Dissertations / Theses on the topic 'Blood air'

Epidemiological evidence is limited regarding the effects of long-term exposure to traffic-related air pollution and to traffic noise on blood pressure (BP). This thesis aims at (a) assessing the long-term co-exposure to traffic-related air pollution and traffic noise and (b) evaluating and disentangling the associations of each of these trafficrelated environmental factors on hypertension, systolic and diastolic BP in the adult population of Girona city (Catalonia, Spain). We studied the spatial correlation between annual average levels of measured nitrogen dioxide (NO2) and modeled traffic noise levels (L24h and Lnight) at 83 outdoor residential locations in Girona city. We used data from the baseline examination (years 2003-2006) of a population-based cohort corresponding to 3836 participants aged 35-84. We assigned outdoor annual average levels of NO2 and traffic noise at the participants’ postal addresses with a land-use regression model and a traffic noise model, respectively. Indoor traffic Lnight levels at the bedrooms were estimated based on the noise protection elements at home. The correlation between NO2 and traffic noise was high and city area-dependent. NO2 and indoor traffic noise showed consistent and independent associations with both BP and hypertension. In contrast, the associations for NO2 could not be disentangled from those for outdoor traffic noise. We also identified potential susceptibility groups. This thesis adds to the limited evidence showing that long-term exposure to trafficrelated air pollution and to traffic noise are associated (and independently) with both BP and hypertension. Further studies are required to confirm these results.
L’evidència epidemiològica és limitada en relació als efectes de l’exposició prolongada a la contaminació atmosfèrica i al soroll provinents del trànsit amb la pressió arterial (PA). Aquesta tesi té com a objectiu (a) explorar l’exposició conjunta a la contaminació atmosfèrica i al soroll del trànsit a llarg termini i (b) avaluar i separar les associacions de cadascun d’aquests dos factors ambientals amb la hipertensió i la pressió sistòlica i diastòlica a la població adulta de la ciutat mediterrània de Girona (Catalunya, Espanya). Vam estudiar la correlació espacial entre els nivells anuals mitjans de diòxid de nitrogen (NO2) mesurat i del soroll de trànsit modelitzat (L24h and Lnit) a l’exterior de 83 localitzacions residencials. Vam utilitzar les dades de l’exploració basal (anys 2003- 2006) d’una cohort poblacional corresponents a 3836 participants de 35 a 84 anys. Vam assignar els nivells mitjans anuals exteriors de NO2 i de soroll de trànsit a les adreces postals residencials de cada participant amb un model de regressió de l’ús del sòl i un model de soroll de trànsit, respectivament. Els nivells interiors de Lnit de trànsit als dormitoris es van derivar en base a les proteccions contra el soroll a casa. La correlació entre l’NO2 i el soroll del trànsit era elevada i depenia de l’àrea de la ciutat. Ambdós l’NO2 i el soroll del trànsit s’associaven consistent i independentment amb la hipertensió i la PA. En canvi, les associacions per l’NO2 no es podien deslligar de les del soroll de trànsit exterior. També vam identificar factors de susceptibilitat potencials. Aquesta tesi incrementa l’evidència escassa sobre que l’exposició prolongada a la contaminació atmosfèrica i al soroll del trànsit s’associen, i independentment, tant amb la PA com amb la hipertensió. Es requereixen més estudis per confirmar aquests resultats.
La evidencia epidemiológica es limitada en relación a los efectos de la exposición prolongada a la contaminación atmosférica y al ruido procedentes del tráfico con la presión arterial (PA). Esta tesis tiene como objetivo (a) explorar la exposición conjunta a la contaminación atmosférica y al ruido del tráfico a largo plazo y (b) evaluar y separar las asociaciones de cada uno de estos dos factores ambientales con la hipertensión y la presión sistólica y diastólica en la población adulta de la ciudad mediterránea de Girona (Cataluña, España). Estudiamos la correlación espacial entre los niveles anuales medios de dióxido de nitrógeno (NO2) medido y de ruido de tráfico modelizado (L24h and Lnoche) en el exterior de 83 localizaciones residenciales. Utilizamos los datos de la exploración basal (años 2003-2006) de una cohorte poblacional correspondientes a 3836 participantes de 35 a 84 años. Asignamos los niveles medios anuales exteriores de NO2 y de ruido de tráfico a las direcciones postales residenciales de cada participante con un modelo de regresión del uso del suelo y un modelo de ruido de tráfico, respectivamente. Los niveles interiores de Lnoche de tráfico en los dormitorios se derivaron en base a las protecciones contra el ruido en casa. La correlación entre el NO2 y el ruido del tráfico era elevada y dependía del área de la ciudad. Ambos el NO2 y el ruido del tráfico se asociaban consistente e independientemente con la hipertensión y la PA. En cambio, las asociaciones para el NO2 no se podían desenredar de las del ruido de tráfico exterior. También identificamos factores de susceptibilidad potenciales. Esta tesis incrementa la evidencia escasa sobre que la exposición prolongada a la contaminación atmosférica y al ruido del tráfico se asocian, e independientemente, tanto con la PA como con la hipertensión. Se requieren más estudios para confirmar estos resultados.

Cupping therapy has become a popular method of alternative medicine. However, no quantitative measures on the effects of cupping therapy on blood flow and skin temperature have been examined. The purpose of this study was to determine the effects cupping therapy on skin temperature and blood flow of the tibial artery. A pre and posttest experimental design was used. Twenty healthy males (20.70 ? 2.83 years) participated. Blood flow and skin temperatures were measured prior to and following a cupping protocol. Blood flow from fire cupping decreased an average of -3%. The skin temperatures during fire cupping increased 0.14?C ? 0.30?C. Blood flow from air vacuum cupping increased an average of 5%. The skin temperatures during air vacuum cupping did not change. The results suggest that there is insufficient evidence for the use of cupping therapy for increasing blood flow and skin temperature.

The aims of this thesis are: 1) to evaluate the performance of low-cost air quality monitors to monitor long-term exposure in rural areas from low- and middle-income countries; 2) to identify the determinants of personal air pollution exposure among women from a semi-rural area in Mozambique; and 3) to evaluate the associations between long-term exposure to ambient air pollution and cardiometabolic health in adults from a peri-urban area in India. We used data from: an experimental study, an observational study, and a cross-sectional epidemiologic study (CHAI). Main results: 1) the performance of low-cost monitors is not reliable yet to replace more expensive research-grade monitors; 2) kerosene-based lighting increased personal air pollution exposure in women from Mozambique; 3) long-term air pollution is associated with elevated blood pressure in women from India; and 4) we found no evidence that long-term air pollution is associated with higher blood glucose levels in peri-urban India.
Els objectius d’aquesta tesi són: 1) avaluar el rendiment dels monitors de qualitat de l’aire de baix cost per monitoritzar l’exposició a llarg termini en àrees rurals en països de renda baixa o mitjana; 2) identificar els determinants de l’exposició personal a la contaminació de l’aire en dones d’una àrea semi-rural de Moçambic; i 3) avaluar les associacions a llarg termini entre l’exposició ambiental a la contaminació de l’aire i la salut cardiometabòlica en adults d’una àrea peri-urbana de la Índia. Hem utilitzat dades provinents de: un estudi experimental, un estudi observacional i un estudi epidemiològic transversal (CHAI). Resultats principals: 1) el rendiment de monitors de baix cost encara no és prou fiable per reemplaçar a monitors més cars i establerts en recerca; 2) la il·luminació amb querosè va incrementar l’exposició personal a la contaminació de l‘aire en dones de Moçambic; 3) l’exposició a llarg termini de la contaminació de l’aire està associada a una major pressió arterial en dones de la Índia; i 4) no hem trobat evidència que la exposició a la contaminació de l’aire estigui associada a nivells més alts de glucosa en sang a la Índia peri-urbana.

Pyrogens are substances that may induce fever in the human body. They can be parts of bacteria, virus or fungi and due to the reaction they may cause in the body, they are routinely looked for in the medical technology industries. A method called in vitro pyrogen test (IPT) has been developed to detect these pyrogens. It is based on the fever reaction in the human body and only requires blood in combination with a solution believed to contain pyrogens. If the result is positive, the production of cytokines is started. The cytokines of interest in the IPT method are those involved in the fever process and two of them are IL-1β and TNF-α, which are the cytokines used as markers of infection in this study. Since the production of cytokines is in proportion to the amount of pyrogens, the inflammation-inducing potential of the sample can be decided. Due to problems in standardizing the method, mainly because it handles with living blood cells, focus is still pointed at improving it. The aim of this study was to optimize parameters within the IPT method by analysing air samples taken in indoor surroundings believed to contain pyrogens. The different parameters included extraction of the filter from the air sampling, incubation of whole blood and sample extract and analysis of the incubation with ELISA (enzyme linked immunosorbent assay). More specific, some of the issues concerned extraction media, time and shaking intensity for the extraction, blood ratio for the whole blood incubation and cytokines suitable for the method. A possible approach for the IPT method, when analysing air samples containing pyrogens, was reached.
Pyrogener kallas ämnen som framkallar feber och de kan exempelvis bestå av hela eller delar av bakterier, virus eller svamp (fungi). En metod som kallas för in vitro pyrogen test (IPT) har utvecklats för att detektera dessa pyrogener. Metoden bygger på att en lösning som misstänks innehålla pyrogener får komma i kontakt med blod från en människa. Efter en inkubering på mellan 4-24 timmar har blodet reagerat på eventuella pyrogener och bildat cytokiner, där mängden cytokiner är proportionell mot mängden pyrogener. De intressanta cytokinerna i den här studien var IL-1β och TNF-α, som båda är involverade i feberprocessen. Det har varit svårigheter med att standardisera metoden, mycket beroende på att det är levande celler som hela metoden bygger på, så syftet med den här studien var att förbättra in vitro pyrogen test. Luftprover tagna i inomhusmiljöer som misstänks innehålla pyrogener har använts i försöken att optimera varje steg i processen. De olika stegen inkluderade extraktion av filter som använts vid luftprovtagningen, inkubering med helblod och provextrakt och analys av inkuberingen med ELISA (enzyme linked immunosorbent assay). Några av de parametrar som undersöktes gällde extraktionsmedium, skaktid och skakintensitet under extraktionen, blodförhållande under helblodsinkuberingen och lämpliga cytokiner för metoden. Studien resulterade i att en metodik, för att analysera luftprov innehållande pyrogener med in vitro pyrogen test, kunde tas fram.

Exposure to traffic-related air pollution (TRAP) has been associated with adverse health outcomes. Physical activity (PA) in polluted air may increase pollutant uptake and hence affect health. The main aim of this thesis is to determine the short-term health effects of TRAP in healthy participants and any possible modifying effect of PA. A crossover real-world exposure study was conducted which compared in 28 healthy participants lung, systemic, and blood pressure responses to four different exposure scenarios: two hours of exposure in a high and low TRAP environment, each at rest and in combination with intermittent moderate PA, that comprised alternating 15-minute rest and cycling intervals. The data was analysed by using mixed effect models for repeated measures. High levels of TRAP induced airway and systemic inflammatory responses, as well as increased blood pressure. Physical activity improved lung function and attenuated the blood pressure increase. Physical activity in high levels of TRAP also induced lung and systemic inflammation, and decreased the circulating levels of the brain-derived neurotrophic factor (BDNF). The short-term exposure to TRAP is associated with adverse health effects. Physical activity has beneficial effects on health, even when performed in high levels of TRAP. The clinical meaning of the decreases in BDNF as a response to the intermitted physical activity in the experimental setting and the more habitual physical activity in daily life remains unclear. This study also suggests that the health effects of traffic-related air pollution and physical activity are predominantly independent in high levels of TRAP.
L'exposició a la contaminació de l'aire relacionada amb el tràfic (CART) s'ha associate amb resultats adversos per a la salut. L'activitat física (AF) realitzada en ambients amb aire contaminat pot augmentar l'absorció de contaminants i amb això produir efectes en la salut. L'objectiu principal d'aquesta tesi va ser determinar els efectes en la salut de l’exposició a la CART a curt termini en participants sans així com qualsevol possible efecte modificador de l’AF. S’ha realitzat un estudi en disseny del creuament amb exposició del “món real” comparant en 28 participants sans les respostes pulmonars, sistèmics i de la pressió arterial en quatre escenaris diferents d'exposició: 2 hores d’exposició en un entorn d'alta i baixa CART, cadascun en repòs i en combinació amb AF moderada i intermitent, que consta de quatre intervals de 15 minuts de descans i ciclisme. Les dades es van analitzar utilitzant models d'efectes mixtes per a mesures repetides. Els nivells alts de CART van induïr una resposta inflamatòria sistèmica i de la via aèria, i un augment de la pressió arterial. L’AF va millorar la funció pulmonar i va atenuar l’augment de la pressió arterial. L’AF en alts nivells de CART també va induïr una inflamació pulmonar i sistèmica y una disminució dels nivells circulants del factor neurotròfic derivat del cervell (FNDC)1. L'exposició a curt termini a CART s'associa amb efectes adversos per a la salut. L’AF té efectes beneficiosos sobre la salut, encara quan es realitza en alts nivells de CART. El significat clínic de les disminucions en el FNDC com a resposta a l’AF intermitent en l'entorn experimental i l’AF més habitual de la vida quotidiana segueix essent poc clara. Aquest estudi també suggereix que els efectes sobre la salut de la CART i l’AF són predominantment independents dels nivells alts de CART. 1 també conegut com “BDNF”, de l'anglès “Brain-derived Neurotrophic Factor”.

