Dissertations / Theses on the topic 'Hyperoxia'
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Tähepõld, Peeter. "Myocardial protection by hyperoxia /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-247-7.
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Cox, April. "Effects of hyperoxia in alzheimers transgenic mice." Scholar Commons, 2005. http://scholarcommons.usf.edu/etd/2836.
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An association between major surgery in the elderly and precipitation of Alzheimers disease (AD) has been reported. Hyperoxia (100%) oxygen is commonly administered after surgery to increase the oxygen content of blood. However, hyperoxia is a potent cerebral vasoconstrictor and generator of free radicals, as is [beta]amyloid (A[beta];). This study was aimed at examining behavioral, neuropathological, and neurochemical effects of hyperoxia treatments in APPsw transgenic mice (Tg+), which have elevated brain A[beta]; levels by 3-4 months of age but are not yet cognitively-impaired. At 3 months of age, Tg+ mice were pre-tested in the radial arm water maze (RAWM) task of working memory and found to be unimpaired. At 4.5 months of age, half of the Tg+ mice received the first of 3 equally-spaced hyperoxia sessions (3 hrs each) given over the ensuing 3 months. The other half of the Tg+ mice were exposed to compressed air during these 3 sessions.
RAWM testing performed immediately following the final gas session at 7.5 months of age revealed significant working memory impairment in Tg+ mice exposed to hyperoxia. The Tg+ group that was exposed to placebo treatment showed a trend towards impairment, however, was not significantly different from the non-transgenic group. Hyperoxia-induced memory impairment in Tg+ mice did not involve changes in brain A[beta] deposition, degenerative cell numbers in hippocampus, neocortical lipid peroxidation, or hippocampal levels of APP, ApoE, COX-2, or GFAP. The combination of excess A[beta] and hyperoxia could have induced greater oxidative stress and cerebral vasoconstriction than either one alone, resulting in a pathologic cerebral hypoperfusion that triggered subsequent cognitive impairment.
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Flynn, Erin Patricia. "Experimental infarct mitigation with hyperoxia at normobaric pressure." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0020/MQ55207.pdf.
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Burghardt, Jacqueline Sarah. "Leukotrienes mediate hyperoxia-induced lung damage in newborn rats." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ34743.pdf.
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Ruusalepp, Arno. "Signal transduction in restenosis and myocardial protection by hyperoxia /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-705-7/.
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Phillips, Gary John. "The role of inflammation in hyperoxia-induced lung injury." Thesis, University of Southampton, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295865.
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Brage, Olivia, and Sara Berglund. "Hyperoxygenering : – I vilken utsträckning exponeras patienter för höga syrgaskoncentrationer under anestesi?" Thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-325645.
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Det har under en längre tid funnits en stor vilja att under den perioperativa fasen ge patienter höga koncentrationer av syrgas med motiveringen att förbättra vävnadsperfusion och därmed den postoperativa återhämtningen. Nyare studier har påvisat de komplikationer vilka hyperoxygenering skulle kunna medföra i form av ökad mortalitet och morbiditet. Syftet med föreliggande studie var att undersöka huruvida patienter utsätts för hyperoxygenering peroperativt. Studien inkluderade 100 patienter och har genomförts genom en deskriptiv retrospektiv journalgranskning med tillägg av jämförande analyser mellan de undersökta operationsavdelningarna. Huvudresultat för studien var att samtliga undersökta operationsavdelningar hyperoxygenerade patienter under anestesi. För hela det undersökta underlaget uppmättes medelvärdet av parametern maximalt PaO2 till 30,7 ±11,7 kPa och medelvärdet av det genomsnittligt inspiratoriska FiO2 uppmättes till 45,5 ±7,6 %. Det högst uppmätta PaO2-värdet var vid en av de undersökta operationsavdelningarna 66,5 kPa. Slutsatsen vilken kan dras av denna studie är att patienter som undergår anestesi hyperoxygeneras till en nivå som visats innebära ökade risker och hyperoxygenering skulle potentiellt kunna vara ett större peroperativt problem än vad som idag är känt.For a long period of time, there has been a great desire to provide high concentrations of oxygen in patients during the perioperative phase with the motivation to improve tissue perfusion and postoperative recovery. Recent studies have shown that hyperoxygenation may result in complications such as increased mortality and morbidity. The purpose of the present study was to investigate if patients are exposed to hyperoxygenation perioperatively. The study included 100 patients and was conducted through a descriptive retrospective journal review, with the addition of comparative analyzes between the investigated surgical departments. The main result of the study was that all investigated surgical departments hyperoxygenated patients under anesthesia. For the entire sample material examined, the average parameter of the substrate PaO2 was measured to 30.7 ±11.7 kPa, and the mean of the average inspirational FiO2 was measured to 45,5 ±7,6 %. The highest measured PaO2 value at one of the surgical departments being investigated was 66,5 kPa. In conclusion, the results from this study shows that patients undergoing anesthesia are presently being hyperoxygenated up to a level associated with increased risks, and that hyperoxygenation potentially is a greater peroperative problem than currently known.
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Bustani, Porus C. "The role of hyperoxia in abnormal development of fetal lung." Thesis, University of Leicester, 2007. http://hdl.handle.net/2381/4567.
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Hyperoxia is closely linked with the development of chronic lung disease of prematurity (CLD) but the fixant mechanisms whereby hyperoxia alters lung architecture in the developing lung remain largely unknown.
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Fussell, Julia. "The influence of hyperoxia and dexamethasone on pulmonary protein synthesis." Thesis, University of Southampton, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.316304.
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Floen, Miranda J. "Thioredoxin-1| Identification of redox substrates and response to hyperoxia." Thesis, University of South Dakota, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10132866.
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Bronchopulmonary dysplasia (BPD) is a serious respiratory complication for the preterm newborn characterized clinically by prolonged respiratory distress and histologically by alveolar simplification and decreased pulmonary vasculature. The development of BPD is well linked to oxidative stress suffered by the newborn as a result of a preterm fetal-neonatal transition, supplemental oxygen, infection, increased inflammation, and mechanical ventilation. Damage suffered by oxidative stress may be through direct mechanisms or through alteration of redox¬sensitive pathways involved in cell death, cell survival, differentiation, and proliferation. Redox¬sensitive modifications regulating protein function and redox-sensitive pathways have mainly been ascribed to oxidative modification of cysteine thiols. As their modification is critical for protein function, maintenance of the thiol redox status is crucial. Thioredoxin-1 (Trx1) functions in maintenance of thiol redox homeostasis, and its redox activity is intimately linked to antioxidant, cytoprotection, proliferation responses, and cytoprotection. While Trx1 targets of redox regulation have been identified, we hypothesize that additional protein may be redox regulated and that Trx1 target profiles may change during oxidative stress. Therefore a novel immunoprecipitation approach, identified as the substrate trap approach, was developed to identify Trx1 targets. The following demonstrates the use of the substrate trap approach for identification of Trx1 redox targets and further application of the approach to identify alterations in target profiles in response to oxidative stress. Use of nuclear targeted substrate trap was successfully employed to enrich from nuclear Trx1 targets. As a final component the characterization of the Trx1 system in mouse from late embryonic development through the first week of life animals were exposed to room air or hyperoxia (model of BPD). Characterization indicates impairment of the Trx1 system in response to hyperoxic injury. As Trx1 is known to regulate proliferation, cell death, survival, differentiation pathways, impairment of the Trx1 system during early neonatal development may potentiate hyperoxic injury and alterations in lung development. Better understanding of Trx1 interactions occur through the substrate trap in a physiological model of BPD will help elucidate redox-signaling pathways involved in BPD pathogenesis.
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Rousseau, Andréas. "Vascular effects of hyperoxaemia and its mechanisms in man /." Linköping : Dept. of Medicine and Care, Univ, 2005. http://www.bibl.liu.se/liupubl/disp/disp2005/med891s.pdf.
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Galvin, Orla Majella. "Hyperoxia-induced retinal endothelial cell injury and the therapeutic potential of Omega-3 polyunsaturated fatty acids." Thesis, Queen's University Belfast, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.680118.
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Duffy, Sandra. "Consequences of in vitro hyperoxia on Plasmodium falciparum tolerance to artemisinin." Thesis, Griffith University, 2021. http://hdl.handle.net/10072/411264.
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Plasmodium falciparum is the major causative agent of malaria in man and is responsible for over 400,000 deaths per year, predominantly in Sub-Saharan Africa. P. falciparum exists in many forms within both the human host and mosquito vector. In clinical malaria the parasite resides within the red blood cells of the human host and is transmitted from one host to another through the blood feeding bite of the female Anopheles mosquito. Malaria, as a disease, is completely curable, and many countries have eradicated malaria, including Australia in 1981. However, malaria remains endemic in most poor countries. Overall, both case numbers and mortality rates are decreasing each year, primarily due to improved preventative measures, and importantly the use of artemisinin combination therapies (ACT) employed globally.
The chink in the armour of chemotherapeutics currently available for the treatment of malaria is parasite drug resistance. Artemisinin was believed to be the exception, as stable in vitro generated artemisinin resistant parasites proved difficult to obtain. However, in 2007, clinical parasite delayed clearance times were observed for the artemisinin derivative, artesunate, used as a monotherapy in Western Cambodia, the epicentre of anti-malarial drug resistance origins. Standard laboratory drug sensitivity tests did not detect differences in parasite sensitivity between those from patients with or without delayed parasite clearance times. The use of artemisinin derivatives as a combination therapy was advocated, but underlying artemisinin tolerance, or partial resistance originating in Western Cambodia, has resulted in the acquisition of partner drug resistance and ultimately failure of standard 3-day ACT treatment regimens.
A single nucleotide polymorphism in a kelch-13 (K13) propeller domain (PF3D7_1343700) was identified through escalating artemisinin drug exposure and recovery in vitro, correlating with extended in vivo parasite clearance times, providing a reliable molecular marker of artemisinin tolerance. This singular study, resulting in the parasite strain F32-ART5, is the only in vitro artemisinin drug resistance study to acquire a K13 mutation (M476I), which in itself was intriguing. Based on the validated scientific foundation that in vitro culturing conditions for P. falciparum can have experimental consequences, the culturing conditions involved in the generation of F32-ART5, and that of several other studies, were reviewed. A significant difference in oxygen levels between the K13 mutant parasite F32-ART5 culturing conditions and other studies was identified. F32-ART5 was generated under hyperoxic conditions (21%O2), known to cause oxidative stress in P. falciparum, whilst other studies employed lower O2 levels of 1-5%.
As well as K13 mutations, a parasite “genetic background” with enhanced antioxidative stress, repair and survival signatures is associated with extended parasite clearance times and acquisition of K13 mutations in founder populations of P. falciparum in Western Cambodia. The coincidence of a K13 mutation acquired in hyperoxic or stressed conditions (F32-ART5), and the relationship between anti-oxidative stress capabilities with K13 mutations in vivo, appeared to be not so coincidental when viewed together. Based on these two observations, it was hypothesised that hyperoxia would cause enhanced tolerance to artemisinin-based drugs, such as dihydroartemisinin. To test this hypothesis, a recently developed in vitro assay was employed, which identifies dihydroartemisinin tolerance of K13 mutant parasites and is referred to as the ring stage survival assay, or RSA.
In this study, the effect of hyperoxic exposure on twelve P. falciparum strains comprising those with naturally acquired K13 mutations, genetically engineered K13 parasite strains, K13 wild type clinical isolates and laboratory strains, were evaluated for dihydroartemisinin tolerance and growth characteristics in response to hyperoxic stimuli. To effectively monitor the impact of hyperoxia on parasite strain tolerance to dihydroartemisinin, a robust and highly reproducible protocol for the ring stage survival assay was established, incorporating a highly structured in vitro culturing programme. The 12 parasite strains were tested for the effect of hyperoxia on growth, as well as dihydroartemisinin tolerance.
Parasite growth effects in hyperoxic conditions were deemed to be “genetic background” associated, with little or no impact of the presence or not of K13 mutations. Dihydroartemisinin tolerance was demonstrated to be K13 dependant, noticeably reduced after hyperoxic exposure, and the degree of parasite survival modulated by the parasite genetic background. The effect of hyperoxic exposure on dihydroartemisinin tolerance was observed to be parasite stage specific, namely between 0-20hr post red blood cell invasion and associated with the growth cycle prior to drug challenge.
