Made available in DSpace on 2015-01-26T13:21:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-08-21Bitstream added on 2015-01-26T13:30:38Z : No. of bitstreams: 1 000795302.pdf: 290369 bytes, checksum: 58bda7f024f4cce4b41311ea8576a046 (MD5) / Introdução: Não está claro na literatura se os valores do índice bispectral (BIS) e da taxa de supressão do traçado de eletroencefalograma (TS), estão relacionados à disfunção cognitiva pós-operatória (DCPO). Objetivo: Avaliar os valores de BIS e TS e sua relação com a DCPO após cirurgia de revascularização do miocárdio (CRM) em pacientes submetidos a anestesia com sevoflurano (SEVO) guiada pelo BIS. Tipo de estudo: Observacional prospectivo. Local do estudo: Hospital de ensino. Pacientes: Noventa pacientes adultos programados para CRM com ou sem circulação extra-corpórea (CEC). Intervenções: A anestesia foi induzida com propofol, remifentanil e atracúrio e mantida com concentrações expiradas de SEVO (ETSEVO) em valores de concentração alveolar mínima (CAMSEVO) adaptada à idade, tendo como alvo valores de BIS de 40-60. O Mini-Exame do Estado Mental (MEEM) para avaliação cognitiva dos pacientes foi aplicado na admissão hospitalar e três meses após a cirurgia. Variáveis estudadas: Os valores de BIS, TS, ETSEVO e CAMSEVO foram registrados a cada 5 minutos durante o procedimento. Redução de um desvio padrão (DP) ou mais no MEEM basal foi definida como DCPO. Resultados: A proporção de DCPO foi de 40%. Os pacientes foram alocados em dois grupos: com (n = 36) ou sem DCPO (n = 54). Não houve diferença significativa na incidência de DCPO entre os pacientes que foram submetidos à CRM com ou sem CEC (p = 1,0). Quanto às características dos pacientes, somente os valores de índice de massa corporal (IMC) foram maiores no grupo sem DCPO (p = 0,009). Valores médios de BSR, ETSEV e MACSEV foram maiores no grupo sem DCPO (p < 0,05). Em uma análise multivariada, valores menores de TS (Razão de Chances-RC 0,008, Intervalo de Confiança-IC 95% [0,001-0,53], p = 0,02), CAMSEVO (RC 0,001, IC 95% [0,001-0,08], p = 0,008), ETSEVO (RC 0,03, IC 95% [0,002-0,66], p = 0,02) e ... / Background: It is still controversial whether bispectral index (BIS) and burst suppression ratio (BSR) values are related to postoperative cognitive dysfunction (POCD). OBJECTIVE: To evaluate BIS and BSR values and their relation to POCD after coronary artery bypass grafting (CABG) surgery in patients undergoing BIS-guided sevoflurane (SEVO) anaesthesia. DESIGN: Prospective, observational study. SETTING: Teaching hospital. PATIENTS: Ninety adult patients scheduled for on- or off-pump CABG surgery. INTERVENTIONS: Anaesthesia was induced with propofol, remifentanil and atracurium and maintained with end-tidal SEVO (ETSEVO) at age-adapted minimum alveolar concentration (MACSEVO) targeting BIS values of 40-60. Mini-Mental State Examination (MMSE) for cognitive assessment of the patients was applied on hospital admission and at 3 months after surgery. MAIN OUTCOME MEASUREMENTS: BIS, BSR, ETSEVO and MACSEVO values were recorded every 5 minutes during the procedure. A decrease of 1 standard deviation or more from the basal MMSE was defined as POCD. RESULTS: The POCD proportion was 40%. The patients were allocated into two groups: with POCD (n=36) or no POCD (n=54). There was no difference of POCD incidence between patients who were submitted to on- versus off-pump CABG (P=1.0). With regard to the patient’s characteristics, only body mass index (BMI) was higher in the no-POCD group (P=0.009). Mean BSR, ETSEVO and MACSEVO values were higher in the no-POCD group (P<0.05). In a multivariable analysis, lower values of BSR (odds ratio-OR 0.008; 95%CI [0.001-0.53]; P=0.02), MACSEVO (OR 0.001; 95%CI [0.001-0.08]; P=0.008), ETSEVO (OR 0.03; 95%CI [0.002-0.66]; P=0.02) and BMI (OR 0.82; 95%CI [0.70-0.96]; P=0.01) were independent predictors of risk for POCD incidence. BIS values did not influence POCD incidence (OR 1.0; 95%CI [0.95-1.11]; P=0.40). CONCLUSION: BIS-guided SEVO anaesthesia titrated to a range between 40 and 60 is not a predictive factor ...

