Thesis--Københavns universitet. / Bibliography: p. 205-[212].

Thesis--Københavns universitet. / Bibliography: p. 205-[212].

Thesis--University of Michigan. / Includes bibliographical references.

The porphyrias are a group of disorders characterized by the excessive excretion of haem precursors in urine and stool. in the past two decades, isotopic studies led to impressive progress in our understanding of both normal and disordered porphyrin metabolism but despite these advanaces, many aspects of latter are still unexplained.

Thesis (M.S.)--West Virginia University, 2002. / Title from document title page. Document formatted into pages; contains ix, 39 p. : ill. Vita. Includes abstract. Includes bibliographical references (p. 32-37).

Thesis (M.S.)--West Virginia University, 1999. / Title from document title page. Document formatted into pages; contains xi, 77 p. : ill. Vita. Includes abstract. Includes bibliographical references.

Thesis (Ph. D.)--University of Iowa, 1927. / Cover title. Autobiography. Bibliography: p. [23].

none

Thesis (Ph. D.)--West Virginia University, 2002. / Title from document title page. Document formatted into pages; contains xv, 145 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 122-145).

Serum uric acid (SUA) is in many ways related to cardiovascular morbidity and mortality. In this thesis, the objectives were to (1) to review the role of SUA in cardiovascular diseases; (2) to study the effects of elevated SUA on vascular function in subjects with high cardiovascular risk; (3) to evaluate the prognostic significance of SUA and vascular function; (4) to study the effect of pharmacological reduction of SUA on vascular function. A literature review was performed at the beginning to summarise the key findings from epidemiological, cross-sectional, and interventional studies that examined the relationship of SUA with cardiovascular diseases, vascular dysfunction, and its associated pathophysiological mechanisms in vascular dysfunction. The results from available studies that evaluated the association of elevated SUA with vascular dysfunction are inconsistent. Therefore the role that elevated SUA plays in the pathogenesis of vascular dysfunction and cardiovascular diseases remains controversial. With this background information in mind, we performed a series of studies to give more evidence to the controversial areas. A cross-sectional study on subjects with high cardiovascular risk was first performed. The markers of vascular function assessed were brachial arterial flow-mediated dilation (ba-FMD), and nitroglycerin-mediated dilation (ba-NMD). It showed that elevation of SUA was independently associated with impairment of ba-NMD, but not with impairment of ba-FMD. This suggested that ba-NMD impairment may be part of the underlying mechanism in the vasculature by which elevated SUA increases the risk of adverse cardiovascular outcomes. To test the above hypothesis, the prognostic significance of SUA and ba-NMD was evaluated by conducting an analysis on the risk of developing major adverse cardiovascular events (MACE) in the above cohort. The outcome variables of MACE (acute coronary syndrome, myocardial infarction, congestive heart failure, stroke etc.) within the follow-up period were collected. The time-to-event analysis demonstrated that both SUA and ba-NMD independently predicted the development of MACE. The causal mediation analysis confirmed that ba-NMD was the mediator between elevated SUA and MACE. Finally, a randomised placebo-controlled trial was performed to assess the effect of pharmacological reduction of SUA on vascular function. A novel herbal agent “UricsilTM” was used as the active treatment. The SUA-lowering effect of UricsilTM was insignificant compared with placebo at 12 weeks. No significant change in vascular function (ba-FMD and ba-NMD) was observed following treatment. The key research finding in this thesis, which demonstrated that ba-NMD is a potential mediator between elevated SUA and MACE, is a novel one. Future clinical and experimental studies could be performed to further enhance our understanding of this potential mechanism. / published_or_final_version / Medicine / Master / Master of Philosophy