Any disability can bring disadvantages in many aspects of human lives. This often affects physical, mental and social areas of life. It depends on many circumstances and factors to what extent and at what intensity disability influences the way of life. The research part of my diploma thesis confirms this fact. Not only the type of disability and its prognosis, the personality and his/her ability to handle difficult situations in life, but also the quality of social relationships and the strength of the social safety net are important factors. Irreplaceable role in caring for people with a disability has comprehensive rehabilitation, which helps not only to improve the health condition, to restore job skills and self-sufficiency, but mainly supports a successful return to the home environment as well as to the regular everyday life.The aim of my thesis was to learn about individual life stories of people struggling with a disability of physical functions, whether due to an illness, injury or another disability, resulting in movement disorders, and to find out how the disability affects their lives. I tried to analyze specific aspects of life and social consequences of disability (coping with disabilities,value orientation, interpersonal relationships, future plans, self-realization). The base of my work is the holistic, i.e. bio-psycho-socio-spiritual approach, I respect the individuality of each individual, his/her attitude to life with a handicap (disability).

O fundamento do sucesso da terapia endodôntica é baseado no controle da contaminação microbiana presente no sistema de canais radiculares. Com essa finalidade, novos sistemas de irrigação têm sido desenvolvidos, demonstrando maior eficácia e segurança, destacando-se a irrigação por Pressão Apical Negativa (ANP) e a Irrigação Ultrassônica Passiva (PUI). O presente estudo in vivo teve como objetivo comparar a ANP e a PUI no reparo apical e periapical de dentes de cães com lesão periapical crônica, tendo como controle a irrigação convencional por Pressão Positiva (PP). Um total de 60 canais radiculares de pré-molares, com lesões periapicais experimentalmente induzidas, foram submetidos ao tratamento endodôntico em sessão única. Radiografias periapicais foram realizadas após a indução das lesões periapicais. Os dentes foram aleatoriamente divididos em 3 grupos: Grupo I - Irrigação por Pressão Apical Negativa (n=20 canais radiculares); Grupo II - Irrigação Ultrassônica Passiva (n=20 canais radiculares) e Grupo III - Irrigação por Pressão Positiva (controle) (n=20 canais radiculares). Após 180 dias, os animais foram eutanasiados, as peças removidas e submetidas ao processamento histotécnico para a análise histopatológica morfológica e morfométrica, em cortes corados com HE, sob microscopia convencional e de fluorescência. A análise radiográfica do tamanho das lesões periapicais foi realizada através da comparação das medidas das áreas das lesões antes e 180 dias após o tratamento endodôntico. Também foi realizada a histoenzimologia para a Fosfatase Ácida Resistente ao Tartarato (TRAP), para a marcação de osteoclastos, e a coloração de Brown e Brenn, para avaliar a presença de bactérias e sua localização. Os resultados obtidos foram submetidos à análise estatística por meio do teste de Kruskal-Wallis. O nível de significância adotado foi de 5%. Observou-se que não houve diferença estatisticamente significante entre os grupos com relação à resposta radiográfica (p=0,91). Na comparação dos parâmetros histopatológicos, o grupo I apresentou resultados mais homogêneos. Houve diferença estatisticamente significante entre os grupos I e III, com infiltrado inflamatório mais suave no grupo I (p=0,02), enquanto o grupo II foi semelhante aos grupos I e III. Na comparação das variáveis numéricas (morfometria em microscopia de fluorescência e TRAP), não foi possível observar diferença significativa entre os grupos (p>0,05). Os resultados deste estudo in vivo demonstraram que a irrigação por ANP resultou em resposta inflamatória mais suave, em comparação ao grupo controle, porém, semelhante à PUI. Nos demais aspectos, a resposta dos tecidos apicais e periapicais, após irrigação por ANP ou PUI, foi semelhante à irrigação convencional por PP. / A successful endodontic therapy relies on the control of microbial contamination of the root canal system. For this purpose, new irrigation systems with greater efficacy and safety have been developed, standing out the apical negative pressure (ANP) and the passive ultrasonic (PUI) irrigation systems. The aim of this in vivo study was to compare apical positive pressure irrigation (PP - conventional irrigation), ANP and PUI in the apical and periapical repair of dogs teeth with chronic periapical lesion. Sixty root canals of premolars with experimentally induced periapical lesions were subjected to a single-session endodontic treatment. Periapical radiographs were taken after inducing the periapical lesions. The teeth were randomly assigned to three groups: Group I: ANP with EndoVac (n=20 root canals); Group II: PUI (n=20 root canals) and Group III: apical positive pressure irrigation (PP - conventional irrigation - control) (n=20 root canals). After 180 days, the animals were euthanized, and the anatomic pieces were removed and subjected to histotechnical processing for histopathological, morphological and morphometric analyses of HE-stained sections under conventional and fluorescence microscopy. The radiographic analysis of the size of periapical lesions was performed by measuring the lesions before and 180 days after the endodontic treatment. Tartrate-resistant acid phosphatase (TRAP) histoenzymology for identification of osteoclasts and Brown and Brenn staining for identification and localization of bacteria were also performed. Data were analyzed statistically by the Kruskal-Wallis test a significance level of 5%. There were no statistically significant differences among the groups regarding the radiographic response (p=0.91). In the comparison of histopathological parameters, Group I presented more homogeneous results. There was a statistically significant difference between Groups I and III, with milder infiltrate inflammatory in Group I (p=0.02). Group II was similar to Groups I and III. Comparing the numerical variables (morphometric analysis under fluorescence microscopy and TRAP), no statistically significant difference could be found among the groups (p>0.05). The results of this in vivo study revealed that ANP caused milder inflammatory response than PP (control group), but similar to PUI. In the other aspects, the response of apical and periapical to ANP and PUI was similar to tissue response to PP.