This study has demonstrated the effect parasite “genetic background”, in combination with K13 mutations on the ability of P. falciparum to modulate tolerance to dihydroartemisinin and other endoperoxide drugs. Without due consideration of in vitro culturing parameters used for P. falciparum, and comprehensive review of why only one study obtained a K13 mutation in vitro, this tolerance modulatory effect associated with the parasite genetic background, that is observed under oxidative stress conditions, may not have been identified. In conclusion, it is proposed that P. falciparum with K13 mutations and an associated “genetic background” are responsive to environmental stimulus and have a fitness advantage when responding to changes in environmental background. In stress conditions this genetic background maintains growth and a base level of DHA tolerance, whilst under non-stressed conditions, it has an even greater advantage due to elevated dihydroartemisinin tolerance. The transmission from stressed to non-stressed conditions could therefore select for the K13 mutations in both conditions.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Environment and Sc
Science, Environment, Engineering and Technology
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A, Ahern Megan, Black Claudine P, Seedorf Gregory J, Baker Christopher D, and Shepherd Douglas P. "Hyperoxia impairs pro-angiogenic RNA production in preterm endothelial colony-forming cells." AMER INST MATHEMATICAL SCIENCES-AIMS, 2017. http://hdl.handle.net/10150/626103.
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Disruptions in the response of endothelial progenitor cells to changes in oxygen environment may present a possible mechanism behind multiple pediatric pulmonary disease models, such as bronchopulmonary dysplasia. Using high-throughput fixed single-cell protein and RNA imaging, we have created "stop-motion" movies of Thymosin. 4 (T beta 4) and Hypoxia Inducible Factor 1 alpha (HIF-1 alpha) protein expression and vascular endothelial growth factor (vegf) and endothelial nitric oxide synthase (eNOS) mRNA in human umbilical cord-derived endothelial colony-forming cells (ECFC). ECFC were grown in vitro under both room air and hyperoxia (50% O-2). We find elevated basal T beta 4 protein expression in ECFC derived from prematurely born infants versus full term infants. T beta 4 is a potent growth hormone that additionally acts as an actin sequestration protein and regulates the stability of HIF-1 alpha. This basal level increase of T beta 4 is associated with lower HIF1 alpha nuclear localization in preterm versus term ECFC upon exposure to hyperoxia. We find altered expression in the pro-angiogenic genes vegf and eNOS, two genes that HIF-1 alpha acts as a transcription factor for. This provides a potential link between a developmentally regulated protein and previously observed impaired function of preterm ECFC in response to hyperoxia.
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Mehdi, Madah Khawn i. Muhammad. "The impact of exposure to constant light and hyperoxia on the retina." Thesis, Strasbourg, 2013. http://www.theses.fr/2013STRAJ025.
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Les yeux forment des avant-postes visuels importants du cerveau. Comme les autres organes, la rétine sensorielle des yeux est vulnérable aux effets nocifs des facteurs environnementaux, tels que la lumière et l'oxygène. Dans ce travail, nous nous sommes concentrés sur l’impact de l’exposition à une lumière constante et l’hyperoxie prolongée sur l'architecture et la fonction rétinienne. Dans la première partie de notre étude, nous avons montré qu’ une exposition de sept jours à une lumière constante perturbe la phagocytose des bâtonnets et cônes et régule négativement leur renouvellement dans la « rétine riche en cônes " d’Arvicanthis ansorgei. Notre étude donne un aperçu sur la physiopathologie des cônes, ce qui représente la principale source de handicap visuel dans une variété de pathologies rétiniennes, y compris la rétinite pigmentaire (RP) et la dégénérescence maculaire liée à l'âge (DMLA). Dans la deuxième partie de notre étude, nous avons montré qu’ une exposition de cinq jours à l’hyperoxie entraîne chez les souris néonatales une perte significative de cellules ganglionnaires dans les régions périphériques de la rétine, et de cellules à mélanopsine (ipRGC). L’exposition prolongée à l’hyperoxie perturbe également la capacité de photoentrainment des animaux probablement due à la perte des ipRGC et la perte de la rhodopsine dans les segments externes des bâtonnets chez les animaux traitésEyes form important visual outposts of the brain. Just like other organs, sensory retina in the eyes is also vulnerable to the injurious effects of environmental factors; such as light and oxygen. In this work, we have focused on the impacts of constant prolonged light and hyperoxia on the retinal architecture and function. In the first part of our study, we show that seven days of constant light disrupts rod and cone phagocytosis and downregulates their turnover in the “cone rich retina” of Arvicanthis ansorgei. The study gives an insight on the cone pathophysiology, which represents the major source of visual handicap in a variety of retinal pathologies, including retinitis pigmentosa (RP) and age-related macular degeneration (AMD). In the second part of our study, we show that five days of hyperoxia treatment in the neonatal mice results in the significant loss of retinal ganglion cells in the peripheral regions; the loss of melanopsin expressing retinal ganglion cells (ipRGC) was found to be significant. Hyperoxia also affects the photoentrainment capability of the animals probably because of the loss of ipRGC and the loss of rhodopsin in the outer segments of the photoreceptors in the treated animals
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Howlett, Clare E. "Inhaled nitric oxide protects against hyperoxia-induced apoptosis in the rat lung." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0018/MQ48155.pdf.
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Tillmans, Frauke [Verfasser]. "Effect of normobaric hyperoxia on leukemic cell lines in vitro / Frauke Tillmans." Ulm : Universität Ulm, 2018. http://d-nb.info/1158664281/34.
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McKechnie, Stuart R. "The roles of hyperoxia and mechanical deformation in alveolar epithelial injury and repair." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/2691.
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The alveolar epithelium is a key functional component of the air-blood barrier in the lung. Comprised of two morphologically distinct cell types, alveolar epithelial type I (ATI) and type II (ATII) cells, effective repair of the alveolar epithelial barrier following injury appears to be an important determinant of clinical outcome. The prevailing view suggests this repair is achieved by the proliferation of ATII cells and the transdifferentiation of ATII cells into ATI cells. Supplemental oxygen and mechanical ventilation are key therapeutic interventions in the supportive treatment of respiratory failure following lung injury, but the effects of hyperoxia and mechanical deformation in the injured lung, and on alveolar epithelial repair in particular, are largely unknown. The clinical impression however, is that poor outcome is associated with exposure of injured (repairing) epithelium to such iatrogenic ‘hits’. This thesis describes studies investigating the hypothesis that hyperoxia & mechanical deformation inhibit normal epithelial repair. The in vitro data presented demonstrate that hyperoxia reversibly inhibits the transdifferentiation of ATII-like cells into ATI-like cells with time in culture. Whilst confirming that hyperoxia is injurious to alveolar epithelial cells, these data further suggest the ATII cell population harbours a subpopulation of cells resistant to hyperoxia-induced injury. This subpopulation of cells appears to generate fewer reactive oxygen species and express lower levels of the zonula adherens protein E-cadherin. Using a panel of antibodies to ATI (RTI40) and ATII (MMC4 & RTII70) cell-selective proteins, the effect of hyperoxia on the phenotype of the alveolar epithelium in a rat model of resolving S. aureus-induced lung injury was investigated. These in vivo studies support the view that, under normoxic conditions, alveolar epithelial repair occurs through ATII cell proliferation & transdifferentiation of ATII cells into ATI cells, with transdifferentiation occurring via a novel intermediate (MMC4/RTI40-coexpressing) immunophenotype. However, in S. aureus-injured lungs exposed to hyperoxia, the resolution of ATII cell hyperplasia was impaired, with an increase in ATII cell-staining membrane and a reduction in intermediate cell-staining membrane compared to injured lungs exposed to normoxia alone. As hyperoxia is pro-apoptotic and known to inhibit ATII cell proliferation, these data support the hypothesis that hyperoxia impairs normal epithelial repair by inhibiting the transdifferentiation of ATII cells into ATI cells in vivo. The effect of mechanical deformation on alveolar epithelial cells in culture was investigated by examining changes in cell viability following exposure of epithelial cell monolayers to quantified levels of cyclic equibiaxial mechanical strain. In the central region of monolayers, deformation-induced injury was a non-linear function of deformation magnitude, with significant injury occurring only following exposure to strains greater than those associated with inflation of the intact lung to total lung capacity. However, these studies demonstrate for the first time that different epithelial cell phenotypes within the same culture system have different sensitivities to deformation-induced injury, with spreading RTI40-expressing cells in the peripheral region of epithelial cell monolayers and in the region of ‘repairing’ wounds being injured even at physiological levels of mechanical strain. These findings are consistent with the hypothesis that alveolar epithelial cells in regions of epithelial repair are highly susceptible to deformation-induced injury.
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Huyard, Fanny. "Impact du stress hyperoxique en période néonatale sur la structure vasculaire : implication des phénomènes de sénescence et rôle possible dans la programmation développementale de l'hypertension artérielle." Thèse, Université de Lorraine, 2013. http://hdl.handle.net/1866/12773.
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Réalisé en cotutelle avec l'Université de Lorraine (France)Ce projet traite de la programmation développementale de l’hypertension artérielle (HTA) à travers des influences néonatales précoces pouvant moduler le développement vasculaire. Les bébés prématurés présentent des défenses antioxydantes diminuées comparés aux nouveau-nés à terme et sont exposés à la naissance à des concentrations élevées en oxygène (O2) engendrant la production d’espèces réactives de l’O2 (ERO). Les conséquences vasculaires à long terme de dommages liés aux ERO en période néonatale et les mécanismes impliqués sont très partiellement compris. Les précédents résultats du laboratoire ont montré qu’un stress hyperoxique néonatal conduit chez le rat adulte à de l’HTA, une dysfonction endothéliale et une rigidité artérielle, éléments de vieillissement vasculaire. Nous émettons l'hypothèse qu'un stress hyperoxique néonatale conduit à long terme à l'altération de la structure vasculaire et à un vieillissement vasculaire précoce. Nous avons démontré une diminution de la prolifération cellulaire, une capacité angiogénique altérée, des dommages à l’ADN et une augmentation de l’expression de protéines de sénescences (des indices de sénescence cellulaire) au-delà de la période néonatale suite à une exposition brève à l’O2 au niveau vasculaire dans un modèle animal (ratons Sprague-Dawley exposés à 80 % d’O2 du 3ème au 10ème jour de vie comparés à des ratons restés à l’air ambiant) et cellulaire (cellules musculaires lisses d'aortes thoraciques d'embryon de rat exposées à 40% O2 pendant 24h ou 48h, puis remises en normoxie pendant 96h). De plus, des altérations des composants de la structure vasculaire indiquant un remodelage vasculaire aortique ont été mises en évidence. Ces changements précèdent tous l’HTA et la dysfonction vasculaire observées dans le modèle animal à l’âge adulte et pourraient y contribuer. L’étude de jeunes adultes nés < 29 semaines comparés à des jeunes adultes nés à terme indique une augmentation de marqueurs de rigidité artérielle (indices d’un vieillissement vasculaire précoce) chez la population prématurée. L’ensemble des résultats démontre un vieillissement vasculaire précoce après une exposition néonatale transitoire à un stress hyperoxique permettant une meilleure compréhension des mécanismes physiopathologiques impliqués dans la survenue des troubles vasculaires retrouvés chez l’adulte et contribue à la mise en place de moyens de prévention chez des patients prématurés.
The scope of this thesis is developmental programming of arterial high blood pressure (HBP) hypertension through early neonatal stimuli that may alter vascular development. Premature newborns have decreased antioxidant defenses compared to term babies and are exposed upon birth to high oxygen (O2) concentration, causing reactive oxygen species (ROS) production. Long term vascular consequences of ROS related damage during the neonatal period and the mechanisms involved remain unknown. Recent data from the laboratory show that neonatal hyperoxic stress leads in adult rat to HBP, endothelial dysfunction and arterial rigidity, characteristic features of vascular aging. We hypothesize that a neonatal hyperoxic stress leads to long term vascular structure alteration explained by an early aging of the vascular system. We showed a decreased proliferation rate, an altered angiogenic capacity, as well as long term DNA damage and increased expression of senescence proteins at a vascular level following O2 exposure in the animal (male Sprague-Dawley pups kept at 80% O2 from postnatal days 3 to 10 vs. rats remained in room air) and cellular models (embryonic vascular smooth muscle cells from rat thoracic aorta exposed to 40% O2 for 24h or 48h followed by 96h recovery in control conditions). In addition, alterations of vascular structure components indicating vascular remodeling was shown before the onset of the HBP at adult age. Those changes precede the HBP and vascular dysfunction observed in our animal model at adult age and could contribute to them. Study of young adults born before 29 weeks vs. young adults born at term showed that young adults born preterm present indices of arterial stiffness vs. term controls. Results of the present thesis demonstrate a major role of premature vascular aging in the surge of vascular diseases in adulthood and contribute to a better understanding of the patho-physiological mechanisms involved and could put into practice new prevention strategies among preterm patients.
