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- Larsen, Filip J.
(author)
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Dietary inorganic nitrate : role in exercise physiology, cardiovascular and metabolic regulation
- 2011
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Doctoral thesis (other academic/artistic)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. |
- Petersson, Joel, 1977-
(author)
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Nitrate, Nitrite and Nitric Oxide in Gastric Mucosal Defense
- 2008
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Doctoral thesis (other academic/artistic)abstract
- The human stomach normally contains high levels of bioactive nitric oxide (NO). This NO derives from salivary nitrate (NO3-) that is converted to nitrite (NO2-) by oral bacteria and thereafter non-enzymatically reduced in the acidic gastric lumen to NO. Nitrate is a common component in vegetables, and after ingestion it is absorbed in the small intestine. Interestingly, circulating nitrate is then concentrated by the salivary glands. Hence, intake of nitrate-rich vegetables results in high levels of NO in the stomach. The physiological effects of the high concentration of NO gas normally present in the gastric lumen have been hitherto unknown, and the present investigations were therefore conducted to address this issue.NO produced in the gastric lumen after nitrate ingestion increased gastric mucosal blood flow and the thickness of the firmly adherent mucus layer in the stomach. The blood flow and mucus layer are essential defense mechanisms that protect the mucosa from luminal acid and noxious agents. Nonsteroidal antiinflammatory drugs (NSAID) are commonly prescribed and effective drugs for treating pain and inflammation, but are associated with severe gastrointestinal side effects. We demonstrated that a nitrate-rich diet protects against NSAID-induced gastric damage, as a result of the increased formation of NO in the stomach. We also showed that the gastroprotective effect attributed to nitrate depended completely on conversion of nitrate to nitrite by the bacterial flora colonizing the tongue, and that the oral microflora is therefore important in regulating physiological conditions in the stomach.In summary, this thesis challenges the current dogma that nitrate intake is hazardous, and on the contrary suggests that dietary nitrate plays a direct role in regulating gastric homeostasis. It is likely that a sufficient supply of nitrate in the diet together with the oral microflora is essential for preventing pathological conditions in the gastrointestinal tract.
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| 3. |
- Lundberg, Johanna, 1975-
(author)
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Social status : a state of mind?
- 2008
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Doctoral thesis (other academic/artistic)abstract
- This thesis is concerned with social stratification of psychosocial factors and social position measurement in population samples collected in mid-Sweden 2000-2006. Traditional resource-based measures of social position (occupation, education) and so far less explored prestige-based measures (subjective status, status incongruence) are tested with respect to their associations with psychosocial factors, emotions, and selfrated health. Three papers in this thesis are based on data from the Life Conditions, Stress, and Health (LSH) study, using a randomly selected population sample. Data for the fourth paper is a regional sample drawn from the health-related survey “Liv och Hälsa 2000”. Statistical methods range from correlation analysis to logistic regression and repeated measures analyses.Results from studies I and IV show that psychosocial factors are unequally distributed within the population in a linear manner, so that the lower the socioeconomic position (SEP), the more unfavourable levels. This is independent of whether we study this in a highly unequal setting such as Russia, or in a more egalitarian society such as Sweden. The stability of psychometric instruments over two years tend to be lower for all instruments among low SEP groups, and differ significantly for self-esteem and perceived control among groups with high and low education, and for cynicism among groups with high and low occupational status. Results from studies II and III point to the relevance of individuals’ own thoughts about themselves, and the potential impact on the self by normative judgements of social position in a certain hierarchical setting. In paper II, the prestige-based measure of subjective status was influenced by resource-based measures, such as self-rated economy and education, but also by life satisfaction and psychosocial factors. The importance of self-evaluation was especially obvious from the study on status incongruence (study III) where the traditionally protective effecs of a high education seem to disappear when combined with a lowstatus occupation. Shaming experiences may play an important role here for our understanding of self-perception.
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