On introduit une nouvelle structure algébrique qui formalise bien les problèmes de reconstruction, assortie d’une conjecture qui permettrait de traiter directement des symétries. Le cadre fournit par cette étude permet de plus d’engendrer des relations qui ont lieu entre les nombres de sous-structures, et d’une certaine façon, la conjecture formulée affirme qu’on les obtient toutes. De plus, la généralisation des résultats précédemment obtenus pour la reconstruction permet de chercher `a en apprécier les limites en recherchant des cas où ces relations sont optimales. Ainsi, on montre que les théorèmes de V.Müller et de L.Lovasz sont les meilleurs possibles en exhibant des cas limites. Cette généralisation aux algèbres d’invariants, déjà effectuée par P.J.Cameron et V.B.Mnukhin, permet de placer les problèmes de reconstruction en tenaille entre d’une part des relations (fournies) que l’on veut exploiter, et des exemples qui établissent l’optimalité du résultat. Ainsi, sans aucune donnée sur le groupe, le résultat de L.Lovasz est le meilleur possible, et si l’on considère l’ordre du groupe, le résultat de V.Müller est le meilleur possible. / A new algebraic structure is described, that is a useful framework in whichreconstruction problems and results can be expressed. A conjecture is madewhich would, provided it is true, help to address the problem of symmetries.A consequence of the abstract language in which the theory is formulated isthe expression of relations between the numbers of substructures of a structure(for example, the number of subgraphs of a given type in a graph).Moreover, a generalisation similar to the one achieved by P.J.Cameron andV.B.Mnukhin of the results of edge reconstruction to invariant algebras isstated. Examples are then provided to show that the result of L.Lovasz isbest possible if one knows nothing about the underlying group, and that theresult of V.Müller is best possible if one knows only the order of the group.Thus, reconstruction problems are set in a theory that generates relationsto address them, and at the same time, provides examples establishing thesharpness of the theorems.

INTRODUÇÃO: Estudos experimentais suportam a evidência de leucopenia persistente desencadeada pela morte encefálica (ME). OBJETIVO: Esse estudo teve como objetivo investigar o comportamento leucocitário na medula óssea e no sangue após a morte encefálica em ratos. MÉTODOS: A morte encefálica foi induzida através da inserção e insuflação rápida de um cateter no espaço intracraniano. Ratos falso-operados (FO) foram apenas trepanados. Decorridas seis horas, as células da medula óssea, coletadas da cavidade femural, foram utilizadas para as contagens total e diferencial e analisadas por citometria de fluxo para a caracterização das subpopulações linfocitárias, a expressão de moléculas de adesão granulocíticas e apoptose/necrose (método de Anexina V/Iodeto de Propídio (PI)). RESULTADOS: Ratos com ME apresentaram uma redução de 30% no número de células da medula óssea devido à redução de linfócitos (40%) e células segmentadas (45%). As subpopulações de linfócitos na medula óssea foram semelhantes nos animais ME e FO (CD3, p=0,1; CD4, p=0,4; CD3/CD4, p=0,4; CD5, p=0,4, CD3/CD5, p=0,2; CD8, p=0,8). A expressão de L-selectina e beta2-Integrinas nos granulócitos também não diferiram entre os grupos (CD11a, p=0,9; CD11b/c, p=0,7; CD62L, p=0,1). Não existem diferenças nas porcentagens de apoptose e de necrose (Anexina V, p=0,73; PI, p=0,21; Anexina V/PI, p=0,29). CONCLUSÃO: Os dados sugerem que a redução na mobilização de células da medula óssea para o sangue, desencadeada pela morte encefálica, não se relaciona a alterações de subpopulações de linfócitos, expressão de moléculas de adesão granulocíticas, ou apoptose e necrose / INTRODUCTION: Experimental findings support the evidence of a persistent leucopenia triggered by brain death (BD). AIMS: This study aimed to investigate leukocyte behavior in bone marrow and blood after BD in rats. METHODS: BD was induced by quickly inflation of an intracranial balloon catheter. Sham operated (SH) rats were trepanned only. Six hours thereafter bone marrow cells harvested from the femoral cavity were used for total and differential counts, and analyzed by flow cytometry to characterize lymphocyte subsets, granulocyte adhesion molecules expression, and apoptosis/necrosis (annexin V/propidium iodide (PI) protocol). RESULTS: BD rats exhibited a 30% reduction in bone marrow cells due to a reduction in lymphocytes (40%) and segmented cells (45%). Bone marrow lymphocyte subsets were similar in BD and SH rats (CD3, p=0.1; CD4, p=0.4; CD3/CD4, p=0.4; CD5, p=0.4, CD3/CD5, p=0.2; CD8, p=0.8). Expression of L-selectin and ?2-integrins on granulocytes did not differ (CD11a, p=0.9; CD11b/c, p=0.7; CD62L, p=0.1). There were no differences in the percentage of apoptosis and necrosis (Annexin V, p=0.73; PI, p=0.21; Annexin V/PI, p=0.29). CONCLUSIONS: Data presented suggest that the down-regulation of the bone marrow triggered by BD is not related to changes in lymphocyte subsets, granulocyte adhesion molecules expression, or apoptosis and necrosis

