O transporte mucociliar (TMC) é um mecanismo básico de defesa do sistema respiratório necessário na resistência à infecção. A efetividade desse mecanismo de defesa depende da composição e profundidade do muco, da integridade e da função dos cílios e da interação muco-cílio. O objetivo deste estudo foi investigar os efeitos crônicos do oxigenoterapia de baixo fluxo via cateter nasal com e sem umidificação sobre o TMC nasal, nas propriedades físicas do muco, na inflamação e nos sintomas de vias aéreas em pacientes com hipoxemia crônica com necessidade de oxigenoterapia domiciliar de longo prazo (>15 horas/dia). Dezoito pacientes (idade média de 68 anos, 7 do sexo masculino, índice de massa corpórea (IMC) médio de 26 kg/m2, 66% com doença pulmonar obstrutiva crônica (DPOC), 60% com hipertensão arterial (HAS) e ex-tabagistas) iniciando oxigenoterapia de baixo fluxo via cateter nasal foram randomizados para o grupo Oxigênio Seco (n=10) ou Oxigênio Umidificado (n=9). Os pacientes foram avaliados nos tempos: basal, 12 horas, 7 dias, 30 dias, 12 meses e 24 meses para o TMC nasal por meio do teste de trânsito da sacarina, as propriedades físicas do muco por meio de ângulo de contato, a inflamação por meio de quantificação do número total de células e diferenciais e da concentração de citocinas no lavado nasal assim como para sintomas por meio do questionário SNOT-20. O sintoma mais importante relatado por pacientes no basal foi tosse que melhorou após 7 dias de oxigenoterapia. No nosso estudo, os pacientes de ambos grupos apresentaram prolongamento significativo (40%) do TMC nasal ao longo do estudo. O lavado nasal mostrou um aumento das proporções de neutrófilos, das células caliciformes e da concentração do fator de crescimento epidermal (EGF) assim como reduções em macrófagos e concentrações de interferon alfa (IFN-alfa), interleucina (IL)-8 e IL-10 ao longo do estudo. Não houve alterações na proporção de células ciliadas, na concentração de IL-6 e no ângulo de contato do muco em ambos os grupos. A tosse e os sintomas de sono diminuiram significativamente em ambos os grupos. Nosso estudo sugere que a umidificação não tem impacto sobre o TMC nasal, as propriedades do muco, a inflamação e os sintomas em pacientes com baixo fluxo de oxigênio via cateter nasal (BFON) / Mucociliary clearance (MCC) is a basic defense mechanism of the respiratory system against respiratory infection. The efficiency of this defense mechanism depends on the mucus composition and mucus depth, on the cilia integrity and function and the mucus-cilia interaction. The aim of this study was investigate the long-term effects of low-flow oxygen via nasal catheter (NLFO) using dry oxygen (Dried-NLFO) or humidified oxygen (Humidified-NLFO) on nasal mucociliary clearance, mucus properties, inflammation and symptoms in patients with chronic hypoxemia requiring long-term domiciliary oxygen therapy ( > 15 hours/day). Eighteen patients (mean age of 68 years, 7 male, mean BMI of 26 kg/m2, 66% COPD, 60% hypertensive and former smokers) initiating NLFO were randomized to Dried-NLFO (n=10) or Humidified-NLFO (n=9). Patients were assessed at baseline and along 12 hours, 7 days, 30 days, 12 months and 24 months for nasal MCC using saccharine test, mucus properties by means of contact angle, inflammation using total number of cells and cytokines concentration in nasal lavage fluid as well as symptoms by SNOT-20 questionnaire. The most important airway symptom reported by patients at baseline was cough that improved after 7 days of oxygen therapy. In our study, nasal MCC prolonged significantly (40%) and similarly in both groups along the study. Nasal lavage showed increased proportions of neutrophils, goblet cells and epidermal growth factor concentration as decreases in macrophages, IFN-a lfa, IL-8 and IL-10 concentrations along the study. No changes in the proportion of ciliated cells, IL-6 and mucus contact angle were observed in both groups. Coughing and sleep symptoms significantly decreased similarly in both groups. Our study suggests that humidification does not impact on nasal MCC, mucus properties, inflammation and symptoms in patients using NLFO

INTRODUÇÃO: A circulação extracorpórea (CEC) é um fator etiológico importante para a lesão pulmonar, observada após cirurgia cardíaca. No entanto, o impacto da CEC na função mucociliar respiratória é desconhecido. O objetivo do estudo foi avaliar os efeitos imediatos da CEC sobre o sistema de transporte mucociliar. MÉTODOS: 22 porcos mestiços das raças Large White e Landrace com peso entre 33 a 47 kg alocados nos grupos controle (n = 10) e CEC (n = 12) completaram o estudo. As técnicas de anestesia e ventilação mecânica foram padronizadas. Após a indução da anestesia, foi realizada traqueostomia e uma amostra do tecido traqueal foi excisado (T0) em ambos os grupos. Todos os animais foram submetidos a toracotomia e CEC aorto-bicaval foi instalada no grupo CEC e mantida