Objetivo: Estudar o efeito da monitorização contínua da oximetria de pulso (SpO2) durante o teste de caminhada de 6 minutos (TC6m), na detecção da hipoxemia induzida pelo exercício, em pacientes com sintomas respiratórios. Métodos: Os pacientes realizaram testes de função pulmonar e TC6m. A saturação e a freqüência cardíaca foram determinadas por um oxímetro de pulso e os dados transferidos simultaneamente para um computador através de telemetria. Comparamos a menor saturação atingida durante o teste com os valores da SpO2 obtidos imediatamente após o TC6m. Também foram comparadas as diferenças clínico funcionais dos pacientes agrupados de acordo com a presença de dessaturação (SpO2 repouso – SpO2 no exercício 4%) e SpO2 88%. Resultados: Foram estudados 452 pacientes (236 homens, 61 ± 13 anos). A capacidade vital forçada (CVF), o volume expiratório forçado no primeiro segundo (VEF1), a relação VEF1/CVF e a capacidade de difusão pulmonar (DCO) foram respectivamente 65,8 ± 18,6% do previsto, 52,6 ± 23,7% do previsto, 62,8 ± 18,8% e 51,7 ± 20,9% do previsto. A média da SpO2 mínima registrada com auxílio de telemetria durante o TC6m foi de 89,9 ± 6,5% e da SpO2 no final do teste foi de 91,1 ± 6,5% (p<0,001). Em 241 pacientes (53,3%) ocorreu dessaturação no TC6m. Foram observados dois padrões diferenciados de dessaturação durante o exercício: um grupo de pacientes dessaturou no início do TC6m e recuperou a SpO2 antes do final do mesmo (57 pacientes, 23,7% dos pacientes que dessaturaram) e o outro grupo apresentou queda da SpO2 persistente até o final do exercício. A SpO2 basal e os valores de função pulmonar foram significativamente mais altos no grupo de pacientes com o primeiro padrão de dessaturação. A SpO2 foi 88% em 148 pacientes; em 26 destes (17,6%) níveis de SpO2 88% foram detectados somente durante o TC6m. Conclusão: Nosso estudo demonstra que a mensuração contínua da SpO2 durante o TC6m é melhor que a mensuração da SpO2 imediatamente após o teste para detectar dessaturação induzida por exercício. / Objective: To study the effect of continuous measurement of pulse oximetry (SpO2) during six-minute walk test (6MWT) on detection of exercise induced hypoxemia in patients with respiratory complaints. Methods: Patients performed lung function tests and 6MWT. SpO2 and pulse rate were obtained by a pulse oximeter and continuously transferred to a computer using telemetry. The lowest saturation reached during the test was compared with the SpO2 measured immediately after the 6MWT. We also compared functional and clinical differences of patients grouped according to desaturation (rest SpO2 - exercise SpO2 4%) and SpO2 88%. Results: We studied 452 patients (236 men, 61 ± 13 years old). Mean forced vital capacity (FCV), forced expiratory volume in 1 s (FEV1), FEV1/FCV and pulmonary diffusion capacity (DLCO) were 65.8 ± 18.6% of predicted, 52.6 ± 23.7% of predicted, 62.8 ± 18.8% and 51.7 ± 20.9% of predicted, respectively. Mean of lowest SpO2 registered using telemetry during 6MWT was 89.9% ± 6.5% and at the end of test 91.1% ± 6.5% (p<0.001). Desaturation was observed in 241 patients (53.3%). There were two different patterns of desaturation: SpO2 decrease at the beginning of the 6MWT with recovery before the test end (57 patients, 23.7% of the patients with desaturation) and SpO2 decrease maintained at the end of exercise. Rest SpO2 and lung function values were significantly higher in patients with the first desaturation pattern. SpO2 88% was observed in 148 patients; in 26 of these cases (17.6%) SpO2 88% levels were only detected during the 6MWT. Conclusion: Continuous SpO2 measuring is better than SpO2 measurement performed immediately after 6MWT in detecting exercise induced desaturation.