As lesões térmicas corporais (LTC) são um sério problema de saúde, atingindo principalmente crianças. A extensão e a profundidade da lesão são fatores que alteram várias estruturas. Alterações gastrintestinais também são relatadas, sendo a principal delas, a atrofia das mucosas, provocando ulcerações e a perda da barreira seletiva. Na presente pesquisa avaliou-se através de técnicas histoquímicas, imunohitoquimicas e de microscopia de luz, as alterações ocorridas nos componentes do plexo mioentérico e na espessura da mucosa do jejuno em três porções: oral (O), média (M) e aboral (A), de ratos adultos com 30% da superfície corpórea exposta ao escaldamento, 4 dias (q4) e 10 dias (q10) após a LTC. Verificou-se em q10 o não restabelecimento da massa corpórea, a diminuição da área do jejuno, bem como espessura de sua mucosa. No plexo mioentérico, a área média do perfil celular dos neurônios NADPH não variou, tendo estes uma menor densidade em q10, sendo estes corpos altamente reativos em q4 e q10. Varicosidades grandes destacaram-se em q4 e q10, quando pela SP e VIP. / Burn is a determinant factor to alter body structures as the striated muscle. It also determines gastrintestinal mucosal atrophy what produce loss of selective barrier. With histochemical, immunohistochemical and light microscopy methods the myenteric plexus (MP) of the jejunum was evaluated in rats submitted to burn injury. The scalding was performed in 30% of the body surface. The MP and the mucosa of the oral (O), middle (M) and aboral (A) parts of the jejunum were analyzed four (q4) and ten (q10) days post-lesion. The loss of weight due the burn is not recovered in q10 where the jejunal surface area and the thickness of the mucosa decreased. The neuronal profile of nitregic neurons was similar in q4, q10. The density of nitregic neurons was lower in q10 showing that the time post injury is an important factor able to alter this parameter. The q4 and q10 groups exhibited neuronal bodies highly reactive to NADPH. The immunoreactivity to SP and VIP in q4 and q10 was expressed mainly in large varicosities.

As metaloproteinases da matriz (MMPs) foram identificadas na saliva, na placa dental, na dentina e no cemento. Este trabalho teve como objetivos: Estudo I (I) - avaliar a expressão de MMP-2 e MMP-9 presentes na saliva total e parotidiana e no fluido gengival crevicular (FGC) de pacientes portadores e não portadores de lesões cervicais não cariosas (LCNC); Estudo II (II) - investigar se a presença de MMP-8 e -9/TIMPs poderia influenciar a remineralização de lesões artificialmente criadas na superfície radicular, com ou sem desgaste por abrasão. Os métodos utilizados foram: (I) Coleta de amostras de saliva e do FGC de 32 pacientes, com (n=16) e sem LCNC (n=16). A atividade gelatinolítica das MMPs foi avaliada através de análise zimográfica e Western Blot. (II): Espécimes de dentina humana radicular foram obtidos. O grupo controle G1(10) não sofreu nenhum tratamento. Os demais segmentos radiculares foram desmineralizados G2(60). O Grupo A não foi submetido à escovação e o Grupo B foi submetido à abrasão por escovação em uma máquina de escovação simulada. G2(10) foi apenas desmineralizado, G3(10) desmineralizado e remineralizado, e os Grupos G4(10), G5(10), G6(10), G7(10) foram desmineralizados e remineralizados em presença de tampão neutro, TIMP, MMP-8 e -9, MMP-8,-9 e TIMP, respectivamente. Para a análise elemental, as concentrações de Ca+2, P, Mg+2 assim como a relação molar Ca/P e Mg/Ca foram determinadas através de uma sonda eletrônica para microanálise (EPMA). A análise qualitativa por retrodispersão (BSE) foi realizada para demonstrar a distribuição global da densidade mineral. Os resultados (I) mostraram que a principal gelatinase presente, tanto na saliva total quanto no FGC, é a proMMP-9. Na saliva secretada pela glândula parótida, não foram detectadas bandas indicando a presença de gelatinases. Os resultados do estudo (II) indicaram que os espécimes escovados apresentaram maior conteúdo de Ca+2 a 20µm e maior conteúdo de Mg+2 a 30 e 50µm. Em presença de TIMPs, ocorreu uma redução do conteúdo de Ca+2 a 20µm. Para os espécimes não escovados, em todas as profundidades, as amostras incubadas com MMPs apresentaram maiores valores de Ca+2. Portanto, pode-se concluir que (I) a comparação entre pacientes com e sem LCNC mostrou não haver diferença estatisticamente significante quanto à atividade gelatinolítica; (II) quando não inibidas pelos TIMPs, as MMPs degradaram o colágeno completamente desmineralizado