Dissertations / Theses on the topic 'Systemic circulation'

Circulating neutrophil activation occurs during cardiac surgery with extracorporeal circulation (ECC) and is implicated in the pathophysiology of inflammatory tissue injury and peri-operative organ dysfunction. However, neutrophil directed antiinflammatory strategies have failed to demonstrate consistent therapeutic benefit indicating that the nature and significance of peri-operative circulating neutrophil activation remains incompletely defined. In particular, conformational activation of the b2 integrin Mac-1 (CD11b/CD18), which is required for neutrophil adhesion competence and facilitation of effector functions, has not previously been investigated during cardiac surgery, and the relative contribution of cellular activation and bone marrow neutrophil recruitment to peri-operative changes in circulating neutrophil phenotype and function is unknown. A novel whole blood flow cytometric technique was used to analyze circulating neutrophil phenotype (total Mac-1, conformationally-active CD11b, CD10, CD16, L-selectin and P-selectin glycoprotein ligand-1) and function in cardiac surgery patients to characterize the nature of changes in Mac-1 expression and activation status, and the effects of relative neutrophil immaturity on circulating neutrophil phenotype and function. The effect of heparin, a known CD11b ligand, on Mac-1 epitope expression was also investigated. Circulating neutrophil numbers observed during ECC were mathematically modeled to determine the acute response of the bone marrow neutrophil reserve to an inflammatory stimulus. Plasma cytokine, chemokine and acute phase mediators were measured in cardiac and lung surgery patients to determine potential regulators of systemic neutrophil recruitment. Neutrophils newlyemergent from the bone marrow were characterized as CD10-/CD16low and exhibited distinct changes in cell surface markers and enhanced functional responses, relative to their more mature CD10+ counterparts. Conformational activation of CD11b occurred peri-operatively and provided a more sensitive measure of circulating neutrophil activation status than changes in total Mac-1 or L-selectin expression, although detection of Mac-1 epitopes was reduced in the presence of heparin. Modeling of circulating neutrophil numbers predicted that post-mitotic maturation time was acutely abbreviated by 8.4 hours during 71 minutes of ECC. Systemic chemokine release occurred with cardiac but not non-cardiac thoracic surgery indicating some specificity of the acute inflammatory response. These findings expand the understanding of peri-operative circulating neutrophil activation and recruitment, and identify potential therapeutic targets to limit neutrophil injurious potential during cardiac surgery with ECC.

Smelter workers who were exposed to air-borne arsenic for a mean of 23 years, and age-matched referents, were examined with clinical, physiological, and neurophysiological methods. Exposure to arsenic in workroom air was estimated to have been around the Swedish occupational limits, which were 500 yg/m before 1975 and 50 yg/ra thereafter. An increased preval ence of Raynaud's phenomenon and a reduced finger systolic blood pressure (FSP) during local and general cooling were found in the smelter workers. Slight, but significant sub-clinical neuropathy, in the form of slightly reduced nerve conduction velocity (NCV) in two or more peripheral nerves, was more common among the arsenic workers than among the referents. There were positive correlations between cumulative exposure to arsenic, reduced NCV in three peripheral motor nerves, and decrease in FSP during cooling. Arsenic levels in urine were 1 ymole/1 (75 yg/1) in the arsenic workers and 0.1 ymole/1 in the referents. In 21 arsenic workers with no or very low exposure to vibra ting hand tools, the FSP during cooling had increased significantly after 3 years wit h the lower arsenic exposure. There was no change in FSP during the summer vacation, whereas urinary levels of arsenic decreased to normal values. Thus there seems to be a slow improvement of finger blood circ ulation which is independent of short-term fluctuations in the exposure to arsenic. No seasonal variation was found in FSP during cooling with the standardized method used. When the NCV-measurements were repeated five years later the difference between arsenic workers and referents had increased, despite the fact that 14 of the 47 arsenic workers had had no exposure to arsenic during the last 1-5 years. These observations indicate, that in subjects with long term exposure to arsenic, sub-clinical neuropathy is not reversible. Ten milligrams of Ketanserin, a serotonin receptor antagonist, was given intravenously to five arsenic workers with cold-induced vasospasm. Skin temperature and FSP during cooling increased significantly with Ketanserin as compared wit h saline solution. After oral treatment, 2 x 40 mg /day for four weeks, no significant increase of FSP during cooling or rise in skin temperature was found in six arsenic workers and eleven patients with Raynaud's phenomenon. The decrease of vasospastic tendency after intravenous injection of Ketanserin indicated that similar mechanisms might operate in arsenic-induced and other types of Raynaud's phenomenon. A general co nclusion from the five studies in this dissertation is that long-term occupational exposure to arsenic has had adverse effects on the peripheral circulation and nerve conduction. The tendency to vasospasm, but not the sub-clinical neuropathy, seemed to be reversible with decreasing exposure.<br><p>S. 1-54: sammanfattning, s. 55-112: 5 uppsatser</p><br>digitalisering@umu

Antinuclear antibodies (ANA) are used in screening and diagnosis of autoimmune connective tissue disorders including systemic lupus erythematosus (SLE). CNS related disorders are prevalent in SLE patients (–80%) and ANA binds specific sites within the brain. To investigate ANA infiltration across the blood-brain barrier (BBB), an ANA injectable Lewis rat model was created using 3 rat groups (saline, ANA, and ANA with histamine; since histamine promotes BBB permeability). ANA serum levels were tested for all three rat groups and rats injected with histamine demonstrated signs of histadelia. Brain slices were obtained and examined for the presence of ANA using immunofluorescence. ANA infiltration across the BBB was observed in ANA injected groups. Though the ANA and ANA histamine groups were significantly different from controls (p<0.034, p<0.030, respectively), no significance between ANA and ANA histamine groups was observed. This model could further be used to examine BBB permeability and potential drug therapy.<br>Department of Physiology and Health Science

Background. Extensive studies have been conducted to simulate blood flow in the human vasculature using nonlinear equations of pulsatile flow in collapsible tube plus a network of vessels to represent the whole vasculature and the cerebral circulation. For non-linear models numerical solutions are obtained for the fluid flow equations. Methods. Equations of fluid motion in collapsible tubes were developed in the presence of gravitational force (Gforce). The Lax-Wendroff and MacCormack methods were used to solve the governing equations and compared both in terms of accuracy, convergence, and computer processing (CPU) time. A modified vasculature of the whole body and the cerebral circulation was developed to obtain a realistic simulation of blood flow under different conditions. The whole body vasculature was used to validate the simulation in terms of input impedance and wave transmission. The cerebral vasculature was used to simulate conditions such as presence of G-force, blockage of Internal Carotid Artery (ICA), and the effects on cerebral blood flow of changes in mean and pulse pressure. Results. The simulation results for zero G-force were in very good agreement with published experimental data as was the simulation of cerebral blood flow. Both numerical methods for solutions of governing equations gave similar results for blood flow simulations but differed in calculation performance and stability depending on levels of G-force. Simulation results for uniform and sinusoidal G-force are also in good agreement with published experimental results, Blood flow was simulated in the presence of a single (left) carotid artery obstruction with varying morphological structures of the Circle of Willis (CoW). This simulation showed significant differences in contralateral blood flow in the presence or absence of communicating arteries in the CoW. It also was able to simulate the decreases in blood flow in the cerebral circulation compartment corresponding to the visual cortex in the presence of G-force. This is consistent with the known loss of vision under increased acceleration. Conclusions. This study has shown that under conditions of gravitational forces physiological changes in blood flow in the systemic and cerebral vasculature can be simulated realistically by solving the one-dimentional fluid flow equations and non-linear vascular properties numerically. The simulation was able to predict changes in blood flow with different configurations and properties of the vascular network.