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Lewallen, Melissa Anjanette. "Chronic Hypoxia and Hyperoxia Modifies Morphology and Vegf Expression of the Lungs of the Developing Chicken (Gallus Gallus Domesticus)." Thesis, University of North Texas, 2012. https://digital.library.unt.edu/ark:/67531/metadc177224/.
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This study determines effects of oxygen levels on morphology and VEGF expression of developing chicken lungs following incubation in normoxia (21% O2), hypoxia (15% O2) or hyperoxia (30% O2), until developmental days 16 or 18. Lung morphology was assessed using light microscopy, while VEGF expression was determined with ELISA. In hypoxia, the proportion of parabronchial tissue and parabronchi including lumina increased from day 16 to 18 (61 to 68% and 74.2 to 82.2%, respectively). Non-parabronchial tissue was higher in hypoxia than in hyperoxia on day 16 (26 to 20%). However, by day 18, there were no differences between groups. VEGF expression was 33% higher in hypoxia than in hyperoxia on day 16 (736 vs. 492 pg/ml). On day 18, VEGF expression was 43% higher in hyperoxia than in normoxia (673 to 381pg/ml), and remained elevated by 40% in hypoxia over normoxia (631 pg/ml). VEGF may be a mechanism by which parabronchial tissue is stimulated from day 16 to 18 following exposure to chronic hypoxia.
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Torrentino-Madamet, Marylin. "Influence des conditions environnementales sur le métabolisme de Plasmodium falciparum." Thesis, Aix-Marseille 2, 2010. http://www.theses.fr/2010AIX20700/document.
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P. falciparum est le principal responsable des formes graves du paludisme. Le parasiteévolue entre deux hôtes (homme et moustique) qui lui imposent différents environnements; ettout particulièrement, des modifications des pressions partielles d’O2 nécessitant des capacitésd’adaptation surprenantes pour un parasite microaérophile. Chez l’hôte vertébré, lesphénomènes de cytoadhésion, ralentissant la progression du parasite notamment au niveau despoumons, augmentent la durée d’exposition aux conditions hyperoxiques.La dynamique de la réponse parasitaire à l’hyperoxie a été étudiée par une approchecombinée de transcriptomique et de protéomique. Certains mécanismes de défense contre lesespèces réactives d’oxygène ont été appréciés, dont une éventuelle fonction oxydasealternative.L’exposition du parasite à 21% d’O2 induit un retard de croissance au niveau de laschizogonie. Le stress oxydatif induit par l’hyperoxie entraîne des perturbations métaboliquescomme une inhibition de la glycolyse en faveur de la respiration et un ralentissement dumétabolisme de la vacuole digestive. Cette action combinée sur le métabolisme mitochondrialet vacuolaire permet au parasite de s’adapter à un environnement hyperoxydant, en régulant laproduction d’espèces réactives d’oxygène. Nos travaux ont montré qu’un inhibiteur de lafonction oxydase alternative, l’acide salicylhydroxamique ou SHAM, avec un effet mineur surla croissance parasitaire en microaérophilie, avait un effet létal sur les parasites en hyperoxie.Une meilleure compréhension de la biologie parasitaire pourrait contribuer audéveloppement de nouveaux traitements antipaludiques associés à une thérapie hyperbariqueP. falciparum is the main species responsible for severe case of malaria. The parasiteevolves between two hosts (human and mosquito), imposing to it different environments;especially changes in the O2 pressure, demanding astonishing adaptation skills for amicroaerophilic parasite. In the vertebrate host, the phenomena of cytoadhesion, which slowdown the spread of the parasite among others in the lungs, increase the timing of exposure tohyperoxic conditions.The parasitic response dynamic to hyperoxia has been analysed by a combinedtranscriptomic and proteomic approach. Some of the defense mechanisms against reactiveoxygen species have been evaluated, among which a potential alternative oxidase function.The exposure of the parasite to 21%O2 atmosphere leads to a growth delay atschizogony level. The oxidative stress resulting from the hyperoxia conducts to metabolicalterations, as an inhibition of the glycolysis in favour of respiration and as a slowdown of themetabolism of the digestive vacuole. This combined action on the mitochondrial and vacuolarmetabolisms allows the parasite to adapt itself to hyperoxic environment, by regulatingreactive oxygen species. Our works have shown that an inhibitor of the alternative oxidasefunction, the salicylhydroxamic acid or SHAM, with a minor effect on the parasite growth inmicroaerophily, had letal effect on parasites in hyperoxia.A better understanding of the parasitic biology could contribute to the development ofnew antimalarial treatments, associated with a hyperbaric oxygen therapy
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Perry, William B. "Global transcriptional analysis of an Escherichia coli recombinant protein process during hypoxia and hyperoxia." Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/28666.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2004.Includes bibliographical references (p. 289-302).
(cont.) The effects of recombinant protein production were observed through expression analysis of induced, uninduced, and Empty-Vector cultures. As expected, recombinant α₁AT production led to increased expression of heat-shock genes, including proteases and chaperones that are known to be involved in α₁AT degradation. Based on expression analysis data, production of recombinant α₁AT also resulted in catabolite repression and decreased amino acid biosynthesis. This work demonstrates the utility of DNA microarrays in analyzing and improving microbial fermentations. Global expression studies have suggested several strategies for increasing the resistance of bioprocesses to the damaging effects of oxygen and recombinant protein production.
Both exposure to oxygen and recombinant protein production are known to have adverse effects on microbial fermentation, including increased proteolytic and oxidative damage to the product. In an effort to characterize the effects of these stresses on the cell, DNA microarrays were used to monitor global gene expression of E. coli producing recombinant human αl-antitrypsin (α₁AT) during exposure to defined aeration conditions. Recombinant α₁AT has been shown to undergo oxygen-dependent degradation during production in E. coli, due in part to activation of the heat-shock response. The goal of this work is to better understand the effects of oxygen in order to improve this recombinant protein production process. In order to study the effects of oxygen extremes, global expression analysis was performed on α₁AT-producing cultures exposed to pure nitrogen, air, and pure oxygen. The most notable effects of oxygen exposure were those of superoxide. This reactive oxygen species is generated upon oxygen exposure and is known to oxidize iron-sulfur clusters. In response to hyperoxic conditions, the SoxRS stress response was activated, as were genes involved in iron uptake and the Isc and Suf repair systems for Fe-S clusters. Supplementation of iron in the growth medium resulted in expression changes consistent with improved formation of Fe-S clusters. Iron supplementation also decreased superoxide stress at the expense of a short-term increase in the peroxide (OxyR) stress response. In addition, iron supplementation dramatically reduced the oxygen dependence of recombinant α₁AT degradation. Regeneration of Fe-S clusters is proposed to improve protein folding and clusters is proposed to improve protein folding and limit activation of the heat-shock response.
by William Bryon Perry.
Ph.D.
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Pilley, Elizabeth Sarah. "Effects of antenatal inflammation and postnatal oxygen fluctuation on developing white matter in a rodent model of prematurity." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/23619.
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Inflammation and oxidative stress are increasingly recognised as important independent mediators of preterm brain injury and have been implicated in the pathogenesis of cerebral palsy and cognitive impairment. Such exposures are common for the premature infant in whom infection and inflammatory morbidities occur in around 60%. Furthermore, many preterm infants require oxygen therapy and respiratory support due to lung immaturity. Epidemiological and experimental studies indicate that in addition to the independent effects of inflammation and extreme hyperoxia on the developing brain, inflammation preconditions the developing brain resulting in variable injury when exposed to subsequent hypoxia-ischaemia. However experimental studies employing exposure to more modest oxygen fluctuations are lacking. This thesis characterises a clinically relevant model of prematurity where the developing brain is exposed to low grade inflammation and oxygen fluctuation around a hyperoxic mean. We hypothesise that antenatal inflammation and postnatal oxygen fluctuation, both alone and in combination, have detrimental effects on developing white matter. Pregnant dams received intraperitoneal lipopolysaccharide (LPS) or saline on G18 and G19. Dams and their pups were then reared in room air or fluctuating hyperoxia (circa 10kPa) for seven days. We measured longitudinal brain and body growth in different experimental groups to 12 weeks. Whole brains were examined for mRNA expression of inflammatory cytokines (TNFα, IL-1β, IL-6 and IL-10) and markers of oxidative injury (iNOS, SOD2). To determine the effect of perinatal insults on developing white matter, we analysed the expression of myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) in the internal and external capsule. We also examined white matter tracts for differences in microglia (CD68), oligodendrocyte progenitor cells (NG2), oligodendroglial cells (Olig2) and cell death (cleaved caspase3). Behavioural studies (Morris Watermaze Test, Elevated Plus Test and Open Field Test) were undertaken at 12 weeks of age to detect any long-term functional difference between the groups. Antenatal inflammation reduces both brain and body growth at P7. This normalises by P14 unless this inflammatory insult has been followed by postnatal oxygen fluctuation, where brain and body growth restriction persists until P14. We defined our inflammatory response at P1 following antenatal inflammation and did not observe elevation of mRNA at P1. We demonstrated increased SOD2 at this time point, indicating a reparative process. At P7 we observed a significant reduction in the oxidative response following combined exposure to antenatal inflammation and postnatal oxygen fluctuation, indicating a potential limit to, or suppression of, the reparative process. In terms of white matter injury, antenatal inflammation reduces myelination at P7. There is no synergistic effect of inflammation and oxygen fluctuation on MBP immunohistochemistry at P7. However, MBP mRNA expression is increased in pups exposed to both insults compared to those exposed to inflammation alone suggesting that the oxygen fluctuation may stimulate MBP production in response to oxidative injury. MBP mRNA levels and protein expression have all normalised by P14. We observed a reduction in total cell number in the external capsule and corpus callosum in the dual insult group, without an increase in caspase. In keeping with other studies we detected no effect of our perinatal insults on NG2+ve oligodendrocytes. Olig2+ve cell numbers were also consistent between experimental groups. In further characterisation of the cellular response, antenatal inflammation followed by postnatal oxygen fluctuation resulted in a decrease in GFAP mRNA at P7, an effect which was reversed and significantly increased by P14 suggesting delayed activation of the innate immune system. No difference was observed in microglial numbers between experimental groups. There was however, increased microglial cell death (CD68 + caspase) in the group exposed to antenatal inflammation. When this insult was combined with postnatal oxygen fluctuation there was a comparative decrease in microglial cell death, which may reflect an earlier peak of microglial cell death, due to an increased and sustained inflammatory stimulus. Morris Watermaze testing demonstrated that pups exposed to both insults took longer than controls to locate the hidden platform on day 1, which is a measure of spatial learning. The Elevated Plus Test and Open Field Test demonstrated that pups exposed to both insults were less anxious and took more risks than pups exposed to single insults. In conclusion, within a clinically relevant preterm model, antenatal inflammation transiently disrupts both brain and body growth and myelination of the motor tracts of the developing brain. Moreover, when combined with postnatal oxygen fluctuation, detrimental effects on growth are amplified and sustained. Decreased cell numbers are also observed within white matter tracts. In terms of long term functionality, these pups display disinhibition of behaviour as young adults. Collectively, this thesis demonstrates that synergistic actions of common low-grade perinatal insults may alter normal neurodevelopment, and that this may carry a risk of neurodevelopmental sequelae for preterm infants.
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Evans, Melissa K. "Effects of hyperoxia and acetate infusion on substrate phosphorylation during the onset of moderate exercise." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0015/MQ55671.pdf.
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Zhao, Yuwei [Verfasser]. "Injuries in the immature hippocampus caused by hyperoxia and its prevention by minocycline / Yuwei Zhao." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2015. http://d-nb.info/106744209X/34.
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Abd, Al-Sahib Hanady. "An investigation of the mechanism(s) of hyperoxia-induced cilial epithelial loss in mammalian bronchial tissue." Thesis, University of Plymouth, 2013. http://hdl.handle.net/10026.1/1613.
