evento frequente após o tratamento para o CCP, com consequências importantes no desempenho da deglutição caracterizadas por resíduo e levar à penetração e aspiração. O tratamento combinado com Rt é um fator associado a estas alterações / BACKGROUND: Treatment for head and neck cancer (HNC) involves several structures and lymphatic tissue that are at risk of injury by surgical and / or radio-chemotherapy treatment. External and internal secondary lymphedema of the head and neck is an important outcome, although underdiagnosed, under-treated and undervalued, and in many cases with an impact on breathing, swallowing and voice functions. OBJECTIVE: To evaluate the presence, stage and characteristics of facial, cervical and laryngeal lymphedema, swallowing, after treatment for HNC. METHODS: The study used the MD Anderson Cancer Center Scales (MDACC) to evaluate the stage of external face and neck lymphedema and the Patterson et al. for internal pharyngolaryngeal edema after a minimum of three months of treatment for HNC at the Head and Neck Surgery Service of the Hospital das Clínicas of FMUSP and ICESP. Swallowing was evaluated by Fiberoptic Endoscopic Evaluation of Swallowing (FEES) in the consistencies of liquid, nectar, pasty and solid. RESULTS: Lymphedema was detected in 97.8% of the evaluations with a predominance of the composite type (73.9%). A high percentage of external lymphedema of the neck (71.7%) and submandibular (63%) were detected, with a predominance of the more advanced levels (2 and 3) indicating a tendency to fibrosis. Internal edema was found in almost all structures and spaces evaluated. At FESS, residue was observed, penetration in all analyzed aspects. The combined treatment with Rt was related to external submandibular, neck lymphedema and internal edema, as well as the alteration in pharyngolaryngeal sensitivity, presence of residue and penetration to pasty. CONCLUSION: Cervicofacial and pharyngolaryngeal lymphedema is a frequent event after treatment for HNC, with important consequences on swallowing performance characterized by residue that lead to penetration and aspiration. Combined treatment of Rt is a factor associated with these changes

O esvaziamento cervical faz parte do tratamento oncológico de pacientes portadores de neoplasias da cabeça e pescoço, onde o ombro está sob risco de alterações relacionadas ao procedimento. A morbidade pós-operatória está diretamente relacionada com a extensão cirúrgica, na qual podem estar associados deslocamentos de retalhos e ressecções de tecidos e estruturas neuromusculares. Sendo assim, a doença nesta região apresenta potencial suficiente para afetar a função e a qualidade de vida relacionada ao ombro dos pacientes. Altos índices de complicações funcionais são encontrados após o esvaziamento cervical, os quais variam de 18 a 77% nas cirurgias com a preservação do nervo acessório. As seqüelas mais comumente encontradas são a dor, disfunção na amplitude de movimento e força muscular do ombro, déficit funcional e piora da qualidade de vida. Este estudo teve por objetivo avaliar a função do ombro, a dor e a qualidade de vida em pacientes portadores de câncer de cabeça e pescoço submetidos a esvaziamento cervical, bem como avaliar os resultados do protocolo de reabilitação fisioterápica proposto. Foram avaliados prospectivamente 88 pacientes (120 ombros) no pré-operatório, 1º mês e no 3º mês após o procedimento, os quais foram submetidos a esvaziamento cervical unilateral ou bilateral por doença maligna na região da cabeça e pescoço. A maioria dos pacientes foi do sexo masculino e com idade média de 56,7 anos (mediana de 56,5 anos). Destes 120 ombros, o nervo acessório foi preservado em 108. Observou-se que a função do ombro apresentou-se significativamente afetada após o esvaziamento cervical, sendo o esvaziamento cervical seletivo, o estadiamento clínico inicial (I/II), a não realização de rotação de retalho miocutâneo de peitoral maior e a não realização de radioterapia os fatores relacionados a uma menor perda relativa para os movimentos do ombro bem como das forças musculares, principalmente de trapézio. Especificamente, o esvaziamento cervical seletivo foi associado a uma menor perda relativa nos movimentos de extensão (p=0,004) e rotação interna (p=0,043) no 1º mês e flexão (p=0,027) e rotação externa (p=0,008) no 3º mês; o estadiamento clínico I/II à abdução (p=0,045), força de trapézio médio (p=0,005), trapézio inferior (p=0,007) e rombóides (p<0,001) no 