Made available in DSpace on 2018-07-27T18:26:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-06-03. Added 1 bitstream(s) on 2018-07-27T18:30:37Z : No. of bitstreams: 1 000873683.pdf: 2162420 bytes, checksum: 8020e5fc7625f96c8be7397dc9a7ec86 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / A fagocitose, por células dendríticas (CD), de células apoptóticas (CA) infectadas induz a produção de TGF-β, IL-6 e IL-23, propiciando um microambiente com condições ideais para diferenciação de células Th17. Recentes resultados obtidos por nosso grupo demonstram que a fagocitose, por CD, de células apoptóticas infectadas resulta também na produção de altos IL- 1 e PGE2. A presença destes mediadores solúveis foi capaz de induzir a diferenciação de células Th17, in vitro, no entanto, a inibição da síntese de PGE2, pelo tratamento com inibidor não seletivo da COX (Indometacina), resultou no aumento da porcentagem destes linfócitos. Neste estudo foi avaliado o efeito da fagocitose de células apoptóticas infectadas com Escherichia coli (CA+Ec) na diferenciação de células Th17 in vivo e o efeito de PGE2 neste processo. A instilação de animais com CA+Ec, induziu a produção das citocinas IL-6, IL-1β e TGF-β no pulmão, o que sugere que a presença de CA+Ec é capaz de gerar um microambiente favorável para induzir a diferenciação Th17. A instilação de CA+Ec promoveu a diferenciação de células Th17, assim como a produção de IL-17. Porém, o tratamento com inibidor de COX resultou no aumento na porcentagem e no número de células Th17 no pulmão. A presença destas células resultou no aumento na porcentagem de neutrófilos no tecido pulmonar que parece refletir na diminuição da carga bacteriana recuperada do pulmão, quando comparado com animais que não receberam o tratamento. Assim, o conjunto destes resultados sugere que a fagocitose de CA+E. coli promove a diferenciação de células Th17. No entanto, a secreção de PGE2, pela fagocitose destas CA+Ec suprime a diferenciação e/ou migração de células Th17 para o pulmão, levando a inibição do recrutamento de neutrófilos e aumento da suscetibilidade às infecções pulmonares. / The phagocytosis of infected-apoptotic cells (iAC) by dendritic cells (DC) induces the production of TGF-β, IL-6 and IL-23, providing a microenvironment to Th17 cell differentiation. Recent data obtained in our group showed that the phagocytosis of infected- apoptotic cells by CD also results in high levels of IL-1β and PGE2. The presence of these soluble mediators was able to induce the differentiation of Th17 cells, in vitro. However, the inhibition of PGE2 synthesis, by non-selective COX inhibitor (indomethacin), result the increase of percentage of Th17. In this study, it was evaluated the effect of phagocytosis of infected-apoptotic cells (AC+E. coli) during the Th17 cell differentiation, in vivo, and the effect of PGE2 in this process. The inoculation of AC+ Ec (in.) into lung induced the production of IL-6, IL-1β and TGF-β in lung, suggesting that the presence of AC+Ec is able to induce a microenvironment favorable to Th17 cell differentiation. The instillation of AC+Ec induced the differentiation of Th17 cells. However, the treatment of the animals with COX inhibitor resulted in an increase in the percentage, and number, of Th17 cells in the lung. The presence of these cells increased in the percentage of neutrophils in the lung and that apparently reflect in bacterial clearance from the lung, compared to animals that received no treatment. Taken all together, the phagocytosis of AC+Ec promotes the Th17 cell differentiation. However, the production of PGE2 by efferocytosis suppresses the differentiation and / or migration of Th17 cells to the lungs, impair the recruitment of neutrophils and increase the susceptibility to lung infections. / FAPESP: 11/17611-7