Background: Carbon monoxide (CO) is a toxic gas, but it is also produced endogenously when haem is degraded. When produced in vivo, CO is believed to have positive biological effects. For example it activates the production of cyclic guanosine mono-phosphate and causes vasodilatation. CO is also believed to have anti-inflammatory properties by binding to Mitogen activated protein (MAP) kinase. Several studies in cells, mice and rats support this opinion regarding both the circulatory as well as the anti-inflammatory properties. However, studies in larger animals regarding circulatory effects have demonstrated contradictory results. The only study in humans regarding anti-inflammatory properties of CO could not demonstrate such effects. Methods: This thesis consists of four different models. In paper I a method for analysis of CO in blood was developed using gas chromatography. In paper II a porcine model was used to investigate the elimination time for CO. The pigs in paper II had a high concentration of CO administered via blood, and CO concentrations were followed over time and kinetically parameters calculated. Circulatory parameters were also measured to evaluate if there were any circulatory changes after CO administration. In paper III CO´s anti-inflammatory properties were investigated in an endotoxin-induced systemic inflammatory model in pigs. Paper III was a randomized study where one group inhaled CO and the other group served as controls. Plasma cytokine concentrations were measured and followed over time as an indication of the inflammatory state. In paper IV, CO concentrations in blood from blood donors at the Blood Centre in Umeå were investigated. The blood donors also completed a questionnaire about age, smoking history and other possible sources for exogenous contamination of CO in the blood. Results and conclusions: In paper I we developed a method suitable for analysis of low concentrations of CO in blood. The half-life of CO at levels of 250 µM in pigs was found to be 60 minutes. CO did not show anti-inflammatory effects after an endotoxin-induced systemic inflammation in pigs. In banked blood CO was present at concentrations up to six times higher than normal concentrations. This could be a risk when transfusing such blood to susceptible patients.

Screening complex biological specimens such as exhaled air, tissue, blood and urine to identify biomarkers in different forms of cancer has become increasingly popular over the last decade, mainly due to new instruments and improved bioinformatics. However, despite some progress, the identification of biomarkers has shown to be a difficult task with few new biomarkers (excluding recent genetic markers) being considered for introduction to clinical analysis. This review describes recent advances in gas chromatographic methods for the identification of biomarkers in the detection, diagnosis and treatment of cancer. It presents a general overview of cancer metabolism, the current biomarkers used for cancer diagnosis and treatment, a background to metabolic changes in tumors, an overview of current GC methods, and collectively presents the scope and outlook of GC methods in oncology.

This study investigated whether oxLDL and/or angiotensin (Ang) II signaling pathways mediate traffic-generated air pollution- exposure induced alterations in blood-brain barrier (BBB) integrity and permeability in a healthy wild type (C57Bl/6) mouse model; additionally, whether these outcomes are exacerbated by a high fat-diet investigated. An environmentally relevant concentration of a mixture of vehicle engine exhaust (MVE) was used. To investigate the hypotheses, 12 wk old male C57Bl/6 mice on either a high fat (HF) or low fat (LF) diet were randomly assigned to inhalational exposure of either filtered-air (FA) or 30 µg PM/m3 diesel exhaust + 70 µg PM/m3 gasoline exhaust (MVE) for 6 hr/day for 30 days. Additionally, we examined mechanisms involved in MVE-mediated alterations BBB integrity using a novel BBB co-culture in vitro model, consisting of mouse primary cerebral vascular endothelial cells on an apical transwell and astrocytes in the basal compartment, which was treated with plasma from the mice on our exposure study. Our in vivo exposure study results showed that MVE inhalation resulted in increased circulating plasma oxLDL and Ang II, compared to FA controls. Additionally, we observed increased cerebral microvascular expression of oxLDL receptors, LOX-1 and CD-36, and Ang II receptor subtype 1 (AT1) in MVE-exposed C57Bl/6 mice, which was further exacerbated with consumption of an HF diet. Increased signaling of both Ang II and oxLDL was associated with decreased BBB integrity, as evidenced by the concurrent reduction in expression of tight junction (TJ) protein claudin-5 and increased permeability of sodium fluorescein (Na-F) from the blood into the cerebral parenchyma. Our results suggest that possible mechanisms involved in oxLDL and/or Ang II-mediated alterations in BBB integrity include oxidative stress and upregulated expression and activity of matrix metalloproteinase (MMP)-9, which is associated with degradation of TJ proteins in the BBB. Our in vitro BBB co-culture results confirm our in vivo findings, as we observe increased BBB permeability (TEER) and decreased integrity (decreased expression of TJ proteins) in the endothelial (apical) layer when treated with plasma from MVE-exposed mice, which was further exacerbated when treated with plasma from MVE-exposed mice on an HF diet. Pre-treatment of the endothelial cells with the AT1 receptor antagonist, Losartan, prior to applying plasma, resulted in attenuation of the alterations observed in endothelial integrity in the BBB co-culture treated with plasma from either MVE+LF or MVE+HF animals. These results suggest Ang II – AT1 signaling mediate, at least in part, the alterations in the BBB integrity observed after exposure to MVE. Moreover, we observed that treatment of the endothelial (apical) layer with plasma from MVE-exposed animals resulted in increased production of inflammatory mediators interleukin-6 (IL-6) and transforming growth factor-β in the astrocyte media (basal compartment). Additionally, these same astrocytes also displayed increased production of angiotensin-converting enzyme (ACE) and also AT1 receptor mRNA expression, while showing decreased expression of the aryl hydrocarbon receptor (AhR) and glutathione peroxidase (GPx). Collectively, these results suggest that exposure to the ubiquitous environmental air pollutant, vehicle engine emissions, results in increased oxLDL and Ang II signaling in the cerebral microvasculature, which is associated with decreased vessel integrity and increased oxidative stress and inflammatory signaling in the CNS. The observed detrimental outcomes are even further exacerbated when coupled with the consumption of an HF diet.

Objetivo: checar se poluentes do ar urbano de São Paulo induzem alterações sangüíneas e cardiopulmonares. MM: camundongos Balb/c foram expostos por 7, 14, 21, 30 e 45 dias em 3 câmaras: Limpa (controle), Intermediária (seletiva ao PM) e Suja (ar externo). Após exposição, os animais foram ventilados (FlexiVent) e coletados dados de mecânica pulmonar, sangue, coração e pulmão. Foram registrados PM, CO, SO2 e NO2 diários. Resultados: aos 21 e 45 dias coincidentes com picos de poluição houve aumento da resistência de via aérea (45d p=0,012), leucocitose (21d p < 0,001 e 45d p=0,039) e vasoconstricção pulmonar (21d p=0,034) nos animais da Câmara Suja, sem alteração de coronárias. Nenhum poluente excedeu limites de qualidade de ar
Objective: verify if air pollution of São Paulo city induces alterations in blood and cardiopulmonary systems. MM: Balb/c mice were exposed during 7, 14, 21, 30 and 45 days to 3 chambers: Clean (control), Intermediate (PM only) and Dirty (external air). After exposure, animals were ventilated (FlexiVent) and collected lung mechanics data and blood, heart and lung. PM, CO, SO2 e NO2 were measured daily. Results: on day 21 and 45, coincidently to peak of pollutions, there was proximal airway resistance increase (45d p=0.012), leukocytosis (21d p < 0.001 and 45d p=0.039) and vasoconstriction of peribronchiolar arterioles (21d p=0.034) in animals of Dirty Chamber with no alterations of coronaries. Neither pollutants exceeded the standard limits

A constante exposição à poluição do ar continua acometendo a saúde das populações, resultando num aumento da morbidade e mortalidade decorrente de problemas respiratórios e cardiovasculares. O estudo é transversal, com o objetivo de avaliar as modificações na pressão arterial sistêmica, e pressão de pulso, em indivíduos do gênero masculino, jovens, expostos à poluição do tráfego no município de Santo André, região metropolitana da Grande São Paulo - Brasil. Os níveis horários diários de poluentes do ar obtidos junto a Companhia de Tecnologia de Saneamento Ambiental do Estado de São Paulo (CETESB), as informações sobre temperatura e precipitação foram obtidas junto ao Instituto Nacional de Meteorologia (INMET). Foi realizada a análise descritiva de todas as variáveis do estudo. Foi utilizado o modelo de equação linear, tendo como variáveis dependentes a pressão arterial sistólica (PAS), pressão arterial diastólica (PAD) e pressão de pulso (PP), os poluentes do ar como vaiáveis independentes, e como variáveis de controle a temperatura mínima, precipitação, período de trabalho e período do dia. Foram analisados 19 agentes de tráfego do município de Santo André. A média de idade do grupo estudado foi de 42,8 (dp = 5,2) anos, variando entre 32 e 51 anos. Quanto ao IMC, temos que a média do grupo estudado foi de 25,2 (dp = 2,8), variando entre 19,2 e 29,4. Observa-se que para cada aumento de um interquartil no nível de PM10 (34g/m3) a PAS aumenta em 1,35 mmHg (IC95%: 0,40; 2,30), a PAD horária aumenta em 1,35 mmHg (IC95%: 0,57; 2,13), e a PP horária aumenta em 1,35 mmHg (IC95%: 0,40; 2,30) na hora de exposição. Os agentes de tráfego no município de Santo André apresentaram aumento da PAS, PAD e PP com a exposição ao PM10 e do O3. Os agentes de tráfego apresentaram aumentos nos níveis da pressão arterial e pressão de pulso com a exposição a poluição do ar em Santo André
The constant exposition to air pollution continues to cause the populations health problems, and its result an increase of morbidity and mortality by respiratory and cardiovascular diseases. This is a cross-sectional study which aims to assess the modifications in the systemic blood pressure and the pulse pressure in young male individuals, exposed to the traffic pollution in Santo André city, metropolitan region of the Greater São Paulo in Brazil. The hourly daily levels of air pollutants were obtained from the Technology Institute for the Environment and Sanitation of São Paulo State (CETESB), the information by temperature and precipitation was obtained from the National Meteorology Office (INMET). There has been carried out a descriptive analysis of all variables of the study. The linear equation model has been used, having as dependent variables the systolic blood pressure (SBP), the diastolic blood pressure (DBP) and the pulse pressure (PP), the air pollutants as independent variables, and as control variables the minimum temperature, precipitation, working period and day time. A number of 19 traffic agents in Santo André city have been analysed. The average age of the studied group was of 42.8 (sd = 5.2) years old, ranging from 32 to 51 years old. Concerning the BMI, we have got the information that the average of the studied group was of 25.2 (sd = 2.8), ranging from 19.2 to 29.4. It is observed that for an interquartile range increased in PM10 (34g/m3), the SBP increases in 1.35 mmHg (CI95%: 0.40; 2.30), the DBP increases in 1.35 mmHg (CI95%: 0.57; 2.13), and the PP increases in 1.35 mmHg (CI95%: 0.40; 2.30) at the exposure time. The traffic agents in Santo André city presented increase of SBP, DBP and PP with the exposure to PM10 and to O3. The traffic agents from Santo André presented higher arterial blood pressure and pulse pressure levels associated with the air pollution exposure in Santo André city