A lesão pulmonar é a principal causa de morte da Esclerose Sistêmica (ES), e as alterações principais são: o acometimento intersticial e o vascular. No presente estudo analisamos através do microscópio confocal a laser 40 artérias pulmonares de pequeno e médio calibre de pacientes com ES e 16 controles. Medimos a área do lúmen, a área total do vaso e fizemos a subtração da área total do vaso menos a do lúmen, e a porcentagem da área do lúmen em relação à área total do vaso. Observou-se que a área do lúmen e a porcentagem da área do lúmen em relação a área total do vaso são significativamente menores na ES em relação ao controle, e que a diferença entre a área total do vaso e a área do lúmen foi maior no grupo ES. Os achados confirmaram a hipótese inicial de acometimento das artérias pulmonares na ES, que se encontram espessadas devido à inflamação, infiltração celular em suas camadas e ativação endotelial<br>Lung injury is the leading cause of death in Systemic Sclerosis (SSc), and the main changes are: the vascular and interstitial involvement. In this study we analyzed through the confocal laser microscope 40 lung arteries of small and medium-sized of patients with SSc and 16 arteries of control group. We measured the lumen area, the total vessel area, made the subtracting the total vessel area minus the lumen area and the percentage between the lumen area and total vessel area. It was observed that the lumen area and the percentage between the lumen area and total vessel area were significantly lower in SSc group compared to control group, and the difference between the total vessel and the lumen area was higher in SSc. The findings confirmed the initial hypothesis of pulmonary arterial injury in SSc, wich are thickened due to inflammation, cellular infiltration into its layers and endothelial activation

Introdução. A Aprotinina parece reduzir o uso de transfusões, o processo inflamatório e o dano miocárdico, pós-CEC. Material e Métodos. Estudo prospectivo randomizado em crianças de 30 dias a 4 anos de idade, submetidas à correção de cardiopatia congênita acianogênica, com CEC e divididas em dois grupos, um denominado Controle (n=9) e o outro, Aprotinina (n=10). Neste, a droga foi administrada imediatamente antes da CEC. A resposta inflamatória sistêmica e disfunções hemostáticas e multiorgânicas foram analisadas por marcadores clínicos e bioquímicos. Foram consideradas significantes as diferenças com p<0,05. Resultados. Os grupos foram semelhantes quanto às variáveis demográficas e intra-operatórias, exceto por maior hemodiluição no Grupo Aprotinina. Não houve benefício quanto aos tempos de ventilação pulmonar mecânica, permanência no CTIP e hospitalar, nem quanto ao uso de inotrópicos e função renal. A relação PaO2/FiO2 (pressão parcial de oxigênio arterial/fração inspirada de oxigênio) apresentou queda significativa com 24 h PO, no Grupo Controle. Ocorreu preservação da concentração plaquetária com a Aprotinina enquanto no grupo Controle houve plaquetopenia desde o início da CEC. As perdas sangüíneas foram semelhantes nos dois grupos. No grupo Aprotinina surgiu leucopenia significativa, em CEC, seguida de leucocitose. Fator de necrose tumoral alfa (TNF-) , Interleucinas (IL)-6, IL-8, IL-10, proporção IL-6/IL-10, troponina I cardíaca (cTnI), fração MB da creatinofosfoquinase (CKMB), transaminase glutâmico-oxalacética (TGO) e fração amino-terminal do peptídio natriurético tipo B (NT-proBNP) não apresentaram diferenças marcantes intergrupos. A proporção IL-6/IL-10 PO aumentou no grupo Controle. A lactatemia e acidose metabólica pós-CEC foi mais intensa no grupo Aprotinina. Não houve complicações com o uso da Aprotinina. Conclusão. A Aprotinina não minimizou as manifestações clínicas e os marcadores séricos de resposta inflamatória sistêmica e miocárdicos, mas preservou quantitativamente as plaquetas.<br>Introduction. Aprotinin seems to reduce the need for transfusion, the inflammatory process and myocardial damage after extracorporeal circulation (ECC). Material and Methods. A prospective randomized study was conducted on children aged 30 days to 4 years submitted to correction of acyanogenic congenital heart disease with ECC and divided into two groups: Control (n=9) and Aprotinin (n=10). In the Aprotinin Group the drug was administered immediately before ECC and the systemic inflammatory response and hemostatic and multiorgan dysfunctions were analyzed on the basis of clinical and biochemical markers. Differences were considered to be significant when P<0.05. Results. The groups were similar regarding demographic and intraoperative variables, except for a greater hemodilution in the Aprotinin Group. The drug had no benefit regarding time of mechanical pulmonary ventilation, permanence in the postoperative ICU and length of hospitalization, or regarding the use of inotropic drugs and renal function. The partial arterial oxygen pressure/inspired oxygen fraction ratio (PaO2/FiO2) was significantly reduced 24 h after surgery in the Control Group. Platelet concentration was preserved with the use of Aprotinin, whereas thrombocytopenia occurred in the Control Group since the beginning of ECC. Blood loss was similar for both groups. Significant leukopenia was observed in the Aprotinin Group during ECC, followed by leukocytosis. Tumor necrosis factor alpha (TNF-), interleukins (IL)-6, IL-8, IL-10, IL-6/IL-10 ratio, cardiac troponin I (cTnI), creatine kinase MB fraction (CKMB), glutamic-oxaloacetic transaminase (GOT) and the aminoterminal fraction of natriuretic peptide type B (NT-proBNP) ndid not differ significantly between groups.The postoperative IL-6/IL-10 fraction increased significantly in the Control Group. Post-ECC blood lactate concentration and metabolic acidosis was more intense in the Aprotinin Group. There were no complications with the use of Aprotinin. Conclusion. Aprotinin did not minimize the clinical manifestations or serum markers of the inflammatory, systemic and myocardial response, but quantitatively preserved the platelets.

Le controle aerien doit assurer la separation des avions en minimisant les retards. Pour des raisons d'efficacite, des systemes d'evitement automatiques sont envisages avec, la ou le trafic est le moins dense, un transfert de responsabilites des controleurs aux avions. Un systeme d'evitement doit proposer des trajectoires d'evitement (assurant la separation). Il peut etre centralise ou embarque (chaque avion genere sa trajectoire). Nous presentons deux methodes pour generer des trajectoires d'evitement normalisees (definies par des instants de manuvres et des sens de deviation) : un algorithme branch and bound utilisant des methodes d'intervalles et un algorithme a*. Deux approches differentes de chacune de ces methodes sont decrites et testees sur des cas-tests de conflits. L'approche globale genere simultanement les trajectoires de tous les avions (systeme centralise). L'approche sequentielle les genere successivement, selon un ordre de priorite (forme sequentielle d'un systeme embarque). Des trajectoires de bonne qualite sont obtenues. Cependant, l'approche globale des methodes d'intervalles est tres couteuse en temps de calcul et celle de l'algorithme a*, en memoire. L'efficacite des approches sequentielles depend de l'ordre de priorite. L'algorithme a*, contrairement aux methodes d'intervalles, permet de considerer des vitesses variables (avions en montee ou en descente). Testee sur un simulateur de trafic reel, sa version sequentielle donne de bons resultats. Une methode de generation de trajectoires par commande continue (forme reactive d'un systeme embarque) est presentee ensuite. A chaque instant le cap de l'avion est modifie au moyen d'un reseau de neurone. L'apprentissage des reseaux de neurone se fait par algorithme genetique. Trois modes d'apprentissages sont compares : utilisation de bases d'apprentissage fixes et renouvelees, et coevolution. Les meilleurs resultats sont obtenus avec les bases renouvelees.