3º mês; a não realização de rotação de retalho de peitoral maior à flexão (p=0,003) no 1º mês e rotação externa (p=0,006) no 3º mês; e a não realização de radioterapia à abdução (p=0,007) no 3º mês. Verificou-se também que após a cirurgia, os movimentos de flexão e abdução, as forças de trapézio médio, trapézio inferior e rombóides e o Escore de Constant são os principais fatores relacionados à dor; assim como a flexão, extensão, rotação interna e rotação externa, forças de trapézio médio, serrátil anterior e rombóides são os fatores relacionados a qualidade de vida (domínios dor, atividade, recreação e ombro). Observou-se ainda que o protocolo de reabilitação fisioterápica, quando realizado de forma completa, pode ser benéfico para os pacientes, minimizando a perda da função pós-operatória e reduzindo no 3º mês após a cirurgia a seqüela instalada no 1º mês nos movimentos de flexão e abdução, bem como na força de trapézio, estes que são os movimentos e força muscular principalmente limitados após o esvaziamento cervical / Neck dissection is the treatment of head and neck cancer patient in whom the shoulder is at risk for changes related to the procedure. The postoperative morbidity is directly related with the surgery, which can be associated with displacement of flaps and resection of tissue and neuromuscular structures. The disease in this region has sufficient potential to affect the function and quality of life related to the shoulder of these patients. High rates of functional complications are found after neck dissection, which vary from 18 to 77% in surgery sparing the accessory nerve. The most common sequels found are pain and changes on range of motion and muscle strength in shoulder function, functional deficits and worsening quality of life. This study aimed to evaluate the shoulder function, pain and quality of life in head and neck cancer patients undergone neck dissection, and evaluate the results of the protocol physiotherapy rehabilitation proposed. We prospectively evaluated 88 patients (120 shoulders) preoperatively, 1st month and 3rd months after the unilateral or bilateral neck dissection due to malignancy in the head and neck region. Most of the patients were male and mean age was 56.7 years (median 56.5 years). Of 120 shoulders, the accessory nerve was preserved in 108. It was observed that the shoulder function had to be significantly affected after neck dissection, being the selective neck dissection, the initial clinical staging (I/II), not undergone the pectoral myocutaneos flap and not submitted to postoperative radiotherapy were the factors related to a lower relative loss on the shoulder movements and the muscle strength, especially considering the trapezius muscle. Specifically, the selective neck dissection was associated with a lower relative loss on the extension (p=0.004) and internal rotation (p=0.043) at 1st month and flexion (p=0.027) and external rotation (p=0.008) in the 3rd month; the clinical staging I / II for abduction (p=0.045), strength of middle trapezius (p=0.005), lower trapezius (p=0.007) and rhomboid (p<0.001) at 3rd month, patients not undergone pectoral myocutaneos flap showed lower losses for flexion (p=0.003) at 1st month and external rotation (p=0.006) at 3rd monts, and patients not submitted to postoperative radiotherapy were at lower risk for losses at abduction (p=0.007) in the 3rd month. It was found that after surgery, the movement of flexion and abduction, the strength of middle trapezius, lower trapezius and rhomboid and the Constant Score were the main factors related to pain, as well as flexion, extension, internal rotation and external rotation, strength the middle trapezius, serratus anterior and rhomboid are the factors related to quality of life (domains pain, activity, recreation and shoulder). Considering the protocol of physiotherapy rehabilitation it was observed that, if done in full, it might be beneficial to patients, minimizing the loss of function and reducing postoperative at 3rd months after surgery the sequel installed at 1st month in the movements of flexion and abduction, as well as the muscle strength of trapezius, which are the movements and muscle strength mainly affected after neck dissection