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Hyperoxia is an essential aid to life support in patients with severe respiratory failure. However, it is recognised as a contributor to the pathological consequences of oxidative stress including oxidative tissue damage, inflammation and cell death resulting in acute or chronic lung injury. The specific mechanisms behind this type of injury are still not completely understood. This study was undertaken with two main aims. Firstly, to evaluate the adverse effects of hyperoxia on the ciliary coverage using a novel large animal model. For the first time, an in vitro bronchus bovine tissue culture model was developed and used to quantify ciliary coverage loss over time. The protection role of antioxidant supplementation with α-tocopherol and ascorbate was also investigated. Secondly, the importance of the tight junction protein ZO-1 in hyperoxia-induced monolayer permeability was investigated using a human bronchial cell line (16HBE14o-) and the potential inflammation effects on bronchial tightness. Additionally studies were carried out in order to find out if antioxidant vitamin treatment can protect against or reduce these effects. Scanning electronic microscopy indicated that hyperoxia caused a time dependent decline (t½ = 3.4 d compared to 37.1 d under normoxia) in ciliary coverage (P < 0.0001). This was associated with an increase in the number of sloughed cells, many apparently intact, into the medium (p < 0.05). Several biochemical parameters were assessed to obtain evidence of oxidative stress caused by hyperoxia in this model including tissue damage (lactate dehydrogenase, LDH, in the medium), lipid peroxidation (thiobarbituric acid reactive substances, TBARS), DNA damage (comet assay used for the first time with primary bronchus culture), protein oxidation (OxyBlot kit) and antioxidant status (total glutathione). Antioxidant vitamins had a significant protective effect on the hyperoxia-induced reduction in percentage ciliary coverage (P < 0.05). Moreover, an increase in the bronchial permeability was shown characterised by a significant decrease (P < 0.05) in transepithelial electrical resistance (TER) under hyperoxic conditions. The reduction of ZO-1 associated fluorescence (P < 0.01) is in compatible with the downregulation of ZO-1 expression assessed by RT-PCR. Levels of the pro-inflammatory cytokines IL-8, IL-6 and TNF-a concentration in the medium, as measured by ELISA, increased significantly (P < 0.001) under hyperoxia, and this was accompanied with a marked increase in the cytokine expression. However, the antioxidant vitamins E and C, partially reduced the impact effects of hyperoxia, both individually and in combination, whilst increases in ZO-1 expression and fluorescence intensity (P < 0.05), as well as the suppression of cytokine secretion and gene expression was modest. Use of these vitamins was not enough to reduce the epithelial permeability significantly compared to normoxia. The data implies that hyperoxia-induced damage to cultured bovine bronchial epithelium and the denudation of cilia over time with increased permeability was due, at least in part, to the decline in TJ protein expression and associated fluorescence intensity. The antioxidant vitamins vitamin E and C had partial protective effects against hyperoxia damage. However, additional studies are called for in order to further understand the possible associations between oxidative stress and inflammation caused by hyperoxia and tight junction proteins, also response to treatment with antioxidant individually or in combination.
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Smit, Elisa. "Effects of hyperoxia and therapeutic hypothermia in an immature rat model of neonatal hypoxicischaemic brain damage." Thesis, University of Bristol, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.685357.
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The introduction of therapeutic hypothermia and the guidance on the cautious use of oxygen during resuscitation of newborn infants are two of the greatest advances in neonatal care over the last decade. The combination of the two has not been researched in great detail, but is of great clinical relevance. This thesis discusses and investigates the use of 100% oxygen following resuscitation in an immature rat model of hypoxiaischaemia in combination with therapeutic hypothermia. Pups on postnatal day 7 are traditionally used in this model. However, pups on postnatal day 10 (P10) are more appropriate as a model for term hypoxicischaemic brain damage and this was developed as a new model. An increase in survival with mild brain injury was seen when using 100% oxygen during resuscitation in P10 pups. This will need to be further explored in larger animal models. An improved cerebral cortical blood flux was seen in pups resuscitated in 100% oxygen, which could be an explanation for the reduction in injury seen in survivors. No change in brain injury was seen following resuscitation in 100% oxygen in a model of severe hypoxia-ischaemia. An attempt was made to create a reproducible and more immature rat model for preterm hypoxia-ischaemia using pups on postnatal day 4. This was however difficult and the process is described. Add-on treatments to cooling are the future for infants with hypoxic-ischaemic encephalopathy and some of these will certainly be introduced as standard care in the coming decade. Further research investigating the side-effects of cooling and redefinition of the treatment (time-window, degree of hypothermia, patient selection) as well as investigating the combination of oxygen, therapeutic hypothermia and some of the new add-on treatments is highly desirable and suggested as a new avenue for exploration.
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Eves, Neil Derek. "The effect of hyperoxia on maximal and submaximal exercise with firefighting gear and self-contained breathing apparatus." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0016/MQ47026.pdf.
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Ciarlone, Geoffrey Edward. "Hypercapnic Hyperoxia Increases Free Radical Production and Cellular Excitability in Rat Caudal Solitary Complex Brain Slice Neurons." Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6481.
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The caudal solitary complex (cSC) is a cardiorespiratory integrative center in the dorsal medulla oblongata that plays a vital role in the central CO2-chemoreceptive network. Neurons in this area respond to hypercapnic acidosis (HA) by a depolarization of the membrane potential and increase in firing rate, however a definitive mechanism for this response remains unknown. Likewise, CO2-chemoreceptive neurons in the cSC respond to hyperoxia in a similar fashion, but via a free radical mediated mechanism. It remains unknown if the response to increased pO2 is merely an increase in redox signaling, or if it’s the result of a pathological state of redox stress. Importantly, free radical production is known to be stimulated by increasing pO2, and can be exacerbated downstream by the addition of CO2 and its subsequent acidosis. Conditions of hyperoxia in combination with HA can therefore become detrimental in several scenarios, including O2 toxicity seizures in divers and stranded submariners, as well as in cases of ischemia-reperfusion injury and sleep apneas. As such, we sought to not only determine how O2 and CO2 interact to affect cellular excitability in the cSC, but also if these cells exhibited increases in redox signaling and/or stress. We employed sharp-electrode intracellular electrophysiology to study whole-cell electrical responses to varied combinations of hyperoxia (0.4 0.95/1.95 ATA O2) and HA (0.05 0.1 ATA CO2). Additionally, we used fluorescence microscopy under similar conditions to study changes in the production rates of various free radicals, including superoxide (˙O2-), nitric oxide (˙NO), and a downstream aggregate pool of CO2/H+-dependent reactive oxygen and nitrogen species (RONS). Finally, we used several colorimetric assays to measure markers of oxidative and nitrosative stress, including malondialdehyde, 3-nitrotyrosine, and protein carbonyls. Our hypothesis for these experiments was that hyperoxia and HA alone could produce effects, but would be more pronounced when used together. As such, we saw that ~89% of cells tested that were sensitive to both hyperoxia and HA showed larger firing rate responses to HA during an increased background O2 (0.9 and/or 1.9 ATA) after showing a smaller response or no response to HA during control levels O2 (0.4 ATA). Additionally, we noted that the rate of ˙O2- fluorescence increased in response to hyperoxia, but only during pharmacological inhibition of its reactions with ˙NO and SOD. Likewise, the rate of ˙NO fluorescence increased during hyperoxia compared to control O2, but only during pharmacological scavenging of ˙O2-. Downstream, our aggregate pool of RONS showed increased rates of fluorescence during both hyperoxia alone and HA in control O2, however the most prominent increases were seen during hypercapnic hyperoxia. Finally, no significant effects were seen when probing for markers of redox stress in response to hyperoxia and hypercapnic hyperoxia. Overall, these results suggest that the increased excitability seen in cSC neurons during hypercapnic hyperoxia is the result of physiological redox signaling rather than pathological redox stress. Further research needs to be done to determine how this redox mechanism is specifically resulting in increased cellular excitability.
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Bak, Zoltán. "Cardiovascular response to hyperoxemia, hemodilution and burns : a clinical and experimental study /." Linköping : Univ, 2007. http://www.bibl.liu.se/liupubl/disp/disp2007/med1013s.pdf.
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Adamson, Samuel John. "Dark-rearing as a non-invasive treatment for Retinopathy of Prematurity: basic mechanisms and a pathway to translation." Thesis, The University of Sydney, 2016. http://hdl.handle.net/2123/17956.
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The persistence of retinopathy of prematurity (ROP) in both the developed and the developing world remains a serious cause for concern. Some 75 years after its first clinical description, we still lack an easily applied strategy to reduce the deleterious effects of oxygen (O2) on the developing retinal vasculature. The aim of the work detailed in this thesis is to provide an early, non-invasive intervention for ROP by targeting the initiating event in the disease – hyperoxia in the retina - rather than treating the downstream effects of hyperoxia, as is presently the case. The hypothesis tested in this thesis is that dark-rearing (DR) infants at risk of ROP during supplemental O2 therapy will increase the metabolic rate of photoreceptors and increase O2 consumption in the retina, offsetting retinal hyperoxia. This thesis provides proof-of-principle that DR can normalize vascular development in the presence of supplemental O2 by maintaining ‘physiological hypoxia’ during the hyperoxic (Phase 1) of ROP, and shows that DR preserves the density and extent of retinal vessels, and reduces the severity of pre-retinal neovascularization in Phase 2 of an established rat model of ROP. In addition, the thesis presents a normative dataset for the rate of retinal vascularization in human infants under “physiological hypoxia” in utero, and provides data towards a criteria for the clinical dentification of “delayed retinal vascularization’ as a basis for initiation of laser treatment, or the application of antivascular endothelial growth factor (VEGF) therapy for infants at risk of progressing to sight-threatening stages of ROP. Finally, the thesis presents data examining the hitherto unidentified system of lymphatic vessels in the human choroid. These observations provide the foundation for further studies exploring the roles of lymphatics in posterior eye diseases, and investigations of novel therapeutic targets in these diseases, such as the lymphangiogenic factors VEGF-C & D.
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Gargne, Ombeline. "Exercice physique et plongée : aspects cardio-vasculaires." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM5043.
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L'étude des mécanismes physiologiques au cours d'une plongée subaquatique estessentielle à la compréhension des accidents qui lui sont associées. Le plongeur subit denombreuses contraintes issues du milieu dans lequel il évolue. Parmi ces contraintes, qui leplus souvent se combinent, nous pouvons citer l'immersion, l'exposition au froid,l'hyperbarie, les variations des conditions d'oxygénation (hypoxie, hyperoxie) et l'exercicephysique. L'objectif de notre travail a été d'apprécier les modifications de la fonction cardiovasculaireet de son contrôle neuro-végétatif induites par ces contraintes rencontrées enplongée chez des sujets sains, novices en plongée, et également chez des chasseurs sousmarins. L'étude de la circulation artérielle et de la fonction endothéliale était basée surl'échographie (bi-dimensionnelle et Doppler). Des mesures de tonométrie d'applanation etautres mesures ultrasonores ont complété nos données hémodynamiques. L'étude du systèmeneurovégétatif était basée sur l'analyse de la variabilité de l'intervalle RR (contrôle cardiaque)et de la variabilité de la pression artérielle (contrôle vasculaire). Après un exercice aigu de pédalage de 45 minutes à haute intensité, l'augmentationpost-exercice du flux sanguin et de la vasodilatation endothéliale a été réduite aux musclesparticipant activement à l'exercice comparé aux muscles non actifs. Pour expliquer cesdifférences, la contribution de l'inflammation locale et du stress oxydatif élevé présents dansles muscles actifs de l'exercice pourrait avoir un rôleDuring a dive, subjects undergo environmental stressors such as immersion, coldexposure, hypoxia, hyperoxia and physical exercise. All these stressors may be responsible forchanges in cardiovascular system and consequently modified autonomic nervous control. Theaim of this work was to assess physiological changes induced by diving to better understandinjuries reported during this activity. Investigations were performed in healthy men and inspearfishermen. Hemodynamic changes and endothelial function were assessed by 2-Dimensional and Doppler echocardiography. Arterial wall compliance was estimated by pulsewave analysis. Autonomic nervous activity was assessed by power spectral density of heartrate variability (cardiac control) and blood pressure variability (vasomotor control). After an acute cycling exercise of 45 minutes in high intensity, the increase postexerciseof the blood flow and the endothéliale vasodilatation was reduced to musclesparticipating actively in the exercise compared with no active muscles. To explain thesedifferences, the contribution of the local inflammation and the important oxydative stress inthe active muscles of the exercise could have a role. Thermoneutral head-out water immersion induce hemodynamic and arterial changes. At rest, we observed a brachial arterial vasodilatation. This might be attributed to endothelialrequest inferred by increase of the peripheral arterial debit flow. Endothelial reactivity did notseem to be modified. With cycling exercise in low intensity,hemodynamic differencesobserved disappear. At rest, normobaric hyperoxia didn't affect blood pressure but induced an increase insystemic vascular resistances
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McCluskey, Samantha D. "Hyperoxia Avoidance| A Comparison of Prehospital Oxygen Initiated at High Flow versus Titration to Target Range; a Retrospective Cohort Analysis." Thesis, Brandman University, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10641492.