na superfície radicular, permitindo melhor recalcificação na superfície subjacente. Esse fenômeno foi também facilitado pela abrasão por escovação. / Matrix metalloproteinases (MMPs) have been identified in saliva, plaque, gingival crevicular fluid (GCF), dentin and cementum. Study (I) aimed at evaluating the presence and quantity of gelatinases MMP-2 and MMP-9 in total and parotid saliva and in GCF (GCF) of subjects with and without NCCL. Study (II) aimed at investigating whether the presence of matrix metalloproteinase (MMP)-8 and - 9/TIMPs would influence the remineralization of artificial root lesions with and without mechanical wear. (I) Total stimulated saliva, parotid saliva, and GCF from patients with (n=16) and without NCCL (n=16) were collected and assessed for gelatin zymography and for western immunoblot analysis. (II) Human root segments from Group A (n=35) were not brushed and from Group B (n=35) were subjected to machine-controlled brushing, simulating mechanical wear. Specimens from Group 1 (control, n=10) were left untreated. Group 2 (n=10), was just demineralized; Group 3 (n=10) was demineralized and remineralized. The other samples G4 (n=10), G5 (n=10), G6 (n=10), G7 (n=10) were subjected to remineralization with HEPES buffer, tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), activated MMP-8 and MMP-9 and activated MMP-8, MMP-9 and TIMP-2, respectively. Ca+2, P, Mg+2 concentrations as well as Ca/P and Mg/Ca molar ratios were determined through an Electron Probe Microanalyser (EPMA). (I) Densitometric analysis revealed that the main gelatinase was proMMP-9. No statistically significant difference was observed for MMP-2 and MMP-9 levels, separately. In parotid saliva, gelatinolytic activity was very low or absent. Western immunoblots revealed that, while little immunoreactivity was detected for MMP-2, there was positive immunoreaction for MMP-9, both in total saliva and in GCF. Gelatinases do not seem to originate from parotid gland. (II) The results indicated that the brushed specimens presented higher Ca+2 levels at 20 µm and higher Mg+2 content at 30 and 50 µm. Ca+2 content at 20 µm decreased in the presence of TIMPs. For the non-brushed specimens, in all depths, samples incubated with MMPs showed highest Ca+2 values. It can be concluded that (I) the main gelatinase present in the oral cavity is MMP-9. No significant differences were found in total gelatinolytic activity among NCCL+ and NCCL- patients. (II) When not inhibited by TIMPs, MMPs degraded the completely demineralized collagen in the root surface, allowing for better recalcification in the deeper areas. This phenomenon was also facilitated by the brushing procedure.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / FundaÃÃo de Amparo à Pesquisa do Estado do Cearà / Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / A LesÃo Central de CÃlulas Gigantes dos maxilares (LCCG) à intra-Ãssea, nÃo tem predileÃÃo por sexo, classifica-se em agressivas e nÃo-agressivas, histologicamente consistem tecido fi-broso e celularizado fusiforme associado a cÃlulas gigantes multinucleadas (CGM), focos de hemorragia e neovascularizaÃÃo, tendo na cirurgia seu habitual tratamento. Novas abordagens terapÃuticas foram propostas, sendo a principal delas o uso de corticÃides intralesionais. Este trabalho analisa retrospectivamente 21 pacientes portadores de LCCG que foram tratados por hexacetonido de triancinolona intralesional, atravÃs do seguinte protocolo: injeÃÃo de hexace-tonido de triancinolona 20mg/ml diluÃdo na soluÃÃo anestÃsica de lidocaÃna 2%/epinefrina 1:200.000 numa proporÃÃo de 1:1; infiltrando 1ml de soluÃÃo para cada 1cm3 de lesÃo, totali-zando 06 aplicaÃÃes em intervalos quinzenais. Estabeleceu-se 04 critÃrios clÃnicos para classi-ficar a resposta ao tratamento: 1- estabilizaÃÃo ou regressÃo clÃnica da lesÃo 2- ausÃncia de sintomas 3- aumento da densidade nos controles radiogrÃficos 4- aumento da resistÃncia a infiltraÃÃo intralesional da droga, bem como, fez-se uma anÃlise imunohistoquÃmica quanto à expressÃo dos Receptores de corticÃides (GCR) e Calcitonina (CTR), Cox-2, proteÃna p16 e amplificaÃÃo gÃnica da Ciclina D1 por CISH, comparando quanto a agressividade e a resposta terapÃutica a corticoterapia intralesional. Dos 21 pacientes incluÃdos neste estudo, 11 eram homens e 10 mulheres, 09 tinham lesÃo em maxila, 12 em mandÃbula. Dez eram lesÃes agres-sivas e 11 nÃo-agressivas, 15 (71,4%) apresentaram uma boa resposta ao tratamento, 04(19%) moderada e 02(9,1%) negativa. Das 