Thesis (M.Phil.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 80-110) Also available in print.

Thesis (M.Med.Sc.)--University of Hong Kong, 2000. / Includes bibliographical references (leaves 57-60). Also available in print.

Thesis (M.Med.Sc.)--University of Hong Kong, 2001. / Includes bibliographical references. Also available in print.

Thesis (Ph.D.)--Memorial University of Newfoundland, 2004. / Bibliography: leaves 223-250.

Thesis (Ph.D.)--University of Nebraska-Lincoln, 2006. / Title from title screen (site viewed on Sept. 12, 2006). PDF text of dissertation: 130 p. : ill. (some col.) ; 1.08Mb. UMI publication number: AAT 3208125. Includes bibliographical references. Also available in microfilm and microfiche format.

Thesis (M.S.)--State University of New York at Binghamton, Chemistry Department, 2005. / Includes bibliographical references.

No description available.

Elevated homocysteine (Hcy) concentration has been identified as an independent risk factor for premature CAD. Associations between Hcy concentrations and established cardiovascular risk factors have occasionally, but not consistently, been demonstrated. Plasma fibrinogen and total Hcy concentrations, along with other risk factors, folate and Bvitamin supplements, and medications, were recorded for 40 males (mean age ± SD: 65 ± 9.8 yr) with CAD. Physical activity was assessed using the Modifiable Activity Questionnaire (MAQ), a written questionnaire which appraises leisure and occupational activities by recall for a 12 month period. Univariate analyses revealed those subjects on beta-blocker therapy (n = 12) had lower fibrinogen concentrations than those not on these medications (n = 28) (277.7 ± 16.7 vs. 316.1 ± 10.9 mg/dl , respectively, p = 0.04). A trend existed for those on beta-blockade to also have lower Hcy concentrations (8.3 ± 0.66 vs 9.7 ± 0.43 µmol/L, respectively, p = 0.058). Subjects in the upper tertile of physical activity had significantly lower fibrinogen concentrations than those in the lower tertile (274.7 ± 38 mg/dl vs. 320.2 ± 63, respectively, p = 0.05). Homocysteine concentration was found to be positively associated with age (p = 0.0008). No significant associations were established with multivariate analyses among fibrinogen, Hcy, physical activity, age, BMI, B-vitamin and folate supplements, beta-blocker therapy, total cholesterol, HDL, LDL, triglycerides, and TC/HDL ratio. These results support the hypothesis that hyperhomocysteinemia is an independent risk factor for CAD. Future studies should consider the favorable effects of beta-blockade, which may be a confounding factor, on Hcy and fibrinogen concentrations. Knowledge of associations may contribute toward understanding of the pathogenesis of CAD. / Master of Science

No / Elevated plasma concentrations of the sulphur-containing amino acid homocysteine (Hcy) is associated with increased risk of atherosclerosis and arterial thrombosis. The mechanism by which Hcy exerts these effects has yet to be fully elucidated, although a variety of possible mechanisms have been proposed, including endothelial dysfunction or haemostatic abnormalities. However, the influence of Hcy on platelets, cells central to the atherothrombotic process, has never been addressed directly in patient studies. Here, the influence of mild hyperhomocysteinaemia (hHcy) on platelet function was explored in patients with peripheral occlusive arterial disease as evidence by intermittent claudication. Claudicants (n=39) were assigned to one of two subgroups depending on their plasma Hcy concentrations. hHcy claudicants had plasma Hcy concentrations of 18.9±1.0 ¿M (n=24), compared to 11.3±0.5 ¿M for normohomocysteinemic (nHcy) claudicants (n=15) and 12.6±0.7 ¿M for age-matched controls (n=15). Platelet function was evaluated ex vivo in both groups and compared to age-matched controls. Platelet activation and sensitivity to nitric oxide-mediated inhibition was assessed by platelet fibrinogen binding and P-selectin expression. At low concentrations of adenosine diphosphate (ADP; 0.1 ¿M) and thrombin (0.02 U/ml), platelets from hHcy claudicants were more reactive than those from age-matched controls, but not nHcy claudicants. Agonist-induced P-selectin expression was significantly raised in hHcy claudicants compared to all other groups. Interestingly no differences were observed between nHcy claudicants and age-matched controls, indicating that claudication per se did not affect platelet function. Since platelet activity in vivo is determined by the exposure to both agonists and antagonists, we subsequently tested the sensitivity of platelets to inhibition by nitric oxide (NO), using the same platelet markers. Platelets from hHcy claudicants were significantly less sensitive to GSNO (1¿100 ¿M)-mediated inhibition than all other groups. GSNO (1 ¿M) induced 42.6±10 and 39±11.5% inhibition of ADP-induced fibrinogen binding for the nHcy claudicants and age-matched controls, respectively. However, in hHcy claudicants only 16.4±9.7% inhibition was observed, significantly less than the other groups (P<0.01). Again no differences between nHCy claudicants and controls were observed. These results suggest the presence of claudication alone does not influence platelet function but if complicated with mild hyperhomocysteinemia, the sensitivity to agonists is increased, and more importantly, their sensitivity to inhibition is greatly reduced. The overall effect would be an increased propensity for platelet activation. The presence of even mildly elevated plasma Hcy could dramatically increase thrombotic risk.

Source: Masters Abstracts International, Volume: 47-06, page: 3552. Adviser: Stephen C. Waring. Includes bibliographical references.