Ce travail analyse les differents aspects de l'information routiere. Il presente l'ensemble des intervenants qui collectent, traitent, elaborent et diffusent les differents messages qui constituent l'information routiere. Cette information, en tant qu'information mediatisee utilisable dans un espace et un temps pragmatique specifiques, est consideree comme une categorie particuliere de l'information pratique. Dans un premier temps, l'ouvrage etudie les causes economiques, sociologiques et historiques des phenomenes de congestion qui conduisent les gestionnaires du trafic a utiliser l'information comme outil d'exploitation des routes. Ensuite, l'information routiere est consideree comme une mediation technique. L'analyse systematique montre que les differents intervenants constituent un systeme technicien ou les outils et les procedures utilises a chaque etape du traitement de l'information contribuent a la construction de la realite. La signification des messages est abordee selon ce meme point de vue technique. Une comparaison des radioguidages et des emissions televisees met a jour les principaux dispositifs employes par les medias pour presenter au public l'etat de la circulation. Une approche complementaire, centree sur l'usager et fondee sur la philosophie de l'action, propose une logique informationnelle des situations d'interpretation des messages. Enfin, le document montre que la connaissance des usagers est un enjeu majeur. Une observation des pratiques professionnelles des journalistes de radio prouve qu'une conception utilitariste de la communication, presente chez de nombreux acteurs, neglige les logiques de diffusion des messages transmis par les autorites. De meme, l'analyse du processus de marchandisation de l'information routiere relativise les modeles applicables aux biens culturels. Elle demontre aussi l'importance des territoires domines par l'automobile et de la stabilisation des usages dans la reussite d'une tentative de marchandisation<br>This dissertation examines the various aspects of traffic information. All those who gather, process, elaborate and transmit road messages are presented. This type of information, transmitted by media and used at specific times and locatious is regarded as a particular category of practical information. The study deals first with the economical, sociological and historical causes of traffic congestion which lead traffic managers to use information as a tool to control road traffic. Then traffic information is studied as a technical medium in which tools and procedures contribute to the build-up of reality. The meaning of road message is also approached from technical view point. A comparison between route guidance on radio and on television discloses the main devices used by the media to present road traffic to the public. Finally the study shows how important it is to know road information users. Radio journalists have utilitarian communication practices. Road information is merchandised and cannot be studied as cultural goods. At last this study emphasizes the importance of automobile territories

La dysfonction des mécanismes de régulation vasculaire, observée dans les états de choc septique (CS), hémorragique (CH) et la cirrhose (C), remet en question l’efficacité des substances vasoactives utilisées. L’objectif de ce travail est l’évaluation hémodynamique, systémique et splanchnique de l’administration d’hydrogène sulfuré [H2S], de terlipressine [TP] et de noradrénaline [NE] au cours des complications des CS, CH et C. Suite à une ischémie/reperfusion (I/R) chez le rat, le sepsis n’a pas d’impact particulier sur le rein, lors de la phase précoce, alors que le débit rénal varie en réponse aux variations de pression artérielle, incluant le phénomène d’autorégulation. Le CS est associé très précocement à une augmentation du flux sanguin dans les capillaires péritubulaires et à une dysfonction rénale limitée par la perfusion de NE. Au cours d’un CH retransfusé et réanimé par un remplissage vasculaire, l’inhibition endogène de H2S aggrave la dysfonction rénale suite à une diminution des vitesses microcirculatoires péritubulaires et favorise un syndrome de fuite capillaire. A l’inverse, l’administration exogène de H2S pourrait provoquer un rétrocontrôle négatif sur l’activité de l’enzyme principale de production de H2S endogène, la CSE. Lors d’une hypertension portale par C chez le rat, la NE augmente la pression porte à faibles doses et augmente la contraction maximale des veines portes in vitro par rapport à la vasopressine, ce qui augmente le risque hémorragique. Au contraire, la TP diminue le débit mésentérique et la pression porte, ce qui favorise la réponse hémodynamique de réduction du risque d’hémorragie digestive<br>The impairment of vascular regulatory mechanisms observed in cirrhosis and shock situations, reduces the effectiveness of vasoactive substances used in treatments. The aim of this study is the hemodynamic, systemic and splanchnic assessments of vasoactive molecules proposed for the treatment of septic shock, hemorrhagic shock and cirrhosis complications (hydrogen sulfide [H2S], terlipressin [TP] and norepinephrine [NE]). In a model of ischemia/reperfusion (I/R), sepsis has no particular impact on the kidney since renal blood flow varies in response to mean arterial blood pressure variations, including an auto-regulation phenomenon. Sepsis is very rapidly associated with hypervelocity of blood flow in peritubular capillaries and renal dysfunction, both of wich are reserved by NE infusion. In hemorrhagic shock model controlled and resuscitated by Gelofusin® perfusion, we demonstrated that inhibition of endogenous H2S worsening renal dysfunction due to decreased renal peritubular microcirculatory velocities and promotes capillary leak syndrome. While the exogenous administration of H2S, could cause a negative feedback on the activity of the principal enzyme of endogenous H2S production, the CSE. During portal hypertension by cirrhosis in rats, NE increases the portal venous pressure, at low doses, and is more efficient than vasopressin on the portal veins of cirrhotic rats in vitro. However TP significantly reduces the mesenteric artery blood flow and the portal vein pressure. Taken together, TP could reduce the variceal bleeding risk associated with cirrhosis in comparison to NE

The goal of non-viral gene delivery is to treat illnesses stemming from gene deficiencies or overexpression without the use of viruses, which can cause severe immunogenic response. Many barriers face the delivery of DNA both in vivo and in vitro and must be overcome by the development of a complex multi-component carrier designed to address each challenge. While it is intuitive to develop a carrier in vitro, the requirements for in vivo gene delivery differ greatly, and often a non-viral carrier optimized in vitro will fail in the bloodstream in vivo due to high surface charge, which encourages blood protein binding, or dissociation of the polyplex leaving the DNA vulnerable to nucleases. It is evident that development of a non-viral gene delivery vector for use in vivo requires an easily amended platform to develop the carrier and a reproducible, calibrated assay to determine the expression of polyplexed DNA in vivo. Polyacridine peptides conjugated to polyethylene glycol (PEG) are a unique and characterizable set of carrier molecules that can be modified by peptide synthesis and various PEGylation strategies. Through the use of bioluminescence imaging and hydrodynamic stimulation (HS), a physical method that provides high levels of expression with small doses of DNA, it is possible to determine the state of polyplexed DNA in the bloodstream after various periods of circulation. The goal of this thesis was to overcome the first barrier of a systemically administered gene delivery system by developing a carrier molecule that reversibly binds to DNA and stabilizes it against metabolism in the bloodstream while avoiding undesirable biodistribution properties. The PEGylated polyacridine peptides presented herein were modified in response to each polyplex's in vivo performance based on pharmacokinetics, biodistribution, and gene expression by HS in mice after intravenous dosing. Modifications to the DNA-binding motif of the peptide were addressed initially along with various formulation strategies. Because PEG is installed to stealth polyplex surface properties, the effect of PEG attributes was also examined through optimization of PEG conjugation, size, and position. The results demonstrate the development of long circulating polyplexes that completely stabilize 1 µg of DNA in the bloodstream for five hours. This result provides a necessary prerequisite to allowing targeted accumulation of a polyplex at the site of action, which is the next step toward a fully-effective, systemically-administered non-viral gene delivery system.