As dilatações vasculares intrapulmonares (DVIP) constituem a anormalidade vascular pulmonar mais freqüente e a principal causa de hipoxemia grave em hepatopatas. A associação de doença hepática, aumento do gradiente alvéoloarterial de oxigênio e DVIP é chamada de "síndrome hepatopulmonar". O objetivo principal deste estudo foi verificar se os níveis de DVIP aferidos por ecocardiografia com contraste estão relacionados à intensidade de shunt intrapulmonar, medida por dois diferentes métodos: cintilografia com 99mTc-MAA e gasometria com O2 a 100%. Foram estudados 28 candidatos a transplante hepático portadores com DVIP identificadas e graduadas por ecocardiografia conforme escala semi-quantitativa (graus I a IV). A idade média foi de 47,5 anos, e a doença hepática foi classificada como Child-Pugh B na maioria dos casos (60,7%). A intensidade das DVIP foi classificada como I, II, III e IV em 13 (46,4%), 9 (32,1%), 2 (7,1%) e 4 (14,3%) casos, respectivamente. Dos 28 pacientes, 21 (75%) tiveram quantificação de shunt pelo método cintigráfico e gasométrico, 6 (21,4%) apenas pelo método cintigráfico e 1 caso (3,6%) pelo método gasométrico apenas. A PaO2 média entre os pacientes com DVIP graus I e II por ecocardiografia foi 89,1 ± 11,0mmHg, enquanto naqueles com DVIP classificadas como graus III e IV foi 74,7 ± 13,2mmHg (p = 0,01). A média dos valores de shunt por cintilografia nos 27 pacientes submetidos ao exame foi 14,9 ± 9,0% do débito cardíaco (mínimo 6,9% e máximo 39%), sendo 11,7 ± 3,8% nos pacientes com DVIP graus I e II, e 26,3 ± 9,7% nos pacientes com DVIP graus III e IV (p = 0,01). A média dos valores de shunt pelo teste com O2a 100% foi 9,8 ± 3,9%, sendo 8,3 ± 2,3% nos pacientes com DVIP graus I e II, e 16,3 ± 2,6% nos pacientes com DVIP graus III e IV (p < 0,001). Observou-se uma relação estatisticamente significativa entre a graduação de DVIP por ecocardiografia e o valor de shunt aferido por gasometria com O2 a 100% (rs = 0,609, p < 0,01) e por cintilografia (rs = 0,567, p < 0,001). Observou-se relação estatisticamente significativa entre os valores de shunt medidos por cintilografia e aqueles medidos por gasometria com O2 a 100% nos 21 pacientes que se submeteram à quantificação de shunt pelos 2 métodos (rs = 0,666, p < 0,001). A avaliação semi-quantitativa do grau de DVIP por ecocardiografia apresentou correlação moderada a boa com os valores de shunt aferidos pelos dois outros métodos estudados, sendo que a melhor correlação foi observada com o teste com O2 a 100%. / Intrapulmonary vascular dilatations (IPVD) are the most common pulmonary vascular abnormality and the main cause of acute hypoxemia in patients with severe liver disease. The association of liver disease, increased alveolar-arterial oxygen gradient and IPVD is known as "hepatopulmonary syndrome". The chief aim of this study was to determine whether IPVD levels, as determined by contrast echocardiography, are related to intrapulmonary shunt intensity, as measured by Tc- 99m MAA scintigraphy and by 100% oxygen gasometry. Twenty-eight IPVD patients, all candidates for liver transplant, were studied. IPVD were identified using echocardiography and graded on the semiquantitative scale (levels I to IV). The mean age was 47.5 years. Liver disease was classified as Child-Pugh B in 60.7% of cases. IPVD intensity was classified as level I, II, III and IV in 13 (46.4%), 9 (32.1%), 2 (7.1%) and 4 (14.3%) cases, respectively. Of the 28 patients, shunt intensity was determined using both scintigraphy and gasometry in 21 patients (75%), by scintigraphy only in 6 (21.4%) and by gasometry only in 1 (21.4%). Mean PaO2 was 89.1 ± 11.0mmHg among level I and II patients and 74.7 ± 13.2mmHg among level III and IV patients (p = 0.01). The mean shunt by scintigraphy was 14.9 ± 9.0% of cardiac output (minimum 6.9% and maximum 39%), being 11.7 ± 3.8% among level I and II patients and 26.3 ± 9.7% among level III and IV patients (p = 0.01). The mean shunt by gasometry was 9.8 ± 3.9%, being 8.3 ± 2.3% among level I and II patients and 16.3 ± 2.6% among level III and IV patients (p < 0.001). There was a significative correlation between IPVD level and shunt intensity: rs = 0.609; p < 0.01 by gasometry and rs = 0.567; p < 0.001 by scintigraphy. In those patients undergoing both tests, a significant relation was found between shunt intensity as measured by scintigraphy and by gasometry: rs = 0.666; p < 0.001. Hypoxemic individuals had significantly higher levels of intrapulmonary vascular dilatation than did nonhypoxemic individuals. Semiquantitative evaluation of IPVD level showed moderate to good correlation with shunt intensity under each of the two methods used, with the better correlation being found under 100% oxygen gasometry.