The reduction behaviour of the olivine iron ore pellet MPBOwas studied in laboratory scale at KTH as well as in the LKABexperimental blast furnace. Initially, a newreduction-under-load, or so-called reduction/softening/melting,test equipment was developed. Experiments using differentreducing conditions, corresponding to different radialpositions of the blast furnace, were conducted. The experimentsincluded different temperature profiles, reducing atmospheresand mechanical loads applied on the sample bed to simulate thevarying conditions in the blast furnace process. The progressof reduction was investigated, as well as the processes ofsintering and contraction during reduction. A model of thecarburisation (pick-up of carbon by the reduced iron) andmelt-down process during rapid contraction was presented. Laboratory testing of MPBO pellets was compared with resultsfrom the LKAB experimental blast furnace. The reduction of ironore pellets in the experimental blast furnace was surveyed by adissection of the furnace after quenching. The high temperaturephenomena occurring when reducing the MPBO pellet, with limitedsoftening and a short temperature range of the melting process,resulting in a thin cohesive zone, were found to be the same inlaboratorytests and in the experimental blast furnace. Thereduction down through the burden of the experimental blastfurnace was similar, but not identical to the results of theRUL experiments. The differences were found to be due todifferent reducing conditions. Therefore, it was concluded thata simulation of the reduction occurring in the blast furnacecan be performed in laboratory scale, provided the experimentalconditions are correctly chosen. Finally, a modification to further improve the properties ofthe MPBO pellets was examined. With the aim to improve theblast furnace process, coating of blast furnace pellets wasinvestigated in laboratory scale, as well as in the LKABexperimental blast furnace. Olivine, dolomite and quartzitewere used as coating agents. In laboratory scale the stickingprevention action of the different coating materials wasverified, in established test methods as well as in new testmethods, modified for blast furnace conditions. Testing of thecoated pellets in the experimental blast furnace revealedseveral advantages; significantly reduced blast furnace fluedust generation, improved gas utilisation and a smoother blastfurnace operation with a potential for a lowered fuel rate. <b>Keywords:</b>Olivine, pellets, pellet testing,reduction/softening/melting, MPBO, blast furnace, reduction,quenching, dissection, coating, sticking, coated pellets.

Chlamydophila pneumoniae (C. pneumoniae) has been suggested as a stimulator of chronic inflammation in atherosclerosis. C. pneumoniae DNA was demonstrated in aortic biopsies in 50% of patients with stable angina pectoris or acute coronary syndrome undergoing coronary artery bypass grafting. C. pneumoniae mRNA, a marker of replicating bacteria, was demonstrated in 18% of the aortic biopsies. Inflammation may have a role in the pathogenesis of thoracic aortic aneurysm, aortic dissection and aortic valve stenosis. C. pneumoniae DNA was demonstrated in aortic biopsies in 26% of thoracic aortic aneurysm patients and in 11% of aortic dissection patients undergoing thoracic surgery and in 22% of stenotic aortic heart valves from patients undergoing aortic valve replacement. No bacterial mRNA was demonstrated in these aortic biopsies, nor in the valves, suggesting that the infection has passed into a persistent state. C. pneumoniae DNA was demonstrated in peripheral blood mononuclear cells in only 5% of aortic valve stenosis patients and not in thoracic aortic aneurysm or aortic dissection patients, suggesting that the bacterium disseminated to the cardiovascular tissue long before the patient required surgery. The copper/zinc ratio in serum, a marker of infection/inflammation, was significantly elevated in thoracic aortic aneurysm patients, supporting an inflammatory pathogenesis. Patients positive for C. pneumoniae in the aortic valve had more advanced coronary atherosclerosis, further supporting a possible role for C. pneumoniae in atherosclerosis. Mice were infected with C. pneumoniae that disseminated to all organs investigated (i.e. lungs, heart, aorta, liver and spleen). Trace element concentrations were altered in infected animals with an increased copper/zinc ratio in serum, a progressively increased iron concentration in the liver and a progressively decreased iron concentration in serum. Iron is important for C. pneumoniae metabolism, and a changed iron homeostasis was noted in infected mice by alterations in iron-regulating proteins, such as DMT1 and hepcidin.