A imunodeficiência comum variável (ICV) é a imunodeficiência primária sintomática mais frequente em adultos, caracterizada pela redução dos níveis séricos de IgG e de ao menos um dos isotipos IgA ou IgM. Em aproximadamente 50% dos casos a imunidade celular também está comprometida, podendo ser detectadas alterações quantitativas e funcionais das populações de linfócitos T. Os pacientes geralmente cursam com infecções crônicas ou recorrentes do trato respiratório e gastrointestinal, sendo comuns também as associações com doenças autoimunes e inflamatórias, doença granulomatosa, linfoproliferações benignas e malignidades como carcinomas e, em especial, linfomas. Como decorrência, os pacientes com ICV mantêm um quadro de inflamação crônica, maior risco de desnutrição, osteoporose e perda de massa muscular, além de menor aptidão cardiorrespiratória e comprometimento da função muscular, os quais mais recentemente têm sido relacionados a alterações de populações linfocitárias T e B em contextos patológicos variados. Este estudo teve por objetivo caracterizar em pacientes com ICV o estado nutricional, a massa óssea, a aptidão cardiorrespiratória e a força muscular e relacioná-los à contagem de subpopulações linfocitárias e parâmetros inflamatórios em sangue periférico. A composição corporal e a massa óssea foram avaliadas por densitometria por dupla emissão de raios-X (DXA), o índice de massa corporal (IMC) a partir do peso e estatura, a aptidão cardiorrespiratória por teste cardiorrespiratório máximo, a força muscular por dinamômetro de mão. As populações linfocitárias de células CD4+, CD8+ e CD19+ no sangue periférico foram avaliadas por citometria de fluxo. Os parâmetros inflamatórios séricos avaliados foram velocidade de hemossedimentação, proteína C reativa (PCR), ferritina, transferrina e beta-2 microglobulina. Realizaram-se testes de comparação entre médias e modelos de regressão linear, assumindo p<0,05. Foram avaliados 34 pacientes com média de idade de 37,3 ± 10,8 anos. Aproximadamente metade dos indivíduos (47,1%) estava eutrófica, 41,2% apresentavam sobrepeso ou obesidade e apenas uma minoria (11,8%) estava desnutrida, sendo a média do IMC do grupo inteiro 24,24 ± 4,64 kg/m2. Apesar da baixa prevalência de desnutrição, 27,7% dos pacientes demonstraram diminuição de massa muscular e 57,6% de massa óssea. Quanto à aptidão cardiorrespiratória e à força muscular, 88,9% e 17,9% dos pacientes foram classificados com baixa aptidão e fraqueza, respectivamente, sendo a média do consumo de oxigênio no pico do exercício (VO2pico) 25,38 ± 6,39 ml/kg/min. No que diz respeito às populações linfocitárias, as médias das contagens de linfócitos foram: CD4+ 615 ± 242 cel/mm3; CD8+ 680 ± 528 cel/mm3 e CD19+ 149 ± 131 cel/mm3. Não foram observadas associações entre a diminuição da capacidade cardiorrespiratória e os valores das diversas subpopulações linfocitárias analisadas. A análise dos modelos de regressão, incluindo variáveis de controle, demonstrou que os níveis mais baixos de linfócitos B CD19+ estavam relacionados à diminuição dos parâmetros de massa muscular; por outro lado, observou-se associação positiva entre a contagem de linfócitos T CD4+ e a massa magra, massa muscular apendicular (MMA), massa muscular apendicular relativa (MAR), densidade mineral óssea (DMO) lombar e seu T-score, DMO de fêmur total e seus T- e Z-scores, não havendo associação com os marcadores inflamatórios. A partir de valores de linfócitos TCD4+, foi gerado um ponto de corte (650 células/mm3), para maior risco de osteopenia e osteoporose (p=0,029). Quando os pacientes foram distribuídos abaixo ou acima desse valor, foi observada diferença estatística quanto ao peso (p=0,004), massa magra (p=0,027), MMA (p=0,022) MAR (p=0,029), circunferência do braço (p=0,013) e panturrilha (p=0,005), conteúdo mineral ósseo total (p=0,005), DMO lombar (p=0,005) e respectivos T- (p=0,005) e Z-scores (p=0,016), DMO de fêmur (p < 0,001) e seus T- (p=0,001) e Z-scores (p=0,001), DMO de colo de fêmur (p=0,035) e T-score (p=0,041), não sendo