Introduktion: Buller definieras som oönskat ljud. Uppfattningen av ett oönskat ljud är mycket individuellt. Det som anses vara oljud för en person, kan upplevas som icke-oljud för en annan person. Buller anses dock generellt som störande ljud och är vanligtvis något som varje individ stöter på under sin vardag som exempelvis på arbetsplatsen, skolan, eller i hemmet. Buller anses vara den miljöstörning som berör flest människor i Sverige. Det är ett växande problem och flygtrafik anses vara en av de mest genomgripande utomhusljudkällorna. Bullerproblem som är förknippade med flygtrafik är koncentrerade i områden nära flygplatser, vilket kan påverka flera tusentals boendes hälsa. Flygtrafikbuller har länge varit ett folkhälsoproblem och många människor som är bosatta i närheten av en flygplats har utvecklat ett antal negativa hälsoeffekter av flygtrafikbuller Syfte: Att undersöka hur boende som är bosatta nära flygplatsen Linköping City Airport upplever och påverkas av flygtrafikbuller.  Metod: Studien har utförts som en enkätundersökning med en kvantitativ tvärsnittsdesign. Webbenkäten som har använts som mätinstrument har konstruerats för att besvara syftet. 292 vuxna individer (>18år), varav 158 män och 133 kvinnor, deltog i studien. Insamlad statistiska data har bearbetats och analyserats i SPSS. För att kunna besvara syftet har följande statistiska tester använts: chi2-test, spearmans-korrelationsanalys och logistisk regressionsanalys.   Resultat och konklusion: Boende som är bosatta i Tannefors visade överlag positiva upplevelser till flygtrafiken och var positivt inställda till flygplatsen. De boende som upplevde störningar minst varje vecka vissa delar av året upplevde att flygtrafikbuller medför svårigheter att utföra olika aktiviteter. Kvinnor i den yngsta åldersgruppen upplevde flygtrafikbuller som mer störande jämfört med män. Män hade en mer negativ inställning till flygplatsen jämfört med kvinnor. Boende som rapporterade sämre hälsotillstånd, sömnproblem och användande av öronproppar eller något annat hörselskydd för att kunna sova bättre, sämre sömnkvalitet, trötthet, obehagskänslor, ledsenhet och nedstämdhet, osällskaplighet och att man föredrar att vara ifred, irritation och vresighet, stress, lock eller tinnitus i öronen meddelade också ett större besvär för flygtrafikbuller.
Introduction: Aircraft noise is an example of unwanted sound. The perception of unwanted sound is very individual. What is considered noise by one person may be perceived as non-noise by someone else. However, noise is generally regarded as disturbing noise and is usually something that each individual encounters in their daily life, such as in the workplace, at school, or at home. Noise is considered to be the form of environmental disruption that affects the most people in Sweden. It is a growing problem, and air traffic is considered to be one of the most pervasive outdoor sound sources. Noise problems associated with air traffic are concentrated in areas close to airports, which can affect the health of thousands of residents. Air traffic noise has long been a public health problem, and many people living near an airport have developed a number of negative health effects due to air traffic noise. Purpose: To study how residents living near Linköping City Airport experience and are affected by air traffic noise.   Method: The study has been conducted as a questionnaire survey with a quantitative crosssectional design. The online survey that has been used as a measuring instrument has been designed to answer the purpose. 292 adult subjects (> 18 years), including 158 men and 133 women, participated in the study. Collected statistical data has been processed and analysed in SPSS. In order to answer the purpose, the following statistical tests have been used: chi2 test, Spearman’s correlation analysis and logistic regression analysis. Results and conclusion: Residents living in Tannefors generally had positive experiences from air traffic and were positive towards the airport. The residents who experienced disturbances at least every week during certain parts of the year felt that air traffic noise caused difficulties performing various activities. Women in the youngest age group experienced air traffic noise as more disturbing compared to men. Men had fewer negative attitudes towards the airport compared to women. Residents who reported poorer health conditions, sleep problems and the use of earplugs or other hearing protectors to be able to sleep better, poorer sleep quality, fatigue, discomfort, sadness and depressed mood, low morale, a desire to be left alone, irritation and grief, stress, clogged ear or tinnitus also started that air traffic noise was a major inconvenience.

The elderly population is increasing at a rapid rate each year, and with the increase in the elderly population there is a need for better medical assistance and devices. The greatest problem this demographic is facing is the ability to age in place. More elderly people are being placed in nursing homes, assisted living homes, moving in with relatives due to disabilities or fear of disabilities caused by a life threaten event such as heart disease, stroke, falling/fainting, or uncontrolled glucose levels. Falling is the number one leading cause of deaths, injuries and incapacity in the elderly. Stroke is the 3rd leading cause of death in the U.S; it is the 2nd leading cause worldwide. Rapid change in glucose levels is another leading cause of disabilities and deaths. Heart disease is the 2nd leading cause of death in the elderly. These life threatening events can be prevented and if treated early enough can allow the person to have a full recovery and continue to age in place. A device was proposed that could monitor these four life threatening events: heart disease, stroke, falling/fainting and changes in glucose levels. This device will monitor the user continuously. Research was conducted to see what other products are on the market and how they detect these events and how reliable they are for the user. A literature review was performed to understand what other people are doing to solve the aging in place problem. Using this and needs assessment of the elderly, the system architecture for the wrist worn device was designed along with a testing plan and procedure. More research needs to be done in certain areas to better improve solutions and technology in the area aging in place of the elderly. Before this device can bridge some of the gaps between the current issues and the solution the device will have to be tested for several things such as its ability to differentiate between stimulated falling/fainting and fall like activities such as sitting then lying. The orientation and position will be tested to see if the device can actually tell where the person is located. The device will have to be tested against well-known devices and see if it gives similar precise and accurate readings in real time.
Master of Science

The project’s main goal was to compose a sulforaphane (SF) enriched functional food bar recipe and prototype as an in-between-snack to aid blood glucose regulation among patients with type 2 diabetes (T2D). The antioxidant SF have by research proved beneficial reducing high blood glucose levels by alteration of hepatic glucose production. In order to compare different recipe alternative, and ensure work quality and efficiency, an iterative biomechatronic design methodology was applied. The project includes a literature study to define project requirements as well as practical experiments to test recipe alternatives. Recipe alternatives was developed on the basis of abovementioned literature, previous research within Lantmännen and a close dialogue with expert design team. Main results being a SF rich functional food bar prototype produced by practical experiments, which recipe meet project requirement. However, the project concludes that further research and analysis is necessary in order to ensure desired levels of SF and by so a product with an equal effect as today’s broccoli powder. Future work includes research and studies regarding stability and degradation of SF in the supplied broccoli powder.

A colheita não-mecanizada da cana-de-açúcar, precedida por sua queima, expõe os trabalhadores e pessoas de cidades vizinhas a altas concentrações de poluentes. Este estudo foi desenvolvido para avaliar os impactos cardiopulmonares e os biomarcadores de estresse oxidativo e atividade inflamatória sistêmica desencadeados pela exposição à poluição proveniente da queima da cana. Cortadores de cana (safristas, n = 113) e voluntários saudáveis da cidade de Mendonça - São Paulo, Brasil - (população de referência, n = 109) foram avaliados com espirometria, variabilidade da frequência cardíaca (VFC), enzimas antioxidantes, dosage do nível plasmático do malonaldeído e de interleucinas pró-inflamatórias durante a pré-safra e a safra. A concentração de PM2.5 aumentou de 8g/m3 durante a pré-safra para 23.5g/m3 na área urbana e 61g/m3 nas plantações de cana, durante a safra. Na safra, evidenciou-se uma diminuição mais acentuada na VFC, função pulmonar e da atividade das enzimas antioxidantes entre os cortadores de cana, em comparação com os voluntários da população de referência. Houve elevação do Malonaldeído em ambos os grupos durante a safra, com um maior aumento entre os safristas. Além disso, encontramos um aumento na pressão diastólica apenas nos cortadores de cana. Tanto os cortadores de cana quanto os voluntários da população local exibiram impactos cardiopulmonares e metabólicos da exposição à poluição durante a safra, com maior magnitude dessas alterações entre os safristas, o que destaca o impacto deletério da poluição atmosférica na população exposta. Esses achados pré-clínicos podem sinalizar processos fisiopatológicos desencadeados pela poluição advinda da queima de biomassa nas populações estudadas
Non-mechanized sugarcane harvesting preceded by burning exposes workers and people of neighboring towns to high concentrations of pollutants. This study was designed to assess cardiopulmonary impacts and biomarkers of oxidative stress triggered by exposure to pollution from sugarcane burning. Sugarcane workers (n=113) and healthy volunteers of a reference population (n=109) from the city of Mendonça (São Paulo, Brazil) were evaluated with spirometry, heart rate variability (HRV), antioxidant enzymes, plasma malonaldehyde and proinflammatory interleukins during non-harvest and harvest periods. Concentration of PM2.5 increased from 8g/m3 during nonharvest to 23.5g/m3 in the urban area and to 61g/m3 in sugarcane fields, during harvest. It was evidenced a more remarkable decrease in lung function, HRV and in activity of antioxidant enzymes among sugarcane workers, compared to individuals from the reference population. Malonaldehyde had elevated in both groups during harvest, with a higher increase among sugarcane workers. Furthermore, we found an increase in diastolic pressure only in sugarcane workers. Both sugarcane workers and volunteers from the local population exhibited significant cardiopulmonary and metabolic impacts of exposure to outdoor air pollution during harvest, with a higher magnitude of these alterations among sugarcane workers, which highlights the deleterious impact of air pollution. These preclinical findings may signal pathophysiological processes triggered by biomassburning outdoor pollution in the populations studied

Hypertension is a global disease that many effected people in developing countries is not aware of. Hypertension is linked with cardiovascular disease. Prehypertension is not a disease but if not correctly treated, it could develop into hypertension. The aim of the study was to investigate if there are any differences in circadian blood pressure between two study groups, one group with normal blood pressure and one group with prehypertension. This study was a explorative study and its design is based on measurements of blood pressure values and a questionnaire was used to help get the data collection. 51 students volunteered to have their blood pressure taken from them and out of these 51, 24 where selected into two groups of 12 each for the Ambulatory blood pressure monitoring. hese 24 students would be a part of our study and an ambulatory (Schiller-102 plus) blood pressure monitor was used to collect the data. The prevalence of prehypertension findings in the clinical testing phase was 37% of the population. There was a variation between the groups during the day (systolic) but there was not a significant difference during the night.

Background: Cellulitis is a common infectious disease. Although blood culture is frequently used in the diagnosis and subsequent treatment of cellulitis, it is a contentious diagnostic test. To help clinicians determine which patients should undergo blood culture for the management of cellulitis, a diagnostic scoring system referred to as the Bacteremia Score of Cellulitis was developed. Methods: Univariable and multivariable logistic regression analyses were performed as part of a retrospective cohort study of all adults diagnosed with cellulitis in a tertiary teaching hospital in Taiwan in 2013. Patients who underwent blood culture were used to develop a diagnostic prediction model where the main outcome measures were true bacteremia in cellulitis cases. Area under the receiver operating characteristics curve (AUC) was used to demonstrate the predictive power of the model, and bootstrapping was then used to validate the performance. Results: Three hundred fifty one cases with cellulitis who underwent blood culture were enrolled. The overall prevalence of true bacteremia was 33/351 cases (9.4 %). Multivariable logistic regression analysis showed optimal diagnostic discrimination for the combination of age >= 65 years (odds ratio [OR] = 3.9; 95 % confidence interval (CI), 1.5-10.1), involvement of non-lower extremities (OR = 4.0; 95 % CI, 1.5-10.6), liver cirrhosis (OR = 6.8; 95 % CI, 1.8-25.3), and systemic inflammatory response syndrome (SIRS) (OR = 15.2; 95 % CI, 4.8-48.0). These four independent factors were included in the initial formula, and the AUC for this combination of factors was 0.867 (95 % CI, 0.806-0.928). The rounded formula was 1 x (age >= 65 years) + 1.5 x (involvement of non-lower extremities) + 2 x (liver cirrhosis) + 2.5 x (SIRS). The overall prevalence of true bacteremia (9.4 %) in this study could be lowered to 1.0 % (low risk group, score <= 1.5) or raised to 14.7 % (medium risk group, score 2-3.5) and 41.2 % (high risk group, score >= 4.0), depending on different clinical scores. Conclusions: Determining the risk of bacteremia in patients with cellulitis will allow a more efficient use of blood cultures in the diagnosis and treatment of this condition. External validation of this preliminary scoring system in future trials is needed to optimize the test.

A major factor in the success of Staphylococcus aureus as a pathogen is its vast arsenal of virulence determinants and, more importantly, the tight and precisely- timed regulation of these factors. Here we investigate the product of the S. aureus gene, SAUSA300_1984, encoding a putative transmembrane protein. This as yet uncharacterized protein belongs to the Abi (abortive infection) family, which are commonly annotated as CAAX-proteases, and are significantly understudied in prokaryotes. In S. aureus the disruption of SAUSA300_1984 results in a drastic reduction of proteolytic and hemolytic activity, as well as diminished pigmentation. This phenotype appears to be mediated through reduced agr expression, as determined by qPCR analysis. Importantly, known regulators of agr, such as CodY, MgrA, and ArlR, demonstrate no significant changes in transcription upon 1984 disruption, whilst major alterations were observed for downstream effectors of agr, such as sarS, RNAIII, rot and hla. Complementation and site-directed mutagenesis of 1984 demonstrated that proteolytic activity (via conserved EE residues) was not required for this phenotype, suggesting a potential protein-protein interaction mechanism of interaction. Proteome analysis of the 1984 mutant confirmed a number of our transcriptional observations, such as an increased abundance of Rot and surface associated proteins, as well as a marked decrease in Agr-system proteins levels, with the most striking being AgrB. Virulence profiling revealed a decreased ability of the 1984 mutant to evade constituents of the innate immune response, and impaired survival during murine models of infection. Given that SAUSA300_1984 is encoded 3 genes downstream of RNAIII, our current working hypothesis is that this Abi protein functions to control agr activity through communication with membrane components of this system, potentially via interaction with AgrB. Confirming this, and determining the upstream effectors of this regulatory system are studies currently ongoing in our laboratory.