Cette etude est une analyse experimentale des causes de forcage des circulations ageostrophiques dans les systemes jet-fronts, c'est-a-dire les systemes dynamiques constitues dans la haute troposphere par un maximum de courant-jet et un front d'altitude. Les circulations ageostrophiques associees a ces systemes sont a l'origine de processus encore mal connus tels que les processus de couplage dynamique entre la haute et la basse troposphere et les processus de foliation de tropopause donnant lieu a des echanges stratosphere-troposphere. L'analyse des termes de forcage des circulations ageostrophiques transverses et longitudinales au flux, induites respectivement par les effets inertiels et ceux de courbure, est obtenue par decomposition des champs ageostrophiques dans le repere naturel du vent total au niveau 300 hpa. Les donnees utilisees sont celles des analyses numeriques du modele du centre europeen de prevision meteorologique a moyen terme, ainsi que du modele peridot de la meteorologie nationale francaise pour 3 journees consecutives de la campagne experimentale fronts 84. L'etude experimentale est completee par des analyses isentropes dans des coupes transverses au courant-jet en utilisant les radiosondages du reseau synoptique, et par une detection des foliations de tropopause en utilisant les donnees satellitaires du canal vapeur d'au de meteosat 2 et de contenu en ozone total de l'atmosphere du spectrometre toms de nimbus 7. L'etude met en evidence plusieurs circulations ageostrophiques transverses indirectes interessant toute l'epaisseur de la troposphere, en accord avec des schemas conceptuels recents deduits d'une analyse des termes de forcage geostrophique de l'equation diagnostique de sawyer-eliassen. Dans les zones de courbure du flux, il est montre que la circulation ageostrophique dominante est la circulation longitudinale forcee par le terme d'advection de courbure. L'analyse conj

Abstract Cardiac surgery with cardiopulmonary bypass (CPB) results in hemodilution, systemic inflammatory response, activation of coagulation and fibrinolysis, and microembolisation, which may all contribute to postoperative organ dysfunction. As an attempt to attenuate these side effects, the use of minimized cardiopulmonary bypass (MCPB) systems has increased. Compared to conventional CPB (CCPB), they are characterized with reduced artificial surface area and blood-air interface. The goal of these alterations has been to reduce systemic inflammation, preserve coagulation function and minimize the need for blood tranfusions. This study was aimed at determining whether or not MCPB attenuates the adverse effects of CPB. In study I, the safety, feasibility and effect on transfusion requirements of MCPB was investigated in unselected coronary artery bypass surgery (CABG) patients. In studies II and III, the incidence of retinal microembolism after CABG and aortic valve replacement (AVR) surgery with MCPB was compared to that of CCPB by means of fluorescein angiography. Furthermore, in studies II and III, the effect of MCPB on systemic inflammation, coagulation, endothelial activation and injury, as well as on platelet activity, was compared to those of CCPB. In study IV, the effect of MCPB on intestinal mucosal damage following CPB was compared to CCPB in a porcine model of prolonged CPB. MCPB appeared as safe and feasible as CCPB in unselected CABG patients (Study I). MCPB was associated with decreased retinal microembolism compared to CCPB in CABG patients (Study II). Conversely, the difference in retinal microembolism in AVR patients was not statistically significant (Study III). MCPB was associated with a decrease in neutrophil activation in CABG and AVR patients as compared to CCPB. However, there were no differences in coagulation, endothelial activation and injury, or in platelet activity (Studies II, III). There were no differences in markers of intestinal mucosal damage between MCPB and CCPB following prolonged CPB in the experimental model (Study IV). The results of this study suggest that MCPB may be used safely with CABG patients, with beneficial effects on hematocrit, and attenuated neutrophil activation. In CABG patients, MCPB is associated with reduced retinal microembolism, suggesting a decreased embolic load to the brain. The clinical feasibility of MCBP requires further technical evolution in the management of valve surgery. The results of the animal model support previous concerns regarding intestinal mucosal damage during CPB<br>Tiivistelmä Sydänkeuhkokoneen käyttö aiheuttaa elimistössä hemodiluution, yleistyneen tulehdusvasteen ja hyytymisjärjestelmän aktivoitumisen sekä mikroembolisaatiota. Ilmiöt ovat yleensä lieviä ja ohimeneviä, mutta voivat johtaa elintoimintahäiriöihin ja pitkittyneeseen toipumiseen sydänleikkauksen jälkeen. Haittojen lievittämiseksi sydänkeuhkokonetta on pyritty kehittämään fysiologisemmaksi. Miniperfuusiolaitteistoissa kiertävän veren kontakti pintamateriaalien ja ilman kanssa jää pienemmäksi ja veren laimenemista tapahtuu vähemmän. Tutkimuksen tavoitteena oli selvittää voidaanko miniperfuusiolla lievittää sydänkeuhkokoneen haittoja. Ensimmäisessä osatyössä selvitettiin miniperfuusion käyttökelpoisuutta ja vaikutusta verensiirtotarpeeseen ohitusleikkauspotilailla valikoimattomassa aineistossa. Toisessa ja kolmannessa osatyössä selvitettiin silmänpohjan mikroembolioiden ilmaantuvuutta miniperfuusion ja perinteisen sydänkeuhkokoneen käytön jälkeen ohitusleikkauspotilailla ja aorttaläppäleikkauspotilailla. Toisessa ja kolmannessa osatyössä selvitettiin lisäksi miniperfuusion vaikutuksia yleistyneen tulehdusvasteen voimakkuuteen, hyytymisjärjestelmään sekä endoteelin aktivaatioon perinteiseen sydänkeuhkokoneeseen verrattuna. Neljännessä osatyössä verrattiin kokeellisessa mallissa miniperfuusion ja perinteisen sydänkeuhkokoneen vaikutuksia suoliston limakalvon eheyteen. Miniperfuusio ilmeni yhtä käyttökelpoiseksi kuin perinteinen sydänkeuhkokone ohitusleikkauspotilaiden hoidossa. Ohitusleikkauspotilailla ilmeni vähemmän silmänpohjan mikroembolioita miniperfuusion jälkeen, mutta aorttaläppäleikkauspotilailla ero ei ollut tilastollisesti merkitsevä. Miniperfuusion käyttöön liittyi vähemmän neutrofiilien aktivaatiota. Tekniikoiden välillä ei ilmennyt eroa hyytymisjärjestelmän eikä endoteelin aktivaatiota osoittavissa merkkiaineissa. Sydänkeuhkokoneen käyttö aiheutti saman tasoisen suoliston limakalvon vaurion miniperfuusiolla ja perinteisellä sydänkeuhkokoneella. Tutkimuksen perusteella miniperfuusiotekniikkaa voidaan käyttää turvallisesti ohitusleikkauspotilaiden hoidossa ja sen käyttö vähentää hemodiluutiota ja neutrofiilien aktivaatiota verrattuna perinteiseen sydänkeuhkokoneeseen. Miniperfuusiolla voidaan vähentää sydänkeuhkokoneen käytön aiheuttamaa silmänpohjan mikroembolisaatiota, joka saattaa viitata vähäisempään aivoverenkierron mikroembolisaatioon. Miniperfuusiotekniikoiden tulee edelleen kehittyä hyödyttämään enemmän myös aorttaläppäleikkauspotilaita. Löydökset koskien sydänkeuhkokoneen aiheuttamia suoliston limakalvovaurioita vahvistavat aiempaa olettamusta suoliston haavoittuvuudesta sydänleikkauksen jälkeen

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease that cause various inflammatory conditions in the body. The pathogenesis of this disease is yet unknown, and the diversity within the patients bring on major obstacle to clinical research for specific diagnostic markers. As a biomarker of SLE, both Interferon Regulatory Factor-5 (IRF5) and Microparticles (MP) have been suggested. Recently a study demonstrated higher concentration of IRF5+ MP in a small number of SLE patients compared to controls.  Aim: The purpose of this study was to validate and analyze IRF5+ MPs in a larger number of SLE patients and compare the results to known SLE subgroup based on IRF5 concentration.  Materials and methods: Totally 50 plasma samples from a larger cohort of SLE-patients (n=35) was analyzed together with population-based controls(n=15). Three different antibodies (in-house and commercial) were used for detection of IRF5+ MP with flow cytometry. Students t-test was used to investigate significant differences between SLE subgroup, controls and compared to the previous values. Results and Conclusion: The concentration of IRF5+ MP in SLE subgroup was significantly higher compared to controls (p&lt;0,05). However, there were no correlations between our results and the values from the previous study, suggesting that both methods measure various forms of IRF5. These results imply that IRF5+ MP could be a possible biomarker for pathogenesis in SLE, but further studies are needed for a better understanding of IRF5, as well as of MP.