durante 90 minutos. Após o desmame da CEC (T90), uma segunda amostra do tecido traqueal foi obtida 180 minutos após a traqueostomia (T180). Amostras de muco foram coletadas na traquéia por meio de broncoscopia em T0, T90 e T180. Frequência de batimento ciliar (FBC) e transporte mucociliar in situ (TMC) foram estudados em epitélio traqueal ex vivo. As características do muco respiratório in vitro foram estudadas por transportabilidade ciliar no palato de rã (VTM), Transporte do muco respiratório in vitro pela tosse (TMT), Ângulo de contato (AC) e da viscosidade do muco por viscosímetro Cone-Plate (VM). RESULTADOS: A FBC diminuiu no grupo CEC (13,09 ± 1,91 Hz vs 11,06 ± 2,1 Hz, p <0,05), mas não no grupo controle (13,42 ± 0,96 Hz vs 12, 98 ± 2,84 Hz). No momento T90, a viscosidade aparente avaliado em 100 RPM estava aumentada no grupo CEC em relação ao controle. Não foram observadas diferenças significativas no TMC, VTM, TMT e AC. No grupo de CEC, foi percebida a perda do epitélio ciliado, edema submucoso e infiltração de células inflamatórias na avaliação histológica da traqueia. CONCLUSÃO: A CEC compromete agudamente o sistema de transporte mucociliar traqueal. Novos estudos são necessários para avaliar se esse comportamento tem implicações clínicas / BACKGROUND: Cardiopulmonary bypass (CPB) is an important etiologic factor for lung injury observed after cardiac surgery. However, the impact of CPB on respiratory mucociliary function is unknown. The objective of this study was to assess the immediate effects of CPB on mucociliary transport system. METHODS: Twenty-two mixed breed of Large White and Landrace pigs with weight between 33 to 47kg assigned to control (n=10) and CPB groups (n=12) completed the study. The techniques of anesthesia and mechanical ventilation were standardized. After anesthesia induction, tracheotomy was performed and a tracheal tissue sample was excised (T0) in both groups. All animals underwent thoracotomy and aorto-bicaval CPB was installed in CPB group and maintained during 90 minutes. After weaning from CPB (T90), a second tracheal tissue sample was obtained 180 minutes after tracheotomy (T180). Mucus samples were collected from the trachea using a bronchoscope at T0, T90 and T180. Ciliary beat frequency (CBF) and in situ mucociliary transport (MCT) were studied in ex vivo tracheal epithelium. In vitro respiratory mucus characteristics were studied by mucociliary transportability in frog palate (MT), Cough clearance (CC), Contact angle (CA) and the mucus viscosity by Cone-Plate viscometer (MV). RESULTS: CBF decreased in CPB group (13.09 ± 1.91 Hz vs. 11.06 ± 2.1 Hz, p < 0.05) but not in control group (13.42 ± 0.96 Hz vs. 12.98 ± 2.84 Hz). At T90 Apparent viscosity evaluated at 100 RPM increased in CPB group compared to control. No significant differences were observed in MCT, MT, CA and CC. In CPB group, it was observed loss of ciliated epithelia, submucosal edema and inflammatory cells infiltration in tracheal histology. CONCLUSION: CPB acutely compromise the tracheal mucociliary transport system. New studies are necessary to investigate if this behavior has any clinical implication

La sélection des meilleurs candidats médicament se base sur des choix multiparamétriques réunissant l’efficacité potentielle, les caractéristiques ADME et le profil de sécurité des nouvelles entités chimiques. En ce sens, la prédiction précoce de la pharmacocinétique est élémentaire pour orienter les prises de décision et donner un cap pertinent aux projets. En raison de son rôle central dans le devenir des médicaments, la clairance métabolique médiée principalement par le foie est l’un des paramètres les plus importants. L’objectif de ce projet était d’améliorer la prédiction de la clairance en se concentrant notamment sur les molécules présentant une bonne stabilité métabolique et qui sont de ce fait encore difficiles à étudier. Les travaux menés dans cette thèse nous ont permis d’étoffer nos connaissances sur les modèles hépatiques in vitro et les méthodes d’extrapolation usuelles mais aussi de découvrir et de développer de nouvelles stratégies de prédiction. Nous nous sommes concentrés en profondeur sur la clairance métabolique et à tout ce qui impacte les prédictions. Le modèle de co-culture microorganisée (MPCC) HepatopacTM qui permet de stabiliser les hépatocytes humains sur plusieurs semaines a ainsi été identifié comme une alternative judicieuse aux modèles de routine lorsque les molécules ne peuvent pas être étudiées en culture 2D classique. L’étude de la fraction libre plasmatique et l’intégration de nouvelles hypothèses physiologiques telles que la théorie de « l’uptake facilité par l’albumine » ont également participé à améliorer les prédictions. Compte tenu des performances du modèle HepatopacTM, nous avons développé une approche innovante basée sur le spotting de précision afin de produire tous types de co-cultures microorganisées. Les co-cultures