Orientador: Suzana Erico Tanni Minamoto / Coorientador: Victor Zuniga Dourado / Banca: Irma de Godoy / Banca: Oliver Augusto Nascimento / Resumo: Introdução: Exacerbação aguda (EA) é uma importante causa de perda de funções em pacientes que sofrem de doença pulmonar obstrutiva crônica (DPOC). Afeta negativamente a qualidade de vida, a função pulmonar, a fraqueza muscular, a utilização dos recursos da saúde e a sobrevida. Entretanto, o exercício físico realizado durante a exacerbação pode melhorar a qualidade de vida e a capacidade física do paciente. Nesse contexto, o presente estudo visa avaliar a influência da realização do exercício físico em pacientes hospitalizado por exacerbação da DPOC (EADPOC). Objetivo: O presente estudo visa avaliar os efeitos do exercício fisico aeróbio de curta duração nos pacientes hospitalizados por exacerbação aguda de DPOC no escore da dispneia, na qualidade de vida e na capacidade física. Pacientes e Métodos: Vinte e dois pacientes foram randomizados em dois grupos, o grupo controle que recebeu o tratamento clínico padrão e o grupo de intervenção que realizou o treinamento de exercício físico juntamente com os cuidados clínicos. Os pacientes foram submetidos às seguintes avaliações após 48 horas da hospitalização e após um mês da alta: espirometria, avaliação nutricional, distância percorrida no teste de caminhada de seis minutos (DP6), qualidade de vida, ansiedade e depressão, índice de BODE e intensidade de dispneia. O programa de exercício físico foi composto por treinamento aeróbio em esteira ergométrica, duas vezes ao dia, por 15 minutos cada sessão até o período da alta hospitalar. Resultados: O domínio impacto e o escore total da qualidade de vida apresentaram maior incremento no grupo intervenção em relação ao grupo controle (p < 0,001) quando comparado os momentos. Houve melhora de ambos os grupos após um mês de alta hospitalar no domínio atividade quando comparado ao momento basal, mas sem diferença entre os grupos. Além disso, apenas o grupo de intervenção apresentou... / Abstract: Introduction: Acute Exacerbation (AE) is an important cause of impairment of function in chronic obstructive pulmonary disease (COPD) patients. Negatively affects the quality of life, lung function, muscle weakness, the use of health resources and survival. However, physical exercise performed during the exacerbation can improve the quality of life and the physical capacity of the patient. In this context, this study aims to evaluate the influence of aerobic exercise in hospitalized COPD patients with exacerbation (AECOPD). Objective: To evaluate the effects of short duration aerobic exercise in AECOPD on dyspnea score, quality of life and exercise capacity. Patients and Methods: Twenty-two patients were randomized in two groups; the control group received standard medical treatment and the intervention group that performed aerobic exercise training. All patients performed spirometry, nutritional assessment, distance covered on the six-minute walk test (6MWD), quality of life (Saint George Respiratory Questionnaire- SGRQ), anxiety and depression ( The Hospital Anxiety and Depression Scale), BODE index and intensity of dyspnea (Baseline Dyspnea Index and Modified Medical Research Council Score) after 48 hours of hospitalization and after one month of discharge. The exercise program consisted of aerobic training on a treadmill twice a day for 15 minutes until to the discharge. Results: The impact domain and the total score of quality of life showed a higher increase in the intervention group compared to the control group (p<0.001) when compared to the moments. Both groups showed improvement in the activity domain of SGRQ after one month of hospital discharge, but they did not show difference between groups. Furthermore, only the intervention group showed significant improvement in the symptom domain of SGRQ (p<0.001) and baseline dyspnea index (p=0.006) after one month. 6MWD and BODE did not show difference between ... / Mestre