Per studiare le ripercussioni metaboliche e produttive di alterazioni della funzionalità del digerente sono state condotte tre sperimentazioni. Nella prima sono state controllate le condizioni di acidosi ruminale in bovine di allevamenti commerciali: in essi non si sono riscontrati valori di ph capaci di indurre seri effetti negativi a livello digestivo-metabolico, ma certamente a rischio. In tali condizioni, i più bassi valori di ph ruminali sarebbero soprattutto indice di una maggiore ingestione di alimenti, favorita anche da migliori condizioni generali di salute delle bovine. Nella seconda sperimentazione, l'applicazione di stress acuti a bovine in lattazione ha prodotto un rallentamento nel transito ruminale, soprattutto in animali in lattazione avanzata, confermando la possibilità che lo stress acuto rappresenti un fattore di rischio per anomalie digestivo/fermentative. Nella terza prova, relativa alla funzionalità del grosso intestino di conigli esposti a diete con diversi livelli di amido, performance produttive leggermente più favorevoli si sono registrate con la dieta più alta in fibra digeribile. A fronte di analoghe caratteristiche del digerente tra le tesi, alcuni parametri ematici ,soprattutto con riferimento allo status ossidativo, hanno permesso di porre in evidenza un quadro metabolico più favorevole associato all'uso di diete meno amidacee. Quindi, alterazioni dei processi fermentativi, possono avere conseguenze sul livello produttivo e sullo stato di salute dell'animale. Per una migliore interpretazione dei dati della funzionalità del digerente appare utile il supporto di taluni parametri ematici.
Three experiments were carried out to study the metabolic and productive effects of some changes of the digestive functionality. In the first experiment, the degree of ruminal acidosis was controlled on dairy cows from commercial farms: the low observed ph values were indices of risks but not so low to have serious adverse effects at digestive-metabolic level. However in these circumstances, the lower ph would be especially indices of a greater feed intake, in turn favoured by a better general animal health. In the second experiment, the application of acute stress to lactating cows showed digesta rumen passage rate of digesta, especially in late lactation, confirming the possibility that the acute stress could be a risk factor for digestive abnormalities. In the third one, on the large intestine functionality of rabbits exposed to diets with different levels of starch, some slightly better performances were obtained with the diet richer in digestible fibre. Though main digestive traits were unaffected by treatments, some blood parameters, particularly those linked to the oxidative status, revealed a more favourable metabolic situation associated with the use of less starchy diets. Hence, alteration of the fermentative processes may impair animal production and/or the animal health conditions. For a better interpretation of the parameters of the digestive system functionality the support of some specific blood parameters appears useful.

La dieta, lo stato nutrizionale e la salute sono questioni strettamente correlate sia nei paesi industrializzati che in quelli in via di sviluppo. In questa tesi di dottorato, l'obiettivo principale è stato quello di valutare lo stato nutrizionale come passo prodromico per migliorarlo per ottimizzare la salute. Nei paesi industrializzati è stato condotto un caso studio sullo stato nutrizionale di una popolazione dell'Italia centrale; l’ingestione di alcuni gruppi di alimenti, di origine animale e vegetale, è stata valutata mediante questionari di frequenza alimentare e alcuni biomarcatori del sangue. I risultati hanno dimostrato che nei controlli della dieta, al fine di accertarne gli effetti a lungo termine sulla salute, le misurazioni dei consumi tramite questionari non possono essere esclusive, ma alcuni indici ematici ed antropometrici potrebbero essere utili. Nei paesi in via di sviluppo, due casi di studio in zone rurali dell’India e della Repubblica Democratica del Congo hanno confermato che la malnutrizione è un problema serio; in particolare nei bambini di 3-5 anni con il 26% di malnutrizione cronica severa in India e oltre il 60% in R D Congo. Possibili percorsi per migliorare le condizioni di vita delle comunità rurali povere includono la produzione di cibi appropriati per una dieta migliore, nuove attività generatrici di reddito, miglioramento della nutrizione infantile, riduzione delle malattie causate dalla contaminazione di alimentari e dell’acqua, metodi di conservazione degli alimenti a livello domestico, etc.; i risultati di diverse prove sono stati discussi.
The diet, nutritional status and health are tightly related issues both in industrialized and developing countries. In this doctoral thesis, the main objective was the assessment of nutritional status as a prodromic step to improve it and consenquently health. In industrialized countries, a case study was the nutritional status of a population of central Italy; the intake of some groups of foods, of animal and plant origin, was estimated by food frequency questionnaires and some blood biomarkers. The results demostrated that in dietary controls, aiming to ascertain the long-term effects on health, consumption measurements by questionnaires cannot be exclusive, but some blood and anthropometric indexes could be also useful. In developing countries, two case studies in rural India and D R Congo confirmed that malnutrition is a serious issue; particularly in 3-5 years old children with 26% of severe chronic malnutrition in India and more than 60% in D R Congo. Possible pathways to improve livelihood of rural poor comunities including appropriate food production for a better diet, new income generating activities, infant nutrition improvement, food and waterborn diseases reduction, household food preservation, etc., have been analyzed and the risults of different related trials have been discussed.

碩士
國立臺灣大學
職業醫學與工業衛生研究所
106
Background Air pollutants may enter the body through inhalation and affect human health. Metals belong to a component of air pollutants, and often exist with small particles, The goal of this investigation is to understand the relationship between air pollution and cord blood vanadium, strontium and arsenic concentrations. Materials and Methods A birth cohort, including 893 pairs of mothers and newborns were recruited between May 2004 to July 2005. Structured questionnaire was completed, which contained basic information on maternal and newborn data, information of home environment, and information on enviromental exposure. Cord blood samples were analyzed by inductively coupled plasma mass spectrometry (ICP-MS), for vanadium, strontium and arsenic. Air pollution data was collected from the EPA air monitoring stations and individual exposure was extrapolated using geographic information system (Arc GIS) Kriging method. Multiple linear regression analysis was performed to determine the relationship between metal concentrations in cord blood and air pollution by SAS 9.4 software. Results After adjusting the mother''s age, education level, family income, maternal smoking, passive smoking, alcohol drinking, gestation weeks, birth season and baby gender, cord blood vanadium was significantly positively associated with PM10. Comparing those living in higher and lower PM10 regions, there was 0.39 μg/L difference in cord blood vanadium. Cord blood arsenic concentration was significantly positively associated with SO2. Comparing those living in higher and lower SO2 regions, there was 0.81 μg/L difference in cord blood arsenic. Conclusion The study found that cord blood vanadium concentrations is associated with maternal exposure to ambient PM10, and cord blood arsenic concentrations is associated with maternal exposure to ambient SO2. Since these two metals are known to be emitted from petrochemical industries, the contribution of the latter to cord blood vanadium and arsenic cannot be totally ruled out.

碩士
國立清華大學
奈米工程與微系統研究所
96
A novel electrolysis-based micropump using air bubble to achieve indirect actuation is proposed and successfully demonstrated. Unlike most other electrochemical micropumps, our micropump could drive microfluid without the pH-value variation and the choking/sticking phenomena of electrolytic bubbles in the main channel. Besides, the room temperature operation and the low driving voltage used for the electrolysis actuation minimize the possibility of cell-damage. It is promising for biomedical applications, especially for the blood transportation. The whole blood is an intrinsically complex material and difficult to be manipulated in the microdevices. Moreover, the on-chip electrolysis-bubble actuator with the features of large actuation force, low voltage and low power consumption enable portable and implantable lab-on-a-chip microsystems. Utilizing the hydrophobic trapeziform pattern located at the junction of the T-shaped microchannel, the micropump drives the pumped fluid in the main channel and isolates it from the electrolytic bubbles. Our proposed micropump can be used for a variety of applications without constraints on the pumped liquid. Polyethylene glycol (PEG) is employed to modify the surface of PDMS microchannel to prevent the platelet adhesion during pumping operation. According to the platelet adhesion test, there is no clotting during blood pumping operation. The pH-value variation and distribution in the side channel and the main channel is also characterized during electrolysis-actuation operation. Experimental results show that the liquid displacement and the pumping rate could be easily and accurately controlled via the signal of two-phase peristaltic sequence and the periodic generation of electrolytic bubbles. With the applied voltage of 2.5 volts, the maximum pumping rate of 121 nl/min and 88 nl/min were achieved for the DI water and the whole blood, respectively, with the microchannel cross section of 100×50 μm. In this thesis, the design, microfabrication process, characterization and the experimental demonstration of this novel micropump are reported.

Red blood cells (RBCs) circulate through the lung and capillaries during their 120-day life span, transporting oxygen and carbon dioxide. They are exposed continuously to reactive oxygen species (ROS) derived from hemoglobin autoxidation. Protection of the RBC membrane from ROS is critical since on oxidation the cell loses its ability to deform in narrow capillaries. We investigated by Western blotting and confocal microscopy membrane recruitment of the key antioxidant enzymes, CuZn-superoxide dismutase (CuZnSOD), catalase, peroxiredoxin-2 (Prx2) and glutathione peroxidase-1 (Gpx1). Prolonged air exposure of human RBCs, which likely increases their O2●¯ levels, resulted in less membrane-associated CuZnSOD but more membrane-associated catalase and Gpx1. Prx2 membrane levels remained unchanged. Challenge with H2O2 or cumene hydroperoxide recruited Gpx1 to the membrane to metabolize lipid peroxides. Localization of catalase, which is always present at the membrane, remained unchanged but membrane-associated Prx2 decreased after peroxide treatment. We also investigated membrane recruitment of the antioxidant enzymes in diabetic vs control rat RBCs. Notably, CuZnSOD increased at the RBC membrane in control animals at 2 versus 4 weeks. We attributed this to the observed increase in PTP1B activity, suggesting that CuZnSOD membrane localization is regulated by phosphorylation of the cytoplasmic domain of Band-3 (CDB3). Catalase decreased at RBC membranes of 4-week diabetic rats whereas Prx2 levels increased. Gpx1 membrane levels did not change in diabetic RBCs suggesting that its membrane binding sites are always saturated to protect against lipid oxidation. Our results provide evidence that CuZnSOD, catalase, Prx2 and Gpx1 respond to damaging ROS in RBCs.

碩士
國防醫學院
公共衛生學研究所
89
Abstract Lead has been used as anti-knocking agent in the gasoline for centuries. The impact of lead toxicity released from traffic pollution is still important despite that lead has already been banned from the gasoline. This study was to measure the air lead concentrations in the total suspended particulate, inhalable particulate, thoracic particulate, and respirable particulate in a toll station. In addition, 72 toll station workers were recruited in this study and the blood lead concentrations were measured. Blood lead level was analyzed by furnace atomic absorption. Air samples were analyzed by Inductively Coupled Plasma (ICP), Integra XL. The results showed that the mean blood lead (PbB) levels of 72 participants was 3.3958 ±1.1505μg/dl (n=72). The maximal level of blood lead was 7.35μg/dl, which was much lower than the acceptable limit of 40μg/dl recommended for adults by WHO. The PbBs in Tai-Sun toll station workers was not higher than those of control toll station (Chi-Do) workers. However, the PbBs in those who drink mineral water and those who do not drink milk were higher than those of counterparts. The effect of protective mask was not significant in this study. Smokers had higher PbBs than non-smokers. Environmental monitoring was performed by using several size-specific samplers, including filter, IOM, cyclone and cascade impactor. The results showed that the lead concentrations among total suspended particulate, inhalable particulate (<100μm), thoracic particulate (<10μm), respirable particulate (<3.55μm), and particulate <1.5μm were 0.123, 0.197, 0.292, 0.499, and 0.334μg/m3, respectively. This result indicated that lead was dominantly adsorbed in small particulates. This study also found that the lead concentrations in different lane of toll station were negatively associated with the number of traffic in that lane. The lead concentrations were also associated with the work shift and change permission. The air lead level in the afternoon shift was lower than that of day shift and evening shift. The air lead level in the lane permitted for change was lower than in lanes of no change. In conclusion, the air lead levels in the toll station varied by traffic number, work shift and the traffic lane. However, the lead concentration in the air was not high enough to induce increased blood lead levels among toll station workers. Key words : Blood lead level, Toll station, Air lead level

碩士
大同大學
機械工程學系(所)
92
Abstract High blood pressure has taken one of the top ten causes of death within the overall population locally. To prevent from high blood pressure, aside from the diet control, the adoption of handy and comprehensive electronic of no professional technique has become the must-have health care item of every household already. This research is aimed to the investigation about the function of air pump within the wrist blood pressure monitor。By using the L9(34) orthogonal arrays adopted by Taguchi, we make the settings for DC motor rotation, cam stroke, hardness of rubber piston, and superficial roughness of Pump Body, totally 4 factors, with 3 levels for experimenting separately. In reference with the experiment results, we found from the reaction charts that the main body of pump will come with the most evident influence for the superficial roughness of pump body; the cam-stroke and DC motor rotation come with the relatively low influence and the hardness of rubber piston actually exerts the least influence among all factors. Furthermore, the optimally conditioned combination for all factors are separately 12500rpm for DC motor rotation, 1.8mm for cam stroke, 50°for hardness of rubber piston and Ra 0.2 for the superficial roughness of pump body.

