Made available in DSpace on 2016-12-08T16:24:18Z (GMT). No. of bitstreams: 1 PGCA14MA140.pdf: 91454 bytes, checksum: d7f6d38c8c463559f1c52096a57acd9b (MD5) Previous issue date: 2014-02-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / We describe the epidemiological, clinical signs and lesions of four outbreaks of acute pulmonary edema and emphysema in cattle (EEPAB) in the states of Santa Catarina and Paraná and its experimental reproduction of disease. Spontaneous disease occurred after transfer of mature cattle grazing and dry for another young and flourishing. All affected cattle were cows of the Dutch and Swiss brown races. The main clinical signs were dyspnea , labored abdominal breathing with the neck extended and mouth open and some had subcutaneous emphysema , besides the decrease in milk production and slow recovery or death . Necropsy findings were restricted to the lung which had dark red color, not collapsed, glossy and hipercriptante with marked interlobular emphysema. Histological lesions in the lung consisted mainly of alveolar and interlobular emphysema interspersed with areas of congestion and edema, hyaline degeneration of the wall of alveoli and infiltration of macrophages and eosinophils , moderate , diffuse . The experimental reproduction of the disease was performed in a beef with administration of 0.7 mg / kg / BW of L - Tryptophan orally in a single dose. The animal died on the seventh day of the experiment. The clinical signs and lesions were similar to those observed in naturally occurring disease / Descrevem-se os dados epidemiológicos, sinais clínicos e lesões de quatro surtos da doença do edema e enfisema pulmonar agudo de bovinos (EEPAB) nos estados de Santa Catarina e Paraná e sua reprodução experimental. A doença espontânea ocorreu após transferência de bovinos de pastagem madura e seca para outra jovem e viçosa. Todos os bovinos afetados eram vacas das raças holandês e pardo suíço. Os principais sinais clínicos foram dispnéia, respiração abdominal dificultosa com o pescoço estendido e boca aberta e alguns apresentavam enfisema subcutâneo, além de queda na produção de leite e morte ou recuperação lenta. Os achados de necropsia foram restritos ao pulmão o qual tinha coloração vermelho escuro, não colabado, de aspecto brilhante e hipercriptante com enfisema interlobular acentuado. As lesões histológicas no pulmão consistiam principalmente de enfisema alveolar e interlobular intercalado por áreas de congestão e edema, degeneração hialina da parede de alvéolos e infiltrado de macrófagos e eosinófilos, moderado, difuso. A reprodução experimental da doença foi realizada em um bovino, com administração de 0,7mg/kg/PV de L-Triptofano por via oral em dose única. O animal morreu no sétimo dia de experimento. Os sinais clínicos e lesões foram idênticos aos observados na doença espontânea

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / A Matriz Extracelular, a estrutura biolÃgica que sustenta as cÃlulas em tecidos animais, à composta de fibras elÃsticas como colÃgeno e elastina. Sabe-se que a atividade enzimÃtica desempenha papel fundamental na manutenÃÃo dessas fibras elÃsticas. O desequilÃbrio entre destruiÃÃo e reparo das fibras elÃsticas pode levar a doenÃas como fibrose e enfizema. Neste estudo, nÃs apresentamos um modelo simples para simular digestÃo enzimÃtica e reparo de fibras sob tensÃo. A fibra à representada por uma cadeia de molas linearmente elÃsticas em sÃrie. A fibra à cercada por duas camadas de sÃtios ao longo dos quais partÃculas representantes de enzimas e fragmentos podem se difundir. Estas partÃculas podem se ligar e se desligar da fibra, simulando o processo de reaÃÃo ao alterar a constante elÃstica local por um fator multiplicativo. Estuda-se a distribuiÃÃo do nÃmero de visitas de partÃculas degradadoras e enrijecedoras Ãs molas em funÃÃo do tempo de difusÃo e a consequente variaÃÃo da rigidez da fibra, sob diversas condiÃÃes iniciais (parÃmetros do modelo). Mostra-se que, devido a caracterÃsticas matemÃticas intrÃnsecas ao modelo, o efeito de degradaÃÃo prevalece sobre o de enrijecimento ainda quando a concentraÃÃo de agentes de ambos os tipos à a mesma. NÃo hà relaÃÃo entre o nÃmero de partÃculas degradadoras e enrijecedoras que garanta a estabilidade da constante elÃstica da fibra. Quanto um fator de anisotropia à incluÃdo no modelo e o comportamento do sistema passa a depender