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Problem: Exposure to high flow oxygen for even short periods of time has been independently linked to increased risk of poor patient outcomes. Evidence supports hypothesis that high flow oxygen may do more harm than good. Cognitive link between hyperoxia and related risk is deficient among prehospital providers. Implementation of hyperoxia avoidance education and evidence based updates to Mesa County, Colorado EMS protocol are predicted to improve provider comprehension and compliance, as well as, reduce patient risk for harm. Purpose: The purpose of this study is to evaluate whether informal introduction to hyperoxia avoidance presented to EMS providers in August 2013 resulted in greater number of patients whose prehospital oxygen was titrated to evidence based range versus high flow. The null hypothesis projects there is no difference between pre-and post-group analysis. Methods: A retrospective review of prehospital patient records was performed utilizing comparative data to analyze difference between independent groups in application of evidence based protocol, number of patients titrated to > 96 percent SpO2, and mean of highest recorded SpO2. Results: Analysis resulted no statistically significant difference between pre-and post-groups for initiation of evidence based oxygen guidelines, (p = .0697). Although SpO2 > 96 percent was common in both groups, the post group resulted a reduction in patients titrated to hyperoxia, (p = .024). Sample population mean of high recorded SpO2 was 97.3 percent with mean difference between groups of 0.5 percent, (p < 0.05). Conclusion: Study outcomes substantiate need for hyperoxia focused education within Mesa County Emergency Medical Services, as well as, indication of protocol generalizability. This manuscript will comprehensively discuss identified problem, study protocol, implication for advanced nursing practice, and areas of future study.
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Manselin, Tom, and Olof Södergård. "Six weeks of high intensity interval training with hyperoxia or normoxia in trained cyclists : A polarized and periodized training approach." Thesis, Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:gih:diva-4262.
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Aim The main aim of this study was to investigate the longitudinal effects on cycling performance using a polarized and periodized scheme that was highly supervised and controlled. The second aim was to investigate the effect of using Hyperoxia. The questions used to address the aim were: (1) How does overall performance change after a six-week training intervention? (2) What is the time-course and pattern of performance changes to the training scheme? (3) How does the performance change within the groups? Method Nineteen male and female cyclists started the study (13 male and 6 female), however only 12 completed it (8 male and 4 female). The characteristics for the 12 subjects were: age (year) 33.6 ± 6.8, height (cm) 177 ± 9.1, body mass (kg) 73.4 ± 8.8. Using a randomized, double blind design, the test subjects were divided in to hyperoxia (HOT) (n = 6) and normoxia (NOT) (n = 6) training groups. Over a six week period the subjects followed a controlled polarized periodization that included 15 high intensity interval training (HIIT) sessions (3 x 8 min, 3 x 8 + 4 min, 4 x 8 min & 4 x 4 min) on maximal sustainable intensity (isoeffort) on a cycle ergometer. The dosage of oxygen was administered intermittently by the oxelerate device. A 20 min all out test was performed as pre- and post test. Results The whole group (n = 12) increased mean power output (W) by 6.4 % (P = 0.002). The relative power output (W/kg) increased significantly 8.2 % (P = 0.0011). The HOT group (n = 6) increased their power output by 8.3 % (P = 0.028) and their relative power output increased by 9.4 % (P=0.011). The whole group (P = 12) significantly increased their VO2mean by 4.1 % (P = 0.03) and in the relative value by 5.4 % (P = 0.01) on the 20 min all out test. The whole group also had a significant increase in VO2peak of 3.7 % (P = 0.04). A very strong correlation could be found between the training data and the performance test. Conclusions The training intervention was favourable for increasing performance and VO2peak in cycling. Usage of hyperoxia during the training intervention increases the performance.Syfte och frågeställningar Huvudsyftet med denna studie var att undersöka de longitudinella effekter på prestation i cykling med hjälp av ett polariserat och periodiserat träningsupplägg som var väl övervakat och kontrollerat. Det andra syftet var att undersöka effekten av att använda hyperoxi. De frågeställningar som hjälpte att besvara syftet var: (1) Hur förändras prestationen efter en sex veckors träningsintervention? (2) Hur anpassar sig försökspersonerna till träningsschemat över tid? (3) Hur förändras prestationen inom grupperna? Metod 19 manliga och kvinnliga cyklister deltog i studien (13 manliga och 6 kvinnliga), 12 fullföljde hela studien (8 manliga och 4 kvinnliga). Karaktäristiken för de 12 försökspersonerna var: ålder (år) 33.6 ± 6.8, längd (cm) 177 ± 9.1, vikt (kg) 73.4 ± 8.8. Försökspersonerna delades in i hyperoxi (HOT) (n = 6) och normoxi (NOT) (n = 6), studien var dubbelblind. Under sex veckor följde försökspersonerna en kontrollerad polariserad periodisering som inkluderade 15 högintensiva intervallträningspass (HIIT) (3 x 8 min, 3 x 8 + 4 min, 4 x 8 min & 4 x 4 min) på högsta genomförbara intensitet (isoeffort) på cykelergometer. Doseringen av syre administrerades intermittent genom Oxelerate-enheten. Ett 20 min all-out test utfördes som för- och eftertest. Resultat Hela gruppen (n = 12) ökade signifikant på prestationstestet (W) med 6.4 % (P = 0.002). Den relativa effekten (W/kg) ökade signifikant med 8.2% (P = 0.0011). HOT (n = 6) ökade signifikant på prestationstestet med 8.3% (P = 0.028) och den relativa effekten ökade med 9.4% (P = 0.011). Hela gruppen (n = 12) ökade signifikant i VO2medel under prestationstestet med 4.1 % (P = 0.03) och i det relativa värdet med 5.4 % (P = 0.01). Hela gruppen hade också en signifikant ökning av VO2peak med 3.7 % (P = 0.04). En mycket stark korrelation hittades mellan träningspassdata och prestationstestet. Slutsats Träningsupplägget är gynnsamt för ökning av prestation och VO2peak i cykling. Användning av hyperoxi under träningsupplägget ökar prestationen.
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Malone, Daniel Joseph. "PERFLUOROCHEMICAL AUGMENTED INTRATRACHEAL DELIVERY OF ANTIOXIDANT ENZYMES AND GENES TO ATTENUATE OXIDATIVE STRESS-INDUCED LUNG AND RESPIRATORY MUSCLE ALTERATIONS." Diss., Temple University Libraries, 2009. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/24041.
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PhysiologyPh.D.
Supraphysiologic concentrations of oxygen are used in the management of critically ill patients across the lifespan. However, hyperoxia (HO) results in alveolar- capillary membrane destruction, pulmonary edema, pleural effusions, infiltration and activation of inflammatory cells, altered pulmonary mechanics and gas exchange prompting increased loading of the respiratory muscle. These abnormalities of pulmonary structure and function increase the work of breathing necessitating increased respiratory muscle force production to maintain alveolar ventilation. When the load placed on the respiratory muscle pump exceeds its capacity, respiratory failure develops and is ultimately fatal unless therapeutic interventions are able to reduce the ventilatory load. The use of perfluorochemical (PFC) liquids as a respiratory medium has been effective in the treatment of respiratory distress syndrome and acute lung injury (ALI) requiring mechanical ventilation. Mechanistically, by eliminating the air-liquid interface, PFC liquids reduce surface tension enabling lung volume recruitment at low inspiratory pressures and have high respiratory gas solubility which supports gas exchange. Additionally, through mechanical as well as cytoprotective mechanisms, intrapulmonary PFC liquids reduce inflammatory cell activation and recruitment. Cell culture, animal and human studies have suggested that acute and chronic lung injury secondary to prolonged HO may be ameliorated by administration of antioxidant enzymes (AOE), with superoxide dismutases (SOD) having significant protective effects. Because the lung is exposed to the highest O2 concentrations, a logical strategy to reduce HO-induced damage is to specifically target antioxidant enzymes to the lungs. However, intratracheal delivery of AOE by vehicles like normal saline may transiently impair lung function and be poorly distributed. PFC fluids have previously been shown to be effective respiratory media for pulmonary administration of various drugs. The premise of the proposed studies are to to characterize hyperoxic lung injury in a spontaneously breathing animal model and to develop therapeutic strategies to reduce oxidatative stress and supplement endogenous AOE. With respect to the diaphragm, we reason that HO-induced lung damage and oxidative stress will increase contractile demand of the diaphragm. If AOE activity could be increased in the lungs and respiratory muscles with AOE proteins or the genes encoding these enzymes, then cell damage, inflammatory changes, damage to the lung and respiratory "pump" might be ameliorated or prevented. The results show that PFC and SOD can attenuate the HO- induced decline in lung mechanics and gas exchange, ameliorate the inflammatory and oxidative stress profiles, and promote lung and muscle structural integrity resulting in a survival benefit. These findings support the novel application of PFC liquids in a spontaneously breathing model and support the concept that PFC preconditioning and AOE supplementation play a protective role by reducing mortality and morbidity in hyperoxic lung injury.
Temple University--Theses
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Parrila, Leah. "Myocardinal contractility and oxygen regulation as a determinant of myocardinal plasticity in the hypoxia and hyperoxia reared American alligator, Alligator mississippiensis." Thesis, California State University, Long Beach, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=1527405.
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Cox, Jr Ruan Rollin. "Aspirin Triggered Resolution Phase Interaction Product D1: A Novel Treatment for Hyperoxic Acute Lung Injury." Scholar Commons, 2015. http://scholarcommons.usf.edu/etd/5931.
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Acute Lung injury (ALI) and the more severe acute respiratory distress syndrome (ARDS) are respiratory maladies that present immense clinical challenges. ALI affects 200,000 individuals annually and features a 40% mortality rate. ALI can be initiated by both pathogenic and sterile insults originating locally in the lungs or systemically. While immense research has been poured into this disease in an effort to find a therapeutic strategy, the heterogeneously diffuse nature of the disease has not yielded a cure for the disease. Death from this disease is strongly attributed to reduced gas exchange from a severely compromised alveolar-capillary barrier. The only way currently to manage this disease is through enhanced ventilation and hyperoxic therapy.
Hyperoxic therapy is a common treatment given to over 800,000 patients each year to treat respiratory maladies such as ALI. Prolonged exposure to oxygen at high concentrations results in the development of a condition known as hyperoxic acute lung injury (HALI). In this disease, the formation of reactive oxygen species damages healthy tissue and impairs gas exchange. Hyperoxia is also a well-documented murine sterile lung injury model that replicates the symptoms of ALI in lung injury patients. The ability of non-lethal dosages of hyperoxia to resolve without lung fibrosis also enables the study of molecules associated with ALI resolution and repair, a process not clearly understood.
Inflammation in ALI is associated with disease progression, however pharmaceutical interventions aimed at targeting the inflammatory cascade have failed in clinical trials for ALI. Recent reports point to an aberrant injury resolution mechanisms that may be more strongly correlated with morbidity and mortality. There seems to be a homeostatic imbalance between endogenous inflammation progression and resolution initiation. This is especially the case with HALI, as significant ROS generation results in depletion of redox regulating antioxidants. Resolution mechanisms associated with ALI in the oxygen toxicity setting is poorly understood.