Amyloid is a form of abnormal protein aggregation within the living body. Massive deposits can lead to organ failure. There is also increasing evidence that smaller pre-amyloid aggregates exert direct toxic effects to cells. To date 25 different proteins are known to occur as amyloid deposition in human tissues, although not all of these conditions are known to be associated with clinical diseases. This thesis deals with the very common form of amyloid localized to the arterial media. The fibril protein called ‘medin’ was identified in 1999. Medin is a 50 amino acid residue internal fragment of the precursor protein lactadherin. Lactadherin, first found in human milk, is expressed in various tissues such as breast epithelium (including carcinomas), macrophages and aorta. The function of the protein is not known but it has several functional domains. There is an EFG like domain, including an RGD-sequence, in the N-terminal part of the molecule. The C-terminal part consists of C1 and C2 coagulation factor V and VIII like domains. Medin is from within the C2 domain. This region is suggested to be involved in phosphatidyl serine binding, important in phagocytosis of apoptotic cells. Medin amyloid was originally described from studies of the aorta. It is shown here that deposits are more widely spread and can be found in many large arteries, particularly within the upper part of the body. The prevalence of medin amyloid increases with age and deposits are found, to a certain degree, in virtually everyone above the age of 60 years. The amyloid is not only found extracellularly but intracellular deposits may also occur. Amyloid is usually associated with elastic lamina or lamellae which often show signs of fragmentation. Given the localization of amyloid to elastic structures of the arterial media, three different vascular diseases were studied: temporal (giant cell) arteritis, thoracic aortic aneurysm and thoracic aortic dissection. Medin amyloid was found in temporal arteries with and without inflammation. In inflamed arteries, amyloid was mainly located along the broken internal elastic lamina. Medin was also demonstrated within giant cells. It is suggested that medin may be an antigen triggering autoimmune giant cell arteritis. In the study of thoracic aortic aneurysms and dissections, we found significant less medin amyloid in diseased aortic tissues compared with a control material. On the other hand, immunoreactive medin, probably in the state of oligomeric aggregates, was regularly found in association with aneurysms and dissections but not in the control material. It is suggested that medin oligomers exert toxic effects on smooth muscle cells which may lead to weakening of the arterial wall with aneurysm or dissection as a consequence.

Early Effects of Castration Therapy in Non-malignant and Malignant Prostate Tissue BACKGROUND. Androgen ablation, the standard treatment for advanced prostate cancer, results in increased apoptosis, decreased cell proliferation and subsequent involution of the prostate gland. The mechanisms behind these responses are largely unknown, but effects in the prostatic epithelium are believed to be mediated by primary changes in the stroma. The purpose of this thesis was to investigate short-term cellular effects of castration-induced prostate tissue involution in mice and humans. METHODS. Prostate tissue factors affected by castration were investigated using cDNA-arrays, micro-dissection, RT-PCR, immunohistochemistry and Western blot analysis. The effects of local insulin-like growth factor-1 (IGF-1) administration were investigated in intact and castrated mice. Non-malignant and malignant epithelial and stromal cells were micro-dissected from human prostate biopsies taken before and within two weeks after castration treatment from patients with advanced prostate cancer. These tissue compartments were analyzed by RT-PCR and/or immunohistochemistry for IGF-1, IGF-1 receptor, androgen receptor (AR) and prostate specific antigen (PSA) expression. Treatment-induced changes in these factors were related to apoptosis and proliferation as well as to clinical data and cancer specific survival. RESULTS. Similar to our observations in mouse ventral prostate (VP), non-malignant and malignant human prostate tissues responded with increased epithelial cell apoptosis and decreased proliferation after androgen withdrawal. Also, the PSA mRNA levels were reduced within the first days after therapy both in non-malignant and malignant human prostate epithelial cells. However, neither of these changes was related to subsequent nadir serum PSA or to survival. Locally injected IGF-1 increased epithelial cell proliferation and vascular volume in intact but not in castrated mice. IGF-1 was found to be mostly, but not exclusively, expressed in the stroma, and it decreased rapidly after castration in both humans and mice. This decrease was, however, largely absent in prostate tumor stroma, and tumor stroma cells showed lower pre-treatment levels of AR than stroma surrounding normal epithelial glands. Furthermore, decreased levels of IGF-1 mRNA in the non-malignant and tumor stroma cells, and in tumor epithelial cells in response to castration, were associated with high levels of apoptosis in epithelial cells after therapy. CONCLUSIONS. In the prostate, IGF-1 may be an important mediator of stroma-epithelial cell interaction that is involved in castration-induced epithelial and vascular involution. Moreover, reduced AR in the tumor stroma may play an important role in prostate cancer progression towards androgen-independency, resulting in inadequate IGF-1 reduction and apoptosis induction in response to castration. Most primary tumors initially respond to castration with markedly decreased PSA synthesis and cell proliferation, and moderately increased apoptosis. Death due to metastatic disease is, however, still common, despite primary tumor regression. This may suggest that tumor cells in metastases respond differently to treatment than primary tumor cells, probably influenced by a different and possibly androgen-independent stroma. Further studies should test the hypothesis that the effect of castration therapy can be enhanced by simultaneous blocking of IGF-1 signaling.

