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- Larsen, Filip J.
(författare)
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Dietary inorganic nitrate : role in exercise physiology, cardiovascular and metabolic regulation
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nitric oxide (NO) is a ubiquitous signaling molecule with a vast number of tasks in the body, including regulation of cardiovascular and metabolic function. A decreased bioavailability of NO is a central event in disorders such as hypertension and metabolic syndrome. NO is also important in the regulation of blood flow and metabolism during exercise. The production of NO has previously been thought to be under the exclusive control of the nitric oxide synthases (NOS) but this view is now being seriously challenged. Recent lines of research suggest the existence of an NO-synthase independent pathway in which the supposedly inert NO oxidation products nitrate (NO3-) and nitrite (NO2-) can be reduced back to NO in blood and tissues. An important additional source of nitrate is our everyday diet and certain vegetables are particularly rich in this anion. In this thesis the possibility that dietary derived nitrate is metabolized in vivo to form reactive nitrogen oxides with NO-like bioactivity has been explored. It is shown that nitrate in amounts easily achieved via the diet, increases the systemic levels of nitrite and reduces blood pressure in healthy humans. Moreover, nitrate reduces whole body oxygen cost during submaximal and maximal exercise; a surprising effect involving improvement in mitochondrial efficiency and reduced expression of specific mitochondrial proteins regulating proton conductance. Alterations in the mitochondrial affinity for oxygen can explain this reduction in both submaximal and maximal oxygen consumption and predicts basal metabolic rate in humans. Finally, in mice lacking endothelial NO synthase, dietary supplementation with nitrate could reverse several features of the metabolic syndrome that develop in these animals. These studies demonstrate that dietary nitrate can fuel a nitrate-nitrite-NO pathway with important implications for cardiovascular and metabolic functions in health and disease.
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| 2. |
- Marchesi, Silvia, MD, 1985-
(författare)
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The effect of mechanical ventilation on the abdominal organs
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During mechanical ventilation (MV), the interplay between abdomen and thorax has been studied unilaterally focusing on the effect that an increased abdominal pressure would have on the thorax. Only a small cluster of studies offered a different perspective showing a lower inflammation and a better lymphatic clearance of edema in abdominal organs when spontaneous breathing was applied compared to MV. Apart from these insights, a deeper understanding of the effect of different MV features on the abdominal organs remains uninvestigated.The aims of the thesis were: to investigate how changes in perfusion and edema influence inflammation and affect each other, and to examine how the management of ARDS could affect abdominal organs by comparing MV with spontaneous breathing and prone with supine position. All the studies were conducted using a porcine model. In three studies, a septic-like status was generated with an infusion of endotoxin; while in one study, a VILI model was used to simulate ARDS.In the first two studies, perfusion and lymphatic drainage were modified in different groups of animals and the impact of the changes on the abdominal organs was assessed. In the other two studies the effect of different ventilation settings on the abdominal organs was investigated: in Paper III, spontaneous breathing(CPAP) was compared with MV (maintaining positive end expiratory pressure – PEEP – and respiratory rate similar in both groups), and, in Paper IV, MV in prone position was compared with MV in supine position. The main findings were that low perfusion increased inflammation in the abdominal organs, but the hemodynamic parameters could not affect intestinal perfusion or edema. Similarly, increased edema was not associated with a decreased perfusion, but it enhanced inflammation in duodenum. MV increased systemic inflammation compared to CPAP, but did not increased inflammation or edema in the abdominal organs. Prone position reduced renal perfusion and was associated to extensive renal micro-thrombosis. In conclusion, both perfusion and edema influence inflammation in the abdomen, even if they seem not to affect one another. Besides, spontaneous breathing develops less systemic inflammation compared to MV, but it was not associated to a lower edema or inflammation in the abdomen; on the other side, prone positioning resulted in a possibly dangerous decrease of renal perfusion.