da tensÃo aplicada à fibra, mostra-se que o aumento da tensÃo em geral contribui para o aumento da atividade enzimÃtica. Este estudo poderà ajudar a entender a progressÃo da degradaÃÃo de tecidos em doenÃas como enfisema e fibrose. / Extracelular matrix, the biological structure that supports cells in animal tissue, is composed of elastic fibers such as collagen and elastin. It is known that enzymes activity plays an important role in maintenance of these elastic fibers. The imbalance between destruction and repair of the elastic fibers can lead to diseases such as fibrosis and emphysema. In this study, we present a simple model to simulate enzymatic digestion and repair of elastic fibers under tension. The fiber is represented by a chain of linearly elastic springs in series surrounded by two layers of sites along which particles representing enzymes and fragments can diffuse. These particles can biding-unbinding in the fiber simulating the reaction process by changing the local stiffness by a multiplicative factor. We study the distribution of the number of visits of particles to the springs as function of time and the consequent change of the fiber stiffness, under different initial conditions (model parameters). We show that, due to no linearity of the model, the degradation effect prevails even when the concentrations of the two type of agents are the same. There is no relation between the number of degradative and rigidifying particles that garantee that the fiber stiffness remains constant. When an anisotropy factor is included on the model and the system behaviour becomes dependent on the tension applied to the fiber, we show that the increase of tension in general contributes to the increase on enzymatic activity. We believe this study can help better understand progression of diseases such as emphysema and fibrosis.

Dans ce travail de recherche doctorale, l’IRM des poumons à temps d'écho courts dite UTE (Ultra-short EchoTime) a été utilisée pour détecter le signal RMN du tissu pulmonaire afin de caractériser et étudier des modèlesexpérimentaux de maladies pulmonaires chez les rongeurs (rats et souris). En particulier, la technique radialeUTE a été appliquée pour détecter des biomarqueurs dans des modèles de broncho-pneumopathie chroniqueobstructive (BPCO) induite expérimentalement chez les rongeurs. La détection du signal RMN en provenancedu parenchyme pulmonaire a fourni de précieux indicateurs de la maladie associés à l'élargissement des alvéolespulmonaires et aux processus inflammatoires. De plus, la simplicité de mise en oeuvre de cette technique(absence de synchronisation cardiaque et pulmonaire) permet de réduire les temps d’acquisition et apparait bienadaptée aux études longitudinales. La mesure répétée du centre de l’espace-k à chaque temps de répétition de laséquence a été utilisée pour développer une méthode de post-synchronisation reposant sur la détection desmouvements cardio-respiratoires, et permettant de produire des images sans artefacts de mouvement. / In this work, ultra-short echo time (UTE) MR imaging of the lungs is presented as a way of detecting pulmonaryMRI signal, thus providing an opportunity to develop new imaging tools for the investigation of experimentalmodels of lung diseases in rodents. The UTE imaging technique (TE=450 μs) was implemented on a 4.7 Tscanner and applied to detect indicators of Chronic Obstructive Pulmonary Disease (COPD) inducedexperimentally in rodents. The improved signal detection from the lung parenchyma provided valuable markersof disease associated with airspace enlargement and inflammation. When used to investigate of inflammationspecificity, this technique had advantages when delineating regions of early cellular infiltration into the site ofinflammation. In the case of edematous signal quantification, the UTE technique was explored to improve thereliability of the volumetric measurements. This technique was demonstrated to be of use when easy protocolimplementation (relatively high throughput and low-cost experiments) and longitudinal studies (limitedinterference with physiopathology) are of concern. The repetitive probing of the k-space center with a temporalresolution of the sequence's repetition time achieved with this technique was used to develop a self-gatingmethod which relies on the tracking of cardio-respiratory motions, yielding images free from motion artifacts.