碩士
長榮大學
職業安全與衛生研究所
96
In this study, fifty three cement workers were recruited from Tainan City and County. Both air and skin sampling were taken to accurately assess the total exposure of Cr6+ from inhalation and dermal contact routes for these cement workers. During the exposure sampling time, a questionnaire was used to investigate the work history and the frequency of dermal contact to cement in a regular work day for each worker. In addition, both urine and blood samples were collected from the workers to estimate the total doses of Cr6+ in their bodies. The concentrations of Cr6+ in the air and skin samples were determined by Ultra Violet-Visible Spectroscopy (UV-Vis). The concentrations of total chromium in the urine and blood samples were measured by Atomic Absorption Spectrometer (AA). The results showed that the measured Cr6+ concentrations in air were far less than the permissible exposure limit of 5 ?慊/m3 in an 8-hour work shift established by Occupational Safety and Health Administration (OSHA). However, the concentrations of total chromium in the end of shift urine samples were 47% greater than 25 μg/L, the Biological Exposure Index (BEI) recommended by American Conference of Governmental Industrial Hygienists(ACGIH). It was concluded that dermal contact was the main route of Cr6+ exposure for cement workers. The relationship between the concentrations of total chromium in the post-shift urine samples and some exposure determinants was explored by conducting a multiple linear regression analysis. It was found that betel nut chewing and the concentrations of total chromium in the pre-shift urine samples were significantly important (R2= 0.3041) in estimating the concentrations of total chromium in the post-shift urine samples. Regarding the analysis of blood samples, the concentrations of total chromium of most workers were very low which was close to the background level of total chromium of general population. No matter the concentrations of total chromium in the samples of blood plasma and red blood cells were lower than the detection limit of total chromium, but the proportion of the concentrations of total chromium in urine samples greater than the BEI value was high. This indicated that the cement workers had certain amount of Cr6+ exposure. However, this amount was not higher than the reduction capacity, 2 ppm, of Cr6+ in blood plasma. When the Cr6+ was absorbed through the skin into the blood, most of the Cr6+ was reduced into Cr3+ which could not cumulate in red blood cells and was excreted by urine. It was suggested that the the protection of cement workers from Cr6+ exposure should focus on the cut-off of dermal absorption of Cr6+. The addition of ferrous sulfate to cement is an appropriate approach to decreasing the dermal exposure to Cr6+ for cement workers. Other alternative of applying cream with some substances which can reduce Cr6+ to Cr3+ and decrease the skin absorption of Cr6+ can also be considered.

碩士
國立臺灣海洋大學
食品科學系
101
Abstract This study investigated the effect of air exposure on the proliferation of erythroid cells in the head kidney and blood of common carp. In order to produce a controlable stress conditions, we exposed the fish to air for 2 h then them returned to the aquarium for another 2 h. This process was repeated one to six times. The common carp experienced to different stressed degree, i.e., control (resting fish), A1, A2, A3, A4, A5, A6 (air exposure 2h ×1, ×2, ×3, ×4, ×5 and ×6) and R1, R2 (recovery after 2 and 4d) were obtained. The results showed that the whole blood cell zinc concentration in the control was 4.06±1.18 μg/ml whole blood. However, the whole blood cell zinc concentration in the A3 group significantly increased to 37.9±20.7 μg/ml whole blood, being 9.3 times higher than the control. In the A4, A5 and A6 groups, the whole blood cell zinc concentration still significantly higher than the control, being 8.0, 4.8 and 4.6 times, respectively. In the recovery groups (R1 and R2), the whole blood cell zinc concentrations were not significantly different from the control. When the blood was divided into plasma and cells, it was found that in the A3 group approximately 90% of the zinc increase in the common carp blood came from its cells. The hematological examinations of the common carp revealed that the mean red blood cell (RBC) level in control group was 0.81 ± 0.22 × 106 cell/mm3. Only in the recovery group (R1), the RBC level significantly increased 1.44 times than the control group. All the other groups showed no significant difference from the control group. The hemoglobin (Hb) levels in A3, A5, R1 and R2 groups were significantly lower than the control group being only about 50% of the control. In addition, the mean corpuscular hemoglobin content (MCH) in all these groups were also lower than the control, which are also about 50% of the control. It is reported that the immature red blood cell in fish differ from the mature ones by a small volume, and a lower hemoglobin level. The hematological studies indicate that a lot of immature red blood cells were formed in the A3 and A5 groups. The “saline solution of 50% hemolysis” and “hemolysis in 0.38% saline solution” of the common carp blood were determined. It was found that the hemolysis in A3, A5, R1 and R2 groups were significantly lower than the control. Zinc concentration in the head kidney cells of common carp subjected to air exposure were studied. The results showed that the zinc significant increased in the A3, A5 and R1 groups, being 5.5, 8.8 and 8.8 times, respectively, higher than the control. The head kidney cells of the stressed common carp were observed under light microscopic examination. It was found that the immature red blood cell in the head kidney and blood increase following the increase of the zinc level in the head kidney. Based on these results, it is concluded that when the common carp were air exposed, within 6 h no erythroid cells were found in the common carp blood. However, 26 h after the experiment (A3 group), a lot of immature red blood cells were observed in the common carp blood, these immature red blood cells came from the head kidney. These immature red blood cells were proliferated by the stimulation of zinc in the head kidney, because the head kidney zinc concentration in the A3 group were 5.5 times higher than the control group. It was reported that zinc can protect the integrity of the cell membrane to tolerate hemolysis, besides, it is also known that binding of zinc to the hemoglobin could increase oxygen affinity. One important reason why common carp can tolerate hypoxia, may be because they can proliferate immature red blood rapidly, only within 1d.

Yes
A simple method is reported for the estimation of in vivo air-tissue partition coefficients of VOCs and of in vitro blood-tissue partition coefficients for volatile organic compounds and other compounds. Linear free energy relationships for tissues such as brain, muscle, liver, lung, kidney, heart, skin and fat are available and once the Abraham descriptors are known for a compound, no more than simple arithmetic is required to estimate air-tissue and blood-tissue partitions.

Background Point-of-care blood gas analysis is considered a standard of care in modern air ambulance operations by many professional organisations for clinical assessment and monitoring of patients. Instances where point-of-care blood gas analysis has identified clinically significant abnormalities which then led to clinical intervention are well documented and have been quantified previously in the air ambulance environment. However, results obtained from point-of-care blood gas analysis are not always required for patient care, nor do they always result in any clinical action on the part of the medical crew. Our question therefore related to the data for a Johannesburg based jet air ambulance service. Methods By means of retrospective case reviews over a one year period, we reviewed the overall frequency of utilisation of point-of-care blood gas analysis on patient transportations within a Johannesburg based jet air ambulance service. We established how often point-of-care blood gas analysis yielded abnormal findings, and how frequently abnormalities detected by point-of-care blood gas analysis resulted in clinical interventions. Results Point-of-care blood gas analysis was undertaken in 266 of 334 patients transported (79.6%). Abnormal findings were noted in 203 of the 338 blood gas analyses undertaken (60.1%). Patient age (p=0.001) and intubation status (p=0.01) were significant influences on number of analyses performed, while flight time was not significant (p=0.07). Clinical intervention followed in 65.5% of instances where abnormalities on blood gas analysis were noted and in 87.6% where clinical corrective intervention was assessed as being possible under prevailing conditions. Of all patients transported, some form of clinical intervention was undertaken following 39.3% of all blood gas analyses undertaken. This therapeutic yield evidenced is equivalent to 2.54 samples analysed per corrective clinical action evidenced. A costing analysis further revealed that this testing is relatively inexpensive per positive finding yielded and subsequent clinical actions. Conclusions Abnormalities detected and subsequent clinical intervention using point-of-care blood gas analysis in this patient population was significant with a clinical yield of 39.3%. Since the costs are also not very high this modality is rightfully considered a minimum standard of care in air ambulance operations. These findings also support the notion that such testing should be carried out routinely on all patients irrespective of clinician interpretation of indication or need

Yes
BACKGROUND: There is considerable interest in the blood–tissue distribution of agrochemicals, and a number of researchershave developed experimental methods for in vitro distribution. These methods involve the determination of saline–blood andsaline–tissue partitions; not only are they indirect, but they do not yield the required in vivo distribution.RESULTS: The authors set out equations for gas–tissue and blood–tissue distribution, for partition from water into skin andfor permeation from water through human skin. Together with Abraham descriptors for the agrochemicals, these equationscan be used to predict values for all of these processes. The present predictions compare favourably with experimental in vivoblood–tissue distribution where available. The predictions require no more than simple arithmetic.CONCLUSIONS: The present method represents a much easier and much more economic way of estimating blood–tissuepartitions than the method that uses saline–blood and saline–tissue partitions. It has the added advantages of yielding therequired in vivo partitions and being easily extended to the prediction of partition of agrochemicals from water into skin andpermeation from water through skin.

碩士
國立中正大學
機械系
93
Near decades, the dioxin have already been proved damage to the human body that including: various kinds of pathological changes , carcinogenic risks and causing human gene mutation. So the pollution of dioxin has already became the focus paid attention to of hygiene unit of various countries in the world. This research uses the data that is the dioxin concentration in blood for the resident near the 19 incineration plant from the Environ mental Protection Administration Executive Yuan ,R.O.C to analyze. It is the comparison between the data of the dioxin concentration in blood for the resident near the incineration plant and the dioxin concentration of the air by statistical method like: One way anova、Pearson、Regression and prove that there are dependence and dominance each other. Using the linear regression builds the linear relational expression that is between age and the dioxin concentration in blood of the resident near the incineration plant. The result of study shows : the dioxin concentration in blood for the resident has not been influenced by the distance of the incineration plant and the expose time of operating. The dioxin concentration in blood and resident's age form positive correlation. Accord to from every statistics, dioxin emission of the incineration plant does not have direct relation with the dioxin concentration in blood of the resident.

碩士
元智大學
電機工程學系
98
In modern days, people spend most of their time within indoor environment, and as the result, the demand for indoor comfortableness is increasing. Very often, a HVAC system is used to reach the demand, and hence the percentage of adoption is rising. However, the current HVAC system can not guarantee the comfortableness；as the situations of warm or cold happened, and users have to modify the settings of HVAC systems accordingly. This research is to address this situation, and aims at constructing a platform both deliver both human comfort and energy conservation. The platform is capable of determine the comfort of the indoor room space based on the data of microcirculation blood flow of the personnel and the optimized operation of air conditioning system can be modified afterwards. The best range for comfort and effective temperature curve was 22 degrees to 23.5 degrees, which was defined by the U.S. Association of Refrigeration and Air Conditioning ANSI / ASHREA Standard 55-2004, is formulated as the best comfortableness curve in this study. Experimental work related to human microcirculation was carried out to analyze the average blood flow in order to establish the relationship between the ambient temperature and the average blood flow. The present findings can aid the development of a HVAC control platform for room comfortableness, which is capable of detecting the average blood flow of humans to determine the temperature setting of this space. This platform will modify the operation level to rise the room space temperature if a human body is changed into the cold state, and vise versa. In conclusion, the present study therefore can help to achieve human comfort and energy conservation purposes. This paper presents the preliminary study of micro-blood flow measurement and analysis and intelligent air conditioning system control, and an indoor comfort platform is built based on this study. It was found that the status of comfort referring to the micro-blood circulation is directly influenced by the indoor temperature. Therefore, a too high or too low setting temperature of air conditioning system can cause uncomfortable and also wastes energy. Further studies to discover the optimized relationship between human comfort and energy can be carried out for the improvement of energy efficiency and indoor space quality.