significativo apenas para o Z-score do colo femoral (p=0,053). Em conclusão, foram observados em pacientes com ICV o predomínio de eutrofia e sobrepeso; baixa aptidão cardiorrespiratória; diminuição da massa muscular e massa óssea, que apresentou associação aos baixos valores de linfócitos T CD4+; e a relação entre a diminuição da massa e força muscular e a redução dos linfócitos B CD19+. Esses resultados são inéditos e sugestivos de que os valores de linfócitos T CD4+ abaixo de 650 células/mm3 possam ser preditivos para a presença de alterações do metabolismo ósseo e da massa muscular em pacientes com imunodeficiência comum variável / Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency in adults, characterized a marked decrease of serum IgG and of at least one of the isotypes IgA or IgM. Around half of the patients also have impairment of cell-mediated immunity, in which T lymphocytes quantity and function changes can be observed. CVID patients frequently have chronic or recurrent respiratory and gastrointestinal infections, autoimmune, autoinflammatory and granulomatous diseases, benign lymphoproliferative disorders and malignancy, such as carcinoma and especially lymphoma. Thus, they are at a chronic inflammatory state, with a higher risk for malnourishment, osteoporosis and muscle mass loss, besides low cardiorespiratory fitness and muscle strength, which was recently related to T and B lymphocytes changes in different disease contexts. This study aimed to characterize nutritional status, bone mass, cardiorespiratory fitness, muscle strength and link them to lymphocyte populations and inflammatory markers of patients with CVID. Body composition and bone mass were assessed by dual-energy X-ray absorptiometry (DXA), body mass index (BMI) by weight and height, cardiorespiratory fitness by maximal cardiorespiratory fitness test, muscle strength by hand dynamometer. Peripheral blood CD4+, CD8+ and CD19+ lymphocytes were assessed by flow cytometry. Serum inflammatory markers erythrocyte sedimentation rate, C reactive protein, ferritin, transferrin and beta-2 microglobulin were measured. Difference between means and linear regression tests were made, assuming p<0,05. Thirty-four patients with mean age of 37.3 ± 10.8 years were assessed in this study. Mean BMI was 24.24 ± 4.64 kg/m2, in which around half (47.1%) were eutrophic, 41.2% were overweight or obese and the minority (11.8%) was malnourished. Despite low prevalence of malnourishment, 27.7% of the patients had low lean mass and 57.6% had low bone mass. Regarding cardiorespiratory fitness and muscle strength, 88.9% and 17.9% were classified as low and weak, respectively, presenting a VO2peak of 25.38 ± 6.39 ml/kg/min. Concerning lymphocyte populations, CD4+ lymphocyte count was 615 ±242 cells/mm3, T CD8+ was 680 ±528 cells/mm3 and B CD19+ was 149 ±131 cells/mm3. There was no association between cardiorespiratory fitness and lymphocytes subsets counts. Regressions models which included controlling variables showed that lower B CD19+ cells are related to the decrease of muscle mass parameters; on the other hand, we observed a positive association between T CD4+ lymphocyte count and lean mass, appendicular lean mass (ALM), relative ALM, total bone mineral content, lumbar spine bone mineral density (BMD) and its T-score, femur BMD and its T- and Z-score, having no association with inflammatory markers. Using T CD4+ values, a cutoff (650 cells/mm3) was generated for increased risk of osteopenia and osteoporosis (p=0,029). When all patients were divided in two groups, above and below this cutoff, it was seen statistical difference for weight (p=0,004), lean mass (p=0,027), ALM (p=0,022), relative ALM (p=0,029), arm (p=0,013) and calf (p=0,005) circumferences, total bone mineral content (p=0,005), lumbar BMD (p=0,005) and its T- (p=0,005) and Z-scores (p=0,005), femur BMD (p < 0,001) and its T- (p=0,001) and Z-scores (p=0,001), femoral neck BMD (p=0,035) and its T-score (p=0,041), but not for femoral neck Z-score (p=0,053). After all, there were observed the following alterations in patient with CVID: predominance of eutrophy and overweight; low cardiorespiratory fitness; decrease of muscle mass and bone mass, which were associated to lower values of T CD4+ lymphocytes; relationship between the decrease of muscle mass and strength and the decrease of B CD19+ count. Similar data has never been published literature and is highly suggestive that T CD4+ lymphocytes count below 650 cells/mm3 in CVID patients can predictive of changes to the bone metabolism and muscle mass