Magister Scientiae (Medical Bioscience) - MSc(MBS) / Nicotine exposure to the fetus through tobacco smoking or nicotine replacement therapy during the whole period of gestation and lactation causes diverse effects on fetal and neonatal lung development, integrity and maturation which compromise the gas exchange function of the lungs and renders this vital organ susceptible to gradual damage and different diseases in latter life. Maternal nicotine exposure during gestation and lactation results in gradual destruction of the lung parenchyma, and this leads to the combination of many small air sacs in one bigger alveoli which is a sign of emphysema. Many researchers speculated that the way in which, nicotine causes emphysema and other damage, is by inducing the formation of many reactive oxygen species (ROS), and creating an imbalance between the oxidants and the antioxidants of the body, which is termed oxidative stress. The aim of this study was to assess the effects of nicotine exposure on the lung of the fetal and neonate rat during gestation and lactation as gas exchanger, and also to see whether the supplementation of tomato juice containing lycopene, a powerful carotenoid antioxidant could protect the lungs against these effects of maternal nicotine exposure. In this study pregnant rats have been divided into 4 groups: a group which received nicotine (1mg/kg body weight/day) subcutaneously, a group that received the tomato juice only (6mg/kg body weight/day per os), a third group that received the combination of tomato juice ( 6mg /kg body weight/ day per os) and nicotine (1mg/kg body weight /day subcutaneously ) . The control group that received saline (1mg/kg body weight /day) subcutaneously and water. The injections were done during pregnancy and lactation until weaning at postnatal day 21. The results showed that maternal nicotine exposure during gestation and lactation leads to a gradual damage of the lung parenchyma and slower formation of the alveoli during the equilibrated phase of the lung growth leading to a decrease in the internal surface area required for gas exchange. Supplementation with tomato juice during gestation and lactation prevents all the adverse effects of maternal nicotine exposure on the lungs of the offspring. Since nicotine induce an increase in the oxidant levels of the mother and the fetus, my results imply that lycopene protected the lungs of the offsprings against the oxidants and thus against changes in the program that controls lung development as the animals age. This is supported by the observation that at postnatal day 84 the antioxidant. / South Africa

Philosophiae Doctor - PhD / exposed to nicotine through the blood and the milk of the mother. Nicotine is thus expected to interact with the developing fetus and the offspring of mothers who smoke or use NRT for smoking cessation, resulting in the interference with normal fetal and neonatal lung development. Maternal cigarette smoke or nicotine exposure produces adverse effects in the lungs of offspring, these include; intrauterine growth retardation, low birth weight, premature birth, reduced pulmonary function at birth, and a high occurrence of respiratory illnesses after birth. This study aimed at investigating the effects of maternal nicotine exposure during gestation and lactation on lung development in the offspring; to establish whether tomato juice can have protective effects on the fetal lung development and function in the offspring; and to determine if nicotine cases premature aging of the lungs of the offspring. It was therefore shown that maternal exposure to nicotine during gestation and lactation ad no significant effect on the growth parameters of the offspring. Maternal nicotine exposure during gestation and lactation had no effect on the growth parameters of the offspring, but resulted in compromised lung structure and function. The morphometric results demonstrated decrease in alveolar number, increase in alveolar size, and decrease in lung parenchyma of the nicotine exposed animals showing a gradual deterioration of the lung parenchyma. Structural alterations include emphysematous lesions, where the latter was accompanied by an increase in alveolar size (Lm), and a decrease in the tissue volume of the lung parenchyma. Thickening of alveolar walls was also evident and serves as an indication of remodeling of the extracellular matrix, also a characteristic of emphysema. A consequence of the gradual deterioration of the lung parenchyma is a decrease in the alveolar surface area available for gas exchange. The present study showed that the emphysematous lesions were conceivably a result of a reduced rate of cell proliferation accompanied by the increase in senescent cells numbers in the alveolar walls of the exposed offspring. The data of this study suggests that maternal nicotine exposure during gestation and lactation induces premature aging of the lungs of the offspring rendering the lungs of the offspring more susceptible to disease later in life. Since these structural changes occurred later in the life of the offspring and long after nicotine withdrawal, it is suggested that it is programmed during gestation and lactation. Smoking and NRT result in an increased load of oxidants in the mother and fetus. It also reduces the level of anti-oxidants and thereby compromising the ability of the mother to