Au cours des dernieres decennies, la demande de trafic au niveau des aeroports a augmente regulierement a tel point que le trafic au sol est devenu critique pour la securite et l'efficacite des operations aeroportuaires. Cette these propose une approche a deux niveaux pour l'analyse et l'optimisation du trafic avion au sol sur les aeroports. Elle est divisee en trois parties: - La premiere partie introduit la problematique generale et son environnement - La deuxieme partie traite la gestion a moyen terme du trafic au sol des avions. Une approche globale pour estimer la capacite theorique et la capacite pratique du trafic avion est proposee. Celle-ci met en Suvre une approche d'optimisation du flux dans un reseau qui conduit a la formulation de differents problemes de programmation mathematique - La troisieme partie traite du niveau tactique et une approche adaptative est developpee pour definir les routes et les horaires associes aux mouvement d'arrivee ou de depart des avions. Une approche de resolution operationnelle est alors proposee.

Le but de cette etude est d'analyser l'influence de l'orographie sur la circulation atmospherique de grande echelle et sur les transports verticaux, dans le cas d'un systeme jet-front. Ce travail est realise a partir de l'analyse des donnees des modeles du cepmmt, peridot, les mesures satellitaires toms/nimbus 7 et les donnees des radars st. L'etude des termes d'advection du tourbillon quasi geostrophique permet de localiser les influences des mouvements de grande echelle (maximum de courant-jet et effets de courbure) sur le champ de vitesse verticale. Ensuite, l'analyse diagnostique basee sur le vent ageostrophique total et le tourbillon potentiel permet de montrer que l'impact de l'orographie peut se traduire par la destruction locale des circulations ageostrophiques synoptiques, et par un plus faible developpement de la foliation de tropopause au-dessus du relief. Un logiciel de calcul de trajectoires cinetiques, dont la precision est evaluee, permet de mettre en evidence que l'impact local du relief modifie fortement la courbure des trajectoires synoptiques des particules, les transports verticaux et les echanges strato-tropospheriques. L'analyse des donnees peridot permet de mieux preciser la position du maximum de courant-jet par rapport au relief en fonction du temps, et de deduire les mouvements verticaux attendus au-dessus des massifs montagneux. L'intensite (0,1 m. S#-#1 en amont du relief et jusqu'a 2,5 m. S#-#1 au-dessus et en aval) et les variations de l'intensite (apparition d'onde) des vitesses verticales enregistrees par les radars st montrent leur capacite a mesurer des mouvements verticaux d'origines synoptique (en amont du relief) et orographique (au-dessus et en aval)

La caractérisation exaustive des variations de l'ADN peut aider à progresser dans de nombreux champs liés à la génomique du cancer. Le séquençage nouvelle génération (NGS en anglais pour Next Generation Sequencing) est actuellement la technique la plus efficace pour déterminer une séquence ADN, du aux faibles coûts et durées des expériences comparé à la méthode de séquençage traditionnelle de Sanger. Cependant, la détection de mutations à partir de données NGS reste encore un problème difficile, en particulier pour les mutations somatiques présentes en très faible abondance comme lorsque l'on essaye d'identifier des mutations sous-clonales d'une tumeur, des mutations dérivées de la tumeur dans l'ADN circulant libre, ou des mutations somatiques dans des tissus normaux. La difficulté principale est de précisement distinguer les vraies mutations des artefacts de séquençage du au fait qu'ils atteignent des niveaux similaires. Dans cette thèse nous avons étudié la nature systématique des erreurs dans les données NGS afin de proposer des méthodologies efficaces capables d'identifier des mutations potentiellement en faible abondance. Dans un premier chapitre, nous decrivons needlestack, un nouvel outil d'appel de variants basé sur la modélisation des erreurs systématiques sur plusieurs échantillons pour extraire des mutations candidates. Dans un deuxième chapitre, nous proposons deux méthodes de filtrage des variants basées sur des résumés statistiques et sur de l'apprentissage automatique, dans le but de d'améliorer la précision de la détection des mutations par l'identification des erreurs non-systématiques. Finalement, dans un dernier chapitre nous appliquons ces approches pour développer des biomarqueurs de détection précoce du cancer en utilisant l'ADN circulant tumoral<br>Comprehensive characterization of DNA variations can help to progress in multiple cancer genomics fields. Next Generation Sequencing (NGS) is currently the most efficient technique to determine a DNA sequence, due to low experiment cost and time compared to the traditional Sanger sequencing. Nevertheless, detection of mutations from NGS data is still a difficult problem, in particular for somatic mutations present in very low abundance like when trying to identify tumor subclonal mutations, tumor-derived mutations in cell free DNA, or somatic mutations from histological normal tissue. The main difficulty is to precisely distinguish between true mutations from sequencing artifacts as they reach similar levels. In this thesis we have studied the systematic nature of errors in NGS data to propose efficient methodologies in order to accurately identify mutations potentially in low proportion. In a first chapter, we describe needlestack, a new variant caller based on the modelling of systematic errors across multiple samples to extract candidate mutations. In a second chapter, we propose two post-calling variant filtering methods based on new summary statistics and on machine learning, with the aim of boosting the precision of mutation detection through the identification of non-systematic errors. Finally, in a last chapter we apply these approaches to develop cancer early detection biomarkers using circulating tumor DNA

Le bruit des transports terrestres est un problème clairement reconnu par la législation française. De même, la Commission Européenne propose actuellement d'étendre le champ de la lutte contre le bruit en créant de nouveaux indicateurs. Par ailleurs, l'utilisation de l'informatique en acoustique extérieure permet de modéliser la propagation des nuisances acoustiques et de réaliser des cartographies sonores.<br />La présente recherche vise à formaliser l'usage de cette nouvelle information géographique par l'analyse spatiale, afin de l'intégrer pleinement dans les processus de décision en aménagement du territoire. Elle a pour cadre une collaboration de recherche entre la Centre Scientifique et Technique du Bâtiment (CSTB) et le laboratoire SEIGAD de l'UJF.<br />Un travail méthodologique a permis d'évaluer les données nécessaires au calcul de propagation du bruit, les modes d'acquisition de ces données, les échelles spatiale et temporelle de traitement ainsi que la définition de la vulnérabilité du territoire au bruit.<br />Sur la base de cet environnement conceptuel, l'objectif est de produire un outil de gestion et d'évaluation des<br />impacts du bruit dans le territoire. Pour cela une interface entre un outil de modélisation du bruit en espace extérieur nommé Mithra et un système d'information géographique est réalisée.<br />Pour valider cette approche de traitement des impacts du bruit, deux maquettes de test sont proposées. La première concerne l'aménagement d'une ligne de tramway dans un quartier urbain dense. La seconde traite du problème des impacts du bruit dans une zone périurbaine. Pour chacune d'elles, l'information géographique relative aux niveaux d'exposition sonore est confrontée à différentes approches de la vulnérabilité du territoire au bruit.