fabriquées grâce à cette technique démontrent que la méthode est robuste, accessible et simple à mettre en œuvre. Notre méthode de spotting a ensuite été utilisée pour faire évoluer le modèle MPCC et l’ouvrir à de nouvelles applications. / The selection of the best drug candidates is based on multiparametric choices combining the potential efficacy, ADME characteristics and the safety profile of the new chemical entities. In this sense, the early prediction of pharmacokinetic is essential to guide decision-making and provide a relevant course for projects. Because of its central role in drug disposition, metabolic clearance mediated primarily by the liver is one of the most important parameters. The objective of this project was to improve clearance prediction by focusing on low clearance compounds that are still difficult to study. This work allowed us to expand our knowledge on in vitro liver models and usual extrapolation methods but also to discover and develop new prediction strategies. We focused on metabolic clearance and all parameters that impact the predictions. Micropatterned co-cultures (MPCCs) of primary human hepatocytes (HepatopacTM), which stabilizes hepatocytes over several weeks, has been identified as a judicious alternative to routine models when the molecules cannot be studied in conventional monolayer culture. The study of plasma protein binding and the integration of new physiological hypothesis such as the "Albumin-Facilitated Uptake" also contributed to improve the predictions. Given the performance of the HepatopacTM model, we have developed an innovative approach using a digital dispensing system to spot collagen and produce all types of micropatterned co-cultures. Co-cultures manufactured by this technique demonstrate that the method is robust, accessible and easy to use. Our spotting method was used to evolve the MPCC model and explore new applications.

Avaliamos a incidência e o clareamento para o vírus do papiloma humano (HPV) dos tipos oncogênicos e não-oncogênicos em uma coorte aberta com 202 mulheres portadoras do vírus da imunodeficiência humana (HIV), e identificamos alguns fatores de risco e proteção associados a cada desfecho utilizando modelos de fragilidade Gama. No modelo de incidência, foram estudados os tempos até incidência de HPV oncogênicos e não-oncogênicos para cada mulher; no modelo de clareamento, foram estudados os correspondentes tempos até clareamento. Comparamos os erros-padrões estimados pela matriz de informação observada com os erros-padrões bootstrap para ambos os modelos e verificamos que a proposta de Verweij & Houwelingen (1994) para a matriz de variâncias e covariâncias dos parâmetros é a mais apropriada. Para a incidência de HPV oncogênicos, identificamos como fator de risco o uso de drogas em que a taxa de incidência para as pacientes que usam drogas é 1.88 (IC 90%, 1.01; 3.5) vezes aquela correspondente a mulheres que não usam e como fator de proteção a renda em que a taxa de incidência de pacientes com renda igual ou superior a 3 salários mínimos é 0.62 (IC 90%, 0.38; 1.00) vezes a taxa referente àquelas com renda menor que 3 salários mínimos. Para a incidência de HPV não-oncogênicos identificamos como fatores de risco a escolaridade e o total de gestações, em que, para a última, a taxa de incidência para as mulheres que tiveram mais do que uma gestação é 1.76 (IC 90%, 1.09; 2.86) vezes a taxa referente àquelas que tiveram uma ou nenhuma. Para o clareamento de HPV oncogênicos identificamos como fatores que indicam um clareamento mais rápido a renda, a idade e o tratamento antirretroviral (ARV), em que, para a última, supondo mulheres com fragilidades iguais, a taxa de clareamento para as pacientes que eram tratadas com o esquema inibidor de protease (IP) é 1.79 (IC 90%, 1.1; 2.9) vezes aquela correspondente a mulheres que não foram tratadas com nenhum tratamento ARV e como fator que indicam um clareamento mais lento o número de parceiros sexuais no último ano, em que, as pacientes com mais de um parceiro tiveram taxa de clareamento 0.39 (IC 90%, 0.16; 0.98) vezes a taxa de clareamento referente à uma mulher que teve um parceiro ou menos. Para o clareamento de HPV não-oncogênicos tivemos como fator que indica um clareamento mais lento o hábito tabagista em que, supondo fragilidades iguais, pacientes fumantes tem a taxa de clareamento 0.53 (IC 90%, 0.32; 0.87) vezes a taxa referente à uma mulher que não fuma. / We evaluated the incidence and clearance for oncogenic and non-oncogenic human papilloma virus (HPV) in an open cohort of 202 women infected with human immunodeficiency virus (HIV), and we identified some risk factors and protective factors for each outcome using Gamma frailty models. In the incidence model, we studied the incidence of stroke by oncogenic and non-oncogenic HPV for each woman; in the clearance model, the corresponding times to clearance were studied. We compared the standard errors estimated