A imunodeficiência comum variável (ICV) é a imunodeficiência primária sintomática mais frequente em adultos, caracterizada pela redução dos níveis séricos de IgG e de ao menos um dos isotipos IgA ou IgM. Em aproximadamente 50% dos casos a imunidade celular também está comprometida, podendo ser detectadas alterações quantitativas e funcionais das populações de linfócitos T. Os pacientes geralmente cursam com infecções crônicas ou recorrentes do trato respiratório e gastrointestinal, sendo comuns também as associações com doenças autoimunes e inflamatórias, doença granulomatosa, linfoproliferações benignas e malignidades como carcinomas e, em especial, linfomas. Como decorrência, os pacientes com ICV mantêm um quadro de inflamação crônica, maior risco de desnutrição, osteoporose e perda de massa muscular, além de menor aptidão cardiorrespiratória e comprometimento da função muscular, os quais mais recentemente têm sido relacionados a alterações de populações linfocitárias T e B em contextos patológicos variados. Este estudo teve por objetivo caracterizar em pacientes com ICV o estado nutricional, a massa óssea, a aptidão cardiorrespiratória e a força muscular e relacioná-los à contagem de subpopulações linfocitárias e parâmetros inflamatórios em sangue periférico. A composição corporal e a massa óssea foram avaliadas por densitometria por dupla emissão de raios-X (DXA), o índice de massa corporal (IMC) a partir do peso e estatura, a aptidão cardiorrespiratória por teste cardiorrespiratório máximo, a força muscular por dinamômetro de mão. As populações linfocitárias de células CD4+, CD8+ e CD19+ no sangue periférico foram avaliadas por citometria de fluxo. Os parâmetros inflamatórios séricos avaliados foram velocidade de hemossedimentação, proteína C reativa (PCR), ferritina, transferrina e beta-2 microglobulina. Realizaram-se testes de comparação entre médias e modelos de regressão linear, assumindo p<0,05. Foram avaliados 34 pacientes com média de idade de 37,3 ± 10,8 anos. Aproximadamente metade dos indivíduos (47,1%) estava eutrófica, 41,2% apresentavam sobrepeso ou obesidade e apenas uma minoria (11,8%) estava desnutrida, sendo a média do IMC do grupo inteiro 24,24 ± 4,64 kg/m2. Apesar da baixa prevalência de desnutrição, 27,7% dos pacientes demonstraram diminuição de massa muscular e 57,6% de massa óssea. Quanto à aptidão cardiorrespiratória e à força muscular, 88,9% e 17,9% dos pacientes foram classificados com baixa aptidão e fraqueza, respectivamente, sendo a média do consumo de oxigênio no pico do exercício (VO2pico) 25,38 ± 6,39 ml/kg/min. No que diz respeito às populações linfocitárias, as médias das contagens de linfócitos foram: CD4+ 615 ± 242 cel/mm3; CD8+ 680 ± 528 cel/mm3 e CD19+ 149 ± 131 cel/mm3. Não foram observadas associações entre a diminuição da capacidade cardiorrespiratória e os valores das diversas subpopulações linfocitárias analisadas. A análise dos modelos de regressão, incluindo variáveis de controle, demonstrou que os níveis mais baixos de linfócitos B CD19+ estavam relacionados à diminuição dos parâmetros de massa muscular; por outro lado, observou-se associação positiva entre a contagem de linfócitos T CD4+ e a massa magra, massa muscular apendicular (MMA), massa muscular apendicular relativa (MAR), densidade mineral óssea (DMO) lombar e seu T-score, DMO de fêmur total e seus T- e Z-scores, não havendo associação com os marcadores inflamatórios. A partir de valores de linfócitos TCD4+, foi gerado um ponto de corte (650 células/mm3), para maior risco de osteopenia e osteoporose (p=0,029). Quando os pacientes foram distribuídos abaixo ou acima desse valor, foi observada diferença estatística quanto ao peso (p=0,004), massa magra (p=0,027), MMA (p=0,022) MAR (p=0,029), circunferência do braço (p=0,013) e panturrilha (p=0,005), conteúdo mineral ósseo total (p=0,005), DMO lombar (p=0,005) e respectivos T- (p=0,005) e Z-scores (p=0,016), DMO de fêmur (p < 0,001) e seus T- (p=0,001) e Z-scores (p=0,001), DMO de colo de fêmur (p=0,035) e T-score (p=0,041), não sendo significativo apenas para o Z-score do colo femoral (p=0,053). Em conclusão, foram observados em pacientes com ICV o predomínio de eutrofia e sobrepeso; baixa aptidão cardiorrespiratória; diminuição da massa muscular e massa óssea, que apresentou associação aos baixos valores de linfócitos T CD4+; e a relação entre a diminuição da massa e força muscular e a redução dos linfócitos B CD19+. Esses resultados são inéditos e sugestivos de que os valores de linfócitos T CD4+ abaixo de 650 células/mm3 possam ser preditivos para a presença de alterações do metabolismo ósseo