protect the fetus. It is hypothesized that this oxidant-antioxidant imbalance will program the lungs to age prematurely. The supplementation of the mother’s diet with tomato juice, rich in lycopene, other anti-oxidants such as vitamin C, as well as phytonutrients protected the lungs of the offspring against the adverse effects of maternal nicotine exposure. This supports the hypothesis mentioned above. The study further showed that the effects of grand-maternal nicotine exposure during gestation and lactation on the lungs of the F1 offspring is also transferred to the F2 offspring. This is most likely via the paternal and maternal germ line. Since tomato juice supplementation of the mother’s diet with tomato juice prevented the adverse effects of maternal nicotine exposure on the lungs of the offspring, it is conceivable that it will prevent transfer of these changes to the F2 generation. / South Africa

Accurate, cross-scanner assessment of in-vivo air density used to quantitatively assess amount and distribution of emphysema in COPD subjects has remained elusive. Hounsfield units (HU) within tracheal air can be considerably more positive than -1000 HU. With the advent of new dual-source scanners which employ dedicated scatter correction techniques, it is of interest to evaluate how the quantitative measures of lung density compare between dual-source and single-source scan modes. This study has sought to characterize in-vivo and phantom-based air metrics using dual-energy computed tomography technology where the nature of the technology has required adjustments to scatter correction. Anesthetized ovine (N=6), swine (N=13: more human-like rib cage shape), lung phantom and a thoracic phantom were studied using a dual-source MDCT scanner (Siemens Definition Flash. Multiple dual-source dual-energy (DSDE) and single-source (SS) scans taken at different energy levels and scan settings were acquired for direct quantitative comparison. Density histograms were evaluated for the lung, tracheal, water and blood segments. Image data were obtained at 80, 100, 120, and 140 kVp in the SS mode (B35f kernel) and at 80, 100, 140, and 140-Sn (tin filtered) kVp in the DSDE mode (B35f and D30f kernels), in addition to variations in dose, rotation time, and pitch. To minimize the effect of cross-scatter, the phantom scans in the DSDE mode was obtained by reducing the tube current of one of the tubes to its minimum (near zero) value. When using image data obtained in the DSDE mode, the median HU values in the tracheal regions of all animals and the phantom were consistently closer to -1000 HU regardless of reconstruction kernel (chapters 3 and 4). Similarly, HU values of water and blood were consistently closer to their nominal values of 0 HU and 55 HU respectively. When using image data obtained in the SS mode the air CT numbers demonstrated a consistent positive shift of up to 35 HU with respect to the nominal -1000 HU value. In vivo data demonstrated considerable variability in tracheal, influenced by local anatomy with SS mode scanning while tracheal air was more consistent with DSDE imaging. Scatter effects in the lung parenchyma differed from adjacent tracheal measures. In summary, data suggest that enhanced scatter correction serves to provide more accurate CT lung density measures sought to quantitatively assess the presence and distribution of emphysema in COPD subjects. Data further suggest that CT images, acquired without adequate scatter correction, cannot be corrected by linear algorithms given the variability in tracheal air HU values and the independent scatter effects on lung parenchyma.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22728号 / 医博第4646号 / 新制||医||1045(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊達 洋至, 教授 萩原 正敏, 教授 松田 道行 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

L’emphysème pulmonaire est, avec la bronchite chronique à laquelle il est généralement associé, une bronchopathie chronique obstructive (BPCO). Ce groupe de maladie a été la sixième cause de mortalité au monde en 1990 et pourrait devenir la troisième en 2020.L’emphysème pulmonaire est défini par un élargissement anormal et permanent des espaces aériens en amont des bronchioles terminales avec destruction des parois alvéolaires sans fibrose évidente. Compte tenu de cette définition, son diagnostic devrait idéalement être basé sur l’histopathologie. Cependant, en pratique clinique, si les EFR sont à la base de la définition de la BPCO, elles ne suffisent pas au diagnostic de l’emphysème pulmonaire.<p><p>La tomodensitométrie (TDM) est une méthode diagnostique d’obtention in vivo de coupes anatomiques qui, formées de milliers de pixels, en font la méthode morphologique la plus précise pour investiguer la structure pulmonaire. Si la juxtaposition de ces pixels – dont la tonalité de gris est fonction de l’atténuation – est à la base de l’image TDM, la même information peut être représentée par la distribution de fréquence de ces atténuations. En présence d’emphysème, la destruction du tissu pulmonaire (et la plus grande proportion d’air) déterminent le déplacement de cette distribution vers les atténuations plus négatives. Plusieurs index TDM dérivés de cette distribution – notamment l’atténuation moyenne, la surface pulmonaire occupée par des valeurs d’atténuation inférieures à un seuil, un percentile particulier de la distribution – sont de possibles mesures de l’étendue de l’emphysème pulmonaire. L’émergence de la technique hélicoïdale, permettant notamment d’explorer tout le parenchyme pulmonaire en une seule apnée, justifie de déterminer les seuils et percentiles adéquats par comparaison à une mesure histologique de référence.