11 nÃo agressivas, 10(90,9%) apresentaram boa resposta e 01 (9,1%) resposta moderada, das 10 agressivas 05(50%), 03(30%) e 02(20%) apresentaram boa, moderada e negativa resposta respectivamente, nenhuma apresentou recidiva apÃs o tra-tamento, com preservaÃÃo que variou entre 04 a 08 anos. Os achados histopatolÃgicos mos-traram uma reduÃÃo da densidade e do tamanho das CG, e um estroma fibro-colagenoso das lesÃes. Dentre os marcadores pesquisados, apenas GCR em CG antes do tratamento mostrou significÃncia estatÃstica (p<0,004) com relaÃÃo a uma boa resposta terapÃutica. O CTR ex-pressou-se em cÃlulas gigantes e mononucleares de forma variada. A p16 apresentou-se ex-pressa em 30% da amostra, COX2 nÃo apresentou expressÃo na lesÃo e 33% da amostra apre-sentou amplificaÃÃo gÃnica da ciclina D1. NÃo mostraram significÃncia estatÃstica nem quanto à agressividade, nem quanto resposta ao tratamento, nenhum dos marcadores, exceto o GCR. O estudo mostrou que a corticoterapia intralesional à efetiva e segura para o tratamento das LCCG, com tendÃncia a melhor resposta nas lesÃes nÃo-agressivas do que nas agressivas. Mostrou ainda que a marcaÃÃo para GCR em CG demonstrou ser um parÃmetro confiÃvel para prever a resposta à terapÃutica com a corticoterapia intralesional e que 33% das LCCG tÃm comportamento neoplÃsico pela amplificaÃÃo gÃnica da ciclina D1. / Central Giant Cells Lesion (CGCL) of the jaws is an intra-bone lesion with no predilection for sex and clinically divided into aggressive and non-aggressive subtypes. Histological, it shows as fibrous tissue with fusiform cells, as well as multinucleated giant cells (GC) clusters, he-morrhagic foci and neovascularization. Surgery is the regular treatment option. As new the-rapeutic approaches have been proposed, intralesional glucocorticoid injection is the main option. This paper assesses retrospectively 21 patients presenting CGCL, treated with intrale-sional triamcinolone hexacetonide by using the following protocol: intralesional injection of triamcinolone hexacetonide 20mg/mL, diluted in a solution of lidocain 2% plus epinephrine 1:200000, at a 1:1 proportion; 1mL of this final solution for each 1cm3 of lesion volume was the injected, with a total of 06 injections, one in every 15 days. Four clinical criteria were sta-bilished to evaluate treatment outcome: 1- Clinical regression or stabilization of the lesion; 2- Absence of symptoms; 3- Raising in density on radiographic controls; 4-Increased resistence when injecting the drug intralesionally. It was also performed immunohistochemical assess-ment for glucocorticoid receptor (GCR) expression, calcitonin receptor (CTR) expression, COX-2 expression, p16 expression and Ciclin D1 gene amplification by CISH, making com-parisons related to aggressivity and to therapeutic outcome. Eleven out of 21 patients of this study were women, and 10 were men. Nine of the patients had lesion located in the maxilla, 12 in the mandible. Ten patients showed aggressive lesions and 11 non-aggressive lesions. Fifteen patients showed good treatment outcome, four patients showed moderate outcome, and two patients showed negative answer to the treatment. Among the 11 patients with non-aggressive lesions, ten showed good outcome and the other, moderate outcome. Among the ten aggressive lesions, five patients showed good outcome, three patients showed moderate outcome and the remaining two patients showed negative answer to the treatment. None of them showed reicidive in a four to eight years follow-up period. Morphologic analysis found positive correlation between volume density of GC/mm2 and lesion aggressiveness, as well as significant reduction in number of GC/mm2 after treatment. Among the markers, only GCR in GC showed statistical relevance associated to the treatment. CTR was espresse in GC and in mononuclear cells in a varying way; p16 was expressed in 30% of the sample; COX-2 was not expressed at all in lesion samples and 33% of the sample showed gene amplification in Ciclin D1. None of the markers showed any statistical significant difference related to aggres-siveness nor to treatment outcome, except for GCR. The study showed the feasibility of the adopted treatment, with tendency to better outcomes in non-aggressive lesion, if compared to the aggressive ones. It also showed evidence pointing to GCR expression in GC as a reliable parameter to predict therapeutic responsiveness to glucocorticoids; and it showed that 33% of CGCL have neoplastic behaviour by Ciclin D1 gene amplification.