In the four early modern revenge tragedies I study, Thomas Kyd’s The Spanish Tragedy, William Shakespeare’s Titus Andronicus, Thomas Middleton’s The Revenger’s Tragedy, and John Webster’s The Duchess of Malfi, the ubiquitous depictions of corporeal violence underscore the authors’ skepticism of the human tendency to infuse bodies – physical manifestations of both agency and vulnerability – with symbolism. The revengers in these plays try to avenge the death of a loved one whose disfigured body remains unburied and often continues to occupy a place on stage, but their efforts to infuse corpses with meaning instead reveal the revengers’ perverse obsession with mutilation as spectacle. In Chapter one, I show how in The Spanish Tragedy Thomas Kyd portrays the characters’ assertions of body-soul unity to be arbitrary attempts to justify self-serving motives. Although Hieronimo treats Horatio’s dead body as a signifier of his own emotions, he displays it, alongside the bodies of his enemies, as just another rotting corpse. In Chapter two, I explore how in Titus Andronicus, William Shakespeare questions the efficacy of rituals for maintaining social order by depicting how the play’s characters manipulate rituals intended to celebrate peace as opportunities to exact vengeance; Titus demands human sacrifice as not just an accompanying element, but a central motive of rituals ostensibly intended to signify commemoration. In Chapter three, I read The Revenger’s Tragedy as illustrating Thomas Middleton’s characterization of the depiction of corporeal mutilation as an overused, generic convention; the play’s revenger, Vindice, attributes multiple, constantly shifting, meanings to the rotting skull of his lover, which he uses as a murder weapon. In Chapter four I argue that in The Duchess of Malfi, John Webster destabilizes spectators’ interpretive capacities; within this play’s unconventional dramatic structure, the main characters use somatic imagery to associate bodily dismemberment with moral disintegration. Corpses, the tangible remains of once vigorous, able-bodied relatives, serve as central components of respectful commemoration or as mementos of vengeance, yet these dead, often gruesomely mutilated bodies also invite repulsion or perverse curiosity. Thus, rather than honoring the deceased, revengers objectify corpses as frightening spectacles or even use them as weapons.