Made available in DSpace on 2014-06-11T19:23:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-12-10Bitstream added on 2014-06-13T20:11:39Z : No. of bitstreams: 1 martins_mta_me_botfmvz.pdf: 1314468 bytes, checksum: 684105e46814a1ad77b0ce2b64c9c305 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Os ovinos são muito susceptíveis às doenças pulmonares, sendo a broncopneumonia mais frequente e responsável por desencadear intensa resposta inflamatória, sistêmica e local, principalmente neutrofílica. O objetivo deste estudo foi analisar a resposta inflamatória sistêmica e pulmonar de ovinos portadores de broncopneumonia moderada e grave e as atividades neutrofílicas através dos testes estimulado (NBT-E) ou não (NBT-NE), com Tetrazólio Nitroazul, no sangue periférico e no lavado traqueobrônquico. Para isso, por exame clínico, 50 ovinos foram selecionados e subdivididos em três grupos: G1 – animais sadios (n=19); G2 – portadores de broncopneumonia moderada (n=21); e G3 – portadores de broncopneumonia grave (n=10). A resposta inflamatória sistêmica foi avaliada pela interpretação do exame físico, leucograma e fibrinogênio plasmático. A resposta inflamatória local, por sua vez, pela associação das alterações respiratórias ao exame físico específico e à celularidade do lavado traqueobrônquico (LTB). A atividade dos neutrófilos sanguíneos dos grupos G1 e G2 foi percentualmente semelhante e a daqueles do LTB nula. O G3 apresentou diminuição da porcentagem de neutrófilos sanguíneos ativados e atividade de NBT significativa dessas células no LTB. Nestas condições experimentais, os resultados demonstraram que o exame clínico minucioso e a associação dos sinais clínicos são fidedignos para a graduação dos estágios da broncopneumonia; a gravidade das respostas inflamatórias, sistêmica e local, é dependente do grau de comprometimento pulmonar e há tendência à leucocitose neutrofílica e ao aumento do número de células nucleadas no LTB conforme a gravidade da doença; há redução do número de neutrófilos ativos circulantes e presença destes no LTB nas broncopneumonias graves / Ovine are highly susceptible to lung diseases, being bronchopneumonia the most frequent and responsible for triggering intense inflammatory response, systemic and local, mainly neutrophilic. The aim of this study was analyze lung and systemic inflammation of moderate and severe bronchopneumonia affected ovine and the neutrophilic activity through stimulated (S-NBT) and not stimulated (NS-NBT) assays with Nitroblue Tetrazolium, on peripheral blood and on tracheobronchial lavage (TBL). For that, 50 animals were selected and divided based on clinical examination into three groups: G1 – healthy animals (n=19), G2 – moderate bronchopneumonia (n=21), and G3 – severe bronchopneumonia (n=10). The systemic inflammation was evaluated by the interpretation of physics parameters, white blood cells (WBC) counts and plasma fibrinogen. The local inflammatory response, in turn, by the association of respiratory abnormalities on physical examination and the TBL cellularity. The systemic neutrophils activity from G1 and G2 were similar, and the lung neutrophils activity was null. The G3 showed a reduction of the activated systemic neutrophils rate, and expressive activity of these cells on the TBL. On these experimental conditions the results showed that a detailed clinical examination associated with the clinical signs is a reliable method for the graduation of the bronchopneumonia severity; the gravity of the local and systemic inflammation relies on the lung commitment degree and there is a tendency to neutrophilic leukocytosis and increase of the nucleated cells number on the TBL, associated with the illness severity; there is a reduction of active circulating neutrophils and its presence on the TBL when the animal is stricken by severe bronchopneumonia