<p><p>Au cours de nos études, nous avons montré que les index TDM dérivés de la distribution de fréquence d’atténuation tels que les surfaces relatives de poumon occupées par les coefficients d’atténuation inférieures à -960 UH (RA960) ou -970 UH (RA970) et le premier percentile (p1) sont les index les plus appropriés. En revanche, toujours sur base de comparaisons histo-morphométriques, d’autre index qui reflètent la géométrie des espaces emphysémateux – tels que la distribution de la taille des groupes de pixels adjacents occupés par des coefficients d’atténuation inférieurs à un seuil ou à un percentile – ne sont pas des index valables.<p><p>La dose d’irradiation peut être abaissée à 20 mAs effectifs. Cette réduction est particulièrement appropriée dans une pathologie susceptible de concerner des patients jeunes et l’objet d’examens répétés. Cependant, la dose d’irradiation influençant ces index, elle doit être maintenue constante au cours de suivis longitudinaux.<p><p>En TDM multi-coupes, ces index sont les plus appropriés quelque soit l’épaisseur des coupes. Cependant, cette épaisseur influençant ces index, elle doit aussi être maintenue constante au cours de suivis longitudinaux.<p><p>L’inspiration incomplète induit une sous-estimation statistiquement significative mais cliniquement insignifiante de l’étendue de l’emphysème pulmonaire. La destruction du tissu pulmonaire et l’hyperinflation ont des influences séparées sur les index TDM, faisant recommander leur ajustement aux valeurs prédites de la CPT.<p><p> / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

Masters of Science / The infants of women who smoke during pregnancy have a lower birth mass than those born of women who abstain. Animal studies reveal that reduced growth due to maternal nicotine exposure during gestation is accompanied by lung hypoplasia. Biochemical analysis suggests that these lungs contain more cells which implies that lung damage occurs. In this study we examined the in vivo effects of maternal nicotine exposure (lmg/Kg/day), the equivalent of 32 cigarettes per day, on the following parameters of fetal and neonatal Wistar rat lung:(i) the content and distribution of glycogen in fetal and neonatal lung (ii) the status of connective tissue in neonatal lung (iii) the cell composition of the alveoli in neonatal lung. Fetal rat lungs of ages 17, 18, 19 and 20 days and neonatal lungs of 1, 7, 14 and 21 day old pups were used. Light microscope techniques and special stains were used to investigate glycogen, connective tissue, macrophage numbers and morphological status of the lungs. Fetal rat lungs of ages 17, 18, 19 and 20 days and neonatal lungs of 1, 7, 14 and 21 day old pups were used. Light microscope techniques and special stains were used to investigate glycogen, connective tissue, macrophage numbers and morphological status of the lungs. Transmission electron microscope (TEM) techniques were employed to investigate the characteristics and composition of the alveolus The results show clearly that maternal nicotine exposure elevates pulmonary alveolar macrophage numbers'(PAM's) and lung glycogen levels. The quantity of elastic fibres in 1 day old neonates was significantly reduced but no changes in the quantity of reticulin and collagen fibres was observed. As a result of this change in connective tissue status, emphysema-like lesions and alveolar collapse was evident in the lungs of nicotine-exposed pups. TEM investigations revealed that changes to the composition of alveoli occurred. These included increased numbers of type II pneumocytes with high numbers of lamellar bodies with degenerative changes. Thickening of the blood-air barrier was also observed. The effect of maternal nicotine exposure has been documented in this study. However, it has not been possible to pinpoint the mechanisms involved but explanations have been proposed. Further research is required to elucidate the mechanisms by which nicotine produces these effects. Information thus obtained could help prevent the harmful effects to the fetus and neonate caused by smoking during pregnancy.

Lung cancer remains the leading cause of cancer deaths in the United States despite public health campaigns aimed at reducing its rate of mortality. Kentucky is the state with the highest lung cancer incidence and mortality. This study aims to assess the impact of misclassification of cause of death from Lung Cancer in Kentucky for the period 1979 to 2002. We will examine the potential competing classification of death for two other smoking-related diseases, Chronic Obstructive Pulmonary Disease (COPD) and Emphysema. Age-adjusted mortality rates for these diseases for white males were obtained from the National Center for Health Statistics. There was little evidence that any misclassification between COPD or Emphysema mortality rates was in agreement with the rising lung cancer rates in Kentucky. The long-term increase in lung cancer mortality in Kentucky is likely because of a combination of risk effects between smoking and other risk-factors for this disease.