Le remodelage ventriculaire gauche est une complication fréquente des patients ayantprésenté un syndrome coronarien aigu, pouvant conduire à terme à une situation d’insuffisancecardiaque. Il est donc important de connaître les facteurs associés à la survenue d’un remodelageventriculaire afin de dépister plus précocement les patients à plus haut risque d’insuffisance cardiaqueet ainsi optimiser leur prise en charge. Ce travail comprend deux axes. Le premier porte sur larecherche de nouveaux paramètres d’imagerie associés à la survenue du remodelage. Nous avonsdans un premier temps réalisé une revue de la littérature concernant la définition du remodelageventriculaire gauche en imagerie par résonance magnétique. Puis, nous avons conduit deux étudesayant pour but de rechercher une association entre (i) le strain atrial gauche et, (ii) le gradient depression intraventriculaire gauche diastolique, évalués en échocardiographie 24-48 heures après lesyndrome coronarien aigu et le remodelage ventriculaire gauche au cours du suivi. Le second axe portesur les biomarqueurs associés au remodelage ventriculaire post-infarctus. Nous avons réalisé une revuede la littérature au sujet des biomarqueurs qui, dosés lors de l’hospitalisation initiale, sont associés àl’existence d’un remodelage lors du suivi. Nous avons ensuite étudié la valeur prédictrice de deuxbiomarqueurs (la néprilysine et le coenzyme Q10) pour la survenue d’un remodelage ventriculairegauche<br>Left ventricular remodeling is a common complication in patients following acutemyocardial infarction and may lead to heart failure. Some baseline parameters are associated withremodeling at follow-up, allowing to better discriminate patients with an increased risk of heart failureto optimize therapeutics. This work has two axes, focused on imaging and biological parametersassociated with left ventricular remodeling, respectively. First, we reviewed past studies that definedremodeling using cardiac magnetic resonance imaging. Then, we studied the association betweensome echocardiographic parameters (left atrial strain and diastolic intraventricular pressure gradient)and left ventricular remodeling after ST-elevation myocardial infarction. In the other axis, wereviewed biomarkers that have been associated with left ventricular remodeling in prior studies. Then,we investigated the association between neprilysin and coenzyme Q10 levels and left ventricularremodeling in STEMI patients

Titre : Etude des associations entre facteurs nutritionnels et risque de cancers cutanés dans les cohortes E3N et EPICLes cancers cutanés sont les néoplasmes les plus fréquents chez les populations de type Caucasien et leur incidence est en constante augmentation. L'exposition aux rayonnements ultraviolets (UV) est le seul facteur environnemental reconnu comme cause avérée de cancer de la peau et actuellement le seul pour lequel une prévention est possible. Cependant, il apparait de plus en plus probable que certains facteurs nutritionnels, notamment les antioxydants, pourraient empêcher les effets néfastes de l'exposition aux UV et ainsi potentiellement représenter des agents de chimio-prévention des cancers cutanés. Il a également été suggéré que certains groupes d'aliments, tels que les agrumes, les compléments alimentaires, les acides gras, la vitamine D et l'alcool pouvaient être associés à un risque accru de cancers cutanés. Cependant, les études menées jusqu'à présent n'ont pas permis d'émettre de conclusion claire : peu d'études prospectives avec un échantillon suffisamment important et disposant de données sur l'exposition solaire sont disponibles. Il est donc nécessaire de faire progresser nos connaissances dans ce domaine afin de mieux cibler les campagnes de prévention des cancers cutanés.L’objectif principal de cette thèse était d’explorer les relations entre les facteurs nutritionnels et le risque de cancers cutanés. Les données utilisées dans ce projet incluent les données de la cohorte E3N, incluant près de 100 000 femmes françaises suivies depuis 1990, les données de la cohorte EPIC, incluant près de 520 000 participants issus de 10 pays européens, et les données du PMP, une étude prospective incluant 700 patients australiens atteints de mélanome suivis depuis 2014. De plus, les données de la littérature sur les liens entre vitamine D et mélanome ont été résumées et poolées dans une revue systématique et une méta-analyse.Nos résultats suggèrent que l’adhérence au régime méditerranéen est associée à risque plus faible de cancers cutanés, plus particulièrement de mélanome et de carcinome baso-cellulaire ; en revanche la prise de compléments alimentaires en bêta-carotène, vitamine A ou E était associée à un risque accru de carcinomes cutanés. De plus, nous avons observé que les consommations d’agrumes ou d’alcool étaient associées à un risque plus élevé de cancers cutanés. Par ailleurs, nos résultats suggèrent qu’une forte consommation d’un régime « riche en viande, poisson et graisses » est associée à l’épaisseur du mélanome. Enfin, les résultats de notre méta-analyse suggèrent que les taux circulants élevés de vitamine D sont associés à un risque accru de mélanome et de carcinomes cutanés.Les travaux de cette thèse ont mis en lumière des relations complexes entre les facteurs nutritionnels et le risque de cancers cutanés. Par ailleurs, ils soulèvent plusieurs questions qu’il serait envisageable d’approfondir dans d’autres études. Si ces résultats sont répliqués, ils pourraient, à terme, avoir un impact sur les stratégies de prévention des cancers cutanés.Mots-clés : cancers cutanés ; régime méditerranéen ; compléments en antioxydants ; agrumes ; alcool ; profils alimentaires ; vitamine D ; cohorte prospective ; méta-analyse<br>Title: Associations between nutritional factors and skin cancer risk in the E3N and EPIC cohortsSkin cancers are the most frequent neoplasms in Caucasian populations and their incidence has been constantly rising. Ultraviolet (UV) radiation exposure is the only environmental risk factor recognized as a cause of skin cancer and the only factor for which prevention is possible. However, it appears increasingly likely that several nutritional factors, particularly antioxidants, could counteract the negative effects of UV exposure and thus potentially represent chemo-preventive agents for skin cancer. It has also been suggested that several food groups, such as citrus, dietary supplements, vitamin D, fatty acids, and alcohol, could be associated with skin cancer risk. However, investigations to date did not allow to draw clear conclusions; few prospective data are indeed available within a sufficiently large sample and available sun exposure data. It is thus crucial to advance our knowledge in this field in order to target skin cancer prevention campaigns more precisely.The objective of this doctoral project was to study the relationships between nutritional factors and skin cancer risk. To achieve our objective, we used data from E3N, a prospective cohort of ~ 100,000 French women followed since 1990, data from EPIC cohort, a prospective cohort involving ~520,000 participants who have been followed-up in 23 centers from 10 European countries, and data from PMP, a prospective study of ~700 melanoma patients diagnosed in Queensland between 2010 and 2014. Additionally, data from the literature were summarized and pooled in a systematic review and meta-analysis.Our results suggest that adherence to the Mediterranean diet is associated with a lower skin cancer risk in women, particularly melanoma and basal-cell carcinoma. Intake of supplements in beta-carotene, vitamin A or E was associated with an increased keratinocyte cancer risk in women. In addition, we found positive linear relationships between citrus intake and skin cancer risk, which were mostly driven by associations with keratinocyte cancers, and between alcohol consumption and overall skin cancer risk. However, our results also suggest that people with high meat, fish, and fat intakes, who thus consumed relatively high levels of omega-3 and high omega-6 fatty acid intakes, are more likely to be diagnosed with thick than thin melanomas. In the meta-analysis, we found positive associations between serum 25(OH)D levels and melanoma and keratinocyte cancer risk.This project highlighted complex relationships between nutritional factors and the risk of skin cancers. It also raised several questions that could be considered for further study. If replicated and confirmed in future research, these findings may ultimately have important implications in skin cancer prevention.Keyword: skin cancer ; Mediterranean diet ; antioxidant supplements ; citrus ; alcohol ; dietary pattern; vitamin D; prospective cohort; meta-analysis