Background: This dissertation comprises research conducted on two distinct projects. Project I focuses on the connection between household air pollution (HAP) from cooking with biomass fuels and blood pressure (BP); this research is situated in the context of a large randomized trial of a cookstove intervention in Ghana, West Africa. The setting of Project II, meanwhile, is the residential environment of New York City, where we explore temperature and humidity conditions in homes and relate these conditions to summertime heat wave risk and to the survival and transmission of respiratory viruses in the winter. Although these projects are quite distinct, each relates to the complex relationship between climate change and health. Reducing HAP to improve health (the focus of Project I) will simultaneously reduce climate change through a reduction in emissions of short-lived climate pollutants into the atmosphere. Meanwhile, furthering our understanding of heat and humidity levels inside urban residences (the focus of Project II) is crucial to our ability to protect health in light of projections for a changing climate. Domestic activities associated with heating, cooling, and cooking are thus very relevant both to human health and to climate change mitigation and adaptation. Objectives and Methods: Our overall objective for Project I was to investigate exposure- response relationships between HAP and BP in a cohort of pregnant women taking part in the Ghana Randomized Air Pollution and Health Study (GRAPHS). We first explored this association in a cross-sectional study (Chapter 1), in which we used 72-hour personal monitoring to ascertain levels of exposure among the GRAPHS women to carbon monoxide (CO), one of the pollutants emitted by traditional wood-fed cooking fires. These exposure data were collected at enrollment into the GRAPHS study, prior to the initiation of cooking with improved cookstoves. We investigated the association between these “baseline” CO exposure levels and the women’s blood pressure at enrollment into GRAPHS. A limitation of this study was that BP was only measured once. We followed this with a second study of 44 women drawn from the same cohort (Chapter 2), for whom we designed BP protocols using 24-hour ambulatory blood pressure monitoring (ABPM), the current gold standard for clinical diagnosis of hypertension. As we were not aware of any prior research in Africa that had employed ABPM, we also designed a parallel BP protocol using home blood pressure monitoring (HBPM) equipment for comparison with ABPM. The use of ABPM with concurrent personal CO monitoring enabled us to investigate hourly associations between CO exposure and changes in BP. We also evaluated BP in these women both before and after the cookstove intervention; this allowed us to investigate whether any changes in BP were associated with switching to an improved cookstove. Our objectives for Project II were to understand the distribution of temperature and humidity conditions in a range of New York City homes during the summer and winter seasons, to evaluate the impact of structural and behavioral factors (e.g. building size, use of air conditioning, and use of humidifiers) on these conditions, and to build models that could help predict indoor conditions from more readily available outdoor measurements. We conducted this research in two ways. We first analyzed a set of indoor temperature and humidity measurements that were collected in 285 New York City apartments during portions of summers 2003-2011 and used these data to simulate indoor conditions during two heat wave scenarios, one of which was more moderate and the other of which was more extreme (Chapter 3). Second, we designed and conducted a new study in which temperature and humidity were monitored in a set of 40 NYC apartments between 2013 and 2015 (Chapters 4-6). This second study enabled us extend our research into the winter season, and also to explore how factors such as air conditioning and humidifier use impacted indoor temperature and humidity. We also investigated relationships between the monitored conditions, self-reported perceptions of the indoor environment, and symptoms that were experienced among household members. Results: In the cross-sectional analysis of CO and BP in the GRAPHS cohort (Chapter 1), we found a significant positive association between CO exposure and diastolic blood pressure (DBP): on average, each 1 ppm increase in exposure to CO was associated with 0.43 mmHg higher DBP [0.01, 0.86]. A non-significant positive trend was also observed for systolic blood pressure (SBP). In our study of the acute relationship between CO exposure and BP (Chapter 2), we determined that peak CO exposure (defined as above the 90th percentile of the exposure distribution, or an average of 4.1ppm) in the two hours prior to BP measurement was associated with elevations in hourly systolic BP (4.3 mmHg [95% CI: 1.1, 7.4]) and diastolic BP (4.5 mmHg [95% CI: 1.9, 7.2]), as compared to BP following lower CO exposures. We also observed a non-significant trend toward lower BP following initiation of cooking with an improved cookstove. Lastly, we demonstrated that ABPM was a feasible and well-tolerated tool for BP assessment in a rural West African setting. For Project II in New York City, we first determined that there was a great deal of variability in indoor summer heat index (HI) between homes in association with similar outdoor conditions, and that this variability increased with increasing outdoor heat (Chapter 3). Our simulation of a moderate heat wave led us to conclude that the hottest 5% of the homes would reach peak indoor heat index (HI) values of 39°C. In a more extreme heat wave simulation, HI in the hottest 5% of homes reached a peak of 41oC and did not drop below 34oC for the entire nine- day simulated heat wave period. Our second indoor monitoring study yielded the following findings: in the summer season (Chapter 4), we found significant differences in indoor temperature and heat index according to the type of air conditioning (AC) in the home. Homes with central AC were the coolest, followed by homes with ductless AC, window AC, and no AC. Apartments on the top floor of a building were significantly hotter than other apartments regardless of the presence of AC. During the winter season (Chapter 5), median vapor pressure in our sample of apartments was 6.5mb. Comparing humidity levels in the apartments to a threshold of 10mb vapor pressure that has been proposed as protective against influenza virus transmission, levels of absolute humidity in the homes remained below this threshold for 86% of the winter: a total of over three months. Residential use of humidifiers was not associated with higher indoor humidity levels. Larger building size (above 100 units) was significantly associated with lower humidity, while the presence of a radiator heating system was non-significantly associated with higher humidity. Lastly, perceptions of indoor temperature and measured temperature were significantly associated in both the summer and the winter (Chapter 6), while sleep quality was inversely related to measured indoor temperature in the summer season only. Reports of heat- stress symptoms were associated with perceived, but not measured, temperature in the summer season. Conclusions: The work presented in this dissertation adds to a growing body of evidence on the importance of exposures in the domestic environment to health and well-being. The research reported here on household air pollution in Ghana documents an exposure-response relationship between air pollution from cookstoves and elevations in blood pressure, on both a chronic and an acute basis. As elevated BP is a known risk factor for cardiovascular disease (CVD), our research provides support for a plausible factor linking HAP exposure to CVD. Meanwhile, our research on temperature and humidity in New York City residences provides concrete data to supplement the very slim literature to date documenting these conditions in the home environment, where Americans spend over half their time. We conclude, first, that AC may not be fully protective against summertime heat risk, and second, that the levels of humidity we observed in residential environments are consistent with levels that have been shown to promote enhanced survival and transmission of respiratory viruses in experimental settings. We suggest that interventions that can reduce exposure to household air pollution and excess indoor heat can also mitigate climate change, and that with thoughtful planning we can improve health at the same time as we foster resiliency in the face of a changing climate.

Epidemiological studies have shown strong and consistent associations between exposure to air pollution and increases in morbidity and mortality. Key air pollutants that have been identified include fine particulate matter (PM) and ozone (O3), both major contributors to smog. However, there is a lack of understanding of the mechanisms involved and the relative contributions of individual pollutants. A controlled human exposure facility was used to carry out inhalation studies of concentrated ambient fine particles (CAP), O3, CAP+O3 and filtered air following a randomized design. Exposures were 2 hrs in duration at rest. Subjects included mild asthmatics and non-asthmatics. This thesis focuses on acute cardiovascular responses including blood pressure (BP), brachial artery reactivity (flow-mediated dilatation [FMD]) and markers of systemic inflammation (blood neutrophils and interleukin [IL]-6). Results showed that for CAP-containing exposures (CAP, CAP+O3) there were small but significant transient increases in diastolic BP (DBP) during exposures. Furthermore, neutrophils and IL-6 increased 1 - 3 hrs after and FMD decreased 20 hrs after CAP-containing exposures. Responses to O3 were smaller, comparable to filtered air. The data suggests that adverse responses were mainly driven by PM. The DBP increase was rapid-developing and quick to dissipate, which points to an autonomic irritant response. The magnitude of the DBP increase was strongly negatively associated with the high frequency component of heart rate variability, suggesting parasympathetic withdrawal as a mechanism. In comparison, IL-6, neutrophil and FMD responses were slower to develop, indicative of an inflammatory mechanism. An intriguing finding was that IL-6 increased 3 hrs after CAP, but not after CAP+O3. Further investigation revealed that exposure to CAP+O3 in some individuals may trigger a reflex inhibition of inspiration, decreasing their tidal volume and inhaled pollutant dose, leading to a reduction in systemic IL-6, a potential protective mechanism. Together the findings support the epidemiological evidence of adverse fine PM health effects. Many questions remain to be answered about the health effects of air pollution including a better understanding of how inhaled pollutants result in cardiovascular effects. It is hoped that the insights gained from this thesis will advance the understanding of air pollution health effects.

Research Doctorate - Doctor of Philosophy (PhD)
Background: Decision aids are structures education packages designed to foster shared decision making between patient physician. They are often used when there is confusion or disagreement associated with the values patients assigned to, and the evidence on, the various outcomes of the intervention in question. Blood transfusion relation to elective surgery is an area that requires both physicians and patients to carefully consider different treatment options. The issues of variation in transfusion practices, different personal values in regards to receiving blood, and the uncertainty as to whether the benefits of technologies aimed at minimising allogeneic blood use (e.g. pre-operative autologous donation or PAD) outweigh the potential harms justify attempts to design a patient decision aid in this area. Aims: The overall aim of the thesis was to develop and pilot test a decision aid describing blood transfusion options to patients planning any type of major elective surgery (such as hip replacement or heart bypass). A series of studies and reviews were necessary to adequately inform the development of the decision aid. Hence, additional aims of the thesis were: to investigate whether the manner in which treatment effects are presented influence the healthcare decisions made by patients (information framing). ; To systematically review the evidence on the benefits and harms of PAD (e.g. need for allogeneic/autologous blood, other clinical outcomes). ; To examine the attitudes, beliefs, understanding and possible misconceptions of the general public, patients, special interest group members (e.g. Hepatitis C Council), and physicians regarding blood transfusion. Methods: The following studies were undertaken to inform the development of the decision aid: a systematic review and meta-analysis exploring the impact of information framing on patient treatment decision making; a systematic review and meta-analysis of controlled observational studies on PAD; and a survey (administered as a computer assisted telephone interview) of the views and opinions of physicians, patients, patients, and the public about blood transfusion. Decision aid development was guided by the Ottawa Decision Support Framework. The initial evaluation stages involved drafting and re-drafting the decision content by a group of experts in the fields of haematology, internal medicine, epidemiology, and health psychology. The final draft of the decision aid was reviewed by health professionals and patients who were about to have or had recently undergone major elective surgery. Participants provided feedback on its acceptability and identified areas for improvement during a semi-structures telephone interview. The decision aid was also quality assessed using the CREDIBLE criteria. Results: The results of a systematic review on information framing indicated that numerical data should be presented in more than one way to ensure patients form an accurate perception of treatment worth. In general, surgical and medical treatments tended to be preferred when information was expressed in a survival (positive) frame compared to a mortality (negative) frame, or when expressed as relative risk reduction (RRR) as opposed to absolute risk reduction (ARR) or number needed to treat (NNT) frames. The systematic review of controlled observational studies on PAD produced similar results to those from randomised controlled trials: PAD statistically significantly decreased the need for allogeneic blood yet increased the likelihood of receiving any transfusion (allogeneic/autologous) compared to usual care. Most studies (75%) did not use a transfusion protocol and seven studies reported using a more liberal protocol for the transfusion of autologous blood compared to allogeneic blood. Due to the paucity of research examining other clinical outcomes such as infection and thrombosis, there is insufficient data to determine the impact PAD may have on these outcomes. In surveys with patients, special interest group members and the public, one-third of respondents voiced concern with receiving an allogeneic blood transfusion, and most respondents overestimated the probability of contracting HIV and HCV through a blood transfusion when compared to other events of equal risk (e.g. being struck by lightning). Approximately 80% of respondents preferred PAD due to the perception that it eliminated all risks associated with a blood transfusion, is 100% compatible, and that it helps others through contributing to the blood supply. Although approximately half of the physicians interviewed used a transfusion trigger or protocol, individual patient characteristics were the main factor driving the decision of whether to transfuse. However, some respondents were critical of those who either did (or did not) use protocols, while others modified the "science of the guidelines" according to the needs of the individual. The final draft of the decision aid asked patients to consider the point at which they would prefer to receive a blood transfusion after major elective surgery (using haemoglobin values or transfusion "triggers" as a guide) and to decide whether or not to use PAD. The decision aid, "Blood Transfusion Options for Planned Surgery: A Decision Aid for Patients", consisted of a 32-page A5 size booklet and 28-minute audio tape or CD. The decision aid included the following sections: information about blood and blood loss; facts about blood transfusions; blood transfusions an you; your transfusion preference after surgery; approaches to replacing blood less; the differences between volunteer-donated and self-donated blood; adverse effects of blood transfusion; frequently asked questions; steps in decision making; and scientific references. A decision slip was included at the back of the booklet for patients to complete and return to their surgeon. Patients felt that the decision aid removed fears and common misconceptions associated with blood transfusion by providing them with more knowledge and realistic expectations of transfusion risks. Importantly, health professionals and patients felt that the information in the decision aid was presented in a balanced way and that it did not coerce patients to choose one particular option over another. Pilot data revealed that although the decision aid was generally well received, a number of revisions will be required before successful implementation. Important changes include; updating all information for recency; providing better explanations of numerical data; reducing the amount of information where appropriate; tailoring the decision aid for use in orthapaedic surgery (due to reduced utilisation rates of PAD); and clarifying the role of transfusion triggers in the decision aid, including whether it is appropriate to involved patients in that stage of the decision making process. The format of the decision aid also needs to be reconsidered (i.e. computer-based or continue with print and audio material) as costs and time restraints were highlighted as potential barriers to its use in practice. Based on the CREDIBLE criteria, the decision aid requires an updating policy, accessible documentation of the development process, and formal evaluation using a before-after pilot-study/randomised controlled trial. Conclusion: The task of developing and evaluating a decision aid on blood transfusion was found to be very complex and demanding. For instance, a number of in-depth studies were needed to adequately inform decision aid development and the decision aid still requires formal evaluation. However, the findings from the research undertaken in the thesis also reinforced the need for a decision aid on blood transfusion - the evidence on the benefits and harms of blood transfusion and PAD is controversial, practice variation exists, and personal values influenced patient and physician views of blood transfusion and PAD. Despite receiving positive feedback from health professionals and patients, the decision aid requires some significant modifications. Reduced utilisation rates of PAD indicate that a generic decision aid for procedures other than major orthopaedic surgery may not be relevant in practice. Although the issues surrounding blood transfusion justify the need for a decision aid, the desire for both patients and physicians for limited patient involvement regarding the decision of when to give a blood transfusion (using transfusion triggers as a guide) suggests that the aims of the decision aid in this area need to be reconsidered. However, as the number of older Australians undergoing major elective surgery rises due to population ageing, the availability of decision aids that adequately inform patients of the benefits and harms of blood transfusion and the option of PAD will be imperative. With further revision and evaluation, this decision aid should fulfill its promise as an effective tool for education patients about blood transfusion.