Objetivo: Estudar o efeito da monitorização contínua da oximetria de pulso (SpO2) durante o teste de caminhada de 6 minutos (TC6m), na detecção da hipoxemia induzida pelo exercício, em pacientes com sintomas respiratórios. Métodos: Os pacientes realizaram testes de função pulmonar e TC6m. A saturação e a freqüência cardíaca foram determinadas por um oxímetro de pulso e os dados transferidos simultaneamente para um computador através de telemetria. Comparamos a menor saturação atingida durante o teste com os valores da SpO2 obtidos imediatamente após o TC6m. Também foram comparadas as diferenças clínico funcionais dos pacientes agrupados de acordo com a presença de dessaturação (SpO2 repouso – SpO2 no exercício 4%) e SpO2 88%. Resultados: Foram estudados 452 pacientes (236 homens, 61 ± 13 anos). A capacidade vital forçada (CVF), o volume expiratório forçado no primeiro segundo (VEF1), a relação VEF1/CVF e a capacidade de difusão pulmonar (DCO) foram respectivamente 65,8 ± 18,6% do previsto, 52,6 ± 23,7% do previsto, 62,8 ± 18,8% e 51,7 ± 20,9% do previsto. A média da SpO2 mínima registrada com auxílio de telemetria durante o TC6m foi de 89,9 ± 6,5% e da SpO2 no final do teste foi de 91,1 ± 6,5% (p<0,001). Em 241 pacientes (53,3%) ocorreu dessaturação no TC6m. Foram observados dois padrões diferenciados de dessaturação durante o exercício: um grupo de pacientes dessaturou no início do TC6m e recuperou a SpO2 antes do final do mesmo (57 pacientes, 23,7% dos pacientes que dessaturaram) e o outro grupo apresentou queda da SpO2 persistente até o final do exercício. A SpO2 basal e os valores de função pulmonar foram significativamente mais altos no grupo de pacientes com o primeiro padrão de dessaturação. A SpO2 foi 88% em 148 pacientes; em 26 destes (17,6%) níveis de SpO2 88% foram detectados somente durante o TC6m. Conclusão: Nosso estudo demonstra que a mensuração contínua da SpO2 durante o TC6m é melhor que a mensuração da SpO2 imediatamente após o teste para detectar dessaturação induzida por exercício. / Objective: To study the effect of continuous measurement of pulse oximetry (SpO2) during six-minute walk test (6MWT) on detection of exercise induced hypoxemia in patients with respiratory complaints. Methods: Patients performed lung function tests and 6MWT. SpO2 and pulse rate were obtained by a pulse oximeter and continuously transferred to a computer using telemetry. The lowest saturation reached during the test was compared with the SpO2 measured immediately after the 6MWT. We also compared functional and clinical differences of patients grouped according to desaturation (rest SpO2 - exercise SpO2 4%) and SpO2 88%. Results: We studied 452 patients (236 men, 61 ± 13 years old). Mean forced vital capacity (FCV), forced expiratory volume in 1 s (FEV1), FEV1/FCV and pulmonary diffusion capacity (DLCO) were 65.8 ± 18.6% of predicted, 52.6 ± 23.7% of predicted, 62.8 ± 18.8% and 51.7 ± 20.9% of predicted, respectively. Mean of lowest SpO2 registered using telemetry during 6MWT was 89.9% ± 6.5% and at the end of test 91.1% ± 6.5% (p<0.001). Desaturation was observed in 241 patients (53.3%). There were two different patterns of desaturation: SpO2 decrease at the beginning of the 6MWT with recovery before the test end (57 patients, 23.7% of the patients with desaturation) and SpO2 decrease maintained at the end of exercise. Rest SpO2 and lung function values were significantly higher in patients with the first desaturation pattern. SpO2 88% was observed in 148 patients; in 26 of these cases (17.6%) SpO2 88% levels were only detected during the 6MWT. Conclusion: Continuous SpO2 measuring is better than SpO2 measurement performed immediately after 6MWT in detecting exercise induced desaturation.