A soja, o milho e o algodão são as culturas de enorme importância econômica no Brasil, pois juntas ocupam grande parte da área agrícola no país. Além disso, essas culturas são essenciais no fornecimento de alimento e fibras para uma crescente população mundial. Vários fatores podem afetar a produção das mesmas, sendo que os nematoides anualmente causam bilhões de dólares de perdas. As principais técnicas disponíveis para o manejo dos nematoides são rotação de culturas, cultivares resistentes e nematicidas químicos. Apesar de o controle químico ser uma ferramenta viável, há poucos nematicidas disponíveis no Brasil. Como inovação entre os nematicidas, o tioxazafen é uma nova molécula de amplo espectro, desenvolvida para aplicação via tratamento de sementes, para o controle de nematoides nas culturas do milho, da soja e do algodão. Portanto, seu desenvolvimento e posterior registro poderão fornecer uma nova alternativa ao manejo integrado de nematoides aos produtores brasileiros. Assim, esse trabalho teve como objetivos avaliar a eficácia do nematicida tioxazafen, por meio do tratamento de sementes, no controle de Heterodera glycines, Meloidogyne javanica e Pratylenchus brachyurus na soja; M. incognita e P. zeae no milho; e M. incognita no algodão. Além disso, foram avaliados possíveis efeitos fitotóxicos do tratamento de sementes com tioxazafen nas mesmas culturas. Ensaios de casa de vegetação foram conduzidos para avaliação do efeito do tratamento de sementes na população de nematoides, em plantas artificialmente infestadas, bem como na massa de raízes e parte aérea das plantas. O tioxazafen demonstrou supressão substancial na população de nematoides em todas as espécies testadas nas três culturas, com atividade igual ou maior que à referência comercial (imidacloprido + tiodicarbe). As melhores doses observadas foram de 0,250 mg de tioxazafen por semente no controle de M. javanica e de P. brachyurus em soja, 0,500 mg por semente no controle de H. glycines na soja e de M. incognita no milho, 0,750 mg por semente no controle de M. incognita no algodão e 1,000 mg por semente no controle de P. zeae no milho. As plantas tratadas com tioxazafen não exibiram sintomas de fitotoxidez e desenvolveram biomassa similar às plantas não tratadas. Esses resultados mostram o potencial do tioxazafen em se tornar um efetivo tratamento de sementes para controle dos principais nematoides da soja, do milho e do algodão no Brasil,com baixos riscos de fitotoxidez. / Corn, soybean and cotton crops are of great economic importance in Brazil. They together account for the greatest amount of planted area in country. These crops are essential for keeping and providing enough food and fiber for a growing world population. Many factors can affect the production of these crops, and the nematodes are among the most relevant, causing crop losses that reach into billions of dollars. The main techniques available for managing nematodes are crop rotation, resistant cultivars and chemical nematicides. Chemical control is one of the key tools, but there are only a few nematicides available in the Brazilian market. Tioxazafen is a novel nematicide for seed treatment designed to provide consistent broad-spectrum control of nematodes in corn, soy, and cotton. Therefore, the registration of this molecule will provide an important tool to Brazilian farmers that suffer losses due to nematodes. Thereby, the current trials aimed to evaluate the efficacy of tioxazafen through seed treatment to control Heterodera glycines, Meloidogyne javanica and Pratylenchus brachyurus in soybean; M. incognita and P. zeae in corn, and M. incognita in cotton. Furthermore, were evaluated if tioxazafen may cause phytotoxicity in these crops. Greenhouse experiments were carried out to evaluate the effects of seed treatments on nematode population densities, and plant shoot and root weight. Tioxazafen demonstrated substantial suppression of nematode population to all species tested in three crops, with activity equaled or exceeded commercial standard nematode seed treatments (imidacloprid + thiodicarb). The best rates observed were 0.250 mg of tioxazafen per seed to control de M. javanica and P. brachyurus in soybean, 0.500 mg per seed to control H. glycines in soybean and M. incognita in corn, 0.750 mg per seed to control M. incognita in cotton and 1.000 mg per seed to control lesion P. zeae in corn. Tioxazafen treated plants also did not exhibit phytotoxicity and grow equally to untreated plants. These results demonstrated the potential of tioxazafen for the control of the main nematodes in soybean, corn and cotton, without the risk of phytotoxicity.

O objetivo deste trabalho foi caracterizar a formação e progressão de lesões periapicais induzidas experimentalmente em dentes de camundongos knockout para receptores toll-like 2 (TLR2 KO) comparados a animais wild-type (WT). As lesões periapicais foram induzidas nos primeiros molares inferiores de 28 camundongos WT e de 27 camundongos TLR2 KO. Decorridos 7, 21 e 42 dias da indução da lesão periapical, os animais foram submetidos à eutanásia em câmara de CO2, as mandíbulas foram removidas e submetidas ao processamento histotécnico. A seguir, cortes representativos foram corados com hematoxilina e eosina (HE), para descrição do tecido pulpar e das regiões apical e periapical, em microscopia óptica convencional, e mensuração da área das lesões periapicais, em microscopia de fluorescência. Espécimes sequenciais foram avaliados por meio de: histoenzimologia para a atividade da TRAP, para identificação de osteoclastos; coloração de Brown & Brenn, para localização de bactérias; e imunoistoquímica, para identificação de marcadores da osteoclastogênese (RANK, RANKL, OPG). Os resultados numéricos obtidos da análise morfométrica da extensão da área das lesões periapicais e do número de osteoclastos foram submetidos à análise estatística por meio dos testes não-paramétricos de Mann-Whitney e Kruskal-Wallis, utilizando o software SAS (Statistical Analysis System) for Windows versão 9.1.3. O nível de significância adotado foi de 5%. Os resultados da coloração de Brown & Brenn e Imunoistoquímica foram expressos de maneira qualitativa. O grupo de animais