Made available in DSpace on 2016-06-07T17:12:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-02-27. Added 1 bitstream(s) on 2016-06-07T17:16:45Z : No. of bitstreams: 1 000864067.pdf: 1027434 bytes, checksum: 3ba974f6664e049332120cf69ad53682 (MD5) / Foi realizado estudo transversal para avaliar e comparar a associação entre estresse oxidativo e estado inflamatório e suas relações com a força muscular, a massa muscular sistêmica, a capacidade funcional de exercício e o estado geral de saúde em tabagistas, pacientes com doença pulmonar obstrutiva crônica (DPOC) leve/moderado e controles não tabagistas. Foram avaliados 32 tabagistas ativos (carga tabágica >10 anos/maço) sem DPOC, 32 pacientes com DPOC leve/moderado [tabagistas ativos ou ex-tabagistas (carga tabágica >10 anos/maço)] e 32 indivíduos não tabagistas. Todos os indivíduos foram submetidos à avaliação clínica e do estado tabágico, espirometria pré e pósbroncodilatador, oximetria de pulso e as concentrações de mediadores inflamatórios [proteína C-reativa (PCR), interleucina (IL) 6, receptores do fator de necrose tumoral alfa (TNFR1 e TNFR2)] e indicadores de estresse oxidativo [produtos finais de glicação avançada (AGEs) e receptor solúvel do produto final de glicação (sRAGE)] foram avaliadas no soro. Foi realizada avaliação da composição do corpo por bioimpedância, da força muscular periférica por dinamometria, da capacidade funcional de exercício (distância percorrida em seis minutos) e da avaliação do estado geral de saúde, por meio do Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) e da Escala Hospitalar de Ansiedade e Depressão (HAD). Tabagistas (p<0,001) e pacientes com DPOC (p<0,001) apresentaram valores superiores de AGEs quando comparados aos controles. Não houve diferença estatisticamente significante entre tabagistas e pacientes com DPOC. As concentrações de sRAGE não diferiram entre os grupos (p=0,92). Tabagistas (p=0,01) e pacientes com DPOC (p=0,01) apresentaram valores superiores da PCR em comparação aos controles, sem diferenças nas demais comparações. As concentrações de IL6 (p=0,07) e TNFR1 (p=0,07) não diferiram entre os grupos. Os valores... / The aim of this study was to evaluate the association between oxidative stress and inflammatory markers and their relationship with muscle strength, systemic muscle mass, exercise capacity, quality of life in smokers, mild/moderate COPD patients and nonsmokers controls. Were evaluated 32 active smokers (smoking history> 10 pack/years) without COPD, 32 mild/moderate COPD patients [current smokers or former smokers (smoking history> 10 pack/years) and 32 nonsmokers. All individuals underwent to medical and smoking status evaluations, spirometry pre and post-bronchodilator and pulse oximetry. The concentration of inflammatory mediators [C-reactive protein (CRP), interleukin (IL) 6, and tumor necrosis factor-alpha receptors (TNFR1 and TNFR2)] and indicators of oxidative stress [advanced glycation end-products (AGEs) and soluble receptors for advanced glycation end-products (sRAGE)] were measured in serum. We assessed body composition by bioimpedance, peripheral muscle strength by dynamometry, exercise capacity (six minutes walk distance) and the health status through the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Hospital Anxiety and Depression Scale (HAD). Smokers (p<0.001) and COPD patients (p<0.001) had higher values of AGEs when compared to controls there was no statistically significant difference between smokers and COPD patients. The sRAGE concentrations did not differ between groups (p=0.92). Smokers (p=0.01) and patients with COPD (p=0.01) showed higher values of CRP compared to controls, there was no statistical significant difference between smokers and COPD groups. The concentrations of IL-6 (p=0.07) and TNFR1 (p=0.07) did not differ between groups. Regarding concentrations of TNFR2, COPD patients showed higher values when compared to smokers (p=0.004) and controls (p=0.004). We identified positive association of smoking (p=0.04), CRP (p=0.03) and IL6 (p=0.03) with the concentrations of AGEs. The ...