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| 3. |
- Nilsson, Manja
(författare)
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Endogenous Nitric Oxide Production and Pulmonary Blood Flow : during different experimental lung conditions
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nitric oxide (NO) is an important regulator of pulmonary blood flow and attenuates hypoxic pulmonary vasoconstriction (HPV). Nitric oxide is synthesized enzymatically in a number of tissues, including the lungs, and can also be generated from reduction of nitrite during hypoxia and acidosis. Inhaled nitric oxide (INO) is a selective pulmonary vasodilator, with no effects on systemic arterial blood pressure due to inactivation by hemoglobin in the blood. INO has distant effects both within the lungs and in other organs, since NO can be transported to remote tissues bound to proteins, or as more stable molecules of nitrite and nitrate. In healthy pigs, INO causes vasoconstriction and down regulation of endogenous NO production in lung regions not reached by INO, and predominantly so in hypoxic lung regions, i.e. augmentation of HPV. In this thesis, distant effects of INO in pigs with endotoxemic- and lavage-induced lung injuries were studied. INO increased the NO production in lung regions not reached by INO in endotoxemic pigs, whereas endogenous NO production was unaffected in pigs with lavage-induced injury. Metabolic and/or hypercapnic acidosis frequently occurs in critically ill patients, but whether acidosis affects the endogenous pulmonary NO production is unclear. The regional NO production and blood flow in hyperoxic and hypoxic lung regions, were studied during metabolic and hypercapnic acidosis. Neither metabolic, nor hypercapnic acidosis changed the endogenous NO production in hyperoxic or hypoxic lung regions. Metabolic acidosis potentiated HPV, whereas hypercapnic acidosis transiently attenuated HPV. In conclusion, the present thesis has demonstrated that INO in experimental sepsis increases the endogenous NO production in lung regions not reached by INO, which may cause increased shunt and poor response to INO. This distant effect is not seen in lavage injuried lungs, an experimental model with less inflammation. Acidosis does not affect the endogenous pulmonary NO production in hyperoxic or hypoxic lung regions. Whereas metabolic acidosis potentiates HPV, hypercapnic acidosis transiently attenuates HPV, due to a combination of hypercapnia-induced increase in cardiac output and a probable vasodilating effect of the CO2-molecule.
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| 4. |
- Wiklund, Jenny, 1975-
(författare)
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Journal - rekonstruktion av kropp och minne
- 2017
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Konstnärligt arbete (övrigt vetenskapligt/konstnärligt)abstract
- Projektet har utvecklats i interdisciplinärt samarbete mellan Jenny Wiklund och KTH, Akademiska Sjukhuset i Uppsala, Uppsala Universitet, Karolinska Institutet, Kungl. Konsthögskolan, Aarhus Arkitektskole, och curator Jan Åman.Projektet har utvecklats skulpturalt vid Kungl. Konsthögskolan. Förstudier har genomförts vid Karolinska Universitetssjukhuset. I finalstudien kombineras studier vid Uppsala Akademiska Sjukhuset, Bild- och Funktionsmedicinskt centrum/Röntgen i tredimensionell visualisering av medicinsk bild med studier i klinisk anatomi vid Uppsala Universitet, för att förenas i skulptural gestaltning och iscensättning.R1 Reaktorhallen iscensätts som ett platsspecifikt monumentalverk. Den fysiska installationen i rummet bildar en temporal kappa om utställningskapitlen i avhandlingsutställningen som handlar om kropp och hjärna. Utställningen berättar om en specifik tidpunkt, utan minne och proprioception. Här finns ingen historia och ingen framtid.Genom utställningen skapas en förståelse för sambanden mellan teoretiskt tänkande och visuell gestaltning. Det är forskning genom konstnärlig och arkitektonisk precision med referenser till konst, arkitektur, medicin och medicinsk teknik. Referenserna är från verkliga objekt i verkliga rum, specifika verk från specifika konstnärer och genom auskultering vid flertalet expertpresentationer, där människor genom närvaro förmedlat sin kunskap.Arkitektur är spatial konstruktion av identitet, här i utställningsform som temporal visuell spatial-estetisk poetik. Formen på framläggningen av avhandlingen är vald efter det huvudsakliga ämnet som utreds, minnet, och dess temporala omskapande av rummet vid varje specifik tidpunkt det framkallas. Det visuella intrycket kommer före alla andra beskrivningar, i logik med den händelse som föregick doktorandprojektets ämne, en minnesförlust, där upplevelsen av rummet kom före språket, kroppen före hjärnan, intränade minnen i form av siffror före en självbiografi.
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