<p>The reduction behaviour of the olivine iron ore pellet MPBOwas studied in laboratory scale at KTH as well as in the LKABexperimental blast furnace. Initially, a newreduction-under-load, or so-called reduction/softening/melting,test equipment was developed. Experiments using differentreducing conditions, corresponding to different radialpositions of the blast furnace, were conducted. The experimentsincluded different temperature profiles, reducing atmospheresand mechanical loads applied on the sample bed to simulate thevarying conditions in the blast furnace process. The progressof reduction was investigated, as well as the processes ofsintering and contraction during reduction. A model of thecarburisation (pick-up of carbon by the reduced iron) andmelt-down process during rapid contraction was presented.</p><p>Laboratory testing of MPBO pellets was compared with resultsfrom the LKAB experimental blast furnace. The reduction of ironore pellets in the experimental blast furnace was surveyed by adissection of the furnace after quenching. The high temperaturephenomena occurring when reducing the MPBO pellet, with limitedsoftening and a short temperature range of the melting process,resulting in a thin cohesive zone, were found to be the same inlaboratorytests and in the experimental blast furnace. Thereduction down through the burden of the experimental blastfurnace was similar, but not identical to the results of theRUL experiments. The differences were found to be due todifferent reducing conditions. Therefore, it was concluded thata simulation of the reduction occurring in the blast furnacecan be performed in laboratory scale, provided the experimentalconditions are correctly chosen.</p><p>Finally, a modification to further improve the properties ofthe MPBO pellets was examined. With the aim to improve theblast furnace process, coating of blast furnace pellets wasinvestigated in laboratory scale, as well as in the LKABexperimental blast furnace. Olivine, dolomite and quartzitewere used as coating agents. In laboratory scale the stickingprevention action of the different coating materials wasverified, in established test methods as well as in new testmethods, modified for blast furnace conditions. Testing of thecoated pellets in the experimental blast furnace revealedseveral advantages; significantly reduced blast furnace fluedust generation, improved gas utilisation and a smoother blastfurnace operation with a potential for a lowered fuel rate.</p><p><b>Keywords:</b>Olivine, pellets, pellet testing,reduction/softening/melting, MPBO, blast furnace, reduction,quenching, dissection, coating, sticking, coated pellets.</p>

Les NOX Homologues représentent une nouvelle famille de protéines transmembranaires dont la caractéristique commune est d'être le cœur catalytique de la production d'anions superoxydes. Elles ont toutes une structure proche de NOX2 (ou gp91Phox selon l'ancienne nomenclature), la mieux caractérisée d'entre elles, et sont organisées en 6 ou 7 domaines transmembranaires. Cette famille compte actuellement 7 membres, NOX1, NOX2, NOX3, NOX4, NOX5 et DUOX 1 et DUOX2 ; elles ont une distribution tissulaire, cellulaire et intracellulaire spécifique les rendant quasi ubiquitaires dans l'organisme. Les fonctions de ces enzymes sont essentiellement rattachées à celles des espèces réactives de l'oxygène (ERO) mais dépendent aussi de leurs localisations. NOX2 est l'enzyme à l'origine de la production des ERO des phagocytes activés et a donc une fonction antimicrobienne. NOX3 est impliquée dans les pathologies du système vestibulaire et les DUOX1 et 2 sont des éléments clés de la biosynthèse des hormones thyroïdiennes. Les autres NOX, (NOX1, NOX4, NOX5), individualisées depuis quelques années seulement, ont une distribution tissulaire et cellulaire d'expression ARNm bien caractérisée, mais les données sur leurs fonctions physiologiques ou physiopathologiques restent fragmentaires ; Ces données sont le plus souvent issues d'expérimentations in vitro ou ex vivo n'évaluant leurs fonctions que de façon indirecte ou dans des systèmes simplifiés. Ainsi, en utilisant un modèle animal de souris déficientes pour le gène NOX1 établi dans le laboratoire, nous avons évalué directement la fonction de NOX1 dans le colon et dans le système vasculaire. <br />La première partie de ce travail a eu pour objectif de déterminer si NOX1 exerce une activité antibactérienne au niveau du colon et participe au contrôle de la translocation bactérienne à travers la muqueuse colique. NOX1 participe à la sévérité de la colite au Dextran Sulfate Sodium par l'intermédiaire de la flore colique et protège de la translocation bactérienne dans un modèle de neutropénie induite. Cependant, ces résultats devront être confirmés car les expérimentations ont toutes été réalisées avec des souris dont le fond génétique n'avait une homologie que de 87.5%. La seconde partie de notre travail devait déterminer si NOX1 exerce une activité régulatrice de la pression artérielle systolique et participe à la survenue de l'hypertension artérielle induite par l'angiotensine II. Nous montrons, avec des souris de génération F6 (homologie>98.5%), que NOX1 participe à la régulation physiologique de la pression artérielle, à la survenue de l'hypertension artérielle induite par l'angiotensine II et à la survenue de dissection aortique. NOX1 agit dans le tissu vasculaire par au moins 3 mécanismes, en favorisant l'accumulation de matrice extracellulaire, en régulant l'expression génique et en diminuant la biodisponibilité du NO.

No description available.