As dilatações vasculares intrapulmonares (DVIP) constituem a anormalidade vascular pulmonar mais freqüente e a principal causa de hipoxemia grave em hepatopatas. A associação de doença hepática, aumento do gradiente alvéoloarterial de oxigênio e DVIP é chamada de "síndrome hepatopulmonar". O objetivo principal deste estudo foi verificar se os níveis de DVIP aferidos por ecocardiografia com contraste estão relacionados à intensidade de shunt intrapulmonar, medida por dois diferentes métodos: cintilografia com 99mTc-MAA e gasometria com O2 a 100%. Foram estudados 28 candidatos a transplante hepático portadores com DVIP identificadas e graduadas por ecocardiografia conforme escala semi-quantitativa (graus I a IV). A idade média foi de 47,5 anos, e a doença hepática foi classificada como Child-Pugh B na maioria dos casos (60,7%). A intensidade das DVIP foi classificada como I, II, III e IV em 13 (46,4%), 9 (32,1%), 2 (7,1%) e 4 (14,3%) casos, respectivamente. Dos 28 pacientes, 21 (75%) tiveram quantificação de shunt pelo método cintigráfico e gasométrico, 6 (21,4%) apenas pelo método cintigráfico e 1 caso (3,6%) pelo método gasométrico apenas. A PaO2 média entre os pacientes com DVIP graus I e II por ecocardiografia foi 89,1 ± 11,0mmHg, enquanto naqueles com DVIP classificadas como graus III e IV foi 74,7 ± 13,2mmHg (p = 0,01). A média dos valores de shunt por cintilografia nos 27 pacientes submetidos ao exame foi 14,9 ± 9,0% do débito cardíaco (mínimo 6,9% e máximo 39%), sendo 11,7 ± 3,8% nos pacientes com DVIP graus I e II, e 26,3 ± 9,7% nos pacientes com DVIP graus III e IV (p = 0,01). A média dos valores de shunt pelo teste com O2a 100% foi 9,8 ± 3,9%, sendo 8,3 ± 2,3% nos pacientes com DVIP graus I e II, e 16,3 ± 2,6% nos pacientes com DVIP graus III e IV (p < 0,001). Observou-se uma relação estatisticamente significativa entre a graduação de DVIP por ecocardiografia e o valor de shunt aferido por gasometria com O2 a 100% (rs = 0,609, p < 0,01) e por cintilografia (rs = 0,567, p < 0,001). Observou-se relação estatisticamente significativa entre os valores de shunt medidos por cintilografia e aqueles medidos por gasometria com O2 a 100% nos 21 pacientes que se submeteram à quantificação de shunt pelos 2 métodos (rs = 0,666, p < 0,001). A avaliação semi-quantitativa do grau de DVIP por ecocardiografia apresentou correlação moderada a boa com os valores de shunt aferidos pelos dois outros métodos estudados, sendo que a melhor correlação foi observada com o teste com O2 a 100%. / Intrapulmonary vascular dilatations (IPVD) are the most common pulmonary vascular abnormality and the main cause of acute hypoxemia in patients with severe liver disease. The association of liver disease, increased alveolar-arterial oxygen gradient and IPVD is known as "hepatopulmonary syndrome". The chief aim of this study was to determine whether IPVD levels, as determined by contrast echocardiography, are related to intrapulmonary shunt intensity, as measured by Tc- 99m MAA scintigraphy and by 100% oxygen gasometry. Twenty-eight IPVD patients, all candidates for liver transplant, were studied. IPVD were identified using echocardiography and graded on the semiquantitative scale (levels I to IV). The mean age was 47.5 years. Liver disease was classified as Child-Pugh B in 60.7% of cases. IPVD intensity was classified as level I, II, III and IV in 13 (46.4%), 9 (32.1%), 2 (7.1%) and 4 (14.3%) cases, respectively. Of the 28 patients, shunt intensity was determined using both scintigraphy and gasometry in 21 patients (75%), by scintigraphy only in 6 (21.4%) and by gasometry only in 1 (21.4%). Mean PaO2 was 89.1 ± 11.0mmHg among level I and II patients and 74.7 ± 13.2mmHg among level III and IV patients (p = 0.01). The mean shunt by scintigraphy was 14.9 ± 9.0% of cardiac output (minimum 6.9% and maximum 39%), being 11.7 ± 3.8% among level I and II patients and 26.3 ± 9.7% among level III and IV patients (p = 0.01). The mean shunt by gasometry was 9.8 ± 3.9%, being 8.3 ± 2.3% among level I and II patients and 16.3 ± 2.6% among level III and IV patients (p < 0.001). There was a significative correlation between IPVD level and shunt intensity: rs = 0.609; p < 0.01 by gasometry and rs = 0.567; p < 0.001 by scintigraphy. In those patients undergoing both tests, a significant relation was found between shunt intensity as measured by scintigraphy and by gasometry: rs = 0.666; p < 0.001. Hypoxemic individuals had significantly higher levels of intrapulmonary vascular dilatation than did nonhypoxemic individuals. Semiquantitative evaluation of IPVD level showed moderate to good correlation with shunt intensity under each of the two methods used, with the better correlation being found under 100% oxygen gasometry.