Chan Yau Chi.<br>Thesis (M.Phil.)--Chinese University of Hong Kong, 2005.<br>Includes bibliographical references (leaves 157-177).<br>Abstracts in English and Chinese.<br>Contents<br>Declaration --- p.i<br>Acknowledgement --- p.ii<br>Abbreviations --- p.iii-iv<br>Abstract in English --- p.v-viii<br>Abstract in Chinese --- p.ix-xi<br>Contents --- p.xii-xvi<br>Chapter CHAPTER I - --- Introduction<br>Chapter 1.1. --- Selective Estrogen Receptor Modulators (SERMs) --- p.1<br>Chapter 1.1.1. --- Raloxifene --- p.6<br>Chapter 1.2. --- Mechanisms of Action of SERMs in Vascular System --- p.7<br>Chapter 1.2.1. --- Estrogen --- p.7<br>Chapter 1.2.2. --- Estrogen Receptors (ERs) --- p.8<br>Chapter 1.2.3. --- General Mechanisms of Action of SERMs --- p.13<br>Chapter 1.2.4. --- Actions of Raloxifene --- p.14<br>Chapter 1.3. --- Effects of SERMs in Cardiovascular System --- p.14<br>Chapter 1.3.1. --- Effects of SERMs on Endothelial Function --- p.15<br>Chapter 1.3.2. --- Effects of SERMs on Vascular Smooth Muscle --- p.17<br>Chapter 1.4. --- Effects of Raloxifene on Vascular Circulations --- p.18<br>Chapter 1.4.1. --- Effects of Raloxifene on Systemic Circulation --- p.18<br>Chapter 1.4.1.1. --- Preclinical Data --- p.18<br>Chapter 1.4.1.1.1. --- Effects on Serum Lipids --- p.18<br>Chapter 1.4.1.1.2. --- Effects on Inflammation Markers and Blood Coagulation --- p.19<br>Chapter 1.4.1.1.3. --- Antioxidative Effects --- p.19<br>Chapter 1.4.1.1.4. --- Effects on Nitric Oxide and Endothelial Function --- p.19<br>Chapter 1.4.1.1.5. --- Effects on Vascular Smooth Muscle --- p.20<br>Chapter 1.4.1.1.6. --- "Vascular Injury, Atherosclerosis and Ischaemia-Reperfusion Injury" --- p.20<br>Chapter 1.4.1.2. --- Clinical Studies - Effects in Post-Menopausal Women --- p.21<br>Chapter 1.4.1.2.1. --- "Effects on Serum Lipids, Lipoproteins and Triglycerides" --- p.21<br>Chapter 1.4.1.2.2. --- Effects on Inflammation Markers and Homocysteine --- p.22<br>Chapter 1.4.1.2.3. --- Effects on Coagulation Markers --- p.23<br>Chapter 1.4.1.2.4. --- Effects on Endothelial Function --- p.23<br>Chapter 1.4.1.2.5. --- Cardiovascular Events --- p.23<br>Chapter 1.5. --- Myogenic Response and Vascular System --- p.24<br>Chapter 1.5.1. --- Initiation and Development of Myogenic Response --- p.25<br>Chapter 1.5.2. --- Regulation of Myogenic Response --- p.26<br>Chapter 1.5.2.1. --- 20-hydroxyeicosatetraenoic acid (20-HETE) --- p.26<br>Chapter 1.5.2.2. --- "Protein Kinase C, Rho/Rho-Kinase, and Tyrosine Kinase" --- p.27<br>Chapter 1.5.3. --- Myogenic Response and Endothelium --- p.31<br>Chapter 1.5.4. --- Estrogen and Myogenic Tone --- p.31<br>Chapter 1.6. --- Objectives of the Present Study --- p.32<br>Chapter CHAPTER II - --- Methods and Materials<br>Chapter 2.1. --- Tissue and Cell Preparation --- p.34<br>Chapter 2.1.1. --- Vessel Preparation --- p.34<br>Chapter 2.1.2. --- Removal of a Functional Endothelium --- p.36<br>Chapter 2.2. --- Myograph and Pressure Myograph Setups --- p.36<br>Chapter 2.2.1. --- Myograph 一 Isometric Tension Measurement --- p.36<br>Chapter 2.2.2. --- Pressure Myograph - Isobaric Diameter Measurement --- p.37<br>Chapter 2.3. --- Intracellular [Ca2+] Measurement in Vascular Smooth Muscle --- p.42<br>Chapter 2.4. --- Chronic Raloxifene Therapyin Spontaneously Hypertensive Rats (SHRs) and Wistar-Kyoto Rats (WKYs) --- p.42<br>Chapter 2.4.1. --- Surgical Procedure - Raloxifene Tubing Insertion --- p.42<br>Chapter 2.4.2. --- "Body Weight, Mean Arterial Blood Pressure and Uterine Weight" --- p.42<br>Chapter 2.4.3. --- Measurement of Raloxifene Tubing Consumption --- p.43<br>Chapter 2.4.4. --- Effect of Chronic Raloxifene Treatment on Artery Reactivity --- p.43<br>Chapter 2.5. --- Ovariectomy and Chronic Raloxifene Therapyin Syrian Golden Hamsters --- p.45<br>Chapter 2.5.1. --- Surgical Procedure - Ovariectomy (OVX) --- p.45<br>Chapter 2.5.2. --- Surgical Procedure - Raloxifene Tubing Insertion --- p.45<br>Chapter 2.5.3. --- High-Cholesterol Food Preparation --- p.45<br>Chapter 2.5.4. --- "Body Weight, Food Consumption and Uterine Weight" --- p.46<br>Chapter 2.5.5. --- Measurement of Raloxifene Tubing Consumption --- p.46<br>Chapter 2.5.6. --- Serum Lipid and Lipoprotein Determinations --- p.46<br>Chapter 2.5.7. --- Effect of Chronic Raloxifene on Artery Reactivity --- p.46<br>Chapter 2.6. --- Solutions and Drugs --- p.49<br>Chapter 2.6.1. --- "Drugs, Chemicals and Enzymes" --- p.49<br>Chapter 2.6.2. --- Solutions --- p.51<br>Chapter 2.6.3. --- Diet Composition for Syrian Golden Hamsters --- p.51<br>Chapter 2.7. --- Statistical Analysis --- p.52<br>Chapter CHAPTER III - --- "Raloxifene Relaxes Rat Pulmonary Arteries and Veins: Roles of Gender, Endothelium, and Antagonism of Ca Influx"<br>Chapter 3.1. --- Abstract --- p.53<br>Chapter 3.2. --- Introduction --- p.54<br>Chapter 3.3. --- Methods and Materials --- p.55<br>Chapter 3.3.1. --- Blood Vessel Preparation --- p.55<br>Chapter 3.3.2. --- Protocols --- p.55<br>Chapter 3.3.3. --- Measurement of Vascular Smooth Muscle [Ca2+]i --- p.56<br>Chapter 3.3.4. --- Drugs --- p.57<br>Chapter 3.3.5. --- Data Analysis --- p.53<br>Chapter 3.4. --- Results --- p.58<br>Chapter 3.4.1. --- Effects of Raloxifene on Pulmonary Arteries --- p.53<br>Chapter 3.4.2. --- Effect of Raloxifene on CaCl2-induced Constrictionin Pulmonary Arteries --- p.59<br>Chapter 3.4.3. --- Effects of Raloxifene on Pulmonary Veins --- p.59<br>Chapter 3.4.4. --- Effect of Raloxifene on CaCl2-stimulated Increases in [Ca2+]i in Pulmonary Arteries --- p.60<br>Chapter 3.5. --- Discussion --- p.67<br>Chapter 3.6. --- Conclusion --- p.69<br>Chapter CHAPTER IV - --- Raloxifene Modulates Pulmonary Vascular Reactivity in Spontaneously Hypertensive Rats<br>Chapter 4.1. --- Abstract --- p.70<br>Chapter 4.2. --- Introduction --- p.71<br>Chapter 4.3. --- Methods and Materials --- p.72<br>Chapter 4.3.1. --- Raloxifene Treatment --- p.72<br>Chapter 4.3.2. --- Blood Vessel Preparation --- p.72<br>Chapter 4.3.3. --- Protocols --- p.73<br>Chapter 4.3.4. --- Chemicals and Drugs --- p.73<br>Chapter 4.3.5. --- Data Analysis --- p.74<br>Chapter 4.4. --- Results --- p.74<br>Chapter 4.4.1. --- Blood Pressure --- p.74<br>Chapter 4.4.2. --- Vasocontraction in Spontaneously Hypertensive Rats --- p.75<br>Chapter 4.4.3. --- Vasorelaxation in Spontaneously Hypertensive Rats --- p.75<br>Chapter 4.4.4. --- Vasocontraction in Wistar-Kyoto rats --- p.76<br>Chapter 4.4.5. --- Vasorelaxation in Wistar-Kyoto rats --- p.77<br>Chapter 4.4.6. --- Comparison of contraction between WKY and SHR rats --- p.78<br>Chapter 4.4.7. --- Comparison of relaxation between WKY and SHR rats --- p.78<br>Chapter 4.5. --- Discussion --- p.93<br>Chapter 4.6. --- Conclusion --- p.96<br>Chapter CHAPTER V - --- Effects of Therapeutic Concentrations of Raloxifene in Pressurized Rat Small Mesenteric Artery<br>Chapter 5.1. --- Abstract --- p.98<br>Chapter 5.2. --- Introduction --- p.99<br>Chapter 5.3. --- Methods and Materials --- p.101<br>Chapter 5.3.1. --- Blood Vessel Preparation --- p.101<br>Chapter 5.3.2. --- Experimental Protocols --- p.102<br>Chapter 5.3.2.1. --- Myogenic Tone Development --- p.102<br>Chapter 5.3.2.2. --- Effects of Raloxifene and 17β-EstradioI on Myogenic Constriction --- p.102<br>Chapter 5.3.2.3. --- Effects of Pharmacological Inhibitors on Raloxifene- or 17β-Estradiol-induced Myogenic Constriction --- p.103<br>Chapter 5.3.3. --- Drugs and Solutions --- p.103<br>Chapter 5.3.4. --- Expression of Results and Statistical Analysis --- p.104<br>Chapter 5.4. --- Results --- p.104<br>Chapter 5.4.1. --- Effects of Raloxifene and 17β-Estradiol on Rat Resistance Mesenteric Arteries1 --- p.104<br>Chapter 5.4.2. --- Effects of Inhibitors of NOS --- p.105<br>Chapter 5.4.3. --- Effect of CTX plus Apamin --- p.106<br>Chapter 5.4.4. --- "Effect of ICI 182,780" --- p.106<br>Chapter 5.4.5. --- "Effects of Wortmannin, LY 294002 and Cycloheximide" --- p.106<br>Chapter 5.5. --- Discussion --- p.122<br>Chapter 5.6. --- Conclusion --- p.125<br>Chapter CHAPTER VI - --- Effects of Chronic Raloxifene Treatment on Vascular Reactivity in Pressurized Septal Coronary Arteries from Hamsters Fed with High-Cholesterol Diet<br>Chapter 6.1. --- Abstract --- p.127<br>Chapter 6.2. --- Introduction --- p.128<br>Chapter 6.3. --- Methods and Materials --- p.129<br>Chapter 6.3.1. --- Preparatory Work --- p.129<br>Chapter 6.3.1.1. --- Animals and Diets --- p.129<br>Chapter 6.3.1.2. --- Preparation of High-Cholesterol (HC) Food --- p.129<br>Chapter 6.3.1.3. --- Surgical Procedure - Ovariectomy (OVX) --- p.129<br>Chapter 6.3.1.4. --- Surgical Procedure - Raloxifene Tubing Insertion --- p.130<br>Chapter 6.3.1.5. --- Blood Vessel Preparation --- p.130<br>Chapter 6.3.1.6. --- "Body Weight, Food Consumption and Uterine Weight" --- p.131<br>Chapter 6.3.1.7. --- Measurement of Raloxifene Tubing Consumption --- p.131<br>Chapter 6.3.1.8. --- Serum Lipid and Lipoprotein Determinations --- p.132<br>Chapter 6.3.2. --- Experimental Protocols --- p.132<br>Chapter 6.3.2.1. --- Development of Myogenic Tone --- p.132<br>Chapter 6.3.2.2. --- Pressure-Diameter Relationships --- p.132<br>Chapter 6.3.2.3. --- The Effect of Acetylcholine --- p.133<br>Chapter 6.3.2.4. --- The Effect of U46619 --- p.133<br>Chapter 6.3.2.5. --- The Effect of L-NAME --- p.133<br>Chapter 6.3.3. --- Drugs and Solutions --- p.133<br>Chapter 6.3.4. --- Expression of Results and Statistical Analysis --- p.134<br>Chapter 6.4. --- Results --- p.135<br>Chapter 6.4.1. --- Effects on Myogenic Response --- p.135<br>Chapter 6.4.2. --- "Effects of Acetylcholine, U46619 and L-NAME" --- p.135<br>Chapter 6.4.2.1. --- Comparison between OHHCD and OvxOHHCD --- p.135<br>Chapter 6.4.2.2. --- Comparison between OvxOHHCD and OvxOHHCDRf --- p.135<br>Chapter 6.4.2.3. --- Comparison between OHHCDRf and OvxOHHCDRf --- p.136<br>Chapter 6.4.2.4. --- Comparison between OHHCD and OHHCDRf --- p.136<br>Chapter 6.5. --- Discussion --- p.155<br>Chapter 6.6. --- Conclusion --- p.156<br>References --- p.157<br>Publications --- p.176