This work aims at studing the role of tachykinin NK-3 receptor (R) and kinin B1R in central autonomic regulation of blood pressure (BP) and to determine whether the B1R is overexpressed and functional in rat models of hypertension by measuring the effect of a B1R agonist on behavioural activity. Assumptions: (1) NK-3R located in the ventral tegmental area (VTA) modulates the mesolimbic dopaminergic system and has a tonic activity in hypertension; (2) B1R is overexpressed in the brain of hypertensive rats and has a tonic activity, which contributes to hypertension via a dopamine mechanism; (3) the inhibition of NK-3R and B1R with selective antagonists, reduces central dopaminergic hyperactivity and reverses hypertension. A model of genetic hypertension and a model of experimental hypertension were used: spontaneously hypertensive rats (SHR, 16 weeks) and Wistar-Kyoto (WKY) rats infused for 14 days with angiotensin II (Ang II) (200 ng / kg / min, subcutaneous (s.c.) with Alzet mini pump). The age-matched untreated WKY rats served as common controls. In the first study (article # 1), the cardiovascular response in SHR was evaluated following intracebroventricular (i.c.v.) and/or intra-VTA injection of an agonist (senktide) and antagonists (SB222200 and R-820) of NK-3R. These responses have also been characterized using selective dopamine antagonists DA-D1R (SCH23390), DA-D2R (raclopride) or non-selective dopamine DA-D2R (haloperidol). Also the VTA has been destroyed by ibotenic acid. The pressor response induced by senktide and the anti-hypertensive response induced by SB222200 or R-820 were more pronounced by intra-VTA. These responses were prevented by pre-treatment with raclopride and haloperidol. The lesion of the VTA has prevented the pressor response relayed by senktide (i.c.v.) and the anti-hypertensive effect of R-820 (i.c.v.). In addition, SB222200 (intra-VTA) prevented the pressor response of senktide (i.c.v.) and conversely, senktide (i.c.v.) prevented the antihypertensive effect of SB222200 (intra-VTA). The second study (article # 2) showed that the B1R antagonist (SSR240612) administered by gavage or i.c.v. reverses hypertension in both models. This anti-hypertensive effect was prevented by raclopride and haloperidol. In contrast, the two B1R antagonists (R-715 and R-954) injected s.c., which do not cross the blood-brain barrier reduced weakly blood pressure in hypertensive rats. In the third study (article # 3), the i.c.v. injection of a selective kinin B1R agonist Sar[DPhe8][des-Arg9]BK caused behavioural responses in SHR and Ang II-treated rats and had no effect in control WKY rats . The responses elicited by B1R agonist were blocked by an antagonist of NK-1 (RP67580), an antagonist of NMDA glutamate receptor (DL-AP5), an inhibitor of nitric oxide synthase (NOS) (L -NNA) as well as raclopride and SCH23390.The responses were modestly affected by the inhibitor of inducible NOS (iNOS). The B1R mRNA (measured by RT-PCR) was significantly increased in the hypothalamus, the VTA and the nucleus accumbens of hypertensive animals (SHR and treated with Ang II) compared with control rats. These neuropharmacological studies suggest that: (1) the NK-3R from the VTA is involved in the maintenance of hypertension in SHR by increasing DA transmission in the midbrain; (2) the B1R in SHR and Ang II-treated rats contributes to hypertension via a central mechanism involving DA-D2R; (3) the central B1R increases locomotor activity and nocifensive behaviours via the release of substance P (NK-1), DA and nitric oxide in both rat models of hypertension. Thus, the brain tachykinin NK-3R and kinin B1R represent potential therapeutic targets for the treatment of hypertension. The modulation of the mesolimbic/mesocortical dopaminergic pathway by these receptors suggests their involvement in other physiological functions (pleasure, motor activity, coordination of the response to stress) and pathophysiology (anxiety, depression).
Ce travail vise à étudier le rôle du récepteur NK-3 des tachykinines (NK-3R) et du récepteur B1 des kinines (B1R) dans la régulation autonomique centrale de la pression artérielle et de déterminer si le B1R est surexprimé et fonctionnel chez le rat hypertendu en mesurant l’effet d’antagoniste B1R sur l’activité comportementale. Hypothèses: (1) le NK-3R localisé dans l’aire tegmentale ventrale (VTA) module l’activité dopaminergique du système mésolimbique et possède une activité tonique dans l’hypertension; (2) le B1R est surexprimé dans le cerveau du rat hypertendu et possède une activité tonique qui contribue à l’hypertension via un mécanisme dopaminergique; (3) l’inhibition des NK-3R et B1R avec des antagonistes sélectifs réduit l’hyperactivité dopaminergique centrale et renverse l’hypertension. Un modèle d’hypertension génétique et un modèle d’hypertension expérimentale ont été utilisés: le rat spontanément hypertendu (SHR, 16 sem) et le rat Wistar Kyoto (WKY) infusé pendant 14 jours avec l’angiotensine II (Ang II) (200 ng/kg/min, s.c. avec mini pompe Alzet). Le rat WKY non traité du même âge a servi de témoin commun. Dans la première étude (article # 1), la réponse cardiovasculaire des SHR a été évaluée à la suite de l’injection i.c.v. et/ou intra-VTA d’un agoniste (senktide) et d’antagonistes (SB222200 et R-820) du NK-3R. Ces réponses ont aussi été caractérisées en utilisant des antagonistes sélectifs des récepteurs DA-D1R (SCH23390), DA-D2R (raclopride) ou non-sélectif DA-D2R (halopéridol). Aussi le VTA a été détruit par l’acide iboténique. La réponse pressive induite par senktide et la réponse anti-hypertensive induite par SB222200 ou R-820 étaient plus marquées par la voie intra-VTA. Ces réponses ont été prévenues par un pré-traitement avec le raclopride et l’halopéridol. La lésion du VTA a prévenu la réponse pressive relayée par le senktide (i.c.v.) ainsi que l’effet anti-hypertenseur du R-820 (i.c.v.). De plus, le SB222200 (intra-VTA) a prévenu la réponse pressive du senktide (i.c.v.) et inversement, le senktide (i.c.v.) a prévenu l’effet anti-hypertenseur du SB222200 (intra-VTA). La deuxième étude (article # 2) a montré que l’antagoniste du B1R (SSR240612) administré par gavage ou i.c.v. renverse l’hypertension artérielle dans les deux modèles. Cet effet dépresseur a été prévenu par le raclopride ainsi que l’halopéridol. Par contre, le traitement avec deux antagonistes du B1R (R-715 et R-954) qui ne traversent pas la barrière hémo-encéphalique a réduit faiblement la pression artérielle chez les rats hypertendus. Dans la troisième étude (article # 3), l’injection i.c.v. d’un agoniste sélectif du B1R, le Sar[DPhe8][des-Arg9]BK a causé des réponses comportementales typiques chez le SHR et le rat traité à l’Ang II mais il n’a pas eu d’effet chez le rat témoin WKY. Les réponses induites par l’agoniste B1R ont été bloquées par un antagoniste du récepteur NK-1(RP67580), un antagoniste du récepteur NMDA du glutamate (DL-AP5), un inhibiteur des synthétases du monoxyde d’azote (NOS) (L-NNA) ainsi qu’avec le raclopride et le SCH23390. Les réponses ont été modestement influencées par l’inhibiteur de la NOS inductible (iNOS). L’ARNm du B1R (mesuré par RT-PCR) était significativement augmenté dans l’hypothalamus, le VTA et le noyau accumbens des animaux hypertendus (SHR et traités à l’Ang II) comparativement aux rats témoins. Ces études neuropharmacologiques suggèrent : (1) que le NK-3R du VTA est impliqué dans le maintien de l’hypertension chez le SHR en augmentant la transmission DA au niveau du mésenséphale. (2) Le B1R chez le SHR et les rats traités à l’Ang II contribue à l’hypertension artérielle via un mécanisme central impliquant le DA-D2R. (3) le B1R central augmente l’activité locomotrice et les comportements défensifs, via la relâche de substance P (NK-1), de DA et de NO dans un modèle d’hypertension génétique et expérimental chez le rat. Ainsi, les récepteurs cérébraux NK-3 des tachykinines et B1 des kinines représentent des cibles thérapeutiques potentielles pour le traitement de l’hypertension artérielle. La modulation de la voie dopaminergique mésolimbique/mésocorticale par ces récepteurs suggère une participation dans d’autres fonctions physiologiques (plaisir, activité motrice, coordination de la réponse au stress) et en pathophysiologie (anxiété, dépression).