Orientador: Carlos Alfredo Joly / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-12T20:33:26Z (GMT). No. of bitstreams: 1 Brigitte_PriscilaAugusta_M.pdf: 2206000 bytes, checksum: 45f6665ec05b449a5637ed3193764cac (MD5) Previous issue date: 2008 / Resumo: Foram estudados aspectos ecofisiológicos da germinação de Hedychium coronarium J. König e suas características quanto à anatomia e à reserva das sementes. O principal foco foi o estudo de seu comportamento sob diferentes condições de oxigenação, sendo estes os tratamentos: normoxia, hipoxia e anoxia. Trata-se de uma espécie exótica, invasora de ambientes brejosos, nos quais há, periódica e naturalmente, uma restrição na disponibilidade de oxigênio dissolvido no solo em virtude da saturação hídrica que ocorre nestas áreas. Sob tais condições, Hedychium apresenta vantagem competitiva e impede a regeneração das plantas nativas. Atualmente presente em praticamente toda a América, é uma espécie originária da Ásia, trazida inicialmente com fins ornamentais, mas hoje é também utilizada como planta medicinal, dentre outras aplicações já dadas à espécie. As sementes utilizadas foram coletadas no Núcleo Picinguaba, do Parque Estadual da Serra do Mar, Ubatuba-SP. Os testes de germinação compararam suas respostas à luz, à alternância de temperaturas e à disponibilidade de oxigênio e determinaram a longevidade das sementes. Também foi verificada a viabilidade das sementes através do teste com tetrazólio. Em relação ao estudo dos tecidos de reserva, foram feitos cortes anatômicos em sementes submetidas a diferentes condições de oxigenação, com posterior coloração com diferentes substâncias, com diferentes afinidades, para verificar quais as reservas presentes e verificar possível diferença quanto ao consumo das mesmas de acordo com o tratamento recebido pela semente durante o processo de germinação. Os resultados demonstraram que a espécie germina indiferente à luz, ou seja, é fotoblástica neutra, e tem sua germinação retardada, porém não diminuída, sob temperaturas que simulam as condições de inverno da região de coleta das sementes utilizadas neste estudo. As sementes mostraram boa viabilidade até cerca de um ano após a dispersão, sendo que, após esse período, a taxa de germinação caiu sensivelmente. Embora esta espécie tolere bem condições de pouca disponibilidade de oxigênio e seja capaz de colonizar ambientes que apresentem esta característica com sucesso, seu melhor desempenho em relação à germinação, ocorre sob condições drenadas e de boa aeração. Os estudos anatômicos indicaram que o processo de germinação foi iniciado sob privação de oxigênio, porém não foi viável pelo período testado (30 dias), pois provocou a morte das sementes. As sementes apresentam dois tipos de tecidos de reservas, perisperma e endosperma, de acordo com o esperado para a família (Zingiberaceae), porém de ocorrência conhecida apenas para poucos grupos de plantas. A composição dos tecidos indica que sua principal reserva é composta por polissacarídeos, sendo amido o principal, encontrado tanto no perisperma, como no endosperma, e proteínas dispersas no citoplasma das células do endosperma. / Abstract: Ecophysiological aspects of Hedychium coronarium J. König and its characteristics concerning anatomy and seeds storage were studied aiming to understand its behavior under different oxygenation conditions, with the following treatment: normoxia, hypoxia e anoxia. This is an exotic species, invasive of water logging environments, where there is, regular and naturally, a restriction on the availability of dissolved oxygen in the soil, because of water saturation in these areas. Under such conditions, the competitive advantage of Hedychium prevents the regeneration of native plants. Currently present in almost all of America, it is a species originated in Asia, initially brought with ornamental purposes, but today is also used as a medicinal plant, among other applications already given to the species. The seeds used were collected in Ubatuba-SP, at "Núcleo Picinguaba", from PESM. Tests for germination compared their responses to light, the alternation of temperatures and availability of oxygen and determine the seeds' longevity. The viability of seeds was also verified through the test with tetrazolium. Regarding the study of storage tissues, anatomical cuts were made in seeds subjected to different conditions of oxygenation, with subsequent staining with different substances, with different affinities, to check the present storages and check possible difference in regard to their consumption according to the treatment received by the seed during germination. The results have shown that the species germinates indifferent to light, i.e, it is a neutral photoblastic, and it has its germination