Orientador: José Reinaldo Cerqueira Braz / Banca: Paulo do Nascimento Junior / Banca: Maria Angela Tardelli / Resumo: Introdução: Não está claro na literatura se os valores do índice bispectral (BIS) e da taxa de supressão do traçado de eletroencefalograma (TS), estão relacionados à disfunção cognitiva pós-operatória (DCPO). Objetivo: Avaliar os valores de BIS e TS e sua relação com a DCPO após cirurgia de revascularização do miocárdio (CRM) em pacientes submetidos a anestesia com sevoflurano (SEVO) guiada pelo BIS. Tipo de estudo: Observacional prospectivo. Local do estudo: Hospital de ensino. Pacientes: Noventa pacientes adultos programados para CRM com ou sem circulação extra-corpórea (CEC). Intervenções: A anestesia foi induzida com propofol, remifentanil e atracúrio e mantida com concentrações expiradas de SEVO (ETSEVO) em valores de concentração alveolar mínima (CAMSEVO) adaptada à idade, tendo como alvo valores de BIS de 40-60. O Mini-Exame do Estado Mental (MEEM) para avaliação cognitiva dos pacientes foi aplicado na admissão hospitalar e três meses após a cirurgia. Variáveis estudadas: Os valores de BIS, TS, ETSEVO e CAMSEVO foram registrados a cada 5 minutos durante o procedimento. Redução de um desvio padrão (DP) ou mais no MEEM basal foi definida como DCPO. Resultados: A proporção de DCPO foi de 40%. Os pacientes foram alocados em dois grupos: com (n = 36) ou sem DCPO (n = 54). Não houve diferença significativa na incidência de DCPO entre os pacientes que foram submetidos à CRM com ou sem CEC (p = 1,0). Quanto às características dos pacientes, somente os valores de índice de massa corporal (IMC) foram maiores no grupo sem DCPO (p = 0,009). Valores médios de BSR, ETSEV e MACSEV foram maiores no grupo sem DCPO (p < 0,05). Em uma análise multivariada, valores menores de TS (Razão de Chances-RC 0,008, Intervalo de Confiança-IC 95% [0,001-0,53], p = 0,02), CAMSEVO (RC 0,001, IC 95% [0,001-0,08], p = 0,008), ETSEVO (RC 0,03, IC 95% [0,002-0,66], p = 0,02) e ... / Abstract: BACKGROUND: It is still controversial whether bispectral index (BIS) and burst suppression ratio (BSR) values are related to postoperative cognitive dysfunction (POCD). OBJECTIVE: To evaluate BIS and BSR values and their relation to POCD after coronary artery bypass grafting (CABG) surgery in patients undergoing BIS-guided sevoflurane (SEVO) anaesthesia. DESIGN: Prospective, observational study. SETTING: Teaching hospital. PATIENTS: Ninety adult patients scheduled for on- or off-pump CABG surgery. INTERVENTIONS: Anaesthesia was induced with propofol, remifentanil and atracurium and maintained with end-tidal SEVO (ETSEVO) at age-adapted minimum alveolar concentration (MACSEVO) targeting BIS values of 40-60. Mini-Mental State Examination (MMSE) for cognitive assessment of the patients was applied on hospital admission and at 3 months after surgery. MAIN OUTCOME MEASUREMENTS: BIS, BSR, ETSEVO and MACSEVO values were recorded every 5 minutes during the procedure. A decrease of 1 standard deviation or more from the basal MMSE was defined as POCD. RESULTS: The POCD proportion was 40%. The patients were allocated into two groups: with POCD (n=36) or no POCD (n=54). There was no difference of POCD incidence between patients who