Polyunsaturated fatty acids such eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are essential fatty acids that show immense antioxidant and anti-inflammatory action in cases of acute injury. The lung mucosa is rich in DHA and following inflammatory insult DHA is readily converted to resolution phase interaction products (resolvins), which have shown immense proresolutionary potential in recent reports of acute injury. In the presence of aspirin, more potent and longer-acting aspirin-triggered resolvins are formed. The effects of resolvins and their aspirin triggered epimers have not been studied in an oxygen toxicity setting and are the focus of this dissertation. For the first time, we show that one of these resolvin molecules, aspirin triggered resolvin d1 (AT-RvD1), can enhance resolution of hyperoxic acute lung injury. In vitro results reveals that AT-RvD1 treatment resulted in reduced interaction of two key players in the HALI inflammatory cascade, the macrophage and alveolar epithelium. AT-RvD1 was able to blunt macrophage cytokine secretion as well as inhibit epithelial cell cytokine secretion and adhesion molecule expression. More importantly, AT-RvD1 blunted cytokine mediated leukocyte-epithelial cell interaction in vitro. In a sublethal hyperoxic injury model, mice given AT-RvD1 following hyperoxia exposure displayed reduced HALI pathological severity. ATRvD1 treatment resulted in reduced alveolar-capillary permeability, tissue inflammation, proinflammatory mediator secretion, epithelial cell death, and leukocyte influx. Taken together these novel results demonstrate the therapeutic potential of resolvins in the oxygen toxicity setting. These results also arouse the idea that resolvins could be used to lessen the comorbidities associated with oxygen therapy and improve recovery times of ALI patients.
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Copeland, Jennifer. "Hypoxic and hyperoxic incubation affects the ductus arteriosus in the developing chicken embryo (Gallus gallus)." Thesis, University of North Texas, 2009. https://digital.library.unt.edu/ark:/67531/metadc12103/.
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Developing chicken embryos have two ductus arteriosus (DA) that shunt blood away from the lungs and to the chorioallantoic membrane, the embryonic gas exchanger. In mammals, DA closure is stimulated by an increase in blood gas O2 that occurs as the animal begins to breathe with its lungs. The goal of this study was to determine the influence of O2 levels during incubation on the vascular reactivity and morphology of the O2-sensitive DA and to examine the effects of changing O2 levels during late incubation on the morphology of the DA from chicken embryos. In comparison to normoxia, hypoxia (15%) reduced venous O2 levels in day 16 and day 18 embryos and reduced aircell O2 values in day 16, day 18, and internally pipped (IP) embryos, whereas hyperoxia (30%) increased venous O2 levels and aircell O2 level in day 16, day 18, and IP embryos. In comparison to normoxia, hypoxia delayed closure of the DA, whereas hyperoxia accelerated DA closure. In comparison to the left DA from externally pipped (EP) normoxic embryos, the left DA from EP hypoxic embryos exhibited a significantly weaker contractile response to O2. The DA from day 18 hypoxic embryos exhibited a significantly weaker contractile response to norepinephrine and phenylephrine when compared with the DA from day 18 normoxic and hyperoxic embryos. The effect of incubation in hypoxia / hyperoxia during different developmental windows on the DA O2-induced contractile response was observed only in IP embryos that were incubated in normoxia for 16 days and were then moved to hyperoxia. Incubation in hypoxia / hyperoxia resulted in differences in embryo mass, yolk mass, and heart mass. There is an association between the decreased contractile response to O2 and delayed closure in the proximal portion of the DA from hypoxic embryos; as well as an increased contractile response to O2 and accelerated closure in the proximal portion of the DA from hyperoxic embryos.
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Bak, Zoltan. "Cardiovascular response to hyperoxemia, hemodilution and burns : a clinical and experimental study." Doctoral thesis, Linköpings universitet, Anestesiologi med intensivvård, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-10633.
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The last decades less invasive monitoring and analytical tools have been developed for the evaluation of myocardial mechanics in clinical praxis. In critical care, these are longed-for complements to pulmonary artery catheter monitoring, additionally offering previously inaccessible information. This work is aimed, during fluid-replacement and oxygen therapy, to determine the physiological interface of ventricular and vascular mechanical properties, which result in the transfer of blood from the heart to appropriate circulatory beds. In prospective clinical studies we investigated previously cardiovascular healthy adults during hyperoxemia, and during preoperative acute normovolemic hemodilution or early fluid resuscitation of severe burn victims. Echocardiography was used in all studies, transthoracic for healthy volunteers and transesophageal for patients. For vascular parameters and for control purposes pulmonary artery Swan-Ganz catheter, calibrated external pulse recordings, whole body impedance cardiography, and transpulmonel thermodilution method were applied. We detected no significant change in blood pressure or heart rate, the two most often used parameters for patient monitoring. During preoperative acute normovolemic hemodilution a reduction of hemoglobin to 80 g/l did not compromise systolic or diastolic myocardial function. Cardiac volumes and flow increased with a concomitant fall in systemic vascular resistance while oxygen delivery seemed maintained. Supplemental oxygen therapy resulted in a linear dose-response between arterial oxygen and cardiovascular parameters, suggesting a direct vascular effect. Cardiac flow decreased and vascular resistance increased from hyperoxemia, and a decrease of venous return implied extracardial blood-pooling. Severe burns result in hypovolemic shock if not properly treated. The commonly used Parkland fluid replacement strategy, with urinary output and mean arterial pressure as endpoints, has recently been questioned. Applying this strategy, only transient early central hypovolemia was recorded, while dimensional preload, global left ventricular systolic function and oxygen delivery or consumption remained within normal ranges during the first 36 hours after accident. Signs of restrictive left ventricular diastolic function were detected in all patients and regional unstable systolic dysfunction was recognized in every other patient, and was consistent with myocardial marker leakage. Severe burns thereby cause myocardial stiffness and systolic regional dysfunction, which may not be prevented only by central normovolemia and adequate oxygenation.On the day of the defence date the status of article II was: In Press.
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Dedja, Arben. "Administration of L-citrulline in an animal model of perinatal lung damage." Doctoral thesis, Università degli studi di Padova, 2012. http://hdl.handle.net/11577/3422175.
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Moderate hyperoxia and induced chorioamnionitis by intrauterine administration of endotoxin LPS into near-term pregnant rats cause alveolar and vascular lung derangement in the newborns. Endogenous nitric oxide (NO), which promotes lung growth, is produced from the metabolism of L-arginine to L-citrulline in endothelial cells. We investigated whether administering L-citrulline by raising the serum levels of L-arginine and enhancing NO endogenous synthesis, attenuates lung injury in a chorioamnionitis and/or moderate hyperoxia-induced model. Material and Methods. Newborn rats (receiving or not intrauterine LPS) were exposed to FiO2=0.6 or room air till 14 days after birth and were administered L-citrulline. Serum and lung tissues were collected for further analysis. The lung sections were subsequently stained with H&E and photomicrographs were obtained at 10X magnification. For vessel density assessment, sections were stained to reveal the presence of von Willebrand Factor Antigen. VEGF and eNOS protein expression was examined by Western blot. High performance liquid chromatography-mass spectrometry was used for simultaneous determination and quantification of ADMA, SDMA, L-arginine, L-citrulline, NMMA and homo-arginine in the serum. Results. The lung histopathology analysis of the Hyperoxia group showed a pattern typically emphysematous, similar to the LPS exposure group, when compared to controls. Exposure to hyperoxia was associated with an arrested alveolarization, inducing a change in lung morphology with patchy areas of parenchymal thickening interspersed with areas of enlarged air spaces. The lung sections of the CITR+hyperoxia and LPS+CITR rats contained smaller and more numerous air spaces, and were more similar to the control lungs. The mean alveolar size was higher in Hyperoxia group vs. controls, or LPS+CITR, in a post hoc comparison unchanged with respect to CITR+hyperoxia, or LPS, or CITR. The secondary crests were higher in the Control and CITR+hyperoxia and LPS+CITR groups than in the Hyperoxia only, or LPS only groups. VEGF gene expression evaluated by real-time quantitative PCR was lower in the Hyperoxia group, than in the CITR+hyperoxia or Control groups. Also, lung sections from Control and CITR+hyperoxia animals showed a similar vWF expression, whereas staining was weaker in the Hyperoxia group. In the CITR+hyperoxia sections there was also evidence of a better organization of the vessel network than in animals exposed to hyperoxia. The amount of eNOS protein normalized in the lung tissue from the L-citrulline treated animals was higher than in the tissues from the Hyperoxia group. Serum assessment with mass spectrometry did not show major differences in the time course and treatment groups. Conclusions. Our main findings were that: (i) administering L-citrulline proved effective in improving alveolar growth after oxygen-induced and antenatal endotoxin exposure lung damage; (ii) VEGF gene and protein were over-expressed in the group treated with L-citrulline. There may have been further protective effects on the alveolar vascular network and, consequently, on matrix maturation in our model and this may be promising with a view to BPD prevention strategies.La corioamnionite indotta dalla somministrazione intrauterina dell’endotossina LPS e da una moderata iperossia nei primi giorni di vita causano uno squilibrio alveolare e vascolare del polmone nel ratto neonato. L’ossido nitrico (NO) endogeno, che promuove la crescita polmonare, viene prodotto nelle cellule endoteliali dal metabolismo del L-arginina verso il suo prodotto, la L-citrullina. Abbiamo studiato l’efficacia della somministrazione di L-citrullina in un modello di danno indotto da corioamnionite e/o da iperossia nei ratti neonati nell’attenuare il danno polmonare intervenendo sulla sintesi del NO endogeno aumentando i livelli di L-arginina. Materiali e Metodi. I ratti neonati (che ricevono o no LPS nella loro fase intrauterina) vengono esposti a un FiO2=0.6, o ad aria ambiente, per 14 giorni dopo la nascita con la somministrazione, per alcuni di loro, della L-citrullina. A vari time-points sperimentali siero e tessuto polmonare vengono raccolti per ulteriori analisi. Le sezioni polmonari vengono colorate con ematossilina & eosina e fotografate a 10X. Per una valutazione della densità vascolare le sezioni sono colorate per la presenza dell’antigene del Fattore di von Willebrand. La VEGF e l’espressione proteica eNOS vengono esaminati con il Western blot. La HPLC Spettrometria di Massa viene usata per determinare e quantificare nel siero ADMA, SDMA, L-arginina, L-citrullina, NMMA e omo-arginina. Risultati. L’esposizione a moderati regimi di iperossia era associata istologicamente con aree estese di tipo enfisematoso, simile al quadro del gruppo esposto al LPS e, inoltre, con un arresto dell’alveolarizzazione e contestuale variazione eterogenea della morfologia polmonare, e ha indotto un cambiamento nella morfometria polmonare con aree irregolari di inspessimento parenchimatoso intervallate da aree con spazi aumentati. Il gruppo ricevente il farmaco presentava un grado di alveolarizzazione più sviluppata con un incremento del numero degli alveoli per mm2, statisticamente significativo rispetto al gruppo con iperossia. Le sezioni polmonari dei gruppi CITR+iperossia e LPS+CITR contenevano spazi più piccoli e più numerosi, simili ai controlli. Il numero delle creste secondarie era più alto nei controlli e nei gruppi CITR+iperossia e LPS+CITR, che nei gruppi con iperossia solo, o LPS sola. L’espressione genica del VEGF era più bassa nel gruppo dell’iperossia, rispetto al gruppo CITR+iperossia, o ai controlli. Inoltre, le sezioni polmonari da animali di controllo o da trattati con CITR+iperossia presentavano un’espressione vWF simile, mentre la colorazione era più bassa nel gruppo con iperossia. Nei campioni da animali trattati con CITR+iperossia era evidente anche un organizzazione migliore della rete vascolare rispetto agli animali esposti solo all’iperossia. La quantità delle proteine eNOS normalizzate nei tessuti polmonari da animali trattati con L-citrullina era più alta che nei tessuti del gruppo con sola iperossia. La valutazione con spettrometria di massa dei campioni di siero non ha mostrato grandi differenze tra i gruppi trattati. Conclusioni. In conclusione abbiamo provato che: (i) la somministrazione della L-citrullina aiuta la crescita alveolare nel danno polmonare da ossigeno, o da esposizione antenatale a endotossina; (ii) il gene e la proteina VEGF sono over-espressi nel gruppo trattato con L-citrullina. Ulteriori effetti protettivi potranno essere manifesti sul network alveolare e vascolare del polmone e, di conseguenza, sulla maturazione della matrice nel nostro modello di danno polmonare; tutto questo potrà essere promettente in vista di una strategia della prevenzione della broncodisplasia polmonare.
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Devor, Devin Patrick. "Effects of Hyperoxia on Thermal Tolerance and Indicators of Hypoxic Stress in Antarctic Fishes That Differ in Expression of Oxygen-Binding Proteins." Ohio University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1362666619.
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Matott, Michael Patrick. "The Effects of Oxygen on the Electrophysiology of CO2/H+-Chemosensitive and -Insensitive Neurons of the Solitary Complex of the Rat." Scholar Commons, 2012. http://scholarcommons.usf.edu/etd/4148.