delayed, but not decreased, under temperatures that simulate the winter conditions of the region where the seeds used in this study were collected. The seeds resist with good viability until about a year after the dispersion, when the germination rate falls significantly.Although well able to tolerate low availability of oxygen and capable of colonizing environments that successfully present this characteristic, its best performance concerning germination occurs under conditions of good aeration and drained conditions. Anatomical studies indicate that the process of germination was initiated, but not viable for the testing period (30 days), under this condition. The seeds feature two types of storage tissue, perisperm and endosperm, according to the expected for the family (Zingiberaceae), but occurring for only a few groups of plants. The composition of tissues indicates that its main storage is composed of polysaccharides, being starch the main one, found both in perisperm and endosperm, and protein scattered in the cytoplasm of cells in the endosperm. / Mestrado / Mestre em Biologia Vegetal

Studies were undertaken to determine the cardiac and ventilatory responses of restrained and unrestrained rainbow trout (Salmo gairdneri) to changes in inspired oxygen and carbon dioxide tensions. The role of blood oxygen carrying capacity in the control of ventilation was investigated, as well as the location and innervation of oxygen receptors activated by hypoxia. Ventilation volume (Vg) was measured directly in restrained fish using a ventilation chamber that separated inspired from expired water, the latter being collected in a graduated cylinder. In receptor localization experiments a wooden tongue depressor held vertically in the buccal cavity in the median plane divided water flows to the gills on each side of the fish. Thus, one set of gills could be irrigated with hyperoxic water to maintain arterial oxygen tension, while hypoxic water was passed over the other set of gills. Blood samples were obtained from cannulae implanted in both the dorsal aorta and right common cardinal vein. Vg increased in hypercapnea (inspired CO₂ tension (PICO₂) 0.5-2.0 kPa) due to increased "stroke volume (frequency remained constant), with higher levels of Vg recorded at higher C0₂ tensions. In fish exposed to PICO₂ levels of 0.5 and 0.9 kPa, raising the inspired oxygen tension (PIO₂) to 60.4 kPa eliminated the ventilatory response to hypercapnea. Hyperoxia had little or no effect on ventilatory responses to (PICO₂) levels of 1.5 and 2.0 kPa. Ventilation volume was inversely related to blood oxygen content (CaO₂) in trout. CaO₂ decreased and Vg increased during hypercapnea (PICO₂ 0.8 kPa), hypoxia (PIO₂12.4 kPa) and anaemia (haematocrit reduced from 22.3% to 14.3%), while CaO₂ increased and Vg decreased during hyperoxic hypercapnea (PIO₂ 60.4 kPa, PICO₂ 0.8 kPa). Increased Vg during hypercapnea is attributed to hypoxaemia produced by Bohr and Root off-shifts which result from increased blood CO₂ tension and reduced blood pH. Oxygen uptake remained constant during all experimental trials, indicating that the manoeuvre of increasing Vg is effective in relieving adverse effects of hypoxaemia. The significance of elevated Vg as a short-term adaptation to hypoxaemia is discussed, Heart rate decreased and ventilation increased in unrestrained fish exposed to gradual hypoxia (PIO₂ decreased from 20 kPa to 4 kPa) at 7°C and 16°C. The initial heart rate of fish acclimated to 16°C was higher than that of the 7°C group, but at the lowest level of PIO₂, heart rates of both groups dropped to the same level. Thus, the cardiac chronotropic response to hypoxia in trout is temperature independent. Receptors causing hypoxic bradycardia are located in the dorsal region of the first gill arch. Hypoxic bradycardia was eliminated by removing the first gill arch, or by sectioning the branches of cranial nerves IX and X innervating the arch. Blood flow through the arch does not appear to be necessary for this response, since ligation of the arch at its ventral insertion on the body wall did not affect hypoxic bradycardia. The pseudobranch has no role in cardiac control since interrupting the flow of blood through, and deafferentation of, the pseudobranch had no effect on the cardiac response to hypoxia. The biological significance of hypoxic bradycardia, and ventilatory-circulatory interaction during hypoxia, are discussed. Ventilatory responses to hypercapnea and hypoxia were unchanged after bilateral section of the nerves to the first gill arch. Receptors in the first gill arch thus have no role in control of ventilation during either hypercapnea or hypoxia. Possible locations for receptors responsible for control of ventilation are discussed. / Science, Faculty of / Zoology, Department of / Graduate