were submitted to on- versus off-pump CABG (P=1.0). With regard to the patient's characteristics, only body mass index (BMI) was higher in the no-POCD group (P=0.009). Mean BSR, ETSEVO and MACSEVO values were higher in the no-POCD group (P<0.05). In a multivariable analysis, lower values of BSR (odds ratio-OR 0.008; 95%CI [0.001-0.53]; P=0.02), MACSEVO (OR 0.001; 95%CI [0.001-0.08]; P=0.008), ETSEVO (OR 0.03; 95%CI [0.002-0.66]; P=0.02) and BMI (OR 0.82; 95%CI [0.70-0.96]; P=0.01) were independent predictors of risk for POCD incidence. BIS values did not influence POCD incidence (OR 1.0; 95%CI [0.95-1.11]; P=0.40). CONCLUSION: BIS-guided SEVO anaesthesia titrated to a range between 40 and 60 is not a predictive factor ... / Mestre

Indiana University-Purdue University Indianapolis (IUPUI) / Rationale: CD55 down-regulation on airway epithelium correlates with local complement activation observed in hypoxia-associated pulmonary diseases. Therefore, we hypothesized that induction of hypoxia inducible factor 1 alpha (HIF-1α) in hypoxic airway epithelium, mediates CD55 down-regulation. Methods: Chetomin and HIF-1α siRNA inhibited HIF-1α in hypoxic SAECs (1% O2), and mice lungs (10% O2). DMOG mediated HIF-1α stabilization in normoxic SAECs and mice lungs (21% O2). Transduction of SAECs with AdCA5 also stabilized HIF-1α. CD55 and CA9 transcripts were measured by RT-PCR. CD55 and HIF-1α protein expression was assessed by western blots. In vivo, immunohistochemistry (IHC) confirmed CD55 and HIF-1α expression. C3a and C5a levels in bronchoalveolar lavage fluid (BALF) were measured by ELISA. Results: HIF-1α was induced in 6 hour hypoxic SAECs (p<0.05), but CD55 transcripts were repressed (p&lt;0.05). CD55 protein was down-regulated by 72 hours (p<0.05). CA9 transcripts were elevated by 48 -72 hours (p<0.05 and p<0.01, respectively). In vivo, CD55 transcripts and protein were down- regulated by 24 hours post-hypoxia (p<0.01) which corresponded to complement activation (p<0.05) in BALF. However, CA9 was increased (p<0.01). Chetomin (100nM) treatment in 6 hour hypoxic SAECs, recovered CD55 transcripts (p<0.01) and protein (p<0.05), but down-regulated CA9 (p<0.05). Similarly, in vivo chetomin (1mg/ml) treatment recovered CD55 protein (p<0.01) and down-regulated CA9 (p<0.01). Silencing HIF-1α (50nM) in hypoxic SAECs restored CD55 transcripts by 6 hours (p<0.05), and protein expression by 24 hours (p<0.05). However, CA9 was repressed (p<0.01). In vivo silencing of HIF-1α (50µg) restored CD55 protein expression (p<0.05) but down-regulated CA9 (p<0.05). Stabilizing HIF-1α in normoxic SAECs via DMOG (1µM), down-regulated CD55 transcripts and protein (p<0.01), but increased CA9 within 6-24 hours (p<0.05 and p<0.01, respectively). HIF-1α induction by DMOG (1mg/ml) in normoxic mice lungs down-regulated CD55 transcripts (p<0.01) and protein (p<0.01), but increased CA9 (p<0.05). Induction of HIF-1α in AdCA5 (50 PFUs/cell) transduced normoxic SAECs, resulted in CD55 protein down-regulation (p<0.05), but increased CA9 (p<0.001). Conclusions: HIF-1α down-regulates CD55 on airway epithelium. Targeting this mechanism may be a potential therapeutic intervention for attenuating complement activation in hypoxic pulmonary diseases.