WT apresentou diferença significante na extensão da área das lesões periapicais e no número de osteoclastos entre os períodos experimentais de 7 e 42 dias (p<0,05) e entre 21 e 42 dias (p<0.05). Por outro lado, no grupo de animais TLR2 KO, as diferenças para a extensão da área das lesões periapicais e número de osteoclastos foram encontradas entre os períodos experimentais de 7 e 21 dias (p<0,05) e entre 7 e 42 dias (p<0,05). Quando os períodos dos grupos foram comparados entre si, foram encontradas diferenças estatísticas entre todos os períodos experimentais, tanto para a análise morfométrica da extensão da área das lesões periapicais, quanto para o número de ostoclastos (p<0,05). A análise descritiva do tecido pulpar e das regiões apical e periapical, por meio da coloração de HE, bem como da localização das bactérias, por meio da coloração de Brown & Brenn, não mostrou diferenças entre os dois grupos de animais. Com relação à Imunoistoquímica, as marcações foram semelhantes entre os dois grupos de animais, exceto para as marcações de RANK, as quais não foram encontradas nas lesões periapicais do grupo de animais TLR2 KO. A partir das metodologias empregadas e dos resultados obtidos pode-se concluir que na ausência do TLR2, os animais desenvolveram lesões periapicais significantemente maiores (com maior presença de osteoclastos) quando comparados aos animais WT, sugerindo o importante papel desse receptor na resposta imune e inflamatória do organismo no sentido de combater a infecção do sistema de canais radiculares e dos tecidos perirradiculares. / The aim of the present study was to characterize the formation and progression of periapical lesions experimentally induced in the teeth of toll-like receptors 2 knockout (TLR2 KO) mice compared to wild-type (WT) mice. Periapical lesions were induced in the lower first molars of 28 WT and 27 TLR2 KO mice. After 7, 21 and 42 of periapical lesion induction, the animals were euthanized in a CO2 chamber, and the mandibles were removed and subjected to histotechnical processing. Representative histological sections were stained with hematoxylin and eosin (HE) for description of the features of the pulp tissue and the apical and periapical regions under conventional optical microscopy, and for determination of the size of the periapical lesions under fluorescence microscopy. Sequential specimens were evaluated by: TRAP histo-enzymology for identification de osteoclasts; Brown & Brenn staining for localization of bacteria; and immunohistochemistry for identification of osteoclastogenesis markers (RANK, RANKL, OPG). Data from the morphometric evaluation of the size of periapical lesions and the number of osteoclasts were subjected to statistical analysis by the nonparametric Mann-Whitney and Kruskal-Wallis tests, using the SAS (Statistical Analysis System) software for Windows version 9.1.3. A significance level of 5% was set for all analyses. Data from the Brown & Brenn staining and immunohistochemical analysis were displayed qualitatively. The group of WT mice presented statistically significant difference in the periapical lesion size and number of osteoclasts between the 7- and 42-day experimental periods (p<0.05) as well as between 21 and 42 days (p<0.05). On the other hand, in the group of TLR2 KO mice, significant differences in the periapical lesion size and number of osteoclasts were found between the 7- and 21-day experimental periods (p<0.05) as well as between 7 and 42 days (p<0.05). Comparison of the periods within each group revealed statistically significant differences among all experimental periods for the morphometric evaluation of the size of the periapical lesions and number of osteoclasts (p<0.05). Descriptive analysis of pulp tissue and apical and periapical regions by HE staining and localization of bacteria by Brown & Brenn staining did not show significant differences between the two groups of animals. The immunohistochemical results showed similar immunostaining in both groups of animals, except for RANK expression, which was not observed in the periapical lesions of the TLR2 KO mice. Based on the employed methodology and the obtained results it may be concluded that in the silence of TLR2, the animals developed superior size of periapical lesions (with higher presence of osteoclasts) compared to WT animals, suggesting the important role of this receptor during the immune and inflammatory response against the infection of root canal system and periapical tissues.

La Tomographie Volumique à Faisceau Conique (TVFC) est une technologie d’imagerie tridimensionnelle très pertinente à utiliser en odontologie. Notre travail a pour objectifs de montrer ses intérêts et les applications spécifiques en endodontie. Après avoir redéfini les conséquences délétères possibles per et post opératoires des traitements endodontiques et expliqué les principes de la TVFC, nous explorons dans un premier temps les effets de la préparation canalaire in vitro à l’aide de la microtomographie à haute résolution puis, dans un second temps, la problématique et les intérêts de la création de reconstructions tridimensionnelles fiables et précises. Cette dernière partie aborde les notions de traitement des images issues de TVFC avant d’expliquer la démarche adoptée pour élaborer une classification tridimensionnelle des lésions inflammatoires périapicales d’origine endodontique sous formes numérique et physique. / Cone Beam Computerized Tomography (CBCT) is a highly relevant three-dimensional imaging technology for use in dentistry. Our work aims to show its interests and specific applications in endodontics. After having redefined the possible deleterious per and post-operative consequences of endodontic treatments and explained the principles of CBCT, we first explore the effects of in vitro canal preparation, using high resolution microtomography and then, in a second time, the problematic and the interests of the creation of reliable and precise three-dimensional reconstructions. This last part deals with the notions of CBCT image processing before explaining the approach adopted to develop a three-dimensional classification of endodontic periapical lesions in digital and physical form.