Oxygen deprivation can be pathological for many organisms, including humans. Consequently, there are several biologically and economically relevant negative impacts associated with oxygen deprivation. Developing an understanding of which genes can influence survival of oxygen deprivation will enable the formulation of more effective policies and practices. In this dissertation, genes that influence adult anoxia survival in the model metazoan system, C. elegans, are identified and characterized. Insulin-like signaling, gonad function and gender have been shown to influence longevity and stress resistance in the soil nematode, C. elegans. Thus, either of these two processes or gender may influence anoxia survival. The hypothesis that insulin-like signaling alters anoxia survival in C. elegans is tested in Aim I. The hypotheses that gonad function or gender modulates anoxia survival are tested in Aim II. Insulin-like signaling affects anoxia survival in C. elegans. Reduction of insulin-like signaling through mutation of the insulin-like receptor, DAF-2, increases anoxia survival rates in a gpd-2/3 dependent manner. The glycolytic genes gpd-2/3 are necessary for wild-type response to anoxia, and sufficient for increasing anoxia survival through overexpression. Gonad function and gender both affect anoxia survival in C. elegans. A reduction of ovulation and oocyte maturation, as measured by oocyte flux, is associated with enhanced anoxia survival in all cases examined to date. Reduction of function of several genes involved in germline development and RTK/Ras/MAPK signaling reduce ovulation and oocyte maturation while concurrently increasing anoxia survival. The act of mating does not influence anoxia survival, but altering ovulation through breeding or chemical treatment does. The male phenotype also increases anoxia survival rates independent of genotype. These studies have identified and characterized over ten different genotypes that affect adult survival of anoxia in C. elegans. Before these studies were conducted, there were no genes known to influence adult anoxia survival in C. elegans. Furthermore, these studies have begun to uncouple mechanisms of longevity and stress resistance.

Orientador: Selma Giorgio / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-07T16:29:57Z (GMT). No. of bitstreams: 1 Silva_WagnerWelberArraisda_D.pdf: 2543782 bytes, checksum: d4c1a96c9dabbacb3872004b7f017fb8 (MD5) Previous issue date: 2006 / Resumo: Nas infecções com o parasito do gênero Leishmania a incapacidade da célula hospedeira destruir os amastigotas leva à lesão a cronificar-se. A persistência e o aumento da carga parasitária levam a formação de um granuloma macrofágico, que resulta em áreas de inadequada perfusão e conseqüente alteração do microambiente tecidual. Assim, neste trabalho avaliamos durante a evolução da lesão de camundongos infectados com L amazonensis a expressão das proteínas HIF-1a e VEGF, que respondem ao estresse microambiental. Paralelamente, investigamos protocolos terapêuticos com HBO que modulem a curva de crescimento da lesão em modelos animais da infecção por Leishmania amazonensis. A expressão de HIF-1a ocorreu nas fases iniciais, crônicas e fases finais da infecção murina com L. amazonensis. Nas lesões cutâneas de camundongos da linhagem BALB/c a expressão de HIF-1a foi de localização difusa na lesão, enquanto que a expressão de HIF- 1a em lesões cutâneas da linhagem C57Bl/6 foi em forma de cluster restrita aos macrófagos parasitados. A expressão de VEGF nas lesões de ambas linhagens de camundongos foi discreta durante todo o período experimental e não aumentou com o tempo de infecção. O tratamento com oxigênio hiperbárico mostrou efeito deletério sobre formas promastigotas aumentando o acúmulo de lipídios citoplasmáticos e o nível de apoptose. O oxigênio hiperbárico diminuiu os efeitos patológicos e modulou a resposta imune. Concluímos que a expressão de HIF-1a durante a evolução da lesão leishmaniótica não está diretamente relacionada à expressão de VEGF e pode ser resultado de múltiplos fatores, que incluem fatores hipóxicos e não hipóxicos. Sugerimos também que o tratamento hiperbárico é capaz de modular a resposta imunológica e diminuir a progressão da lesão durante a leishmaniose murina / Abstract: The incapacity of host cell in killing amastigotes during Leishmania infections causes to chronic lesions. The increase of parasite burden leaves to macrophage accumulation and consequently granuloma formation that result in inadequate perfusion and tissue microenvironment alterations. Thus, in this work we evaluated the HIF-1a and VEGF expression, proteins that responses for environmental stress, during the course of L.amazonensis infection. We