by the observed information matrix with bootstrap standard errors for both models and found that the variance and covariance matrix of the parameters proposed by Verweij & Houwelingen (1994) is more appropriate. For the incidence of oncogenic HPV, identified as a risk factor drug use and the incidence rate for patients who use drugs is 1.88 (90% CI, 1.01; 3.5) times the rate for those who do not use and as a protective factor income where the incidence rate is 0.62 (90% CI, 0.38; 1.00) times the rate for those earning less than 3 minimum wages. For the incidence of non-oncogenic HPV identified as risk factors schooling and total pregnancies, in which, for the latter, the incidence rate for women who had more than one pregnancy is 1.76 (90% CI, 1.09; 2.86) times the rate for those which have one or none. For clearance of oncogenic HPV identified as factors that indicate a faster clearance income, age and antiretroviral therapy (ART), in which, to the last, with women assuming equal frailties, the rate of clearance for patients who were treated with the protease inhibitor (IP) regimen is 1.79 (90% CI, 1.1; 2.9) times the rate for those who were not treated with any antiretroviral regimen and as a factor that indicates slower clearance the number of sexual partners in the last year, and for patients with more than one partner the clearance rate 0.39 (IC 90%, 0.16; 0.98) times the rate referring to a woman who had up to a partner. For the clearance of non-oncogenic HPV had a factor which indicates a slower clearance smoking habit, assuming equal frailties, smokers have the clearance rate 0.53 (90% CI, 0.32; 0.87) times the rate referring to a woman who does not smoke.

La simulation de la dynamique des systèmes multicorps avec contact frottant joue un rôle important dans un grand nombre d'applications industrielles.Elle est même devenue une partie importante du développement de nouveaux produits, de la vérification et même de l'optimisation de leur conception pour améliorer les anciens produits.Les travaux présentés dans cette thèse font partie d'une collaboration entre l'équipe BiPoP, équipe de recherche de l'INRIA Grenoble, et Schneider Electric.Le but principal de ces travaux est de comprendre l'influence du jeu dans les articulations, ainsi que l'influence du dimensionnement industriel et les tolérances géométriques sur lecomportement global des liaisons mécaniques. Plus spécifiquement nous avons étudié le mini-disjoncteur C-60 (domaine dans lequel la sécurité humaine doit être garantie), pour répondre à cette demande de robustesse, tout en respectant les tolérances sur les pièces constituant le disjoncteur C-60.Le jeu radial dans les articulations pivot est une source de variabilité dans les conditions initiales du système, mais également dans la dégradation de ses performances.La dégradation du système se présente toujours sous forme de vibrations, de bruit, de forces de réactions très grandes dans les articulations, de mauvaise précision et exactitude de la sortie.Le but est d'étudier l'influence des conditions initiales et le déplacement hors-plan, ainsi que l'effet de polarisation en trois dimensions.Un objectif supplémentaire est de développer un banc d'essai virtuel efficace pour reproduire les mesures obtenues sur un vrai banc d'essai en laboratoire, en utilisant la plateforme logicielle SICONOS qui utilise la méthode NSCD (Non Smooth Contact Dynamic) introduite par J.J. Moreau et M. Jean.Le schéma NSCD a prouvé son efficacité numérique: il est capable de traiter des problèmes de complémentarité, le contact ainsi que les impacts et les lois de frottement multivaluées.Le but est de comprendre quelle est la meilleure description géométrique pour simuler de très petits jeux.L'étude complète est divisée en deux parties. La progression part du cas planaire pour arriver au cas spatial, et la complexité suit le même chemin.Dans le cas planaire, on analyse un mécanisme à quatre barres avec du jeu quand une des articulations est commandée en boucle ouverte, ou par retour d'état linéaire ou non-linéaire(PD, linéarisation par retour d'état, ou commande passive).L'accent est mis sur la quantification de la dégradation des performances quand du jeu est ajouté dans les articulations. On montre alors que les commandes par retour d'état se comportent de façon robuste.Dans le cas spatial, le mécanisme C-60 est analysé précisément pour explorer les possibilités de relaxer les tolérances industrielles sur les pièces sans compromettre ni les performances ni la sécurité. L'influence de l'entrée, du modèle et des incertitudes numériques sur le modèle C-60 est étudiée.L'influence induite par le jeu et le coefficient de frottement dans les articulations sur la performance du produit est étudiée.Pour valider le modèle de simulation, des expériences sont effectuées sur des prototypes d'essai et les résultats sont comparés avec les simulations numériques.Nous avons trouvé une bonne