RESUMO: A síndrome da apneia obstrutiva do sono (SAOS) é uma perturbação respiratória relacionada com o sono, que tem vindo a ser cada vez mais prevalente. Esta condição clínica é responsável por uma multiplicidade de comorbilidades, com destaque para a hipertensão arterial sistémica (HTA). A etiopatogenia da SAOS inclui quatro principais características clínicas, nomeadamente a hipóxia crónica intermitente (HCI), a hipercapnia, o aumento da pressão intratorácica e a fragmentação do sono. Destas, a HCI assume-se como um factor chave no desenvolvimento de HTA. A SAOS é uma das causas principais de HTA resistente, o que significa que ainda não existe uma correta estratégia terapêutica para controlar este tipo particular de HTA. De facto, o efeito anti-hipertensivo da pressão positiva contínua nas vias aérea (CPAP), a terapêutica “gold-standard” para a SAOS, é moderado, e mesmo os fármacos anti-hipertensivos tradicionais mostram alguma ineficácia no controlo da HTA induzida pela SAOS, impelindo a procura de novas ferramentas terapêuticas. Assim, a investigação de novos alvos terapêuticos tem-se tornado uma área bastante promissora. Modelos animais de SAOS, reproduzindo uma das suas características fulcrais, a HCI, têm sido utilizados para investigar mecanismos de HTA associados à HCI, de forma a procurar novas abordagens terapêuticas, como é o caso desta dissertação. O objetivo geral desta tese é, então, a descoberta de um novo alvo terapêutico para tratar a HTA induzida pela HCI, com a utilização de um modelo animal. A maioria das abordagens terapêuticas para a HTA da HCI consistem no bloqueio do sistema simpático e/ou do sistema renina-angiotensina-aldosterona (SRAA), com alguns resultados positivos, mas ainda com resultados clínicos pouco expressivos. Na verdade, resultados anteriores do nosso grupo mostraram que o carvedilol (bloqueador α-e βadrenérgico) não teve nenhum efeito anti-hipertensivo num modelo animal de HTA induzido por HIC. Isso levou-nos a deduzir que outras vias de sinalização diretamente estimuladas pela HCI ao nível celular deveriam ser investigadas e manipuladas farmacologicamente, de forma a inferirmos o seu efeito na pressão arterial. Tendo em conta o seu envolvimento na regulação de processos adaptativos de longo-prazo, acreditamos que fatores de transcrição poderão ser elementos de ligação plausíveis entre os ciclos de hipóxia intermitente imediatos e os efeitos deletérios de longo prazo da SAOS-HCI, como a HTA. Tendo isto em conta, assumimos que o fator de transcrição receptor de aril hidrocarboneto (AHR) pudesse ser um putativo elemento mecanístico entre a HCI e a HTA com base em quatro argumentos principais: 1) O factor indutível pela hipóxia 1α (HIF-1α), que faz parte duma via de sinalização estimulada pela HCI, e o AHR partilham o mesmo parceiro de ligação nas suas vias de activação canónicas, sugerindo uma eventual ligação entre o HIF-1α e o AHR; 2) O AHR tem um papel importante na regulação da pressão sanguínea; 3) Alguns dos mecanismos moleculares que originam a HTA são comuns para o AHR e para a HCI (ativação do SRAA, stress oxidativo, disfunção endotelial, regulação de áreas cardiovasculares centrais (por exemplo no tronco cerebral); 4) A HCI, como estado inflamatório crónico que é, pode levar à sobreprodução de certos metabolitos que são ligados do AHR, como os metabolitos da quinurenina. Desta forma, a hipótese de trabalho desta tese está alicerçada em duas premissas principais: a HCI sobre-regula a via do AHR que, consequentemente, contribui para o desenvolvimento da HTA. Esta tese pretende investigar, pela primeira vez, o efeito da HCI na via do AHR e as consequências na HTA induzida pela HCI da sua manipulação farmacológica. De forma a concretizarmos este objetivo, ratos Wistar Han machos, com idades compreendidas entre as 8 e as 12 semanas, foram expostos a um paradigma ligeiro de HCI (5.6 ciclos/hora, 10.5 horas/dia, das 9.30h às 20h). Iniciámos as nossas experiências expondo grupos de ratos a vários períodos de HCI (14, 21 e 60 dias), e para cada período foi também utilizado um grupo controlo de animais expostos a condições de normóxia (Nx) durante o mesmo intervalo de tempo (n=5-8 animais por grupo). No final da exposição, os animais foram occisados e recolheu-se sangue e alguns órgãos (córtex e medula renais, fígado, tecido adiposo visceral, baço e hipocampo). Desses órgãos, procedemos à extração do ácido ribonucleico (ARN) total para se proceder à análise de reação em cadeia da polimerase (RCP) para alguns genes, nomeadamente relacionados com a via do AHR (Ahr, Cyp1a1, Cyp1b1, Cyp1a2, Arnt), da família do HIF (Hif1a, Epas1, Hif3a, Vegfa), da via do NF-kB pathway (Rela, Nfkb2, Il6, Il1b), do SRAA (Ren, Ace, Agtr1) e marcadores de transição epitelio-mesenquimal e de fibrose (Fn1, Vim, Cdh1, Col1a1, Acta2). Além disso, considerando que a HCI é uma condição caracterizada pela presença de stress oxidativo, analisou-se, por cromatografia líquida de alta performance, a dinâmica da cisteína, um tiol antioxidante, em rins de ratos expostos aos vários períodos de HCI. Também se quantificou, através de cromatografia liquida acoplada a espetrometria de massa, vários metabolitos do triptofano no plasma e urina em vários períodos de HCI (1, 7, 14, 21 e 60 dias) e em rins de animais expostos a 21 dias de HCI. No seguimento dessas experiências, modulou-se farmacologicamente a via do AHR com um antagonista, CH-223191 (5 mg/kg, uma vez por dia, por gavagem, em 1 m de óleo vegetal). Este antagonista foi utilizado em dois conjuntos principais de experiências. Um conjunto foi desenhado para verificar o potencial efeito preventivo deste composto na HTA induzida pela HCI, enquanto o outro conjunto foi desenhado mais especificamente para aferir o potencial efeito reversor deste composto. A pressão arterial e a frequência cardíaca foram medidas por radiotelemetria às 8h (período ativo, luzes apagadas) e às 18h (período inativo, luzes acesas). Após 21 dias de HCI, genes do SRAA estavam sobre-expressos no rim, bem como alguns genes da família dos HIFs (Hif1a, Epas1 and Hif3a). Rela estava sobre-regulado após 21 dias de HCI e o Nfkb2 após 60 dias, ambos no córtex renal. As expressões de mRNA do Nfkb2 e do Il6 estavam aumentadas, reflectindo os efeitos inflamatórios da HCI sobre o tecido adiposo. Durante o mesmo período de tempo (21 dias), um processo de transição epitelio-mesenquimal parecia estar a ocorrer no rim, com sobre-expressões dos genes de Fn1 e Vim.A dinâmica renal da cisteína também se alterou com a hipóxia. Ao longo do tempo, o conteúdo total de cisteína diminuiu, bem como a fração ligada às proteínas. Além disso, uma variação em forma de U no par redox (cisteína reduzida:oxidada) foi também observada, sugerindo que o rim é susceptível à lesão oxidativa desencadeada pela HCI. Adicionalmente, observou-se, no rim, um elevado rácio quinurenina:triptofano, revelando um estado pró-quinurenina, um conhecido ligando do AHR, que poderá promover, potencialmente, a activação do AHR. Em contraste, no plasma, encontraram-se vários metabolitos relacionados com a via da serotonina aumentados. O antagonista do AHR, CH-223191, foi capaz de prevenir e reverter parcialmente a HTA durante a fase ativa dos ratos (ou seja, no período em que as luzes estão desligadas). Contudo, durante o período inativo (fase em que as luzes estão ligadas e que ocorre simultaneamente com os ciclos de HCI), o efeito anti-hipertensivo do antagonista foi inexistente. Adicionalmente, o composto não recuperou a perda do perfil “dipping” da pressão arterial e da frequência cardíaca causado pela HCI. Em conclusão, a via do AHR parece estar sobre-activada no rim, após a exposição à HCI, e a sua modulação farmacológica interferiu no aumento da pressão arterial induzida pela HCI, tendo um significante efeito anti-hipertensivo durante o período ativo dos animais. Estes resultados estimulam estudos futuros de forma a clarificar o pleno potencial desta via como novo alvo terapêutico para tratar a HTN induzida pela HCI e SAOS, bem como o seu mecanismo de ação.
ABSTRACT: Obstructive sleep apnea (OSA) is a sleep-related breathing disorder that has becoming a more prevalent clinical condition in recent years. This clinical condition is responsible for a wide range of comorbidities, in particular systemic hypertension (HTN). OSA’s etiopathogenesis includes four clinical features, namely, chronic intermittent hypoxia (CIH), hypercapnia, increased intrathoracic pressure and sleep fragmentation. Among them, CIH is a well-established factor in the development of HTN. OSA is a major cause of resistant HTN, which means that the correct therapeutic strategy to control this particular type of HTN is still undefined. In fact, the antihypertensive effect of continuous positive airway pressure - CPAP (OSA’s gold standard therapeutic procedure) is moderate, and even traditional antihypertensive drugs show some lack of efficacy to control OSA-induced HTN, urging to find new suitable antihypertensive drugs. Therefore, the investigation for novel therapeutic targets is a hot topic in the field of OSA. Animal models of OSA, reproducing its major feature, CIH, have been used to investigate the mechanisms of HTN associated to CIH, in order to seek new therapeutic approaches, as this is the case of the present dissertation. The general goal of this thesis is to find a novel therapeutic target to HTN induced by CIH, with the use of an animal model. Most of the pharmacological approaches for HTN in CIH consisted in the abrogation of the sympathetic and/or the renin-angiotensin-aldosterone systems (RAAS), with some positive results, but still with weak outcomes. Indeed, previous results from our group showed that carvedilol (an α-and β -adrenergic blocker) had no antihypertensive effect in an animal model of HTN induced by CIH. These facts led us to deduce that other signaling pathways directly stimulated by CIH at cellular level should be investigated and pharmacologically manipulated to infer its effect over BP. We believe that transcription factors, as they are involved in long-term adaptive regulations, are plausible mechanistic bridges between the immediate cyclical intermittent hypoxia cycles and the long-term deleterious effects of CIH-OSA, as HTN. With this in mind, four major arguments converge to sustain the assumption that the transcription factor aryl hydrocarbon receptor (AHR) might be a putative mechanistic link between CIH and HTN: 1) Hypoxia inducible factor 1α (HIF-1α), a hypoxic signaling pathway known to be triggered by CIH, and AHR share the same binding partner to assist their canonical activation routes, suggesting a potential crosstalk/interplay between HIF-1 and AHR; 2) AHR has an important role in the regulation of blood pressure; 3) Some of the molecular mechanisms leading to HTN are common for AHR and CIH (RAAS activation, oxidative stress, endothelial dysfunction, regulation of central cardiovascular areas (for instance, in brainstem); 4) CIH, as a chronic inflammatory state, can lead to the overproduction of certain metabolites known to be AHR ligands (e.g. kynurenine metabolites). Thus, the working hypothesis of this thesis is the following: CIH upregulates the AHR circuitry, and consequently contributes to the development of systemic HTN. This thesis aims to investigate, for the first time, the effect of CIH on the AHR circuitry and the consequences of its pharmacological manipulation on HTN induced by CIH. In order to pursue this objective, male Wistar Han rats, aged 8-12 weeks, were exposed to a mild CIH paradigm (5.6 cycles/hour, 10.5 hours/day, from 9.30am to 8pm). We initiated our experiments by exposing groups of rats to a time-course of CIH. Groups of rats were exposed to 14, 21 and 60 days of CIH, and for each time-point, a corresponding control/normoxic (Nx) group was also used (n=5-8/group). At the end of the exposure, the animals were sacrificed and blood and several organs (renal cortex, renal medulla, liver, visceral adipose tissue, spleen and hippocampus) were collected. From those organs, we extracted total ribonucleic acids (RNA) to perform quantitative polymerase chain reaction analysis (qPCR) for several genes, namely genes involved in the AHR pathway (Ahr, Cyp1a1, Cyp1b1, Cyp1a2, Arnt), hypoxia inducible factor (HIF) family (Hif1a, Epas1, Hif3a, Vegfa), NF-kB pathway (Rela, Nfkb2, Il6, Il1b), RAAS members (Ren,Ace, Agtr1) and epithelial-mesenchymal transition and fibrosis markers (Fn1, Vim, Cdh1, Col1a1, Acta2). Moreover, considering that CIH is an oxidative stress disorder, we analyzed, by HighPerformance Liquid Chromatography with Fluorescence Detection (HPLC-FD), the dynamic of cysteine (Cys), an important antioxidant thiol, in the renal tissues of rats exposed to the CIH time-course. We also quantified several tryptophan metabolites by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in plasma and urine of several time-points (1, 7, 14, 21 and 60 days) and in kidney of CIH-exposed rats (21 days). Following these experiments, we modulated pharmacologically the AHR pathway, with an AHR antagonist, CH-223191 (5 mg/kg, once a day, by oral gavage in 1 ml of vegetable oil). We used the antagonist in two major sets of experiments. One set was designed to investigate particularly the preventive role of this compound on CIH-induced HTN, while the other aimed to determine its capacity to revert this outcome. BP and HR measurements were determined by radiotelemetry, at 8am (active period, lights-off) and 6pm (inactive period, lights-on). Following 21 days of CIH exposure, RAAS genes were overexpressed in the kidney, as well as some HIF family genes (Hif1a, Epas1 and Hif3a). Rela mRNA expression was upregulated after 21 days and Nkfb2 after 60 days of CIH, in the renal cortex. Visceral adipose tissue mRNA expressions of Nfkb2 and Il6 were increased, reflecting the inflammatory effects of CIH on the adipose tissue. In the same time-point (21 days), expression of epithelial-mesenchymal transition genes was increased (Fn1 and Vim overexpressions) in the kidney. Kidney cysteine dynamic was altered with hypoxia. Over time, we found an overall decrease in total cysteine content and in the protein bound fraction, and a U-shaped variation in their redox couple (reduced/oxidized), suggesting that kidney is susceptible to the oxidative damage triggered by CIH.In addition, we observed, in the kidney, an elevated kynurenine:tryptophan ratio (KTR), revealing a pro-kynurenine state, which may lead to AHR activation. In contrast, we found increased plasma levels of several serotonin-related metabolites. The AHR antagonist, CH-223191, was able to prevent and revert partially the HTN during the active phase of the animals (lights-off period). However, during the inactive phase (lights-on, simultaneous to the hypoxic cycles), the antihypertensive effect of the AHR antagonist was absent. Also, the compound did not recover the loss of the dipping profile of BP and HR originated by CIH. In conclusion, the AHR pathway seems to be overactivated in the kidney, upon CIH exposure, and its pharmacological modulation was able to counteract the increased BP, showing a significant antihypertensive during the active period. These results stimulate further studies to clarify the full potential of this pathway as a novel therapeutic target to HTN induced by CIH/OSA, as well as their mechanisms of action.
PTDC/MED-TOX/30418/2017

碩士
國立勤益科技大學
資訊工程系
102
The main reason to cause lethal heart rhythm VF / VT is that ICU patients have been found out the concentration of ions were imbalance in blood in the process of first aid. However, the recently diagnosis can only use blood testing to see whether the concentration of ions is normal or not, while it should take more than 30 minutes and usually delay the best first aid time then finally lead death. In this study, we use TRIZ theory, to solve the problem which the concentration of sodium, potassium calcium in blood are imbalance cause VF/ VT (lethal heart rhythm) by emergency course of ICU patient. We conduct the innovative research thinking. We analyze our thinking and reference step by step through using TRIZ theory. We can design a machine that monitor the concentration of minerals in blood in real time. Then we can monitor, inspect, record, building the database and treat the medicine by the concentration of minerals in blood. to cure the patient that the concentration of sodium, potassium, calcium are imbalance. In TRIZ Systematic Innovation, it use Problem Description, Problem Definition, then use 9 Windows Method to consider the useable and unusable resources and the constraints it may happen. Also, consider the useful and harmful effects, then find out the usable resources and harmful effects that need to be avoid. After that, redefined problems thinking the authenticity of the problems then drawing out the system model using ideality to help delimiting problems, and finally find out the IFR (Ideal Final Result). The choosing tools are to guide the problems already solved to correct solution tools. To think and find out the useful principles and parameters to solve the problems in 40 Inventive Principles and 39 Engineering Parameters and choose the improving factors and worsening factors from Contradictions Matrix then thinking and proving. After all design the products.