e da massa muscular em pacientes com imunodeficiência comum variável / Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency in adults, characterized a marked decrease of serum IgG and of at least one of the isotypes IgA or IgM. Around half of the patients also have impairment of cell-mediated immunity, in which T lymphocytes quantity and function changes can be observed. CVID patients frequently have chronic or recurrent respiratory and gastrointestinal infections, autoimmune, autoinflammatory and granulomatous diseases, benign lymphoproliferative disorders and malignancy, such as carcinoma and especially lymphoma. Thus, they are at a chronic inflammatory state, with a higher risk for malnourishment, osteoporosis and muscle mass loss, besides low cardiorespiratory fitness and muscle strength, which was recently related to T and B lymphocytes changes in different disease contexts. This study aimed to characterize nutritional status, bone mass, cardiorespiratory fitness, muscle strength and link them to lymphocyte populations and inflammatory markers of patients with CVID. Body composition and bone mass were assessed by dual-energy X-ray absorptiometry (DXA), body mass index (BMI) by weight and height, cardiorespiratory fitness by maximal cardiorespiratory fitness test, muscle strength by hand dynamometer. Peripheral blood CD4+, CD8+ and CD19+ lymphocytes were assessed by flow cytometry. Serum inflammatory markers erythrocyte sedimentation rate, C reactive protein, ferritin, transferrin and beta-2 microglobulin were measured. Difference between means and linear regression tests were made, assuming p<0,05. Thirty-four patients with mean age of 37.3 ± 10.8 years were assessed in this study. Mean BMI was 24.24 ± 4.64 kg/m2, in which around half (47.1%) were eutrophic, 41.2% were overweight or obese and the minority (11.8%) was malnourished. Despite low prevalence of malnourishment, 27.7% of the patients had low lean mass and 57.6% had low bone mass. Regarding cardiorespiratory fitness and muscle strength, 88.9% and 17.9% were classified as low and weak, respectively, presenting a VO2peak of 25.38 ± 6.39 ml/kg/min. Concerning lymphocyte populations, CD4+ lymphocyte count was 615 ±242 cells/mm3, T CD8+ was 680 ±528 cells/mm3 and B CD19+ was 149 ±131 cells/mm3. There was no association between cardiorespiratory fitness and lymphocytes subsets counts. Regressions models which included controlling variables showed that lower B CD19+ cells are related to the decrease of muscle mass parameters; on the other hand, we observed a positive association between T CD4+ lymphocyte count and lean mass, appendicular lean mass (ALM), relative ALM, total bone mineral content, lumbar spine bone mineral density (BMD) and its T-score, femur BMD and its T- and Z-score, having no association with inflammatory markers. Using T CD4+ values, a cutoff (650 cells/mm3) was generated for increased risk of osteopenia and osteoporosis (p=0,029). When all patients were divided in two groups, above and below this cutoff, it was seen statistical difference for weight (p=0,004), lean mass (p=0,027), ALM (p=0,022), relative ALM (p=0,029), arm (p=0,013) and calf (p=0,005) circumferences, total bone mineral content (p=0,005), lumbar BMD (p=0,005) and its T- (p=0,005) and Z-scores (p=0,005), femur BMD (p < 0,001) and its T- (p=0,001) and Z-scores (p=0,001), femoral neck BMD (p=0,035) and its T-score (p=0,041), but not for femoral neck Z-score (p=0,053). After all, there were observed the following alterations in patient with CVID: predominance of eutrophy and overweight; low cardiorespiratory fitness; decrease of muscle mass and bone mass, which were associated to lower values of T CD4+ lymphocytes; relationship between the decrease of muscle mass and strength and the decrease of B CD19+ count. Similar data has never been published literature and is highly suggestive that T CD4+ lymphocytes count below 650 cells/mm3 in CVID patients can predictive of changes to the bone metabolism and muscle mass