correlation entre les résultats numériques et expérimentaux.L'analyse statistique~(analyse du pire cas, et par des simulations basées sur la méthode de Monte-Carlo) a été réalisée pour trouver la dispersion des conditions fonctionnelles.En plus des variations dimensionnelles, la tolérence aux variations géométriques comme la forme, l'orientation et la position, est analysée.Ce travail de recherche devrait aider les concepteurs à simuler le comportement du système mécanique avec une articulation de révolution imparfaite,depuis l'étape de conception préliminaire jusqu'à la fin de la conception pour avoir une amélioration significative de la planification et du budget. / Dynamic simulation of multibody systems with unilateral contact and friction plays an important role in a wide range of industrial applications. It has become an integral part of new product development, verification/optimization of the design and to enhance the old products.This work is a part of collaboration between the BiPoP research team of INRIA Grenoble and the Schneider Electric company.The main goal of this thesis is to understand the influence of clearances in the revolute joints on the overall behaviour of the linkage mechanisms and specifically on the C-60 miniature circuit breaker where human safety must be guaranteed.In other words, the objective is to address the robustness of the C-60 breaker with respect to the production tolerances, which areexpressed in the form of dimensional and geometrical variations on the parts. These variations are the source of clearance in the joints of the mechanism.The radial clearance in the revolute joints is a source of variability in the initial conditions of the system and also the degradation of the system's performance. The degradation of the system isalways in the form of vibration, noise, very high reaction forces at the joints.The aim is to study the influence of initial conditions and the out-of-plane motion, so the polarization effect in three dimensional case.Another objective is to develop the time efficient virtual test bench to reproduce the measurements of real test bench in the laboratory using the open-source simulation software SICONOS which is based on the NonSmooth Contact Dynamic method (NSCD) introduced by J.J. Moreau and M. Jean.The NSCD scheme is proven to be a quite efficient numerical method, capable of handling complementarity conditions, as well as impacts and set-valued friction laws.The goal is to understand what is the most appropriate geometricdescription which allows to simulate very small clearances.The complete study is divided in two main sections.The progress through these partsgoes from the planar to the spatial case, the complexity follows the same advance.In the planar case, a four-bar mechanism with joint clearance, when one joint is actuated by collocated open-loop or state feedback controllers (PD, statefeedback linearization, passivity-based) is analysed. The focus is put on how much the performancedeteriorates when clearances are added in the joints. It is shown that collocated feedback controllersbehave in a robust way.In the spatial case, the C-60 mechanism is analysed precisely to explore the possibilities to relax the manufacturing tolerances on the parts withoutany compromise on either performance or the human safelyThe influence of the input, model and numerical uncertainties on the C-60 model is studied. The joint-wise influences of the clearance and coefficient of friction on theproduct performance are studied.To validate the simulation model, experiments are carried-out on the prototype samples and the results are compared with the simulations.We found quite good correlation between the virtual and experimental results.A statistical analysis~(worst-case and Monte Carlo simulation) has been carried out to find out the dispersion of the functional conditions.In addition to dimensional variations, the geometrical variations such as form, orientation and position tolerances are also analyzed.This research work shall help the designers to simulate the real time behaviour of the mechanical systems with the imperfect revolutejoint from the pre-design stage till the end of the design, to have good improvement on schedule and budget.