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This study tested the hypothesis that decreasing the control O2 level from 95% to 40% (5% CO2 + 55% N2) maintains viability in caudal solitary complex (cSC) neurons in transverse slices (~300-400ꝳ) prepared from neonatal rat (P2-22) maintained at 32-34°C. The underlying rationale is to reduce exposure to redox and nitrosative stimuli generated during several hours of exposure to 95% O2 that produces a tissue O2 tension throughout the slice which is in excess of 203 kPa (2.0 atmospheres absolute,ATA) oxygen. Whole cell recordings of cSC neurons maintained in 40% O2 exhibited spontaneous firing and had similar membrane potentials (Vm) and input resistances (Rin) as cSC neurons maintained in 95% O2. Neurons maintained in 40% O2, however, had significantly lower intrinsic firing rates than those maintained in 95% O2. 67% of neurons maintained in 40% O2 control were stimulated by hyperoxia, compared to 81% of neurons maintained in 95% O2 that were stimulated by reoxygenation from relative hypoxia. cSC neurons maintained in 40% O2 also exhibited CO2/H+-sensitivity, including CO2/H+-excitation (31%) and CO2H+-inhibition (31%) and most CO2/H+-sensitive neurons were also stimulated by hyperoxia and reoxygenation or inhibited by lower O2. It is also suggested that acute exposure to lower concentrations of O2 may increase the incidence of CO2-inhibited cSC neurons. Anoxia reduced or eliminated all firing in essentially all cSC neurons. Our findings indicate that brainstem slice viability is retained in 40% O2 control and that hyperoxia is a general stimulant of many cSC neurons, including chemosensitive neurons. We therefore recommend that 40% O2 be used for brainstem electrophysiology studies.
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Benderro, Girriso Futara. "AMBIENT OXYGEN AVAILABILITY MODULATES EXPRESSION OF VASCULAR ANGIOGENIC FACTORS AND CAPILLARY REMODELING (ANGIOPLASTICITY) IN THE MOUSE BRAIN." Case Western Reserve University School of Graduate Studies / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=case1350159484.
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Ocsan, Ryan. "Pathophysiological and pharmocological studies on cardiac c-kit expression." Thesis, The University of Sydney, 2014. http://hdl.handle.net/2123/12144.
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Cardiac hypertrophy and dilatation are cardiovascular outcomes which impact negatively on the body and over time, progress to heart failure. Models of these pathological conditions, induced through various interventions, have been explored in the context of cardiovascular remodelling and stem cell activity. In chapter 3, we demonstrated that with N(G)-nitro-l-arginine methyl ester (L NAME) administration, the level of c-Kit expression in the mouse heart significantly decreased with acute treatment (by 5 days L-NAME treatment) and these reduced levels continued to persist with chronic L-NAME treatment (6 weeks), as cardiac hypertrophy simultaneously developed by 6 weeks. It is suggested that both hyperplasia and hypertrophy of individual cardiomyocytes (hyperplasia occurring at the initial stages before hypertrophy supervenes) are likely contributing to the overall increase in both the left ventricular wall width and also a reduction in interstitial space. The reduction in c-Kit+ cells within the myocardium was thought to be a consequence of resident stem cell differentiation, mediated by hypertrophic stimulation, combined with reduced recruitment due to decreased nitric oxide (NO) production (NO is involved in stem cell recruitment via up-regulation of stromal cell-derived factor-1 (SDF-1) levels). In chapter 4, metformin administration was shown to attenuate the reduction in cardiac stem cells that occurs in the heart during a hypertrophic stimulus (i.e. L-NAME administration). This is suggested to be likely due to an increase in adenosine monophosphate (AMP)-activated protein kinase (AMPK) activity, resulting in increased endothelial nitric oxide synthase (eNOS) activity and inhibition of the mammalian Target of Rapamycin (mTOR) signalling. The effect of metformin administration on cardiac stem cell dynamics is likely to result in positive cardiac remodelling in the context of cardiac hypertrophy, by limiting the extent of pathological hypertrophy. In chapter 5, the combined treatment of L-NAME and angiotensin-converting-enzyme (ACE) inhibition (captopril) demonstrated a greater decrease in c-Kit expression compared to the effects of L NAME or captopril treatment alone, suggesting that both ACE inhibition and L NAME have independent regulatory actions on c-Kit expression. The presence of ACE inhibition appeared to mediate an earlier effect on c-Kit expression levels at 2 days compared to L-NAME treatment, which has been demonstrated to occur at day 5. It is thought that the mechanism by which captopril reduced c-Kit expression was primarily via induction of ACE2/Angiotensin (Ang) 1-7 activity. Interestingly, despite the known therapeutic benefits of ACE inhibition on cardiac function in the clinical setting, high dose captopril treatment in this study demonstrated ventricular wall thinning consistent with features of heart failure. In chapter 6, we undertook an extensive analysis of morphological changes in the heart in hypoxic or hyperoxic conditions. Intermittent hyperoxia did not result in significant wall thickening in the left ventricle, whereas intermittent hypoxia did. In the context of stem cells, c-Kit+ cells were increased with intermittent hyperoxia and decreased with intermittent hypoxia, the latter suggesting an association with the development of cardiac hypertrophy. Overall, what is demonstrated in this thesis is that stem cells may play a role in various disease models of cardiovascular health. The stem cell response in most cases appears to be acute, occurring within days of pathological stress, and then subsiding. It is most likely, after this, that the hallmarks of cardiovascular pathology such as maladaptive remodelling take place. Despite the limitations of the experiments, a framework for further investigations has been set and understanding the mechanisms of the stem cell response would be fundamental to extending the positive influence of stem cells on cardiac remodelling beyond the acute phase.
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Hirani, Nikhil A. "The regulation of interleukin-8 from macrophages by acute hypoxia and hyperoxia : a role in the pathogenesis of the acute respiratory distress syndrome (ARDS)." Thesis, University of Edinburgh, 2002. http://hdl.handle.net/1842/28236.
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Adequate oxygenation is a critical requirement for normal cellular function in humans. In patients with conditions such as major trauma, sepsis and aspiration injury there is often significant local and widespread tissue hypoxia as a consequence of inadequate oxygen supply or impaired oxygen utilisation. In this thesis, the role of acute hypoxia and hyperoxia were investigated in a novel animal model of acute lung injury. Bronchoscopic instillation of HC1 acid in an anaesthetised, ventilated rabbit resulted in reproducible acute neutrophilic lung injury in the instilled lobe. The contra-lateral lung acted as a site of potential indirect lung injury. Systemic hypoxaemia was induced by reduction in the inspiratory oxygen fraction. Compared to normoxic controls (arterial PaO2 ~ 11 KPa), acute hypoxia (PaO2 ~ 5 KPa) for up to 2 hours increased intrapulmonary IL-8 mRNA, but not protein expression in the acid-injured lung. Delivery of 100% oxygen for 2 hours (PaO2 ~ 60 KPa) following acute hypoxia, increased both intrapulmonary IL-8 mRNA and IL-8 protein levels. The increase in IL-8 protein was attenuated if the reoxygenation phase was controlled to return arterial PO2 to normoxic levels (~ 11 KPa). Acute hypoxia/hyperoxia may represent a potential mechanism by which intrapulmonary IL-8 levels are rapidly raised in patients at-risk of ARDS. In human blood monocyte derived macrophages, it was shown that acute hypoxia alone rapidly upregulated IL-8 gene expression. A number of other proinflammatory cytokines were conversely down regulated by hypoxia. The IL-8 increase occurred in association with raised nuclear levels of AP-1 and C/EBP-β, but not NF-κB. Hypoxia induced expression of the transcription factor HIF-1α. However cobalt chloride and desferroxamine, HIF-1α-inducing hypoxia mimics, did not upregulate IL-8, suggesting that IL-8 regulation was HIF-1 independent. Both the pattern of chemokine expression and transcription factor activation with hypoxia differed from that induced by lipopolysaccharide (LPS), an archetypal pathogenic stimulus.
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Manzano, Roberta Munhoz. "Modelo de lesão pulmonar em coelhos prematuros: influência da idade gestacional e da concentração de oxigênio." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5141/tde-12012012-092414/.
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INTRODUÇÃO: A lesão pulmonar da nova displasia broncopulmonar se caracteriza por uma diminuição da septação alveolar e do desenvolvimento vascular, ocorre um bloqueio no desenvolvimento pulmonar e consequentemente uma diminuição da alveolarização. A lesão pulmonar ocorre devido à associação de diversos fatores, incluindo a prematuridade, defesas antioxidantes inadequadas, e a ativação da resposta inflamatória. A exposição prolongada ao oxigênio também resulta em anormalidades na formação e na morfologia dos alvéolos, com redução tanto do volume pulmonar como da área de superfície interna alveolar. O objetivo do presente estudo foi comparar dois modelos de indução de lesão pulmonar através da exposição à hiperoxia prolongada em coelhos. MÉTODOS: Coelhas grávidas da raça New-Zealand-White foram sedadas para realização do parto cesáreo no 28º dia de gestação (termo = 31dias), coelhos prematuros foram expostos ao ar ambiente ou FiO295%. Outro grupo nasceu no 29º dia de gestação e foi exposto ao ar ambiente ou a uma FiO2=80%. Os animais foram mantidos em incubadora com controle de temperatura e alimentação e uma fórmula especial de leite similar ao leite de coelha por 11 dias. Desta forma, foram constituídos quatro grupos de estudo: Ar ambiente com 28 dias de gestação (Ar 28); exposição ao oxigênio (FiO2 95%) com 28 dias de gestação (O2 28); ar ambiente com 29 dias de gestação (Ar 29); exposição ao oxigênio (FiO2 = 80%) com 29 dias de gestação (O2 29). Após o sacrifício os pulmões foram fixados com 30 cmH2O de pressão transtraqueal. As lâminas do tecido pulmonar foram submetidas às seguintes colorações: hematoxilina e eosina para análise morfométrica; Weigert, resorcina-orceína modificado para a análise das fibras elásticas e Picrosirius para análise do colágeno. Foi realizada a contagem do Intercepto Linear Médio (Lm), determinada a Área de Superfície Interna (ISA), o número de alvéolos por campo microscópico, o espessamento septal e a proporção de fibras elásticas e colágenas. Análise Estatística: As variáveis contínuas foram analisadas por ANOVA One Way e a análise da sobrevida foi realizada através de uma curva de Kaplan-Meyer. O nível de significância adotado foi de 0.05. RESULTADOS: A sobrevida nos grupos de 29 dias foi melhor quando comparados com o grupo 28 dias. A hiperoxia bloqueou o desenvolvimento normal do pulmão, demonstrado por um aumento no Lm, uma diminuição significativa na ISA, uma diminuição no número de alvéolos, um aumento na espessura do septo interalveolar e também um aumento na proporção de fibras elásticas e uma diminuição na proporção de fibras colágenas nos dois grupos de animais expostos ao oxigênio em relação aos grupos que permaneceram em ar ambiente. CONCLUSÕES: Em coelhos prematuros o uso de uma concentração de oxigênio menor e um dia a mais de gestação reduziu a taxa de mortalidade mantendo os achados histopatológicos compatíveis aos da displasia broncopulmonar em humanosINTRODUCTION: The lung injury of the \"new\" bronchopulmonary dysplasia is characterized by a decrease in alveolar septation and vascular development, resulting in a pulmonary arrest and a decrease in alveolarization. Lung damage occurs due to the association of many factors, including prematurity, inadequate antioxidant defenses and activation of the inflammatory response. Prolonged exposure to oxygen also results in abnormalities in the formation and morphology of the alveoli, with reduced lung volume and alveolar internal surface area. The aim of this study was to compare two models of lung injury induced by prolonged exposure to hyperoxia in rabbits. METHODS: New Zealand-White pregnant rabbits were sedated to perform a cesarean section on day 28 of gestation (term = 31days), premature rabbits were exposed to room air or FiO295%. Another group of animals was born at day 29 of gestation and was exposed to room air or FiO2=80%. The animals were kept in an incubator with temperature control and fed with a special milk formula similar to rabbit milk for 11 days. Four study groups were formed: Room air and 28 days of gestation (Air 28); exposure to oxygen (FiO295%) and 28 days of gestation (O2 28); room air and 29 days of gestation (Air 29 ); exposure to oxygen (FiO2=80%) and 29 days of gestation (O2 29). For microscopic evaluation, after sacrifice the lungs were fixed in situ at a constant inflation pressure of 30 cm H20. Lung slices were processed for hematoxylin-eosin staining - for morphometric analysis, Weigert\'s resorcin-orcein modified for the analysis of elastic fibers and Picrosirius - for analysis of collagen. The mean linear intercept (Lm), the internal surface area (ISA), the number of alveoli, the septal thickness and the proportion of elastic and collagen fibers were quantified. Statistical analysis was by One Way ANOVA for continuous variables, survival analysis was performed using a Kaplan-Meyer plot. The level of significance was 0.05. RESULTS: Survival in both 29 days groups was better when compared with 28 days groups. Hyperoxia impaired the normal development of the lung, demonstrated by an increase in Lm, a significant decrease in ISA, a decrease in the alveoli number, an increase in the septal thickness and an increase in the proportion of fibers elastic and a decrease in the proportion of collagen fibers in oxygen exposed animals. CONCLUSIONS: In premature rabbits using a lower concentration of oxygen and one more day of gestation reduced the mortality rate maintaining the histopathological findings similar to bronchopulmonary dysplasia in humans
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Gamboa, Teresa Paula Rocha Soeiro Tavares. "Repercussões crónicas nas vias aéreas da hiperóxia neonatal : modelo experimental." Doctoral thesis, Faculdade de Ciências Médicas. Universidade Nova de Lisboa, 2007. http://hdl.handle.net/10362/5516.