The oldest-old (people aged 80 or older) constituted 5 % of the population in Sweden in 2000, an increase from 1.5 % fifty years earlier. The immune system undergoes dramatic changes at high age, sometimes referred to as “immunosenescence”. However, the natures of these changes, and in particular, their clinical consequences are incompletely understood. In a previous longitudinal study, a set of immune parameters were identified and termed immune risk phenotype (IRP) because of an association with increased mortality. The IRP consists of changes in the T lymphocyte compartment, in particular an inverted CD4/CD8 ratio. The IRP was found to be associated with cytomegalovirus (CMV) infection, which through expansions of cytolytic anti-viral CD8 cell responses was ascribed a role in the development of IRP. The general aim of this thesis was to increase the knowledge of changes in the immune system and their clinical consequences in the oldest-old. The population-based random sample of the longitudinal NONA-Immune Study (n = 138, mean age 90 years at baseline) was used for all investigations. In paper I, the effects on sample size of various exclusion protocols for immune studies of the elderly was examined. The commonly used SENIEUR protocol, selecting individuals representing ‘normal ageing’, excluded 90 % of nonagenarians. Based on different protocol criteria, individuals were grouped into ‘very healthy’, ‘moderately healthy’ or ‘frail’. The prevalence of CMV was similar across the groups. Further, differentiated CD8 populations associated with CMV, i.e. those expressing CD56, CD57 and CD45RA while lacking expression of CD27 and CD28, were equally distributed across the groups of the oldest-old, but were, as expected, significantly increased in the elderly compared to a middle aged control group. The findings showed that lymphocyte subsets associated with IRP might serve as significant biomarkers of ageing independent of the overall health status, also supporting the notion that immunological studies of the oldest-old should be done in population-based non-selected populations. The IRP and the presence of low-grade inflammation, for example increase of   IL-6 in plasma, constitute major predictors of 2-year mortality in the oldest-old. In paper II, the CD4/CD8 ratio and IL-6 were found to predict 97 % of observed survival and 57 % of deaths over 2 years. The impact of IRP and IL-6 on 2-year survival was independent of age, sex and several diseases. The longitudinal design allowed temporal evaluations, suggesting a sequence of events starting with IRP and leading to inflammation in the decline state.                                      Four-year mortality in the oldest-old (paper III) was found to be mainly related to markers of inflammation and IRP. Individuals with both inverted CD4/CD8 ratio and high IL-6 level had significantly higher 4 year mortality (82 %) compared to individuals with CD4/CD8 ratio ³ 1 and low IL-6 level (29 %) at baseline. The presence of IRP and increased IL-6 level showed some associations with presence of diseases; in particular, IL6 was associated with the presence of cognitive impairment. However, despite being strong predictors of mortality, IRP and IL-6 could not be linked to any specific cause of death, probably due to the multi-factorial nature of these factors.                                                                                                                             The prevalence of antinuclear antibodies (ANA) in the oldest-old was higher compared to younger controls (paper IV). The difference across age was most pronounced in men, showing low levels at younger age, whereas the prevalence among the oldest-old men reached a similar level as in women. There was no association between the presence of ANA and IRP, CMV status or health status in the oldest-old.

Une courbe de fragilité sismique qui présente la probabilité de défaillance d'une structure en fonction d'une intensité sismique, est un outil performant pour l'évaluation de la vulnérabilité sismique des structures en génie nucléaire et génie civil. On se concentre dans cette thèse sur l'approche par simulations numériques pour la construction des courbes de fragilité sismique. Une étude comparative des méthodes paramétriques existantes avec l'hypothèse log-normale est d'abord réalisée. Elle permet ensuite de proposer des améliorations de la méthode du maximum de vraisemblance dans le but d'atténuer l'influence de l'excitation sismique lors de son processus de construction. Une autre amélioration est l'application de la méthode de simulations par subsets pour l'évaluation de la probabilité de défaillance faible. Enfin, en utilisant la méthode de calcul de l'évolution des fonctions de densité de probabilité qui permet d'évaluer la probabilité conjointe entre la réponse structurale et les variables aléatoires du système et de l'excitation, nous proposons également une nouvelle technique non-paramétrique de construction des courbes de fragilité sismique sans utiliser l'hypothèse de la loi log-normale. La validation des améliorations et de la nouvelle technique est réalisée sur des exemples numériques.