A pneumonia é uma das principais causas de morte na população idosa. O prejuízo do transporte mucociliar pode aumentar a susceptibilidade à infecção respiratória. Nosso objetivo foi avaliar os efeitos do envelhecimento, isolado e combinado com diabetes ou hipertensão, sobre a transporte mucociliar nasal e as propriedades do muco. De 440 pacientes contactados por telefone, 252 pessoas participaram do estudo: 79 saudáveis (18-94 anos, 50 homens), 38 indivíduos com diabetes (14-85 anos, 13 homens), 51 indivíduos com hipertensão (23-90 anos, 12 homens) e 84 indivíduos com diabetes e hipertensão (18-84 anos, 33 homens). Os indivíduos foram divididos em dois grupos principais, saudável e co-morbidade. Cada grupo foi separado em três sub-grupos de faixas etárias: (a) <40 anos, (b) 40-59 anos e (c) 60 anos. Foram avaliados os dados demográficos, os dados clínicos, o questionário de Qualidade de Vida SF-36, o pH nasal, o transporte mucociliar nasal por meio do teste de tempo de trânsito da sacarina (TTS), as propriedades do muco in vitro por meio da transportabilidade do muco por alto fluxo e o ângulo de contato. Neste estudo, observamos no grupo saudável uma maior frequência de mulheres (p=0,040) no sub-grupo 60 anos (70%) comparado com <40 anos (35%) e 40-59 anos (22%). Nos indivíduos saudáveis não observamos diferença entre as faixas etárias quanto aos seguintes parâmetros: sumário do componente físico do SF-36 (51±7), sumário do componente mental do SF-36 (51±9), pressão arterial sistólica (116±7 mmHg), pressão arterial diastólica (76±6 mmHg), freqüência cardíaca (74±10 bpm), frequência respiratória (17±3 rpm), oximetria de pulso (97±1%), glicemia (98±8 mg/dl), pH nasal (6,7±1,3), TTS (9,5±2,7 min), transportabilidade do muco por alto fluxo (46±18 mm) e ângulo de contato do muco (42±7°). No entanto, no grupo co-morbidade, o subgrupo 60 anos apresentou aumento do índice de massa corpórea (p=0,021), da pressão arterial sistólica (p<0,001), da frequência respiratória (p<0,001) e do TTS (p=0,003) e redução do sumário do componente físico SF-36 (p<0,001) em comparação com o sub-grupo <40 anos. Observamos correlação entre TTS e idade associada a co-morbidades (p<0,001). Nosso estudo sugere que o envelhecimento combinado com o diabetes e/ou a hipertensão podem reduzir a eficiência do transporte mucociliar nasal / Pneumonia is a leading cause of death in elderly populations. Impairment of mucociliary clearance may increase susceptibility to respiratory infection. We aimed to evaluate the effects of aging alone and in combination with diabetes or hypertension on nasal mucociliary clearance and mucus properties. Of 440 subjects contacted by telephone, 252 entered the study: 79 healthy subjects (18-94 yrs, 50 male); 38 with diabetes (14-85 yrs, 13 male); 51 with hypertension (23-90 yrs, 12 male); and 84 with both diabetes and hypertension (18-84 yrs, 33 male). The subjects were divided into healthy and co-morbid groups. Each group was separated into three subgroups by age: (a) <40 yrs, (b) 40-59 yrs, and (c) 60 yrs. We assessed demographic data, clinical data, quality of life questionnaire (SF-36), nasal pH, nasal mucociliary clearance using the saccharine transit test (STT) and in vitro mucus properties by examining the high-flow clearability and contact angle. In this study, in the healthy group there was a high frequency of female (p=0.040) in the sub-group 60 yrs (70%) compared with <40 yrs (35%) and 40-59 yrs (22%). In healthy group, there were no differences between age groups in SF-36 physical component summary (51±7), SF-36 mental component summary (51±9), systolic blood pressure (116±7 mmHg), diastolic blood pressure (78±6 mmHg), heart rate (74±10 bpm), respiratory rate (17±3), pulse oximetry (97±1%), glycemia (98±8 mg/dl), nasal pH (6.7±1.3), STT (9.5±2.7 min), high-flow clearability (46±18 mm), and mucus contact angle (42±7o). In the co-morbid group, however, subjects aged 60 yrs had higher body mass indices (p=0.021), systolic blood pressures (p<0.001), respiratory rate (p<0.001), STT (p=0.003) and decreased SF-36 physical component summary scores (p<0.001) compared to the subjects aged <40 yrs. There was a significant correlation between STT and aging associated with co-morbid conditions (p<0.001). Our study suggests that aging combined with diabetes and/or hypertension can reduce nasal mucociliary clearance efficiency

A queima de biomassa produz gases tóxicos e partículas suspensas que contribuem para a poluição atmosférica. Este estudo avaliou os efeitos da colheita de cana-de-açúcar queimada sobre o transporte mucociliar (TMC) nasal, as propriedades físicas do muco nasal e celularidade e concentrações de citocinas em lavado nasal (LN) de cortadores de cana-de-açúcar e residentes de região urbana próxima aos canaviais (Mendonça, São Paulo). Métodos: Avaliamos 154 jovens não tabagistas (idade entre 18 e 43 anos) sendo 73 residentes e 81 cortadores na: (a) Pré-safra: 4 meses sem exposição à queimada de biomassa (fevereiro e março), e na (b) Pós-safra: aproximadamente 7 a 8 meses de exposição (outubro e novembro). Avaliamos: o TMC nasal por meio do teste da sacarina (TTS), as propriedades físicas do muco por meio da transportabilidade por alto fluxo e ângulo de contato, a expressão de fator de necrose tumoral (TNF)-, interleucinas (IL)-4, IL-6, IL-8 e IL-10 em LN, celularidade total e diferencial em LNsinais vitais e ocorrência de eventos respiratórios. Resultados: Na Pré-safra, comparados com os residentes, cortadores apresentaram menor pressão arterial média (95,5±9,1 e 88,7±9,4 mmHg, respectivamente; p<0,001), frequência cardíaca (76±13 e 70±10 