碩士<br>國立臺灣師範大學<br>科學教育研究所<br>95<br>This study investigated how students interpreted the representational structures of images and the the relationships between images and texts during the process of scientific texts reading from the perspective of Systemic Functional Linguistics (SFL). Nighty four seventh grade students who had finished the program of blood circulation were selected as participants of this study. All participants filled out questionnaire developed by the researcher. In addition, all participants were separated into high, middle and low groups based on the scores of science in mid-term exam. Then six participants were chosen randomly from each group to take the one-to-one and semi-structural interview. Content analysis was used to analize the content of images. The foci of data analization were on two aspects. One was the frequencies of all kinds of interpretations about the representational structures through image reading. And the other was the frequencies of connections between text segregations and representational structures of texts. First, the results showed that the image reading was affected by the complexity of representational structures. The analytical process of conceptual representations was more conherent for those with text-attribute. But on the contrary, the analytical process was much more related with the participants’ prior knowledge for those without text-attribute. Most of the processes of actions were directional narration in narrative structures reading. Furthermore, the interpretations competed with each other for the one composed of narrative and conceptual structures. Second, the relation between image and word was built up by the meaning of “carrier” in conceptual representation. Moreover, the interpretations for complete sentence and representational structures were more likely in the conceptual aspect. Instead, the interpretations for imcomplete sentence were close to those in the word segregation. Finally, implications for science education would be discussed as well.