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on April 1, 2010). Vita. Thesis advisor: Habib Zaghouani. "May 2008" Includes bibliographical references.

INTRODUÇÃO: Estudos experimentais suportam a evidência de leucopenia persistente desencadeada pela morte encefálica (ME). OBJETIVO: Esse estudo teve como objetivo investigar o comportamento leucocitário na medula óssea e no sangue após a morte encefálica em ratos. MÉTODOS: A morte encefálica foi induzida através da inserção e insuflação rápida de um cateter no espaço intracraniano. Ratos falso-operados (FO) foram apenas trepanados. Decorridas seis horas, as células da medula óssea, coletadas da cavidade femural, foram utilizadas para as contagens total e diferencial e analisadas por citometria de fluxo para a caracterização das subpopulações linfocitárias, a expressão de moléculas de adesão granulocíticas e apoptose/necrose (método de Anexina V/Iodeto de Propídio (PI)). RESULTADOS: Ratos com ME apresentaram uma redução de 30% no número de células da medula óssea devido à redução de linfócitos (40%) e células segmentadas (45%). As subpopulações de linfócitos na medula óssea foram semelhantes nos animais ME e FO (CD3, p=0,1; CD4, p=0,4; CD3/CD4, p=0,4; CD5, p=0,4, CD3/CD5, p=0,2; CD8, p=0,8). A expressão de L-selectina e beta2-Integrinas nos granulócitos também não diferiram entre os grupos (CD11a, p=0,9; CD11b/c, p=0,7; CD62L, p=0,1). Não existem diferenças nas porcentagens de apoptose e de necrose (Anexina V, p=0,73; PI, p=0,21; Anexina V/PI, p=0,29). CONCLUSÃO: Os dados sugerem que a redução na mobilização de células da medula óssea para o sangue, desencadeada pela morte encefálica, não se relaciona a alterações de subpopulações de linfócitos, expressão de moléculas de adesão granulocíticas, ou apoptose e necrose / INTRODUCTION: Experimental findings support the evidence of a persistent leucopenia triggered by brain death (BD). AIMS: This study aimed to investigate leukocyte behavior in bone marrow and blood after BD in rats. METHODS: BD was induced by quickly inflation of an intracranial balloon catheter. Sham operated (SH) rats were trepanned only. Six hours thereafter bone marrow cells harvested from the femoral cavity were used for total and differential counts, and analyzed by flow cytometry to characterize lymphocyte subsets, granulocyte adhesion molecules expression, and apoptosis/necrosis (annexin V/propidium iodide (PI) protocol). RESULTS: BD rats exhibited a 30% reduction in bone marrow cells due to a reduction in lymphocytes (40%) and segmented cells (45%). Bone marrow lymphocyte subsets were similar in BD and SH rats (CD3, p=0.1; CD4, p=0.4; CD3/CD4, p=0.4; CD5, p=0.4, CD3/CD5, p=0.2; CD8, p=0.8). Expression of L-selectin and ?2-integrins on granulocytes did not differ (CD11a, p=0.9; CD11b/c, p=0.7; CD62L, p=0.1). There were no differences in the percentage of apoptosis and necrosis (Annexin V, p=0.73; PI, p=0.21; Annexin V/PI, p=0.29). CONCLUSIONS: Data presented suggest that the down-regulation of the bone marrow triggered by BD is not related to changes in lymphocyte subsets, granulocyte adhesion molecules expression, or apoptosis and necrosis

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-01-12T13:26:08Z No. of bitstreams: 1 thaisabranchesbuenosabinobertges.pdf: 1644405 bytes, checksum: 3b8373f3de0b6d396b5af331c1897b4a (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-01-25T17:14:55Z (GMT) No. of bitstreams: 1 thaisabranchesbuenosabinobertges.pdf: 1644405 bytes, checksum: 3b8373f3de0b6d396b5af331c1897b4a (MD5) / Made available in DSpace on 2016-01-25T17:14:55Z (GMT). No. of bitstreams: 1 thaisabranchesbuenosabinobertges.pdf: 1644405 bytes, checksum: 3b8373f3de0b6d396b5af331c1897b4a (MD5) Previous issue date: 2015-09-14 / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / A cicatrização é um evento complexo que tem por objetivo restaurar a integridade anatômica, histológica e funcional de um tecido que sofreu lesão por diferentes etiologias. O potencial de modulação do sistema imunológico e das reações inflamatórias locais, por técnicas não invasivas, é alvo de diversos trabalhos e apesar de tal efeito modulador já ser comprovado clinicamente e corroborado por estudos histomorfológicos, os mecanismos celular e molecular de ação local e sistêmica das principais