bpm, respectivamente; p<0,003), e células ciliadas (61±20 e 47±18%, respectivamente; p<0,001). Além de TTS mais prolongado (10,4±4,6 e 11,8±5,1, respectivamente; p=0,035), e maior porcentagem de macrófagos em LN (21±15 e 43±15%, respectivamente; p<0,001). Na Pós-safra, comparados com os residentes, os cortadores apresentaram menor pressão arterial média (96,5±9,1 e 92,8±9,6 mmHg, respectivamente; p=0,042), frequência cardíaca (76±14 e 63±11 bpm, respectivamente; p<0,001), IL-4 (0,4±0,5 e 0,3±0,6 pg/ml, respectivamente; p=0,001), células ciliadas (64±19 e 52±14%, respectivamente; p<0,001), células caliciformes em LN (13±14 e 4±5%, respectivamente; p<0,001), assim como maior número de células totais (24±29 e 32±30 104células/ml, respectivamente; p=0,040), neutrófilos (1±2 e 2±3%, respectivamente; p<0,001), eosinófilos (0±0 e 0±1%, respectivamente; p<0,001), macrófagos (21±16 e 40±13%, respectivamente; p<0,001) e IL-6 (2,8±3,4 e 4,0±3,7 pg/ml, respectivamente; p=0,026) em LN. Não houve diferenças significantes nas propriedades físicas do muco, na quantificação da secreção de IL-8 e TNF-, e na porcentagem de linfócitos em LN entre os dois grupos e ao longo do estudo. Conclusão: A queimada de cana-de-açúcar induz alterações na primeira barreira de defesa do sistema respiratório em residentes e em cortadores da área urbana próxima aos canaviais observada por aumento no CO exalado, aumento de celularidade total e redução da concentração de IL-10 em LN em residentes, e prolongamento do TTS acompanhado de aumento na expressão de IL-6 e células ciliadas em LN em cortadores / Biomass burning produces toxic gases and suspended particle that contribute for high levels of air pollution. We aimed to assess the effects of sugarcane harvesting on nasal mucociliary clearance (MCC), mucus physical properties, and celularity and cytokines concentrations in nasal lavage (NL) of sugarcane workers and residents that live near to sugarcane fields (Mendonça, São Paulo). Methods: We evaluated 154 young non-smoking subjects, aged between 18 to 42 years (residents, n=73 and sugarcane workers, n=81) at two time-points: (a) non-harvesting, 4-months of no exposure to biomass burning (in February and March), and (b) harvesting, after 7 to 8-months of exposure to biomass burning (in October and November). We evaluated: Nasal MCC was assessed by saccharine transit test (STT), mucus physical properties were evaluated by sneeze clearability and contact angle, expression of tumor necrosis factor-, interleukin (IL)-4, IL-6, IL-8 e IL-10 in NL and total and differential cells counts in NL, vital signs and respiratory events. Results: At Non-harvesting, compared with residents, sugarcane workers presented lower mean blood pressure (95.5±9.1 and 88.7±9.4 mmHg, respectively; p<0.001), heart rate (76±13 and 70±10 bpm, respectively; p<0.003), and ciliated cells (61±20 and 47±18%, respectively; p<0.001) and prolonged STT (10.4±4.6 and 11.8±5.1, respectively, p=0.035), and higher percentage of macrophages in NL (21±15 and 43±15%, respectively; p<0.001). At Harvesting, compared with residents, sugarcane workers presented lower mean blood pressure (96.5±9.1 and 92.8±9.6 mmHg, respectively; p=0.042), heart rate (76±14 and 63±11 bpm, respectively; p<0.001), IL-4 (0.4±0.5 and 0.3±0.6 pg/ml, respectively, p=0.001), ciliated cells (64±19 and 52±14%, respectively; p<0.001), goblet cells (13±14 and 4±5%, respectively; p<0.001), and higher number of total cells (24±29 and 32±30 104cells/ml, respectively; p=0.040), neutrophils (1±2 and 2±3%, respectively, p<0.001), eosinophils (0±0 and 0±1%, respectively, p<0.001), macrophages (21±16 and 40±13%, respectively, p<0.001) and IL-6 concentration in NL (2.8±3.4 and 4.0±3.7 pg/ml, respectively, p=0.026). There were no significant differences in mucus physical properties, concentration of IL-8 and TNF-, and percentage of lymphocytes in NL between the two groups and along the study. Conclusion: Sugarcane burning induces changes in the first defense barrier of the respiratory system in residents of the urban area near of the sugarcane fields and in sugarcane workers which were observed by increase in exhaled CO and total cell count, and a decrease in IL-10 concentrations in NL in residents, and prolonged STT accompanied by an increase in IL-6 concentration and percentage of ciliated cells in NL in sugarcane workers

The purpose of this review was to identify the history of and advances in cystic fibrosis (CF). New treatment plans, medication developments, and a historical perspective of airway clearance therapy (ACT) will be presented. The importance of treatment compliance and time management in the care of cystic fibrosis patients will also be discussed. Furthermore, the development of cystic fibrosis clinics and the pivotal role they play in the treatment of the disease will be addressed. Lastly, a brief discussion concerning the need for and process of lung transplantation will be reported.

Oil spills in the marine environment can threaten vulnerable ecosystems that support ecologically and economically significant organisms, such as the eastern oyster (Crassostrea virginica), in coastal habitats. The use of chemical dispersant (Corexit 9500) was applied as a cleanup effort in response to the Deepwater Horizon blowout to minimize crude oil slicks, but also resulted in increased concentrations of polycyclic aromatic hydrocarbons in the water column. The effects of increased soluble fractions of crude oil and dispersant components may be harmful to marine organisms. This study aimed to investigate possible sublethal impacts to the eastern oyster at multiple life history stages in order to understand potential implications on performance at an organismal, population, and ecosystem levels. Specifically, this study addressed 1) veliger swimming, 2) pediveliger settlement rates, 3) pollutant induced larval inactivity and 4) adult clearance rates after acute exposures to relevant concentrations (10 – 100 µL L-1) of water accommodated fractions of crude oil (WAF) and with a combination of chemical dispersant (CEWAF). No significant differences were observed in any tested swimming kinematics between controls and WAF or CEWAF treatments after 24 hour exposures for early staged veligers at concentrations up to 100 µL L-1 WAF and CEWAF. However, settlements rates of competent pediveligers were significant decreased compared to control (52.1 % s.d. 1.66) rates at concentrations of 50 µL L-1 WAF (30.9% s.d. 6.16) and 10 (41.2 % s.d. 0.857) and 50 (22.0% s.d. 1.23) µL L-1 CEWAF. Later staged larvae also showed increased vulnerability to oil pollution given that a higher percentage of organisms were inactive (48.3% s.d. 4.80) compared to early staged larvae (12.7% s.d. 7.68 ) after initial exposure at 50 µL L-1 CEWAF. Based on this result, we assumed effects of oil pollution were not manifested until the later larval life history stage evident by metamorphosis failure during the complex settlement transformation that results in reduced spat and eventually reduced adult oysters. Adult oysters were also exposed to increasing concentrations of WAF and CEWAF for 24 hours and feeding experiments were conducted in both clean seawater and the same oiled seawater conditions as their initial exposure. Oysters fed in oiled seawater had decreased clearance rates, but oysters fed in clean water had increased clearance rates, suggesting feeding efficiency can be returned to control rates when moved to the presence of clean water. However, our long term study conducted in clean seawater suggested of the oysters exposed to crude oil only (9.31 L h-1 g-1 s.d. 2.04) are able to return to clearance rates comparable to controls (7.69 L h-1 g-1 s.d. 1.89) after the 33 day time period but oysters exposed to crude oil with a combination of chemical dispersant (2.12 L h-1 g-1 s.d. 1.08) were not. Decreased feeding efficiency can have negative impacts on water quality in estuarine ecosystems that support productive habitats. Understanding the impacts of crude oil, and crude oil with a combination of chemical dispersant on ecologically significant organisms can aid in future oil spill response decisions in order to minimize environmental impacts.

Revegetation is required to conserve the biological diversity of over-cleared and fragmented agricultural regions. This dissertation represents an application of spatial information technologies to environmental management. It makes a significant contribution to the integration of general landscape-scale principles into restoration ecology. New and established quantitative, spatial analytical techniques are used in environmental modelling, ecological assessment and in setting geographic priorities for strategic revegetation planning in the Mt. Lofty Ranges in South Australia. This is one of the first assessments of the adequacy and representativeness of remnants in an agricultural region and one of the first attempts to apply these landscape-scale conservation principles to the field of restoration ecology. The adequacy of the remnant ecological system is assessed in terms of the landscape structure. Landscape ecological principles provide a basis for setting geographic priorities for the revegetation of an adequate remnant ecological system. Although seldom quantified, it is often thought that remnants in agricultural regions are not representative of the regional physical environmental heterogeneity. The representativeness of remnant vegetation is assessed in the study area and a complex effect of land clearance and reserve selection on representativeness is revealed which has significant implications for strategic revegetation planning. Land clearance has precluded the use of information on the spatial distribution of biological diversity in agricultural regions. Hence, a surrogate is required in strategic planning for the restoration of a representative regional ecological system. The degree of vegetation/environment convergence is assessed to investigate the viability of using the physical environment as a surrogate for the distribution of biological diversity. An index of coincidence is developed specifically for this purpose. An environmental classification is then derived for use in setting geographic priorities for the restoration of a representative regional ecological system. Three complementary techniques are used to find the simplest classification possible that does not have overly broad environmental classes. Geographic priorities are suggested according to the distribution and representativeness of environment types in the study area. In the light of the results of this dissertation, a research direction for restoration ecology in agricultural landscapes is mapped out. / Thesis (Ph.D.)--Department of Geographical and Environmental Studies; Department of Applied and Molecular Ecology, 2000.