The lungs are the primary organ of the respiratory system. Their main function is to provide freshly breathed oxygen (O²) to the blood capillaries, while taking carbon dioxide (CO²) from them and expelling it to the atmosphere. Lung conditions such as Acute Respiratory Distress Syndrome (ARDS), Idiopathic Pulmonary Fibrosis (IPF), Coronavirus Disease (COVID-19), etc., cause impaired gas exchange that is life-threatening. In this dissertation, I developed 1) a physiology-based dynamic pulmonary system to study the lung normo- and patho-physiology, and 2) a model-based constrained optimization algorithm to do parameter estimation in order to non-invasively assess lung health. The goals of this work are 1) to accomplish a respiratory personalized medicine example for clinical decision support, and 2) to further the understanding of respiratory physiology, via a mechanistic physiology-based model and system identification techniques. The mechanistic model presented in this thesis comprises six subsystems: 1) a lung mechanics module that computes airflow transport from the mouth and nose to the alveoli (gas exchange units), 2) a respiratory muscles and rib cage mechanics module that simulates the effect of the respiratory muscle contraction on the lungs and the rib cage, 3) a microvascular exchange system that describes fluid (water) and mass (albumin and globulin) transport between the pulmonary capillaries and the alveolar space, 4) an alveolar elasticity module that computes alveolar compliance as a function of the pulmonary surfactant concentration and the elastic properties of the lung tissue fiber, 5) a pulmonary blood circulation that describes blood transport from the heart to the pulmonary system, and 6) a gas exchange system that describes O² and CO² transport between blood in the pulmonary capillaries and gas in the alveoli. Each subsystem was developed based on the latest knowledge of lung physiology and was validated using patient data when available or published and validated physiology-based models. To our knowledge, the combined six-module model would be the most rigorous and expansive lung dynamic model in the literature. This dynamic respiratory system can be used to describe human breathing under healthy and diseased conditions. The model can readily be used to test different what-if scenarios to find the optimal therapy for the patients. Further, I tailor the proposed lung model and adopt system identification techniques for noninvasive assessment of the lung mechanical properties (resistance and compliance) and the patient breathing effort. Pulmonary syndromes or diseases, such as ARDS and COPD (Chronic Obstructive Pulmonary Disease) evoke alterations in lung resistance and compliance. These two parameters reflect, by and large, the state of health and functionality of the respiratory system. Hence tracking these two parameters can lead to better disease diagnosis and easier monitoring of the respiratory disease progression. For spontaneously breathing patients on ventilatory support, the estimation of the lung parameters is challenging due to the added patient’s breathing effort. This dissertation presents a model-based nonlinear constrained optimization algorithm to estimate, breath-by-breath, the lung resistance, the lung compliance, as well as the patient breathing effort due to the respiratory muscle activity, using readily available non-invasive measurements (airway opening pressure and airflow).

No description available.

COPD is the third leading cause of death in the United States and is the sixth leading cause of death for low-to middle income countries (Downs & Appel, 2006; GOLD, 2011). COPD is a largely preventable disease due to the lifestyle factors that heavily contribute to disease onset and severity. Although traditionally COPD research has focused on health outcomes related to risk factors, compliance, comorbid psychological and physical conditions, and treatment interventions, a growing body of research suggests religious and spiritual factors may play an equally important role in health outcomes for several medical conditions, including pulmonary disease. However, studies of this kind have not specifically examined COPD nor have they examined the role of religious and spiritual beliefs in COPD management among ethnic minority patients. As such, the current study aimed to examine whether spiritual ethnic minority patients with COPD hold religious fatalistic attitudes and less active religious problem solving . A sample of 35 ethnic minority patients from the Louis. B. Stokes Cleveland VA Medical Center (LSCVAMC) Outpatient Pulmonary Clinic in Cleveland, OH. were recruited to participate in the study. Due to the acknowledgeable limitations of the present study, results are preliminary but convey associations between religious health fatalistic beliefs and religious problem solving approaches. Implications and areas of future study are discussed.