terapias adjuvantes disponíveis, a laserterapia de baixa intensidade e o ultrassom terapêutico, ainda não estão totalmente esclarecidas. O objetivo do presente estudo foi comparar os efeitos da terapia a laser de baixa intensidade e do ultrassom terapêutico, isolados e associados no processo de reparo tecidual, de feridas cutâneas cirúrgicas em ratos Wistar, com pesquisa da produção in situ de TGF-β1, TGF-β2 e IL-17 por imuno-histoquímica, além de avaliar, por histomorfometria, a deposição de matriz colagenosa na área em cicatrização por estudo retrospectivo em material emblocado em parafina (n = 24), cujas amostras foram divididas em: um grupo controle (GI), um submetido apenas à laserterapia (GII), um submetido apenas ao ultrassom (GIII) e um submetido às duas terapias associadas (GIV). Os dados foram expressos em média e desvio padrão, sendo considerado p < 0,05 para indicar resultados estatisticamente significantes. A expressão de TGF-β1 foi significativa quando as amostras de GIV foram comparadas com GII e GIII. Em relação a IL-17, as amostras de GI e de GII apresentaram maior porcentagem de células coradas, e a diferença foi significativa entre GII e GIII, e entre GII e GIV. / Wound healing is a complex event that aims to restore anatomical, histological and functional integrity of a tissue injury suffered by different etiologies. The potential modulation of the immune system and local inflammatory reactions by noninvasive techniques is the subject of several studies and although such modulating effect already being clinically proven and confirmed by histopathologic studies, the cellular and molecular mechanisms of local and systemic actions of main adjuvant therapies available, the low level laser therapy and ultrasonic energy, are still unclear. The aim of this study was to compare the effects of laser therapy of low intensity and the therapeutic ultrasound, isolated and associates in the tissue repair process in surgical wounds in Wistar rats, with research in situ production of TGF-β1, TGF-β2 and IL-17 by immunohistochemistry, and to evaluate by histomorphometry, the deposition of collagenous matrix in the area in healing by retrospective study in emblocado material paraffin (n = 24), the samples were divided into: a control group (GI) one subject only to laser therapy (GII), a submitted only to the ultrasound (GIII) and submitted to the two associated therapies (GIV). Data were expressed as mean and standard deviation, being considered p < 0.05 to indicate a statistically significant results. The TGF-β1 expression was significant when samples of GIV were compared with GII and GIII. With regard to IL-17, samples of GI and GII had a higher percentage of stained cells, and the difference was significant between GII and GIII, and between GII and GIV.

Background: Leukocytes in peripheral blood (PB) are prognostic biomarkers in head and neck squamous cell carcinoma cancer patients (HNSCC-CPs), but differences between HNSCC-CPs and healthy adults (HAs) are insufficiently described. Methods: 10-color flow cytometry (FCM) was used for in-depth immunophenotyping of PB samples of 963 HAs and 101 therapy-naïve HNSCC-CPs. Absolute (AbsCC) and relative cell counts (RelCC) of leukocyte subsets were determined. A training cohort (TC) of 43 HNSCC-CPs and 43 HAs, propensity score (PS)-matched according to age, sex, alcohol, and smoking, was used to develop a score consecutively approved in a validation cohort (VC). Results: Differences in AbsCC were detected in leukocyte subsets (p < 0.001), but had low power in discriminating HNSCC-CPs and HAs. Consequently, RelCC of nine leukocyte subsets in the TC were used to calculate 36 ratios; receiver operating characteristic (ROC) curves defined optimum cut-off values. Binary classified data were combined in a score based on four ratios: monocytes-to-granulocytes (MGR), classical monocytes-to-monocytes (clMMR), monocytes-to-lymphocytes (MLR), and monocytes-to-T-lymphocytes (MTLR); ≥3 points accurately discriminate HNSCC-CPs and HAs in the PS-matched TC (p = 2.97 × 10−17), the VC (p = 4.404 × 10−178), and both combined (p = 7.74 × 10−199). Conclusions: RelCC of leukocyte subsets in PB of HNSCC-CPs differ significantly from those of HAs. A score based on MGR, clMMR, MLR, and MTLR allows for accurate discrimination.