also investigated protocols for hyperbaric oxygen therapy that module the lesion progress in animal models infected with L. amazonensis. HIF-1a expression occurred in the early, chronic and in final stages of murine infection with L. amazonensis. BALB/c mice lesions showed a homogeneous expression of HIF-1a while footpads from C57Bl/6 mice showed HIF-1a expression restrict in clusters of heavily infected macrophages. The VEGF expression was not correlated to the evolution of lesion or the HIF-1 production in both stains. The hyperbaric oxygen treatment showed deleterious effects on promastigotes increasing cytoplasmtic lipids and apoptosis level. The HBO decreased pathological effects and modulated the immune response. The results suggest that the HIF-1a expression during lesion progress induced by L.amazonensis in both murine strains is the result of multiple factors, including hypoxic and non hypoxic factors. There is no direct relation between HIF-1a and VEGF expression during experimental cutaneous leishmaniasis. We also indicated that hyperbaric oxygen therapy was able to modulate immune response and decrease of lesion progress during murine leishmaniasis / Doutorado / Doutor em Parasitologia

Publicación a texto completo no autorizada por el autor / Desarrolla el aislamiento de los flavonoides de la hoja de Erythroxylum coca y determina la capacidad antioxidante y su actividad neuroprotectora en rodajas de cerebro de rata Holtzman mediante el método de anoxia reoxigenación. El extracto hidroalcohólico al10%, de hojas fue tratado y analizado por cromatografía en papel, reacciones de coloración y espectrofotometría ultravioleta. La actividad antioxidante fue evaluada utilizando la actividad secuestradora del DPPH y la actividad neuroprotectora al reducir los niveles de Lactato deshidrogenasa y malondialdehido. Se obtuvo una capacidad antioxidante expresada como porcentaje de inhibición de 96,802 %, y la reducción de los niveles de Lactato deshidrogenasa fue de 67,28% y 48,59% para la concentración de 0,068 % y 0,094 % (p<0,05) del extracto de flavonoides de hoja de coca extraido con acetato de etilo. Se concluye que, los flavonoides presentes en la hoja de Erythroxylum coca tiene actividad neuroprotectora en rodajas de cerebro de ratas. / Tesis

Indiana University-Purdue University Indianapolis (IUPUI) / High choline uptake and increased choline kinase activity have been reported in many cancers. This has motivated the use of choline as a biomarker for tumor imaging. Tumors in general are heterogeneous in nature with respect to oxygen tension. There are regions of hypoxia and normoxia that are expected to have different metabolism but regulation of choline metabolism under hypoxia is poorly understood. It is important to clarify the status of choline metabolism in hypoxic microenvironment as it will have an impact on potential of choline as a cancer biomarker. The primary goal was to determine the status of choline phosphorylation in hypoxic cancer cells and its effect on uptake of choline. This was examined by tracer studies in cancer cells exposed to hypoxia. It was observed that hypoxia universally inhibits choline uptake /phosphorylation in cancer cells. Decreased choline phosphorylation resulted in transient uptake of choline radiotracers in cultured cancer cells and 9L tumors suggesting potential problem in using choline as a biomarker for cancers in hypoxic microenvironment. To investigate the mechanism behind decrease in choline phosphorylation, steady state levels of choline metabolites were measured and choline kinase catalyzed choline phosphorylation step was found to be rate-limiting in PC-3 cells. This suggested that modulation in choline kinase levels can alter choline metabolism in hypoxic cancer cells. Expression and activity assays for choline kinase revealed that choline kinase expression is down-regulated in hypoxia. This regulation involved transcriptional level mediation by HIF1 at the conserved HRE7 site in choline kinase promoter. To further understand the importance of down-regulation of choline kinase in hypoxia, stable prostate cancer cell lines over-expressing choline kinase were generated. Effect of over-expression of choline kinase in hypoxia was evaluated in terms of malignant phenotypes like proliferation rate, anchorage independent growth and invasion potential. Both over-expression of choline kinase and hypoxia had a pronounced effect on malignant phenotypes of prostate cancer cells. Further study showed that increased choline kinase activity and hypoxic tumor microenvironment are important for progression of early-stage, androgen-dependent LNCaP prostate cancer cells but confer little survival advantage in undifferentiated, androgen-independent PC-3 prostate cancer cells.