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RESUMO: O objectivo deste trabalho foi avaliar se a exposição crónica neonatal à hiperóxia mo-derada induz alterações funcionais e estruturais persistentes nas vias aéreas. Desenvolveu-se um modelo animal, no rato, a partir do qual se retiraram implicações para a compreensão das repercussões crónicas da hiperóxia neonatal sobre as vias aéreas de displasia broncopulmonar (DBP), em duas fases distintas: imediatamente após a exposi-ção neonatal a 50%O2 (grupo 50%O2) e após três semanas de recuperação em ar ambiente (grupo 50%O2+Ar).Compararam-se os resultados da resposta do músculo liso de traqueia (MLT) à esti-mulação in vitro com metacolina e salbutamol e avaliaram-se as alterações quantitativas da área de MLT, bem como as alterações qualitativas da estrutura da traqueia. Demonstrou-se que a exposição a 50% de oxigénio não tinha repercussões imediatas sobre a resposta in vitro do MLT à estimulação colinérgica, mas que induzia um aumento do relaxamento em resposta ao salbutamol. A contractilidade do MLT em resposta à estimula-ção com metacolina no grupo 50%O2+Ar foi significativamente superior à do grupo de con-trolo da mesma idade e também superior à observada no grupo 50%O2, enquanto que a resposta ao salbutamol se voltou a aproximar dos valores de controlo após a recuperação em normóxia. Não se observaram diferenças estatisticamente significativas na área de MLT entre os grupos experimental e de controlo, o que se deve provavelmente ao número reduzido de amostras avaliadas e à variabilidade deste parâmetro no grupo de controlo; contudo, verifi-cou-se um aumento médio de 15% imediatamente após a exposição à hiperóxia que persis-tiu após o período de recuperação.As alterações qualitativas sobre a arquitectura da traqueia, avaliadas por microscopia óptica, revelaram no grupo 50%O2 aumentos da espessura da matriz extracelular e da den-sidade de mastócitos desgranulados na submucosa e adventícia vizinhas do MLT, sem outras alterações relativamente ao grupo de controlo com 15 dias. As alterações da matriz extrace-lular foram reversíveis após a recuperação em ar ambiente. A densidade de mastócitos per-maneceu superior à do grupo de controlo de 36 dias de idade, apresentando-se em maior contiguidade com o MLT relativamente ao grupo 50%O2. Em síntese, demonstrou-se que a hiperóxia neonatal crónica em níveis moderados in-duz alterações da resposta contráctil do MLT e da estrutura da traqueia que podem ter ex-pressão funcional após a exposição ter cessado. Assim, o contributo original do presente trabalho foi o desenvolvimento de um modelo animal que permite avaliar os mecanismos pelos quais a hiperóxia é capaz de induzir, isoladamente, alterações crónicas da contracti-lidade, do relaxamento do ML e da estrutura das vias aéreas que podem ser responsáveis pela HRB persistente em doentes sujeitos a oxigenioterapia neonatal.-------------ABSTRACT: The aim of this work was to evaluate whether chronic neonatal exposure to hyperoxia in-duces persistent structural and functional airway changes. An animal model was developed, using neonatal rats, in order to understand the chronic effects of neonatal hyperoxia on the airways, in bronchopulmonary dysplasia, in two distinct phases: immediately after neonatal exposure to 50%O2 (50%O2 group) and after three weeks of recovery at ambient air (50%O2+Ar group).The results from the tracheal smooth muscle (TSM) response to in vitro stimulation with metacholine and salbutamol were compared and quantitative changes in TSM area, as well as qualitative changes in tracheal structure were evaluated. It was demonstrated that while exposure to 50% oxygen had no immediate effects on in vitro TSM response to cholinergic stimulation, it induced an increase in relaxation as a result of salbutamol administration. TSM contractility as a result of methacholine administration in the 50%O2 + Ar group was significantly higher than that of the same-age control group, and also higher than the one observed in the 50%O2 group, whereas the response to salbutamol admini-stration was once again closer to the control values after recovery in normoxia. There were no statistically significant differences in the TSM area between the experi-mental and control groups, which is most likely due to the reduced number of samples evalu-ated and to the variability of this parameter in the control group. However, there was an aver-age increase of 15% immediately after exposure to hyperoxia, which persisted after the recov-ery period. Qualitative changes in tracheal architecture, evaluated by optic microscopy, revealed that the 50%O2 group suffered an increase in the thickness of the extracellular matrix and degranu-lated mast cell density in the submucosa and adventitia adjacent to the TSM, without further changes when compared with the control group at 15 days of age. The changes in extracellular matrix were reversible after recovery in ambient air. Mast cell density remained higher than that of the control group at 36 days of age, and more contiguous to TSM than the 50%O2 group. In conclusion, it has been demonstrated that moderate levels of chronic neonatal hyperoxia in-duce changes in TSM contractile response and tracheal structure, which may be functionally ex-pressed after discontinuation of exposure. Therefore, the original contribution of the present work was the development of an animal model which allows the evaluation of the mechanisms through which hyperoxia alone can induce chronic changes in contractility and relaxation of SM and also in airway structure that can be responsible for the persistent airway hyperrespon-siveness found in patients who were submited to neonatal oxygen therapy.
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Theunissen, Sigrid. "Intérêt de l'apport en chocolat noir dans la prévention des effets de la plongée à l'air et en apnée sur l'endothélium vasculaire." Phd thesis, Université de Bretagne occidentale - Brest, 2013. http://tel.archives-ouvertes.fr/tel-01063135.
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Objectifs : Comparer les effets de la plongée à l'air et en apnée sur la vasodilatation d'origine endothéliale et le stress oxydant. Ensuite, tenter de prévenir la dysfonction endothéliale post-plongée par une supplémentation en antioxydants. Méthodes : La fonction endothéliale des grosses artères est évaluée par la dilatation flux-dépendante (FMD) et celle des petites par pléthysmographie. Les concentrations plasmatiques de monoxyde d'azote (NO) furent évaluées en mesurant les nitrites/nitrates par colorimétrie. Les effets de 30g de chocolat noir furent testés en supplémentation 1h30 avant la plongée à l'air et 1h avant l'apnée. Résultats : La FMD diminue dans les 2 types de plongée. Le taux de NO est inchangé après la plongée à l'air alors qu'il augmente après l'apnée. En eau froide, le taux de NO se voit réduit chez les plongeurs en apnée. Lorsque le chocolat noir est administré en supplémentation à des plongeurs, la FMD est augmentée aussi bien après la plongée à l'air qu'en apnée. Le NO augmente après la plongée à l'air alors qu'il ne change pas après l'apnée. Conclusion : En apnée comme en plongée à l'air, la diminution de la FMD suggère qu'elle est liée à un stress oxydant puisqu'elle est prévenue par le chocolat noir. Le chocolat noir est un bon moyen préventif pour la dysfonction endothéliale aussi bien en plongée à l'air qu'en apnée. L'absence de variation du NO suggère que la diminution de la FMD est la conséquence d'une activité du système nerveux autonome et/ou d'une altération du muscle lisse vasculaire. Les mécanismes observés en plongée sont un bon modèle pour la personne âgée où du stress oxydant et une dysfonction endothéliale sont également retrouvés.
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Bruzzese, Laurie. "Réponses cellulaires du système adénosinergique à la dysoxie." Thesis, Aix-Marseille, 2015. http://www.theses.fr/2015AIXM5046.
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La dysoxie (hypoxie/hyperoxie) résulte de l’inadéquation entre la consommation en oxygène et ses apports, provoquant altérations du métabolisme cellulaire et impact physiopathologique majeur. L’hypoxie et l’inflammation font intervenir les facteurs HIF-1a et NF-kB qui activent le système adénosinergique. L’hypoxie augmente la concentration d’adénosine, entraîne une surexpression d’A2AR et induit une immunosuppression lymphocytaire T. Nous avons fait l‘hypothèse que l’inflammation via NF-kB influençait la suppression lymphocytaire adénosinergique; qu’une hyperhomocystéinémie favoriserait l’inflammation en modifiant la viabilité lymphocytaire; qu’in vivo, la réponse adénosinergique était modulée par l’hyperoxie. Des lymphocytes T ont été soumis à une inflammation (agents mitogènes) et à une hypoxie chimique (CoCl2). Nous avons analysé l’expression de NF-kB, HIF-1α, A2AR et évalué les concentrations en adénosine, adénosine déaminase, AMPc, et homocystéine. Enfin, nous avons étudié les effets de l’hyperoxie/hyperbarie sur la réponse adénosinergique. L’hypoxie stimule la réponse adénosinergique : NF-kB induit HIF-1α qui augmente l’expression d’A2AR, favorisant l’immunosuppression. L’inhibition de NF-kB par H2S bloque l’immunosuppression via HIF-1α/A2AR. In vivo, l’hyperoxie inhibe la réponse adénosinergique via la diminution de l’expression d’A2AR. Hypoxie et hyperoxie ont un effet en miroir sur le système adénosinergique. Manipuler la concentration en O2 permet de piloter système immunitaire et inflammation via A2AR. L’utilisation d’H2S pourrait traiter des pathologies à fort impact en santé publique, tels des troubles cardiovasculaires favorisés par l’hyperhomocystéinémieDysoxia (hypoxia/hyperoxia) results from an impaired balance between oxygen-supply concentration and cellular metabolism causing various disorders. Hypoxia and inflammation involve HIF-1a and NF-kB factors and are linked via the adenosinergic response. Hypoxia increase adenosine concentration and A2A receptors (A2AR) expression which induces T-lymphocyte suppression. We hypothesized that during hypoxia, inflammation influences adenosinergic immunosuppression via NF-kB. As homocysteine promotes inflammation, which is considered as a risk factor, we hypothesized that hyperomocysteinemia affects T-cell viability and adenosinergic response. Effects of hyperoxic and hyperbaric conditions on adenosinergic system remain unclear. NF-kB, HIF-1α, and A2AR expression were studied using T-cells stimulated by mitogens under hypoxic conditions (CoCl2). Adenosine, adenosine deaminase, cAMP concentration and homocysteine metabolism were analyzed. Effect of hyperoxia on the adenosinergic pathway was addressed in a rat model using pressure chambers. HIF-1α production was induced by hypoxia, A2AR expression increased following NF-kB activation that enhanced lymphocyte-suppression. Inhibition of NF-kB by H2S resulted in improved cell-viability by down-regulating A2AR-mediated-immunosuppression. Hyperhomocysteinemia increased H2S production (transsulfuration-pathway). We also found in rat that hyperoxia repressed the adenosinergic response. Manipulating blood oxygen level constitutes an effective mean to control the immune response and inflammation via the adenosinergic system. Acting on A2AR expression via H2S production may control cardiovascular-disorders with high impact on public health
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Binder, Leonore [Verfasser], Babett [Gutachter] Bartling, Stefanie [Gutachter] Endesfelder, and Jan-Henning [Gutachter] Klusmann. "The influence of hyperoxia on intracellular reactive oxygen species formation and antioxidant enzyme systems in mouse lungs / Leonore Binder ; Gutachter: Babett Bartling, Stefanie Endesfelder, Jan-Henning Klusmann." Halle (Saale) : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2021. http://d-nb.info/1234451492/34.
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