Objectifs : Développer un traitement HIFU (High-Intensity Focused Ultrasound) des anomalies placentaires au moyen d’un transducteur torique. Les essais ont été menés à partir d’un modèle ex-vivo, puis la faisabilité, l’efficacité et l’innocuité du traitement a été évaluée sur un modèle de guenons gestantes. Les premières applications thérapeutiques envisagées à l’échelle humaine, concernent le traitement du syndrome transfuseur-transfusé (STT) et les accrétions placentaires pour lesquelles un protocole d’essai clinique a été établi. Matériels et méthodes : Un transducteur torique fonctionnant à 3 MHz et muni d’une cellule d’imagerie échographique intégrée fonctionnant à 7,5 MHz ont été utilisés. Des simulations numériques de séquences de traitement HIFU ont été menées à partir d’une étude préliminaire sur la caractérisation acoustique du tissu placentaire humain. Ces séquences ont été testées au cours d’une étude ex-vivo sur des placentas humains. Deux modèles ex-vivo ont été conçus. Dans un premier temps, un modèle de traitement extracorporis. Dans un second temps, des traitements HIFU ont été réalisés à des distances variables du transducteur, par modification de la taille du ballonnet, afin de simuler un traitement per-césarienne. Le transducteur était placé au contact de la face foetale du placenta afin de simuler la séreuse utérine. A partir des résultats issus de ces essais ex-vivo, un protocole in-vivo sur des guenons gestantes a été mené afin de valider la faisabilité, l’efficacité et l’innocuité de la réalisation de lésions HIFU dans le placenta de guenons gestantes de manière totalement non-invasive. La qualité du monitoring échographique était évaluée au cours des trois études, et corrélée à l’analyse macroscopique. Une étude histologique a également été menée. Résultats : L’atténuation placentaire a été mesurée à partir de 12 échantillons placentaires humains pour un âge gestationnel compris entre 17 et 40 semaines d’aménorrhées (SA). L’atténuation augmentait en fonction de l’âge gestationnel et était compris entre 0,072 et 0,098 Np.cm-1.MHz-1. Lors d’un premier essai ex-vivo, 33 échantillons placentaires humains ont été inclus et soumis à une séquence HIFU, le temps d’insonification était de 55 secondes, la puissance acoustique utilisée était de 90 Watts. Au total, vingt-cinq lésions élémentaires étaient produites pour un diamètre et une profondeur moyens respectifs de 7,1 ± 3,2 et de 8,0 ± 3,1 millimètres. Huit lésions HIFU ont également été produites à partir de la juxtaposition de 6 tirs, pour un diamètre et une profondeur moyenne respectifs de 23,0 ± 5,0 et 11,0 ± 4,7 millimètres. Aucune lésion située en amont de la lésion produite n’a été observée pour une épaisseur de paroi abdominale similaire à celle d’une guenon gestante (10,8 ± 1,7 millimètres). Dans un second temps, 8 placentas humains pour un âge gestationnel compris entre 39 et 40 SA, ont été soumis à une séquence de traitement HIFU sans interposition de paroi abdominale. Le temps d’exposition était de 75 secondes pour une puissance acoustique de 90 Watts. Les lésions placentaires ont été produites à 2 (n=4), 6 (n=4), 7 (n=4) et 8 (n=7) millimètres de la surface du placenta. Au total, 19 lésions placentaires ont été produites, pour un diamètre et une profondeur moyenne respectifs de 14,6 ± 2,1 et de 14,1 ± 2,3 millimètres. Au cours de l’étude in-vivo, 8 guenons ont été incluses pour un âge gestationnel moyen de 72 ± 4 jours. Les puissances acoustiques utilisées étaient de 65, 80, 110 et 120 Watts pour un temps de traitement de 30, 15, 20 et 20 secondes respectivement. Au total 6 lésions placentaires ont été produites à l’issu de 13 insonifications pour des diamètres moyens de 6,4 ± 0,5 mm, 7,8 ± 0,7 mm et une profondeur moyenne de 3,8 ± 1,5 mm [etc…] / Objectives: To develop a High-intensity Focused Ultrasound (HIFU) treatment for placental abnormalities. Trials were first conducted using an ex-vivo model. Then the safety, feasibility and efficacy were demonstrated using a pregnant monkey model. The first therapeutic applications for human concern the treatment of the twin-to-twin transfusion syndrome (TTTS) and placenta accreta, for which, a clinical trial has already been established. Materials and Methods: A toroidal HIFU transducer, with an integrated ultrasound imaging probe was used. Numerical simulations have allowed identifying HIFU treatment parameters based on a preliminary experiment measuring the acoustic attenuation of human placentae. These HIFU parameters were tested during an ex-vivo study on human placentae. Two models were used. First, an extracorporis model of treatment was developed. Second, a percesarean model was developed. HIFU lesions were performed at different distances from the transducer, by adjusting the quantity of water between the transducer and tissues. The transducer was placed in contact with the fetal side of the placenta in order to simulate the uterine serosa. Using the results of these studies, an in-vivo study was conducted in a pregnant monkey model. The aim was to evaluate the feasibility, the efficacy and the harmlessness of the HIFU treatment applied to the placenta non invasively. The ultrasound monitoring was assessed during these three studies, and was correlated to the macroscopic examination. A histological study was also performed. Results: The placental attenuation was measured using 12 placental samples for a gestational age from 17 to 40 weeks of gestation (WG). The attenuation coefficient increased according to the gestational age, and was ranged from 0,072 to 0,098 Np.cm-1.MHz-1. During the first experimental ex-vivo study, 33 human placental samples were included and treated with HIFU. The treatment parameters were an exposure time of 55 seconds and an acoustic power of 90 Watts. Twenty-five HIFU singles lesions were created with an average diameter and depth of 7.1 ± 3.2 and 8.0 ± 3.1 millimeters, respectively. Eight HIFU lesions were also created by juxtaposing 6 single HIFU lesions. The average diameter and depth of these juxtaposed lesions were 23.0 ± 5.0 and 11.0 ± 4.7 millimeters, respectively. No secondary lesion was observed in overlying abdominal tissues. The thickness of these intervening tissues was similar to a pregnant monkey (10.8 ± 1.7 millimeters). In a second set of experiments, 8 human placentae for a gestational age ranging between 39 and 40 weeks were treated without intervening tissues. The time of exposure was 75 seconds and the acoustic power was 90 Watts. The placental lesions were created at 2 (n=4), 6 (n=4), 7 (n=4) and 8 (n=7) millimeters from the surface of the placenta. In total, 19 placental lesions were created with an average diameter and depth of 14.6 ± 2.1 and 14.1 ± 2.3 millimeters, respectively. Eight pregnant monkeys were included in the in-vivo experiments. The average gestational age was 72 ± 4 days. The placenta was treated non-invasively with acoustic powers of 65, 80, 110 and 120 Watts for a time of exposure of 30, 15, 20 and 20 seconds, respectively. In total, 6 placental lesions were created from 13 insonifications. The average diameters and depths of these lesions were 7.8 ± 0.7 and 3.8 ± 1.5 mm, respectively. No significant variation in maternal or fetal parameters was observed. All placental lesions appear hyperechoic in sonograms and well correlated with the macroscopic measurements. The ultrasound monitoring was better invivo when compared with ex-vivo results. The histological examination demonstrated a well delimited lesion of coagulation in all cases

The most frequent sequelae following an obstetric brachial plexus lesion without complete functional recovery concern the impaired shoulder rotation movements and the associated structural changes of the growing glenohumeral joint. <p>This pathology is often unrecognized and may lead to a limitation in active movements, a pathologic and less efficient motion pattern in the affected limb, and the development of a severely incongruent and dysplastic glenohumeral joint prone to further arthrosis.<p><p>Hypothesis<p><p>Glenohumeral dysplasia after obstetric brachial plexus lesion has multiple etiologies: A hypothetic obstetric trauma may precede the motor imbalance, due to the initial palsy and prevalent recovery of the medial rotators of the shoulder.<p>The correction of the muscular imbalance, by neurotization of the lateral rotators (supra- and infraspinatus muscle) using a local nerve transfer or by a later muscle transfer surgery, improves function, seems to prevent the development of joint dysplasia and limits the articular deformities once they are present. <p>The early (peripartal) glenohumeral subluxation must be recognized and treated immediately to prevent the development of a severe joint contracture and dysplasia.<p> <p>Material and methods<p><p>Two retrospective and one prospective study evaluate how surgery may correct the muscular imbalance.<p>In a first series of 65 children, we analyse the recovery of the supra- and infraspinatus muscle after a nerve transfer onto the suprascapular nerve.<p>In a second retrospective analysis on 114 children, we study the outcome after secondary surgery (anterior joint release, modified Hoffer muscle transfer) dedicated to improve active and passive lateral rotation of the shoulder.<p>A prospective study of 50 magnetic resonance (MRI) scans of the glenohumeral joint describes the articular deformities.<p>Finally, 10 children presenting a very early glenohumeral subluxation have undergone a closed orthopaedic reposition and plaster immobilisation and were followed for a minimum of 2 years.<p><p>Results<p><p>In the first group, neurotization of the suprascapular nerve has been performed either by a dorsal or a ventral approach at a mean age of 14 months. The mean follow up is of 3 years and the improvement in aLR(ABD) is 68°and only 25°in aLR(ADD). None of these children with improved active lateral rotation of the shoulder developed clinical signs of a glenohumeral dysplasia within the follow up period.<p><p>Among the 114 children operated between 6 months and 44 years with a shoulder release, 74 had an isolated release procedure, 40 an associated tendon transfer or a suprascapular neurotization. The mean improvement in passive lateral rotation with the arm adducted (pLR (ADD)) was 60°. Active lateral rotation was possible in 63 % of children who underwent an isolated joint release.<p>The Hoffer muscle transfer was performed in 29 children and improved the aLR (ABD) by 60° (mean postoperative follow-up of 30 months). No signs of severe glenohumeral dysplasia developed in these children later on.<p><p>The prospective study of 50 consecutive MRI scans in children presenting at the consultation with a rotatory imbalance of their shoulder, as a sequel from obstetric brachial plexus palsy (Bahm et al. 2007) shows 37 congruent joints, 10 dorsal subluxations, 2 dorsal luxations and one complete dislocation associated with the formation of an independent neoglenoid. The humeral head was deformed in 12 cases; the glenoid in 34 children (flat in 23, biconcave 7 times, convex 3 times).<p><p>The follow up of 2 years in 10 children who underwent an immediate closed reposition shows evidence of joint congruence with a limited (30°) pLR (ADD), definitely lower than after a surgical release.<p><p>Conclusion<p><p>Some osteo-articular deformities secondary to neuromuscular diseases are well described ;those following an obstetric brachial plexus lesion are insufficiently recognized. Their etiology is unclear.<p>At the level of the shoulder joint, these sequels might be very important.<p>Our neuroorthopaedic hypothesis concerning a multifactorial etiology and treatment strategy raises the need of an early and precise screening of the deforming forces to render normal biomechanics and function.<p>The surgical strategy includes the reconstruction of the responsible motor nerve and the improvement of the passive and active range of motion of the shoulder in lateral rotation<p>It seems to be efficient to limit the progression to severe glenohumeral dysplasia and further arthrosis.<p> / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished