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Desempenho exergético do corpo humano e de seu sistema respiratório em função de parâmetros ambientais e da intensidade de atividade física. / Exergy performance of the human body and its respiratory system as a function of environmental parameters and intensity of physical activity.Izabela Batista Henriques 23 August 2013 (has links)
A análise exergética é aplicada ao corpo humano a fim de determinar o comportamento exergético padrão do corpo e do seu sistema respiratório para um indivíduo saudável em diferentes condições ambientais e intensidades de atividade física. Para isso, são calculadas as taxas de exergia destruída e as eficiências exergéticas do pulmão e do corpo como um todo para diferentes altitudes, períodos de aclimatação, temperaturas, umidades relativas e intensidades de atividade física. São utilizados modelos do corpo e do sistema respiratório disponíveis na literatura, assim como um modelo exergético do corpo. Para a análise exergética do sistema respiratório é proposto um modelo exergético baseado no modelo de transferência de calor e massa presente na literatura. A análise exergética é aplicada a dois volumes de controle: o corpo e o sistema respiratório, que compreende as vias aéreas e os pulmões. No primeiro volume de controle ocorre transferência de exergia para o ambiente através de convecção e radiação, assim como fluxos de exergia através da respiração e evaporação, além da geração de exergia pelo metabolismo exergético. No volume de controle relativo ao sistema respiratório, os fluxos de exergia estão associados ao ar inspirado e expirado e ao sangue venoso e arterial. A transferência de exergia ocorre através do calor gerado pelo metabolismo e do trabalho dos músculos respiratórios. Há também uma variação da exergia relativa ao metabolismo exergético do pulmão. Os resultados obtidos indicam que a eficiência exergética do pulmão diminui com a altitude e atividade física, enquanto a do corpo aumenta para ambos os parâmetros. Com relação à aclimatação, o período no qual as eficiências exergéticas são máximas é a partir de vinte dias. No que diz respeito à variação da temperatura e da umidade relativa, observa-se que quanto maior a intensidade da atividade física, menor a temperatura próxima do conforto. Nota-se que as eficiências do corpo e do pulmão têm comportamentos distintos, sendo o corpo mais influenciado pela intensidade da atividade física, enquanto o sistema respiratório é mais suscetível a alterações das condições ambientais. / Exergy analysis is applied to human body in order to determine the exergy behavior pattern of the body and its respiratory system for a healthy subject under different environmental conditions and physical activity intensities. In order to do so, destroyed exergy rate and exergy efficiencies are calculated for different altitudes, acclimatization periods, temperatures, relative humidities and exercise intensities. An integrated model of the body and its respiratory system and an exergy model of the body are utilized. To perform the exergy analysis of respiratory system, an exergy model based on that available in literature is proposed. Exergy analysis is applied to two control volumes: the human body as a whole and the respiratory system, which comprises the lungs and the airways. In the first control volume, the exergy rate transferred to the environment due to convection and radiation is considered, as well as the exergy flow rate associated with respiration and transpiration and the internal exergy generation caused by the exergy metabolism. In the second one, the exergy rates and flow rates are associated with the venous blood and the inspired air in the inlet and the arterial blood and expired air in the outlet. An internal exergy variation due to the exergy metabolism of the lung, an exergy transfer associated with the metabolism of the lung and the work performed by the respiratory muscles were also taken into account. The results indicate that the exergy efficiency of the lung decreases as the altitude and exercise intensity increase, while the exergy efficiency of the body increases for both parameters. Regarding acclimatization period, the greatest exergy efficiencies are obtained after twenty days. Concerning temperature and humidity variations, the higher the activity level, the lower the thermal comfort temperature. It is also possible to observe distinct behaviors between body and lung. The body is more influenced by the physical activity intensity, while the respiratory system is more affected by environmental parameters.
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Avaliação da função respiratória de crianças dos municípios de Anchieta e Guarapari (ES) através da espirometria e sua correlação com a qualidade do ar / Evaluation of lung function of children from the municipalities of Anchieta and Guarapari (ES) by spirometry and its correlation with air qualityCamila Alves Silva do Amaral 18 November 2013 (has links)
INTRODUÇÃO: A região de Guarapari e Anchieta, ao sul do estado do Espírito Santo apresenta um parque industrial em crescimento que gera na população local uma preocupação em relação à piora da qualidade do ar e aos efeitos adversos sobre a população residente. Neste estudo avaliamos os impactos da exposição à poluição do ar gerada por uma mineradora e pelotizadora de ferro sobre a saúde respiratória de crianças e adolescentes residentes no entorno do empreendimento. MÉTODOS: Estudo de painel com 121 escolares entre 8 e 16 anos de idade, matriculados em escolas de Anchieta, área exposta às emissões industriais, e Guarapari, área não exposta, no estado do Espírito Santo. Mensalmente, entre maio de 2008 e maio de 2009 foram realizados exames de espirometria. Foram aplicados questionários para obtenção de dados biodemográficos e um questionário validado - ISAAC, para investigar informações referente a presença de asma e alergias respiratórias e cutâneas. Rede de monitoramento da qualidade do ar que mede material particulado forneceu informações diárias sobre as concentrações deste poluente para o período analisado. A correlação entre a exposição aos poluentes do ar e os parâmetros de função respiratória (razão entre valores medidos e preditos) foi analisada através de duas abordagens. Na primeira, foram comparadas as médias mensais de volume expiratório forçado no primeiro segundo, capacidade vital forçada, pico de fluxo expiratório, razão entre volume expiratório forçado e capacidade vital forçada, fluxo expiratório forçado de 25 e 75% da manobra de capacidade vital forçada e tempo de expiração forçada entre os dois grupos. Para esta análise, foi adotado o teste-t de student. Na segunda abordagem, a associação entre os parâmetros respiratórios e o material particulado inalado foi investigada através de modelos de regressão de efeitos mistos, incluindo-se nos modelos controles para: variáveis meteorológicas, presença de asma e alergias respiratórias e, quando necessário, índice de massa corpórea. RESULTADOS: 86 crianças concluíram o estudo. As médias mensais da razão entre volume expiratório forçado no primeiro segundo e capacidade vital forçada e pico de fluxo expiratório, em alguns meses, foram menores na área exposta enquanto que o inverso ocorreu para o tempo expiratório final. Houve relação inversamente proporcional entre a variação do material particulado e todos os parâmetros de espirometria exceto o tempo expiratório. Para uma variação de 14,03 ?g/m3 no PM10 foram observadas reduções de 1,13% (IC 95%: 0,13; 2,14) no volume expiratório forçado no primeiro segundo (média móvel de cinco dias), de 0,95% (IC 95%: 0,32; 1,58) na relação entre volume expiratório forçado no primeiro segundo e capacidade vital forçada (média móvel de três dias), e de 2,96% (IC 95%: 1,46; 4,46) no pico de fluxo expiratório (média móvel de cinco dias). Em relação ao tempo expiratório houve um efeito diretamente proporcional, com um acréscimo de 3,54% (IC 95%: 0,88; 6,20) na média móvel de três dias. CONCLUSÃO: Mesmo com níveis de material particulado dentro dos padrões nacionais de qualidade do ar foi observada piora da função respiratória em crianças e adolescentes residentes nos Municípios de Anchieta e de Guarapari (ES) / INTRODUCTION: The region of Guarapari and Anchieta, in the South of the State of Espírito Santo has a growing industrial park that generates in the local population a concern to either the worsening of air quality and the adverse effects on the resident population. In this study we evaluated the impacts of exposure to air pollution generated by a mining company and iron idles on the respiratory health of children and adolescents living in the vicinity of the enterprise. Methods: Panel study with 121 students between 8 and 16 years of age, enrolled in schools of Anchieta, exposed area to industrial emissions, and Guarapari, unexposed area, in the State of Espírito Santo. Every month, between May 2008 and May 2009 spirometry tests were carried out. Questionnaires were applied to data acquisition on biodemographic issues and a validated questionnaire to investigate information on the presence of asthma and respiratory and skin allergies (ISAAC). PM10 monitoring network provided daily information on this pollutant concentrations for the period under examination. The correlation between exposure to air pollutants and lung function parameters (ratio between measured and predicted values) were analyzed through two approaches. In the first, monthly averages of forced expiratory volume in one second, forced vital capacity, peak expiratory flow, ratio of forced expiratory volume and forced vital capacity, forced expiratory flow 25 and 75 of the maneuver forced vital capacity and forced expiration time were compared between the two groups. For this analysis, was adopted the student\'s t-test. In the second approach, the association between respiratory parameters and the inhaled particulate matter was investigated via mixed effects regression models, including controls for meteorological variables, the presence of asthma and respiratory allergies and, when necessary, body mass index. Results: 86 children completed the study. Monthly averages of the ratio of forced expiratory volume in one second and forced vital capacity and peak expiratory flow, in a few months, were lower in the area exposed while the reverse occurred for the forced expiratory time. There were inversely proportional relationships between the variation of particulate matter and all the spirometry parameters except the expiratory time. For a variation of 14.03 ?gm3 in PM10 a 1.13% (CI 95: 0.13; 2.14) reduction was observed in forced expiratory volume in one second (fiveday moving average), 0.95% (CI: 0.32; 95 1.58) on the relationship between forced expiratory volume in one second and forced vital capacity (three-day moving average), and 2.96% (95 CI: 1.46; 4.46) in peak expiratory flow (fiveday moving average). In relation to the expiratory time there was a directly proportional effect, with an additional 3.54% (Ci: 0.88; 6.20) in three-day moving average. Conclusion: even with levels of particulate matter inside the national air quality standards was observed worsening of respiratory function in children and adolescents living in the municipalities of Anchieta and Guarapari (ES)
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Výkon a vybrané kardiorespirační parametry u profesionálních sportovců ve třetím až čtvrtém týdnu po prodělání onemocnění COVID-19 / Power output and selected cardiorespiratory parameters in elite athletes during the third to fourth week after COVID-19 infectionNovák, Jan January 2021 (has links)
Title: Power output and selected cardiorespiratory parameters in elite athletes during the third to fourth week after COVID-19 infection Objectives: The aim of this thesis is to compare power output and selected cardiorespiratory parameters in elite athletes before and three to four weeks after COVID- 19 infection. Since the elite athletes undergo these health checks on a yearly basis, it is possible to compare the data before and immediately after the infection without difficulty. Methods: This thesis has a character of a quantitative research based on testing the outcomes with confirming or denying hypotheses. Out of the total of 64 elite athletes with the CPET data after the infection 17 athletes, fulfilling other criteria, were selected. I was provided with the data by Centrum sportovní medicíny z. s.. These values became the foundation for statistical hypotheses testing. Analysis of the data was done by means of a pair t-test in R software. Results: There were no significant differences in the majority of the spirometry parameters. Only the inspiration vital capacity was significantly higher (p = 0,004) after the COVID-19 infection in 14 athletes with 0,21±0,18 l improvement. There were significant differences in five of CPET parameters. Load in RCP was significantly lower (p = 0,011) in 13...
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Roles of Secreted Virulence Factors in Pathogenicity of Haemophilus Influenzae: A DissertationRosadini, Charles V. 12 May 2011 (has links)
Haemophilus influenzae is a pathogenic Gram-negative bacterium that colonizes the upper respiratory tract of humans and can cause otitis media, upper and lower respiratory infections, and meningitis. Factors important for H. influenzae to colonize humans and cause disease are not fully understood. Different bacterial pathogens are armed with virulence mechanisms unique to their specific strategies for interacting with their hosts. Many of the proteins mediating these interactions are secreted and contain disulfide bonds required for function or stability. I postulated that identifying the set of secreted proteins in H. influenzae that require periplasmic disulfide bonds would provide better understanding of this bacterium's pathogenic mechanisms.
In this thesis, the periplasmic disulfide bond oxidoreductase protein, DsbA, was found to be essential for colonization and virulence of H. influenzae. Mutants of dsbA were also found to be sensitive to the bactericidal effects of serum. However, the DsbA-dependent proteins important for pathogenesis of this organism have not been previously identified. To find them, putative targets of the periplasmic disulfide bond pathway were identified and examined for factors which might be important for mediating critical virulence aspects. By doing so, novel virulence factors were discovered including those important for heme and zinc acquisition, as well as resistance to complement. Overall, the work presented here provides insight into requirements for H. influenzae to survive within various host environments.
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Effect of extracellular matrix and mechanical strain on airway smooth musclePasternyk, Stephanie Marika, 1983- January 2009 (has links)
No description available.
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Sledování poškození plicní funkce infekčním onemocněním COVID-19 pomocí spirometrie / Monitoring of lung function impairment by infectious disease COVID-19 using spirometryPetrásková, Eva January 2021 (has links)
The thesis is focused on the comparison of functional examination of the patients lungs, before and after coronavirus disease 2019 (COVID-19), as well as on the comparison of physiological data for a individual person with measured values after the disease. The relationship between lung function and smoking, sex, age and time gap after COVID undergone was monitored. The screening was accomplished by spirometry in a pneumology surgery and the obtained data were processed in practical part of my thesis. The theoretical part of the diploma thesis describes the respiratory system and lungs functional testing. In addition, infectious disease COVID-19 is described herein. The aim of the thesis was to select suitable patients, who have suffered from the COVID-19 disease, but without other serious respiratory problems, make a measurements and statistically evaluate the correlation between the measured results. The experiment involved 66 people aged between 21-94, of which 43 were men and 23 women. It has been shown a predominantly negative effect of COVID-19 in the values of the examined indicators in spirometric measurements, similarly, the impairment was seen more in men than in women. The role of younger age has been proven in the better results of spirometric measurements. However, the differences in...
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Experimentální výzkum transportu a depozice aerosolů v dýchacím traktu člověka / Experimental research on aerosol transport and deposition in human respiratory tractLízal, František January 2012 (has links)
Human health is significantly influenced by inhaled aerosols. Insight to the aerosol transport and deposition mechanisms is a prerequisite for both, toxicological protection against harmful particles and efficient application of inhaled therapeutic aerosols. The purpose of this doctoral thesis was to gain new knowledge of this topic on the basis of in vitro measurements. Phase-Doppler Anemometry was chosen for aerosol transport measurement, for it allows simultaneous measurement of particle size and velocity. Results were processed by means of statistical methods and frequency analysis. Deposition of spherical aerosol particles was measured by Positron Emission Tomography, while deposition of fibrous aerosol was measured by Phase-Contrast Microscopy combined with automated image analysis. All experiments were performed on physical models created on the basis of the real lung geometry. New knowledge of flow characteristics, transition from laminar to turbulent flow, effect of breathing pattern or particle size on aerosol transport and deposition in human lungs are outcomes of this work. Significant effect of the oral cavity was ascertained due to comparison of aerosol deposition in realistic and semi-realistic model with cylindrical smooth walls. Acquired data not merely extended our knowledge of aerosol behavior in lungs but it can also be used for validation of numerical simulations.
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Análise dos critérios para ajuste do suporte ventilatório da ventilação mecânica / Analysis of criteria for ventilatory support adjustment of mechanical ventilationAssunção, Renata Pletsch 22 November 2016 (has links)
Introdução: A assistência ventilatória adequada é imprescindível para o tratamento do paciente ventilado artificialmente. A busca por parâmetros para realizar o ajuste ótimo e que tenham aplicação fácil a beira leito como, por exemplo, métodos não-invasivos, são desejáveis. Objetivo: analisar a acurácia diagnóstica das variáveis do padrão respiratório, da P0.1 esofágica e traqueal, para o ajuste da assistência ventilatória em pressão de suporte. Métodos: Vinte e sete pacientes internados em unidade de terapia intensiva foram consecutivamente incluídos no estudo. Todos pacientes estavam no modo de pressão de suporte, que foi aumentada para 20 cmH2O e diminui em passos de 3 cmH2O, até 2 cmH2O ou antes se o paciente apresentasse sinais de desconforto respiratório. Os pacientes foram monitorizados com cateteres para medidas de pressão esofágica e gástrica, com uma peça proximal ao tubo para mensurar a pressão traqueal a partir da oclusão da via aérea e com um pneumotacógrafo para medidas de fluxo. Durante todos níveis de suporte, foram gravados os dados dos cateteres esofágicos, gástricos, da traquéia, dados hemodinâmicos e do padrão respiratório. O ajuste da assistência ventilatória foi classificado como adequado, insuficiente e excessivo de acordo com critérios pré-estabelecidos. Resultados: Foram analisados 210 períodos com diferentes pressões de suporte e em 49% destes períodos a assistência foi excessiva, enquanto em 3,8% a assistência foi insuficiente. No início do estudo, enquanto os pacientes ainda estavam com a assistência ventilatória ajustada pela equipe assistente, 48,2% apresentavam assistência ventilatória excessiva. Pela pequena incidência de períodos com assistência ventilatória insuficiente, não foi avaliado a acurácia das variáveis para diagnóstico de assistência insuficiente. Para diagnosticar assistência ventilatória excessiva, a variável do padrão respiratório que se mostrou mais acurada foi a frequência respiratória, com sensibilidade de 90% e especificidade de 88% quando a frequência respiratória foi menor que 17 incursões por minuto. Outras variáveis do padrão respiratório não mostraram elevada acurácia. Também para o diagnóstico de assistência excessiva, foi elevada a acurácia da P0.1 esofágica (sensibilidade de 81% e especificidade de 70% quando P0.1 <= 1,9) e da P0.1 traqueal (sensibilidade de 81% e especificidade de 70% quando P0.1 <= 2,1). Conclusão: A ocorrência de assistência ventilatória excessiva foi significativamente maior que a assistência ventilatória insuficiente. A frequência respiratória menor que 17 foi a variável do padrão respiratório com maior acurácia para diagnosticar assistência ventilatória excessiva. As P0.1 esofágica e traqueal também tiveram acurácia elevas, mas menores que a frequência respiratória . / Introdution: The adequate assistance is essential for the treatment of mechanically ventilated patient. The search of parameters to achieve the optimal adjustment and with easy application to bedside, for example, non-invasive methods. Objective: Analyze the diagnostic accuracy of the breathing pattern variables, esophageal and tracheal P0.1 for adjustment of mechanical ventilation in pressure support ventilation. Methods: Twenty-seven patients in intensive care unit were consecutively included in the study. All patients were in the pressure support mode, which was raised to 20 cmH2O and decreased in steps of 3 cmH2O up to 2 cmH2O or earlier if the patient had signs of respiratory distress. Patients were monitored with catheters for esophageal and gastric pressure measurements, with the T-piece was used close to the tube to measure tracheal pressure during an airway occlusion and a pneumotachograph for flow measurements. Data was recorded for all support levels to esophageal, gastric, and tracheal pressures, also hemodynamic data and ventilatory pattern. The adjustment of mechanical ventilation was classified as adequate assistance, overassistance and underassistance according to pre-established criteria. Results: Two hundred and ten periods were analyzed with different pressures of support and 49% of these periods were overassistance, while 3,8% these periods were underassistance. At baseline, while patients were still ventilatory assistance set by assistance staff, 48,2% had overassistance. Due to the low incidence of periods with underassistance, the variables accurancy has not been evaluated. The variable breathing pattern that was more accurate diagnosing overassistance was the respiratory rate (90% sensitivity and specificity of 88 % when the respiratory rate was less than 17 breaths per minute). Other variables of the breathing pattern did not show high accuracy although esophageal P0.1 (sensitivity 81 % and specificity of 70 % when P0.1 <= 1,9) and tracheal P0.1 (sensitivity 81 % and specificity of 70 % when P0.1 <= 2,1) were high accuracy diagnosing overassistance. Conclusion: The occurrence of overassistance was significantly higher than underassistance. The respiratory rate below 17 was the variable breathing pattern more accurate to predict overassistance. The esophageal and tracheal P0.1 also had high accuracy but lower than the respiratory rate
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Análise dos critérios para ajuste do suporte ventilatório da ventilação mecânica / Analysis of criteria for ventilatory support adjustment of mechanical ventilationRenata Pletsch Assunção 22 November 2016 (has links)
Introdução: A assistência ventilatória adequada é imprescindível para o tratamento do paciente ventilado artificialmente. A busca por parâmetros para realizar o ajuste ótimo e que tenham aplicação fácil a beira leito como, por exemplo, métodos não-invasivos, são desejáveis. Objetivo: analisar a acurácia diagnóstica das variáveis do padrão respiratório, da P0.1 esofágica e traqueal, para o ajuste da assistência ventilatória em pressão de suporte. Métodos: Vinte e sete pacientes internados em unidade de terapia intensiva foram consecutivamente incluídos no estudo. Todos pacientes estavam no modo de pressão de suporte, que foi aumentada para 20 cmH2O e diminui em passos de 3 cmH2O, até 2 cmH2O ou antes se o paciente apresentasse sinais de desconforto respiratório. Os pacientes foram monitorizados com cateteres para medidas de pressão esofágica e gástrica, com uma peça proximal ao tubo para mensurar a pressão traqueal a partir da oclusão da via aérea e com um pneumotacógrafo para medidas de fluxo. Durante todos níveis de suporte, foram gravados os dados dos cateteres esofágicos, gástricos, da traquéia, dados hemodinâmicos e do padrão respiratório. O ajuste da assistência ventilatória foi classificado como adequado, insuficiente e excessivo de acordo com critérios pré-estabelecidos. Resultados: Foram analisados 210 períodos com diferentes pressões de suporte e em 49% destes períodos a assistência foi excessiva, enquanto em 3,8% a assistência foi insuficiente. No início do estudo, enquanto os pacientes ainda estavam com a assistência ventilatória ajustada pela equipe assistente, 48,2% apresentavam assistência ventilatória excessiva. Pela pequena incidência de períodos com assistência ventilatória insuficiente, não foi avaliado a acurácia das variáveis para diagnóstico de assistência insuficiente. Para diagnosticar assistência ventilatória excessiva, a variável do padrão respiratório que se mostrou mais acurada foi a frequência respiratória, com sensibilidade de 90% e especificidade de 88% quando a frequência respiratória foi menor que 17 incursões por minuto. Outras variáveis do padrão respiratório não mostraram elevada acurácia. Também para o diagnóstico de assistência excessiva, foi elevada a acurácia da P0.1 esofágica (sensibilidade de 81% e especificidade de 70% quando P0.1 <= 1,9) e da P0.1 traqueal (sensibilidade de 81% e especificidade de 70% quando P0.1 <= 2,1). Conclusão: A ocorrência de assistência ventilatória excessiva foi significativamente maior que a assistência ventilatória insuficiente. A frequência respiratória menor que 17 foi a variável do padrão respiratório com maior acurácia para diagnosticar assistência ventilatória excessiva. As P0.1 esofágica e traqueal também tiveram acurácia elevas, mas menores que a frequência respiratória . / Introdution: The adequate assistance is essential for the treatment of mechanically ventilated patient. The search of parameters to achieve the optimal adjustment and with easy application to bedside, for example, non-invasive methods. Objective: Analyze the diagnostic accuracy of the breathing pattern variables, esophageal and tracheal P0.1 for adjustment of mechanical ventilation in pressure support ventilation. Methods: Twenty-seven patients in intensive care unit were consecutively included in the study. All patients were in the pressure support mode, which was raised to 20 cmH2O and decreased in steps of 3 cmH2O up to 2 cmH2O or earlier if the patient had signs of respiratory distress. Patients were monitored with catheters for esophageal and gastric pressure measurements, with the T-piece was used close to the tube to measure tracheal pressure during an airway occlusion and a pneumotachograph for flow measurements. Data was recorded for all support levels to esophageal, gastric, and tracheal pressures, also hemodynamic data and ventilatory pattern. The adjustment of mechanical ventilation was classified as adequate assistance, overassistance and underassistance according to pre-established criteria. Results: Two hundred and ten periods were analyzed with different pressures of support and 49% of these periods were overassistance, while 3,8% these periods were underassistance. At baseline, while patients were still ventilatory assistance set by assistance staff, 48,2% had overassistance. Due to the low incidence of periods with underassistance, the variables accurancy has not been evaluated. The variable breathing pattern that was more accurate diagnosing overassistance was the respiratory rate (90% sensitivity and specificity of 88 % when the respiratory rate was less than 17 breaths per minute). Other variables of the breathing pattern did not show high accuracy although esophageal P0.1 (sensitivity 81 % and specificity of 70 % when P0.1 <= 1,9) and tracheal P0.1 (sensitivity 81 % and specificity of 70 % when P0.1 <= 2,1) were high accuracy diagnosing overassistance. Conclusion: The occurrence of overassistance was significantly higher than underassistance. The respiratory rate below 17 was the variable breathing pattern more accurate to predict overassistance. The esophageal and tracheal P0.1 also had high accuracy but lower than the respiratory rate
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Gene Expression patterns in High-Altitude Pulmonary Edema: A Gene Microway AnalysisKrause, Lauren Kendall 25 March 2008 (has links)
Multiple modulating genes and environmental factors have been implicated in the pathogenesis of high-altitude pulmonary edema (HAPE). However, at the present time, there exists an incomplete understanding of the molecular mechanisms and pathways which underlie constitutional susceptibility. Genome-wide measurements of gene expression in peripheral blood mononuclear cells (PBMCs) were performed using microarray technology. Comparison of gene expression profiles of HAPE-susceptible and resistant individuals resulted in the identification of several previously undescribed candidate genes. RhoA and Rho-kinase (ROCK), regulators of vascular smooth muscle contraction, were differentially regulated in the HAPE-susceptible cohort, as compared to both HAPE-resistant patients with acute mountain sickness (AMS+) and healthy controls (p=0.0014; p=0.0020). Furthermore, biological pathways involving RhoA and Rho-kinase were strongly upregulated in subjects with HAPE. These findings represent the first description of the RhoA/Rho-kinase signaling pathway in HAPE. Currently, few pharmacologic therapies have been demonstrated to be effective in the prevention and treatment of HAPE. The results of this study provide early evidence that Fasudil, a selective Rho-kinase inhibitor, may represent a novel therapeutic intervention effective in the prevention and/or treatment of high-altitude pulmonary edema.
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